key: cord- -ltatgq e authors: kesserwani, hassan title: cerebral microbleeds - to treat or not to treat, that is the question: a case report with a note on its radiologic deconstruction and therapeutic nuances date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ltatgq e with the ubiquity of susceptibility weighted imaging (swi), cerebral microbleeds (cmbs) are fast becoming a prevalent phenomenon. they are tightly associated with age, neurodegeneration and diverse vascular etiologies. cmbs have a unique radiological signature. their morphology, number and topology are quite informative. they also pose a therapeutic conundrum, as they are associated with the risk of cerebral hemorrhage. we present the case of an -year-old woman who has a vascular dementia, binswanger's syndrome, and coronary artery disease, who presented with more than five cmbs. we present this case in order to highlight the dilemma of anti-platelet therapy in this group of patients and we demonstrate the cardinal radiologic features of cmbs. we then segue into the pathologic correlates of cmbs and associated risk factors. we finally analyze the risk of anti-platelet therapy in the presence of cmbs, and we unfold the latest data on cmb number and anti-platelet therapy. cerebral microbleeds (cmbs) are an increasingly recognized diagnostic entity. they represent microhemorrhages in brain parenchyma. pathologically, these microbleeds are hemosiderin-laden macrophages. deep seated microbleeds, in the corona radiata and basal ganglia, are more commonly seen in hypertension. cortical lesions are commonly seen with amyloid angiography. parasagittal linear streaks are more typical of brain trauma and diffuse axonal injury [ ] . in the rotterdam study of close to patients, cmb prevalence increases with age, from . % in people aged to years to . % in people older than years. . % of all patients had at least one cmb [ ] . systolic blood pressure, hypertension, smoking, lacunar infarcts and white matter lesions were associated with cmbs in a deep or infra-tentorial region, whereas apo-lipoprotein e (apo e ) and diastolic blood pressure were related to cmbs in a lobar location [ ] . there is an elevated risk of both hemorrhagic, odds ratio . ( . - ) , and ischemic strokes, odds ratio of . ( . - . ) , in patients with recent ischemic stroke or transient ischemic attacks (tia) and cmbs [ ] . radiologically, cmbs appear magnified on susceptibility weighted images (swi) due to their paramagnetic properties and this is known as a blooming artifact. cmbs appear dark, hypo-intense, on all swi images. however, this finding can be due to either iron or calcium deposits. in order to differentiate, phase mapping is obtained [ ] . these are rapid acquisition images at no extra cost. if the magnetic resonance imaging (mri) scanner software is endowed with a left-handed reference frame such as siemens, the cmbs appear hyperintense on the phase map. if the mri scanner software is endowed with a right-handed reference frame, the cmbs will appear hypo-intense on phase maps. to orient oneself, we can look at the superior sagittal sinus or a venous tributary, and establish the "color" of the mri acquisition sequence on the phase map. in the left-handed reference frame, the sinus will appear bright. in the right-handed system such as a general electric scanner, the cmbs appear dark by noting the dark sagittal sinus or a venous tributary. the reverse situation is seen in the left-handed siemens scanner; here the cmbs and sagittal sinus appear bright. swi images and phase mapping are advanced imaging techniques that are sensitive to cerebral microbleeds. they utilize long echo sequences and gradient echo sequences (gre). these image acquisitions rely on the magnetic susceptibility of tissues, whether paramagnetic or diamagnetic. paramagnetism occurs when atoms have an odd number of electrons. hence, they have a net magnetic dipole moment, which aligns and reinforces an applied magnetic field. if the number of electrons is even, that is paired, then there are no dipoles to align. however, the applied magnetic field distorts the motion of electrons via the lorentz force. the induced magnetic dipoles anti-align with the applied magnetic field, and reduce the applied magnetic field. such a material is diamagnetic. the filtered phase images or phase map exploit the magnetic properties of tissues; paramagnetic (such as iron) and diamagnetic (such as calcium), which have opposite signal intensities in phase mapping [ ] . we present the case of an -year-old woman with binswanger's disease characterized by a vascular dementia, lower half parkinsonism and more than five cmbs. binswanger's disease is a subcortical vascular dementia characterized by loss of executive function: planning, insight and foresight, with relative preservation of memory. it is frequently accompanied by a gait disorder. she has the typical risk factors of binswanger's disease including chronic hypertension, coronary artery disease, hyperlipidemia and is a lifelong smoker. the question at hand states: is anti-platelet therapy safe in this patient with more than five micro-hemorrhages (cmbs) in the brain? the data to answer this question is evolving [ ] . in this article, we lay out the pathologic correlates of cmbs, gently outline the radiological nuances involved in analyzing cmbs and finally we display the latest data addressing the role of anti-platelet therapy. as cmbs are incidentally discovered on routine mri studies, whether to continue or discontinue anti-platelet or anticoagulant therapy, is an open question. the clinician has to individualize therapy, weigh the benefits of therapy and consider the pros and cons, until more definitive data becomes available. we report the case of a previously active and independent -year-old divorced female patient who over the course of two years, especially last year, has become increasingly forgetful and confused. she left the stove on at least twice and once boiled eggs without water, forgets relevant family conversations and repeats questions frequently. she was no longer able to balance her checkbook and has become increasingly distracted, "spacey" and "not together", as per her daughter's testimony. her daughter also noted that she cannot keep up with conversations when there are more than two people conversing. sometimes she cannot finish a sentence, has become increasingly argumentative and quit driving five years ago due to anxiety from a car accident. her hygiene has declined, sometimes forgets to bathe or fix her hair, forgets to do laundry, but when remembers may wash clean clothes. in the past, she worked at convenience stores and focused on inventory. the patient now presents emotional lability with excessive crying, with abandonment of social activities, such as reading the newspaper and watching sitcoms. her medications include atorvastatin mg, lisinopril mg, escitalopram mg, baby aspirin mg and mirtazapine mg daily. her past medical history is significant for at least a -year-history of hypertension, coronary artery disease and hyperlipidemia. there is no family history of dementia. she has smoked cigarettes, at least one pack a day, for years. on examination, her blood pressure (bp) is / and a pulse of beats per minute. her height is five foot and three inches with a weight of pounds and a body mass index (bmi) of . . precordial examination revealed no murmurs and carotid auscultation revealed no bruits. her gait was stooped and shuffling, with adequate arm swing. no retropulsion was noted. at most, she had a mild symmetric bradykinesia but without a rest, postural or kinetic tremor. no sequence motion of the hands was noted with rapid finger apposition. cognitively she appeared distracted and a little paranoid despite a mini-mental state score (mmse) of / , which usually indicates a mild dementia when the score goes below . visuo-motor skills were impaired with pantomime mimic. she has ideomotor apraxia with tool use, using the hand as the tool object. deftness with a coin, limb-kinetic praxis, was preserved. despite the presence of a grasp reflex and a snout reflex, a palmo-mental reflex was absent. but gegenhalten (paratonia) was noted in the arms, with compensatory increasing resistance with increasing velocity of flexion at the elbow. her cranial nerve examination was significant for a lively gag reflex. power was preserved in the arms and legs, with symmetry. her deep tendon reflexes were lively in the arms and legs, with a negative plantar extensor response bilaterally. of note, stereognosis and graphesthesia were preserved in the hands. due to her dementia presentation and clinical findings of lower half parkinsonism, an mri scan of the brain was obtained revealing severe subcortical white matter disease ( figure ). susceptibility weighted images (swi) and phase map images reveal cerebral micro-bleeds (mcbs), more than five lesions; note hypo-intensity of bleeds on both sequences implying a right-handed reference frame ( figure ). cmbs and betraying the right-handed reference frame of the mri system (red arrows). these images look similar but are different acquisition sequences; note difference in peri-ventricular white matter intensity between both sequences (yellow arrow). mri: magnetic resonance imaging; cmb: cerebral micro-bleeds; swi: susceptibility weighted images. a carotid duplex scan and a transcranial doppler ultrasound did not reveal any significant cervical carotid or intra-cranial artery stenosis respectively. she has stable coronary artery disease and more than five cmbs on susceptibility mri of the brain. hence one faces a therapeutic dilemma; with such extensive cerebral white matter disease and stable coronary artery disease, is anti-platelet therapy warranted in the presence of more than five cmbs? our solution was to continue the statin, atorvastatin mg and aspirin mg daily for the following reasons. we considered substituting cilostazol, an anti-platelet phosphodiesterase inhibitor for aspirin, as we do know that when cilostazol is compared with aspirin, the risk of cerebral and gastrointestinal hemorrhage is lower, with a . % relative risk reduction of ischemic strokes, but only in patients with prior ischemic strokes [ ] . however, there is no data for the effectiveness of cilostazol in stable coronary artery disease. we decided to continue low dose aspirin therapy in order to protect her coronary arteries. we continued statin therapy, atorvastatin mg daily, as this too has anti-thrombotic effects on both the coronary and cerebral circulation. she was encouraged to quit smoking. for her cognitive impairment, the patient was started on an acetylcholine-esterase inhibitor, donepezil mg daily. the risk of an ischemic or hemorrhagic stroke in patients with less than five or more than five cmbs, treated with antiplatelets, will be outlined in the discussion section. as outlined earlier, cmbs are radiologically small round or ovoid regions of signal loss seen on paramagnetic mri sequences. cmbs are due to hemosiderin-laden macrophages. cmbs are a direct result of extravasation of erythrocytes from diseased arterioles and capillaries damaged by hypertension, such as the small perforating arteries of the deep gray and white matter, in the basal ganglia and the lobar regions. in caucasians with intracerebral hemorrhage, cmbs in a lobar distribution are associated with cerebral amyloid angiopathy (caa). caa leads to progressive deposition of β-amyloid in small cortical and leptomeningeal arterial walls, increasing their fragility [ , ] . lipohyalinosis, also known as fibrinoid necrosis, occurs in small vessels in hypertensives, affecting deep perforating arteries, which branch off from large arteries in the basal ganglia, white matter, brain stem and cerebellum. the fibrinoid deposition in the tunica media of the blood vessel wall is due to blood-brain barrier disruption leading to destruction of smooth muscles and the extracellular matrix. this leads to the formation of micro-aneurysms and micro-hemorrhages. hyaline arteriolosclerosis is characterized by thickening of the arteriolar wall by collagen deposits around the basement membrane, leading to fragility and cmbs [ , ] . the pathologic and radiologic findings of cmbs are summarized below ( table ) . size of lesion < millimeters; round or ovoid microbleed -extravasation of erythrocytes hyperintensity on gre/swi in patients with cerebral amyloid angiopathy (caa), the prevalence of cmbs is %. the distribution of cmbs in caa is lobar, mirroring the histopathology of amyloid angiopathy in cortical vessels. this lobar pattern is also seen in alzheimer's disease. involvement of the leptomeningeal vessels explains the occurrence of superficial siderosis that is observed in both caa and alzheimer's disease [ ] . cmbs also occur more frequently in patients with vascular dementia displaying a more central distribution pattern, and may involve the thalamus, brainstem and cerebellum [ ] . in diffuse axonal injury, cmbs are typically located in the corpus callosum and at the gray-white matter junction, and tend to have a more radial configuration following the perivascular spaces compared with the more spherical cmbs occurring with neurodegeneration or hypertension [ ] . radiation vascular injury begins above a dose of grays (gy). it can acutely involve the small vessels, through fibrinoid necrosis and telangiectasis with vessel permeability and vasogenic edema. chronically, the larger vessels are affected with vessel wall thickening, thrombosis and fibrinoid necrosis. cmbs occur in at least % of patients who have undergone radiation treatment, in pediatric and adult patients. the rate of cmb formation increases significantly two years after radiation treatment and is associated with cognitive impairment [ ] [ ] [ ] . cavernous angiomas have a popcorn-like high signal intensity on t -weighted images and a hypo-intense hemosiderin ring on t -weighted images. small type iv cavernous angiomas may be indistinguishable from cmbs. cavernous angiomas can be classified into four types: type i -extra-lesional blood beyond cavernous angioma; type ii -mixture of subacute and chronic blood; type iii -area of hemosiderin with a small central core; and type iv -area of hemosiderin deposition without a central core. because of a lack of a central core, type iv lesions are only visible on swi images as hypo-intense spots, identical with cmbs [ ] , type iv lesions being the most similar to cmbs. swi hypo-intensity and t hyper-intensity have been deployed to detect micro-metastases. these signal characteristics are five times more common in melanoma metastases than in lung cancer metastases. three quarters of melanoma metastases have one or the other signal characteristic and a quarter have both findings. this combination of findings was sixteen times more common with melanoma metastases than with lung cancer metastases. melanin leads to t shortening and the propensity of melanomas bleeding, with methemoglobin accumulation, can lead to t shortening. the susceptibility effects on swi are due to the presence of metal ions: iron, copper, manganese, and zinc. of note, % of melanomas had no t shortening and were only detected with swi [ ] . there are strong associations of cmbs with age and hypertension, more likely deep in the brain. carrying the apo-lipoprotein e (apo e ) gene increases the risk of lobar cmbs most frequently in the parietal lobes [ ] . cmbs are strongly correlated with volume of white matter disease [ ] . the presence and number of cmbs also correlates with the congestive heart failure/left ventricular systolic dysfunction, hypertension, age ≥ years, diabetes mellitus, stroke or tia or thromboembolism, vascular disease (chads -vasc) scores, which is used to estimate ischemic stroke risk in patients with atrial fibrillation. in a study of japanese patients with atrial fibrillation and controls without atrial fibrillation, patients with atrial fibrillation had a significantly higher prevalence of cmbs. there is also evidence that lobar cmbs may be more common than deep cmbs in patients with atrial fibrillation [ ] . the various causes of cmbs with their topography and mechanisms are listed below ( table ) . knudsen et al. [ in the study by lau et al., in patients who were prescribed anti-platelet therapy, the five-year risk of recurrent ischemic stroke and hemorrhagic stroke both increased with the number of cmbs [ ] . high cmb burden, greater than or equal to five, was an independent risk factor for recurrent ischemic stroke, hemorrhage stroke, all cause mortality, and nonvascular death. patients with greater than or equal to five cmbs experienced a three-fold higher risk of recurrent ischemic stroke and a -fold increased risk of hemorrhagic stroke than those without cmbs. for the patients with less than five cmbs, the five-year absolute risk of ischemic stroke was much higher than the incidence of intracranial hemorrhage. for those with greater than or equal to five cmbs, the risk of fatal and disabling ischemic and hemorrhagic strokes was similar in the first year, but this calculus changed from the second to fifth year, where the risk of a hemorrhagic stroke was much higher, almost times higher [ ] . in summary, cmbs are associated with a higher risk of ischemic strokes than hemorrhagic strokes during the first year, regardless of the number of cmbs and treatment with anti-platelets is recommended, if indicated. for more than or equal to five cmbs, this issue is still contentious, as a head to head study is not available. however, withdrawal of anti-platelet therapy may be considered depending on the risk profile. these findings are summarized below ( table ) . findings suggest that anti-platelet use is safe when cmb number is below five, but questionable when cmb number exceeds five from year two to year five [ ] . our case highlights the dilemma the clinician faces in patients who carry more than five cmbs on an mri of the brain and who have co-existent co-morbid diseases, such as coronary artery disease. as we highlight in the discussion section, anti-platelet therapy in patients who harbor more than five cmbs can be associated with as high as a -fold increased risk of an intracranial bleed, especially in those patients who are receiving anti-platelet therapy for more than one year. we tackle this therapeutic conundrum by considering an alternative therapy with cilostazol, a phosphodiesterase inhibitor, which is less likely to lead to an intracranial bleed. however, this approach was deemed insoluble, as there is no evidence for the effectiveness of cilostazol for coronary artery disease. the literature of cmbs is extensive. in this article, we streamline a lot of the data and address the key points. in particular, we unravel the radiological signature of cmbs, its pathophysiologic correlates, outline the risk factors and common diseases associated with cmbs and at the end of the discussion we address the risk of ischemic and hemorrhagic strokes in patients with cmbs who are receiving anti-platelet therapy. human subjects: consent was obtained by all participants in this study. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. cerebral microbleeds: histopathological correlation of neuroimaging prevalence and risk factors of cerebral microbleeds: an update of the rotterdam scan study cerebral microbleeds and recurrent stroke risk: systematic review and meta-analysis of prospective ischemic stroke and transient ischemic attack cohorts cerebral microbleeds: imaging and clinical significance cerebral microbleeds: a guide to detection and interpretation antiplatelet treatment after transient ischemic attack and ischemic stroke in patients with cerebral microbleeds in large cohorts and an updated systematic review benefit of cilostazol in patients with high risk of bleeding: subanalysis of cilostazol stroke prevention study fibrinoid necrosis of small brain arteries and arterioles and miliary aneurysms as causes of hypertensive hemorrhage: a critical reappraisal stroke patients with cerebral microbleeds on mri scans have arteriolosclerosis as well as systemic atherosclerosis clinical diagnosis of cerebral amyloid angiopathy: validation of the boston criteria use of antithrombotic drugs and the presence of cerebral microbleeds: the rotterdam scan study the difference in location between traumatic cerebral microbleeds and microangiopathic microbleeds associated with stroke -tesla susceptibility-weighted imaging to assess the effects of radiotherapy on normal-appearing brain in patients with glioma radiation-induced microbleeds after cranial irradiation: evaluation by phase-sensitive magnetic resonance imaging with . tesla presence of cerebral microbleeds is associated with worse executive function in pediatric brain tumor survivors the natural history of familial cavernous malformations: results of an ongoing study improved detection of metastatic melanoma by t *-weighted imaging white matter lesion progression in ladis: frequency, clinical effects, and sample size calculations cerebral microbleeds and asymptomatic cerebral infarctions in patients with atrial fibrillation covid- is associated with an unusual pattern of brain microbleeds in critically ill patients (preprint) key: cord- -x sobzyw authors: mohakud, nirmal k; yerru, hari; rajguru, monalisha; naik, sushree s title: an assumed vertical transmission of sars-cov- during pregnancy: a case report and review of literature date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: x sobzyw the ongoing coronavirus disease (covid- ) pandemic caused by severe acute respiratory syndrome coronavirus (sars-cov- ) has affected persons of all ages, including the newborns. few published case reports and case series have described the possibility of vertical transmission of covid- . in the present report, we describe a young primigravida at weeks of gestation, who presented with a four-day history of low-grade fever, malaise, and breathing difficulty. she underwent testing of nasopharyngeal swab sample by real-time polymerase chain reaction (rt-pcr), which was positive for covid- . cesarean section was done, and a preterm low birthweight baby was delivered. the baby required resuscitation at birth and was mechanically ventilated for a shorter duration. a tracheal aspirate that was taken at hours of life tested positive for covid- . the course and outcome of the newborn are described here along with the possibility of vertical transmission. the ongoing coronavirus disease (covid- ) pandemic caused by severe acute respiratory syndrome coronavirus (sars-cov- ) has affected persons of all ages, including the newborns [ ] . few published case reports and case series have described the newborns affected with covid- [ , ] . in these publications, assumptions have been made (vertical vs horizontal) regarding the mode of transmission from the infected mothers. although few publications have suggested a vertical (in utero) transmission, others have refuted this mechanism, and instead, emphasize a horizontal mode of transmission [ ] [ ] [ ] [ ] [ ] . in the present report, we describe a premature newborn, who was born to a primigravida mother with hellp (hemolysis, elevated liver enzymes, and low platelet count) syndrome and moderate covid- pneumonia. the newborn tested positive at hours of life for covid- by real-time polymerase chain reaction (rt-pcr) of the tracheal aspirate sample [ ] . it has to be noted that hellp syndrome is a serious complication in pregnancy that occurs in . %- . % of all pregnancies, and in %- % of severe pre-eclampsia cases [ ] . a primigravida aged years under quarantine complained of sore throat, low-grade fever, and malaise. she got tested and found positive for covid- . after two to three days, she developed breathing difficulty, decreased fetal movements, edema, and visual disturbance. finally, she got referred to us for the subsequent management of her illness. she had already received two doses of tt (tetanus toxoid) injections and was on vitamin and mineral supplements (iron/folic acid and calcium tablets) regularly. she was also taking thyroxine tablet ( µg) once daily for hypothyroidism. she developed hypertension in the second month of pregnancy. ultrasound done at weeks of gestation revealed a single, live fetus (weight = g), and the amniotic fluid index (afi) was . she was conscious at admission with the following vital parameters: temperature . ˚f, pulse rate /min, respiratory rate /min, and blood pressure / mmhg. general examination showed pallor, edema, and icterus. there was ml of bloody urine in the urinary bag. she was finally diagnosed to have hellp syndrome with hypothyroidism and moderate covid- pneumonia ( table ) [ ] . the newborn threw a seizure after two hours for which relevant investigations were done ( injection phenobarbitone was started along with intravenous antibiotics (cefotaxime plus amikacin). there was no further recurrence of seizure. as the condition of the newborn improved, he was extubated to continuous positive airway pressure (cpap) after hours of mechanical ventilation. rt-pcr of the tracheal aspirate sample that was taken after hours found positive for covid- . however, he showed consistent improvement, was weaned off oxygen, and discharged in a healthy condition. while reviewing the literature, we could find a few published case reports and case series on neonatal sars-cov- (covid- ) infection. the authors in one review reported cases of newborns tested positive at birth, whose mothers were infected in the third trimester of pregnancy [ ] . the time interval (mean, between delivery, and infection) was three days (range, - ). the rt-pcr was negative when performed on cord blood and amniotic fluid. however, covid- was tested positive in the nasopharyngeal samples of only six newborns: (at hours of life), (at hours of life), and (at hours of life). the authors kept following possibilities in their review of these cases: contact with infected parents or healthcare professionals (transmission at birth) or via breastfeeding, and droplet inhalation. however, these newborns were born through cesarean delivery, separated immediately from their mothers, and instead placed in another room for isolation. in addition, it has to be remembered that breast milk does not transmit covid- [ ] . therefore, vertical transmission (transplacental/in utero) remains a possibility, which is difficult to rule out [ ] . similarly, in the index case, the mother was possibly infected in the third trimester and underwent a cesarean section. the newborn was transferred to the neonatal icu without contact with his mother. to date, there is a lack of clarity regarding the criteria of congenital covid- infection. the authors of one study described that three newborns born to mothers with covid- infection had positive antibodies (igm and igg) at birth [ , ] . whether they need to be labeled as congenital infections (vertical transmission) is debated (because igm antibodies do not cross the placenta) [ ] . in a case series including newborns, tested positive for covid- by rt-pcr of nasopharyngeal and anal swab samples on day and day of life. they developed severe pneumonia [ ] . the authors were not sure about the timing of transmission (perinatal or postnatal), as they were born by cesarean section, like the index case, and were immediately separated from the mothers. in the present report, the index newborn was tested positive at hours of life without any features of symptomatic covid- infection [ ] . published studies have shown that maternal covid- infection can cause premature delivery, respiratory distress, and intrauterine fetal death [ , , ] . these complications result from severe hypoxemia as a result of pneumonia in the mother. in the present report, decreased fetal movement and perinatal asphyxia could be explained by these factors as the mother had moderate covid- pneumonia with hellp syndrome. the present report has some limitations. due to lack of logistics, the presence of the covid- virus was not confirmed in body fluids (amniotic fluid, cord blood) or tissue specimens (placental tissue) that might have further clarified the mode of transmission. in addition, covid- antibody testing also could not be performed in the newborn. our report shows that covid- infection may possibly get transmitted vertically to the fetus. more research is needed to better elucidate the mechanisms involved in this process. human subjects: consent was obtained by all participants in this study. issued approval na. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. china novel coronavirus investigating and research team: a novel coronavirus from patients with pneumonia in china effects of coronavirus disease (covid- ) on maternal, perinatal and neonatal outcomes: a systematic review clinical presentation and outcomes of pregnant women with covid- : a systematic review and meta-analysis severe covid- during pregnancy and possible vertical transmission evidence and possible mechanisms of rare maternal-fetal transmission of sars-cov- antibodies in infants born to mothers with covid- pneumonia possible vertical transmission of sars-cov- from an infected mother to her newborn neonatal early-onset infection with sars-cov- in neonates born to mothers with covid- in wuhan, china a neonate born to mother with covid- during pregnancy & hellp syndrome: a possible vertical transmission hellp syndrome: understanding and management of a pregnancy-specific disease clinical characteristics of neonates born to mothers with covid- coronavirus disease in neonates: what is known and what needs to be known. cureus. we are thankful to dr. shlok saxena, dr. srinitya kollu, and dr. mirabai das for their help during the case management and providing inputs to our case. key: cord- -ofph ac authors: chegondi, madhuradhar; kothari, harsh; chacham, swathi; badheka, aditya title: coronavirus disease (covid- ) associated with febrile status epilepticus in a child date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ofph ac infection associated with the novel severe acute respiratory syndrome coronavirus (sars-cov- ) has been named coronavirus disease (covid- ). the emerging literature suggests that sars-cov- infection affects children of all age groups. covid- as a cause of febrile seizures and status epilepticus is not yet reported in children. we report the case of a two-year-old child who presented to our pediatric intensive care unit with febrile status epilepticus and was diagnosed to have covid- infection. the child recovered fully and was discharged home after three days. the novel severe acute respiratory syndrome coronavirus (sars-cov- ) emerged in wuhan city, hubei province, china, in december . infection associated with it was named coronavirus disease . ever since the first case was identified, covid- rampantly spread all over the world and resulted in more than million cases and , deaths globally [ ] . the emerging literature suggests that the sars-cov- infection can affect children, including all age groups, predominantly males, and cause milder disease compared to adult patients [ , ] . in the united states, . % of all confirmed covid- cases are children (≤ years), and %- % of them were hospitalized [ ] . recently, two pediatric covid- cases were reported with afebrile seizures [ , ] . however, covid- as a cause of febrile seizures and status epilepticus has not yet been reported. we report the case of a two-year-old child who presented to our pediatric intensive care unit (picu) with febrile status epilepticus and was diagnosed to have covid- infection. a two-year-old, previously healthy female was transferred from a community hospital emergency department (ed) to our picu with new-onset febrile seizure that presented as status epilepticus. the child started with a tactile fever and reduced oral intake a few hours earlier on the day of admission. her parents took her to the local ed, where she was noted to have a temperature of . °c with generalized tonic-clonic seizures. an intravenous (iv) access was established, and the patient received a dose of lorazepam. furthermore, she was given four more doses of lorazepam and levetiracetam to abort seizures. after that she was noted to have respiratory depression and oxygen desaturation. she was endotracheally intubated with propofol and rocuronium and placed on a mechanical ventilator. given the ongoing covid- pandemic, appropriate personal protective measures were taken during the endotracheal intubation. the patient also received a dose of iv acetaminophen and one normal saline bolus ml/kg for borderline blood pressure post-intubation. infectious workup was pursued in the setting of febrile seizure, and screening labs were obtained. blood culture and urine culture were collected, and a dose of ceftriaxone mg/kg was given. ethanol, salicylate, and acetaminophen levels were normal. her urine drug screen was negative. her complete blood count showed leukocytosis with a white cell count of . × /µl, neutrophil predominance, and microcytic anemia. she had no thrombocytopenia or lymphopenia. her c-reactive protein was mildly elevated at . mg/dl; her electrolytes, blood glucose, urea, creatinine, and liver function test were unremarkable. her lactic acid was elevated at mmol/l. the urine analysis showed mild ketones and protein without evidence of urinary tract infection. the respiratory viral panel was negative. covid- testing was sent, and the result was pending. a ct image of the brain was normal. per the parent report, the child is fully immunized and did not have nasal congestion, cough, or gastrointestinal symptoms. the parents denied seizures or covid- exposure in the family. however, her father had cough and congestion for the previous few days and was not tested for covid- . the patient was transferred to our picu on propofol infusion. upon arrival to picu, she was appropriately sedated on the mechanical ventilator, and was normothermic, with stable hemodynamics. the child was able to move all extremities in deep stimulation, and her bilateral pupils were equal and reactive to light. admission blood gas and repeat lactate were normal, and her chest x-ray showed patchy infiltrates bilaterally (figure ). a repeat nasopharyngeal swab using real-time polymerase chain reaction for covid- was sent and returned positive. within two hours following admission, the child had a recurrence of seizure, which was aborted with a dose of lorazepam and a loading dose of fosphenytoin. the neurology service was consulted, and the patient was started on maintenance levetiracetam. the child was kept on continuous electroencephalogram (ceeg) monitoring for hours. ceeg showed generalized slowing without recurrence of seizures. a lumbar puncture was performed, and cerebrospinal fluid (csf) was sent for analysis. csf showed one nucleated cell per mm , less than red blood cells per mm , protein mg/dl, and glucose mg/dl. the csf viral meningitis and encephalitis panel was negative. due to testing restrictions, we were unable to send for covid- testing in csf or serology. the patient was continued on ceftriaxone, and vancomycin was added. on day of the picu stay, she was extubated under deep sedation to nasal cannula oxygen, and then was gradually weaned off to ambient air. she remained afebrile throughout her picu stay, and antibiotics were discontinued as -hour cultures were negative. the child was discharged the following day on levetiracetam maintenance and advised to follow up with the neurology outpatient clinic in two weeks. the sars-cov- virus is one of the beta coronaviruses, which also includes severe acute respiratory syndrome virus (sars-cov), the middle eastern respiratory syndrome (mers) virus, hcov-hku , and hcov-oc [ ] . alpha coronaviruses include hcov- e and hcov-nl [ ] . among human coronaviruses (hcovs), hcov- e, -oc , -nl , and -hku strains are endemic worldwide [ ] . hcovs mostly cause upper respiratory tract illness (urti) and can cause severe lower respiratory tract illness in children with underlying comorbidities. however, in covid- cases, urti is less frequent [ ] . among pediatric covid- cases in the united states, fever and cough present in % and % of the cases, respectively, and intensive care admission was required in . % of them [ , ] . in children, the extrapulmonary manifestations of hcov include acute gastroenteritis, myocarditis, and multi-organ failure [ ] . hcov-associated neurological features include meningitis, encephalitis, acute flaccid paralysis, acute disseminated encephalomyelitis, and refractory status epilepticus [ , ] . among the coronaviruses, hcov-hku has been reported as a common cause of febrile seizures in children [ ] . neurological involvement in covid- patients has been described. a retrospective study from china reported that common neurological symptoms in adult patients with covid- include headache, dizziness, and rarely seizures [ ] . karimi et al. reported frequent seizures in a young adult with covid- [ ] . in pediatric covid- cases, headache is less frequently reported compared to adult patients [ ] . however, as we were writing this case report, we could not find febrile seizures in children that were associated with covid- , though afebrile seizures were reported [ , ] . the possible mechanisms of coronavirus-associated neurological manifestations are direct virus invasion and effect of inflammatory mediators [ ] . a study by huang et al. reported that covid- is associated with cytokine storm, and these cytokines might result in neuronal excitability and seizures [ ] . it has been shown that hcov-o ,- e, and sars-cov are neuroinvasive [ , ] . fatal encephalitis has been described with hcov-oc in immunocompromised children [ , ] . in these children, the csf analysis was negative, but the brain biopsy rna sequencing was positive for hcov-oc . however, in our index case, csf was normal, and rapid improvement in sensorium suggests that covid- -associated encephalitis is unlikely. due to limited covid- testing capability, we could not check the csf for sars-cov- . in children, covid- incidence is lower, and severe disease is rare compared to adults. the majority of children with covid- present with cough and fever. febrile seizures have been described with hcov infections in children, especially with hcov-hku . our index case illustrates that sars-cov- associated covid- can present with febrile seizure and febrile status epilepticus in children. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. johns hopkins coronavirus covid- resource center chinese pediatric novel coronavirus study team: sars-cov- infection in children epidemiology of covid- among children in china cdc covid- response team: coronavirus disease in children-united states covid- precipitating status epilepticus in a pediatric patient new-onset seizure as the only presentation in a child with covid- international committee on taxonomy of viruses human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system clinical features of patients infected with novel coronavirus in wuhan, china. lancet. neurologic manifestations of severe respiratory viral contagions coronavirus hku and other coronavirus infections in hong kong neurological manifestations of hospitalized patients with covid- in wuhan, china frequent convulsive seizures in an adult patient with covid- : a case report effects of coronavirus infections in children fatal encephalitis associated with coronavirus oc in an immunocompromised child human coronavirus oc associated with fatal encephalitis key: cord- -n c m hn authors: choudhury, ivana; han, haowei; manthani, kaushik; gandhi, sandeep; dabhi, rameshchandra title: covid- as a possible cause of functional exhaustion of cd and cd t-cells and persistent cause of methicillin-sensitive staphylococcus aureus bacteremia date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: n c m hn we report a case of a -year-old male with a history of diabetes mellitus, osteomyelitis, methicillin-sensitive staphylococcus aureus (mssa) bacteremia who recently completed an extended intravenous course of cefazolin eight days back, and presented with mssa bacteremia complicated by epidural abscess, endocarditis, and aortic root abscess. meanwhile, the patient was tested positive for severe acute respiratory syndrome coronavirus (sars-cov- ) by reverse transcription-polymerase chain reaction (rt-pcr). even with aggressive antibiotic treatment, the patient remained bacteremic and developed endocarditis with a worsening aortic root abscess. we suspect coronavirus disease (covid- ) as a cause for the infectious paradox and will discuss the possible mechanisms in this case report. the current coronavirus disease (covid- ) pandemic has burdened the modern health care system. similar to severe acute respiratory syndrome coronavirus (sars-cov) and the middle east respiratory syndrome (mers), sars-cov- is primarily known to cause ailments to the human respiratory system. other complications have been reported, including cardiovascular disease, renal failure, and sequelae of a hypercoagulable state [ ] [ ] [ ] . to our current knowledge, there is sparse clinical evidence suggesting the correlation between covid- infection and its effect on the human immune system, making patients more susceptible to certain infections. although cytokines and immune regulation are vital for body response to infection, dysregulation or excessive responses may cause harm. there is a positive correlation between cytokine storm and disease severity. high expression of th and th cytokines has been detected in covid- patients which accounts for acute respiratory distress syndrome (ards), multi-systemic organ failure, and high rate of mortality and morbidity [ ] . however, the correlation between covid- immune exhaustion and mortalities from infectious etiologies have not been extensively reported to date. a -year-old male recently treated for methicillin-sensitive staphylococcus aureus (mssa) bacteremia secondary to presumed source of non-healing diabetic foot ulcer (completed a six weeks course of intravenous (iv) cefazolin eight days ago, negative transesophageal echocardiogram (tee)) presented to our emergency department with lower back pain with extension to the left flank region, urinary incontinence, and an altered mental status. other past medical and past surgical history was remarkable for diabetes mellitus, chronic foot osteomyelitis, aortic stenosis (status post transcatheter aortic valve replacement (tavr) in later replaced with a bioprosthetic aortic valve (bavr) in ), and persistent atrial fibrillation (on warfarin). initial vital signs: temperature: . °f, blood pressure: / mmhg, pulse: beats/min, respiratory rate: /min, oxygen saturation: % on room air. physical exam was significant for two right lower extremity foot ulcers that did not have any surrounding erythema, necrosis or other signs of infection. no splinter hemorrhage, osler's nodes, or janeway lesions were noted. laboratory results were as follows: white blood cell (wbc) count: . ( ^ /µl) with neutrophilia, glucose: mg/dl, magnesium: . mg/dl, lactate: . mg/dl, aspartate transaminase: units/l, erythrocyte sedimentation rate: mm/hr, c-reactive protein: . mg/l, procalcitonin: . ng/ml. urinalysis was remarkable for large blood, protein, negative wbc esterase, nitrite, and but had few bacteria. computer tomography (ct) of the abdomen/pelvis revealed possible recent passing of a stone, cystitis, and pyelonephritis. the patient was admitted to the hospital for additional workup. due to concern of multi-drug resistant infections, iv vancomycin and piperacillin/tazobactam were initiated, as well as iv fluids per sepsis protocol. meanwhile, the patient was also found to be positive for sars-cov- by reverse transcription-polymerase chain reaction (rt-pcr) during admission and was started on a course of hydroxychloroquine. his blood cultures grew mssa, and the patient was restarted on iv cefazolin subsequently. the patient's initial transthoracic echocardiogram (tte) was remarkable for a bioprosthetic aortic valve with normal mobility (figure ). per the modified duke's criteria for diagnosing infective endocarditis (ie), the patient met one major criteria (positive blood cultures), which gives him a diagnosis of definite ie. upon reviewing the patient's tee two weeks prior at the other facility, there was no evidence of cardiac valve vegetation, and the patient had a normal ejection fraction. daily blood cultures continued to grow mssa and hence, the antibiotic was changed to iv daptomycin. magnetic resonance imaging (mri) of the lumbar spine (l-spine) revealed an epidural abscess and concurrent osteomyelitis at the vertebral levels of l -l ( figure ). surgical intervention was not pursued due to the patient's positive covid infection and underlying comorbidities. a repeat tte performed several days later revealed vegetation on a bioprosthetic aortic valve (as seen in figure ) with periannular abscess extending up to the root and ascending aorta ( figure ). according to modified duke's criteria, the patient now met two major criteria for definitive ie (echocardiographic evidence of vegetation on the bioprosthetic aortic valve, and two positive blood cultures indicative of ie). oral rifampin was added to the iv daptomycin. the day when oral rifampin was added, the patient's blood cultures showed no growth of bacteria. therefore it is unknown if rifampin played a role in the patient's clearance of mssa from the blood. during his hospital stay, the patient then retested positive for covid- , and was started on oral ciprofloxacin and iv ceftaroline. several days later, the patient tested negative for covid- . a repeat mri l-spine revealed marginal improvement of the epidural abscess. the patient was discharged to subacute rehabilitation with oral rifampin and iv daptomycin. unfortunately, two weeks later the patient was readmitted for chest pain, and tte revealed an increase in the size of the aortic root abscess with new-onset systolic dysfunction (ejection fraction of %) ( figure ). due to the extensive risks associated with surgical management of the abscess and replacement of the valve, the patient and his family determined that hospice care was most appropriate. spinal epidural abscess (sea) is an uncommon pyogenic infection of the central nervous system primarily affecting patients above years and is primarily treated with surgical decompression and abscess drainage along with prolonged antibiotic therapy [ , ] . risk factors include alcohol abuse, obesity, chronic kidney disease, diabetes mellitus, injection drug use, or indwelling catheter use [ ] . clinical manifestations of sea include back pain (nontraumatic or traumatic), neck pain, paresthesia, radiculopathy, focal neurological deficits, bowel or bladder incontinence, fevers, acute mental status changes [ ] . in a retrospective, case-control study measuring patients diagnosed with sea, all portions of the vertebral spine may be affected, with the majority of cases occurring in the lumbar spine. in this study, . % of all cases only received antibiotic therapy, while % underwent neurological drainage and debridement of the sea [ ] . empirical antibiotics should cover mssa, methicillin-resistant staphylococcus aureus (mrsa), and streptococci [ ] . meanwhile, despite receiving iv antibiotics, our patient progressed into aortic valve abscess and endocarditis. in one prospective cohort study involving patients, prosthetic valve endocarditis (pve) is present % of the time in patients with ie. the most common causative organism is staphylococcus aureus ( % of patients), followed by coagulase-negative staphylococcus ( . % of patients) [ ] . health care-associated pve occurred in . % of patients in this cohort study, while % of health care-associated pve occurred within the first year of tavr placement [ ] . it was also found that persistent bacteremia or a hospital-acquired nosocomial infection is strongly linked with staphylococcus aureus ie, with nosocomial infection defined as developing ie after hours of hospitalization with no previous signs or symptoms of ie [ ] . despite having a negative tte and tee prior to visualizing the pve, it is important to note that persistent mssa bacteremia was likely the strongest risk factor in his development of a pve. however, it is important to discuss if the patient's positive covid- infection played a role in his immune system's ability to fight off the mssa infection. in one prospective study of patients, patients with ie associated with mssa infection significantly had a higher rate of major embolism than mrsa patients, as well as a significantly more unknown origin of bacteremia [ ] . ie complicated mrsa infection is usually associated with nosocomial origin, surgical site infection, prior surgery within six months, or persistent bacteremia in the setting of a catheter [ ] . however, the mortality rate was higher in patients with mrsa than in patients with mssa. to protect itself from the host's immune system, bacteria can protect itself with biofilm formation on an implanted or indwelling device, particularly staphylococcus aureus and staphylococcus epidermis [ , ] . while it does not have proven efficacy against biofilmencoated bacteria, rifampin may adequately penetrate biofilms while reducing the adherence of bacteria to surfaces [ ] . while rifampin is not recommended under american heart association guidelines for the treatment of ie, one retrospective cohort study involving patients found that many clinicians are more likely to add rifampin to the standard antibiotic therapy for the treatment of mssa ie in patients who have prolonged bacteremia or appear severely ill [ ] . multiple recent clinical trials in vitro suggest that covid- causes a functional exhaustion of cluster of differentiation (cd) t-cells and natural killer (nk) cells due to persistent stimulation from the virus, thus inducing t-cell exhaustion [ ] [ ] [ ] . a retrospective study in wuhan, china found that patients in the intensive care unit (icu) confirmed to have covid- had markedly reduced cd and cd t-cells [ ] . cytotoxic t lymphocytes (ctl) are part of the immune system response that play a role against viral pathogens. cd t-cells secrete interferons (ifn-γ), perforin and granzymes to eradicate viruses, while cd + helper t cells enhance cd cells and b cells to help them clear the viral pathogen [ , ] . cd cells are vital to the role of cd t-cells and b-cells for cellular and humoral immune responses, so in patients with cancer or chronic infections, both cd and cd t-cells can become exhausted and lose function [ ] . for a patient with mssa bacteremia and covid- , such as ours, cd and cd tcell functional exhaustion may be why our patient required an extended course of iv antibiotic therapy. unfortunately, we didn't check this patient's cd /cd counts during his hospital course. while further research is needed, it is important to monitor a covid- positive patient being treated for bacteremia, spinal epidural abscess, or cardiac valvular vegetations, as covid- may cause an immunocompromised state, thus making the patient more susceptible to bacterial infections. overall, this patient presented with recurrent bacteremia and multiple organ infections. although the diabetic ulcers may have served as the source of the mssa infection, due to the noninfectious site of the wound, we suspect that the cause is a reactivated bacteremia due to a dual immunocompromised state secondary to diabetes mellitus and covid- . we suspect this because it is unusual to have a pve after months of a bioprosthetic aortic valve replacement, and it is also unusual to have multiple abscesses occur eight days after stopping iv antibiotics. our patient presented with a recurrent and persistent mssa bacteremia and osteomyelitis, complicated by a spinal epidural abscess, bioprosthetic valve endocarditis and aortic root abscess despite appropriate antibiotic therapy. in covid- patients, we see many patients' hospital courses complicated by cytokine storms and end-stage organ failure. however, clinicians should remember that covid- causes an immunocompromised state due to the functional exhaustion of cd and cd t-cells. our case has suggested further research and observational studies into the correlation between covid- and other infectious processes. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. cardiovascular disease and covid- covid- and kidney failure in the acute care setting: our experience from seattle covid- update: covid- -associated coagulopathy the pathogenesis and treatment of the 'cytokine storm' in covid- a case of extensive epidural abscess concomitant with intracranial involvement due to staphylococcus aureus successfully treated with ceftriaxone in combination with linezolid and rifampin. eneurologicalsci spinal epidural abscess in adults: a -year clinical experience at a tertiary care academic medical center contemporary clinical profile and outcome of prosthetic valve endocarditis methicillinresistant versus methicillin-sensitive staphylococcus aureus infective endocarditis penetration of rifampin through staphylococcus epidermidis biofilms unpredictable effects of rifampin as an adjunctive agent in elimination of rifampin-susceptible and -resistant staphylococcus aureus strains grown in biofilms addition of rifampin to standard therapy for treatment of native valve infective endocarditis caused by staphylococcus aureus reduction and functional exhaustion of t cells in patients with coronavirus disease (covid- ) increased expression of cd marker on t-cells in covid- patients functional exhaustion of antiviral lymphocytes in covid- patients cd t-cell immunotherapy for chronic viral infections and cancer key: cord- - aeqe fh authors: passerini, matteo; terzi, roberta; piscaglia, marco; passerini, simone; piconi, stefania title: disseminated cryptococcosis in a patient with metastatic prostate cancer who died in the coronavirus disease (covid- ) outbreak date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: aeqe fh we report the case of a -year-old patient with a history of prostate cancer affected by bone metastasis. he presented to our attention for ulcerous and necrotic cutaneous lesions unresponsive to antibiotics. the spread of cutaneous lesions and the onset of neurological symptoms suggested a cryptococcal disease, which was confirmed by lumbar puncture and cutaneous biopsy. we present the diagnostic and therapeutic approach to this case. cryptococcosis is an invasive fungal infection due to cryptococcus neoformans or cryptococcus gattii; the former is the principal pathogenic member of the genus and has a worldwide distribution [ ] . cryptococcosis is typical of immunocompromised patients, and among them historically hivpositive patients, but there are some reports of presumed immunocompetent patients [ , ] . this disease can affect different organs: meningoencephalitis is the most described manifestation followed by pulmonary and cutaneous disease. the clinical presentation is heterogeneous, ranging from a mild disease to a life-threatening condition. it often presents with a subacute course with a delayed diagnosis, especially if a patient has various comorbidities. a -year-old male patient affected by stage iv prostate cancer with bone metastasis at diagnosis presented to our wound care clinic complaining of ulcers on the right forearm that appeared two weeks prior following a referred domestic trauma. during the physical examination, we observed two ulcers on the right forearm: a cm x cm proximal posterior ulcer covered by fibrin and a -cm proximal anterior ulcer with odorous exudate. there was no presence of crackles on palpation of the area surrounding the ulcers. following a cutaneous swab, which resulted positive for unspecified yeast, the patient was admitted to our clinic. besides the aforementioned cancer disease, the patient's medical history included hypertension, cholelithiasis, colon-sigma diverticulosis, and a recent discharge from another hospital for sepsis, bladder rupture, and multifocal pneumonia without microbiological evidence, which were treated successfully with piperacillin/tazobactam. the patient's pharmacological therapy consisted of bicalutamide, high-dose dexamethasone ( mg a day for more than three months), oxycodone/naloxone, pregabalin, celecoxib, zoledronate, irbesartan, amlodipine, bisoprolol, proton pump inhibitors, and delorazepam. ct scan of the right forearm revealed an extended inflammation of the dermis and hypodermis and excluded any abscesses or signs of necrotizing fasciitis ( figure ). blood tests revealed the presence of moderate inflammation with a crp (c-reactive protein) of mg/l wbc (white blood cell) count of . x /l, creatinine of . mg/dl, and alt (alanine aminotransferase) of u/l. at the time of admission, the patient was afebrile. for the cutaneous lesion, empiric therapy was started with piperacillin/tazobactam . g every eight hours along with advanced dressings determined by the wound care physician. in the following days, we observed an extended loss of organic substance ( figure a) with a progressive expansion of the ulcers ( figures b, c ) despite the surgical curettage performed by the plastic surgeon and the advanced dressings performed by the wound care physician. initially, the lesions were only on the forearm (a) and then spread to the hand (red arrows) as papules (b), which became ulcers (c). note the progressive extension of the initial wound. nnegative-pressure wound therapy was started without success, and the cultured foam samples isolated methicillin-resistant staphylococcus aureus (panton-valentine negative). therefore, we initiated vancomycin g every hours plus meropenem g every hours followed by a course of daptomycin mg every hours for the isolation of vancomycin-resistant enterococcus in the rectal swab. despite the aforementioned therapy, the cutaneous lesion did not improve but instead advanced. two new cutaneous lesions manifested on the right hand and left thigh. both were red and non-tender papules and very similar to the initial presentation as reported by the patient prior to admission ( figure b ). subsequently, echocardiography excluded infectious endocarditis (video ) and an mri of the right arm excluded osteomyelitis ( figure ). to note, during hospitalization, blood tests showed only a minimal increase in the inflammation markers. in the following days, the patient complained of frequent episodes of confusion and tremor associated with an increasing headache. ct of the brain was negative, electroencephalogram showed a diffuse pattern of encephalopathic suffering, and the neurological examination performed by a specialist showed metabolic encephalopathy. due to the association between the failure of broad-spectrum antibiotics and the onset of neurological symptoms, especially headache, we performed a lumbar puncture ( table ) that isolated cryptococcus neoformans. the cryptococcal antigen on serum was positive, and a cutaneous biopsy of the ulcers confirmed the presence of the yeast. therefore, we started induction antifungal therapy with amphotericin b plus flucytosine and switched to consolidation therapy with fluconazole mg following a repeat of the lumbar puncture ( we observed a rapid improvement of the neurological signs and the healing of the lesion on the left thigh, which had not yet ulcerated. the ulcers on the right arm gradually improved and the patient was transferred to another hospital in order to undergo a skin filling with collagen and then a plastic surgery (figure ) with an autologous skin graft ( figure ) . the surgery was successful and the patient was then switched to a maintenance therapy with fluconazole mg from october . at the beginning of april , during the terrible outbreak of sars-cov- (severe acute respiratory syndrome coronavirus ), the patient, who lived in lombardy, where the largest epidemic outbreak has developed in italy, died after a respiratory failure. he presented no signs and symptoms of recrudescence of cutaneous and neurological cryptococcosis, but the cryptococcal antigen was still positive. up until now, most of the information we have regarding cryptococcosis is based on experience from hiv-positive patients. however, in recent years, thanks to the introduction of an effective antiretroviral therapy, hiv-positive patients have constituted an ever-smaller percentage of the total cases of cryptococcosis [ , ] . in a u.s. cohort study of patients diagnosed with cryptococcosis, ( %) were hivpositive, ( %) were transplant patients, and ( %) were nhnt (non-hiv, nontransplant patients) [ ] . nhnt patients constitute a heterogeneous group that includes patients ranging from seemingly healthy to heavily immunodepressed [ , ] . specific studies on this patient population are yet to be conducted due to both the high variability of the patients and their relatively recent increase in number. recent studies have shown how the clinical presentation and mortality of this group of patients is different from that of hiv-positive patients, to whom most clinicians are accustomed [ ] . in fact, these patients most frequently present with extra-meningeal manifestations, of which the most frequent is pulmonary; cases of skin, osteoarticular, and soft tissue infections have been reported. in a recent study of nhnt patients, ( %) had infections other than pulmonary, bloodstream, or central nervous system. these included cultures from skin (n = ), urine (n = ), joint aspirates (n = ), ascites (n = ), lymph node biopsy (n = ), bone biopsy (n = ), and ocular fluid (n = ) [ ] . there is no typical cutaneous lesion of cryptococcosis, but skin involvement is typically characterized by various non-specific presentations (e.g., papules, pustules, nodules, abscesses, edema, panniculitis, and ulcers) and can be due to a primary infection or due to a secondary systemic hematogenous spread [ ] [ ] [ ] . therefore, once a diagnosis is established, the infection of the brain and lungs must be excluded [ ] . our patient presented with two large and necrotic ulcers on his right forearm and was treated with broad-spectrum antibiotics. the initial cutaneous swabs detected an unspecified yeast, which was interpreted as a contamination. the association between the failure of different antibiotics and the onset of neurological symptoms suggested a form of encephalitis; therefore, we performed lumbar puncture in order to exclude an opportunistic infection. the studies cited above and the clinical course of our patient showed that cutaneous symptoms in an immunocompromised patient should always alert about the possibility of an opportunistic infection such as cryptococcosis. the failure of a broad-spectrum course of antibiotics and the onset of neurological signs can be further differentials in the diagnosis. furthermore, the immunological studies, such as peripheral blood lymphocyte typing and immunoglobulin tests, could be useful to inform clinical management and suspect an opportunist infection, even in immunosuppressed non-hiv patients. the domestic trauma, the extensive interval between the onset of the lesions and the first neurological sign (the headache was first noted days following admission), and the isolation of an unspecified yeast on the first skin swab would lead us to think that the port of entry of the infection was the skin. however, the scarce data that are present in the literature and the typically subacute course of a cryptococcal meningeal infection often lead a patient to overlook these neurological symptoms, especially if the patient has multiple co-morbidities. even if this case is suggestive of the skin being the primary infected organ, we cannot directly assume this. an important teaching we learnt from this case is the necessity of direct communication and case discussion between the clinician and the microbiologist in the lab for a more careful and thorough interpretation of contaminations versus true infections in the patient sample. this is particularly important if there is a high clinical suspicion of an opportunistic infection. the clinical case presented required a considerable expenditure of resources and energy. in fact, in search of a diagnosis, the hospitalization lasted several weeks consisting of the almost daily treatment with advanced dressings as well as the treatment of complications that arose during his stay. in addition, the follow-up was costly due to a long and difficult rehabilitation. the sudden death of this patient from respiratory failure during the coronavirus epidemic has been a further event in the recent weeks showing us the disparity between medical efforts and clinical results, causing us to put into question our work as healthcare professionals. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. microbiology and epidemiology of cryptococcus neoformans infection cryptococcosis in the era of aids-- years after the discovery of cryptococcus neoformans cryptococcosis in human immunodeficiency virusnegative patients in the era of effective azole therapy predictors of mortality and differences in clinical features among patients with cryptococcosis according to immune status cryptococcus neoformans empyema in a patient receiving ibrutinib for diffuse large b-cell lymphoma and a review of the literature cryptococcal infections in non-hiv-infected patients presentation and mortality of cryptococcal infection varies by predisposing illness: a retrospective cohort study cutaneous cryptococcus (cryptococcosis). statpearls an unusual presentation of primary cutaneous cryptococcosis behind the leg: cryptococcal meningitis, not cellulitis sugiyama e: a large deep skin ulcer as an initial manifestation of systemic cryptococcosis the authors would first like to thank the patient and his family who showed us a human way to fight against the disease. this made us find the time and energy to share this clinical case even in this difficult moment for lombardy due to the covid- outbreak. we would also like to thank all the medical staff, including nurses and paramedics, who tried to be allies of the patient in this impossible fight day-by-day. key: cord- -dii zszf authors: khan, sheharyar; choudry, erum; mahmood, syed uzair; mulla, aisha y; mehwish, syeda title: awake proning: a necessary evil during the covid- pandemic date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: dii zszf the spread of covid- has been exponential throughout the globe. though only a small percentage of infected individuals reach the critical stage of the disease, i.e., acute respiratory distress syndrome (ards), this percentage represents a significant number of patients that can overwhelm the healthcare system. patients presenting with ards need mechanical ventilation, as their lungs are unable to oxygenate blood on their own due to fluid accumulation. one way to manage this excess pressure of fluid build-up around the lung tissues is to relieve the dorsal alveoli by prompting the patient to lie face down on the stomach; this is called awake proning. it is a procedure that is directed towards the recruitment of lung parenchyma when infected with pneumonia or when the condition has worsened into ards. this helps in relieving the pressure from the dorsal lung surface that has markedly higher perfusion than the ventral surface. awake proning delays the use of mechanical ventilation and facilitates the patients with severe ards or severe pneumonia in maintaining the supply of oxygen to the body tissues. since medical institutes are overburdened and limited ventilators are available, awake proning can reduce not only the burden on hospitals but also decrease the need for ventilators. covid- is a respiratory viral illness that is responsible for taking the lives of more than , , people all around the world as of june , . becoming a rampant worldwide phenomenon, the number of patients with covid- rises exponentially on a daily basis [ ] . it is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus- (sars-cov- ) [ ] . the illness that it causes starts with mild symptoms like fever, dry cough, and sore throat and, in several people, with a recent loss in the senses of smell (anosmia) and taste (ageusia) [ ] [ ] . as it progresses, the disease presents with more severe symptoms like viral pneumonia, which causes acute respiratory distress syndrome (ards). ards is a condition of distress in respiration that results in poor ventilation, as well as poor perfusion of oxygen into the alveoli and, therefore, into the bloodstream. this poor perfusion causes hypoxic conditions, and congestive chest pain occurs along with a sense of drowning. the lungs are filled with exudate due to pneumonia and the alveoli start collapsing, which makes the condition even worse. once a patient presents with ards and needs mechanical ventilation via intubation, the survival rate drops from % to % [ ] . to prevent hypoxia and continue the process of gaseous exchange, it is vital that the effect of the exudate filling the lung parenchyma is decreased, and awake proning plays a major role in rescuing the lungs. awake proning limits the lung collapse by making the dorsal alveoli available for gaseous exchange. the patient is made to lie on their stomach, which has been proven to be of value in decreasing the rate of intubation according to several studies [ ] . acute respiratory distress syndrome is a condition that results in pulmonary deficiency and in the case of severe symptoms, a need for mechanical ventilation arises. it is an acute and progressive onset of hypoxemia that is detected by the presence of bilateral infiltrates on the chest x-ray or a computed tomography (ct) scan. ards presents with a marked increase in the vascular permeability of the capillaries in the alveoli. this increased permeability is due to the damage caused to the endothelial layers of the capillaries, which result in an increased fluid passage into the alveolar lumen. apart from vascular tissue damage, the excessive release of factors like sphingosine- phosphate (s p) that binds to its receptor, s p , which regulates vascular permeability. regarding the basic physiology of vascular stability, angiopoietin- (ang- ) attaches to its receptor, tie- , and stabilizes the vascular structure as the blood flows through the capillary bed by the activation of syx and rho a. angiopoietin- (ang- ) competes with ang- to bind with the receptor sites at tie- and promotes the destabilization of the vascular structure. hence, factors like s p and ang- are indicators of ards [ ] . the body's natural inflammatory response and the cells responsible for innate immunity like neutrophils are also responsible for the condition to escalate into ards. upon activation, neutrophils release the molecules that are cytotoxic in nature, like enzymes, bioactive lipids, cytokines, and reactive oxygen species. these molecules, when released in excess, are responsible for cell necrosis and tissue damage. these damaged tissues induce autophagy as well as apoptosis, which are classical markers of ards [ ] . table lists the biomarkers of ards that can be identified in serum [ ] . all the instances mentioned above result in the rapid increase of fluid accumulation inside the thoracic space surrounding the lung tissue, and the fluid presses against the alveoli. the shape of the lungs inside the human body favors heavy perfusion towards the back or dorsal side of the body. there is a comparatively lower rate of perfusion towards the front or ventral side of the body. when a patient is diagnosed with pneumonia or ards, the fluid collected in the thoracic space puts additional pressure on the delicate alveoli, which may lead to alveolar collapse [ ] . in addition to an increase in pressure over alveoli, fluid also hinders efficient gaseous exchange to meet the requirement of the body. together, these factors cause a decreased availability of oxygen for the tissues and results in hypoxemia. hence, the patients diagnosed with pneumonia or ards often present with atelectasis (lung collapse) in the dorsal region. this condition arises because the patient, lying supine, accumulates fluid in the dorsal alveoli, i.e., the region with higher perfusion [ ] . in ards, there is an excessive accumulation of secretion in the peripheral lung parenchyma, which exerts pressure against the fragile alveolar walls and impedes gaseous exchange. a method to redirect this excessive fluid away from the dorsal lung parenchyma is to manage it via awakeproning,whichis majorly directed towards conserving the alveolar structure of the lungs [ ] . the procedure is focused on limiting the collapse of the alveoli and reducing the fluid accumulation on the areas with a higher perfusion rate, i.e., the dorsal region. the prone position is achieved when the patient lies on their stomach or front, this helps in the recruitment of the alveoli previously collapsed into the dorsal surface of the chest cavity [ ] . in prone positioning, the intra-abdominalorgansmoveundergravitationalpull in a downward (gravitational) and forward (toward the thorax) direction,which aimsthe excesspleuralpressure at the ventral region of the alveoli as opposed to the dorsal regionin the case of lying in a supine position. redistribution of the pressure towards the ventral region also helps in preventing the compression of dorsal alveoli and aids in better breathing [ ] . figure illustrates the steps of awake proning. note: reassess the respiratory rate and saturation after minutes of repositioning the patient and later after every to minutes. awake proning is associated with an improved mortality rate after an incident of ards or severe pneumonia. this procedure is noninvasive and provides instant results. in emergency situations where the patient's vitals keep worsening, applying prone positioning helps in improving the oxygen saturation instantly. several studies show that awake proning improves oxygen saturation in merely five minutes [ ] . . it maintains an optimal respiratory rate and enhances the gaseous exchange in a favorable range [ ] . . ventilation stays homogenous throughout the lung parenchyma, and redistribution of the blood flow is improved with higher efficacy, which, in turn, improves the ventilation/perfusion ratio (v/q ratio). . an intrapulmonary shunt prevents the proper oxygenation of blood in the lungs. the areas shunted are prone to hypoxia and may result in tissue damage. by prone positioning, this shunt is reduced and lung compression is decreased. therefore, oxygen levels improve [ ] . . awake proning also helps decrease the accumulation of excess interstitial fluid in the dorsal part of the lungs. lying on the stomach directs the fluid to collect in the ventral region where there is comparatively less perfusion [ ] . . no specialized instruments are needed for the procedure, and it can be done easily in emergency situations [ ] . a recent study conducted in new york regarding the effectiveness of self-proning came out with promising results. the study was based on quick proning of patients that presented with moderate to severe ards after an incident of covid- . the patients were put into the prone positions for about hours a day while the breathing cycles started showing improvements after five minutes of assuming the position of awake proning. fifty patients with confirmed hypoxia were under focus for this study and their median saturation of oxygen in blood was %, which was raised to % after the provision of supplemental oxygen. after five minutes of lying in the prone position, the levels of oxygen saturation were raised to %, and the patients were also put on supplemental oxygen. in this study, intubation was not needed in nearly two-thirds of the admitted patients. these patients were shifted towards the non-invasive procedures of oxygen provision like bi-level positive airway pressure (bipap) and awake proning [ ] . another study focused on patients who were not intubated. these patients were subjected to prone positioning times over the course of treatment. the patients presented with ards and breathing difficulties. the respiratory rate and blood oxygenation were substantially improved, during and after the cycle of pronation and there were patients who had improved breathing after pronation. the blood oxygen levels also improved after the cycles of prone positioning, and endotracheal intubation was avoided in patients with ards, which would have been the only option to opt from if awake proning was not administered [ ] . furthermore, a study had subjects with covid- and severe ards. the median blood oxygen levels were found to be % and after the aid of supplemental oxygen, these levels improved to %. prone position was maintained, and the blood oxygen before and after proning was noted. at five minutes of proning, the levels went up to %. in this study, however, patients failed to respond to the treatment by proning and had to undergo endotracheal intubation. for emergency support, the numbers suggest that proning provided improved levels of oxygen saturation in the patients who would have been treated with endotracheal intubation and mechanical ventilation [ ] . one of the indications of awake proning is the need for quick relief from the dyspneic condition. covid- patients in a critical condition escalate into moderate, severe, or critically severe ards. this calls for the need for a quick fix until their condition stabilizes [ ] . the two types of awake proning are indicated for different situations: a. short-term awake proning: it may have limited use but there are instances when short-term awake proning is the best option to handle the patient's condition. the time period of short proning spans from three hours to eight hours [ , ] . . it is indicated to treat mild to moderate hypoxemia. . it helps in airway drainage and improves refractory maneuvers in relation to atelectasis. . lower lobe atelectasis is most effectively treated with short-term prone positioning. . improved breathing rate and decreased crackles during each breathing cycle can be observed. b. long-term awake proning: it is the most widely used maneuver to administer awake proning and has shown the most significant results. the time period of long-term awake proning spans for more than eight hours. . it is indicated to treat severe hypoxemia. . severe ards is most effectively treated with long-term awake proning. the condition is characterized by a steep decline in blood oxygenation and severe dyspnea indicating loss of efficient breathing. it is the last stage in the development of covid- infection [ ] . awake proning is contraindicated in the following situations [ however, the presence of these contraindications should be balanced with the need for the treatment. the risks associated with awake proning should be considered in relation to the necessity of the procedure at the time of treatment, making it a necessary evil. physicians may encounter a few complications associated with awake proning, as illustrated in a setback of lying prone for an extended period is that it causes pain in the back, neck, and lower limbs. this pain is caused by the body's weight being projected on to the spine. sleeping in a prone position hinders the spine to position itself accurately and leads to a multitude of problems. if the spine remains unstable, the nerves exiting the spinal segment might impinge and cause pain in the area it supplies. this could feel like tingling or numbness and, in extreme cases, may cause severe pain. in rare cases, the airway can be obstructed and it may present as obstructive sleep apnea. it is recommended that patients suffering from ards be advised to acquire a prone position while they are conscious but while falling asleep, a neutral position should be advised [ ] . a covid- patient presenting with severe pneumonia or ards can be managed with awake proning as a supportive treatment to relieve symptoms. awake proning helps in improving oxygenation by the optimization of the lung parenchyma and the recruitment of the alveoli along the dorsal surface with higher perfusion, hence, better ventilation is provided to the body. prone positioning helps in protection against ventilator-induced lung injury (vili), as the need for mechanical ventilation is avoided for some time by the distribution of stress and strain in a homogenous manner throughout the parenchyma of the lungs. the long-term use of awake proning is, however, not indicated for mild and moderate cases of ards. awake proning does not require any special instrumentation and can be done in an emergency situation. it presents itself as a tool that can improve the oxygen saturation of a patient suffering from hypoxemia due to conditions such as ards. with the shortage of ventilators and their high demand during the covid- pandemic, we recommend that each medical institute should invest in or should seek help to acquire prone position comfort cushions or bolsters as they help maintain awake proning rather than opt for expensive ventilators. disclosures covid- ): current status and future perspectives coronavirus disease (covid- ): a perspective from china. radiology. olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (covid- ): a multicenter european study higher mortality rate in ventilated covid- patients in large sample lower mortality of covid- by early recognition and intervention: experience from jiangsu province angiopoietin signaling in the vasculature interactions between mechanical and biological processes in acute lung injury biomarkers for the acute respiratory distress syndrome: how to make the diagnosis more precise the gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung acute respiratory distress syndrome caused by pulmonary and extrapulmonary disease: different syndromes? prone positioning in severe acute respiratory distress syndrome self-proning in covid- prone position in acute respiratory distress syndrome. rationale, indications, and limits fifty years of research in ards. gas exchange in acute respiratory distress syndrome prone positioning combined with high-flow nasal cannula in severe noninfectious ards prone positioning improves oxygenation in spontaneously breathing nonintubated patients with hypoxemic acute respiratory failure: a retrospective study early self-proning in awake, non-intubated patients in the emergency department: a single ed's experience during the covid- pandemic prone ventilation reduces mortality in patients with acute respiratory failure and severe hypoxemia: systematic review and meta-analysis role of the heart in the loss of aeration characterizing lower lobes in acute respiratory distress syndrome prone positioning improves survival in severe ards: a pathophysiologic review and individual patient meta-analysis prone position and mechanical ventilation is it bad to sleep on your stomach in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -y t xw authors: lahiri, durjoy; ardila, alfredo title: covid- pandemic: a neurological perspective date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: y t xw even though severe acute respiratory syndrome coronavirus (sars-cov- ) has been observed to principally affect the respiratory system, neurological involvements have already been reported in some published work. we have reviewed original articles, case reports, and existing open-source data-sets to delineate the spectrum of neurological disorders potentially observed in sars-cov- positive cases. neurological involvement in coronavirus disease (covid- ) corresponds to three situations: (a) neurological manifestations of viral infection, (b) post-infective neurological complications, and (c) infection in patients with neurological co-morbidity. neurological manifestations can further be subdivided into the central nervous system (headache, dizziness, alteration of the sensorium, ataxia encephalitis, stroke, and seizures) and peripheral nervous system (skeletal muscle injury and peripheral nerve involvement including hyposmia and hypogeusia) symptomatology. post-infective neurological complications include demyelinating conditions. reduced mobility and dementia as co-morbidities may predispose a patient to have a viral infection. it is concluded that the pandemic of covid- presents for a neurologist some unique challenges. we observe that sars-cov- may have various neurological manifestations and in many cases, neurological features may precede typical respiratory symptoms. coronavirus disease (covid- ) has been declared a pandemic on the th of march, by the world health organization. the epicenter of this pandemic has shifted in quick succession from china to europe to the united states of america in a matter of weeks. since the middle of march , south-east asia has also seen a rise in the number of affected persons and it remains to be seen if there will be another twist in the story of this pandemic. one of the essential weapons to fight a pandemic of this stature is to gather as much knowledge as possible about the transmission dynamics and clinical manifestations while the quest for an effective vaccine keeps continuing. even though severe acute respiratory syndrome coronavirus (sars-cov- ) has been observed to mainly affect the respiratory system, neurological involvements have already been reported in some published work. several medical news bulletins, blogs, and articles across the globe have also raised concerns about brain invasion by this particular strain of coronavirus. this is actually not surprising given our previous experience of neuro-invasion by severe acute respiratory syndrome coronavirus (sars-cov) and the middle east respiratory syndromerelated coronavirus (mers-cov). the body of literature on neurological aspects of sars-cov- is small but growing. however, we believe, an organized summary of the available information at this point would be indispensable to neurologists across the globe. being well informed about the neurological presentations would not only help them have a high index of clinical suspicion but also take necessary precautions. therefore, a brief literature review along with a critical appraisal of the evidence gathered so far is presented here from the perspective of a neurologist. in the present paper, we have reviewed the recently published or pre-print original articles, case reports, and existing open-source data-sets in order to delineate the spectrum of neurological disorders in sars-cov- positive cases. the putative mechanisms described to explain the neuro-invasion by a coronavirus (and one similar another rna virus, influenza a) are hematogenous spread and retrograde axonal transport [ ] [ ] [ ] [ ] . however, in light of contemporary evidence, some of the other possible routes of neuroinvasion by the sars-cov- deserve to be mentioned. direct viral invasion of the brain leading to clinical encephalitis has been suspected after the treatment team of beijing ditan hospital confirmed the presence of sars-cov- in the cerebrospinal fluid (csf) of patients with covid- by genome sequencing [ ] . covid- is widely known to cause respiratory insufficiency, and therefore, hypoxia needs to be considered among the major putative mechanisms of brain injury [ ] . cytokine storm, which is a well known immune reaction of this particular viral infection, may lead to inflammation and injury of the central nervous system (cns) tissue. this idea is further supported by the observation that interleukin (il)- , an important member of the cytokine storm, is positively correlated with the severity of covid- symptoms [ ] . the affinity of the viral particle towards angiotensin-converting enzyme- (ace- ), a cardio-cerebral vascular protection factor, has been in discussion in recent papers [ ] . the expression of ace- in the nervous system and skeletal muscles can indeed explain some of the neurological features reported so far. it has been postulated that the viral attachment to the ace- at the level of the blood-brain barrier may jeopardize the protective mechanism surrounding the encephalon, giving way to viral encephalitis. in a similar vein, spinal cord membranes expressing ace- can culminate into myelitis-like features following sars-cov- infection. concern has also been raised that the viral particles binding to ace- in cerebral blood vessels may actually raise the luminal pressure of those vessels leading to intracerebral hemorrhage [ ] . thus there are multiple mechanisms elaborated so far in the available literature that can explain the observed as well as anticipated neurological features of this ailment. early data on covid- suggest neurological involvement in a variable percentage of cases with particular expression in more severe patients [ ] . neurological involvement in covid- can be discussed in three sections: ( ) neurological features of viral infection, ( ) post-infective neurological complications, ( ) infection in patients with neurological co-morbidity. another issue that deserves to be mentioned is the precautions to be taken for neurologically ill patients who require immunosuppressive agents. the latter group mostly consists of multiple sclerosis, myasthenia gravis, and autoimmune encephalitis. neurological manifestations of viral infection reported so far can further be subdivided into cns and peripheral nervous system (pns) features. cns features include headache, dizziness, ataxia, alteration of sensorium, encephalitis, stroke, and seizures, while pns features mostly refer to skeletal muscle injury and peripheral nerve involvement in the form of hyposmia and hypogeusia. headache can be a symptom of viral infection and usually remains associated with fever. studies have reported an incidence of headaches ranging from to % in covid- cases [ ] [ ] [ ] [ ] . however, concerns have already been raised in recent correspondence if this particular symptom is a manifestation of viral meningitis or, for that matter, encephalitis, which may reveal itself subsequently in the form of drowsiness and seizures. japanese colleagues shared their recent experience in dealing with a young male patient without any contact or travel history who presented features of meningitis before being diagnosed with the infection of sars-cov- [ ] . the issue becomes more substantial as one considers the report of virus detection in csf of a covid- patient. another very recent report describes the occurrence of acute hemorrhagic necrotizing encephalopathy in covid- patient [ ] . in this particular case, however, the csf examination for sars-cov- was not carried out, although bacterial culture and tests for other viruses were essentially negative. therefore, neurologist needs to pay attention and analyze even a simple symptom such as headache in a known covid- case, especially if the headache is out of proportion to rise in temperature and is associated with certain other features such as vomiting and altered sensorium. another noteworthy observation is the occurrence of cerebrovascular events (cve) associated with this ailment. the initial retrospective case series study from wuhan, china, reported that . % ( / ) of the cases showing neurological involvement could be attributed to acute cve [ ] . notably, four cases had an ischemic stroke, while cerebral hemorrhage was found in a single patient who died later on. another recent paper from the same center, which analyzed participants, elaborates that . % ( / ) cases had some sort of new-onset cve [ ] . the majority of them presented acute ischemic stroke ( patients), while hemorrhagic stroke (one patient) and cerebral venous sinus thrombosis (one patient) were also found but uncommonly. therefore, thrombotic manifestations were way more frequent than hemorrhage. this observation may possibly be linked to the finding that patients with cve were more likely to have enhanced inflammatory response as reflected in their c-reactive protein (crp) and ddimer levels. it is within the realm of possibilities that the viral infection may have given way to an inflammatory storm that ultimately culminated in accelerated thrombosis. the term "accelerated thrombosis" seems more meaningful if seen in the context of another finding in this particular retrospective study. patients with cve were not only significantly older than those without cve but also were more likely to have pre-existent vascular risk factors. this observation is particularly relevant in the indian scenario because vascular risk factors are common in the population, and so is the incidence of stroke. moreover, any viral infection in a stroke patient not only delays recovery but also may actually worsen the neurological deficit, the latter being sometimes attributed to hemorrhagic transformation. the mortality rate was indeed found to be higher in covid- stroke patients, with % indicating a worse prognosis in this group of patients. the above discussion brings out the two-way relationship between covid- and stroke, which a neurologist has to bear in mind while attending patients in these difficult circumstances. the issue becomes more complicated when one considers treating a patient with ischemic stroke in the background of coronavirus infection. the application of antiplatelets and anticoagulants is tricky because the virus is known to cause prominent respiratory involvement, and according to some authors, the involvement of the nervous system may be partly responsible for respiratory impairment. impaired consciousness has so far been reported in . % hospitalized patients of covid- [ ] . severely affected patients are more likely to present impaired consciousness. there can be multiple underlying reasons for a patient with covid- to present with altered sensorium, which include viral encephalitis, metabolic perturbation, infectious toxic encephalopathy, seizures with post-ictal confusion, and stroke (either strategic area involvement or large lesion with edema). a recent document, (published in neurology today online) by italian neurologists (addressed to their us colleagues) mentions the importance of recognizing poorly defined neurological features in confirmed as well as presumptive cases of covid- . among these symptoms, altered sensorium indeed has drawn the attention of the neurologists mostly because it delays diagnostic procedures as the virus is widely known to be a respiratory pathogen. a detailed look at the description of a single case of encephalopathy in association with covid- reveals that an altered level of consciousness may precede typical respiratory symptoms by days [ ] . given the transmission dynamics of the infection, this information is extremely important as health care providers at the emergency department may get inadvertent exposure while handling patients with altered sensorium. in a consecutive series of covid- related acute respiratory distress syndrome (ards) patients (n= ) reported from france, altered consciousness, including agitation and confusion, has been documented in more than two-thirds of the cases. additionally, % of the recruited patients in this study had prominent cortico-spinal signs [ ] . in this context, telephonic conversation with the physician in charge of an infectious disease hospital in kolkata (india) reveals that headache is more of a generalized symptom in both old and young patients, while delirium is a frequent presentation among the elderly. the hospital presently is catering to more than confirmed cases of covid- , while around presumptive cases are in isolation. in the wuhan study, ataxia was found in only one patient, although a detailed description or anatomical substrate of this particular symptom was not available in this paper [ ] . we at our center recently encountered a -year-old man presenting with acute onset cerebellar ataxia followed by encephalopathy, who was finally diagnosed with sars-cov- induced pneumonia. notably, in our patient neurological manifestation preceded respiratory features by days. the association of seizure and covid- can be multi-faceted. an early report suggested a very low incidence ( . %) of seizure disorder [ ] . however, as numbers start growing across the globe, this issue is anticipated to become a non-negligible one. firstly, a seizure may be a manifestation of viral invasion into the cns. secondly, this particular infection is known to cause fatal pneumonia that gives way to severe hypoxemia, which may result in brain injury and seizures thereof. metabolic perturbations and septic encephalopathy are some of the other concerns that need to be taken care of while attending a patient with seizure. the latter causes belong to the so-called group of "acute symptomatic seizure". thirdly, known epileptic patients with covid- may experience increased frequency and severity of seizures, particularly because of threshold lowering that remains associated with fever. a patient (mentioned above) with the encephalopathic presentation of covid- had underlying gliosis in the right temporal region resulting from an old embolic stroke. he received prophylactic antiepileptic given the probability of subclinical seizures in the background of a structural brain lesion [ ] . seizures supposedly would complicate the clinical situation by the agency of skeletal muscle injury, which is already a well-known manifestation of the disease. the fact that neurological complications are more frequent in severely ill patients and also cardiovascular risk factors are predictors of severity, the drug interaction potential of several antiepileptic drugs would deserve attention in such clinical situations. therefore from a neurologist's perspective, seizure in a covid- patient will have some important implications both from diagnostic as well as therapeutic perspectives. symptoms of skeletal muscle damage often associated with liver and kidney involvement have already been noted. the reported incidence is . %, and like other neurological features, this one is also associated with a severe form of the illness [ ] . it can be speculated that patients with pre-existing renal or hepatic impairment will be highly vulnerable to develop features of multi-organ failure in the backdrop of skeletal muscle injury. muscle enzymes, including creatine kinase and lactate dehydrogenase (ldh), are seen to be highly elevated in the symptomatic patients -an observation that confirms muscle membrane damage. the exact mechanism of muscle damage, however, has not been established. possibilities include viral muscle invasion through ace- receptor tropism and immune-mediated muscle fiber damage. further studies will be required to elucidate the mechanisms underlying skeletal muscle injury in covid- . it has been reported that hypogeusia, as well as hyposmia, are fairly consistent symptoms of sars-cov- infection [ , ] . hypoplasia has also been reported but infrequently. these are all categorized as manifestations of peripheral nerve involvement, while another reported feature is neuralgia. however, noteworthy is that the olfactory nerve is considered part of the cns, and hyposmia may actually be a reflection of olfactory bulb involvement rather than peripheral neuropathy. similarly, hypoplasia, if due to optic neuropathy, may reflect cns manifestation because optic nerve, as per classical teaching, is an extension of the brain. with more number of patients recovering from the sars-cov- infection, it is imperative that post-infective complications would draw attention with time. cns demyelinations have been documented previously following coronavirus infection [ ] . an early report of guillain-barre syndrome (gbs) is available from china, although there is a concern regarding the causality in this particular case [ ] . the patient developed typical symptoms of sars-cov- infection after seven days of hospitalization for gbs. retrospective analysis, however, supports that she might have been harboring the infection since the beginning, as reflected in her blood counts (lymphocytopenia and thrombocytopenia). the authors duly speculate that the initial symptoms may have been too mild to be detected in this patient (as fever is present in less than half of the cases during the initial phase). a very recent correspondence describes five cases of gbs collected from three hospitals of northern italy among to cases of sars-cov- infection over three weeks [ ] . three of these cases fit criteria for the axonal variant of gbs, while the remaining two had prolonged distal latencies suggesting demyelinating neuropathy. although each of these cases had a usual latency of five to ten days before the onset of neurological symptoms, one of the patients, similar to the previous one reported from china, was found negative on viral reverse transcription-polymerase chain reaction (rt-pcr) at the outset only to be detected positive subsequently. this observation is ominous because of two reasons: ( ) there is a chance of inadvertent exposure to the infectious virus in the neurology ward both for attending health care staffs and other patients; ( ) gbs is a disorder known to rapidly affect respiratory muscles particularly if bulbar involvement sets in which can cause sudden poorly explained worsening of a patient's status if the diagnosis of covid- has not already been established. another report from china describes a case of acute myelitis, possibly affecting the cervical spinal cord, as evidenced by the clinical features, in a known patient of sars-cov- infection [ ] . in this particular description also the neurological symptoms were co-incident with the febrile period of the illness pointing towards para-infectious demyelination rather than postinfective complication in true sense. lymphocytopenia accompanied by raised markers of inflammation (crp and procalcitonin) was documented by the treating physicians. the patient received anti-viral therapy along with immune-suppressive and recovered from his limb weakness. although the literature is scarce at this point in time, the idea that sars-cov- can cause para-/post-infective complications affecting the neuroaxis at different levels seems realistic, and supposedly patients with the inflammatory storm will be more likely to manifest this. additionally, since about % of hospitalized patients need assistance in intensive care wards, neurological monitoring must also be aimed at verifying the onset of the so-called "critical illness neuro-myopathy" type pns problems. these issues are known to delay weaning from ventilation and pose a significant burden on the health care delivery system. during this hour of the pandemic, another group of patients will deserve the attention of neurologists. this group comprises of neurologically ill patients who have already been in follow-up for some time. the need for different groups of patients will vary according to the nature of their illness. data is insufficient at this point in time to conclude if chronic neurology patients are more predisposed to acquire infection. however, patients with reduced mobility and those on immune-suppression therapy may be anticipated to be more susceptible to infection. recent correspondence has already discussed the challenges that will be faced by dementia patients during this period of social distancing and home isolation [ ] . obviously the crisis will be more for those subjects who depend on others for daily life activities. the situation will be similar for patients with prominent motor problems. due to their restricted mobility, social distancing is supposed to affect them for worse. reduced mobility and dementia may also predispose a patient to have a viral infection. so once again, the association becomes two-way. contemporary neurology has seen wide use of immune-suppressive agents to combat several disorders of both cns and pns. the prototypical among these disorders is multiple sclerosis that calls for long term immunosuppression. the data so far on covid- reveals that old age, as well as immune-dysregulated subjects, are more likely not only to acquire the infection but also to manifest increased severity. therefore, similar to the oncology ward, patients in the neurology ward admitted receiving cyclic immunosuppressive drugs need attention. appropriate caution has to be practiced while dealing with such cases both from the part of the neurologist as well as the patient's relatives. a recent article on this topic recommends that the benefits of continuing immunotherapy in patients with multiple sclerosis (ms) and related disorders may outweigh the risks of medication withdrawal in the apprehension of covid- . this is particularly because most infections, as in the general population, are anticipated to be mild an d self-limiting. however, the authors emphasize the need for individualized decisionmaking in such circumstances because one size" may not fit all, and some of the patients may land up in severe infection leading to discontinuation of therapy [ ] . with the growing number in recovery from sars-cov- infection, rehabilitation issue is supposed to become a crucial one. personal communication with neurologists working in the field in italy reveals that there is early evidence for the need for rehabilitation, including neurological aspects, in clinically recovered patients. it can be assumed that the psycho-social effects of long term social distancing and home isolation will require adequate psychological rehabilitation measures as the pandemic will start waning off. since the onset of the sars-cov- outbreak, if there is one pulmonary manifestation that has received maximum focus, it is ards. evidence suggests a significant percentage of ards survivors may suffer long-term cognitive impairment [ ] . several factors, including mechanical ventilation, have been observed to cause a decline in higher brain functions following ards. acute injury to the blood-brain barrier has been implicated as the underlying mechanism for cognitive impairment following ards. the effect of such injury may be amplified if there is a pre-existing cognitive impairment that corresponds to chronic bloodbrain barrier damage. patients with brain injury, on the other hand, have been found to develop neurogenic pulmonary edema. therefore, it is postulated that the so-called brain-lung axis works both ways. the above observations are particularly relevant in the present circumstances, given the need for mechanical ventilation in the majority of the severely affected covid- patients. as the pandemic continues to unfold, the number of people getting off mechanical ventilation will rise, and long-term cognitive outcomes will come into view. it can be anticipated that not only we shall witness cognitive decline lasting for months in this group of patients, but also some of them may progress to premature onset of dementia. over time, the need to raise awareness among the neurologists is being increasingly recognized. the case record protocol for "first few cases (ffx) and their close contacts" published by who has a separate column to mention the neurological findings in addition to respiratory signs and symptoms [ ] . this underlines the importance of recognizing the neurological manifestation of the illness. a recently published guideline from china lists some important precautionary measures that need to adapt by the neurologists to combat the pandemic [ ] . the bottom line is to have a high index of clinical suspicion, particularly when working in an endemic zone. this will not only help early initiation of therapy but also will halt the chain of transmission. the pandemic of covid- presents for a neurologist some unique challenges. we observe that sars-cov- may have various neurological manifestations, and in many cases, neurological features may precede typical respiratory symptoms. holistic knowledge of the spectrum of neurological consequences of covid- is important to get a hold on the spread of the virus. the most vital clinical information which we gather is that impaired consciousness may be a presenting feature of covid- , and therefore, a high index of suspicion for such patients will be the key to prevent or, at least, lessen exposure to health care providers and other patients. with the gradual subsidence of the outbreak, it can be anticipated that several postinfectious complications will surface up while rehabilitation measures will also deserve attention. adequate caution has to be practiced while managing chronic neurology patients, particularly those requiring immune-modulator therapy since formulated guidelines are lacking at this point. the above summary of the neurological manifestations of covid- will help neurologists have a basic preparation, which is of utmost importance to prevent horizontal infections. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system neurologic alterations due to respiratory virus 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hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china. jama. covid- associated acute hemorrhagic necrotizing encephalopathy: ct and mri features a first case of meningitis/encephalitis associated with sars-coronavirus- neurological complications of coronavirus disease acute cerebrovascular disease following covid- : a single centre, retrospective, observational study neurologic features in severe sars-cov- infection neurologic complications of coronavirus infections detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis guillain-barré syndrome associated with sars-cov- infection: causality or coincidence acute myelitis after sars-cov- infection: a case report dementia care during covid- treating multiple sclerosis and neuromyelitis optica spectrum disorder during the covid- pandemic long-term cognitive impairment after acute respiratory distress syndrome: a review of clinical impact and pathophysiological mechanisms first cases of coronavirus disease (covid- ) in france: surveillance, investigations and control measures consensus for prevention and management of coronavirus disease (covid- ) for neurologists we are sincerely thankful to stefano f. cappa (professor of neurology, university school for advanced studies, iuss-pavia) and yutaka tanaka (professor of neurology, tanaka clinic, nara, japan) for their valuable inputs in preparing the present version of the manuscript. key: cord- -irmwqjfh authors: beiu, cristina; mihai, mara; popa, liliana; cima, luiza; popescu, marius n title: frequent hand washing for covid- prevention can cause hand dermatitis: management tips date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: irmwqjfh coronavirus disease (covid- ) continues to spread globally, outpacing the capacity and resources of health systems worldwide. a therapeutic vaccine is not yet on the rise, and preventive measures are the current approach to restraint the transmission of cases. as the virus is highly contagious via respiratory route (droplets from infected persons, widely spread by coughing or sneezing) and via contact with contaminated surfaces, community transmission and spread can be decreased through the practice of regular and diligent hand hygiene. frequent hand washing implies a prolonged exposure to water and other chemical or physical agents and may induce several pathophysiologic changes, such as epidermal barrier disruption, impairment of keratinocytes, the subsequent release of proinflammatory cytokines, activation of the skin immune system, and delayed-type hypersensitivity reactions. adverse dermatologic effects, such as excessive skin dryness or even contact dermatitis (particularly the irritant subtype and, to a lesser extent, the allergic subtype), can occur, especially in individuals with a history of atopic dermatitis. these skin conditions are perfectly manageable, and applying a moisturizer immediately after washing hands or after using a portable hand sanitizer is the cornerstone in preventing the development of eczematous changes in the hands. in the current global context, the potential occurrence of these dermatological adverse events should in no way cause people to deviate from strict hand hygiene rules. covid- stands for "coronavirus disease ," and it refers to an outbreak of acute respiratory infection caused by a novel coronavirus. the specific coronavirus strain was initially referred to as -ncov ( novel coronavirus) and finally designated as sars-cov- (severe acute respiratory syndrome coronavirus ). it was first identified in late in the city of wuhan, hubei province of china, and it rapidly spread throughout other eastern countries (e.g. south korea, japan, iran) as well as europe and the united states [ ] . on march , the who (world health organization) declared the covid- outbreak a global pandemic and all countries were urged to undertake effective measures for reducing transmission [ ] . vaccines active against covid- are not available, and ongoing prospects in formulating and developing preventive or therapeutic vaccines against sars-cov- are limited [ ] . in this context, public health actions to prevent transmission are crucial in slowing the spread of the pandemic. one of the essential recommendations that the who has issued for the populous is to wash their hands frequently and correctly. in the process, intensified hand washing may generate various changes in skin texture and even hand dermatitis. this article aims to review the potential dermatological adverse effects that may arise due to frequent hand washing, as well as practical tips for preventing these uncomfortable skin reactions. all clinical images included in the review section of the article were taken in the department of oncologic dermatology of emergency university hospital "elias" in bucharest, using a digital camera (nikon d ; nikon corporation, tokyo, japan). frequent hygienization of hands may generate various changes in skin texture, ranging from the development of cutaneous xerosis (dryness of the skin) up to irritant contact dermatitis (icd) or, rarely, even allergic contact dermatitis (acd). overall, these skin disorders are induced by various physical, chemical, and immunological mechanisms. when measures of diligent hand hygiene are implemented, these mechanisms may be activated mainly by the following circumstances. . prolonged skin exposure to water and humid environment: it creates extensive swelling of stratum corneum (the skin's outermost layer) and disruption in the ultrastructure of intercellular lipids, and heightens the skin's permeability and sensitivity to physical or chemical irritants [ ] . in addition, prolonged wearing of protective gloves can generate excessive sweating and increased humidity, thus further increasing the inflammatory response elicited towards irritants. . repeated use of soaps, surfactants, detergents, or solvents: these substances used for domestic cleaning are weak irritants and are usually very well tolerated. nevertheless, repeated exposure to these substances can lead to chronic cumulative icd (figure ) , mainly due to their capacity to remove skin surface lipids, damage skin proteins, denature epidermal keratin, and even induce alteration of the cell membrane of keratinocytes [ ] . furthermore, patients with a personal or family history of atopic dermatitis have a chronically dysfunctional cutaneous barrier that increases their sensitivity to skin irritants ( figure ) [ ] . rarely, some individuals may even develop acd (figure ) , a t-cell-mediated, delayed-type hypersensitivity reaction, to an ingredient in a hand hygiene-related product, such as soaps or detergents [ ] . the patient initiated preventive hand washing measures two months ago, without hydrating the hands afterward and developed severe skin dryness, fissuring (white arrow), and scaling. also the irritant-induced changes have progressed to hyperkeratosis and acanthosis (black arrows), highlighting the cumulative exposure. confluent, erythematous, scaly itchy patches, with small vesicles (highlighted in the white circles), on the hands of a patient with allergic reaction induced by chemicals in detergents and soaps. . repeated use of alcohol-based hand sanitizer: the who states that using hand rubs that contain at least % alcohol is a reasonable alternative if water and soap are not available, and as long as the hands are not visibly dirty [ ] . frequent use of these products can also result in skin dryness and irritation. on the other hand, allergy against alcohol itself is unknown and acd attributable to other compounds added to alcoholic hand gels is extremely rare. this was illustrated by the experience of a large hospital in switzerland where health workers routinely used a commercial alcohol-based hand sanitizer for years, without reporting any allergic reactions to the product [ ] . in these times, it is very important to adapt our hand washing habits to ensure efficient protection against the spread of covid- while lowering the risk of skin adverse reactions. in this respect, we find very useful the adoption of the following protective measures. . as the who recommends, hands should be washed thoroughly (including fingernails, interdigital web spaces, wrists) for at least seconds, using lukewarm water and soap, particularly after being in public areas, before meals, after coughing or sneezing, after using the toilet, and whenever the hands are dirty. . after washing, we advise rinsing the hands by using gentle maneuvers, without causing a physical irritation to the skin. . applying moisturizing skin care products after hand cleansing is the essential step in keeping the skin hydrated and preventing further abnormal skin reactions. these hydrating products should be liberally applied, multiple times per day, particularly immediately after hand washing. . there are several subtypes of moisturizers but to efficiently improve the quality of the skin barrier it is largely indicated to combine humectants with occlusive emollients. humectants (e.g., topical urea, propylene glycol) are capable of attracting water to the stratum corneum from the environment and from the deeper layers of the skin. occlusive emollients (e.g., petrolatum-based products, lanolin, mineral and vegetable oils, waxes) prevent water loss and alleviate irritation. a combination of the two is useful for attracting and sealing water at the level of the corneum layer and soothing the skin. . thick greasy creams and ointments (e.g., petroleum jelly) provide higher protection against xerosis than lotions. to reduce the risk of contact sensitization, it is highly recommended to use fragrance-free and hypoallergenic products. . when soap and water are not available, the cdc advises that the use of alcohol-based hand sanitizers (that contain at least % alcohol), is an effective alternative in destroying the virus. since these can be irritating, it is important to hydrate the skin immediately after. applying a moisturizing cream afterward does not interfere in any way with the properties and efficiency of this type of sanitizers. . for individuals working with protective gloves, it is highly recommended to wash hands and apply moisturizer whenever gloves are taken off. also, to lower the humidity, they should be changed systematically and applied only on dry hands. . for people with highly sensitive skin, which easily develop disturbing forms of dermatitis, short courses of topical corticosteroids may be used to reduce the signs and symptoms of inflammation. covid- and italy: what next? who declares covid- a pandemic sars-cov- and covid- : the most important research questions water disrupts stratum corneum lipid lamellae: damage is similar to surfactants effects of four soaps on skin trans-epidermal water loss and erythema index tolerability and cosmetic acceptability of a body wash in atopic dermatitis-prone subjects methylisothiazolinone in rinse-off products causes allergic contact dermatitis: a repeated open-application study can we contain the covid- outbreak with the same measures as for sars? replace hand washing with use of a waterless alcohol hand rub in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. compliance with hand hygiene recommendations is essential in preventing the spread of covid- and, under no circumstances, should be diminished by the eczematous changes that may occur in the hands. in this context, the potential development of hand dermatitis is preventable and manageable by using the appropriate skin care products. regular skin hydration is a key component in preventing hand dermatitis as a consequence of frequent washing. key: cord- -q qndic authors: onyeaka, henry k; zahid, shaheer; patel, rikinkumar s title: the unaddressed behavioral health aspect during the coronavirus pandemic date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: q qndic the novel coronavirus ( -ncov) pneumonia has been declared a pandemic, citing more than , cases of the coronavirus illness in more than countries and territories around the world. public health emergencies have been demonstrated to have an impact on the behavioral health of the affected population as they may experience fear, anxiety, anger and post-traumatic stress disorder as consequences of their experiences. these effects may persist among affected individuals long after the outbreak has been controlled. to date, data on the behavioral distress and psychiatric morbidity of those suspected or diagnosed with the -ncov and their treating health professionals are lacking. although the centers for disease control and prevention (cdc) has outlined some behavioral health guide for affected individuals, how best to respond to psychological challenges during the crisis is not known. there is an urgent need to provide robust and timely psychosocial support in the face of such an outbreak. the novel coronavirus ( -ncov) pneumonia, which originated in the hubei province in china at the end of , has gained intense attention nationwide and globally. in the united states, since the first case was detected in washington, dc, in mid-january , the virus has continued to spread. as of march , , a total of , confirmed cases have been reported in jurisdictions ( states, district of columbia, puerto rico, guam and us virgin islands) and has resulted in deaths [ ] . on march , the world health organization (who) declared -ncov a pandemic, citing more than , cases of the coronavirus illness in more than countries and territories around the world and the sustained risk of further global spread. while the exact origin remains largely unknown, the virus has been shown to cause respiratory illness ranging from mild to severe and is spread via human to human transmission. at the moment, the therapeutic strategies to deal with the infection are only supportive and preventive. based on the available information regarding the virus, upgraded quarantine and isolation measures have been suggested to resist the spread of the virus. the centers for disease control and prevention (cdc) has issued detailed guidelines and recommendations to stem community spread of the virus. of the affected population [ ] . individuals and their families with confirmed or suspected -ncov may experience fear, anxiety, anger and post-traumatic stress disorder as consequences of their experiences. these effects may persist among affected individuals long after the outbreak has been controlled. furthermore, contact tracing and the mandatory quarantine isolation for two weeks, which is a crucial part of the public health responses to the -ncov pneumonia outbreak, could be a precursor for increased psychological distress such as posttraumatic stress disorder, anxiety and anger among suspected or confirmed cases [ , ] . also, the estimated global economic shutdown and recession is expected to heighten fears and anxiety. health professionals, especially those directly caring for people with confirmed or suspected -ncov pneumonia, are susceptible to both high risk of infection and behavioral health distress. the literature has documented high levels of psychological distress among healthcare workers in previous outbreaks. they may experience fear of contracting and spreading the virus to their families, friends or colleagues. in a cross-sectional study by wu et al., the healthcare workers who had been quarantined, or worked in the high-risk location such as severe acute respiratory syndrome (sars) wards, or had friends or close relatives who contracted sars, were significantly more likely to have high post-traumatic stress symptom levels than those without these exposures [ ] . to date, data on the behavioral distress and psychiatric morbidity of those suspected or diagnosed with the -ncov and their treating health professionals are lacking. although the cdc has outlined some behavioral health guide for affected individuals, how best to respond to psychological challenges during the crisis is not known. there is an urgent need to provide robust and timely psychosocial support in the face of such an outbreak. therefore, using lessons learned from prior epidemics like sars, middle east respiratory syndrome and the ongoing -ncov in china, some potential methods to mitigate the psychosocial impact of the pandemic should be emphasized. first, it is the provision of clear, accurate and updated information about the virus to both health workers and patients in order to allay their anxiety and fear. second, robust behavioral health services should be deployed to deliver behavioral health support to patients and health workers with additional training of more healthcare professionals in psychological first aid delivery to the high-risk population. lastly, given the present challenge of cross-infection from the onsite and face-to-face delivery of healthcare, telehealth and other remote forms of behavioral health delivery should be encouraged. the current -ncov outbreak may stretch the already limited behavioral health services, and prompt measures must be instituted to avert the potential acute and long-term psychological sequela that may ensue. coronavirus disease long-term psychiatric morbidities among sars survivors the psychological impact of quarantine and how to reduce it: rapid review of the evidence mental health status of people isolated due to middle east respiratory syndrome the psychological impact of the sars epidemic on hospital employees in china: exposure, risk perception, and altruistic acceptance of risk in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -flskltdf authors: malik, jahanzeb; javaid, muhammad; majedi, omaid; ishaq, uzma; zahid, tayyaba title: paying in blood: a case of thrombocytopenia in covid- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: flskltdf novel coronavirus disease (covid- ) primarily involves the respiratory system. consumptive coagulopathy is seen in acute respiratory distress syndrome (ards) and multi-organ failure (mof). usually, only severely sick patients develop mild thrombocytopenia. we present a case of mildly symptomatic young adult, presenting with severe thrombocytopenia. she responded well to corticosteroids. since its advent in december , the novel coronavirus disease (covid- ) has infected thousands of people globally with nearly deaths [ ] . covid- primarily produces a respiratory and systemic illness progressing to acute respiratory distress (ards) and multi-organ failure (mof) [ ] . it can also involve other organ systems such as hematopoietic and the immune system [ ] . infection with covid- typically presents with fever and upper respiratory symptoms like cough and dyspnea. a small proportion of mildly symptomatic patients present with atypical symptoms like diarrhea, thrombocytopenia, or bleeding tendencies [ ] . commonly, intravascular consumptive coagulopathies are only observed in severely ill patients [ ] . a narrow threshold for the identification of covid- should be practiced in the mild disease to prevent delayed diagnosis. we present a case of covid- , diagnosed with an isolated thrombocytopenia. a -year-old previously healthy laboratory technician at our institute developed malaise and severe body aches for the past one day. there were no respiratory symptoms, fever, rigors, and chills. she did not report any loss of smell or taste and there were no gastrointestinal symptoms. she gave no history of substance abuse and did not take any medications. there was no history of bleeding or purpura. her physical examination was unremarkable. hematology and biochemistry were ordered. the results showed significant thrombocytopenia. the platelet count was × /l and hemoglobin was . g/dl. there was a relative decrease in lymphocytes ( %). her erythrocyte sedimentation rate (esr) and c-reactive protein were mm/hr and mg/l while her d-dimers were negative. peripheral blood smear showed decreased platelets of × /l and no schistocytes. viral serology was negative for hcv-ab, hiv-ab, hbsag and igm, herpes, and cytomegalovirus. abdominal ultrasound did not show visceromegaly. chest x-ray and echocardiography were normal. ns- for dengue and a thick and a thin smear for malaria was also negative. a hematologist consult was made and a bone marrow biopsy showed increased megakaryocytes (figures , , ). considering the looming pandemic, her rt-pcr for covid- was also sent, which came out to be positive. on the following day, her platelets dropped to × /l and there was myeloid predominance on the peripheral smear. she was transfused four units of platelets. subsequent platelet counts improved to × /l. she was started on prednisolone mg/kg in three divided doses. on the third day, her platelet count was stable at × /l. it increased to × /l on the fourth day and to × /l on the fifth day. on the seventh day, prednisolone was stopped as the platelet count reached × /l. her second rt-pcr for covid- was negative. she was discharged from our institute and on the first follow up after one week, her platelets were × /l. she remained stable on the subsequent follow-ups. the exact mechanism of hematopoietic abnormalities is not known in covid- , but the proposed hypothesis is the increased autoantibodies and immune complexes clear the platelets from the circulation by the immune system. this leads to more platelet destruction and thrombocytopenia [ ] . several studies and case series have described a cascade of consumptive coagulopathies that cause thrombocytopenia [ , ] . such studies state that decreasing trend of platelets confer a grave prognosis of covid- infection and lead to a severe disease [ ] . one study has postulated that the virus significantly impacts the hematopoietic system leading to pancytopenia [ ] . the observation in our patient could be an immunologic reaction commonly seen in viral infections. surprisingly, all major studies have shown mild thrombocytopenia is a complicated course for the patient [ ] . one study demonstrated severe thrombocytopenia with pulmonary and neurological complications. however, in mildly symptomatic patients, isolated thrombocytopenia is not frequently described. there is only one case report published recently on idiopathic covid- associated thrombocytopenia [ ] . our patient was also mildly symptomatic and after ruling out all major causes of decreased platelets, it was postulated to be associated with the virus. variable presentations can lead to a missed diagnosis of covid- . this case report was intended to present a rare case and highlight the proposed mechanism for thrombocytopenia with the immune system working against the hematopoietic cell lines. the role of corticosteroids is evident in this disease and large randomized controlled trials should be conducted for better evidence as a treatment option. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. age-dependent risks of incidence and mortality of covid- in hubei province and other parts of china respiratory conditions in coronavirus disease (covid- ): important considerations regarding novel treatment strategies to reduce mortality. med hypotheses. mechanism of thrombocytopenia in covid- patients atypical presentation of covid- in a frail older person thrombocytopenia is associated with severe coronavirus disease (covid- ) infections: a meta-analysis coagulation abnormalities and thrombosis in patients with covid- exploring possible mechanisms for covid- induced thrombocytopenia: unanswered questions abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia coagulopathy in covid- : focus on vascular thrombotic events thrombocytopenia is independently associated with poor outcome in patients hospitalized for covid- isolated severe thrombocytopenia in a patient with covid- : a case report key: cord- -ls vud authors: khan, farah; eskander, noha; limbana, therese; salman, zainab; siddiqui, parveez a; hussaini, syed title: refugee and migrant children’s mental healthcare: serving the voiceless, invisible, and the vulnerable global citizens date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ls vud millions of children are on the run worldwide, with many unaccompanied children and adolescents undertaking risky journeys to flee war, adverse circumstances, and political persecution. the grueling journey and multiple stressors faced by the refugee children, both accompanied and unaccompanied during the pre-migration, migration, and in the country of destination, increase their risk for psychiatric disorders and other medical conditions. unaccompanied refugee migrant children have higher prevalence of mental health disorders than accompanied refugee peers. long after reaching the host country, the refugee, migrant, and asylum-seeking juveniles continue to face adversities in the form of acculturation. in assessing medical fitness and healthcare mediations for refugees and migrant children, special consideration should be given to certain areas such as their distinct history, whether they are with their family or separated or unaccompanied, and whether they have been peddled or have been left behind. an alarming number of children travel with family or alone without proper care to flee organized violence, war, and persecution in their native country. some cross their national borders to become refugees and seek asylum in other countries, a legal process recognized by the united nations. without a family or an adult, these children are often at risk of being exploited and abused. most of the refugee children live in nearby countries close to their own native place of origin that happen to be low-or middle-income countries [ ]. in , in italy about % of children arriving by sea were separated and unaccompanied [ ] . in , the high-income countries resettled , refugees [ ] . in , juveniles under years of age incorporated about half of the refugee population [ ] . in , uganda recorded , child refugees, the largest number of unaccompanied and separated child refugees with the overwhelming majority aged under and a couple thousand aged under . from - , turkey has been hosting . million refugees, the largest refugee population [ ] . in , the most common country of origin among child asylum seekers happens to be syrian arab republic. in , germany registered % of all child asylum applications lodged in europe ( , children), while the highest number of first-time applicants with regard to its population was greece [ ] . the grueling journey faced by the refugee children, both accompanied and unaccompanied during the pre-migration, migration, and in the country of destination, is associated with multiple stressors resulting in elevated risks for psychiatric disorders and other medical conditions [ ] . the clinicians should be aware that exposure to war, a long arduous journey with minimum or no care, and ongoing stressors that refugee kids have experienced are associated with physical, developmental, and mental health problems. this migration is in itself dangerous, and apart from mental and other health costs to it there is also an increased risk of disabilities, and vulnerabilities to acute and chronic ailments. this article discusses some of the commonly seen mental health conditions and other medical conditions in refugee and migrant children from the reviewed articles. it also provides an insight into the refugee mental health struggles during the coronavirus (covid- ) pandemic and the migrant detention facilities. studies were selected and reviewed after applying the inclusion/exclusion criteria on pubmed. the following were the inclusion criteria: ( ) age years and younger, ( ) both female and male, ( ) articles in english, and ( ) studies published within the last one year. exclusion criteria were age above years and non-english articles. the articles selected from pubmed were broken down as seen in table . after applying inclusion/exclusion criteria and using regular keywords, the total number of articles selected after review and refined search were as they fit the selection criteria. the articles removed were not included for lack of relevant data. the flowchart seen in figure shows the starting keywords used, and the number of articles obtained on pubmed for literature search with the applied filters. finally, the total number of used articles is displayed alongside those which were not selected. barriers, economic opportunities, lack of understanding of the healthcare system, knowledge about available resources, issues pertaining to accessing health and other services, trust factor, financial problems, transportation issues, and the larger policy and political context of local authorities [ , ] . primary care physicians, pediatricians, and mental health providers can build trust through culturally competent and trauma-informed care, assess for healthcare needs, provide vaccination update and preventative care, and screen for mental health, communicable diseases, disabilities, and other medical health conditions thereby attending to the holistic needs of the vulnerable child and adolescent refugees. refugee children are less likely to avail pertinent health and social care than non-refugee children peers [ ] . most host countries offer some kind of health screening for refugees, both child and adult, upon entering the country of destination [ ] . in assessing medical fitness and healthcare mediations for refugees and migrant children, special consideration should be given to certain areas such as their distinct history, whether they have migrated along with their family or have been separated from family, are unaccompanied, whether they have been peddled, or have been left behind [ ] . children's right to medical care is guaranteed by all the world leaders and member states of the who european region and is compiled in the convention on the rights of the child (crc), a convention guaranteeing the highest attainable standard of healthcare and treatment of illness and rehabilitation of the refugee, migrant, and asylum-seeking children similar to the children native to the host country [ ] . the most vulnerable children include the asylum seekers and the undocumented or unregistered migrants. asylum seekers have usually been tested with war and/or political oppression in their native country and live in uncertainty and temporary circumstances regarding their future. the undocumented children often live in dangerous environments with little or no availability of basic societal rights, in abuse, poverty, brutality, and social boycott, and among threats of deportation [ ] . migrants face a myriad of issues during various aspects of their journey between countries. during the pre-migration phase of this process, there is a lack of access to health/dental care, scarcity of food, and exposure to diseases. during the journey, lack of access to health/dental care and food scarcity continue to be problems. additionally, human trafficking, violence, and injuries during the trip are also present. finally, in the country of destination, difficulty in finding resources presents itself as the largest barrier. these resources include health/dental care, education, therapy, and other basic amenities. this process repeats itself and becomes a cycle if migrants are deported back to their country of origin and seek to migrate once again [ ] . refugees and migrants arriving in the host country, many of which have different cultures and languages from their native country, go through a course of learning and acclimatization to the new civilization. this stressful process of acculturation compounds the migration strain thereby amplifying the psychological distress. children and adolescents, who are enrolled in school, generally learn the new host country language faster and conform to the new culture faster than parents, who may be secluded giving rise to new challenging family issues. family tensions can cause disharmony, separation, and even assault, with associated adverse effects on a child's mental health [ ] . some of the needs of the refugees and migrants include access to mental health services; the youths have a need for civil activities and community acceptance while the parental urgency is to feel culturally protected. competency in a local language of the host country, and support from local community, school, and local authorities make their transitions easier and decrease the acculturation stress. figure shows some of the mental and other health challenges of the refugee and migrant children. communicable diseases: cramped and overpopulated settlement and lack of cleanliness and sanitation in facilities housing refugee and migrant children put them at increased risk for diarrhea and skin infections [ ] . the third-world countries show a higher prevalence of tuberculosis, malaria, intestinal parasites, and hepatitis b and c, than the developed nations. these chronic infections are present in increased prevalence in refugee and migrant juveniles [ , ] . a study reports of unaccompanied refugee and migrant children who were arriving in germany with multidrug-resistant bacteria colonization at higher rates, and other records of a surge of measles, which is vaccine-preventable, have also been seen in asylum-seeking juveniles [ , ] . clinicians should have a low threshold to screen for sexually transmitted infections (stis) in adolescent refugees as they have the highest rate of curable stis worldwide [ ] . some of the commonly seen non-communicable diseases include obesity and psychological problems in migrant children [ ] . obesity could be due to stress or change in dietary habits. vitamin d deficiency is often caused by lack of exposure to sunshine in winter [ , ] . other conditions like malnutrition and multivitamin deficiencies are most likely to be prevalent too due to lack of access to food and health care in the migration journey. as per unhcr data, about , of refugee children in were unaccompanied minors [ ] . segregation from parents can be harmful to a child's health and prosperity, mostly mental health, as parents lay the foundation for the societal and environmental base for children [ ] . unaccompanied refugee minors have a higher prevalence of psychiatric disorders than accompanied refugee peers [ ] . when accompanied by families, and after having experienced the migration trauma, children are often "hidden from sight" with no regard to their own personal wishes. mental health must be seen as a complex primary healthcare need and should be served in a holistic and family-oriented manner whenever possible. research studies have shown that freshly arrived migrant and refugee juveniles are at a high risk of psychosocial and mental issues due to exposure to organized crime and migration stress [ ] . these are most commonly internalizing disorders -anxiety, depression, and post-traumatic stress disorder (ptsd) [ , ] . a study of asylum seekers with serious mental health problems, in the netherlands, found that parental symptoms of ptsd were associated to infants' troubled attachment and that parental apathy was related to parental ptsd [ ] . a cohort study found that caregivers' ordeal history and postmigration adversities were correlated with greater ptsd, rigid parenting, and an increase in child conduct problems [ ] . expressive symptoms, however, were found to be equal to that in children of the host country [ ] . longitudinal studies have shown that the high rate of internalizing symptoms tended to wear off slowly over a period of time, with expressions of ptsd fading away in about seven years after arrival to the host country [ ] . some frequently reported emotional and behavioral mental health problems among bhutanese refugee youth include fighting, loneliness, depression, and being scared. other symptoms of oppositional defiant disorder, intermittent explosive disorder, conduct disorder, generalized anxiety disorder, major depressive disorder, and disruptive mood dysregulation disorder were also seen among them [ ] . migrant and refugee juveniles frequently have to compromise more when parents are suffering from psychiatric disorders after dreadful experiences and migration strain. parents with mental health challenges battle to give their children a feeling of support and stability [ ] . migration stress with socioeconomic deprivation takes a toll on the parents and increases the risk for child abuse [ ] . early and adequate cognitive, mental, and emotional support for parents suffering from behavioral disorders is thus a vital support for children. refugees may hesitate to seek mental health help due to a culturally based stigma around mental health issues [ ] . family separation and parental death drives adolescents to take on parental roles for younger siblings. recognition of these roles will enable physicians to provide suitable emotional and social support. risk factors in the host country, such as financial hardships, parental separation, and aggression/bullying, were analyzed as vital determinants of mental health at follow-up [ ] . in recent years, cognitive behavioral psychotherapy, eye movement desensitization and reprocessing (emdr), and narrative exposure therapy for migrant and refugee children who have experienced war and displacement have been established for the evaluation and treatment of ptsd and depression [ ] . strengths of refugee children include personal resilience, parental support, close-knit family structure, and lasting association with their religious and cultural identity from the country of origin [ ] . the staggering majority, %, of the global refugee population is accepted in developing regions with limited access to quality mental health even before the pandemic [ ]. now, they are overwhelmed with mental health crisis, as warned by the unhcr. while many refugees and internally displaced people are exceptionally resilient, their abilities to cope are now being stretched to the limit. the loss of daily wages and livelihoods is taking a toll on their mental health and causing psychosocial hardships. social distancing measures and limited mobility are compounding emotional distress with reports of self-harm increasing among the refugees. the covid- precautions and reduced staffing levels during this pandemic are also impacting the availability of aid and mental health support as refugees are often unable to travel, and many face-to-face activities have been cancelled. the unhcr is stepping up efforts to ensure the continuity of care by providing mental health services remotely through multi-lingual telephone hotlines and over the internet through online sessions. in addition, they are ensuring that people who need medication can continue treatment during lockdown [ ] . the teaching recovery techniques approach is used to decrease children's discomfort and post-traumatic symptoms and to improve peer and kinfolk relations [ ] . this psychosocial intervention is meant for juveniles who have experienced dreadful circumstances. children are assembled in organized groups focused at augmenting emotional management, survival competency, and conflict resolution skills. these techniques also help the children to express themselves. there is also a parent component session to educate about intervention and on skills to reinforce care of their children. ladnaan intervention is a culturally adapted parenting guidance program combined with local civic orientation for somali-born parents living in sweden. a trained community educator of somali origin facilitates the program. parents report higher success and satisfaction after completing the course and convincing improvement in behavioral problems in their children. in this -week session, parents are educated on local community information, receive lectures and take part in workshops, and exchange views on the parent-child liaison, attachment, child growth, and development of interpersonal skills [ ] . mind-spring is a mental health disorder prohibition plan in belgium, denmark, and the netherlands. it provides psycho-education, and psychosocial and parenting skills for refugee and asylum-seeking parents in a culturally conscious manner in their own native language [ ] . it deals with topics on mental health such as stress, ordeal, depression, personality, acculturation, and mental health fitness. the program promotes exchanging thoughts on experiences and provides parents with information about mental health expertise to recognize signs of suffering and mental ailment in themselves. it also educates the parents about obtaining help if and when needed. parents also obtain the required skills and support in the parenting process and how to ploy collateral parenting issues. studies have shown that educational institutions play a vital role in conserving and promoting the health and well-being of refugee and migrant children. successful school-based mental health prevention requires experts trained in cultural proficiency, who can interpret the mental health requirements and risks of refugee and migrant children, and who can conform the learning program to the needs of the individual child and family [ , ] . hearing all voices was a pilot project undertaken by child to child in london aimed at promoting social inclusion, commitment in education, and local community involvement among vulnerable youth, with a prime focus on refugee, migrant, and asylum-seeking youth [ ] . the pharos school prevention program conducts classroom-based program in the netherlands with the aim of developing social involvement among migrant children with local host community children and adults while simultaneously attending to individualized requirements of each child [ ] . health assessments are performed for refugee and migrant children in a school setting in malmo city, sweden. here, the school nurse meets the juveniles and their caregivers for a health assessment to define and address each child's healthcare requirements. an analytical interview is followed by a broad general examination of the body, including dentition, eyesight, and hearing. mental health is briefly assessed and vaccination history is analyzed. referrals are made based on the necessity of specialized services. national governments have a significant role in establishing living circumstances for refugee and migrant children as most freshly settled refugee families rely on national and local authorities' support for habitation and existential expenses. governments determine the rights of children to access health care maintenance and educational benefits in their country. policies that exemplify humanity should be planned and implemented for the refugees/migrants and asylum seekers. a detailed individualized health evaluation by a healthcare professional on arrival to the host country should determine the healthcare needs and screen for communicable diseases; disability should be assessed and vaccinations should be updated. this response will help detect infections early on, allow timely treatment to be given, and will be most cost effective in the long run. the availability of medical translators and native cultural arbitrators is important to ensure the best healthcare outcome for refugee and migrant children. blueprints to improve welfare, and access to education and health in refugee and migrant children should have a comprehensive framework that targets risk factors on individual, family, and community levels. culturally sensitive, parent and other caregiver support curriculum and interventions in the school and local community centers should be promoted. transferring children between multiple locations should be minimized as it disrupts the peer networks and educational flow; this also holds good for unaccompanied children with substitute caregivers. in order to build good relations with substitute caregivers, unaccompanied children need consistent long-term, definitive housing with the same guardians. the most vital physical, social, and psychological support for children are their parents; therefore, family reunions should be expedited [ ] . the united states of america has built the largest immigration detention system in the world. in , a staggering , migrant children including infants, toddlers, kids, and teens were held in custody in facilities across usa. these facilities lack enough clinicians or specialized care for the detained children [ ] . immigration detention has adverse and detrimental consequences for the well-being of those detained, but studies have found that it is most inimical to children [ ] . the negative impacts of detention on mental health are more brutal for children than for adults; therefore, detention should not be weaponized for deportation of migrant children. if this is inevitable, then the facilities harboring children should have childfriendly areas, and avenues for healthcare and education should be provided. children on the move also suffer brutality, injustice, and misconduct from law enforcement officials -local police, border guards, and detention officers. such events cause children to quickly learn to mistrust authorities. these adverse psychological effects may last years after release from detention [ ] . children are global citizens and their rights move with them; therefore, their healthcare needs should not be defined by geographic borders. mounting evidence suggests welcoming and supportive policies for refugee, migrant, and asylum-seeking children can prevent psychological distress and mental health disorders in these vulnerable children. all-inclusive policies that aim at protecting the rights of every child should be enforced globally. children should not be held in detention centers indefinitely in subhuman conditions away from their parents/primary caregivers. reuniting children with their families should be prioritized and expedited. it is imperative to enforce preventative mental health policies and refrain from practices that abuse human rights. healthcare providers should consider volunteering in refugee and migrant camps, and also in local community free clinics that are accessed by refugee and migrant children. this will ensure adequate staffing in detention facilities specially during the pandemic where the invisible, voiceless, and vulnerable refugee and migrant children along with the adult refugees and migrants can get timely medical attention and treatment for their healthcare needs. research is needed on improving resilience building and for appraising the impact of precise interventions that could improve outcomes. more longitudinal studies are needed to assess interventions that increase better mental health mediterranean situation health of refugee and migrant children: technical guidance . who regional office for global trends -forced displacement latest statistics and graphics on refugee and migrant children health considerations for immigrant and refugee children migrant children in europe: entitlements to health care. models of child health appraised barriers to access to health care for newly resettled sub-saharan refugees in australia structural and socio-cultural barriers to accessing mental healthcare among syrian refugees and asylum seekers in switzerland rights of accompanied children in an irregular situation a systematic review of risk and protective factors associated with family related violence in refugee families assessing the burden of key infectious diseases affecting migrant populations in the eu/eea infectious diseases of specific relevance to newly-arrived migrants in the eu/eea multidrug-resistant bacteria in unaccompanied refugee minors arriving in frankfurt am main measles among migrants in the european union and the european economic area toward global prevention of stis): the need for sti vaccines the health of migrant children in switzerland serum levels of -hydroxyvitamin d in mothers of swedish and of somali origin who have children with and without autism high prevalence of somali population in children presenting with vitamin d deficiency in the uk. arch dis child risk of mental health and nutritional problems for left-behind children of international labor migrants incidence of psychiatric disorders among accompanied and unaccompanied asylum-seeking children in denmark: a nation-wide register-based cohort study mental health problems of syrian refugee children: the role of parental factors mental health in syrian refugee children resettling in the united states: war trauma, migration, and the role of parental stress the effect of post-traumatic stress disorder on refugees' parenting and their children's mental health: a cohort study prevalence of serious mental disorder in refugees resettled in western countries: a systematic review attachment representation and sensitivity: the moderating role of posttraumatic stress disorder in a refugee sample we left one war and came to another: resource loss, acculturative stress, and caregiver-child relationships in somali refugee families exile and mental health in young refugees the transmission of trauma in refugee families: associations between intra-family trauma communication style, children's attachment security and psychosocial adjustment psychological interventions for post-traumatic stress disorder and depression in young survivors of mass violence in low-and middle-income countries: meta-analysis unhcr urges prioritization of mental health support in coronavirus response interventions for children affected by armed conflict: a systematic review of mental health and psychosocial support in low-and middle-income countries klingberg-allvin m: a support program for somali-born parents on children's behavioral problems school and community-based interventions for refugee and asylum seeking children: a systematic review hearing all voices in london us held record number of migrant children in custody in global protection and the health impact of migration interception mental health of unaccompanied asylum-seeking adolescents previously held in british detention centres key: cord- - sgfx oq authors: mansour, amani; atoui, rola; kanso, kamal; mohsen, rami; fares, youssef; fares, jawad title: first case of an infant with covid- in the middle east date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: sgfx oq the novel coronavirus (covid- ) has been declared a worldwide pandemic. it was initially thought to spare children and adolescents as significantly smaller number of cases have been reported in the pediatric population in comparison to adults. here, we report the case of a -month-old female infant from lebanon who presented with fever and severe diarrhea and tested positive for covid- . her symptoms started six days prior to presentation with no cough, rhinorrhea, or other respiratory manifestations reported. chest radiography showed lobar consolidation and bronchial infiltrates. blood culture was positive for streptococcus pneumoniae. stool and urine cultures were negative. she was treated with ceftriaxone and metronidazole. her rt-pcr test was negative after five days of treatment, suggesting that children can clear the virus faster than adults. the patient likely contracted the virus from her parents, who because of the fear of social stigma hide recent history of respiratory illness. these findings serve as a practical reference for the clinical diagnosis and medical treatment of children with covid- . the novel coronavirus disease (covid- ) is the result of an infection with the severe acute respiratory syndrome coronavirus (sars-cov- ), a member of betacoronavirus. initial cases were detected in wuhan, a city in china, near the end of [ ] . the virus is believed to replicate in the respiratory system during the prodromal period, and exhibits human-to-human transmission patterns through respiratory droplets and contact routes [ , ] . the disease causes mild to severe illness, with symptoms appearing - days after exposure and most commonly comprising fever, cough, and shortness of breath. most severe illness occurs in older adults but comparison with the pediatric population can be challenging as documented cases in infants and children have been scarce [ , ] . as of mid-march , covid- has spread rapidly and widely to become a global pandemic [ ] . outbreaks have been reported in china, south korea, iran, italy, spain, and the united states. many other european, asian, african, and north and south american countries have been reporting cases [ ] . nevertheless, the middle east countries have been lagging in terms of publishing clinical outcomes [ ] . here, we report the first case in the middle east of a -month-old lebanese female, previously healthy, who had symptomatic covid- . the patient was transferred from another hospital due to increasing hypoactivity and severe diarrhea. the referring hospital had ruled out coronavirus infection due to the absence of cough. parents reported that the infant was healthy and had regular food intake until symptoms started six days prior to presentation. they denied exposure to or contact with infectious risk factors and affirmed that no cough/rhinorrhea symptoms were present. upon examination, the patient was febrile ( °c) with a respiratory rate of breaths per minute and a heart rate of bpm. chest auscultation revealed rhonchi. differential diagnoses included gastroenteritis, pneumoniae, and covid- , and the patient was put on isolation as a preliminary measure. laboratory studies revealed leukocytosis with a white cell count of , cu mm (range: , - , ) and elevated c-reactive protein level reaching . mg/l (range: - ) ( table ) . cultures for blood, urine, and stool were taken. a chest radiograph showed left upper lobe consolidation and bilateral lower lobe infiltrates (figure ). this warranted nasopharyngeal swabs for an rt-pcr to test for sars-cov- . imaging of the infant's chest shows large consolidation at the left apical lobe with bronchial infiltrates that are dominant at the left base, and asymmetrical lung bases (a). the heart size is normal, the rib cage is intact, and the diaphragmatic arches are in normal position (a). a discrete blunting at the left pleural sinus can be observed (b). in the meantime, the patient was put on a hydration regimen and was started on ceftriaxone ( mg/kg/day) and metronidazole ( mg/kg, every eight hours). on day of admission, the patient became afebrile and exhibited improvement in physical activity. on day , the result of the rt-pcr test returned positive for covid- . blood culture was positive for streptococcus pneumoniae. stool and urine cultures were negative. upon further investigation, the father admitted that he had 'flu-like' symptoms two weeks before presentation but denied travel history or contact with a defined case of covid- . the mother also confessed having similar symptoms but did not seek medical consultation at the time. this hinted that the patient likely contracted the virus from her parents, who, in turn, might have been infected through community transmission. the family was transferred to a designated quarantine for isolation. on day , the rt-pcr test of the infant was negative, and the patient's symptoms had resolved. cases of covid- in children are not as rare as they might have been thought [ , ] . this is the first case reported from the middle east that involves a -month-old female infant. around . % of cases with covid- were reported to be among the pediatric population in china [ ] . ages ranged between and years, with males being predominantly affected [ ] [ ] [ ] . uniquely, our patient presented with fever and diarrhea; cough and other respiratory symptoms were not reported. previous covid- studies in the pediatric population noted that common symptoms include fever, cough, sore throat, and rhinorrhea. diarrhea has not been reported yet [ , ] . this warrants a more comprehensive definition of the symptoms that govern covid- in the pediatric population, as gastrointestinal symptoms have been documented in our case and among adults [ ] . the rt-pcr test was negative after five days of treatment and days after the onset of symptoms. this suggests that children might clear the virus more rapidly than adults. similarly, previous research in children indicates that the rt-pcr test becomes negative within days (range: - ) after the presentation of symptoms [ ] . the first rt-pcr test took two days for the result to generate, whereas the subsequent test was much faster, and the result was obtained on the same day due to the expansion of the testing capacity by the lebanese ministry of public health. fear of social stigma drove the patient's parents to hide information of their respiratory tract illnesses. it is important to address this issue at public health levels and to stress and highlight the social responsibility associated with reporting any relevant medical data related to the covid- pandemic. moreover, health communication and promotion strategies must be improved to increase awareness and literacy on the current pandemic, and brush off rumors and misinformation that can cause fear and panic [ ] . this is the first case reported from the middle east on an infant presenting with fever and diarrhea that tested positive for covid- . cases of covid- in children are not as rare as they might have been thought. covid- related pediatric symptoms can exhibit an array of presentations, including diarrhea. most cases recover well with symptomatic care. this case serves as a practical reference for the clinical diagnosis and medical treatment of infants with covid- . human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. genomic characterisation and epidemiology of novel coronavirus: implications for virus origins and receptor binding a familial cluster of infection associated with the novel coronavirus indicating potential person-to-person transmission during the incubation period sars-cov- infection in children detection of covid- in children in early an epidemiological study on covid- : a rapidly spreading disease coronavirus disease (covid- ) and pediatric patients: a review of epidemiology, symptomatology, laboratory and imaging results to guide the development of a management algorithm a bibliometric analysis of covid- research activity: a call for increased output a -day-old female infant infected with covid : presenting with pneumonia, liver injury, and heart damage novel coronavirus infection in hospitalized infants under year of age in china a case series of children with novel coronavirus infection: clinical and epidemiological features clinical and ct features in pediatric patients with covid- infection: different points from adults epidemiological characteristics of pediatric patients with coronavirus disease in china clinical characteristics of covid- patients with digestive symptoms in hubei, china: a descriptive, cross-sectional, multicenter study health communication research in the arab world: a bibliometric analysis key: cord- -hmqq w a authors: yurdaisik, isil title: effectiveness of computed tomography in the diagnosis of novel coronavirus- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: hmqq w a coronaviruses (cov) belong to the coronavirus genus of the coronaviridae family. all covs are pleomorphic rna viruses containing crown-like peplomers of - nm in size. this virus is a zoonotic pathogen seen with a wide range of clinical features from asymptomatic state to intensive care in humans. so far, seven human coronaviruses have been identified with the last one being coronavirus- (covid- ). these pathogens typically lead to mild disease, but sars and mers type coronaviruses have caused severe respiratory disease and even mortality within the last years. covid- virus has rapidly spread worldwide after china and is continuing to cause huge economical and social impacts. given the scarcity of resources including healthcare staff, hospital capacities, test kits, etc., timely diagnosis and treatment of this virus are of paramount importance. however, there is no vaccination or drug developed for the treatment of this disease up to today. because the spreading rate of the virus is very high worldwide and there is no definitive treatment, diagnosis becomes even more important. the objective of this review is to evaluate the use of chest computed tomography, one of the commonly used radiologic imaging modalities, in the diagnosis of covid- in light with the current literatüre. a series of pneumonia cases with unknown causes have been reported from the wuhan state of china. a few days later, this mysterious causative agent of pneumonia was declared as a novel coronavirus [ ] . after severe respiratory syndrome coronavirus (sars-cov) in and middle east respiratory syndrome coronavirus (mers-cov) in , novel coronavirus (covid- ) was introduced in the human population as a highly pathogenic and large-scale epidemic coronavirus [ ] . this novel virus was previously named as severe acute respiratory syndrome (sars) coronavirus- , and later the virus was named as covid- by the world health organization (who). on january , , the who officially declared that covid- became an epidemic as an international public health emergency. on march , , covid- was characterized as a pandemic by the who [ ] . as of april , , , confirmed covid- cases and , deaths were reported in europe region [ ] . coronaviruses (cov) belong to the coronavirus genus of the coronaviridae family. all covs are pleomorphic rna viruses containing crown-like peplomers of - nm in size. this virus is a zoonotic pathogen seen with a wide range of clinical features from an asymptomatic state to intensive care in humans. although most coronaviruses affect animals, these are zoonotic pathogens that can be transmitted between animals and humans. so far seven human coronaviruses have been identified with the last one being covid- . these pathogens typically lead to mild disease, but sars and mers type coronaviruses have caused severe respiratory disease and even mortality within the last years. today, the covid- virus has rapidly spread worldwide after china and is continuing to cause huge economic and social impacts. given the scarcity of resources including healthcare staff, hospital capacities, test kits, etc., timely diagnosis and treatment of this virus are of paramount importance. there is no vaccination or drug developed for the treatment of this disease up to today. because the spreading rate of the virus is very high worldwide and there is no definitive treatment, the diagnosis becomes even more important [ ] . the objective of this review is to evaluate the use of chest computed tomography (ct), one of the commonly used radiologic imaging modalities, in the diagnosis of covid- in light with the current literature. epidemiology was identified in china for the first time, but it has rapidly spreaded all over the world in a short time and currently is increasingly reported in all continents. the number of cases outside china outpaced the number and rate of new cases in china [ ] . epidemiological studies have reported that the outbreak was associated with wild animals sold in a seafood market in wuhan province [ ] . however, later confirmed cases without a history of exposure to this market indicated human-to-human transmission of covid- . as the epidemic progressed, human-to-human transmission has become the main transmission route of the virus. all ages are sensitive to covid- . however, the virus is more fatal in the elderly population. the infection is transmitted through droplets produced during cough and sneezing [ ] . according to recent studies in the literature, viral loads are higher in the nasal cavity compared to the throat; thus, there is no significant difference between symptomatic and asymptomatic people [ ] . infected droplets can spread a few meters, accumulating on surfaces. covid- can survive for days under positive atmospheric conditions, although it can be destroyed in shorter than one minute using common disinfectants such as sodium hypochlorite and hydrogen peroxide. the infection occurs by inhalation of these droplets or touching the mouth, nose, and eyes with the hands after touching contaminated surfaces. the incubation period of covid- is thought to be within days after the exposure. however, the majority of cases have been seen within - days of exposure [ ] . in a study including patients with a confirmed diagnosis of covid- , median incubation duration was found as four days [ ] . clinical features of covid- vary from asymptomatic state to acute respiratory distress syndrome and multiorgan dysfunction. common clinical manifestations include fever (not in all cases), cough, sore throat, headache, and shortness of breath. in a study, fever was reported as %, cough as %, and shortness of breath as % of covid- patients [ ] . however, there are still no specific clinical features to reliably distinguish covid- from other viral respiratory infections. in a part of patients, the disease may progress to pneumonia, respiratory failure, and death at the end of the first week. according to a study from china, around % of the patients presented with severe symptoms and % required intensive care [ ] . in italy and spain, % to % of the hospitalized patients were reported to require intensive care [ ] . the first approach in covid- is to early detect suspected cases, immediately isolate these people, and implement infection control measures. the diagnosis of covid- is established with fever, cough, and/or dyspnea together with a history of contact with an infected person in a distance shorter than approximately meters and/or travel to the areas, where the disease is common within the last days. however, covid-cases may be asymptomatic and even may not have a fever. this disease is confirmed with positive molecular testing. according to the american centers for disease control and prevention (cdc), test priority criteria in suspected covid- patients that were updated as of march , are as follows [ ] : hospitalized patients with signs and symptoms compatible with covid- . elderly people (≥ years) and people with chronic medical conditions and/or immunocompromised status (e.g. diabetes mellitus, heart disease, using immunosuppressive medications, chronic lung disease, chronic kidney disease) who can be at risk for a poor outcome. including healthcare personnel, people with a history of close contact with other persons with suspected or laboratory-approved covid- or travel to the affected geographic areas up to days before the onset of symptoms. molecular tests used for the diagnosis of covid- are performed on respiratory samples (throat swab, nasopharyngeal swab, sputum, and endotracheal aspirates). the virus can also be identified in stool and blood in severe cases. the diagnosis of covid- is mainly established with reverse transcription-polymerase chain reaction (rt-pcr) test. however, this test requires strict laboratory specifications and the results take a long time [ ] . other laboratory investigations are usually non-specific. indicators such as white blood cells, platelets, creactive protein (crp), and erythrocyte sedimentation rate (esr), alanine aminotransferase/aspartate aminotransferase (alt/ast), prothrombin time, creatinine, ddimer, and low-density cholesterol (ldl) are also studied. nevertheless, these markers have been associated with disease severity and are not specific to covid- [ ] . chest x-ray is one of the diagnostic modalities used to help the diagnosis of covid- . this image usually shows bilateral infiltrates. however, the results of this method can be normal at the beginning of the disease. chest ct is more sensitive and specific in the diagnosis of covid- compared to x-ray. ct images usually show infiltrates, ground-glass opacities (ggo), and sub-segmental consolidation. in addition, ct is abnormal also in asymptomatic patients without clinical findings related to the involvement of the lower respiratory tract. ct scans have been used also in suspected covid- patients with a negative molecular diagnosis, and repeated molecular tests were positive in most of these patients [ ] . imaging plays an important role in the diagnosis and management of covid- . chest ct is used as the first-line imaging method in suspected cases and is a useful tool for monitoring the changes during treatment. correct diagnosis of viral pneumonia based on chest ct indicates isolation and plays an important role in the management of patients suspected to have an infection, especially in the absence of scientifically proven treatment methods. findings on ct may reflect the severity of the disease. therefore, ct is an important imaging technique in helping the diagnosis and management of covid- patients, and publications about the radiologic appearance of covid- pneumonia are increasing in the literature. as this disease increasingly becomes a global concern, it is more crucial for radiologists to be familiar with ct images of covid- and to have basic knowledge about the clinical course and size of this infection. radiologists to have sufficient knowledge about the clinic and chest ct imaging of covid- will help early detection of the infection and evaluation of the disease course. so far reported common ct features regarding covid- are as follows [ ] : ct images are usually examined in four distributions as craniocaudal, transverse, lung region, and scattered. thin slice chest ct is more effective in the early detection of covid- [ ] . some case series and case reports investigating chest ct imaging features of covid- have been published [ ] [ ] [ ] [ ] . it has been reported that ct abnormalities are more likely to be bilateral, to have a peripheral distribution, and to involve the lower lobes [ ] . in a study comparing covid- patients in china and patients with other viral pneumonia in the usa, peripheral distribution, ggos, thin reticular opacities, vascular thickening, and reverse halo sign were more common, while central and peripheral distribution, air bronchogram, pleural thickening, pleural effusion, and lymphadenopathy were more rare in covid- cases [ ] . in a study from wuhan, china, it was reported that covid- had abnormal findings on chest ct even in asymptomatic patients [ ] . in that study, chest ct findings of patients with covid- were examined. examinations were performed by two radiologists who were blind to rt-pcr testing results. according to the results of the study, ct images showed bilateral lung involvement in %, peripheral distribution in %, and diffuse distribution in % of the patients. the most common chest ct findings included ggo together with poorly defined margins, smooth or irregular interlobular septal thickening, air bronchogram, and thickening of adjacent pleura [ ] . remarkably, in a study by shi et al., early ct changes were seen in the asymptomatic patient group, and these findings supported the observations in a familial cluster with covid- pneumonia [ ] . however, some studies have reported positive rt-pcr results in the absence of ct changes or abnormal ct results in the presence of initial false-negative rt-pcr results [ ] . predominant detection of ggos on ct in covid- makes this method more sensitive. in a study by song et al., the most common chest ct findings were reported as ggo appearance in covid- patients [ ] . in a case series of patients by chung et al., ggo was the most common ct finding by %, and bilateral disease was found in % of covid- patients [ ] . however, ct findings may be normal also in confirmed cases [ ] . in a study by radiologists from wuhan, china, it was found that chest ct had a low misdiagnosis rate in covid- and this method can help standardization of imaging and a rapid diagnosis [ ] . on the other hand, it has been reported that the use of ct is limited in the detection of specific viruses and making a distinction between viruses [ ] . in a study from wuhan including patients who underwent rt-pcr testing and chest ct, the sensitivity of positive results by the consensus of two radiologists was found as % when pcr tests were used as a reference. however, in the same study, the specificity of ct was only % [ ] . it was reported that this low specificity may be associated with other etiologies leading to ct findings. in general, chest findings of chest ct in covid- overlap with the findings of other infections such as h n , sars, and mers, and this limits the specificity of ct. effectiveness of ct in covid- should be carefully evaluated because the majority of the existing data come from the studies conducted in the far east. according to the studies in the literature, the preference of ct in china is resulted from the wide availability of this method, because access to ct is relatively easier in china [ ] . in most of these studies, it was reported that chest ct was positive in the presence of negative test results [ ] . rt-pcr results can be affected by sampling errors and low viral load [ ] . in previous studies about sars, the sensitivity of rt-pcr has been shown to be insufficient within the first five days of the disease [ ] . in addition, findings of this rapidly spreading conditions have not been completely published or are not updated. cdc currently does not recommend the use of ct for the diagnosis of covid- . according to the cdc, viral testing is the only specific diagnosis method, and even in the case of covid- radiologic findings with ct, the results must be confirmed with viral testing [ ] . according to lee et al. who are radiologists in hong kong university, the variability of covid- presentations leads to difficulties in establishing the diagnosis. the authors emphasized that there are more things to learn from this contagious viral pneumonia, and further studies are needed on the relationship between ct findings and clinical progression [ ] . ct scans of a patient with covid- are shown in figures - . air bronchograms and fibrosis were developed. bilateral milimetric central aeration areas on d image. sectional routine image better shows lesion details, and d images better depict involvement area in the lung. there is debate in the literature on the use of chest ct for the diagnosis of covid- . as this epidemic progresses, various presentations of covid- will be increasingly observed, and the correlation between ct and rt-pcr findings will be more commonly studied. as the picture becomes clearer, the radiologic-pathologic correlation will be better understood, potential imaging predictors will be determined in more detail, and the role of radiology in the management of covid- will be increased. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the 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differentiating covid- from viral pneumonia on chest ct radiological findings from patients with covid- pneumonia in wuhan, china: a descriptive study ct imaging features of novel coronavirus ( -ncov). radiology. ct imaging of the novel coronavirus ( -ncov) pneumonia . radiology. wuhan ct scans reliable for coronavirus (covid- ) diagnosis, limited for differentiation correlation of chest ct and rt-pcr testing in coronavirus disease (covid- ) in china: a report of cases pneumonia associated with novel coronavirus: can computed tomographic findings help predict the prognosis of the disease? clinical progression and viral load in a community outbreak of coronavirus-associated sars pneumonia: a prospective study early diagnosis of sars coronavirus infection by real time rt-pcr acr recommendations for the use of chest radiography and computed tomography (ct) for suspected covid- infection thank physicians and all other healthstaff worldwide for their incredible efforts to fight this outbreak. key: cord- - i mpvn authors: zhang, qian; shan, khine s; abdollahi, shahrzad; nace, travis title: anosmia and ageusia as the only indicators of coronavirus disease (covid- ) date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: i mpvn the patient is a -year-old woman with a history of vertigo and seasonal allergies who presented to the hospital with the chief complaint of headache. radiological findings were negative for intracranial abnormalities. the headache was due to trigeminal neuralgia. she had concurrent complaints of anosmia and ageusia without fever, respiratory symptoms, or obvious risk factors. however, it was determined to test the patient for coronavirus disease (covid- ) infection despite extremely low clinical suspicion. unfortunately, she was found to be covid- positive after she was discharged from the hospital while she remained asymptomatic. there is currently a lack of published case reports describing covid- patients with the sole symptoms of anosmia and ageusia in the united states of america. , or coronavirus disease , originated from wuhan, china, in december . it is caused by novel enveloped single-stranded ribonucleic acid (rna) betacoronavirus, which is known as the severe acute respiratory syndrome coronavirus (sars-cov- ) [ ] . this disease has since quickly spread worldwide within a few months. the world health organization (who) reports that there are a total of , , global cases along with , total deaths as of april , [ ] . typical symptoms include fever, cough, and shortness of breath [ ] . while these symptoms are the typical presentations, other symptoms are gaining more attention as possible indicators of the disease as our understanding of the disease is rapidly evolving. these atypical symptoms include olfactory and gustatory dysfunctions [ ] . there is a lack of evidence in the current medical literature of anosmia or ageusia in patients suspected of having covid- infection. the center for disease control (cdc) currently does not include these findings as symptoms of covid- but does state that medical awareness should be increased in this setting [ ] . likewise, the who does not include these symptoms as part of the differential diagnosis but does mention that other unconventional symptoms, such as myalgia, nasal congestion, runny nose, sore throat or diarrhea, do exist [ ] . physicians are sounding the alarm to this lack of attention and evidence in the medical literature. this case report details a year-old woman with the chief complaint of right-sided headache along with anosmia and ageusia but was eventually found to be sars-cov- positive. our patient is a -year-old woman who presented to the emergency department (ed) with the chief complaint of right-sided headache for the past week. she had a past medical history of asthma, vertigo, seasonal allergies, and anxiety. her headache was located predominantly at the right temporal, retro-ocular, and retro-auricular regions. she described the headache as an "electrical sensation" that was associated with occasional nausea, blurry vision in both eyes accompanied by a metallic taste in the mouth with a loss of smell sensation. she denied any fever, sore throat, rhinorrhea, cough, myalgia, vomiting, dysphagia, neck pain, chest pain, shortness of breath, weakness, or sensory disturbances. the review of systems was otherwise unremarkable. she had magnetic resonance imaging (mri) in the outpatient setting last year due to vertigo and the result was unremarkable. she was generally healthy otherwise and did not take any medications except for occasional loratadine for seasonal allergies. she is currently retired, lives at home, denies any smoking history or recent traveling. she was recommended by her primary care physician (pcp) to take amoxicillin to treat for sinusitis as the possible underlying cause of her symptoms. however, she elected to defer the treatment but rather decided to present to the ed for further evaluation. in the ed, her initial vital signs were: temperature . °f, blood pressure / mmhg, respiratory rate breaths per minute, heart rate beats per minute, and oxygen saturation % on ambient air. physical examination was completely unremarkable. the only abnormal laboratory results were: erythrocyte sedimentation rate (esr) mm/hr, alanine transaminase (alt) u/l. computed tomography (ct) head without contrast showed no acute intracranial abnormality ( figure ). her headache was thought to be related to trigeminal neuralgia and was prescribed gabapentin mg twice a day. there were also concerns for possible covid- infection due to anosmia and ageusia but additional testing was deferred due to the lack of fever, respiratory distress, and laboratory abnormalities. this decision was made upon extensive discussion with the infectious disease specialist, as the clinical suspicion for covid- was extremely low because it could be related to her seasonal allergies. the patient remained stable overnight. her headache improved on days - of hospitalization. mri of the brain found stable extensive white matter changes without acute ischemic findings ( figure ) . she was eventually placed in airborne isolation and sars-cov- was sent to rule out covid- infection despite low clinical suspicion. she was subsequently discharged from the hospital and was instructed to self-quarantine given pending results. sars-cov- came back to be positive after one day. she was notified over the phone and was recommended to continue to self-quarantine and seek medication attention if there are new symptoms. stable extensive white matter changes without the presence of acute infarction mri: magnetic resonance imaging the most common covid- symptoms include fever ( . % on initial presentation and . % during hospitalization), cough ( . %), nasal congestion ( . %), nausea or vomiting ( . %), and diarrhea ( . %) based on a research study of patients from china. however, both anosmia or ageusia were not mentioned as both common and atypical symptoms in this study. significant laboratory findings that were listed include lymphocytopenia, thrombocytopenia, leukopenia, elevated c-reactive protein, creatinine kinase, and d-dimer [ ] . however, there are other, newly emerging initial presenting symptoms that were absent in the chinese patients, as covid- spreads quickly across the globe. they include asymptomatic carriers and other nonspecific symptoms that do not generally arouse suspicion of a possible covid- infection. most hospitals in the united states utilize covid- screening criteria that include cough, fever, and/or respiratory distress. unfortunately, these screening criteria may miss out on silent carriers and those with atypical presentations. furthermore, italy and france surprisingly reported a large population of patients with symptoms of anosmia and/or ageusia in a covid- confirmed diagnosis. in a letter to the editor submitted to the journal obesity, jean-françois gautier and yann ravussin stated that they have observed cases of anosmia in patients following two to three days of fatigue and headache [ ] . epidemiologist hendrik streek mentioned that two-thirds of the patients have anosmia and ageusia lasting several days in germany [ ] . in addition, % of covid- confirmed cases in south korea have had the primary initial symptom of anosmia [ ] . one preliminary study from china by mao et al. reported that . % of the patients with covid- had anosmia and . % had ageusia [ ] . in another study of patients from italy by vaira et al., . % of patients had chemosensory dysfunction not associated with rhinitis or nasal obstruction. however, these data have been underestimated as symptoms of anosmia and ageusia were not always addressed [ ] . our patient had a very low clinical suspicion of covid- infection, as she was afebrile along with no respiratory symptoms despite having anosmia and ageusia in the setting of headache caused by trigeminal neuralgia. fortunately, she was adequately tested given that cases of atypical presentation have been reported in the past. gane et al. described a similar case report of a patient with positive covid- who presented with isolated anosmia but was otherwise asymptomatic [ ] . there are a few hypothesized mechanisms of action on why covid- patients may develop anosmia and ageusia despite their association with sars-cov- not having been yet established. it could be due to direct damage of the virus on olfactory and gustatory receptors [ ] . the nasal epithelium contains olfactory epithelium (oe) and olfactory sensory neurons (osns). oe contains basal stem cells that are responsible for renewing sustentacular cells and osns. it also contains microvillar cells and mucus-secreting bowman's gland cells. sustentacular cells structurally support sensory neurons, detoxify, and maintain the salt and water balance. it is thought that sars-cov- infects cells through interaction between its spike (s) protein and the angiotensin-converting enzyme (ace ) protein on target cells. this interaction requires cleavage of the s protein by the cell surface protease tmprss . therefore, ace and tmprss are required for sars-cov- to infect cells [ ] . the study of mouse and human rna sequencing datasets by brann et al. showed that oe expresses two key genes required for sars-cov- entry: ace and tmprss . osns, on the contrary, did not show any gene expression. sustentacular cells in oe express these genes at levels comparable to those found in lung cells. thus, it suggests that sars-cov- may infect oe that contains sustentacular cells, leading to damage of oe and disturbing the function of osn. loss of sustentacular cells and the inability to regenerate oe over time can result in long-lasting anosmia. in addition, damage to microvillar cells in oe might alter iron gradients and thus affect the function of sensory neurons. damage to the bowman's gland cells could cause disruption of the olfactory neuroepithelium. however, due to the relatively new identification of sars-cov- -associated anosmia, no formal experiments have been performed to explore sars-cov- 's influence on oe. moreover, it is unclear whether the olfactory abnormality is due to dysfunction in the higher-order olfactory structures. it has shown previously that viruses including coronavirus can propagate to olfactory bulb or piriform complex even though the exact mechanisms of action are unknown. it is also unclear whether the impact of sars-cov- on smell is responsible for the alteration in taste perception [ ] . even though the association of anosmia with sars-cov- is currently not well-known, previous respiratory viruses, such as coronaviruses, have shown to cause problems with smell receptors and have been associated with post-viral anosmia [ ] . a very recent multicenter european study reported that . % of patients with sars-cov- presented with olfactory dysfunction prior to other symptoms. there was also a high prevalence (around %) of olfactory or gustatory dysfunction among those patients with sars-cov- [ ] . thus, further research on the prevalence, duration, and severity of anosmia and ageusia in patients with covid- is needed, as it is important to guide the prompt diagnosis, treatment, and prevention of covid- in the setting of an ongoing pandemic. the understanding of covid- is rapidly evolving, as we are in the middle of an unforeseen, ongoing pandemic. symptoms of covid- patients range widely from fever, respiratory symptoms, to newly reported findings of anosmia and ageusia from south korea, italy, and france. awareness of a possible covid- infection should be raised in patients with the sole presentation of anosmia and ageusia despite the lack of published case reports or research findings on its exact mechanisms of action. extra attention is sometimes a game-changer for patient care and safety especially as we are situated in uncharted territory. covid- discoveries are being made every day and healthcare providers should closely follow its footsteps to ensure the best care is delivered to all patients. clinical characteristics of coronavirus disease in china situation report - accessed a new symptom of covid- : loss of taste and smell . obesity (silver spring) what are the symptoms of covid- there's an unexpected loss of smell and taste in coronavirus patients neurological manifestations of hospitalized patients with covid- in wuhan, china: a retrospective case series study anosmia and ageusia: common findings in covid- patients isolated sudden onset anosmia in covid- infection. a novel syndrome? non-neural expression of sars-cov- entry genes in the olfactory epithelium suggests mechanisms underlying anosmia in covid- patients sixty seconds on olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (covid- ): a multicenter european study human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -nypkr authors: drexler, richard; hambrecht, jan m; oldhafer, karl j title: involvement of medical students during the coronavirus disease pandemic: a cross-sectional survey study date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: nypkr background: the coronavirus disease (covid- ) pandemic affects the education of medical students around the world and countries have had differing responses in dealing with this dynamic situation. the role of medical students in fighting this pandemic is controversial and it is yet to be elucidated how they can best be of service. the aim of this study is to evaluate the working fields of volunteering students and the impact of the pandemic on final year students from a student's perspective. methods: an anonymous online survey was conducted amongst medical students from hamburg (germany), using an institutional online data collection program. results: a total of questionnaires ( . %) were completed. of these, participants were students from academic year three to five ( . %) and students were in the final year of medical school ( . %). of the students from academic year three to five, students ( . %) signed up for voluntary duties during the pandemic. interestingly, only . % of the students were called for voluntary work in hospitals or health authorities. final year students had already been working in hospitals since before the outbreak, with . % of them assisting doctors in the treatment of covid- positive patients during their placements. using a -point likert scale, the students who volunteered self-assessed their work as more useful and received more gratitude than final year students (p< . ). conclusions: the majority of medical students are willing to make a significant contribution in the response to covid- and do not wish to be overlooked. furthermore, the current pandemic offers novel educational opportunities for medical students. the coronavirus disease (covid- ) pandemic has spread globally with major outbreaks in the usa, italy and spain. although the end is not yet in sight and the final lasting impact of covid- is difficult to gauge, it is clear that the current situation is overwhelming for health care systems and economies around the world. as the pandemic progresses, staff shortages will likely occur, and this raises the question of who will step up to the plate in this ongoing crisis. in this context, the role of medical students is unclear and contentious [ ] [ ] . due to legal requirements, social distancing was implemented and in-person medial classes have been cancelled and replaced with online lectures and virtual teaching for most medical students [ ] . however, the educational situation is crucial for final year students, as they are completing clinical clerkships. these students are normally integrated into medical teams as well as clinical routines and gaining clinical experience is a crucial aspect for success in future residencies. nevertheless, student participation in clinical care varies across medical schools and different countries. some countries, such as italy, china and the united kingdom, integrated the medical students into their health care systems or graduated students early [ ] [ ] [ ] . on the contrary, other countries cancelled clerkships and restricted patient contact for medical students [ ] [ ] . in germany the treatment of final year students varied across hospitals, but non-final year students were encouraged by the german minister of health to volunteer in healthcare facilities [ ] . it is clear that there is a dissonance between medical students' roles during the covid- pandemic and the progression of patient-centered medical education. in this study, we present medical students' involvement during the covid- pandemic. we evaluate the usefulness of volunteering students as a response to the pandemic as well as the assessment from a student's perspective during volunteering. in addition, we describe the impact of the pandemic on final year students and their clinical education. an online survey was designed and sent to medical students enrolled at the campus hamburg (germany) of the semmelweis university budapest (hungary) via personalised institutional email. the survey was conducted using an institutional online data collection program. two surveys were performed, one survey for medical students from academic year three to year five and a separate survey for final sixth-year students. the surveys consisted of single, multiple-choice, and -point likert scale questions and recruitment began on may , . the survey was open from may , , to may , , and available in german. inclusion criteria were students currently active from academic year three to six at the medical faculty hamburg of the semmelweis university budapest. ten external students piloted the survey prior to publication, and minor amendments to wording to improve clarity were made. after a period of data collection, three researchers checked the database for errors and false data independently from each other. four main topics were addressed: ( ) reasons for volunteering or rejection of volunteering; ( ) work circumstances of volunteering students; ( ) critical self-reflection of usefulness of volunteering and ( ) impact of covid- pandemic on planned clerkships and future plans after graduation. students from academic year three to five were initially asked if they had registered as volunteers. individuals who volunteered until may , , then answered a more detailed questionnaire about reasons, working field, type of activity, working hours, and contact to covid- -positive patients. furthermore, they selfreflected their volunteer work answering a -point likert scale ("strongly disagree", "disagree", "neutral", "agree", "strongly agree"). the final year students were asked about the changing workload since the beginning of the covid- pandemic, contact to covid- positive patients, possible infection, and the impact on future residencies. in closing, final year students self-reflected their clerkship answering the -point likert scale as described above. all study procedures were reviewed and approved by the ethics committee hamburg, germany (wf- / ). no patient data was included. we informed participants that their answers would be anonymously used for statistical analyses and that they would not be transmitted to third parties. variables were processed and analysed using ibm spss statistics for mac version (ibm corp., armonk, ny, usa). data were reported as number with percentage. differences in proportions were analysed with the chi-square test or fisher exact test. differences in -point likert scale between third to fifth year and final year students were compared, using the two-sample t-test as stated by norman [ ] . a two-sided p-value less than . was considered as statistically significant. the survey was sent to medical students including third-year students ( . %), fourth-year students ( . %), and fifth-year students ( . %). the remaining students ( . %) were in the final year of medical school. in total, questionnaires ( . %) were completed. of these, participants were non-final year students ( . %) and students were in final year ( . %). we enrolled students from academic year three to five with an equal distribution within the years (p= . , table ). these students were affected by the cancellation of in-person medical classes, which were consequently replaced by online lectures. the students were therefore enabled to volunteer in hospitals or aid health authorities during the covid- pandemic. of the students, the majority ( . %) registered as volunteers, while students ( . %) did not ( table ) . depending on their first answer, students were asked what motivated them to sign up as volunteers or to decline the opportunity. the volunteering students had quite similar answers with the majority indicating a sense of duty to society ( . %), interest in medical activity ( . %), and social commitment ( . %) as their incentives. the main reason given for not signing up was a lack of time due to studying commitments or part-time jobs ( . %). however, six students ( . %) were either part of a high-risk group or had a first-degree family member at risk. finally, students ( . %) received notification that their clinical clerkships were cancelled due to the on-going pandemic. multiple answers were possible, in total: answers. multiple answers were possible, in total: answers. as previously stated, students signed up for voluntary commitment but only students ( . %) were called for work. these students were asked further questions regarding their work circumstances in the survey ( table ). the majority ( . %) were called within a week after signing up. almost half of the students ( . %) were assisting health authority bodies, which involved telephone consultations or data administration ( . %). five students ( . %) volunteered in the hospital, either on the ward, in icu, or in the emergency department. the remaining volunteers worked in the ambulance service ( . %) or worked in general practices ( . %). during their voluntary work, six students ( . %) had physical contact with patients who tested positive for covid- . however, none of these students were suspected of having or tested positive for covid- . to evaluate the usefulness and gratitude of the voluntary work during covid- pandemic, the volunteering students were confronted with several statements that were answered using a -point likert scale (figure ) . when self-reflecting on their work, % of the students felt helpful and % were under the impression that other medical staff valued their work. approximately half of the volunteers acquired new skills through their work and only % felt overburdened. academic year three to five. the final year students have a special status as they were already working in hospitals at the beginning of the covid- pandemic. therefore, a second survey was specifically designed to evaluate the impact of covid- on their workload and clinical education. the response rate was . % and consisted of final year students ( table ) . when comparing the students' workload before and during the covid- pandemic, most students ( . %) experienced a reduced workload. of note, students ( . %) were directly involved in treating covid- positive patients. during their rotations students ( . %) were suspected to be covid- positive, but ultimately tested negative. as previously described for the first survey, the final year students were confronted with different statements regarding their role during the covid- pandemic ( figure ). only . % of the students evaluated their work as helpful and felt their contribution was valued by other medical staff. in addition, . % agreed that they developed new skills due to the covid- pandemic. most importantly, students felt the pandemic had a negative impact on education; especially bedside teaching for example, was experienced by . % of students. focussing on future perspectives, the majority ( . %) felt the pandemic had a negative impact on their planned residencies or research activities after graduation. we described the perspectives of two student groups during the covid- pandemic. on one hand, the volunteering students from academic year three to year five, and on the other, the final years in their practical placements. both groups were equally involved in covid- patient care ( . % vs. . %, p> . ). however, final year students were more often suspected of being covid- positive (p< . ). when evaluating the role of both groups using a -point likert scale, significant differences were observed. the volunteering students evaluated their work as more helpful and more of them felt they had acquired new skills (p< . ). in addition, volunteers' work was appreciated and valued more by the medical staff in comparison to final year students conducting their clinical placements (p< . ). the covid- pandemic has spread around the world and poses a significant challenge ubiquitously for all health care systems. in the wake of finding solutions for possible staff shortages, the role of medical students is contentious as they could significantly contribute to the ongoing crisis. to address this eminent topic, we performed an online survey amongst medical students from hamburg, one of germany's epicentres during the pandemic. we evaluated the willingness to volunteer among third to fifth-year medical students. the actual demand for students was also evaluated as well as the practicality for volunteers in hospitals and health authorities. in addition, our study focussed on the ever-changing clinical education experienced by final year students. these students were already in the final months of their practical placements when the pandemic broke out. as the traditional didactic, in-person teaching shifted towards online lectures and virtual seminars since the beginning of the pandemic, most students wanted to contribute to the fight against the covid- pandemic [ , [ ] [ ] [ ] [ ] . the results of our survey underline the willingness of medical students to contribute to the handling of the crisis as . % of the students signed up for voluntary commitment. of the remaining students who were unwilling to volunteer, nearly % were either already employed in a part-time job in hospitals or unable to sign up due to a higher risk of severe illness from covid- . however, it was remarkable that only . % of the students had been called for voluntary work, mainly in the realm of hospital care or health authorities. this low number begs the question if hospitals in germany really need student volunteers and gives the impression that hospitals are capable of solving staff shortages without the helping hands of medical students. one explanation might be that lower numbers of infections were experienced here than had been anticipated. however, when looking at current reports from several countries it becomes clear, that this abrupt conclusion cannot simply be drawn and medical students are indeed able to have a positive impact during the covid- pandemic [ , ] . this is reiterated by the fact that % of the final year students in this study were already involved in the treatment of covid- patients and the role of medical students in general could prove to be indispensible in the on-going fight against the pandemic. furthermore, it is noteworthy that staff shortages and the demand for medical students correlates with the extent of the pandemic outbreak and the strain on the respective country's healthcare system. as major outbreaks were experienced in italy and the uk, medical students played a central role in dealing with the crisis in comparison to germany [ ] [ ] [ ] . however, bearing in mind the unequivocal will of medical students to participate in the fight against covid- , the role of medical students must be considered. focussing on our results, volunteering students supported doctors in patient care or worked at a covid- hotline service. students who took over these tasks unburdened doctors from administrative duties so that they could entirely shift their focus to essential care of critically ill patients. in our study, volunteering students were encouraged to self-reflect on the usefulness of their tasks via a -point likert scale. the majority of students considered their work as useful and felt it was valued by medical staff. this emphasizes that students could undertake certain tasks with a symbiotic advantage for both doctors and students, and is consistent with ideas by miller and colleagues [ ] . however, it is doubtful if these students are sufficiently trained to undertake roles with more responsibility, such as assisting with invasive ventilation of patients [ ] . the student group most affected by the covid- pandemic is undoubtedly students in their final year, due to restricted patient contact, reduced bed-side teaching and even cancelled clerkships [ , [ ] [ ] [ ] [ ] . therefore, it is unsurprising that . % of the final year students in this study reported a negative influence on their clinical education. in addition, the dissonance in suitable roles for final year students during the pandemic has lead to huge dissatisfaction in our study cohort. final year students have gone through years of rigorous training, are nearing graduation, and therefore could have a decisive role and make a significant contribution during this pandemic. even though clinical education is currently not the main focus, the integration of final year students into critical care of covid- patients could be of indispensable value for teaching certain skills, such as critical care or ventilation therapy. furthermore, it can prove useful for crisis management preparation with regard to possible future pandemics. the ongoing pandemic is a challenging time for maintaining clinical education for students on the cusp of graduation, but could be regarded as a worthwhile opportunity to educate them beyond the traditional curriculum. innovative ideas are urgently needed in order to implement these novel-learning opportunities and simultaneously integrate final year students as full members into critical care or emergency teams. there have been a few promising approaches introduced in recent literature [ , , ] . rasmussen and colleagues initiated fast-track courses in ventilation therapy and nursing assistance for medical students attending aalborg university and successfully integrated the majority of these students into medical care teams [ ] . another promising approach came from klasen and colleagues who developed a training curriculum including all necessary aspects for working in a triage-test-center for diagnostic swab-testing. after educating medical students according to this new curriculum, they were assigned to emergency teams that evaluated hundreds of patients daily and provided over swabs during a five-week period [ ] . these concepts combine the contribution of medical students to the pandemic with the utilization of these novel learning opportunities. these newly acquired unique clinical skills further the student's opportunities in their future career as a physician. more importantly, rasmussen and klasen demonstrate how medical students' role was crucial to the fight against the covid- pandemic. the involvement of medical students is entirely dependent on the gravity of the situation in the respective country. our study showed the current situation in one of the worst-affected cities in germany and evaluated the medical students' involvement in the covid- response from the students' perspective. in addition, ramussen and klasen et al. introduced concepts functioning in denmark and switzerland [ ] [ ] . it would be favourable to share further experiences from various other countries, which would show the integration of medical students into clinical settings. this could prove invaluable in the ongoing fight against covid- and much can be learned from different countries' approaches. nevertheless, the students' point of view must be taken into consideration in order to benefit future generations of medical students and patient care. it is our hope that the covid- pandemic leads to the development of alternative plans in how medical students could be positively utilised in future pandemics and in other exceptional circumstances, so that hospitals and medical schools are better prepared for future crises. we are convinced that pandemics, especially the current one, could offer various educational opportunities for medical students and should not lead to educational disadvantage and feelings of overall dissatisfaction. the majority of medical students are willing to make a significant contribution in the response to covid- and do not wish to be overlooked. furthermore, the current pandemic offers novel educational opportunities for medical students. however, it is mandatory that medical schools and hospitals implement functioning concepts in which students are integrated into clinical settings. disclosures medical students are not essential workers: examining institutional responsibility during the covid- pandemic the role of medical students during the covid- pandemic virtual bedside teaching rounds on patients covid- : medical students and fy doctors to be given early registration to help combat covid- covid- : medical schools are urged to fast-track final year students guidance-on-medical-students-participation-in-direct-patient consequences of covid- on international medical graduates and students applying to residencies in the united states likert scales, levels of measurement and the "laws" of statistics let us help'-why senior medical students are the next step in battling the covid- pandemic we signed up for this! -student and trainee responses to the covid- pandemic coalition for medical education-a call to action: a proposition to adapt clinical medical education to meet the needs of students and other healthcare learners during covid- senior medical students in the covid- response: an opportunity to be proactive. acad emerg med. medical students for healthcare staff shortages during the covid- pandemic wab team instead of swat team -students as front-line force during the covid- pandemic covid- : medical students should not work outside their competency, says bma the impact of covid- on medical education medical student involvement in the covid- response letter: covid- impact on the medical student path to neurosurgery a bold response to the covid- pandemic: medical students, national service, and public health students supporting critical care -a contention plan to prevent the decompensation of icus in the covid- pandemic: translating bjorn ibsens' polio-lessons to modern times human subjects: consent was obtained by all participants in this study. ethics committee hamburg, germany issued approval wf- / . all study procedures were reviewed and approved by the ethics committee hamburg, germany (wf- / ). no patient data was included. we informed participants that their answers would be anonymously used for statistical analyses and that they would not be transmitted to third parties. . animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -hp yft authors: basnet, sangita; koirala, sameena; pandey, basu; koirala, janak title: covid- containment efforts of a low-resource nation: the first four months in nepal date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: hp yft a novel coronavirus (severe acute respiratory syndrome coronavirus or sars-cov- ) was identified in hospitalized patients in wuhan, china, in december . it rapidly spread across the globe within the span of a few months. nepal is a low-resource country with limited critical care delivery infrastructure. coronavirus (covid- ), the disease caused by the virus, could potentially cause a medical catastrophe in nepal. we reviewed all pertinent documents published in the public domain by the ministry of health and population of nepal and other relevant literature. we aimed to describe the key strategies nepal embraced in the first four months in its attempt to curtail the disease immediately following the identification of its first case and the challenges it faced. in our review, we determined that the key steps taken by nepal included border control to prevent the importation of cases, strict quarantine in facilities for anyone entering the country, early case detection, and isolation of all infected cases irrespective of symptoms. testing capabilities, quarantine facilities, and isolation beds were also rapidly increased. we discuss how nepal achieved some success in the first four months between january , , when the first case was identified, to may , . however, it faced several challenges that ultimately led to an exponential rise in cases thereafter. in december , a novel coronavirus, subsequently termed severe acute respiratory syndrome coronavirus (sars-cov- ), was identified in hospitalized patients in wuhan, china [ ] . coronavirus disease (covid- ) , the disease caused by the virus, was declared a pandemic by the world health organization (who) on march , [ ] . nepal is a small mountainous nation in asia situated between its much larger neighbors, india and china. with % of its million population living below the $ . per person per day international poverty line, and a gross national income of $ per capita, it is one of the poorest countries in the world [ ] . china borders nepal on its north and has extensive sociopolitical relations with the himalayan nation. at the time covid- emerged, there were close to nepali students in wuhan, the epicenter of the disease [ ] . the first case of covid- was a -year-old nepali man, returning from wuhan university of technology, who once the first case was identified, nepal started preparing for the epidemic, focusing mainly on the identification and management of cases [ ] . a high-level coordination committee under the chairmanship of the prime minister and minister of defense was formed for oversight of preparation and response activities. five hub hospitals and satellite hospitals were designated covid- hospitals, requiring dedicated space for the isolation of infected individuals. expert teams were formed to formulate guidelines for the treatment, testing, and management of covid- . ongoing communication was established among the central and provincial health emergency operation centers and the ministry of health. temperature monitoring was instituted at the tribhuvan international airport, the only international airport in nepal. on march , , mandatory self-quarantine of all individuals arriving from the eight nations (china, italy, spain, iran, south korea, germany, france, and japan) that had community spread was initiated. health screening consisting of a questionnaire for symptoms and a temperature check was instituted at points of entry (poe) from neighboring nations, india and china. strategies to prevent the entry of the disease (march , , to march , ) the high-level committee on covid- in kathmandu decided on march to make every attempt to prevent the entry of the virus into nepal [ ] . on march , all entry visas were suspended and all land poe shut down [ ] . passengers that had arrived in nepal were requested to stay in self-quarantine and report to the sukraraj tropical and infectious disease hospital in case of symptoms [ ] . surveillance and containment efforts (march , , to may , ) the second case, a -year-old who had arrived in kathmandu from france, tested positive for sars-cov- on march , . this led to the decision to lock down the nation on march . only essential services, including pharmacies and grocery stores, could open. citizens could only leave their houses at designated time periods [ ] . all domestic and international flights were halted. maintaining physical distancing, masks, hand washing, and hand sanitizers were encouraged. towards the end of march, there were five cases that had arrived from china, europe, and dubai that tested positive and were placed in isolation in covid- -designated hospitals in kathmandu. trained personnel under the epidemiology and disease control division (edcd) were mobilized to conduct extensive contact tracing based on their flight details and movement history to identify individuals with a potential infection. a team was even mobilized to a village outside the capital city to investigate contacts of a case in kathmandu [ ] . terrified villagers enforced lockdown and quarantine, imposing their own rules utilizing ageold "mukhiya" (village chief) traditions, at times even preventing their own relatives working in neighboring towns from entering their villages by barricading entry points [ ] . this state of lockdown continued for almost three months until mid-june. lockdown/quarantine measures were strictly reinforced by the security sector (police, border management, corrections). police presence was expansive and powerful. they implemented cash fines, confiscation of vehicles, and even imprisonment for failure to adhere to quarantine measures. the number of hospitals for the management of covid- was increased to designated hospitals, hub hospitals, and provincial hospitals [ ] . isolation beds were created rapidly in all seven provinces. by may , isolation and quarantine beds were increased to and , , respectively [ ] . an attempt was made to strengthen intensive care units and add additional ventilators. by the end of march, however, there were just icu beds with ventilators nation-wide, and over half were situated within the capital city [ ] . various private and public organizations aided in the training of health care workers and provided them with gowns, gloves, masks, and eye protection. the scarcity of personal protective equipment (ppe), particularly n masks and gowns, has been an ongoing concern. the high-level coordination committee formed a covid- crisis management committee (ccmc) chaired by the deputy prime minister and defense minister to monitor, coordinate, and manage all covid- prevention, control, and treatment activities. furthermore, to make this more effective, district level crisis management centers were also established. the testing capability was scaled up rapidly ( figure ) [ ] . by may , around reverse transcription-polymerase chain reaction (rt-pcr) assays were being done every day. early february, an rt-pcr primer for sars-cov- was made available at the national public health laboratory (nphl) in kathmandu. by may , there were such laboratories providing services around the nation. since these were newly set-up facilities consisting of personnel with limited experience, a nine-member expert team was formed to validate the tests. furthermore, samples of all presumptive cases were cross-verified at nphl before the final diagnosis. a protocol for the establishment of an rt-pcr laboratory was set forth, requiring at least a masters-level microbiologist with some experience in molecular microbiology. even though all flight services were suspended, nepal remained vulnerable to the transport of the virus from its two neighboring nations, china and india. high mountains separate nepal from china on the north, hence, there are limited poe that have remained closed since late january . however, the extensive open border to the south with india is easily accessible through several official and unofficial ground-crossing poe. to prevent the importation of the disease, starting april , "import nirdeshika" (protocol) was initiated at all poe [ ] . accordingly, a certificate of disinfection for transport vehicles, a selfdeclaration form, and a health check of all personnel were required at the health desk. vehicles were kept in the holding yard for disinfection. any suspicion prompted the individuals to be escorted to designated isolation/quarantine centers. mapping of migrant and vulnerable populations was conducted by nepal army and personnel trained and deployed by the edcd. hotspots were determined based on poe into nepal and reported by vigilant citizens, border control, security forces, healthcare workers, and, recently, by mobile tracking. on april , a decision was made to form a three-member case investigation and contact tracing teams (cictts), consisting of a public health professional, laboratory technician/assistant, and paramedic/nurse, utilizing local manpower to expedite and simplify screening and testing. accordingly, in early may, such teams were trained by the edcd and mobilized [ ] . all international travelers into nepal, via air or ground, and those who did not have feasible home-based quarantine facilities or were violating it were kept in quarantine centers for a minimum of days [ , ] . the who advised that all confirmed cases, even mild cases, should be isolated in health facilities, to prevent transmission and provide adequate care [ ] . accordingly, both confirmed and suspect cases were kept under strict isolation in designated covid- hospitals. guidelines were created to monitor quarantine management by the government of nepal. food and daily necessary commodities were provided by the government. by may th, , individuals were in quarantine in facilities around the nation, including schools, tents set up in open fields, other large public buildings and arenas. a rapid diagnostic test (rdt) for serology was initiated in nepal in early april as a supplement to rt-pcr [ ] . by mid-april, all districts throughout nepal were equipped for rdt testing. this gave the opportunity for rapid, on-site tests for surveillance purposes that required minimum skill. wide-spread testing was attempted on individuals entering nepal (figure ). adapted from the government of nepal, ministry of health and population. health sector response to novel coronavirus. [ ] figure demonstrates algorithms for the testing protocol established on april , , for all quarantined individuals and the mechanism for management and discharge once a suspect case was confirmed by rt-pcr [ ] . additionally, since rdt may not show the presence of positive antibodies in early stages and positive cases may be missed, if the cohort tested negative, % of the individuals in the cohort would receive pcr testing for surveillance. positive cases were discharged after two samples of rt-pcr results negative hours apart. figure elaborates the protocol for case investigation and contact identification of probable and suspect individuals, in addition to confirmed cases [ ] . adapted from the ministry of health and population. epidemiology and disease control division. standard operating procedure for case investigation and contact tracing of covid- . interim version. [ ] as of may , , rt-pcr assays and , rdt had been conducted with testing rates of and per , population, respectively [ , ] . on may , in order to increase the rate of testing in the limited number of facilities, pcr of pooled samples of individuals in quarantine and low risk for covid- was started at a ratio of : . social media campaigns, including viber, facebook, websites, in addition to pamphlets, radio, and television focused on educating the public on strategies to prevent transmission [ ] . two toll-free call centers were established in order to provide counseling and information to citizens. a mobile application was set up for individuals to be able to assess their health status. if their self-assessment was concerning, health care workers from the ministry of health contacted them for the further need for testing or management. daily briefings were broadcast by the health ministry via television and radio to share the current state to update the public and debunk false information. after the initial cases introduced into kathmandu by flight in early march as detailed above, there was a cohort of a few dozen indian nationals adjacent to the border entering nepal from india by land that tested positive. early may, there was community transmission, resulting in a handful of sars-cov- positive cases in individuals who were living in nepal. then, the surge in cases in the second week of may occurred as a result of infected nepali migrant workers returning home. males between and years of age consisted of % of confirmed cases. as of may , all but infected cases were asymptomatic or had mild symptoms, with no deaths or even intensive care admissions (figure ) [ ] . the rate of infection in nepal has been increasing exponentially. just in the final three days of the four-month period of this review, confirmed cases doubled from to [ ] . a little over a month later, right before the publication of this article, it has increased to over , with deaths. this exponential increase is as a result of an influx of infected cases crossing the open border between india and nepal as the rate of infection in india escalated [ ] . the economic upheaval caused by the shut-down in india forced thousands of nepali migrant workers to attempt to enter nepal [ ] [ ] . additionally, indian nationals traveled into nepal for religious, social, and trade reasons. there is no requirement for a visa or passport for citizens of these two nations to cross over. most individuals enter nepal via unguarded territories to avoid quarantine thus increasing the risk of community spread of the virus [ ] . this influx has resulted in overwhelmed government-run quarantine and isolation facilities with shared confined spaces. this has, most likely, resulted in the in-facility transmission of the disease. poverty makes home quarantine a poor alternative in a country like nepal where large families live in crowded homes with scarce water and bathroom facilities. ultimately, this can result in unchecked community transmission [ ] . most individuals in quarantine are tested only at the end of two weeks with the serological method before being released to go home [ ] . this increases the period of close contact. inadequate resources and funding compounded by a lack of automated pcr machines limits prompt testing with rt-pcr, which could have led to earlier triage. a major barrier is nepal's dependence on external support and the import of essential health commodities for the covid response, including the diagnostic tools (rt-pcr and serology). at the beginning of the outbreak, nepal also lacked adequate molecular testing facilities and trained manpower except for a few places. inadequate trained manpower and insufficient essential facilities will make it difficult to manage the surge of symptomatic and critical covid- patients. there are medical doctors per , population. two-thirds are working in the few major cities of nepal, including kathmandu [ ] . one recent study reported that medical doctors and nurses were physically present in only % and % of surveyed primary healthcare centers, respectively. furthermore, % of staff consisted of semiskilled and unskilled workers [ ] . additionally, nepal lacks enough hospital beds, intensive care units, ventilators, drugs, and necessary ppes as well as expert manpower such as trained intensivists, respiratory therapists, skilled intensive care unit (icu) nurses, and infectious disease and other sub-specialists [ ] . the country needs to expand its ability for the epidemiological surveillance system and research, both of which are in infantile form at present. not enough field staff and community workers are included or trained in surveillance and contact tracing work. this can lead to difficulty in the identification of cases as the surge continues to escalate. similar to the rest of the world, nepal is seeing more suffering, hunger, disease, and poverty as a result of the lockdown [ ] . a report from john's hopkins bloomberg school of public health projects up to under-five deaths in nepal over just six months due to a reduction in the coverage of essential maternal and child health interventions, including family planning, antenatal and postnatal care, child delivery, vaccinations, food, water, and preventive and curative services [ ] [ ] . almost % of the population in the country, living below the $ . per person per day international poverty line, who are already at risk may be further pushed into extreme poverty as a result of covid- [ ] . nepal is seeing a nationwide increase in suicide rates, by % according to some reports, attributed to the lockdown and poverty [ ] . despite nepal's poverty and lack of infrastructure, an early comprehensive covid- preparedness plan was successful in deflecting the epidemic for the first few months. effective measures included a strictly enforced lockdown, border control to prevent the importation of cases, mandatory institutionalized quarantine for all entering the country, identifying cases by implementing extensive contact tracing, and isolation of all cases irrespective of symptoms. for four months, starting with the first case on january to may , , these measures were very effective at flattening the curve. there were about cases until early may without evidence of community spread, until the further entry of the virus via international travelers. the greatest limitation is the open border with india with thousands of migrant nepali workers returning home. right before this publication, there are almost a hundred-thousand individuals in cramped quarantine facilities, and of the districts are affected. however, most of these cases are being reported from quarantine facilities and community transmission has not been reported in most parts of the country so far. continuing a strict lockdown may not be sustainable for the country anymore except in areas with evidence of community transmission. better provisions for quarantine, ramping up rt-pcr services, increased surveillance, and contact tracing may mitigate some of the issues. additionally, continued behavior interventions, such as social and physical distancing, the use of masks, and hand hygiene, must be encouraged. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. a novel coronavirus from patients with pneumonia in china world health organization. who coronavirus disease (covid- ) dashboard the world bank in nepal air medical evacuation of nepalese citizen during epidemic of covid- from wuhan to nepal the first novel coronavirus case in nepal covid- nepal: preparedness and response plan (nprp) a survey of adult intensive care units in kathmandu valley hospitals outside kathmandu ill-prepared to fight coronavirus outbreak ministry of health and population. health sector response to novel coronavirus ( -ncov) government of nepal ministry of home affairs, department of immigration mustang locals and village heads impose their own rules to control covid- health ministry releases updated list of hospitals designated for covid- patients in nepal health sector emergency response plan. covid . pandemic rolling updates on coronavirus disease (covid- ) ministry of health and population. epidemiology and disease control division. standard operating procedure for case investigation and contact tracing of covid- nepal's covid- struggle continues amid a concerning surge ministry of home affairs. nepal covid- dashboard asymptomatic patients to be quarantined or sent home as ministry expects , cases in a week human resources for health (hrh) and challenges in nepal distribution and skill mix of health workforce in nepal the asia foundation. nepal. coronavirus dispatches early estimates of the indirect effects of the covid- pandemic on maternal and child mortality in low-income and middle-income countries: a modelling study the world bank in nepal. recent economic developments suicide cases on the rise, mental health experts warn of a 'grim situation the authors would like to thank saugat shrestha for reviewing the manuscript. key: cord- -vpzrk u authors: mandal, amrendra; konala, venu madhav; adapa, sreedhar; naramala, srikanth; gayam, vijay title: gastrointestinal manifestations in covid- infection and its practical applications date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: vpzrk u the latest novel coronavirus (covid- ) outbreak, which emerged in december in wuhan, hubei, china, is a significant cause of the pandemic. this outbreak is caused by severe acute respiratory syndrome coronavirus (sars-cov- ) and is also commonly known as covid- . a typical symptom includes cough and fever, but a considerable number of patients can manifest gastrointestinal (gi) symptoms, including diarrhea, which can be the initial presentations and may or may not present with respiratory symptoms or fever. covid- virus may be present in stool samples of patients infected with covid- , and angiotensin-converting enzyme (ace ) is a receptor for this virus, which is substantially present in gi epithelial cells. the wide availability of this receptor facilitates covid- infection to be proactive and multiply in the gi tract. although no antiviral treatments have been approved, several approaches have been proposed, and at present, optimized supportive care remains the mainstay of therapy. elective endoscopic procedures should be delayed, but the urgent procedures should be performed as indicated. due to the rapidly evolving data on covid- , it is difficult to keep up with the outpouring of information. we reviewed the mechanisms, clinical manifestation, impact on pre-existing liver diseases, and recommendations endorsed by the several gi societies for the management and prevention of its transmission. unexpected pneumonia was observed in early december in wuhan, china [ ] . subsequently, a newly emerged coronavirus was labeled as sars-cov- (severe acute respiratory syndrome coronavirus ) by the coronavirus study group of the international committee on taxonomy of viruses [ ] [ ] [ ] . coronavirus resulted in a significant pandemic, with the incubation period to be . days (average), ranging from . - . days [ ] . a wide variety of symptomology and radiographic appearances create difficulty for clinicians to identify covid- and differentiate it from other more frequent respiratory infections. the usual symptoms include fever, cough, difficulty in breathing, and myalgia or fatigue, but atypically isolated sudden onset anosmia as well as a loss of taste in covid- infection has also been reported [ ] [ ] [ ] . it has also been shown that covid- persists on inanimate surfaces for up to nine days; thus, it can be infective without close contact with an infected person [ ] . interestingly, patients with covid- infection also demonstrated gi manifestations with diarrhea, vomiting, and abdominal pain [ ] . studies have also recognized the presence of covid- virus in anorectal swabs as well as stool samples despite the virus being disappeared in the upper respiratory tract samples [ ] [ ] [ ] . the studies demonstrated that the covid- receptor, i.e., angiotensin-converting enzyme (ace ), is observed to be also expressed in gastrointestinal (gi) epithelial cells [ ] . at the same time, these suggest that covid- can be proactive and can significantly multiply in the gi tract. although no antiviral treatments have been approved so far, several approaches have been proposed. this article aims to review the mechanisms, clinical manifestation, impact on pre-existing digestive diseases, and recommendations endorsed by the several gi societies for the management and prevention of its transmission. we also examine how it could impact gastroenterologists, hepatologists, transplant surgeons, and review the recommendations from different societies to mitigate the infection during the procedures. although covid- is transmitted through respiratory droplets and close contact, indirect contact by contaminated inanimate objects also takes part in virus transmission to some extent [ , ] . ace has been shown in the previous study as a receptor for different coronaviruses such as sars-cov. it has also been shown that covid- uses ace as a viral receptor for the entry process [ ] . there are existing data than ace is known to be rich in the epithelial cells of the lungs and gi tracts in humans, which might facilitate the evidence of this possible route for covid- infection [ ] . it is highly expressed in the glandular cells of gastric, duodenal, and rectal epithelia, supporting the entry of covid- into the host cells. in a study that analyzed covid- patients, ( . %) were found to be positive for covid- in stool, with a duration of positive stool ranging between and days [ ] . interestingly, ( . %) patients were persistently positive for covid- infection in stool even after a negative polymerase chain reaction (pcr) test in their respiratory specimens. in another study that followed pediatric patients and evaluated their nasopharyngeal and rectal swabs, children were persistently tested positive on rectal swabs even after nasopharyngeal clearance of the virus [ ] . zhang et al. described the presence of viral rna in the anal swabs and fecal specimens of patients with covid- [ ] . therefore, there is evidence of fecal-oral transmission in covid- infection, and therefore rectal swab may also play a role in establishing a viral clearance. furthermore, a cohort study demonstrated a significant enhancement of ace expression in cholangiocytes ( . % of cells) as compared with liver cells ( . % of cells), indicating that covid- can lead to direct damage of intrahepatic bile ducts. however, the histopathological study of liver tissue from covid- patients did not show viral inclusions in the liver specimens [ ] . there may be other possibilities of liver abnormality in covid- patients, such as drug used in the treatment itself or systemic inflammatory response induced by cases of pneumonia [ ] . the recent literature suggests that there may be mild-to-moderate injury to the liver, with elevation in aminotransferases, decline in albumin levels, and rise in prothrombin time in a patient infected with covid- , whereas up to % of patients previously infected with sars-cov had liver impairment [ ] . the transaminases, such as aspartate aminotransferase (ast) and alanine transaminase (alt), are elevated more than total bilirubin in the range of - % in hospitalized covid- patients [ ] . low serum albumin is the marker of disease severity. in one study, gamma-glutamyl transferase was elevated in ( %) and elevated alkaline phosphatase levels in ( · %) of patients with covid- during hospitalization [ ] . the histopathological examination revealed microvesicular steatosis and mild lobular activity in patients who presented with gi symptoms usually have a longer time from the onset of symptoms to hospital admissions than patients without these symptoms ( . days vs. . days). early symptoms in the majority of covid- patients have fever, myalgia, cough, and sore throat, as manifested with the other acute respiratory virus infections [ , ] . the majority of patients with covid- infections present with mild symptoms, and most admitted patients have pneumonia with ground-glass opacities on chest imaging. diagnosis becomes even more difficult considering the probability of a large number of mild or asymptomatic patients who are not recognized as a covid- infection [ , ] . in one initial retrospective study from wuhan, gi symptoms, such as diarrhea ( %- . %), nausea, and vomiting ( %- . %), were not very common [ , ] . however, with evolving studies related to covid- , up to . % ( patients) reported having gi symptoms at presentation in china. they presented with symptoms such as anorexia, diarrhea, vomiting, and abdominal pain [ ] . covid- infection may present with a severe infection in chronic liver diseases such as viral hepatitis b or c [ ] . in the study of , patients, ( . %) patients had hepatitis b virus (hbv) infection, and severe cases had hbv infection ( . % vs. . %) than non-severe cases [ ] . currently, there are no available data on the pre-existing chronic liver disease, such as non-alcoholic fatty liver disease and alcohol-related liver disease, and their impact on the outcome of covid- . it is also not known if covid- infection aggravates cholestasis in those with pre-existing cholestatic liver diseases such as primary biliary cholangitis or primary sclerosing cholangitis or with underlying cirrhosis [ ] . there is little information about the impact of covid- infection in patients with chronic liver disease. patients with chronic liver disease should be considered for the evaluation of covid- if manifested with hepatic encephalopathy, and patients with hepatic hydrothorax, portopulmonary hypertension, or hepatopulmonary syndrome also need to be considered for aggressive airway management [ ] . there are no data on whether hepatocellular carcinoma (hcc) causes severe covid- infection. however, one case series revealed worse covid- outcomes with non-hepatic tumors [ ] . whether patients with other gi cancers are more susceptible to covid- infection than those with non-gi cancers also remains unknown [ ] . the american association for the study of liver diseases (aasld) recommends continuing the usual hcc surveillance imaging in patients with hcc. a delay of roughly two months may be reasonable for surveillance, as the possible duration of the pandemic cannot be estimated at this time. however, if indicated, hcc treatment is recommended to initiate without further delay due to pandemic [ ] . at present, there is no exact information on covid- infection and its effects on decompensated cirrhosis or those in the waiting list for liver transplantation (lt). almost all organ procurement organizations (opos) are currently investigating for covid- and will begin with negative donors; although, the capacity to investigate recipients before the proceeding with transplant may be limited. at present, there are no clear data on the impact of covid- infection on patients with decompensated cirrhosis or those already on the waiting list for the lt. so far, there is no report of covid- infection in transplant recipients [ ] . nevertheless, the recipient might get transmission of covid- infection from a donor during lt, and, thus, donor screening is vital, as demonstrated in the earlier sars-cov outbreak [ ] . lt surgeons are recommended to follow guidelines provided by the transplantation society and also follow the local health department guidelines. the evolving studies related to covid- infection show that the innate immune response may be the primary driver for lung injury due to covid- , and, in fact, immunosuppression may be protective [ , ] . however, patients on immunosuppressive agents may have persistent viral detection in post-transplant status with covid- infection and may involve in the community spread as well; thus, these patients need to be monitored to prevent the spread of infection along with monitoring of symptoms [ ] . the current guidelines recommend not to decrease immunosuppression and also recommend against stopping mycophenolate for stabilized post-transplant patients with covid- infection [ ] . there are no data to suggest that the patients on biologics and immunosuppressive drugs in patients with inflammatory bowel disease (ibd) are more prone to covid- infection. organization for the study of inflammatory bowel disease (ioibd) have issued helpful resources due to rising in covid- infection as it relates to ibd medications [ ] . the recommendation is to encourage the patients to stay on their ibd medications such as aminosalicylates. however, reducing the dose of steroids is suggested by ioibd with a dose of mg or above once daily to avoid adrenal insufficiency. immunomodulators such thiopurines (azathioprine, -mercaptopurine, cyclosporine, methotrexate) and tofacitinib (jak inhibitor) inhibit the immune response to viral infections, and the patients should not stop taking these medications. biologics and biosimilars, including certolizumab pegol, adalimumab, infliximab, and golimumab, are immune-suppressing drugs, and patients are encouraged to continue taking these medications [ ] . appropriate management strategies for patients with covid- infections are rapidly evolving with therapeutic challenges, and optimal agents to treat an infection or prevent progression to critical illness remain unclear. pharmacological agents such as convalescent plasma from patients who have recovered from viral infections are being used for patients with covid- infection as there was some reported success during sars-cov- , middle east respiratory syndrome (mers), ebola, and h n influenza [ ] . however, the safety and efficacy of recovered convalescent plasma transfusion in symptomatic covid- -infected patients have not been established, and, currently, no guideline exists in the usa, but this treatment is tried on a case-to-case basis. other agents, such as remdesivir, chloroquine, and hydroxychloroquine, are showing some good results in small studies and are currently being used in the usa after the evaluation of cardiac parameters [ ] [ ] [ ] . the other adjunctive medications, such as lopinavir/ritonavir, tocilizumab, and corticosteroids, are also being used without many benefits [ ] [ ] [ ] . the clinical efficacy and safety for the different agents are still under research, and, at present, optimized supportive care remains the mainstay of therapy. the primary route of covid- transmission is through aerosolized droplets, with the possibility of fecal-oral transmission [ ] . considering that covid- infection can be transmitted from an asymptomatic person and also remains detectable in stool specimens even after negative viral rna from the lung specimen, the several gi societies have come up with joint guidelines to protect the vulnerable persons in the societies, patients, and healthcare professionals [ ] . more than % of all covid- infections may be transmitted before the index case manifesting symptoms [ , ] . moreover, patients with gi symptoms have a longer time from onset to hospitalizations. physicians should recognize that gi symptoms, such as diarrhea, maybe a presenting feature of covid- , and a high index of suspicion requires earlier at-risk patients presenting with gi symptoms. the aasld recommended testing for hbv and hepatitis c virus (hcv) in patients with elevated liver enzymes and monitoring liver function tests if treated with remdesivir and tocilizumab [ ] . caution should be taken regarding the use of investigational medications such as remdesivir, tocilizumab, and hydroxychloroquine for covid- infection in pre-existing liver diseases. hcc surveillance may be delayed roughly to two months in patients with cirrhosis, hbv, and hcv and proceeded with hcc treatment without delay if needed [ ] . the joint gi societies strongly recommend considering rescheduling non-urgent endoscopic procedures as these procedures are considered aerosol-generating [ , ] . in general, all elective procedures should be delayed, such as screening and surveillance colonoscopy in asymptomatic patients, endoscopic ultrasound (eus) for intermediate-risk pancreatic cysts, and motility procedures [ ] . however, urgent/emergent procedures should not be delayed, such as gi bleeding treatment, esophageal foreign body impaction, endoscopic retrograde cholangiopancreatography (ercp) for acute cholangitis, eus drainage for symptomatic pancreaticobiliary disease, and palliation of gi obstruction [ ] . the several covid- -related studies reporting about gi manifestation have been compared in table . in this review, we summarized that gi symptoms may be a presenting feature of covid- infection and that a high index of suspicion requires earlier at-risk patients presenting with gi symptoms. we also summarized the guidelines from the joint gi societies for elective gi procedures as well as urgent or emergent procedures and the impact of covid- infection on the several digestive diseases and their management during a pandemic situation. coronavirus infections-more than just the common cold a distinct name is needed for the new coronavirus a novel coronavirus 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mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -mnj zmkn authors: hussain, nowair; chung, emily; heyl, jonathan j; hussain, bisma; oh, michael c; pinon, candis; boral, soumya; chun, david; babu, benson title: a meta-analysis on the effects of hydroxychloroquine on covid- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: mnj zmkn introduction since december , severe acute respiratory syndrome coronavirus (sars-cov- ) has rapidly spread throughout the world with a large medical and economic impact. on march , , the world health organization (who) classified sars-cov- as a pandemic. as a result of this worldwide public health crisis, politicians, elected officials, and healthcare professionals emergently began trialing hydroxychloroquine (hcq) in efforts to treat and prevent the transmission of the virus. this meta-analysis was performed to assess the effects of hcq on patients with covid- . methods this meta-analysis adheres to the preferred reporting items for systematic reviews and meta-analyses (prima) guidelines. selected articles published between december and july were found utilizing the following search engines: pubmed, google scholar, cochrane library, disasterlit, clinicaltrials.gov, medrxiv, and embase. two independent physician reviewers screened eligible articles that met the inclusion and exclusion criteria of the analysis. the outcome measures analyzed were mortality rate, rate of disease progression/improvement, rate of disease severity, and adverse effects of treatment. six out of studies that met the study’s eligibility criteria were selected and further analyzed, with a total of participants (n= ). conclusion from the studies analyzed, it was found that groups treated with hcq had an overall mortality rate that was . times greater than that of the control group. hcq treated patients had higher rates of adverse clinical outcomes and side effects compared with the control populations. lastly, there was a . times higher rate of improvement in the group of hcq treated patients with mild to moderate symptoms as compared to the control group. coronavirus disease (covid- ) originated in wuhan, hubei province of china on december , [ ] [ ] [ ] [ ] . the rapid spread of the virus led the world health organization (who) to announce covid- as a pandemic on march , [ ] . the spread of sars-cov- resulted in an enormous public health crisis with high patient mortality and significant economic consequences [ , ] . furthermore, covid- is a complex, multifaceted, multi-system disease process that spares no one [ ] . the covid- acute respiratory distress syndrome consists of a period of cytokine storm, which is noted particularly in the later stages of advanced severe respiratory failure [ ] . covid- patients have increased levels of plasma pro-inflammatory cytokines and chemokines [ ] [ ] . these cytokines and chemokines are il b, il ra, il , il , il , il , basic fgf , gcsf, gmcsf, ifng, ip , mcp , mip a, mip b, pdgfb, tnfa, and vegfa [ ] [ ] . high patient mortality is caused by the disarray of these host cytokines, causing damage to the lungs and leading to multi-system organ failure [ ] [ ] . the sars-cov- virus has an affinity for the ciliated cells of the respiratory conducting airway, with increased viral replication as it progresses further along the respiratory tract and gastrointestinal mucosa [ ] . the sars cov- infection occurs in three distinct stages: an asymptomatic stage, an upper airway stage, and, finally, the conducting airway response stage, which leads to the classically seen ground-glass infiltrates on chest x-ray and clinical hypoxia with progression to acute respiratory distress syndrome (ards) and multi-system dysfunction [ ] . in stage , the virus binds to the angiotensin-converting enzyme (ace ) receptor, a transmembrane protease, serine (tmprss ). tmprss is ubiquitous in the human body; it is found in the nasal cavity and lung and is also expressed throughout the intestine and prostate [ ] . ace receptors can also be found in the heart, esophagus, kidneys, stomach, bladder, and ileum [ , ] . as sars-cov- progresses down the respiratory tract, the virus begins to activate a more potent immune response and certain patients may manifest clinically with respiratory failure and ards. most patients will have a mild disease, with the disease restricted to the upper respiratory tract [ ] . about one out of five sar-cov- infected patients will progress to more severe respiratory disease and further to ards [ ] . the proposed mechanism is the destruction of type ii pneumocytes once the virus reaches the alveoli [ ] . the virus would then begin the replication process within these cells and the cell would undergo apoptosis, releasing viral particles. this cellular apoptosis results in diffuse alveolar damage with the formation of hyaline membranes, which decrease gas exchange and lead to clinical hypoxia. furthermore, the healing of the affected areas may worsen the patient's condition through more severe parenchymal scarring and fibrosis. because the cytokines mentioned above have binding sites within the lungs, they may serve as therapeutic targets. -aminoquinolones such as hydroxychloroquine (hcq) and chloroquine have gained a lot of steam in the medical field and media for their possible efficacy against covid- . hcq has immunomodulatory properties and was originally developed as an antimalarial drug with further applications in patients with rheumatoid arthritis and systemic lupus erythematosus [ ] . in vitro studies of hcq have additionally shown antiviral properties; it supposedly prevents covid- related ards [ , [ ] [ ] . the treatment of covid- positive patients with hcq has been met with controversy, as there have been no large multicenter randomized control trials to support its use. up to this point, there is a lack of statistically significant reduction in morbidity or mortality in covid- patients who have undergone hcq trials. the treatment of covid- with a combination of hydroxychloroquine and azithromycin was first proposed in a controversial, small non-randomized trial from the south of france that concluded that the drug combination was effective for the treatment of covid- [ ] . criticism was brought on immediately when it was presented for peer review due to many methodological flaws, with the biggest being the lack of a randomized control group [ ] . this led to various expert researchers criticizing the efficacy of hydroxychloroquine, with the majority concluding no statistically significant difference between treatment groups. the emergent approval of hcq at the height of the covid- pandemic was considered controversial but necessary given the overwhelming lack of effective treatment options at that time. the controversy was limited not only to the unknown efficacy and side-effect profile of hcq but also to the limited supply of the drug [ ] . this systematic review and meta-analysis adheres to the preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines ( figure ) [ ] . the search terms used were hydroxychloroquine, chloroquine, azithromycin, covid- , coronavirus, and sars-cov- . using these terms, the systematic search strategies used were boolean and fuzzy logic, truncated terms, and wild cards. selected articles published between december and july were found utilizing the following search engines: pubmed, google scholar, cochrane library, disasterlit, clinicaltrials.gov, medrxiv, and embase. two independent physician reviewers screened eligible articles that met the analysis' inclusion and exclusion criteria. the inclusion criteria were ( ) age range - , ( ) prospective control trial, and ( ) use of hydroxychloroquine, chloroquine, lopinavir-ritonavir, or azithromycin. the exclusion criteria were ( ) presence of a co-morbid medical condition, i.e., advanced heart, liver, or renal disease or diabetes mellitus, ( ) treatment with remdesivir, convalescent plasma, corticosteroids, vaccines, il- inhibitors, t-cell therapy, α-ketoamide inhibitors, resiniferatoxin, teicoplanin, favipiravir, extracorporeal therapy, or hcq prophylaxis. the outcome measures analyzed were hcq's effect on covid- mortality rate, rate of disease progression/rate of improvement, rate of disease severity, and adverse effects of treatment. six out of studies that met the study's eligibility criteria were selected and further analyzed, with a total of participants (n= ). data collected from six different studies looked at the effects of hcq on patients with clinically proven covid- infection. these six studies have been labeled s , s , s , s , s , and s for better data visualization. each study varies in sample sizes and the distribution of treatment and control groups. the defined outcomes studied in this meta-analysis are: ) the mortality rate of patients after applying hcq on patients with covid- ) the rate of progression/improvement of covid- disease ) the rate of covid- disease severity, for example, after applying the hcq treatment, the rate of which patients went on to develop severe conditions such as acute hypoxic respiratory failure and adult respiratory distress syndrome. the random-effects model was used on the assumption that the study effect estimates show more variance when drawn from a single population [ ] . therefore, this follows the so-called assumption of exchangeability [ ] . this means that in a random-effects model fit, not only do assumptions of the effects of individual studies deviate from the true intervention effect of all studies due to sampling error but that there is another source of variance introduced by the fact that the studies do not stem from one single population [ ] . the studies are sampled from a "universe" of populations [ ] . in this study, the random effect model is a suitable choice because it is a risky assumption to state all the studies along with their respective effect sizes stem from a single homogeneous population. among the six studies considered for meta-analysis, information on mortality rates was available in two of them, details of which are provided below (tables - ) . these studies are perfectly homogeneous as tau^ is (equivalently, h^ is ). see figures - for more information. study has more uncertainty in its results as evident due to the wide spread of the horizontal line. studies and both do not cross the effect line at , indicating that they are not in agreement with the mortality rate of hcq treated covid- positive patients. there is a marginal asymmetry between the studies, however, as the number of studies is small, this result can be attributed purely to chance rather than any actual publication bias. among the six studies considered for meta-analysis, information on disease progression rates are available in four of them, details of which are provided below (tables - ). these studies are a bit heterogeneous, though by a very small amount. see figures - for more information. interpretation study has more uncertainty in its results as evident by the width of the horizontal line [ ] . all studies, except study , are in agreement with the results of a disease progression rate of hcq treatment in patients with covid [ ] . the studies are symmetric except study , which falls outside the triangle. this is in line with the conclusion drawn from the funnel plot. however, as evidenced by the funnel plot, study has very low power and thus its effect can be ignored. among the six studies considered, information on disease severity rates are available in four, the details of which are provided below (tables - ). here, the estimated average log relative risk is equal to ˆμ=- . ( % ci: - . to . ) [ ] . for easier interpretation, these values are transformed back to the relative risk scale through exponentiation (i.e., exp(ˆμ) = . with % ci: . to . ). the interpretation of these results suggests that the disease severity rate in hcq treated individuals is on average . that of the non-hcq individuals. the null hypothesis h : μ= can be rejected (p < . ). these studies exhibit heterogeneity by a moderate amount. see figures - for more the side effects of -aminoquinolones are known to be dose-dependent increased risks for retinopathy, methemoglobinemia, and gastrointestinal (gi), renal, and cardiac toxicity [ ] . hcq co-administered with medications such as azt further increases the risk of toxicity, particularly prolongation of the qt interval on electrocardiogram. the borba et al. study revealed that males aged with severe covid symptoms and heart disease are at high risk for developing hcq-related cardiac complications such as qt prolongation at higher doses of hcq [ ] . this toxicity is especially noted when combined with azt, which is known to prolong the qt interval in populations with cardiac disease [ ] . the studies by tang et al. [ ] and chen j et al. [ ] showed greater hcq-related gi side effects as well. in a post-marketing study by the food and drug administration (fda), it was also shown that the use of -aminoquinolones increased rates of cardiac arrhythmias, ventricular tachycardia, fibrillation, and torsades de pointes. their analysis also noted adverse cardiac events in combination with the use of other qt-prolonging medications such as azithromycin [ ] . as a result, the fda has cautioned the use of hcq in covid- patients, especially outside of the inpatient hospital setting [ ] . similarly, this meta-analysis supports that hcq treated patients are more likely to have adverse side effects. it also appears that treatment with hcq has a fatality rate of approximately . higher than with the control group. the non-randomized study performed by gautret et al. in the south of france included a total of young patients with positive pcr test results and milder covid- disease with no advanced comorbid medical conditions. a % reduction in viral load was noted at one week with a low dose of hcq with azt [ ] . this study was not powered to detect mortality outcomes. similarly, yang et al. [ ] , mingxing et al. [ ] , and chen j et al. [ ] studied females with a median age of and mild covid- related upper respiratory/pneumonia symptoms, without co-existing comorbid medical disease. patients were stated to have improved time to clinical resolution in the hcq treatment arm [ , [ ] [ ] . these results seem to be in line with the meta-analysis' of a slight disease improvement in covid- patients treated with hcq as compared with the controls. furthermore, recent studies show a gender disparity, in that females show better outcomes as compared to similar male cohorts [ ] . this gender disparity is seen in a recent study that noted that male patients with advanced age or multiple comorbid medical conditions are at higher risk for mortality [ , ] . the studies in this meta-analysis did not include these high-risk patients with underlying complex co-morbid medical conditions, severe cases of covid- , ards, or critical care patient populations. of note, the studies included in this meta-analysis have various definitions of control groups, which might affect the conclusion. however, with respect to the disease progression and severity meta-analysis, it appears that most of the studies are in agreement with the results, with slight exceptions, which might be attributed to chance. to get a more robust conclusion, the metaanalysis can be performed on more studies rather than six prospective control trials. currently, there are hcq clinical trials in the active recruitment phase [ ]; as the pandemic continues to unfold, these future large multicenter randomized controlled clinical trials may be included in the meta-analysis to conclude the size effect of hcq on covid- . covid- ) pandemic and economic impact preferred reporting items for systematic reviews and meta-analyses: the prisma statement early transmission dynamics in wuhan, china, of novel coronavirusinfected pneumonia who announces covid- outbreak a pandemic coronavirus timeline: tracking the critical moments of covid- coronavirus disease case surveillance -united states in vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus (sars-cov- ) the epidemiology and pathogenesis of coronavirus disease (covid- ) outbreak covid- : pathogenesis, cytokine storm and therapeutic potential of interferons extrapulmonary manifestations of covid- virology, epidemiology, pathogenesis, and control of covid- pathogenesis of covid- from a cell biology perspective sex differences in sars-cov- infection rates and the potential link to prostate cancer mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology in vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine hydroxychloroquine and azithromycin as a treatment of covid- : results of an open-label non-randomized clinical trial current and resolved drug shortages and discontinuations reported to fda statistical methods for immunogenicity assessment a pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease- (covid- ) effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus (sars-cov- ) infection. a randomized clinical trial efficacy of hydroxychloroquine in patients with covid- : results of a randomized clinical trial treating covid- with chloroquine hydroxychloroquine in patients mainly with mild to moderate covid- : an open-label, randomized, controlled trial hydroxychloroquine: small effects in mild disease center for drug evaluation and research office of surveillance and epidemiology. pharmacovigilance memorandum search of: hydroxychloroquine. recruiting studies: covid -list results our study looks at three disease outcome measures of treatment with hcq in patients with covid- : mortality rates, progression rates, and severity rates. in terms of mortality rates, it appears treatment with hcq has a fatality rate that is . times greater than that of the control group. similarly, hcq treated patients are more likely to have an adverse clinical outcome and side effects. lastly, there was a . -times higher rate of clinical improvement in the group of hcq treated patients, with mild to moderate symptoms as compared to the control group. human subjects: all authors have confirmed that this study did not involve human participants or tissue. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- - ejmefxv authors: zhang, xiao chi; jarou, zachary j; danovich, dimitry; kellogg, adam r; lutfy-clayton, lucienne; kenney, adam; edens, mary ann; hillman, emily title: international medical graduate advising recommendations from the council of residency directors in emergency medicine advising student committee date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ejmefxv international medical graduate (img) physicians applying to residency training programs in a country different from where they completed medical school, bring beneficial diversity to a training program, but also face significant challenges matching into an accreditation council for graduate medical education (acgme)-accredited residency program. despite the growing number of img applications in emergency medicine (em), there is a paucity of targeted recommendations for img applicants. as a result, the council of residency directors (cord) advising students committee in em (asc-em) created a dedicated img advising team to create a set of evidence-based advising recommendations based on longitudinal data from the national residency match program (nrmp) and information collected from em program directors and clerkship directors. img applicants should obtain at least two em standardized letters of evaluation (sloes), review img matched percentages for programs-of-interest, analyze their objective scores with the previous matched cohorts, and rank at least programs to maximize their chances of matching into em. international medical graduates (img) can offer a wealth of medical knowledge, as well as cultural and academic diversity to a domestic emergency medicine (em) residency program. while img applicants, both united states (u.s.) citizen (u.s. img) and non-u.s. citizen img (non-u.s. img) comprise only % of the entire em application pool, they are the third-largest group, second only to u.s. allopathic seniors (u.s. senior, %) and osteopathic (d.o., %) applicants [ ] . despite the value of their unique perspectives and skills, img applicants face the challenge of being "screened" out early during the application process [ ] . non-u.s. img applicants must find institutions that will sponsor visas during their training and participate in a rigorous certification process through the educational commission for foreign medical , graduates (ecfmg). historically, the number of available em residency positions has exceeded the number of u.s. senior applicants, allowing img, and other "non-traditional" applicants to fill in these gaps [ ] . however, recent data suggest that the number of img applications has tapered off in the last few years despite the fairly stable rate of em spots filled by u.s. seniors [ ] . in , there were , emergency medicine postgraduate year (pgy- ) positions with , total applicants; em had a . % fill rate with only unfilled positions [ ] . approximately % of those spots were matched to u.s. seniors and % were filled by osteopathic applicants. in the past five years, only . % of available em positions were filled by u.s. citizen img and . % by non-u.s. citizen img on average [ ] . in , the council of residency directors (cord) advising students committee in em (asc-em) -formerly known as the student advising task force -published the student advising recommendations and resources to guide prospective em applicants and their advisors [ ] . while these recommendations were generated based on the available literature, member opinion, and existing advising resources, the authors recognized special applicant population groups, such as img, require tailored guidelines beyond the traditional prospective em applicant recommendations. given the paucity of targeted recommendations for img applicants, the cord asc-em formed an img advising team for generating advising recommendations that highlight the existing application hurdles for img applicants and compile evidence-based guidelines for both the students and their advisors. where a paucity of objective evidence exists, expert opinion from the cord asc-em was obtained. our primary objective is to provide recommendations from the asc-em img advising team to maximize the img applicants' chances of matching into an accreditation council for graduate medical education (acgme) em residency program. investigators from the cord asc-em identified best-practice advising information through the collation of available literature, existing advising resources, members' opinions, and the national resident matching program (nrmp) data collected from to , specifically focusing on the admission patterns for img applicants in comparison to u.s. senior applicants. investigators also independently interviewed various em program directors (pds), assistant program directors (apds), and clerkship directors (cds) during national cord conferences between and on their perception of hiring img residents. drafted recommendations were then made available for real-time commentary to the entire asc-em, composed of em faculty and residents across the country as part of the modified delphi review process. furthermore, the investigators sought out additional feedback from the cord members through listserve and blog posts for their perspectives on img applicants. all comments were reviewed and addressed summatively by the investigators and commentators via digital communications before convening together to make the final list of recommendations. upon reviewing all available medical literature and collective data from on-line resources through numerous iterative consensus national cord conference meetings, the cord asc-em img advising team developed six recommendations as a task force, soliciting comments, revision, and approval as part of a collaborative effort to improve the advising of img applicants. the recommendations, as listed below, were designed to serve as a single, referenceable document for img applicants, and contained both general and targeted guidelines for a successful em application process. . identify the challenges: while u.s. img and non-u.s. img are slightly different cohorts, it is challenging for em program directors to be familiar with the myriad of international medical schools; for this reason, img may be considered higher academic risks and held at a higher level of scrutiny. according to data obtained via the cord listserv in , more than half of all residency programs use screening filters; % of programs reported screening to exclude non-u.s. img, and % reported screening to exclude u.s. img [ ] . additionally, hiring img residents may result in additional financial burdens to a residency program as some medical institutions only sponsor certain types of visas, and for others, the department has to fund the position. as a result of these challenges, img need to demonstrate objective mastery of the medical arts via top grades, strong letters of evaluations, exemplary united states medical licensing exam (usmle) scores, and a robust cv in order to secure an em residency position. . emergency medicine rotations: img applicants should complete at least two em clerkship rotations at institutions with an existing em residency. multiple rotations enable applicants to be exposed to a variety of practice patterns, locations, and program designs while allowing program directors to better assess an applicant's progress from each clinical environment. summer months (july, august, and september) are the most popular months for em rotations, although many hospitals often reserve these positions for students from their affiliated medical school. in order to find viable rotation options, img applicants can review their institution's record of where their students have rotated and matched in the previous years, as well as directly contact the departments where they are interested in rotating. students can also consider using web-tools like emergency medicine residents' association (emra) match residency and clerkship. this interactive software allows prospective applicants to search for clerkship positions and residency programs [ ] . users can filter programs that accept a high percentage of img residents and search for clerkships that consider img students. securing em rotations may be challenging, as only % ( / ) of available clerkships with complete data on emra match accept img applicants [ ] . . residency program selection: recent geographic trend analysis from the nrmp data showed higher u.s. img matched percentages in the northeastern and southeastern u.s., with higher matching rates of u.s. img residents (figure ) [ ] . although these data trends do not reflect the intrinsic values from img students, img applicants seeking to pursue an em residency in specific us geographic locations may benefit from reviewing these geographic trends to maximize their match rate. source: [ ] . standardized letter of evaluation (sloe): one of the most important goals as an em applicant is to secure an sloe during an away rotation in the emergency department. a sloe is cited by em program directors as the most important factor in their decision to offer an interview and cited as the top five factors when assembling their rank lists, rivaling the importance of usmle performance [ ] . as a result, in order to reflect their em qualifications, img should rotate through em clerkships with associated em residency programs with the goal of obtaining two sloes. while rotations at non-academic emergency departments may be easier to obtain, the letters of recommendation from these institutions do not follow the standard objective; in the absence of an sloe, these letters will not carry sufficient weight to assist the img applicant in obtaining interviews. step clinical knowledge (ck) performance: applicants are strongly encouraged to have both usmle step and step ck results available when the electronic residency application service (eras) opens. in the match, the mean step and scores for matched u.s. img were and respectively and for non-u.s. img were and , respectively [ ] . the average for us allopathic seniors who matched was and respectively [ ] . img applicants with either score below (the average step score for unmatched us allopathic seniors) should consider consulting with their faculty mentors and consider applying to another specialty simultaneously as a parallel plan [ , ] . . interviews and rank list: although no number of interviews guarantees a % match rate, the standard recommendation for us img applicants is to apply to enough em residencies in order to rank at least programs [ ] . for non-us img applicants, the rank list needs to be even longer. according to nrmp data, a longer rank list correlated with higher match rate for img applicants: matched u.s. and non-u.s. img have higher mean rank lists ( . and . ) than their unmatched counterparts ( . and . ) [ ] . during the interview, img applicants should reflect on their unique academic and cultural background, and highlight their unique service, leadership skills, and any applicable research. to date, this study represents the first evidenced-based recommendation with the emergency medicine leadership consensus for img students applying to emergency medicine residency. these recommendations were designed for the typical img applicant during normal application seasons; individual img applicants should be encouraged to review these recommendations to tailor to their specific needs and circumstances. while these recommendations may provide a helpful guiding framework to non-img applicants, they were synthesized based on a careful assessment of nrmp data of img applicants, evaluating for adjustable, critical elements of their application that can improve their chances of matching. based on the above recommendations, the cord asc-em has developed an online standalone resource for img applicants with key recommendations made available on the vocal cord blog, which has more than , followers and is used as a reference guide by the entire cord community [ ] . the img recommendations post was viewed over times in less than one year. img and their advisors are encouraged to utilize these recommendations as general guidelines; however, each applicant still needs an individualized approach. similar to what was done with other cord asc-em advising resources, the resource is endorsed by cord, cdem (clerkship directors in emergency medicine), emra, and the aaem (american academy of emergency medicine). to date, it has disseminated via multiple avenues to students and their advisors. while these recommendations were established utilizing the most up-to-date nrmp data, consensus expert opinions from em program and clerkship directors, the investigators recognize that there is a still limited scope of resources and lack of published data on img. furthermore, the investigators acknowledge that even though there are demographic differences between u.s. img and non-u.s. img applicants, there is insufficient data to create a separate cord asc-em recommendation distinguishing both subpopulations. furthermore, the geographic trend of matched-img applicants per em residency [ figure ] may obscure individual programs in states with numerous residencies that accept high numbers of img. the investigators acknowledge that recommendations informed by experience and expertise remain subject to inherent prejudice and bias. finally, the authors understand that due to unforeseen circumstances of the novel coronavirus disease (covid- ) global pandemic, these recommendations may temporarily not apply as many institutions are restricting visiting students and in-person interactions with faculty [ ] . however, we are confident that as the situation resolves, and medical schools and hospitals re-equilibrate, these recommendations will once again apply. based on cord survey results and available nrmp data (as of ), the cord asc-em created a list of evidence-based recommendations for img applicants applying to acgme em residency programs to maximize their chance of matching. img applicants should recognize the inherent challenges in applying to em, consider completing at least two em clerkships (if applicable) with the goals of obtaining sloes, review img matched percentages for programsof-interest, compare their examination scores with the previous matched cohorts, and rank at least programs (or more) to maximize their chances of matching into em. the cord asc-em img advising team believes this advising resource will form a foundation for img and their advisors to better understand the em application process. human subjects: consent was obtained by all participants in this study. thomas jefferson university issued approval n/a. this study was exempt based on the thomas jefferson university irb policies. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. emra and cord student advising guide: an evidence-based approach to matching in em results and data: main residency match student-advising recommendations from the council of residency directors student advising task force association: about emra match nrmp main residency match: match rates by specialty and state data release and research committee: results of national resident matching program, charting outcomes in the match: international medical graduates national resident matching program, charting outcomes in the match: us allopathic seniors the vocal cord addressing challenges in obtaining emergency medicine away rotations and standardized letters of evaluation due to covid- pandemic the authors would like to acknowledge the cord advising students committee for their assistance in the completion of this study. key: cord- -jwgtjisx authors: mehrabi, sara; fontana, silvia; mambrin, francesca; nguyen, hoang quyen; righi, elda; tacconelli, evelina; mansueto, giancarlo title: pitfalls of computed tomography in the coronavirus (covid- ) era: a new perspective on ground-glass opacities date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: jwgtjisx aim to study ground-glass opacities (ggo) not only from the coronavirus (covid- ) pneumonia” perspective but also as a radiological presentation of other pathologies with comparable features. methods we enrolled patients admitted to policlinico universitario g. b. rossi who underwent non-contrast-enhanced (nce) or contrast-enhanced (ce) chest computed tomography (ct) between march and april . all patients with ct-detected ground-glass opacity (ggo) were included. all patients resulted as covid- negative at the reverse transcription-polymerase chain reaction (rt-pcr) assay. we studied the different pathologies underlying ggo features: neoplastic diseases and non-neoplastic diseases (viral pneumonias, interstitial pneumonias, and cardiopulmonary diseases) in order to avoid pitfalls and to reach the correct diagnosis. results all ct scans detected ggos. symptomatic patients were / ( . %). at the clinical presentation, they reported fever and dry cough; in six out of cases, dyspnea was also reported ( %). thirty-three ( ; %) showed ggo at ct: / ( . %) presented pure ggo, and / ( . %) showed ggo with consolidation. the rt-pcr assay was negative in %. we investigated other potential underlying diseases to explain imaging features: neoplastic causes ( / , . %) and non-neoplastic causes, in particular, infectious pneumonias ( / , , %, viral and fungal), interstitial pneumonias ( / , , %), and cardio-pulmonary disease ( / , , %). conclusions ggo remains a diagnostic challenge. although ct represents a fundamental diagnostic tool because of its sensitivity, it still needs to be integrated with clinical data to achieve the best clinical management. in the presence of typical imaging features (e.g. ggo and consolidation), the radiologist should focus on the pandemic and manage a suspect patient as covid- positive until proven to be negative. coronavirus pneumonia is caused by a novel virus from the coronaviridae family, from which the severe acute respiratory syndrome (sars) and middle east respiratory syndrome (mers) viruses also originated, causing two epidemics in and , respectively. according to the previous study, the disease develops in three phases: early (days - ), intermediate (days [ ] [ ] [ ] , late (after day ) [ ] . even if chest ct can detect lung anomalies before symptom onset, the findings follow a temporal pattern and are consistent with clinicopathological development: the first and most common feature is ground-glass opacity (ggo), which represents early alveolar damage, with bilateral subpleural distribution in the lower lobes; then, areas of consolidation appear and tend to coalesce on the underlying ggos. later, in this background, the "crazy paving" pattern can be seen, with thickened interlobular septa and intralobular lines. lymphadenopathies and pleural effusion are rarely seen [ ] . chest ct plays a pivotal role in the detection and early management of covid- pneumonia; despite its sensitivity, it lacks specificity because of the wide spectrum of pathologies that can show ggo. the aim of our study is to show chest ct findings that could mimic covid- pneumonia; in the covid- era, we should not forget other lung diseases that could be misinterpreted in our experience. it is, therefore, fundamental to correlate ct findings with clinical history and lab data to achieve the correct diagnosis and an integrated scenario for every patient [ ] . ground-glass opacity is defined as hazy opacity that does not obscure underlying bronchial structures or pulmonary vessels at computed tomography (ct). it represents many histopathological processes because the underlying mechanism may be partial airspace filling; interstitial thickening with inflammation, edema, fibrosis; and neoplastic proliferation. ggo is a frequent focal lung finding representing cancer; it can also represent lung infections, lung edema, or interstitial diseases (where ggo can represent disease activity and may precede irreversible fibrosis). since it is a non-specific radiological finding, it is fundamental to know the underlying physiopathology to narrow the differential diagnosis [ ] . we retrospectively enrolled patients aged between and years ( males and females), admitted to verona a.o.u.i. -policlinico universitario g. b. rossi, who underwent non-contrast-enhanced (nce) and contrast-enhanced (ce) chest ct between march and april . when ce-ct was performed, we used a high iodine concentration contrast agent (ultravist , bayer schering pharma ag, berlin, germany). we included all patients with ct images positive for ggo. covid- patients were excluded from this study. patients tested for covid- underwent a reverse transcription-polymerase chain reaction rt-pcr assay on a nasopharyngeal swab. patients with other infective pneumonia were confirmed with bronchoalveolar lavage (bal), viral panel, serologic tests, or blood cultures. cts were performed with the patient supine at full inspiration, using a -row mdct scanner (brilliance ict, philips healthcare, amsterdam, netherlands). scanning parameters were tube voltage kv and tube current modulation ma. images were reconstructed with a slice thickness of mm or mm. all images were reconstructed on both lung (width, hu; level: - hu) and mediastinal (width, hu; level: hu) settings. the number of symptomatic patients was / ( . %). at clinical presentation, they reported fever and dry cough, and six out of ( %) cases also reported dyspnea. thirty-three ( ; %) showed ggo at ct; / ( . %) presented pure ggo and / ( . %) presented ggo with consolidation. covid- pneumonia was suspected because of the ct report and clinical presentation so an rt-pcr assay by nasopharyngeal swab was performed; interestingly, the virus was not detected in any patient. we investigated other potential underlying diseases: neoplastic causes ( / , . %) and non-neoplastic causes, in particular, infectious pneumonias ( / , , %, viral and fungal), interstitial pneumonias ( / , , %), and cardio-pulmonary disease ( / , , %). the different meaning of ggo in every category was also investigated. since ggo lesions can be caused by a wide spectrum of pathologies, a ggo is a non-specific radiological finding. it does not represent a confirmed diagnosis, even in the covid- era. it is, therefore, necessary to understand the underlying histopathology and to integrate imaging with clinical and lab data to achieve the correct diagnosis. according to our experience, in the current paper, we distinguished between the neoplastic and non-neoplastic causes of ggo. for each category, we analyzed the diagnostic pitfalls and discussed management during radiological practice. a -year-old male patient, a health worker, presented to the emergency department, with a history of dry cough. he did not report any significant comorbidity, nor malignancies in his clinical history. in suspicion of covid- pneumonia (clinical and epidemiological criteria), an rt-pcr assay on nasopharyngeal swab was performed. later, he underwent a chest ct scan. the report showed a pure ground-glass nodule in the apical segment of the left superior lobe (figures - ) . the result of the rt-pcr was negative. considering the mild symptomatology and the presence of pure ggo, early-stage covid- pneumonia could have been diagnosed; nevertheless, it is important to consider lung cancer as an incidental finding. according to the fleischner society guidelines, a -months follow-up was recommended [ ] . ggo is a common sign of lung cancer. according to the world health organization (who) classification, adenocarcinoma and its precursors are classified into preinvasive lesions (atypical adenomatous hyperplasia (aah) and adenocarcinoma in situ (ais)), minimally invasive adenocarcinoma (mia), typically presenting as a pure ggo nodule greater than mm in diameter, and invasive adenocarcinoma. in general, lung adenocarcinomas are thought to follow a path in which aah progresses to ais, followed by invasive adenocarcinoma. most pure ground-glass nodules (ggn -without solid component) are preinvasive adenocarcinomas, often behaving as indolent tumors; semisolid nodules tend to be adenocarcinomas, as well as invasive because of the intrinsic histological difference in the solid component: the more they grow, the more invasive they are [ ] . the ggos of ais usually manifest as regions of slightly higher attenuation relative to the opacity of aah due to the histopathologic difference in the number of cellular components within the nodule or the thickness of alveolar walls. pure ggns greater than . mm in diameter have been reported to represent invasive adenocarcinoma [ ] [ ] . a -year-old male presented with a two-week history of high fever (t-max . °c), cough, and muscle ache. blood tests showed mild lymphopenia ( /mmc) and high c-reactive protein (crp) levels ( mg/l, normal value < ); therefore, an ongoing infective process was suspected. considering the possibility of covid- pneumonia, rt-pcr was performed twice for the persistence of typical symptoms and because of chest ct findings, highly suspect for viral pneumonia. the ct scan reported a consolidating area in the medial segment of the middle lobe and ggos in the lower left lobe (figures - ) . since the rt-pcr persisted negative, a bal was performed and influenza a virus detected by multiplex pcr. the differential diagnosis among viral pneumonias appears to be extremely difficult: there is a significant overlap in the imaging appearance and overlapping with other inflammatory lung diseases; furthermore, blood exams are highly unspecific, too, showing generally lymphopenia and slightly increased crp. the ct patterns of viral pneumonia are related to the pathogenesis of the viral infection and are affected by the immune status of the host and the underlying pathophysiology of the viral pathogen. moreover, viruses of the same family have similar pathogenesis; consequently, viral pneumonia caused by different viruses from the same virus family exhibits a similar pattern on chest ct images [ ] [ ] . ggos represent areas of alveolar damage and, in patients developing acute respiratory distress syndrome (ards), fluid-refilled alveoli. covid- is a new type of viral pneumonia; previous studies have demonstrated frequent ct findings, in particular, bilateral ggo and interstitial thickening, similar to other viral pneumonias, specifically sars, and mers, belonging to the same viridae. sars and mers outbreaks were also due to a coronavirus: consequently, studying and understanding those epidemics may be helpful in managing the current pandemics [ ] . a and b influenza viruses belong to the orthomyxoviridae family. in individuals with chronic comorbidities (diabetes, cardiac failure), severe complications leading to ards may occur. chest ct shows bilateral reticular areas of opacity, sometimes with focal areas of consolidation, usually in the lower lobes. patchy ggos can be associated with the areas of consolidation. pleural effusion is rare. a -year-old female affected by sjögren syndrome underwent a scheduled chest ct scan to assess lung involvement. ggos were reported bilaterally, predominantly in the lower lobes, along with interstitial thickening (figures - ) . despite the typical imaging features and the onset of mild symptoms, the report excluded covid- pneumonia; interstitial inflammatory involvement was correctly diagnosed. ct findings, along with clinical history, led to the correct diagnosis: it could have been misinterpreted since, in the covid- era, every patient should be considered positive until proven negative. rt-pcr confirmed negative. the female patient affected by sjogren syndrome with lip. patchy ggos (arrows) seen predominantly in the lower lobes. the patient developed fever and dyspnea. despite the typical onset symptoms and the presence of imaging features suspect for covid- , rt-pcr was negative. lip: lymphocytic interstitial pneumonia; ggo: ground-glass opacity; covid- : coronavirus ; rt-pcr: reverse transcription-polymerase chain reaction interstitial pneumonias are a heterogeneous group of diffuse parenchymal lung diseases caused by a combination of inflammation and fibrosis. the primary site of injury is the interstitium, which includes the space between the epithelial and endothelial membranes; airspaces, airways, and vessels are often affected [ ] . interstitial pneumonias may be idiopathic or secondary to a variety of other causes, including collagen vascular diseases, pneumoconiosis, infection, and smoking. the american thoracic society and european respiratory society classification includes seven clinicopathologic entities: idiopathic pulmonary fibrosis (ipf), nonspecific interstitial pneumonia (nsip), cryptogenic organizing pneumonia, acute interstitial pneumonia (aip), respiratory bronchiolitis (rb)-associated interstitial lung disease (ild), desquamative interstitial pneumonia (dip), and lymphoid interstitial pneumonia (lip) [ ] . lip is regarded as a variant of diffuse pulmonary lymphoid hyperplasia primarily affecting the interstitium and it is distinguished from low-grade malignant lymphoproliferative diseases with immunohistochemical analysis. lip is frequently associated with systemic disorders (sjögren syndrome, acquired immunodeficiency virus (aids), hashimoto thyroiditis) [ ] . abnormalities on ct in patients with lip are usually bilateral and may be diffuse or have lower lung predominance. a typical finding is ggo, representing diffuse interstitial phlogistic involvement, along with interlobular thickening. centrilobular nodules and perivascular cysts are also common, representing inflammatory infiltration of the peribronchiolar interstitium [ ] . a -year-old male underwent a heart transplant due to severe dilatative cardiomyopathy associated with mitral failure. he also reported centrilobular emphysema in his clinical history. during hospitalization and rehabilitation, direct contact with a covid- -positive patient was reported. since the patient developed a cough, a chest ct scan was performed, reporting patchy bilateral ground-glass opacities affecting both the superior and inferior lobes, along with mild bronchiectasis (figure ). patchy ggos (arrow) in a patient with a cough who reported a covid- -positive contact. ggo: ground-glass opacity; covid- : coronavirus completely similar to the most recent lung findings: covid- pneumonia was excluded ( figure ) . the rt-pcr negative swab confirmed the radiological report. the same patient as in figure : a careful review of the ct performed in january shows identical bilateral ggos (arrow), confirming imaging features as consistent with emphysema and, therefore, ruling out covid- pneumonia. ct: computed tomography; ggo: ground-glass opacity; covid- : coronavirus ct in centrilobular-emphysema shows small, well-defined or poorly defined areas of low attenuation surrounded by normal lung; centrilobular pulmonary arteries or arterioles mark the center of each lobule. the low-attenuation areas may range from - mm. small airway disease is often a component of both emphysema-predominant disease and airway-predominant disease involving larger airways. isolated small airway disease can also occur as a primary expression of copd [ ] . in addition to centrilobular nodules, ct in cigarette smokers could show the typical imaging features of infiltrative lung disease, including ggos and reticular anomalies, which likely correspond to variable combinations of respiratory bronchiolitis, airspace enlargement with fibrosis, and smoking-related interstitial fibrosis [ ] . in these findings, the histopathological mechanism underlying ggo is small airway obstruction or fibrosis, which causes vasoconstriction in that area of the lung, shunting blood away from areas of impaired gas exchange, with hyperperfusion of the adjacent normal lung, leading to relatively increased attenuation with a subsequent "mosaic attenuation" aspect [ ] [ ] . ggo seen on ct can represent a wide spectrum of pathologic conditions, such as inflammatory disease and lung neoplasms. the analysis of several parameters, such as bilateral/unilateral involvement localization in the lung parenchyma, superimposed consolidation, and the presence of lymphadenopathies and pleural effusion and associated abnormalities will avoid most pitfalls, indicating a possible diagnosis of the underlying cause and offering a consistent differential diagnosis. nevertheless, ggo remains a diagnostic challenge and, therefore, a systematic approach is necessary to ensure an optimal workup. covid- pneumonia is a novel disease, therefore, special attention to differential diagnoses with clinical and radiological presentations that may mimic it is recommended. although ct represents a fundamental diagnostic tool because of its sensitivity, it still needs to be integrated with clinical data to achieve the best clinical management. this principle should be applied not just in the covid- era but also in all pathologies that could have very similar radiological findings. however, in the presence of typical imaging features (e.g. ggo and consolidation), the radiologist should focus his attention on the pandemic and manage a suspect patient as covid- positive until proven to be negative since it is of primary importance to manage covid- pneumonia as early as possible in order to prevent the contagion from continuing to spread. human subjects: consent was obtained by all participants in this study. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. a novel coronavirus from patients with pneumonia in china initial ct findings and temporal changes in patients with the novel coronavirus pneumonia ( -ncov): a study of patients in wuhan, china mosaic attenuation: etiology, methods of differentiation, and pitfalls fleischner society: glossary of terms for thoracic imaging automated assessment of malignant degree of small peripheral adenocarcinomas using volumetric ct data: correlation with pathologic prognostic factors. lung cancer pure ground-glass opacity neoplastic lung nodules: histopathology, imaging, and management ground-glass opacity lung nodules in the era of lung cancer ct screening: radiology, pathology, and clinical management viral pneumonias in adults: radiologic and pathologic findings ct of viral lower respiratory tract infections in adults: comparison among viral organisms and between viral and bacterial infections radiological findings from patients with covid- pneumonia in wuhan, china: a descriptive study what every radiologist should know about idiopathic interstitial pneumonias european respiratory society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias lymphoid interstitial pneumonia. a narrative review diffuse lung cysts in lymphoid interstitial pneumonia: high-resolution ct and pathologic findings ct-definable subtypes of chronic obstructive pulmonary disease: a statement of the fleischner society clinically occult interstitial fibrosis in smokers: classification and significance of a surprisingly common finding in lobectomy specimens mosaic attenuation: etiology, methods of differentiation, and pitfalls respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, and desquamative interstitial pneumonia: different entities or part of the spectrum of the same disease process? key: cord- - lilrqts authors: capone, stephen; abramyan, shogik; ross, brent; rosenberg, joshua; zeibeq, john; vasudevan, viswanath; samad, reza; gerolemou, louis; pinelis, evgeny; gasperino, james; orsini, jose title: characterization of critically ill covid- patients at a brooklyn safety-net hospital date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: lilrqts background the novel coronavirus disease (covid- ) pandemic continues to spread across the country with over million cases and , deaths in the united states as of july . outcomes have been poor, with reported admission rates to the intensive care team of % in china and mortality among critically ill patients of % in seattle. here we explore the disease characteristics in a brooklyn safety-net hospital affected by the severe acute respiratory syndrome coronavirus (sars-cov- ) pandemic. methods a retrospective chart review of covid- positive patients at the brooklyn hospital center who were treated by the intensive care team prior to april , . data was extracted from the electronic health record, analyzed and correlated for outcome. results impact of various clinical treatments was assessed, showing no change in median overall survival (os) of both hydroxychloroquine with azithromycin or vitamin c with zinc. supplemental therapies were used in selected patients, and some were shown to increase median os and patients requiring vasopressor support or invasive mechanical ventilation showed decreased os. there was no statistically significant difference in overall survival based on ethnicity, healthcare status, or individual medical comorbidities, although a negative trend exists for diabetes. despite this, there is a trend towards increasingly poor prognosis based on the number of comorbidities and class obesity. conclusions despite the fact that we show no significant differences in mortality based on ethnicity, insurance status, or individual medical comorbidities, we show a high overall mortality. there is also a trend towards increased overall mortality in class obesity, which should be further investigated. we suggest that these findings may be attributed to both socioeconomic factors and an increased incidence of total medical comorbidities in our patient population. impact of various clinical treatments was assessed, showing no change in median overall survival (os) of both hydroxychloroquine with azithromycin or vitamin c with zinc. supplemental therapies were used in selected patients, and some were shown to increase median os and patients requiring vasopressor support or invasive mechanical ventilation showed decreased os. there was no statistically significant difference in overall survival based on ethnicity, healthcare status, or individual medical comorbidities, although a negative trend exists for diabetes. despite this, there is a trend towards increasingly poor prognosis based on the number of comorbidities and class obesity. despite the fact that we show no significant differences in mortality based on ethnicity, insurance status, or individual medical comorbidities, we show a high overall mortality. there is also a trend towards increased overall mortality in class obesity, which should be further investigated. we suggest that these findings may be attributed to both socioeconomic factors and an increased incidence of total medical comorbidities in our patient population. the novel coronavirus disease (covid- ) pandemic continues to spread across the country with over million cases and , deaths nationwide as of july . outcomes have been poor despite our best efforts, with reported admission rates to the intensive care unit upwards of % in china and italy, and mortality among these patients as high as % in seattle [ ] [ ] [ ] [ ] . in new york city (nyc), the epicenter of this outbreak, patients showed an overall mortality of . % and those requiring mechanical ventilation, approximately one-third of critically ill patients, had mortality between . and . % [ , ] . a recent report noted an overall mortality of critical care patients in manhattan of almost % [ ] . the brooklyn hospital center is a -bed community safety-net hospital in brooklyn, ny. the purpose of this study was to explore the disease characteristics in a brooklyn safety-net hospital affected by the severe acute respiratory syndrome coronavirus (sars-cov- ) pandemic and the clinical course and outcomes of this uniquely diverse population. this study was performed at the brooklyn hospital center and approved by the institutional review board (# ). a retrospective review of the electronic medical record (emr; allscripts healthcare solutions) was utilized to identify all patients at our institution with confirmed sars-cov- infections (n= ). all tests were performed by nasopharyngeal or sputum samples and qualitative detection of nucleic acid performed by reverse transcriptase polymerase chain reaction (rt-pcr; abbott, chicago, il). we then identified each individual patient admitted to the hospital and managed by the intensive care team (n= ). this included patients in the medical intensive care unit (micu), surgical intensive care unit (sicu), cardiac care unit (ccu), cardiac telemetry unit (cscu), cardiac progressive care unit (cpcu), and postanesthesia care unit (pacu). clinical outcomes were assessed until our study cutoff date of april , . pre-existing medical comorbidities were identified in the emr and noted. all demographic and clinical data were manually extracted from the individual emr by physicians. even if patients were not offered a mechanical ventilator due to do-notresuscitate (dnr) status, they were included in the study. all statistical analyses were performed using prism v. . . (graphpad software, llc, san diego, ca). statistical significance was defined as p< . . descriptive statistics were reported as means with interquartile ranges, as relevant. categorical variables were reported as total number and percentages. no imputation was made for missing data. characteristics of each group were compared by analysis of variance (anova). survival curve analyses were performed using log-rank (mantel-cox) tests. correlation tests were utilized to calculate pearson correlation coefficient (pearson r) values and multiple linear regressions utilized least squares. days to death was calculated from the date of admission and patients who were discharged from the hospital were censored at that time, though it should be noted that patients arrived at differing stages of covid- , with some being directly admitted to the intensive care service while others admitted to the inpatient unit prior to upgrade to this service. during the study period from march , to april , , we tested patients, with positive results and pending, of which we identified admitted to the hospital. of the admitted patients, ( . %) were admitted to the intensive care service prior to april , , with still currently admitted ( . %) at the end of the study period. the median age of the cohort was years and . % were african american or hispanic ( table ) . median length of stay (los) for all critically ill patients was days from hospital admission, and after controlling for dnr status the overall all-cause mortality was . % ( / , figure ). median hospital overall survival (os) for inpatient covid- patients was significantly longer than intensive care patients ( days vs. days, p<. , figure ) . preliminary evidence has suggested that minority groups have been disproportionately affected by covid- , with a higher percentage of minority patients occupying the intensive care unit than the general population with a higher overall mortality [ , [ ] [ ] [ ] . amongst those admitted to the icu, we observed no statistically significant difference in mortality among different ethnic groups ( the average age of the cohort was . years, . % were male, and a vast majority of patients were on medicare or medicaid ( . %). complete demographic, social, and clinical data separated by ethnicity is summarized in table . patients were divided into demographic groups as follows: african american (n= ), hispanic (n= ), caucasian (n= ) and other (n= ). statistical analysis showed no difference in baseline clinical characteristics between these groups, including age (p= . ), gender (p= . ), or body mass index (bmi, p= . ). we also found an overall average body mass index (bmi) of . , which is categorized as obesity by the centers for disease control and prevention (cdc) [ ] . a combination of hydroxychloroquine and azithromycin was used on patients ( / , . %). standard dosage of hydroxycholoroquine/azithromycin was mg q for three doses, then daily/ mg qd, respectively. a combination of vitamin c and zinc was also utilized in patients ( . %) and supplemental intravenous immunoglobin in eight patients ( . %). vasopressor support was required in of these critically ill patients ( . %). approximately % of patients were treated empirically with therapeutic anticoagulation for suspected pulmonary embolism (pe) or thrombotic microangiopathy based on provider judgement. invasive mechanical ventilation was required in ( . %) of patients admitted to the icu. breakdown of these treatments by ethnicity are summarized in table . multiple linear regression analysis of each individual clinical treatment yielded multiple statistically significant results (figure ). both treatment with hydroxychloroquine and azithromycin and vitamin c plus zinc were associated with no impact on overall survival (p= . ; p= . ), whereas both intravenous immunoglobin (ivig) and anticoagulation were associated with an increased likelihood of survival, though low sample size should be noted (p= . ; p= . ). overall all-cause mortality was . % in patients receiving anticoagulation ( / ) and % in patients receiving ivig ( / ). various anticoagulation was used including heparin ( / , . %), enoxaprin ( / , . %), combination of heparin plus enoxaprin ( / , . %), or heparin plus tissue plasminogen activator (tpa; / , . %) and was unknown for one patient ( / , . %). as expected, use of vasopressor support and invasive mechanical ventilation were associated with a decreased likelihood of survival (p< . , p= . ). figure ). median os for was shorter for patients with atrial fibrillation versus those with renal failure (median os days vs. days, respectively; figure ). complications pe: pulmonary embolism; dvt: deep vein thrombosis we then investigated the impact of healthcare insurance status of the patient on overall survival. patients were divided by insurance, of whom ( . %) were on either medicare or medicaid, which is consistent with our standard patient population. further stratification showed patients receiving medicare ( / , . %) compared to receiving medicaid ( / , . %). statistical analysis showed no significant difference in survival based on insurance status (p= . , figure ) with median overall survival of , , , and days for medicare, medicaid, self-pay, and private insurance, respectively. we quantified prevalence of specific comorbidities, including obesity, diabetes, hypertension, asthma, vascular events, chronic kidney disease, gastroesophageal reflux disease, and human immunodeficiency virus (summarized in table ). our population has similar rates of individual medical comorbidities to published populations [ ] [ ] [ ] , with . % ( / ) of critically ill patients having one or more documented comorbidity and . % ( / ) with two or more. survival curve statistics for individual medical comorbidities were compared ( figure ). when compared against themselves, there was no significant difference in median os for a single comorbidity (p= . ). we then aimed to see if an individual comorbidity had an impact on likelihood of death in these patients. multivariate correlation analysis yielded no statistically significant results when comparing individual comorbidities to death (figure ) but showed a trend towards diabetes modestly decreasing survival (pearson r= . ; p= . ). deceased patients were then isolated and a multiple linear regression analysis was performed to compare each comorbidity to the overall days to death which yielded no statistically significant results. obesity has been suggested as a significant contributing factor to the progression of covid- [ ] . when analyzed separately, we show no significant difference in overall survival based on normal/overweight vs. obese (p= . , os vs. days). as obesity can be stratified into subsets and anecdotal experience suggested an increased mortality with increased body mass index (bmi), we performed further analysis of os within these subgroups. figure ). comparison between patients with a singular comorbidity (n= ) to those with two or more (n= ) showed a strong trend towards decreased survival (p=. , figure ). patients with no comorbidities were excluded due to low sample size. median os for patients with one comorbidity was days, whereas median os for patients with two or more comorbidities decreased to days. the median charlson comorbidity index (cci) for the entire cohort was . ( % -year mortality) [ ] . when compared between ethnicities, analysis showed no difference in cci between groups (p= . ). cci averages of . vs. . vs. . were calculated for currently admitted, deceased, and discharged patients, respectively. comparison between deceased vs. discharged patients shows a statistically significant decrease in cci in discharged patients ( . vs. . , p= . ). preliminary data across multiple states has shown a disproportionate number of minority patients being impacted by the covid- pandemic [ - ]. our findings support and extend these prior reports with . % of our critically ill patients identified as african american or hispanic. further, we also observed a high prevalence of comorbidities in our cohort, which is likely a reflection of the social determinants of health (i.e. low income) in the population we serve. here we present a comprehensive analysis of critically ill covid- patients at our community safety-net hospital in brooklyn, new york, with the most diverse patient population reported. we began by analyzing outcomes of patients based on treatment modalities. prior work has suggested the efficacy of combination hydroxychloroquine and azithromycin, which has been heavily utilized at our institution, but we show no association with mortality or median os (p= . ), consistent with recently reported data [ ] [ ] [ ] [ ] . it should be noted that the incidence of new-onset atrial fibrillation and renal failure were elevated in our patient population ( / , . %; / , . %, respectively), and atrial fibrillation was associated with hydroxychloroquine and azithromycin use in . % of cases. presence of new-onset atrial fibrillation was also associated with a poor prognosis, showing a decrease in median os from days to nine days and an overall mortality of . %. this increased incidence of atrial fibrillation and the lack of impact on overall mortality and median overall survival suggests that the use of hydroxychloroquine and azithromycin must be carefully weighed against each individual patient's risk factors and pre-existing comorbidities. while used in a minority of patients, intravenous immunoglobin and anticoagulation were both associated with an increased median os. we suggest that the efficacy of anticoagulation may correlate to the increased incidence of thrombotic events seen in covid- patients, which have the potential to lead to major sequelae, including organ failure and potentially death [ ] [ ] [ ] . while these events themselves were relatively rare in our patients ( . % overall), % of these patients ultimately succumbed to covid- . when dividing the patients based on ethnicity or by insurance status, analysis of both total mortality and median overall survival was not statistically significant. this was an unexpected finding, but we propose various reasons for these results. first, our population is disproportionately diverse and our comparator group of caucasian patients had a small sample size (n= ). second, ethnicity and healthcare status are not mutually exclusive from other poor prognostic indicators, mainly incidence of pre-existing comorbidities, and may in fact contribute to their presence. a lack of access to care among these patients is a significant underlying factor in the presence of comorbidities, which can ultimately lead to poor outcomes in covid- . while ethnicity and insurance status may not directly impact overall mortality or median overall survival, these factors must be considered on a larger scale as having an indirect impact. although there has been significant speculation that individual medical comorbidities may impact the outcomes of covid- patients, we have been unable to identify any significant individual factor. we do note a trend towards decreased survival in patients with diabetes (p= . ), but no individual factor showed a statistically significant impact on overall mortality or median os. more likely, we propose that the overall health status of each individual patient based on the number of medical comorbidities plays a significant role in the progression and severity of covid- . this is evidenced by the strong trend showing a decrease in median os of critically ill patients from to days with two or more pre-existing comorbidities (p= . ) and an increased mortality of . % ( / ) compared to . % ( / ) in patients with a single comorbidity. this is consistent with our findings showing a strong trend towards lower cci in discharged patients when compared to currently admitted and deceased patients. obesity has also been suggested as a risk factor. obesity as a whole did not show any association with overall survival or mortality, but when separating out class obesity, we note a trend towards increased mortality and decreased median os. we suggest that this becomes a mechanical problem during severe covid- acute respiratory distress syndrome (ards) due to increased intra-abdominal pressure, negative transpulmonary pressure, closure of dependent airways producing shunting and contributing to severe oxygenation failure, high positive endexpiratory pressure (peep), and hemodynamic instability coupled with the inability to overcome the weight of the chest wall [ , ] . there are multiple limitations of this study. first, we present statistics and outcomes from a single community hospital in brooklyn, new york. second, because the data was extracted from the electronic health record, there is the possibility that data was not documented in the system as it would be in the physical chart. third, it was also assumed that discharged patients were alive at the cutoff date of april , . fourth, a significant portion of our critically ill patients remained admitted under the intensive care service ( / , . %) at our cutoff point. fifth, patients with dnr orders were included in the study and did not undergo aggressive intervention. and lastly, we must consider the rapid nature of the changing understanding and treatment of covid- . our management of these patients was based on the medical consensus at the time and continues to evolve with increased reporting of data and outcomes. despite the fact that we show no significant differences in mortality based on ethnicity, insurance status, or individual medical comorbidities, we show a high overall mortality. there is also a trend towards increased overall mortality in class obesity, which should be further investigated. we suggest that these findings may be attributed to both socioeconomic factors and an increased incidence of total medical comorbidities in our patient population. many of these variables are not mutually exclusive, with most of our patients being from a diverse population with limited access to medical care and multiple comorbidities. we also report no association between overall survival and hydroxychloroquine in combination with azithromycin, but increased overall survival was associated with patients that received supplemental anticoagulation or intravenous immunoglobin. human subjects: consent was obtained by all participants in this study. the brooklyn hospital center issued approval . animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. clinical characteristics of coronavirus disease in china characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china critical care utilization for the covid- outbreak in covid- in critically ill patients in the seattle region -case series clinical characteristics of covid- in presenting characteristics, comorbidities, and outcomes among patients hospitalized with covid- in the new york city area epidemiology, clinical course, and outcomes of critically ill adults with covid- in new york city: a prospective cohort study factors associated with hospitalization and critical illness among , patients with covid- disease a new method of classifying prognostic comorbidity in longitudinal studies: development and validation hydroxychloroquine and azithromycin as a treatment of covid- : results of an open-label non-randomized clinical trial outcomes of hydroxychloroquine usage in united states veterans hospitalized with covid- no evidence of clinical efficacy of hydroxychloroquine in patients hospitalised for covid- infection and requiring oxygen : results of a study using routinely collected data to emulate a target trial observational study of hydroxychloroquine in hospitalized patients with covid- incidence of thrombotic complications in critically ill icu patients with covid- large-vessel stroke as a presenting feature of covid- in the young coagulopathy and antiphospholipid antibodies in patients with covid- covid- does not lead to a "typical" acute respiratory distress syndrome lung recruitability in sars-cov- associated acute respiratory distress syndrome: a single-center, observational study we would like to give a special thank you to the brooklyn hospital center department of surgery and the department of medicine, division of critical care and the center for critical care services for their continued services during this covid- pandemic. key: cord- -gsevwptc authors: waltz, jeffrey; kocher, madison; kahn, jacob; leddy, rebecca; chamberlin, jordan h; cook, daniel; burt, jeremy r title: improving ct-derived fractional flow reserve analysis: a quality improvement initiative date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: gsevwptc objectives the aim of this study was to identify factors and quality improvement strategies to improve coronary computed tomography angiography (ccta) studies referred for fractional flow reserve derived from ct angiography (ffrct) analysis. methods thirty randomly selected cctas were analyzed for quality control. a uniform ccta protocol was implemented by an in-house steering committee, emphasizing the importance of adequate heart rate control and nitroglycerine usage. sixty additional randomly selected cctas were evaluated for quality at multiple time points during intervention, and ffrct acceptance rate was analyzed at the conclusion. results prior to the implementation of this quality improvement program, our overall institution-specific percent acceptance rate was . % for ffrct compared to the national average of > %. post-intervention, this was improved to an average acceptance rate of % for ffrct analysis. conclusions establishment and strict adherence to ccta imaging protocols with appropriate training and adequate buy-in of ct technologists and nurses is a viable way of improving the quality of imaging and subsequent patient care. current guidelines recommend the use of non-invasive anatomic imaging, including coronary computed tomography angiography (ccta), for first-line testing in patients with suspected intermediate-risk stable coronary artery disease (cad) [ , ] . ccta and invasive coronary angiography have high accuracy for the detection of coronary artery stenoses based on anatomy evaluation, but they are less helpful for the identification of functionally significant, flow-limiting stenoses of approximately - % [ , ] . fractional flow reserve derived from ct angiography (ffrct) has been shown to be an effective adjunct to ccta in the diagnosis of flow-limiting stenosis and determining prognosis [ ] . ffrct utilization is now being recognized by large insurers who are covering the cost of this added service. the purpose of our institution's ccta-ffrct program is to improve the accuracy of diagnosis and management of cad, avoid additional unnecessary procedures, reduce cost, and improve patient and physician satisfaction. although ffrct has been shown to be a valuable tool in the evaluation of intermediate-range stenosis on ccta, the analysis is highly sensitive to scanning protocol and artifacts [ ] . it has been shown that image quality of ccta is closely associated with the heart rate at the time of study acquisition [ ] . the rejection rate of ffrct in the literature ranges from % to % mainly due to differences in imaging acquisition, study incompletion such as missing best diastolic or systolic reconstructions for myocardial segmentation, patient-specific factors including body habitus and motion, and artifacts including calcium blooming, motion, and low contrast [ , ] . in contradistinction, the rejection rate at our facility of radiologist-referred ffrct was discovered to be as high as %, limiting comprehensive evaluation of coronary artery stenoses and further patient management. produced as well as the overall acceptance of ccta studies for ffrct analysis. our primary measure was the overall improvement of ffrct analyses provided in order to maximize yield of the study and improve patient management. an initial review of a subset of randomly chosen ccta studies out of a total of studies performed in july and august was completed by a sub-specialist cardiovascular radiologist to determine the overall quality of the studies in addition to factors limiting the utility of the studies. ccta studies were assessed according to cad-rads criteria, a standardized method of assessing the highest-grade coronary artery lesion for adequacy of study: excellent (no artifacts), good (minor artifact but good diagnostic quality), acceptable (moderate artifacts), or poor/suboptimal (severe artifacts) [ ] . the first three categories, excellent, good, and acceptable, were deemed as diagnostic and acceptable for ffrct evaluation, whereas the last category, poor/suboptimal, was deemed non-diagnostic and therefore unsuitable for ffrct evaluation referral. a non-diagnostic study was defined as poor quality in one or more coronary artery segments, which would further preclude ffrct evaluation. in an attempt to optimize the quality of the studies, direct lines of communication were established with the ct technologists and nurses to reveal protocol and acquisition shortcomings. to evaluate potential issues, a question and answer session with a brief didactic lecture was given by an expert cardiovascular radiologist to the ct technologists and the nursing staff, including an overview of coronary artery imaging and the purpose of performing ccta and ffrct at our institution. from this discussion with the technologists and nurses, the lead cardiac imager noted several confounding factors described by the staff that were potentially leading to poor image quality. these included a lack of a standardized protocol regarding administration of nitroglycerine and beta-blockers and a lack of understanding of how to assess studies for quality control on the scanner. the standardized coronary artery disease -reporting and data system (cad-rads) method of assessment was used to evaluate the final images obtained for all patients. the scoring system ranges from cad-rads (complete absence of stenosis) to cad-rads (presence of at least one totally occluded coronary artery) and allows for specific recommendations to be included in the radiology impression for appropriate management. all ccta examinations at our institution with a cad-rads of ( - % stenosis) were referred for ffrct analysis unless otherwise indicated. finally, a complete ffrct analysis was performed on all studies meeting our hospital's inclusion criteria. to evaluate the effect of pre-scan medication use on overall ccta image quality at our institution, the radiology nurses were instructed to give every patient nitroglycerine and a beta-blocker, if required and not contraindicated, to achieve a heart rate of < and preferably < . all patients were to receive . mg of sublingual nitroglycerine and the additional premedication instructions for heart rate ( table ) . metoprolol dose and route of administration *oral medications were to be administered - hours prior to ccta. **metoprolol prn was to be an iv push of mg metoprolol every minutes up to eight doses for a target heart rate of beats per minute and held for a systolic blood pressure of less than mg. the nurses were then instructed to contact the cardiovascular radiologist on call if there was a contraindication to heart rate control or nitroglycerine administration. a list of contraindications for both nitroglycerine and beta-blocker administration was provided ( figure ). nursing checklist provided to the radiology nurses to be completed prior to nitroglycerine and metoprolol administration for the ccta examination. a second random sample of ccta cases performed during the month of november was reviewed by the same expert cardiovascular radiologist to assess for early post-intervention changes following the initial medication changes to confirm that improvement could be seen in the visual quality score. an in-house steering committee was created comprising radiology administration, cardiovascular radiologists, cardiologists, an emergency medicine physician, ct technologists, and radiology nursing staff. the purpose of the committee was to make the ccta acquisition protocol uniform. a proposed imaging pathway was developed with consensus by the steering committee members, which emphasized the need for consistent medication administration prior to scanning. an electronic order set was created within our electronic medical record to aid in the consistency of this protocol. the steering committee recommended that one-on-one training be provided to the technologists regarding appropriate scanning parameters, contrast dosages, and injection rate ( table ) . monthly meetings were conducted by the same cardiovascular radiologist with the head technologists to discuss problem areas and concerns. siemens force dual source ct; image during inspiration -acquire imaging from the carina through apex of the heart; run a test bolus; most patients will receive retrospective gating for function and also get coronary artery calcium scan figure is an overall timeline demonstrating our intervention strategy and assessments, and figure demonstrates the overall ccta acquisition workflow created. figure illustrates the individual improvement steps that were performed in order to reach our goal of improved ccta acquisition for successful ffrct analysis. the second analysis was performed to evaluate the effect of the metoprolol and nitroglycerine trial. the quality assessment again consisted of cctas, this time with diagnostic studies and only studies with one or more poor quality coronary artery segments. of the nine non-diagnostic studies, three ( %) were due to cardiac motion, five ( %) were due to respiratory motion, and one ( %) was due to suboptimal contrast bolus timing. given the success of the initial pre-scan medication trial at improving imaging quality, a standardized protocol was created and implemented by the in-house steering committee. one-on-one training with the ct technologists, including training for improved breath holds, was implemented to further improve protocol compliance. one-sample correlation power calculation for follow-up duration revealed a power of . , and the power calculation for patient number (n = ) revealed a power of . ( figures a, b) . a linear weighted correlation showed a moderately strong linear correlation between months after the initiative began and the proportion of accepted studies (r = . ; p < . ) ( figure ). further ffrct analysis was requested from pre-intervention until two months following the intervention (figure ) . our ffrct acceptance rate increased to an average of % over the last three months of data collection. number of cases is represented by the bars (right-sided graph legend), and the acceptance rate is represented by the line graph (left-sided graph legend). bar graph generated using ggpubr: 'ggplot ' based publication ready plots, r package version . . (https://cran.r-project.org/package=ggpubr). initial rejection rates for ffrct analysis reported throughout the literature range from % to %, with significant cardiac motion commonly cited as a reason for rejection [ , ] . pontone et al. found that temporal resolution, section thickness, and heart rate are independent predictors of rejection for ccta ffrct analysis [ , ] . they postulated that their own study had a low rejection rate of . % because of the use of dual-source technology and wide-coverage single-source scanners. while prior studies have shown that the use of nitrates and beta-blockers improves accuracy of the ffrct analysis, overall analysis of success rates remain moving targets [ ] [ ] [ ] . vasodilation plays a role in improving overall analysis and visualization of the entire length of the coronary artery; however, this also must be balanced with decreased cardiac motion for quality assessment [ ] . these studies emphasize that many factors must be optimized and controlled in order to produce a high-yield study that can be referred for ffrct analysis, but specific protocols for imaging acquisition and specific factors influencing the analysis remain incompletely understood. we took a holistic approach to correcting the ccta quality issues at our institution. thus, we are limited in our evaluation regarding the extent to which each of the individual factors that we adjusted for affected the outcome measure of rejection/acceptance of ffrct analysis. a significant limitation present in this study is the sample size of each group. however, we felt that a random sample of studies, representing approximately % of the ccta studies/month, was an adequate representation. continuing data acquisition of prospective patients sent for ffrct analysis, as well as increasing the retrospective sample data, could increase the overall power of the study. finally, we do not want to underestimate the need for ct technologist and radiology nurse buy-in and retraining. when the issues were brought to their attention and they were subsequently given training, this likely controlled for many confounders that were problematic in ffrct analysis acceptance rate and ccta quality. prior to intervention, our institution-specific overall ffrct analysis acceptance rate was lower than average. initial review demonstrated that ccta studies were deemed poor quality, of which eight were secondary to motion. given that motion was a key contributory factor in visual quality inspection in addition to the success of ffrct analysis, other unidentified factors needed to be controlled for in a holistic and protocoldriven manner. additional measures that were also taken during the education process, which certainly contributed to improved outcomes, were not directly assessed, including education on appropriate use of vasodilators. this likely resulted in better visualization of coronary vasculature. moreover, a checklist was provided to the nursing staff to be completed prior to ccta, which encouraged documentation of baseline cardiovascular status as well as relevant medical questions, factors that may affect or preclude the ccta. encouraging the nurses and technicians to call for any questions also worked to allow more open communication with the cardiac imagers, especially with more complex cases. providing a standardized protocol for adequate heart rate control allowed us to decrease cardiac motion but also provided more strict acquisition parameters to control for other unknown variables, which proved to be an important aspect of improving the ffrct analysis acceptance rate. in short, our holistic approach and newly issued standard protocol likely controlled for other factors, thus improving our ffrct analysis acceptance rate. human subjects: all authors have confirmed that this study did not involve human participants or tissue. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. esc guidelines for the diagnosis and management of chronic coronary syndromes sts multimodality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease: a report of the american college of cardiology foundation appropriate use criteria task force angiographic versus functional severity of coronary artery stenoses in the fame study fractional flow reserve versus angiography in multivessel evaluation clinical use of coronary cta-derived ffr for decision-making in stable cad determinants of rejection rate for coronary ct angiography fractional flow reserve analysis noninvasive ffr derived from coronary ct angiography: management and outcomes in the promise trial cad-rads(tm) coronary artery disease -reporting and data system. an expert consensus document of the society of cardiovascular american college of radiology (acr) and the north american society for cardiovascular imaging (nasci) prognostic value of absence or presence of coronary artery disease determined by -slice computed tomography coronary angiography a systematic review and meta-analysis clinical use of ct-derived fractional flow reserve in the emergency department quality-of-life and economic outcomes of assessing fractional flow reserve with computed tomography angiography: platform -year outcomes of ffrct-guided care in patients with suspected coronary disease: the platform study influence of coronary calcification on the diagnostic performance of ct angiography derived ffr in coronary artery disease: a substudy of the nxt trial ct angiography (cta) and diagnostic performance of noninvasive fractional flow reserve: results from the determination of fractional flow reserve by anatomic cta (defacto) study image quality in coronary ct angiography: challenges and technical solutions the intention of this project was to evaluate the factors contributing to the high rate of ffrct rejection at our institution, identify high yield interventions, and assess its effect on the quality of ccta studies key: cord- -zbipv er authors: alalwan, adel a; taher, abdulraqeeb; alaradi, ali h title: a hemodialysis patient with severe covid- pneumonia date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: zbipv er coronavirus disease (covid- ) is an infectious disease caused by a novel coronavirus that has spread rapidly, resulting in a worldwide pandemic. even though end-stage renal disease (esrd) patients are particularly susceptible to covid- infection and can develop severe to critical disease, there are limited studies and case reports about covid- in esrd patients. we report a case of a -year-old gentleman with esrd on regular hemodialysis. we describe the clinical presentation of this patient, the diagnostic process, the laboratory and imaging investigations, as well as the course of treatment. he positively responded to a -day course of lopinavir-ritonavir, ribavirin, azithromycin, and hydroxychloroquine. in december , a novel coronavirus was recognized as the cause of a group of pneumonia cases in wuhan, a city in the hubei province of china. it quickly spread, resulting in an epidemic throughout china, followed by a worldwide pandemic with almost million confirmed cases. in february , the world health organization (who) named the disease covid- , which stands for coronavirus disease . the virus that causes covid- was named severe acute respiratory syndrome coronavirus (sars-cov- ) [ ] . although severe covid- disease can occur in otherwise healthy individuals of any age, it predominantly affects adults with advanced age or underlying medical co-morbidities [ , ] . end-stage renal disease (esrd) is a severe medical condition with a high prevalence of co-morbid conditions including diabetes, hypertension, and cardiovascular disease [ ] . even though esrd patients are particularly susceptible to covid- infection and can develop severe to critical disease, there are limited studies and case reports about covid- in esrd patients. we report a case of an esrd patient on regular hemodialysis with severe covid- pneumonia. this report describes the clinical presentation of this disease in a hemodialysis patient, the diagnostic process, the laboratory and imaging investigations, as well as the course of treatment. a -year-old hemodialysis patient presented with a history of productive cough with whitish sputum and worsening shortness of breath for four days duration. his shortness of breath was not associated with orthopnea or paroxysmal nocturnal dyspnea. his wife was confirmed to have covid- disease three days before his symptoms started. he denied any history of fever, sore throat, nasal congestion, or headache. he was later admitted in a special isolation hospital designated for covid- / suspected covid- patients in bahrain. he has a medical history of hypertension, diabetes mellitus type , ischemic heart disease, and esrd. he has been on hemodialysis three-times-weekly through a tunneled vascular catheter. his regular medications include sevelamer, calcitriol, rosuvastatin, amlodipine, and perindopril. his blood sugar is controlled without medications. based on the ministry of health in bahrain guidelines, the hemodialysis facility where the patient was receiving his scheduled dialysis took specific precautions to reduce transmission and protect the patients. the facility was disinfected and the patient's close contacts (including healthcare staff and other patients) were traced, tested for the virus, and asked to self-isolate for days [ ] . all his close contacts tested negative. on admission, the patient was vitally stable, afebrile and was maintaining an oxygen saturation of % on room air. although he was able to lie flat, he had labored breathing and his respiratory rate was approximately breaths per minute. he was kept on a face mask with an oxygen flow of - l / min (pao / fio ratio of ). on chest examination, he had symmetrical breath sounds bilaterally, with coarse inspiratory crackles that were more prominent on the right side. his cardiovascular examination showed normal heart sounds with no murmurs or added sounds and his jugular venous pressure was not raised. he did not have peripheral edema. his abdominal and neurological examinations were unremarkable. laboratory tests on admission showed a white blood cell count of . x per l with % neutrophils, . % lymphocyte (absolute lymphocyte count . cells/ µl), and . % eosinophils. his hemoglobin was . g/dl and his platelet count was x per l. his urea was . mmol/l and his creatinine was µmol /l. his sodium was mmol/l, potassium . mmol/l , chloride mmol/l, bicarbonate mmol/l, calcium . mmol/l, phosphorus mmol/l and magnesium . mmol/l. c-reactive protein (crp) and procalcitonin (pct) were . mg/l (reference range - mg/l) and . µg /l (reference range - µg /l) respectively. his esr was mm/hour, serum ferritin µg /l, and d-dimer . mg/l. his liver function tests and cardiac enzymes were within the normal range. approximately hours after admission, the patient was shifted to an isolated high dependency unit for additional monitoring after further desaturation despite oxygen therapy (pao / fio ratio ). an urgent portable chest x-ray revealed bilateral patchy lower lobe predominant airspace opacification more diffusely involving the right lung, and more peripherally in the left lung ( figure ). a nasopharyngeal swab was taken from the patient and it was positive for sars-cov- virus nucleic acid. in addition, a septic workup was sent to rule out any bacterial co-infection. the patient was diagnosed with severe covid- disease. he was started on an antibiotic regimen designed for covid- pneumonia as well as empiric antibiotic therapy for possible co-infection. he received a day course of lopinavir-ritonavir, ribavirin, azithromycin, and hydroxychloroquine. he also finished a day course of vancomycin, meropenem, and a -day course of oseltamivir. the antibiotic dosages have been adjusted for esrd and hemodialysis. he was kept on deep venous thrombosis prophylaxis with heparin subcutaneous injections and received his regular medications. an electrocardiogram (ecg) was done every alternate day to monitor the qt interval on antibiotic therapy which did not exceed msec. his ecg showed baseline findings including a first-degree atrioventricular block with poor r-wave progression, and no acute ischemic changes were noted. his repeated echocardiogram on this admission did not reveal any new findings. he had a left ventricular ejection fraction of - % with persistent regional wall motion abnormalities noted in septal and apical regions. his central and peripheral blood cultures were sterile on two separate occasions. he also had a sterile endotracheal aspirate culture. the patient responded gradually to medical therapy and his oxygenation continued to improve until he was successfully weaned from oxygen. he continued to receive his hemodialysis sessions as scheduled bedside. his fluid balance was monitored closely, and adequate ultrafiltration was ensured. his blood count, electrolytes, and ecg findings remained consistent during the hospital stay. after days in the high dependency unit, his condition improved clinically, and he was shifted out to the ward under isolation settings. a repeated sars-cov- virus nucleic acid swab was negative. although the patient's radiographic findings lagged behind the improvement in clinical condition, his repeated chest x-ray showed partial interval resolution of the opacities which was more evident in the left lung and upper zone of the right lung ( figure ). covid- is an infectious disease that is mainly transmitted from person to person via respiratory droplets. covid- pneumonia appears to be the most common serious manifestation of the disease. it is predominately characterized by fever, cough, dyspnea, and bilateral infiltrates on chest imaging [ , ] . atypical presentations of covid- disease are frequent in hemodialysis patients and they are usually difficult to distinguish from other symptoms common among these patients. wang et al. reported five cases of covid- disease in hemodialysis patients in zhongnan hospital of wuhan university. they found that only three out of five had a fever and that the typical triad of fever, cough, and dyspnea was not present in any of the patients reported [ ] . in our case, the patient did not have any documented fever spikes on admission or during the hospital stay. the patient was diagnosed based on the ministry of health in bahrain guidance for covid- case definitions and the chinese clinical guidance for covid- pneumonia diagnosis and treatment (trial version ). he was labeled as suspected case based on having close contact with a confirmed covid- case and presenting with respiratory symptoms, imaging features suggestive of covid- pneumonia as well as lymphopenia on admission. the diagnosis was confirmed by identifying sars-cov- virus nucleic acid by real time reverse-transcription polymerase chain reaction (rt-pcr). the case was further classified as a severe disease due to having an oxygen saturation below % at rest on admission and having more than % lung involvement on imaging within hours [ , ] . our patient exhibited laboratory findings common among covid- patients [ , ] . he had lymphopenia as well as raised inflammatory markers (esr, crp, serum ferritin, d-dimer). although the majority of covid- pneumonia patients have normal serum procalcitonin (pct), the patient had slightly elevated pct on admission. tang et al. noted that pct has limitations in hemodialysis patients with covid- pneumonia because it tends to be chronically elevated in these patients [ ] . common abnormal radiographic findings in the chest x-rays of covid- pneumonia patients were consolidation and ground-glass opacities, with bilateral, peripheral, and lower lung zone distributions. our patient had typical chest x-ray findings ( figure ) ; thus ct-scan was not needed for diagnosis [ ] . the patient management plan was based on evidence-based medicine as well as the protocols published by the ministry of health in bahrain for the treatment of severe covid- pneumonia. the covid- treatment approach remains uncertain with no therapies clearly proven effective. in addition to supportive care, the patient was started on a covid- regimen composed of lopinavir-ritonavir, ribavirin, azithromycin, and hydroxychloroquine [ ] . the dosages of the administered therapy were adjusted for esrd and hemodialysis to ensure their safety and efficacy. the qt interval was also closely monitored in our patient because esrd patients are at high risk for developing qt interval prolongation and life-threatening arrhythmias with the covid- regimen. they are particularly vulnerable due to their susceptibility to electrolyte disturbances such as hypocalcemia and hypomagnesemia. the evidence on the possible efficacy of the proposed regimen for severe covid- pneumonia is largely from case reports and observational studies. lopinavir-ritonavir and ribavirin have been used successfully as monotherapies in the treatment of mild covid- pneumonia in hemodialysis patients [ , ] . in , chu et al. noted a favorable clinical response with lopinavir/ritonavir and ribavirin combination in sars-cov patients when compared with the historical outcomes of ribavirin and corticosteroids [ ] . the combination of azithromycin and hydroxychloroquine was also suggested to be associated with a more rapid resolution of virus detection compared with hydroxychloroquine alone [ ] . empiric antibiotic therapy for possible co-infection was also initiated. the choice of empiric antibiotics was based on clinical judgment, the bacterial pathogens commonly isolated at the patient's hemodialysis facility, and his own bacterial culture history. oseltamivir was added to empiric therapy because influenza pneumonia was included in the initial differential diagnosis based on clinical presentation and chest x-ray findings. after discharging the patient, he will be in home quarantine for another days. he will be tested again for the virus at day and day post-discharge. he will also be monitored closely for any respiratory and gastrointestinal symptoms. meanwhile, precautions will be taken to isolate the patient in the dialysis facility and minimize his contact with the healthcare staff. safety measures will also be taken in transporting the patient to and from the dialysis facility. esrd patients with covid- can present atypically and the index of suspicion should be high in the setting of a pandemic to avoid exposure to healthcare staff and other hemodialysis patients. covid- therapy in esrd is especially challenging due to the requirement of renal dose adjustment of various medications and the propensity of esrd patients to develop qt prolongation due to concomitant hypocalcemia and other electrolyte imbalances. further clinical trials and observational studies are required to clearly understand the whole spectrum of clinical presentations and the optimal diagnostic and treatment methods for covid- disease in hemodialysis patients. human subjects: consent was obtained by all participants in this study. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. who director-general's opening remarks at the mission briefing on covid- - clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease -united states usrds annual report: epidemiology of kidney disease in the united states . natl institutes heal natl inst diabetes dig kidney dis bahrain covid- protocols clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china. jama. epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study covid- in hemodialysis patients: a report of cases diagnosis and treatment protocol for novel coronavirus pneumonia covid- ) pneumonia in a hemodialysis patient acr recommendations for the use of chest radiography and computed tomography (ct) for suspected covid- infection role of lopinavir/ritonavir in the treatment of sars: initial virological and clinical findings chloroquine and hydroxychloroquine as available weapons to fight covid- the treatment plan of the patient was carried on in close collaboration with physicians from the infectious disease division, respiratory division, and intensive care unit at the ministry of health, bahrain. key: cord- -tu u b d authors: gaunkar, ridhima b; nagarsekar, aradhana; carvalho, karla m; jodalli, praveen s; mascarenhas, kennedy title: covid- in smokeless tobacco habitués: increased susceptibility and transmission date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: tu u b d as the coronavirus disease (covid- ) pandemic continues to sweep across the globe, the world is responding by implementing public awareness campaigns, social distancing measures, and other preventive strategies to arrest the spread of this lethal disease. infection with the severe acute respiratory syndrome coronavirus (sars-cov- ) exacts a heavy toll on patients with existing comorbidities. smokeless tobacco (slt) consumption is of particular concern in countries in south asia with high population densities, as it facilitates exposure to sars-cov- within or between communities by the act of public spitting. salivary droplets generated in this act are a potential threat because they can transmit this airborne infection. moreover, large gatherings at tobacco retail outlets, frequent hand-to-mouth contact, and sharing of apparatus by slt habitués could also aid in increasing the spread of sars-cov- . slt-induced higher expression of angiotensin-converting enzyme receptors along with the presence of furin in the oral mucosa and dysfunctional immune responses among slt habitués increase viral dissemination and an individual’s susceptibility to covid- . issuing rigorous regulations to restrict the use of various forms of slt products and the obnoxious act of spitting in public can assist in arresting the spread of covid- . widespread education campaigns enlightening the community regarding the adverse effects of slt consumption and its relationship with covid- , along with providing effective assistance to quit for those who are addicted, would decrease the spread of covid- . the coronavirus disease (covid- ) pandemic continues to sweep across the globe, with the severe acute respiratory syndrome coronavirus (sars-cov- ) infecting over five million people and killing over a quarter million worldwide to date. a pall of uncertainty and fear has descended upon the world, and the sars-cov- virus has brought changes to all aspects of life. according to the world health organization (who), sars-cov- is transmitted through the spread of virus-containing droplets (i.e., < -m distance) and/or contaminated surfaces [ ] . the who announced that covid- could become an endemic disease, although they warned that it is difficult to predict its course. to control the devastation caused by the infection, the world is responding with an amalgamation of strategies: social distancing, lockdowns (complete, partial, only in areas of high incidence), testing (voluntary and compulsory, focusing on risk groups), and a plethora of other prophylactic measures [ ] . the biggest challenge lies in identifying and isolating asymptomatic carriers and preventing exponential community transmission [ ] . systemic disease states such as diabetes mellitus, hypertension, and cardiac and pulmonary diseases increase disease susceptibility and mortality [ ] . the results from previous studies suggest that deleterious habits such as cigarette smoking and vaping could increase the susceptibility to covid- [ ] . there has not been much research on the increased risk of contracting covid- for smokeless tobacco (slt) users, although the use of these products is widely prevalent in south asia and the western pacific region. in this review, we explore the possibility of increased susceptibility and infectivity of slt habitués to covid- . slt is a broad group of unburned tobacco products that are used orally (chewed and spat out) or inhaled nasally. many asian and western pacific countries use an array of slt products such as snus, tobacco tooth powders, snuff, gutkha, khaini, tobacco powder, mawa, jarda, mishri, and tobacco paste [ ] [ ] [ ] . currently, the south asian region accounts for % of the global consumption of slt, with a majority in bangladesh ( %), india ( %), and myanmar ( %) [ ] . slt is a stimulant that causes an increase in heart rate, blood pressure, and epinephrine levels. there is a strong and proven association between the use of slt and death due to cardiovascular disease, cerebrovascular disease, and cancer [ ] . the increased cellular tropism in oral mucosa and altered immune response among slt habitués can increase an individual's susceptibility to covid- infection. this, compounded by the act of public spitting, frequent hand-to-mouth contact, and sharing of apparatus among slt habitués, could potentially aid in increasing disease transmission. the recognition of viral host cell receptors and their interaction with the host cell is crucial in studying viral tissue tropism and pathogenesis. an individual's susceptibility to viral infections is attributed to the presence of a host cell surface attachment site (receptor) and a conducive intracellular environment to favor virus replication and release [ ] . coronaviruses belong to the family of coronaviridae and contain a large, single, plus-stranded ribonucleic acid (rna) genome. there is a spike protein (s glycoprotein) on the surface of sars-cov- that binds to angiotensin-converting enzyme (ace ) receptors on the host cell membrane and facilitates viral entry into target cells. the s glycoprotein is primed by host membrane proteases (i.e., proprotein convertase) and then cleaved (at the s /s cleavage site) by the host-derived enzyme furin into two subunits, s and s . the s subunit facilitates viral and host membrane fusion through the heptad repeats hr and hr [ ] [ ] [ ] [ ] . studies have shown that the ace receptor is expressed in the oral epithelial cells of the tongue, buccal mucosa, gingiva, minor salivary gland ducts, t and b lymphocytes, and fibroblasts of the oral sub-mucosa. this suggests that sars-cov- exhibits tropism for the oral cavity [ ] . sars-cov- -positive individuals exhibit oral symptoms such as amblygeustia and dry mouth, which could be explained by the dysfunction of the ace receptors in virally infected oral tissue [ ] . several inherent factors could result in increased infectivity of the oral cavity by sars-cov- [ ] . immunostaining studies have revealed a high expression of the furin enzyme in the human tongue [ , ] . the presence of a furin-like cleavage site in the viral spike protein enhances the invasiveness of the virus to the host cell [ ] . the nicotine-induced increased expression of the ace receptor in the oral mucosa would favor viral tropism [ ] . thus, slt induces higher expression of ace receptors, and, combined with the presence of furin in the oral mucosa, there would be an increased susceptibility of slt habitués to covid- ( figure ) [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the known action of the enzyme furin and the nicotine-induced increased expression of the ace receptor result in covid- viral tropism to the oral mucosal tissues in smokeless tobacco habitués [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . tmprss , transmembrane protease serine ; ace , angiotensin-converting enzyme ; er, endoplasmic reticulum; covid- , coronavirus disease smokeless tobacco habitués: comorbidity due to an altered it has been shown that frequent and prolonged use of various forms of slt causes immunosuppression by affecting the adaptive (helper t cells, cd +cd + regulatory t cells, cd + t cells, b cells, and memory t/b lymphocytes) and innate (dendritic cells, macrophages, and natural killer cells) immune mechanisms. chronic inflammation of oral mucosa caused by slt results in a release of prostaglandins and cytokines such as interleukin- , interferon-α, tumor necrosis factor, and transforming growth factor β at the site of irritation, which could potentiate a pro-inflammatory cytokine response as well as cause immune system dysfunction [ ] [ ] [ ] . when virally infected immune cells disrupt the cellular and humoral immune response, this subjects slt habitués to cardiovascular, respiratory, and autoimmune diseases, as well as allergies, cancers, and transplant rejection [ ] . it has also been shown that the group of covid- patients with the worst outcomes had at least one of these comorbid conditions [ ] . this dysfunctional immune response in slt habitués against sars-cov- results in increased viral dissemination and cellular destruction via cytokine storm. this likely increases the chances that an slt habitué would contract covid- ( figure ) [ ] [ ] [ ] . slt chewing and spitting in public is a widespread, acceptable custom in many countries of south asia [ ] . the habit of spitting in public places unleashes a stream of saliva droplets directly in the path of commuters, pedestrians, and any nearby people [ ] . physiologically, saliva is a biomixture of crevicular fluid, desquamated oral epithelial cells, and microorganisms, and may contain blood, respiratory secretions, gastric acid from reflux, and food debris, all of which may be infectious [ ] . infected saliva generated during spitting can increase transmission of various respiratory infections through droplets spread to the mouth, nose, or eyes of individuals who are in close proximity [ ] . it has been validated that saliva is a viable sample source for sars-cov- detection when compared to nasopharyngeal or oropharyngeal swabs [ , ] . positive results were obtained from salivary samples collected from covid- patients who were analyzed using reverse transcriptase-polymerase chain reaction, which is considered the gold standard for detecting viruses in respiratory secretions and blood [ ] . it has been proved that saliva can harbor the virus in an active replicative state [ , ] . interestingly, individuals in whom pharyngeal and bronchoalveolar swabs proved to be negative showed positive salivary results on the same day [ ] . during hospitalization, the median viral load of the early saliva specimens among infected patients was . × copies/ml (range: . × to . × copies/ml). saliva specimens collected thereafter showed reduced salivary sars-cov- rna levels after hospitalization [ ] . another striking feature noted was that patients who had otherwise tested negative through nasal swab and had cleared from all clinical symptoms still tested sars-cov- rna-positive, suggesting that low levels of sars-cov- rna could be excreted in saliva even after clinical recovery [ ] . slt chewing increases salivary secretion, which is followed by a very strong desire to spit [ , ] . saliva droplets generated by spitting are formed as particles in a mixture of moisture with droplet nuclei of microorganisms. it has been observed that saliva can form into an aerosol along the air flow and become a medium for virus transmission [ , ] . the size of the saliva droplets determines the risk of viral transmission to host cells. large droplets (diameter > μm) tend to settle in the air quickly, and, therefore, the spread is limited to individuals nearest to the aerosol source. most communicable respiratory infections are transmitted through large droplets within a short distance or by contacting contaminated surfaces. small droplets are likely to evaporate into droplet nuclei (diameter < μm) in the environment and may be transmitted over short distances (< m). long-distance aerosol transmission is also determined by the length of time that the saliva droplets reside in the air (physical decay), the period during which pathogens remain viable in saliva droplets (biological decay), and the rate of acquisition of these infective droplets [ , ] . in india, slt consumption is a habit more commonly observed in socioeconomically deprived and less literate indian men [ ] . however, in a few states of india, the slt consumption in women is very high and is comparable to that of the male population [ ] . slt users often deface public places in many indian cities by spitting, a practice prevalent in tiny congested low socio-economic dwellings and urban slums. the remainder of the community is subsequently at increased risk of contracting a range of communicable diseases. india is particularly vulnerable because it bears the burden of the second largest population in the world, at approximately persons/km [ ] . at present, asia's largest slum (dharavi in mumbai) has become an area with very high infection rates for covid- , where slt consumption is a popular part of daily life [ ] . moreover, slt habitués gather in large numbers at retail tobacco outlets, where social distancing is not practiced. very recently, the government of india passed an order under the disaster management act that prohibits the sales of slt products and bans spitting in public places. however, the order was then amended, and, under section (b), the sale of slt products is once again permitted, but the prohibition of spitting in public places was maintained [ ] . frequent hand-to-mouth contact is one of the major avenues for transmission of viral infections such as covid- . the actual act of slt chewing involves placing these products inside the oral cavity using fingers several times during the day [ , ] . moreover, it has also been observed that there is a sharing of these products at workplaces [ ] . thus, slt habitués may be more vulnerable to covid- due to the possibility of transmission from frequent hand-to-mouth contact. because slt products are often produced by numerous methods in small cottage industries and sold in unregulated markets, effective regulation is difficult. this issue is intensified by limited research and a lack of a robust evidence base. several parties in the who framework convention on tobacco control consider slt use as a regional concern limited to southeast asia [ ] . eradicating the use of slt in asia and other parts of the world would be beneficial to human health by preventing the development of chronic disease as well as the dissemination of communicable diseases. a uniform, incremental taxation regime, the prohibition of public spitting, bans on illegal slt export between countries, standardized and validated testing of the content of slt products, implementation of large and clear pictorial warnings on packaging, and forbidding sales to minors should be strictly enforced to flatten the curve of the growing slt menace [ ] . tobacco cessation should be accelerated using evidence-based cessation and prevention strategies such as varenicline, nicotine replacement therapies, and behavioral interventions, which may help slt users to quit [ ] . there should be increased public awareness through increased social media usage during this pandemic to effectively wean habitués away from their usual triggers to consume tobacco. in countries such as india, it is a public health challenge to teach slt habitués to frequently wash their hands with soap and water or alcohol-based hand sanitizer (approved by the centers for disease control and prevention) to ensure optimal hand hygiene and reduce the risk of community transmission of covid- [ ] . once a novel vaccine is found to be safe and effective against covid- , it would be justifiable to prioritize assistance for young slt users who are in the preparation or action transtheoretical stage [ ] of quitting. this could act as an incentive to accelerate the quitting process and arrest the spread of covid- infection. it is imperative to prioritize research aimed at exploring the potential association of slt use with covid- to develop evidence-based policy options. this review reveals that slt addiction is likely to worsen the progression and prognosis of covid- infection by nicotine-induced increased expression of the ace receptor and action of the furin enzyme in the oral cavity. furthermore, the use of slt also increases the transmission of infection by users who engage in public spitting, frequent hand-to-mouth contact, and sharing of tobacco apparatus. hence, we cannot overlook the fact that cessation of slt product usage by habitués can contribute to reducing the risk of infection and spread of covid- . at the outset, the trajectory of covid- 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countries across the globe: call to action for full implementation of who fctc measures why smokeless tobacco control needs to be strengthened assessment of readiness to quit tobacco among patients with oral potentially malignant disorders using transtheoretical model in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -uvq hzga authors: malik, zohra r; razaq, zareen; mokraoui, nassim; zrodlowski, tomasz; bansod, snehal title: a case of a covid- -positive patient date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: uvq hzga the coronavirus (covid- ), discovered in , has been creating havoc since it first emerged in china and is now spreading worldwide. its presentation is somewhat similar to influenza. we hereby discuss the salient features of the coronavirus and present the case of a -year-old male who was tested positive for covid- . virus sars-cov- (severe acute respiratory syndrome coronavirus- ) or the novel coronavirus ( -ncov) belong to the broad family of coronaviruses (subgenus sarbecovirus). viruses use a nested set of messenger ribonucleic acids (mrnas) to replicate. there are four genera of coronaviruses: alpha, beta, gamma, and delta. two of these genera are known to infect humans: alpha coronaviruses (the human coronavirus e (hcov- e) and human coronavirus nl (hcov-nl )) and beta coronaviruses (human coronavirus hku (hcov-hku ), human coronavirus oc (hcov-oc ), the middle east respiratory syndrome-related coronavirus (mers-cov), and the severe acute respiratory syndrome coronavirus (sars-cov)) [ ] . the hcov (human coronavirus) is responsible for up to % - % of the upper respiratory tract infections globally [ ] . historically, hcov's were only responsible for mild infections until , with the emergence of the severe acute respiratory syndrome (sars) that started in the guangdong province of china. in , hcov was responsible for an outbreak of another epidemic, mers (middle east respiratory syndrome). the cov- is an enveloped, single-stranded, positive-sense ribonucleic acid (rna) virus. the virus has a spheric shape, - nm in diameter, surrounded by glycoprotein spikes (s) of - nm of length that gives them a crown-like appearance [ ] . about genomes of the sars-cov- has been isolated. the genome has approximately , to , bases in length and is encased in a nucleocapsid. it has four to five structural proteins: spike (s) protein, membrane (m) protein, nucleocapsid (n) protein, haemagglutinin-esterase fusion glycoprotein (hef), and small envelope protein (e). the spike proteins allow the fusion with the host cell membrane. the nonstructural protein (nsp ) spike protein is identical in % to the other sars-and mers-cov nsp s and has a high affinity to the human angiotensin-converting enzyme (ace ) receptors [ ] [ ] . the nucleocapsid proteins hold the rna genome and form the nucleocapsid. the hemagglutinin-esterase glycoprotein is found only in the beta coronaviruses, hcov-oc , and hku . the membrane and envelope proteins are responsible for the assembly and release of the virus. the most recent outbreak of the coronavirus (cov) started in december in the wuhan hubei province in china and has so far affected countries [ ] . a large number of infected people from the wuhan province were in contact with an animal market, which supports the possibility of a zoonotic origin. hcov spreads via respiratory transmission. based on available data of sars and mers, the centers for disease control and prevention (cdc) has estimated an incubation period for the covid- to be between two and days [ ] . the severity of symptoms depends on the patient's age and immune status [ ] . there have been reported cases involving large populations showing people with varying incubation periods and the severity of symptoms based on age and immune status. the most common symptoms include fever, cough, and shortness of breath. additional symptoms, such as fatigue, hemoptysis, and diarrhea, are also reported. the most common radiographic finding is diffuse bilateral ground-glass opacities found bilaterally and predominantly in the lower lobes. common laboratory findings include leukopenia, lymphopenia, and thrombocytopenia with elevated c-reactive protein (crp) levels [ ] . we hereby present the case of a -year-old man with a past medical history of alpha thalassemia who came to the emergency department (ed) with generalized weakness, fever, chills, productive cough with scant yellow sputum, myalgia, and arthralgia for days. the patient endorsed a lack of appetite and an episode of non-bilious vomiting with epigastric pain and dysuria. at presentation, the patient denied chest pain, shortness of breath, palpitations, or diarrhea. the patient had not traveled outside of the united states (us) and had no known allergies. physical examination was remarkable for scattered rhonchi bilaterally. the patient was not found to be in any distress. heart sounds were normal. the patient was alert and oriented to time, place, and person. cranial nerves, ii-xii, were grossly intact, sensation was intact to touch, and strength was / throughout the upper and lower extremities bilaterally. in the ed, his vital signs included a temperature of . °f, blood pressure (bp) of / mmhg, a mean arterial blood pressure of mmhg, heart rate of beats/minute, respiratory rate of /minute, and saturation of % on room air. laboratory results were as follows: white blood count (wbc) . lx /ul (normal . an echocardiogram (ekg) showed normal left ventricular systolic function. left ventricular ejection fraction, estimated by two-dimensional ( d) ekg at % - %. blood, urine, and sputum cultures were all negative. chest x-ray showed bilateral ground-glass opacities in the lower lobes (figures - ). an acid-fast bacillus smear was negative. the patient was placed on airborne, droplet, and contact isolation because of the high suspicion of coronavirus infection. the patient was empirically started on hydroxychloroquine and azithromycin. the pulmonologist was consulted. the screening test came out to be positive for covid- . the covid- taskforce, new york city department of health (nyc doh), and cdc covid- protocol were in full effect. the plan was made to discharge the patient on self-quarantine for days to limit transmission to others. the current understanding regarding transmission of the coronavirus to this day is still being researched. the suspected cause has been researched from the initial source of the outbreak in wuhan, china. there was an association between the initial patients and a local seafood market which sold live animals. the patients were mostly workers or visitors to that area which has since been closed. however, the transmission of the virus outside of wuhan has been more linked to person-to-person contact. this was suspected when reports of the virus were being made in places, such as hubei and the us, where individuals did not have exposure to animal/seafood markets. transmission by this method has been thought to be due to respiratory droplets from person to person. close contact with infected individuals (within six feet) through respiratory droplets (coughing/sneezing) landing in the mouths/noses of people nearby or inhaled through the lungs are the suspected mode of transmission of the virus between people. in addition, there are still reported cases of the virus in locations where it is still not known how or where the individuals were exposed [ ] [ ] [ ] . though there have been reported cases in other countries initially attributed to those with travel to china or contact with travelers from china, there are ongoing local transmissions being found in areas where individuals had no contact with people traveling not only from china but other countries with known ongoing cases (italy, iran, japan) [ ] . in the us especially, there are known cases of covid- in individuals who have not had travel or contact with anyone with known covid- , which raises the possibility of local transmission in these suspected areas. so far, several countries are still dealing with widespread ongoing transmission, some even with restrictions to entry to the us (china, iran and italy), while others are simply dealing with widespread transmissions or sustained community transmissions without restricted entry to the us [ ] [ ] [ ] [ ] . prevention is the key. all cases are reported to the cdc. covid- can prove to be deadly in immunocompromised individuals and individuals with comorbidities; otherwise, the illness in healthy people is no more than the flu. prevention is the key to avoiding crowded places and limiting exposure to others. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. middle east respiratory syndrome coronavirus: another zoonotic betacoronavirus causing sars-like disease coronavirus infections-more than just the common cold recovery in tracheal organ cultures of novel viruses from patients with respiratory disease human coronavirus nl employs the severe acute respiratory syndrome coronavirus receptor for cellular entry crystal structure of nsp endoribonuclease nendou from sars-cov- . biorxiv. response team: update: public health response to the coronavirus disease outbreak-united states the epidemiology and pathogenesis of coronavirus disease (covid- ) outbreak clinical characteristics of coronavirus disease in china novel coronavirus situation report - early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia covid- ) a familial cluster of infection associated with the novel coronavirus indicating potential person-to-person transmission during the incubation period key: cord- - vd tr j authors: gupta, anupam k; jackson, max; genuit, thomas; roberts, john title: is it safe to perform lung surgery during the coronavirus pandemic? date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: vd tr j background: coronavirus disease (covid- ) patients are rapidly growing in our community. patients with compromised lungs and older age are supposedly at high risk of poor outcomes with covid- . we aimed to evaluate the covid- impact on lung surgery during this pandemic at our hospital. methodology: this is a retrospective study of all lung surgery patients at our hospital in boca raton over three months (february to april ). all patients who remained for at least one-day inpatient post-lung surgery were assessed to see if they had an increased incidence of coronavirus infection during the hospital stay or at the follow-up office visit. results: a total of patients underwent thoracic surgery. it was found that there was no incidence of coronavirus infection in these patients. conclusion: with adequate precautions, older patients can undergo lung surgery during this pandemic. there was no incidence of covid- found among the patients during the hospital stay or at the first follow-up in the office. also, the postoperative course was not adversely affected. coronavirus disease (covid- ) was identified in wuhan, china, in december of and has subsequently grown into a global pandemic [ ] [ ] [ ] [ ] [ ] . as of april , , the world had over , , reported cases. the united states of america had over , cases, with the state of florida having , cases [ ] [ ] [ ] [ ] [ ] [ ] . palm beach county had over , cases, with deaths [ , ] . as of april , , we have reported cases requiring intensive care unit (icu) care at our tertiary medical center boca raton regional hospital ( bedded hospital) in florida and over coronavirus positive patients. there is no clear evidence as to why some people are more susceptible to the coronavirus infection [ , ] . this study was conducted to evaluate whether it is safe to perform lung surgery in the community where there is a rapidly increasing number of coronavirus patients. ours is a retrospective study performed at boca raton regional hospital, palm beach county, in florida. boca raton regional hospital is a bedded tertiary level center. from february , , to april , , the patients who underwent lung surgery were evaluated for the incidence of coronavirus infection during the hospital stay and on postoperative follow-up. patients underwent surgery after triage and if they fulfilled guidelines set by the american college of surgeons and hospital review board, so that hospital resources were not exhausted during an increasing number of covid cases in our community. the patients underwent screening for coronavirus infection based on history and imaging (chest x-ray and computed tomography), and a suspected person underwent nasal polymerase chain reaction (pcr) for coronavirus. a single positive test was to categorize the patient as a coronavirus-infected patient; in patients with high clinical suspicion, two consecutive negative pcr test results ruled out coronavirus infection. we evaluated electronic medical records for demographics, type of surgery, laboratory, radiological data, symptoms, and duration of stay in the hospital. the data collected and presented as absolute numbers and percentages. use of personal protective equipment with regular handwashing and clinical care were followed as per guidelines set by the society of thoracic surgeons during the care of these patients. the inclusion criterion for selecting the patients was as follows: patients undergoing lung/thoracic surgery needing at least one-day hospitalization from february , , to april , . the exclusion criteria were as follows: ( ) non-thoracic surgery patients, ( ) patients who did not have any surgery performed, and ( ) patients who underwent procedures on an outpatient basis. during the duration of the study, we had two resident doctors and four nurses from the thoracic surgery team who tested positive for coronavirus infection on the nasal pcr test. nine healthcare providers involved in patient care underwent quarantine for two weeks after the development of symptoms/positive pcr tests during the duration of this study. a total of patients underwent lung/thoracic surgery from february to april , ( table ) . a total of lung surgeries (wedge/lobectomy/pneumonectomy) were for non-small cell cancer of the lung. six underwent video-assisted thoracic surgery for empyema. the mean age of patients in the study was . years. thirty-nine patients were older than years. patients' postoperative hospital stay ranged from to days (prolonged stay for one patient was due to complications secondary to a leak post-esophageal surgery; however, the patient was negative for covid- on the nasal pcr test), with a mean of . days. the mean icu stay duration was . days. during the hospital stay, each of the patients received chest radiographs/computed tomography as needed for their management. all patients' follow-up was within two weeks from the time of discharge. there was a % follow-up at the office and the patients underwent evaluation for symptoms, imaging, and blood work as needed. we had no patients who needed further assessment or testing for covid- on follow-up. one patient needed readmission for breathlessness secondary to pneumothorax; five patients developed symptoms/radiographic signs of covid- and tested negative for covid- with two consecutive nasal pcr tests. there were zero incidences of covid- -positive cases, and the mean duration of hospital stay remained similar when compared to prior months. in january , the first case of covid- was reported in the united states [ ] . subsequently, there has been a rapid increase in cases in the united states and our community in florida [ , ] . the mode of transmission is primarily respiratory droplets and close contact [ ] [ ] [ ] [ ] [ ] [ ] [ ] . coronavirus binds to angiotensin-converting enzyme receptor- and dipeptidyl peptidase- receptors on bronchial epithelial cells and type pneumocytes [ ] [ ] [ ] [ ] . symptoms can vary from being asymptomatic to having a dry cough, breathlessness, and even death [ ] [ ] [ ] [ ] . the current centers for disease control (cdc) report suggests that all demographics of the global population can get infected with coronavirus [ ] [ ] [ ] [ ] . the cdc classifies individuals over more than years of age who are at risk of more severe disease than younger people [ ] [ ] [ ] [ ] . there is also a report that patients with underlying chronic pulmonary disease and lung cancer are at an increased risk of severe infection [ ] [ ] [ ] [ ] . diagnosis is confirmed by real-time reverse transcriptase pcr from respiratory and blood samples [ ] [ ] [ ] . imaging like chest x-ray showing reticular shadow and small patchy opacities, and computed tomography findings of bilateral multilobar ground-glass opacities are suggestive of coronavirus infection [ ] [ ] [ ] . blood work usually shows a normal or decreased leukocyte count [ ] [ ] [ ] [ ] [ ] [ ] . currently, there is no effective treatment for coronavirus infection, and because of the strain on hospital resources to manage the covid- pandemic, hospitals have reduced elective cases [ , , ] . while some patients can delay lung surgery, other patients' failure to receive surgical care can have a severe impact on their quality of life [ , ] . with thoracic oncology cases, the patients are at a high risk because of their impaired lung function and can have potentially poor outcomes [ , ] . a set of guidelines by the thoracic surgery outcomes research network to triage patients is being followed at most centers around america; however, these guidelines are based on assumptions [ , ] . in older patients with lung cancer, lung surgery if carried out with adequate precautions does not lead to an increased incidence of covid- , as noticed in the patients at our hospital. also, the postoperative course is not adversely affected in a community with a rising number of covid- patients, as there was no incidence of covid- in the hospital or on the follow-up visit in our older patients with compromised lungs. one limitation of this study was that our patient population is small, and further studies would help in establishing the safety of lung surgery during this pandemic. human subjects: consent was obtained by all participants in this study. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. first case of novel coronavirus in the united states an interactive web-based dashboard to track covid- in real time clinical characteristics of coronavirus disease in china early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia people who are at higher risk for severe illness clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china. jama. covid- ) pneumonia in two patients with lung cancer evidence based management guideline for the covid- pandemic -review article brief review on covid- : the pandemic caused by sars-cov- . cureus. clinical characteristics of coronavirus disease in china covid- guidance for triage of operations for thoracic malignancies: a consensus statement from thoracic surgery outcomes research network people at increased risk, and other people who need to take extra precautions key: cord- -n tm qr authors: gaballa, salem; aljaf, avan; patel, kashyap; lindsay, jane; hlaing, kyaw m title: covid- fears may be worse than the virus: a case of cardiogenic shock secondary to post-myocardial infarction ventricular septum rupture date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: n tm qr since the beginning of the coronavirus disease (covid- ) pandemic, there has been a growing and justifiable fear of catching the virus from the emergency rooms, thus decreasing the hospital visits. with virginia state slowly reopening and hca local hospitals resuming elective procedures, the number of emergency room visits, are recovering and increasing. we report a sad and unfortunate case of an -year-old female who was experiencing pressure-like chest pain but presented to the emergency room five days later out of fear of catching covid- from the hospital. on presentation to the ed, she was found to have an non-st-elevation myocardial infarction, which required urgent stenting of the left anterior descending artery. unfortunately, several hours later, she developed fatal cardiogenic shock due to ventricular septal rupture. we are reporting this case to highlight one of the many potential bad outcomes as a result of a delay in seeking necessary medical attention due to the fear of contracting the virus. ventricular septal rupture (vsr) is an uncommon but fatal mechanical complication of myocardial infarction (mi). this event occurs two to eight days after infarction and is more likely to occur in the anterior septum than in the posterior septum ( % vs. %) and often precipitates cardiogenic shock [ ] . the differential diagnosis of postinfarction cardiogenic shock includes free ventricular wall rupture and the rupture of the papillary muscles. the incidence of postinfarct vsr had declined over the years due to early reperfusion capabilities. postinfarction vsr is a surgical emergency, and the presence of cardiogenic shock is an indication for emergent intervention [ , ] . the best survival chances are reported when patients undergo early surgical repair. an -year-old caucasian woman with a known history of hypertension and arthritis presented to the emergency department with non-exertional, epigastric, non-radiating, sharp chest pain for the past several days. the patient stated that her chest pain was relieved by sublingual nitroglycerine. the patient stated that she was scared to come to the emergency department, as she didn't want to catch coronavirus disease (covid- ) from the hospital. the patient denied any shortness of breath or palpitations. her physical examination was unremarkable. laboratory data on admission was notable for white blood cells (wbcs) of . cells/mcl (normal range: , - , cells/mcl), d-dimer of . mg/l (normal value < . ), initial troponin of . ng/ml (normal value < . ng/ml), and repeat troponin of ng/ml. electrocardiogram (ekg) showed normal sinus rhythm with t-wave inversions in the anterolateral leads ( figure ) . the patient was initiated on a heparin drip according to the acute coronary syndrome protocol and was titrated appropriately according to activated partial thromboplastin time (aptt) results. a loading dose of aspirin was given with atorvastatin mg and metoprolol tartrate mg twice a day. the cardiology service was consulted, and subsequent cardiac catheterization showed significant stenosis of the left anterior descending artery (lad) s/p placement of a drug-eluting stent ( figure ) . she was given dual antiplatelet therapy (aspirin mg + clopidogrel mg daily) post-percutaneous coronary intervention (pci). echocardiogram showed a reduced ejection fraction (ef) of - %, with wall motion abnormalities in the lad territory. the patient developed cardiogenic shock, requiring three vasopressors (epinephrine, dobutamine, and vasopressin). unfortunately, she continued to deteriorate, and eventually triggered a code blue. the family was notified of her condition and they decided to change goals of care to comfort care measures. the patient expired a few minutes later. vsr is an uncommon mechanical complication of mi. studies show that post-mi septal wall perforations occur at a rate of approximately - %. vsr usually occurs within the first - days, within the zone of necrotic myocardial tissue. clinical studies report an average time of . days from mi to vsr. according to serpytis et al., the risk factors for higher mortality from acute vsd include female sex, advanced age, arterial hypertension, anterior wall acute mi (ami), absence of previous ami, and late arrival at the hospital [ ] . the age range of patients who sustain a postinfarction vsr is wide, ranging from to years [ ] . the pathophysiology of postinfarction vsr is explained by near occlusion of the septal blood supply that usually comes from the lad, the posterior descending branch of the right coronary artery, and the circumflex artery when it is dominant. infarctions associated with a vsr are usually transmural and extensive. around % of vsrs occur with infarction of the anterior wall and % with infarction of the posterior or inferior wall. posterior vsr may be accompanied by mitral valve insufficiency secondary to papillary muscle infarction or dysfunction [ ] . the postinfarct pathological changes that contribute to septal rupture involve coagulation necrosis of ischemic tissue with neutrophilic infiltration, eventually causing thinning and weakening of the septal myocardium, which usually happens within three to five days postinfarct. however, vsr occurring within hours of presentation is more likely due to the dissection of an intramural hematoma or hemorrhage into the ischemic myocardium. these changes are explained by the physical shear stressors at the border of an infarct zone, combined with a hypercontractile, and remote myocardial segment. clinically, it is usually seen with inferior infarction with the vsr noted in the inferior basal septum, abutting the hyperdynamic mid-septum that is perfused by the lad [ , ] . per becker et al., the pathological features of cardiac free wall rupture, which is applicable to vsr, are categorized into three types. type i rupture shows an abrupt, slit-like tear and occurs in acute infarcts at < hours. type ii rupture demonstrates the erosion of the infarcted myocardium and occurs in a sub-acute infarct within three to five days. type iii rupture is concomitantly associated with aneurysm formation, significant thinning of the septum, and subsequent rupture, which occurs in older infarcts over five days [ ] . vsr results in biventricular failure due to left-to-right shunting, right ventricular (rv) volume, and pressure overload, thus increasing pulmonary venous return and secondary left-sided volume overload. the most obvious physical sign is a typically harsh, loud, and holosystolic murmur heard best at the lower left and usually right sternal borders, with occasionally widespread radiation. in some cases, the murmur is heard best at the apex and may be mistaken for acute mitral regurgitation. a thrill can be detected in up to % of patients. rv volume overload results in an accentuated pulmonic component of the second heart sound, left and/or right s gallop, and tricuspid regurgitation. on the other hand, the increased transmitral flow results in a mid-diastolic rumble. the hemodynamic stability depends on the size of infarction, the severity of left-to-right shunting, and rv dysfunction. in hemodynamically stable patients, the presence of a murmur or the findings of echocardiography may be the only tipoff to the early diagnosis. the physical signs of cardiogenic shock are profound hypotension, cold and clammy extremities, pulmonary edema, and oliguria. when the right ventricle is involved, the hepatic dysfunction and coagulopathy may occur [ ] . there are no electrocardiographic characteristics of postinfarction vsr, but ekg can provide some clues. persistent st-segment elevation is common with a concomitant ventricular aneurysm. ekg can also help in predicting the anatomical location of the septal rupture. there are no electrocardiographic characteristics of postinfarction vsr, but ekg can provide some clues. persistent st-segment elevation is common with a ventricular aneurysm. ekg can help to predict the anatomic location of the septal rupture. the diagnosis can be confirmed with transthoracic echocardiography, which can identify ventricular septum defects in the d image and demonstrate the flow across the septum using color doppler. in addition to that, it can identify evidence of rv dilation and pulmonary hypertension and exclude the other differentials of hemodynamic instability. when the patient has poor acoustic windows due to mechanical ventilation or body habitus, a transesophageal echocardiogram (tee) should be considered. in patients undergoing coronary angiography, a left ventricular angiogram also can easily lead to the diagnosis by showing the shunting of contrast dye from the left ventricle to the right ventricle [ ] . in uncommon cases where the suspicion is still high, and transthoracic echocardiogram or tee may reveal no definitive diagnosis, confirmation of the diagnosis may require insertion of a pulmonary artery balloon catheter to document the left-to-right shunt. in hemodynamically stable patients, cardiac mri is able to show the delineation of the infarcted tissue and also the ruptured septum. however, this is not a standard diagnostic tool [ ] . initial pharmacological therapy may be used as an attempt to stabilize the patient hemodynamically. vasodilators can be used as it will improve the cardiac output by decreasing the afterload and the left-to-right shunt. on the other hand, inotropic agents should not be used alone as it will increase the cardiac output without changes in the ratio of pulmonary to systemic flow, thus increasing the left ventricular work and myocardial oxygen consumption. the severity of cardiogenic shock in some patients precludes vasodilator treatment and often mandates vasopressor support. intra-aortic balloon pump (iabp) offers essential and temporarily hemodynamic support as a bridge to urgent intervention. iabp reduces the left ventricular afterload, thus increasing cardiac output and decreasing the left-to-right shunting. iabp also improves diastolic pressure, thus increasing the coronary blood flow and improving the myocardial oxygen supply [ , ] . surgical intervention is the definitive treatment for postinfarction vsr. arnaoutakis et al. reported on surgical outcomes in , vsr patients from the society of thoracic surgeons national database [ ] . they concluded that early surgery is indicated to minimize the risk of mortality and morbidity. thus, the diagnosis of vsr should prompt a heart team discussion of options. this discussion should take into account that, for some patients, surgery is futile as mortality approaches %. very elderly patients and those with poor rv function often fall into this group. elderly patients, female gender, shock, inferior infarction, pre-operative iabp use, pre-operative dialysis, mitral insufficiency, and timing of repair are risk factors for increased postoperative mortality [ , ] . due to the unpredicted hemodynamic instability, early surgical repair should be considered in hemodynamically stable patients with preserved end-organ function and favorable anatomy. in patients undergoing surgery, coronary angiography should be performed if not already performed before the diagnosis of the mechanical complication [ , ] . if associated with severe coronary artery disease, an additional coronary artery bypass grafting for surgical closure of the rupture should be performed. surgical repair of vsr is associated with relatively high mortality and suboptimal results, with a postoperative residual shunt in up to %. given these poor results, the technique of percutaneous vsr device closure has been developed. such a less invasive approach with a catheter-based intervention may offer improved survival or provide hemodynamic stabilization as a bridge to surgery. it might be used as an adjunctive therapy for residual post-surgical shunts [ , ] . although the incidence of postinfarct vsr has declined over the years due to early reperfusion capabilities, the delay in seeking medical care due to covid- has the potential to reverse this trend. vsr is a life-threatening mechanical complication of mi leading to cardiogenic shock and subsequent death. therefore, therapy must be initiated emergently. in addition to inotropic agents and vasopressors that could be used in patients with cardiogenic shock, iabp may be used as a temporary hemodynamic bridge for surgical repair. surgical repair should be carried out on an emergency basis, even if the patient is hemodynamically stable. patients who develop vsr with multiorgan failure may not be a candidate for surgery and should consider palliative care. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. ventricular septal rupture following acute myocardial infarction operative management of postinfarction ventricular septal defect surgical management of postinfarction ventricular septal rupture post-infarction ventricular septal defect: risk factors and early outcomes risk factors, angiographic patterns, and outcomes in patients with ventricular septal defect complicating acute myocardial infarction outcome and profile of ventricular septal rupture with cardiogenic shock after myocardial infarction: a report from the shock trial registry ventricular septal rupture after acute myocardial infarction jp: cardiac tamponade. a study of hearts the in vivo morphology of post-infarct ventricular septal defect and the implications for closure interventional post-myocardial infarction ventricular septal defect closure: a systematic review of current evidence identification and treatment of complications of myocardial infarction post infarction ventricular septal defect -can we do better esc guidelines for the management of acute myocardial infarction in patients presenting with st-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with st-segment elevation of the european society of cardiology (esc) surgical repair of ventricular septal defect after myocardial infarction: outcomes from the society of thoracic surgeons national database amplatzer septal occluder to treat iatrogenic cardiac perforations current surgical approach to acute ventricular septal rupture percutaneous closure of postinfarction ventricular septal defect: in-hospital outcomes and long-term follow-up of uk experience immediate primary transcatheter closure of postinfarction ventricular septal defects key: cord- -ikk d wz authors: knio, ziyad o; shelton, j. alan; o'gara, tadhg title: heated air delivery by micro-sauna: an experimental treatment prototype concept for coronavirus disease date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ikk d wz coronavirus disease (covid- ) has gained international attention as it poses a significant threat to global health. currently, medical researchers are working to exhaust all strategies that may prove beneficial in combating this disease. heat has been shown to destabilize other coronavirus strains in testing environments, and it has been hypothesized that heated air may destabilize viral pathogens in vivo as well. the present report describes the engineering of a micro-sauna prototype for the delivery of heated air. concept formulation, process highlights, and the final prototype are all discussed. the prototype can deliver air heated to - degrees celsius in a safe and tolerable manner. the goal of this technical report is to further encourage the study of heated air as a potential covid- treatment. coronavirus disease (covid- ), caused by severe acute respiratory syndrome coronavirus (sars-cov- ), remains a global health emergency. as of april , , the world health organization reports an aggregate of , , total confirmed cases and , total deaths around the world [ ] . the medical community is making considerable efforts to advance the understanding of this international emergency. strategies for preventing covid- transmission and infection have generally been classified as either pharmacologic initiatives or non-pharmacologic initiatives [ ] . from a pharmacologic standpoint, antiviral agents, antimalarial agents such as chloroquine and hydroxychloroquine, and vaccination have received a great deal of attention [ ] [ ] [ ] . non-pharmacologic initiatives to date consist of health promotion strategies for disease mitigation and suppression, both within healthcare systems (transmission precautions, personal protective equipment), and for adoption by the general public (isolation and/or quarantine, social distancing, etc.) [ , ] . these strategies and this categorization, however, are neither exhaustive nor complete. in accordance with the current mission to limit the spread and the impact of covid- , it is of paramount importance that medical researchers consider all available modalities that may prove useful in treating this disease. heat has been shown to destabilize other coronavirus strains [ ] . it has been hypothesized that heated air in vivo may destabilize viral pathogens as it does in vitro, though the evidence to support these claims is low quality [ ] . despite the lack of evidence, the negligible risk profile and the potential benefit warrant the investigation of heated air as therapy, whether for symptomatic benefit or, ideally, a reduction in viral shedding. the present report describes the engineering of a micro-sauna prototype for the delivery of heated air in a safe and tolerable manner. it is hypothesized that its administration may benefit subjects of varying degrees of illness severity, from those seeking primary prevention to patients who are critically ill. the goal of this technical report is to further encourage the study of heated air as a potential covid- treatment. the prototype is intended to deliver air heated to - degrees celsius (c). this temperature was selected as it is similar to that of dry saunas, and therefore should be well tolerated. given that sars coronavirus strain cov-p has been shown to neutralize in a mimic-human environment after -, -and -minute exposure at , , and degrees c, respectively, the selected - degrees c temperature range should theoretically have a great therapeutic window in vivo [ ] . an initial attempt featured connecting a respirator mask to a bucket containing water heated to degrees c. the most important take away from this experiment was that degrees c water vapor delivered to the respiratory tract was not well tolerated in humans. a subsequent experiment included porting a hairdryer into a -inch cube with a modified respirator mask connected. in this experiment, air temperatures dropped dramatically through the length of the hose. moreover, the velocity with which air was delivered was not well tolerated. it was concluded that an ideal prototype would feature the following: (a) heating elements larger than those in a hairdryer, (b) a concentrated area of heated air delivery to minimize the heat to the user's face and body, (c) air delivery within a narrow temperature range, and (d) a short distance from the heat source to the respirator interface. the final prototype ( figure ) features an electric heater, electric metallic tube (emt) conduit connector, anesthesia mask (medline industries inc., northfield, il, usa), and proportionalintegral-derivative (pid) controller with thermocouple (inkbird tech. co., shenzhen, prc). an electric heater with resistive heat strips was selected over an infrared radiant heater because it did not require a fan to operate and it had a compact form factor. the internal circuitry was modified to bypass the tilt switch and the temperature sensor in order to use a microcontroller for more precise control of the heating elements. the vent holes on top of the heater were covered with a piece of sheet metal with a hole cut into it to allow connection of a fitting for a respirator interface. the heater was wrapped in aluminum bubble wrap insulation, and then had a box built around it using one-inch styrofoam insulation held together with nails and duct tape. a premium topvalve anesthesia mask was connected to a / -inch emt conduit connector that threaded into the sheet metal attachment site. finally, a pid controller with thermocouple was employed to manage the heating elements such that the temperature inside the micro-sauna could be maintained within a range of approximately . degrees c. of note, the pid controller was successful, whereas an arduino microcontroller with relays was not. the present report demonstrates the feasibility of engineering a micro-sauna prototype for heated air delivery. the current prototype was designed for use as a home remedy, or for administration to hospitalized patients under investigation and non-critically ill covid- patients. this strategy should be explored as a potential covid- treatment, given that heat and ultraviolet irradiation have shown promise in eliminating sars-cov-p viral infectivity in near-human testing conditions, and may in fact reduce viral shedding in humans [ , ] . even a reduction in symptom severity would be reason to administer heated air. there is a rapidly growing body of literature around covid- prevention and/or treatment strategies, with several studies proposing rather unique approaches [ ] [ ] [ ] . despite the grand attention that covid- has received, this is the first report to consider employing heated air as part of a covid- treatment approach. the motivation for considering heated air is based in an updated cochrane review by singh et al. in [ ] . despite the review investigating heated, humidified air for the "common cold," there is literature to support that this mechanism should translate to coronavirus strains [ ] . of the trials included in the cochrane review, only one defined viral titers as the primary outcome of interest [ ] . during the five-day study period, there was no difference in mean rhinovirus titers, or proportion of subjects testing positive, between the cohort receiving - degrees c vapor (n= ) and the cohort receiving placebo (n= ). such conclusions are limited by sample size. further, - degrees c, while marginally greater than physiologic temperature, may have been a limiting factor. duan et al. in observed sars-cov-p viral stability at degrees c but non-infectivity at degrees c and greater [ ] . the moderate temperatures in the cochrane review may explain, in part, the inconclusive results in viral titer reduction and in the remaining studies examining symptom severity [ ] . the micro-sauna prototype, with its delivery of air heated to - degrees c, is more likely to be successful. the limitations of this report, as with any technical report, relate to its replicability and applicability. it is the authors' hope that the detailed report on both the concept formulation and the micro-sauna's construction will aid in replicability. the authors anticipate that the widespread use of micro-saunas may prove to be challenging, as there are many practical considerations around mass production of a medical device. for instance, the design for this prototype's subsequent model features a stainless steel exterior that may be sanitized and transported with inpatient beds such that the micro-sauna can be used in critical care settings. additionally, it is unlikely that heated air can be tested as a stand-alone therapy for ethical reasons; its prescription as an adjunct to any indicated pharmacologic treatments may make interpretation of its independent effect challenging. nevertheless, the successful development of this experimental treatment prototype may prove to be useful in future infectious disease research. heated air delivery by a micro-sauna treatment prototype may prove beneficial in treating viral pathogens. endpoints to consider include symptomatic benefit, viral shedding, length of hospital stay, and mortality rate. a micro-sauna delivering air heated to - degrees c can be feasibly engineered from an electric heater, emt conduit connector, anesthesia mask, and pid controller with thermocouple. following confirmation of its safety profile, this strategy should be explored as a potential covid- adjunct treatment in varying patient care settings. human subjects: all authors have confirmed that this study did not involve human participants or tissue. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. covid- ) situation reports emerging prophylaxis strategies against covid- . monaldi arch chest dis first case of novel coronavirus in the united states hydroxychloroquine and azithromycin as a treatment of covid- : results of an open-label non-randomized clinical trial the covid- vaccine development landscape impact of non-pharmaceutical interventions (npis) to reduce covid mortality and healthcare demand response team. impact of non-pharmaceutical interventions (npis) to reduce covid- mortality and healthcare demand stability of sars coronavirus in human specimens and environment and its sensitivity to heating and uv irradiation heated, humidified air for the common cold . cochrane database syst rev current status of epidemiology, diagnosis, therapeutics, and vaccines for novel coronavirus disease (covid- ) can chinese medicine be used for prevention of corona virus disease (covid- )? a review of historical classics, research evidence and current prevention programs safety testing improvised covid- personal protective equipment based on a modified full-face snorkel mask effect of inhalation of hot humidified air on experimental rhinovirus infection winston-salem mixxer inc., nonprofit community makerspace, provided the space, facilitated coordination among designers of various disciplines, and shared the resources to allow the development of this prototype. we thank collaborators dakota pahel-short and matias silva for their critical contributions in prototype design and engineering. we also thank members alex stone and gary pellett for electronics engineering support, and aaron pendergast for supplying the pid controller. key: cord- - m a authors: gino, bruno; wang, zhujiang; d'entremont, philip; renouf, tia s; dubrowski, adam title: automated inflating resuscitator (air): design and development of a d-printed ventilator prototype and corresponding simulation scenario based on the management of a critical covid- patient date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: m a recent surges in covid- cases have generated an urgent global demand for ventilators. this demand has led to the development of numerous low-cost ventilation devices, but there has been less emphasis on training health professionals to use these new devices safely. the aim of this technical report is twofold: first, to describe the design and manufacturing process of the automated inflating resuscitator (air), a d-printed ventilator training device which operates on the principle of pushing a bag valve mask; second, to present a simulation scenario that can be used for training health professionals how to use this and similar, low-cost, d-printed ventilators in the context of ventilator shortages caused by covid- . to this end, the air was designed in an expedient manner in accordance with basic functionality established by the medicines and healthcare products regulatory agency (united kingdom) for provisional clinical use in light of covid- . in late , a cluster of pneumonia cases with unknown etiology were identified in wuhan, china. despite significant containment efforts, covid- has since spread widely. as of june , , there have been , global mortalities, with , of those coming from canada [ ] . critical covid- cases are characterized by respiratory failure requiring mechanical ventilation. in some countries, the demand for ventilators has far exceeded existing supplies. in italy, for instance, physicians have been forced to allocate ventilator access on the basis of triage criteria such as age and likelihood of survival [ ] . there is therefore an urgent need for alternative ventilators, which has led to the development of numerous devices. however, there has been less emphasis on how to train health professionals to use these new devices safely. consequently, in this report we describe the design and development of the automated inflating resuscitator (air), a d-printed ventilator training device. this technical report begins by considering the design elements that went into the air prototype, with reference to guidelines recently established by the medicines and healthcare products regulatory agency (mhra, united kingdom) [ ] . air contains the core components of a functional ventilator, with the possibility of further modular augmentation. in addition to the description of the ventilator, we also present a simulation case using air to train safety, operational ability, crisis resource management, and communication skills. the development of the air prototype followed mhra guidelines of the minimally acceptable ventilator to be used in hospitals during the current covid- pandemic [ ] . these guidelines influenced the choice of materials, design, and operative functions. this section discusses these considerations by focusing on four areas: . bag valve mask . oxygen flow . pressure valve . infection control the bag valve mask (bvm) was chosen for the construction of the air as it is inexpensive, easy to use, widely available, and already has its own safety features. bvms were created to temporarily replace mechanical ventilators during situations where mechanical ventilators are not available, and they function by manually providing positive pressure ventilation for patients who no longer have the ability to breathe [ ] . by incorporating the bvm, the air is intended to keep patients who need mechanical ventilation on ventilatory support, temporarily stabilizing their condition until a traditional mechanical ventilator becomes available. there are two main types of bvm: flow-inflated and self-inflated. flow-inflated bvms require a continuous gas flow or must be connected to an electrical source. self-inflated bvms expand after the bag is uncompressed. therefore, a self-inflated bvm, known also under the proprietary name ambu® (ambu a/s, copenhagen, denmark), was chosen for the air because it has this characteristic and because it is portable and easy to use [ ] . a bvm has four parts: exhalation port, patient valve, self-inflated bag, and an oxygen inlet. optional components include a positive end-expiratory pressure (peep) valve, an oxygen reservoir, and a pressure gauge [ ] . figure a presents a mechanical diagram of bvm components and is intended for engineering purposes. figure b illustrates how these components are assembled on an actual device. each air component was purchased, fabricated from commonly available commercial material, or printed using a d printer (see appendix ) . the self-inflated bag is placed separately from electrical components for safety purposes, which also allows it to be easily removed or replaced. the speed of the motor and the position of the bag can be adjusted to control the breath rate and tidal volume (tv) respectively. solidworks design model and stereolithography (stl) files can be downloaded from github here. figure provides a design overview of the air model. table . the operator can select their own motor system if the following requirements are met: the rated rotation speed falls in the range of - rotations per minute (rpm); rated torque is at least newton centimetres (n⋅cm). ventilation mode vcv influence the positive expiratory pressure (pep) and tv generated regardless of the bvm brand [ ] . in adults, resuscitators must be able to function properly with high oxygen flows, as during an emergency the flow meter can be changed and the resuscitator must remain in optimal condition. this consideration must be reviewed by all professionals who will eventually use the air. a malfunctioning manual or automatic resuscitator can put the patient at risk by providing an inadequate amount of oxygen [ ] . there are clinical situations in which professionals must personalize the amount of oxygen and, consequently, the percentage of oxygen mixed with atmospheric air offered to each patient. some bvms have been tested using oxygen flows of , , and litres per minute (l/min) with and without an oxygen reservoir, and this oxygen flow influences the fraction of inspired oxygen (fio ) offered to the patient [ ] . it is therefore important to know how an oxygen reservoir can influence the fio offered by the bvm device. evidence suggests that a bvm that allows the oxygen reservoir to be coupled, when tested without this accessory, reaches % fio when patients receive an oxygen flow greater than or equal to l/min [ ] . therefore, due to the possibility of variation in the performance of the bvm as a function of the oxygen flow used, healthcare professionals must adjust the flow so that the device provides the adequate amount of oxygen for each specific situation. in this case the healthcare professional must choose the specific venturi valve printed on a d printer and connect it to air so that fio best adapts to the patient's condition [ ] . the principles that govern bvm function also apply to the air; therefore, since the former can supply ambient air when no gas source is connected, the latter can be used in situations requiring limited fio , such as fio at % of the ambient air [ ] . when connected to the source of % oxygen, it is recommended to use a flow of to l/min at the entrance of the bag. the professional handling the air or bvm must also be aware that the position of the oxygen inlet, differences in oxygen flow supplied to the bvm, use of the oxygen reservoir, and the type of oxygen inlet valve can each contribute to fio variability for different resuscitator brands [ ] . the professional handling the air or bvm should keep in mind that the position of the air inlet, differences in oxygen flow supplied to the bvm, use of the oxygen reservoir, and type of air inlet valve can each contribute to fio variability for different resuscitator brands [ ] . there are two valves in the reservoir. a safety outlet valve relieves pressure inside the reservoir if excessive airflow is provided or if there is no manipulation of the bag. if the volume of gas in the reservoir is insufficient to fill the bag, another safety inlet valve allows the entry of ambient air. the peep valve can be attached to the expiratory port of the air. it prevents alveolar derecruitment during manual or automatic ventilation [ ] . another important consideration is the addition of the pressure relief valve to the bvm. in clinical practice health professionals do not usually monitor pressures while using a bvm. instead they use experiential knowledge based on direct patient observation. these professionals usually adjust the pressure by evaluating the expansion of the rib cage and resistance to ventilation, perceived subjectively by the operator's hands. however, in an emergency situation, one may not be able to view chest expansion continuously, or adequately perceive resistance to insufflation. for this reason, a pressure relief valve must be added to the bvm to ensure performance and safety of the device based on the needs of each patient. the pressure relief valve is not found on all brands of bvm. one must be added if there is none. when connecting the bvm to the device, it must be used with the pressure regulating valve unlocked and the pressure should be monitored with a manometer if one is available [ ] . mhra protocol guided the addition of the following features [ ]: . all parts coming into contact with the patient's breath are disposable or designed to be reusable. . all working components are contained within an impermeable casing. healthcare workers are able to manually wipe clean all external surfaces. . the air can connect to a viral hygroscopic filter. the air must be used by a professional who is familiar with the characteristics of bvms and the factors that impact ventilatory outcomes with these devices. in the event of power failure or component breakdown, the self-inflated bag can be easily removed from the air so that ventilation can continue manually. in this case, air will function similar to an unmodified bvm, although we have added safety mechanisms to air following protocols established by the mhra [ ] . the successful operation of air, therefore, incorporates two sets of skills: handling the bvm air's self-inflated bag, or bvm, can be used automatically or manually. this bag is made of a malleable material and must expand after each compression. the frequency of re-inflation determines the maximum minute volume, which in turn impacts the expiratory flow rate and thus the inspiratory:expiratory (i:e) ratio [ ] . as mentioned, the use of the oxygen reservoir will impact the fio offered [ ] . in addition, fio can be modified with venturi valves, which can be printed on d printers [ ] . operators should be able to manipulate fio using both of these components. air should be used only by qualified and trained professionals. for optimal use, training scenarios should prioritize both technical skill related to the device itself, and nontechnical skill related to the environment in which the device will be used. these skills can be organized into four categories: safety, operation, crisis resource management, and communication. . safety: proper knowledge and use of personal protective equipment (ppe) must be demonstrated at all times. also, the air non-rebreathing valve can become contaminated with patient fluids during ventilation. for this reason, it is necessary to frequently check the equipment throughout ventilation. other infection and contamination protocols must be adequately and regularly observed, and the participant should demonstrate sufficient functional knowledge to use air safely in each of its operative settings. the participant should gain a thorough understanding of the air's operative range and capacity. this understanding should be accompanied by technical skill, exhibited by the ability to quickly choose, interconvert, and modify operating modes in response to changing patient conditions. this operative competence is essential for patient safety. inaccurate compressions of the bvm bag can cause hypoventilation, hyperventilation, barotrauma, and reduced cardiac output. therefore, the same logic must be followed for air and similar devices. . crisis resource management: since the air is intended for limited-resource, high-acuity environments, participants should engage in scenarios that simulate these conditions. participants should be able to assess environmental cues, identify possible constraints, and prioritize action accordingly. successful assessment of this measure will require that participants demonstrate situational awareness, which can be divided into three stages: perception (recognizing basic features and dynamics of scenario); comprehension (integrating perceptions into holistic image and understanding relationship to goals); and projection (extrapolating information from first two stages to determine future status of situation) [ ] . communication is an important component in patient outcomes, and high-fidelity simulations have been identified as a method of promoting communication skills relevant to emergency procedures [ , ] . training scenarios should therefore emphasize communication between and within healthcare teams. successful assessment of this measure will require that participants demonstrate effective communication in the following three stages: information (accurately exchanging information using a technique such as 'read back, answer back'); understanding (constructing an acceptable, shared picture of the situation based on information); and coordination (working with others in synchronous, collaborative manner based on understanding) [ ] . communication with the patient and their family is also essential, particularly (in the context of covid- ) as a method of contact tracing. the following is presented to the participants as a stem of the simulation case: bvm, but the risk of the viral propagation remains great. there is only one traditional mechanical ventilator in the hospital and it is already being used by a -year-old female patient with severe respiratory failure but not covid- . referral hospitals are not receiving transfers due to the high influx of covid- patients." the patient's history is reported by his -year old son, who is waiting in hospital reception with his fiveyear-old daughter (the patient's granddaughter). seven days ago the patient started a dry cough with a fever. the dry cough worsened in the last two days, becoming productive and associated with severe shortness of breath. earlier this morning he was found in his bed, unconscious and breathing heavily. ten days ago, the patient's son and granddaughter returned from italy. on the evening of their return they visited the patient for dinner. today the child has a mild runny nose. the patient's son had a mild cold three days ago and is feeling well today. in this scenario, three individuals are infected by sars-cov- (the virus that causes covid- ) and the entire simulation will be based on the necessary care relevant to this information. the main areas of focus are safety, including the proper use of ppe; operating air when there is no mechanical ventilator available; crisis resource management; and effective communication during a high-acuity clinical event. these learning objectives are displayed in table . . safety: participants should be able to properly select and use, or describe the selection and use of all relevant ppe prior to interaction with the patient and air. this simulation can be performed in a controlled environment using a manikin with realistic lungs or an actor. respiratory parameters should be adjusted to simulate a critical covid- patient. these parameters must be measurable from the point of view of being stabilized by our air for a period of time determined by the facilitators. benchtop simulators can be used for the development of relevant psychomotor/technical clinical skills, such as airway management with the insertion of oropharyngeal airways (opa), endotracheal intubation, insertion of the chest tube, and other procedures. this simulation is intended for healthcare professionals operating in a ventilation shortage, who will have to use air or similar devices. therefore, other devices can be used if their basic operative function is sufficiently similar to air. facilitators should make this determination ahead of time in order to modify relevant portions of the scenario and also the assessment of operative skill ( table : learning objective ) as required. this simulation will be performed in a rural or remote hospital environment with few resources. the recommended materials, drugs, and equipment are listed in appendix . upon request, participants receive a list of patient data, including allergies, medications, and medical history (see appendices and ). the facilitators will be also given a list of the sequence to be followed in the patient's intubation procedure (figure ) . the facilitators choose the best path to be taken by the participants. ideally, the simulation is intended for healthcare professionals working in emergency care in rural areas or seeking additional training in the treatment of patients with severe respiratory failure. as the simulation takes place in a hospital environment, there is access to images and laboratory investigations. however, these resources may be limited or not. this will be at the facilitators' discretion and in accordance with local capacity. further, the facilitators should decide which regional, national, or international protocols will be observed. since these guidelines are currently being developed, we will not adopt any in particular. two healthcare professionals, both of whom are comfortable caring for patients with severe respiratory failure, should act as facilitators. these professionals should have experience with the use of traditional ventilators and manual resuscitators. one should be designated as the primary facilitator, providing guidance to the participants and helping with the general organization and execution of the case, while the second facilitator will be present to assess individual performance. facilitators are responsible for providing participants with the appropriate information as requested, including vital signs and other relevant physical examination results (see appendices and ). facilitators should examine the scenario in advance to identify possible limitations or technical problems, and they should also take time to fully familiarize themselves with air's functionality. the participants start the case in an emergency room (er), which contains a doctor and a nurse (the number of professionals can be changed). the only traditional mechanical ventilator is already in use by a non-covid- patient, who has required ventilatory support since last night. this small hospital is km from toronto where, despite a far greater number of intensive care unit (icu) beds with ventilators, there is a long list of patients who also need this equipment. the toronto hospital informs your staff that it is unable to receive new critically ill patients. however, the local team has access to a mechanical ventilator that was developed from a bvm. this is the only available device capable of keeping a patient with severe respiratory distress alive for a prolonged period of time. in this simulation case, we presented three people that are infected by sars-cov- . a -year-old elderly man with severe respiratory failure, an asymptomatic year-old adult man, and a -year-old child with only a mild runny nose (these last two are in the waiting room). before starting the simulation, participants must be submitted to the fictional contract, which recognizes that all processes occurring during the simulation should be treated as if they were "real", so that the objectives of the simulation can be achieved. during this period, facilitators present the simulation scenario and all necessary precautions, before introducing the air and describing its function. finally, participants are encouraged to assign roles in preparation to receive the patient. if there is a limited supply of participants, the paramedics team can only be reported by the facilitators, as the main objective of this simulation is training with the use of air and care involving a patient with covid- . figure displays the sequence to be followed in the patient's intubation procedure. justification: they can be contaminated and contaminate people nearby. guide the correct use of the surgical mask for those with respiratory symptoms (cover mouth and nose). findings: the patient's son and granddaughter are having trouble using the mask correctly. justification: misuse of the mask can contaminate people nearby. determine the availability of room used for infection control (e.g., negative pressure room). if none is available, adjust airflow through receiving room to minimize risk of airborne transmission. make seasonal modifications as necessary. findings: in the summer: the window is closed, the fan is on and the door is open. in winter: the draft heater is on. justification: the air stream can carry aerosols to other rooms and contaminate nearby environments. confirm that the team has properly disinfected the room and instruments used (including air) before and after patient visits with % alcohol or % sodium hypochlorite. findings: participants did not ensure the room, instruments, and air were adequately cleaned before receiving the patient. justification: failure to adequately and regularly clean surfaces before and after patient visits increases infection risk. wash hands with water and liquid soap or use % alcohol before using ppe. justification: lesions of the mucosa of the uvula and posterior wall of the hypopharynx, compressions of vessels, evolving with cyanosis of the tongue and macroglossia for a few hours, compression of the lingual nerve, with anesthesia in endotracheal tube or cricothyroidotomy ( figure ) . topography of the path of this nerve, compression of the recurrent laryngeal nerve and, consequently, uni or bilateral vocal fold paralysis, leading to dysphonia and compression of the hypoglossal nerve, with transient paralysis of tongue movements. verbalize intention to exchange the laryngeal mask for a definitive airway (endotracheal tube or cricothyroidotomy) (figure ). findings: participants do not verbalize their intention to change the non-definitive airway to a definitive one. justification: lack of coordination among team members can lead to loss of time in requesting the necessary equipment for this procedure. pre-oxygenate the patient using the bvm with sufficient flow to guarantee o to % (minimum l/min) (figure ). adjust air parameters prior to patient connection (table ) . findings: participants do not adjust air parameters before connecting patient. justification: time is wasted adjusting air parameters after patient is connected. transfer patient from bvm to air using a kelly clamp (figure ). findings: participants do not clamp the tube before switching from bvm to air. justification: a kelly clamp is important for clamping the tube when there is a need to change circuits/ventilators, in order to minimize aerosol production ( figure ). initiate continuous sedation. target rass: - ( figure ) . ration equipment and medications appropriately. findings: participants waste tubes, drugs, etc. justification: resources are already limited and wasting equipment and medications can lead to huge losses. request laboratory/imaging tests only when required (see appendix ) . findings: participants order laboratory or imaging tests when they are not necessary. justification: wasting laboratory/imaging tests will prevent these resources from helping patients who need them. collect information about medical care limitations from the referral hospital before patient arrival obtain all relevant patient information from paramedics and/or prehospital team. findings: participants do not collect patient information from paramedics, such as why they were called, how they found the patient, vital signs, who their companions are, where they are and how many there are. justification: not collecting information from the prehospital team can lead to poor patient care and a high risk of contamination by the team because they are not prepared to receive a suspect from covid- . share patient information with the rest of their team. findings: participants who collected complete patient information do not share it with the rest of the team. justification: failure to share information with the rest of the team can put patient care at risk and also a high risk of contamination by the team. clearly and confidently communicate a plan based on patient information. findings: participants neglect the importance of the correct use of ppe, the importance of exchanging a non-definitive airway for a definitive one, the importance of requesting a mechanical ventilator for long-term use and / or transfer to an icu and the importance of an effective communication to gather all information about the lack of available resources. back' to maintain a shared understanding of the situation, allowing them to develop collaborative action accordingly. obtain patient's medical history. findings: participants do not collect the patient's complete medical history. justification: failure to collect a complete patient history can lead to diagnostic errors, ineffective treatment, risk of contamination by the medical team and ineffective isolation conduct with family members suspected of being infected with covid- , causing them to contaminate close people. make an effort to establish trust and rapport with the patient's family. during this session, the "debriefing with good judgement" model can be used [ ] . this model uses an advocacy-inquiry approach to initiate a process of self-reflection, frame analysis, and behavioural change. in this method, facilitators address unexpected actions by first indicating their own expectation regarding correct action (advocacy), and then testing that expectation by investigating the cognitive frame that led to participant action (inquiry). the rationale behind this strategy is to clearly identify discrepancies between expected and performed actions without eliciting a defensive or otherwise counterproductive response on the part of the learner [ ] . in this way, the facilitator attempts to cultivate favourable conditions for selfreflection. participants should have the opportunity to share their positive and negative experiences, and facilitators should invite suggestions on how the simulation can be improved. this can be followed by a didactic session in which facilitators demonstrate appropriate use of ppe, as well as operative functions of the air and bvm. facilitators can also take this time to share and discuss strategies for nontechnical skills relevant to crisis resource management and team communication. lastly, facilitators may provide details relevant to the medical regulation of communication between institutions and local ambulance teams. the aim of this technical report was twofold: first, to describe the design and manufacturing process of the air, a d-printed ventilator training device which operates on the principle of pushing a bvm; second, to describe a simulation scenario that can be used for training health professionals how to effectively and safely use this and similar, low-cost, d-printed ventilators in the context of ventilator shortages caused by covid- . the development and manufacturing of the ventilator followed an iterative design cycle between clinical experts (er doctors), mechanical engineers, and education researchers. the team used mhra guidelines to develop the initial ventilator. the development and manufacturing took four weeks, with equipment costs of $ cad, and human resource commitments: doctors - hours, engineers - hours, researchers - hours. proper assessment of the clinical functioning of this prototype is outside of the scope of this technical report, and will be presented in a follow-up case study. based on the recommendation of scalese et al. describing the effectiveness of simulation training for highacuity clinical environments, we have also developed a simulation scenario [ ] . our scenario helps front line health professionals become familiar with the use of air in terms of safety and operations. further, the scenario was aimed to train crisis resource management and communication skills when operating air in the context of a ventilation shortage. while the scenario is based on covid- , it can be adapted to various settings where access to care and resources may be limited. our scenario also emphasizes the care of every patient who needs ventilatory support, not only those caused by covid- , as the deficiencies here can significantly impact care for all types of critically-ill patients. the air prototype exhibits most of the minimum mhra specifications, but additional components should be added prior to clinical use [ ] . to this end, the most urgent areas of future research are described below: gas or electricity supply failure; inspiratory airway pressure exceeded; inspiratory and peep pressure not achieved (equivalent to disconnection alarm); tv not achieved or exceeded. tv; frequency; peep; fio ; ventilation mode; actual current airway pressure. monitors should display continuously so the user can verify settings and modify as needed. if pressure support mode is provided there must be real time confirmation of each patient's breath and an alarm if below acceptable range. the first aim of this report was to describe the design and manufacturing process of a d-printed ventilator training device, the automated inflating resuscitator (air), which operates on the principle of pushing a bag valve mask (bvm). the current air prototype exhibits many of the mhra safety requirements, but an assessment of clinical viability falls outside the scope of this report. the modular design does however provide a template upon which further functions can be added. the second aim of this report was to describe a simulation scenario that can be used for training frontline workers in how to use air and similar ventilators. the scenario was designed to train safety, operative ability, crisis resource management, and communication skills. the context focused on ventilation shortages caused by covid- , but it may be adapted to simulate other conditions where similar ventilation devices are used. videolaryngoscope (disposable blades number and ) (if available); . conventional laryngoscope (curved blades numbers and , straight blade number ); . orotracheal tube epinephrine: mg/ml; . . % nacl solution or ringer lactate ml; . norepinephrine: mg/ml. equipment . mechanical ventilation circuits (bvm and air); . monitor & capnograph (if available); . infusion pump with channels or infusion pumps; . for peripheral access: pair of procedure gloves, alcohol swab, micropore cm, scissors, tourniquet, peripheral venous catheter, two-way connection, tray; . for central access: single, double or triple lumen catheter, central access puncture tray, chlorhexidine degermante, alcoholic chlorhexidine, sterile apron, gloves, mask, cap, glasses, micropore tape; ml and ml syringes world health organization: coronavirus disease (covid- ) situation report - resuscitation and intensive care: clinical ethics recommendations for the allocation of intensive care treatments in exceptional, resource-limited circumstances medicines and healthcare products regulatory agency: rapidly manufactured ventilator system manual resuscitators and spontaneous ventilation-an evaluation self-contained resuscitation equipment alterations in peak inspiratory pressure and tidal volume delivered by bras pneumol comparison of the fio delivered by seven models of the self-inflating bag-mask system evaluation of adult disposable manual resuscitators . respir care textbook of neonatal resuscitation covid- and the role of d printing in medicine to bag or not to bag? manual hyperinflation in intensive care the use of a pressure manometer enhances student physiotherapists' performance during manual hyperinflation the effect on expiratory flow rate of maintaining bag compression during manual hyperinflation design and evaluation for situation awareness enhancement city mouse, country mouse: a mixed-methods evaluation of perceived communication barriers between rural family physicians and urban consultants in newfoundland and labrador emergency management of anaphylaxis: a high fidelity interprofessional simulation scenario to foster teamwork among senior nursing, medicine, and pharmacy undergraduate students non-technical skills for surgeons system handbook v debriefing with good judgment: combining rigorous feedback with genuine inquiry simulation technology for skills training and competency assessment in medical education animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. this can be constructed out of a trash bag; . shoes: shoes that are easily cleaned and don't need to be touched are preferred. shoe covers aren't recommended as removing them may increase exposure. seven days ago the patient started with a dry cough associated with headache and fever of . °c. he used paracetamol, which improved headache and lowered fever to . °c for one day and returning to - °c the next day. the dry cough became productive days ago associated with severe dyspnea and a fever that did not go down with the medication. this morning his son tried to call him but unsuccessfully. going to his house he found him unconscious and breathing hard in his bed. the patient was admitted by paramedics, under positive pressure ventilation, using a laryngeal mask and using a bvm with filters to contain virus. medications nonemedical history appendectomy at age . bacterial pneumonia at age , treated with azithromycin and recovered fully. has never smoked or drank alcohol. swims every day and has eaten well for years. father died in a car accident years ago and his mother died years ago of natural causes. no history of diseases. no siblings. human subjects: all authors have confirmed that this study did not involve human participants or tissue. key: cord- -x up nvp authors: filatov, asia; sharma, pamraj; hindi, fawzi; espinosa, patricio s title: neurological complications of coronavirus disease (covid- ): encephalopathy date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: x up nvp coronavirus disease (covid- ) is a pandemic. neurological complications of covid- have not been reported. encephalopathy has not been described as a presenting symptom or complication of covid- . we report a case of a -year-old patient who traveled from europe to the united states and presented with encephalopathy and covid- . coronavirus disease (covid- ) was first detected in december in china and has rapidly spread to the rest of world. the world health organization (who) has recently declared covid- a pandemic, with more than , reported cases to date. covid- is a novel corona virus that probably emerged from an animal source, which is now spreading rapidly from person to person. the typical symptoms of covid- can range from mild to severe respiratory illness. the most common symptoms that have been reported thus far are fever, cough, and shortness of breath. the elderly population, especially those with underlying medical problems like chronic bronchitis, emphysema, heart failure, or diabetes, are more likely to develop serious illness [ , ] . neurological complications in covid- infected patients have not been widely reported. since elderly patients with chronic medical conditions are at an increased risk of altered mental status in the setting of acute infections, patients with covid- infection can also present with acute encephalopathy and changes in their level of consciousness. here we report a case of a patient who presented with encephalopathy and was found to be infected with covid- . a -year-old male with past medical history of atrial fibrillation, cardioembolic stroke, parkinson disease, chronic obstructive pulmonary disease (copd), and recent cellulitis presented to the emergency department with a chief complaint of fever and cough. the patient had a full workup, including routine labs and chest x-ray, which were nonrevealing. the patient was discharged home under the suspicion that this was an exacerbation of his copd. the patient went home on oral antibiotics. the patient returned to the emergency room (er) within hours with worsening symptoms, including headache, altered mental status, fever, and cough. the patient is originally from the netherlands and presented to our hospital seven days after arriving to the united states. the patient was admitted to the hospital for further workup. all protective measures and precautions for suspected covid- infection were taken. the patient was placed in isolation. repeat chest x-ray demonstrated small right pleural effusion with bilateral ground glass opacities (see figure ). ct chest revealed patchy bibasilar consolidations and subpleural opacities. both throat sputum and nasopharyngeal cultures were negative for strep. blood cultures were negative, and urine analysis was negative. influenza a and b tests were negative. : chest x-ray shows multifocal airspace opacities and "ground-glass opacities", characteristic signs of covid- infection. due to the severe alteration in mental status, neurology was consulted. upon examination, the patient was found encephalopathic, nonverbal, and unable to follow any commands; however, he was able to move all his extremities and was reacting to noxious stimuli. no nuchal rigidity was noted. a ct scan of the head and eeg were ordered immediately. the ct scan of the head showed no acute abnormalities. there was the presence of an area of encephalomalacia in the left temporal region, consistent with the prior history of embolic stroke (see figure ) . the eeg showed bilateral slowing and focal slowing in the left temporal region with sharply countered waves (see figure ). the patient was started on antiepileptic medication prophylactically given the possibility of subclinical seizures in this patient with an area of encephalomalacia and epileptiform discharges in the right temporal region. the patient was treated empirically with vancomycin, meropenem, and acyclovir. a lumbar puncture did not reveal any evidence of central nervous system infection (see table ). due to his progression in symptomatology, he was then tested for covid- and found to be positive. the patient developed respiratory failure and required intubation and was transferred to the icu. based on anecdotal experience from other medical centers, the patient was started on hydroxychloroquine and lopinavir/ritonavir, and was continued on broad-spectrum antibiotics. the patient currently remains in the icu, critically ill with poor prognosis. appearance clear covid- is a pandemic than ranges from mild disease with nonspecific signs and symptoms to acute respiratory symptoms to severe pneumonia with respiratory failure and septic shock. current evidence suggests that covid- patients commonly had neurological symptoms manifested as acute stroke ( %), consciousness impairment ( %), and skeletal muscle injury ( %) [ ] . elderly patients with chronic conditions are at an increased risk of altered mental status in the setting of acute infections. since covid- affects more the elderly and those with preexisting conditions, patients with prior neurological conditions and acute respiratory symptoms are at an increased risk of encephalopathy on initial presentation. the cerebrospinal fluid studies in our patient were normal; therefore, covid- does not cross the blood-brain barrier and does not cause meningitis or encephalitis. our case highlights the importance of identifying encephalopathy as a presenting sign of covid- . patients with covid- testing positive with common features of cough, fever, and shortness of breath can present to the er with encephalopathy, or can develop encephalopathy during their hospital stay. neurologist will be consulted, and practitioners have to know that this may encounter in the acute setting. given that there is limited data on neurological symptoms, health care providers benefit from accurate and real-life data to better treat their patients. if patients with neurological conditions are not considered to have covid- , this may present a nationwide issue to health care team members treating patients and in turn the general public if they are discharged and further exposed to other people. health care providers should be aware that patients with covid- can present with encephalopathy in the acute setting and during hospitalization. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. clinical characteristics of coronavirus disease in china clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china. jama. neurological manifestations of hospitalized patients with covid- in wuhan, china: a retrospective case series study key: cord- -oyhzot z authors: malik, fazila-tun-nesa; ishraquzzaman, mir; kalimuddin, md; choudhury, sohel; ahmed, nazir; badiuzzaman, mohammad; ahmed, mir n; banik, dhiman; huq, tawfiq s; al mamun, mohammad abdullah title: clinical presentation, management and in-hospital outcome of healthcare personnel with covid- disease date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: oyhzot z objective healthcare personnel (hcp) are undoubtedly one of the major frontline fighters in the coronavirus disease (covid- ) pandemic. therefore, it comes as no surprise that many hcp have become infected by covid- globally. the infection of hcp has received great attention in social media and is frequently reported from different parts of the world. however, there are few scientific reports addressing this aspect of the covid- pandemic. the aim of this study was to evaluate the characteristics of clinical presentation, treatment, and outcome of covid- infection among the hcp of our setting. methods this cross-sectional study was performed in the national heart foundation hospital & research institute of bangladesh from april to july , . hcp employed in this hospital who experienced fever or respiratory symptoms or came in close contact with covid- patients at home or their workplace were included in this study. the presence of covid- disease was confirmed by real-time reverse transcriptase-polymerase chain reaction on nasopharyngeal samples. a total of hcp were sampled and had a positive corona test. structured interviews were conducted to document symptoms for all hcp with confirmed covid- . data analysis was performed in july . results out of , hcp, subjects tested positive for covid- . among the hcp, infection rate was . %. the mean age of the study population was . ± . years (range: - yrs), of whom ( %) were female. most of this cohort were nurses ( [ . %]) and physicians ( [ %]), and the remaining ( . %) were other staff. the mean duration of onset of symptoms to test was . ± . days. the most common symptoms were fever ( . %), fatigue ( . %), cough ( %), body ache ( . %), headache, and anosmia ( . %). most subjects had mild disease ( [ %]), three ( . %) of the hcp had moderate disease and one ( . %) had severe disease. ten of the hcp ( . %) were asymptomatic. most of them were treated either by ivermectin plus azithromycin or ivermectin plus doxycycline. only ( . %) of the hcp were hospitalized, while others were treated either in home isolation ( . %) or in institutional isolation ( . %). recovery was almost uneventful except one healthcare worker who died. conclusion most hcp had mild symptoms and a few of them were asymptomatic also. hcp with mild covid- symptoms may be treated in home or institutional isolation. as they are a vulnerable group for infection, providing adequate protection to hcp is absolutely mandatory to safeguard them from this pandemic. out of , hcp, subjects tested positive for covid- . among the hcp, infection rate was . %. the mean age of the study population was . ± . years (range: - yrs), of whom ( %) were female. most of this cohort were nurses ( [ . %]) and physicians ( [ %]), and the remaining ( . %) were other staff. the mean duration of onset of symptoms to test was . ± . days. the most common symptoms were fever ( . %), fatigue ( . %), cough ( %), body ache ( . %), headache, and anosmia ( . %). most subjects had mild disease ( [ %]), three ( . %) of the hcp had moderate disease and one ( . %) had severe disease. ten of the hcp ( . %) were asymptomatic. most of them were treated either by ivermectin plus azithromycin or ivermectin plus doxycycline. only ( . %) of the hcp were hospitalized, while others were treated either in home isolation ( . %) or in institutional isolation ( . %). recovery was almost uneventful except one healthcare worker who died. severe acute respiratory syndrome coronavirus (sars-cov- ) spreads rapidly by human-tohuman transmission. the transmission is primarily by a combination of spread by droplet, direct and indirect contact and may possibly be airborne as well. therefore, the highly contagious sars-cov- poses an unprecedented threat to frontline workers like health care personnel (hcp). hcp can easily be infected from patients while providing medical care to them. the absence of definite curative treatment or vaccines makes the scenario even more difficult. protective measures against sars-cov- are of particular importance for hcp in direct contact with patients suffering from covid- in the ambulatory as well as hospital setting. the european society of cardiology (esc) and society for cardiovascular angiography and interventions (scai), american college of cardiology (acc), and the american college of emergency physicians (acep) guidance documents have suggested a high level of protection for hcp in the worst transmission scenario of sars-cov- infection [ , ] . the level of protection of hcp depends on patient risk status, setting and procedure performed. newly admitted patients in a cardiology ward should be regarded as possibly infected by sars-cov- [ , ] . incidence of hcp infection varies widely ranging from % - % [ ] [ ] [ ] [ ] [ ] [ ] . this variation may be due to comparison of hcp with different populations, either with total number of hcp or with number of infected patients in the hospital. it needs to be remembered that hcp are infected either by nosocomial acquisition or community transmission. the apparent higher rate of infection among hcp may be due to lack of awareness among staff, insufficient protective measures, social gatherings outside the workplace, or contact with known patients with covid- in the community. the aim of this study was to evaluate demographic and clinical characteristics, management, and in-hospital outcome of covid- among hcp with self-reported fever or respiratory symptoms in a tertiary cardiac care hospital. the cross-sectional study was conducted in the non-covid tertiary cardiac care hospital (national heart foundation hospital & research institute, dhaka, bangladesh) employing , hcp. from april to july , , hcp with self-reported fever or respiratory symptoms or close contact with the patient at home or at the workplace in the last days were tested for sars-cov- infection. oral consent was obtained from all subjects. relevant hospital staff were trained for appropriate specimen collection (sufficiently deep swab), storage, packaging, and transport. using a standardized technique, trained doctors or laboratory technicians obtained the nasopharyngeal swabs. after collection, swabs were placed in a transport medium and delivered to the laboratory. diagnosis of covid- was confirmed by real-time reverse transcription-polymerase chain reaction assay. structured interviews were conducted to document symptoms for all hcp with confirmed covid- . sample size calculation and analysis for statistical significance were not performed because of the descriptive nature of this study. categorical variables were presented as numbers and percentages and continuous data as mean and standard deviation. the analysis was performed with spss statistical software version . (spss inc., chicago, il, usa). data analysis was performed in july . it was also noted that the infection rate among hcp was highest in the month of may during the early stage of the pandemic in bangladesh. subsequently, the infection rate plateaued among the hcp in our hospital ( figure ). [ ] ). second, community transmission also plays an important role. some of the hcp were infected in the community during the initial stage of the pandemic due to lack of awareness, social gatherings outside the workplace, contact with known patients with covid- in the community, and lack of personal protection outside the workplace. hcp took level ii protection which includes disposable surgical cap, medical protection mask, work uniform, gown, disposable surgical gloves, and goggles or face shield for those who were in contact with patients. third, the incubation time of covid- ranges from - days. during the latent phase, it is difficult to recognize patients with the disease. insufficient protective measures at the beginning of this pandemic put hcp at a higher risk. fourth, in many patients the virulence of sars-cov- may not be severe. many patients were asymptomatic or with few symptoms and rarely some patients presented with atypical symptoms [ ] . such patients could greatly jeopardize the health of staff in the hospital and in the community. fifth, due to lack of disease knowledge, in the early period of this pandemic it was strenuous to identify patients with covid- . a total of . % ( ) of hcp with covid- were asymptomatic. in the early stage of the covid era, asymptomatic patients could be one reason for the rapid spread of infection worldwide [ ] . the transmission potential of asymptomatic carriers of sars-cov- was the same as the viral load detected in asymptomatic patients and was similar to that detected in symptomatic patients [ ] . these asymptomatic hcp might become a risk factor for patients, colleagues, and the community. therefore, early identification of asymptomatic carriers among hcp is of paramount importance and asymptomatic carriers should be isolated from family and colleagues to avoid cross-infection. the prevalence and clinical manifestations of covid- among hcp in two hospitals in the netherlands were evaluated in the early phase of the pandemic [ ] . in this study, hcp were also infected with sars-cov- in the community, in addition to nosocomial acquisition of sars-cov- . out of , hcp employed, , ( %) reported fever or respiratory symptoms and were tested in this cross-sectional study. among them hcp were infected with sars-cov- ( . %), representing % of all hcp employed. most patients were female ( . %) and the median age was years (range, - years). among them % were nurses and % were physicians. others with direct patient contact were % and without direct patient contact were %. most hcp experienced mild disease. guan et al. [ ] analyzed the data on , patients with laboratory-confirmed novel coronavirus ( -ncov) acute respiratory disease (ard) from hospitals in provinces/provincial municipalities through january th, and revealed . % were hcp. wu et al. along with cardiac manifestations, one of the common extra-pulmonary manifestations of covid- is diarrhea. studies have shown that sars-cov- infects the gastro-intestinal (gi) tract via its viral receptor angiotensin converting enzyme (ace ), which is expressed on enterocytes of the ileum and colon [ ] . a meta-analysis of studies involving , covid- patients from six countries revealed gi symptoms in . % of the patients with anorexia ( . %), diarrhea ( . %), nausea/vomiting ( . %), and abdominal pain/discomfort ( . %) [ ] . in the stool specimen of the first covid- patient in the united states ribonucleic acid (rna) of sars-cov- was detected, raising the concern for fecal-oral transmission of the virus [ ] . in our study . % ( ) of patients had diarrhea. the incidence of diarrhea among hcp in other studies is %- . % [ , ] . anosmia, a manifestation of olfactory dysfunction (od), is a prominent sign of sars-cov- infection. sudden onset of anosmia may be the only presenting symptom of patients with covid- [ , ] . a mild symptom such as dry cough may be present before the onset of anosmia [ ] . a retrospective study that included confirmed covid- patients and revealed % ( ) of patients presented with anosmia. anosmia generally developed . days after the onset of the infection and % of patients recovered within four weeks [ ] . ace is a functional receptor for sars-cov- , and its expression and distribution in the nervous system suggest that sars-cov- can cause neurological manifestations through direct or indirect pathways [ ] . goblet cells and ciliated cells in the nasal mucosa may be the initial site of sars-cov- infection, indicating primary sars-cov- transmission is through infectious droplets [ ] . multiple evidence indicates that the nasal cavity is a vital area susceptible to sars-cov- infection [ ] . higher viral loads in the patient's nasal cavity than in the pharynx of both symptomatic and asymptomatic individuals hint at the nasal cavity as the first gateway for the initial infection [ ] . anosmia was present in about one-third ( . %) of our study population. in our study . % of the infected hcp had mild disease. this is almost the same as other studies [ , ] . we also need to highlight that in our study most affected hcp were young adults (mean age only years) as in other studies [ ] . we postulate that the immunity of these young subjects was strong. our hcp were identified with covid- infection very early compared to non-hcp. possibly the viral load could have been low in these subjects. however, we could not measure the viral load for our study population. the time between symptom onset and covid test was shorter. the mean duration of onset of symptoms to test was . ± . days. treatment was initiated as early as possible. the above indicates that early diagnosis and treatment are essential for a better outcome of patients with covid- . most of the hcp with infection were treated outside the hospital or in institutional isolation ( . %). this might indicate that treating patients with mild symptoms outside a hospital setting can be a feasible method, particularly in the pandemic covid era when there is a serious crisis of hospital beds. on april the latest estimate of medical doctor deaths reached in italy, which is . % of total hcp deaths; followed by nurses at . % ( ), nurse aides at . % ( ) , and dentists at . % ( ) [ ] . factors contributing to the elevated number of fatalities among hcp in italy may be i) the sheer intensity of the covid- outbreak; ii) the recruitment of elderly retired doctors and iii) shortages of personal protective equipment (ppe), particularly in non-hospital care [ ] . mortality per institute will definitely be low. as we mentioned previously, one hcp from our hospital died. the mortality rate among hcp was . %, which is comparable with other studies [ ] at . %. payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. esc guidance for the diagnosis and management of cv disease during the covid- pandemic management of acute myocardial infarction during the covid- pandemic: a consensus statement from the society for cardiovascular angiography and interventions (scai) covid- ) infection among health care workers and implications for prevention measures in a tertiary hospital in wuhan, china prevalence and clinical presentation of health care workers with symptoms of coronavirus disease in dutch hospitals during an early phase of the pandemic clinical characteristics of coronavirus disease in china characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention covid- integrated surveillance: key national data clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china. jama. early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia sars-cov- viral load in upper respiratory specimens of infected patients gastrointestinal and hepatic manifestations of covid- : a comprehensive review gastrointestinal manifestations of sars-cov- infection and virus load in fecal samples from the hong kong cohort and systematic review and meta-analysis first case of novel coronavirus in the united states anosmia as a prominent symptom of covid- infection isolated sudden onset anosmia in covid- infection. a novel syndrome sudden and complete olfactory loss function as a possible symptom of covid- features of anosmia in covid- neurologic manifestations of hospitalized patients with coronavirus disease sars-cov- entry factors are highly expressed in nasal epithelial cells together with innate immune genes covid- and anosmia: a review based on up-to-date knowledge registry of doctor deaths during covid- epidemic deaths from covid- in healthcare workers in italy-what can we learn? most of the hcp presented with mild symptoms. as they frequently have contact with covid- patients and also have asymptomatic cases, periodic testing for covid- among hcp is recommended to prevent further spread. hcp with mild covid- symptoms may be treated in home or institutional isolation. as they are a vulnerable group for infection, providing adequate protection to hcp is absolutely mandatory to safeguard them from this pandemic. the infection of hcp may have a major negative impact on the capacity to treat patients, on the morale of professionals, and on public confidence during a pandemic, so protection of hcp is of paramount importance. adequate protection is recommended to all hcp to fight against the highly contagious coronavirus. key: cord- -gdplbrsf authors: arget, michael; kosar, justin; suen, brandon; peermohamed, shaqil title: successful treatment of legionnaires’ disease with tigecycline in an immunocompromised man with a legion of antibiotic allergies date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: gdplbrsf legionella species are gram-negative bacilli that are relatively rare causes of community-acquired pneumonia but can be associated with significant morbidity and mortality if unrecognized or improperly treated. limited data exist regarding the use of tigecycline, a third generation glycylcycline, in the treatment of legionnaires' disease. we present an immunocompromised patient with legionnaires' disease and allergies to both fluoroquinolones and macrolides, which are first-line treatment options for legionnaires' disease. he was successfully treated using tigecycline, a third generation glycylcycline, indicating that tigecycline may serve as a safe and effective alternative therapeuticl option for treatment of legionnaires’ disease. legionnaires' disease is a relatively rare cause of community-acquired pneumonia caused by legionella species; however, %- % of patients who are hospitalized with legionnaires' disease require invasive mechanical ventilation and average mortality rates for sporadic disease range from % to % [ ] . legionnaires' disease is caused by inhalation of legionella species, which are intracellular, gram-negative bacilli ubiquitously found in the environment [ ] [ ] . host risk factors for legionnaires' disease include male gender, age older than years, cigarette smoking, diabetes, end-stage renal failure, organ transplantation and immunosuppression, such as glucocorticoids or anti-rejection drugs following organ transplantation [ ] . travel is an important and underappreciated risk factor associated with legionellosis in a community setting [ ] . treatment options for legionnaires' disease include macrolides, fluoroquinolones, or tetracycline; however, preferred therapies for immunocompromised patients with legionnaires' disease include levofloxacin and azithromycin [ ] [ ] [ ] . we describe an immunocompromised and severely ill patient with legionnaires' disease and who also has allergies to both fluoroquinolones and macrolides; he was successfully treated using tigecycline, a third generation glycylcycline, indicating that tigecycline may serve as a safe and effective alternative therapeutic option for treatment of legionnaires' disease in select cases. a -year-old caucasian man presented to the emergency department in autumn with one week of dyspnea, productive cough, myalgia, and fever. he denied any chest pain or hemoptysis. his past medical history was significant for hypertension, diabetes mellitus, chronic kidney disease, and non-hodgkin's lymphoma with receipt of an allogeneic stem cell transplant years prior. given prior complications due to graft versus host disease, he was receiving prednisone at a maintenance dose of mg daily for several years. he had multiple documented allergies to penicillin, sulfa drugs, macrolides and fluoroquinolones, with reported reactions including rash, hives, and anaphylaxis. approximately one week prior to the onset of symptoms, he was traveling in the midwest united states with his partner and staying in various hotels. upon arrival to the hospital, he was noted to have a heart rate of beats per minute, a blood pressure of / mmhg, a respiratory rate of breaths per minute with an oxygen saturation of % requiring eight liters of supplementary oxygen, and an oral temperature of . °c ( . °f). he was in acute respiratory distress and had evident decreased breath sounds and crackles bilaterally. he was noted to have normal heart sounds without any murmurs, rubs, or gallops. he did not have any rash on examination. two sets of blood cultures were collected and sputum samples were sent for culture as well as stains and polymerase chain reaction (pcr) testing for pneumocystis jirovecii (p. jirovecii). a nasopharyngeal sample was collected for respiratory virus pcr testing for influenza a and b, respiratory syncytial virus a and b, coronavirus, parainfluenza virus, rhinovirus, enterovirus, adenovirus, bocavirus, and metapneumovirus. in addition, a serum cytomegalovirus (cmv) pcr and legionella urine antigen were sent. he was empirically started on meropenem, vancomycin, oseltamivir, and intravenous pentamidine. despite initiation of broad spectrum antimicrobials, he continued to deteriorate with increasing oxygen demands, persistent fever, hemodynamic instability, and worsening radiographic infiltrates ( figure ). showing worsening bilateral pulmonary opacification (arrows). sputum and blood cultures were negative for any bacterial growth; sputum stains and pcr were negative for p. jirovecii. his serum cmv pcr was negative. his nasopharyngeal swab for respiratory virus testing was negative for influenza a and b, respiratory syncytial virus a and b, coronavirus, parainfluenza virus, rhinovirus, enterovirus, adenovirus, bocavirus, and metapneumovirus; however, his legionella urine antigen was positive. according to his pharmacy records, he had previously received and tolerated a five-day course of moxifloxacin approximately one year prior to this hospital admission. given his diagnosis of legionnaires' disease, intravenous moxifloxacin therapy was initiated. however, shortly following receipt of his first dose of moxifloxacin, he developed an allergic reaction with a generalized, erythematous, maculopapular rash and angioedema, necessitating administration of epinephrine. given his documented allergies to both fluoroquinolones and macrolides, hemodynamic instability, and concern for poor gastrointestinal absorption of oral antimicrobials, he was subsequently treated with intravenous tigecycline with an initial, loading dose of mg, followed by mg twice daily for a total of days of therapy. intravenous doxycycline is not readily available in our institution. his oxygen requirements decreased and fever resolved following hours of treatment with tigecycline. all other antimicrobials were discontinued once the diagnosis of legionnaires' disease was made. there was no recurrence of infection after three months of follow-up; his repeat chest radiograph showed resolution of his bilateral air space opacities. later in discussion with the north dakota department of health and centers for disease control and prevention, it was determined that there was an ongoing outbreak of legionnaires' disease associated with five cases over a -month period; all cases including our patient had stayed at the same hotel. subsequent environmental testing of the hotel was negative, but this may have been impacted by a recent deep clean of the hotel's ventilation system. legionnaires' disease and its causative pathogen were first recognized in , following a common-source outbreak of severe pneumonia involving people at an american legion convention in philadelphia, pennsylvania in [ ] . outbreaks and clusters of cases of legionnaires' disease have been associated with contaminated cooling towers, whirlpools, hospital decorative water fountains, hot spring spas, and water births [ ] [ ] . legionnaires' disease can be associated with a prodromal illness with symptoms including fever, headache, myalgia, and anorexia; however, the clinical presentation of legionnaires' disease is often nonspecific and difficult to distinguish from other causes of communityacquired pneumonia [ ] [ ] . blood and sputum cultures are relatively insensitive in diagnosing legionnaires' disease; in contrast, urine antigen testing has a sensitivity of %- % and specificity greater than % [ ] . urine antigen testing for legionella only detects legionella pneumophila serogroup (lp ) and is most sensitive for the detection of the pontiac subtype of lp , which causes the majority of cases of community-acquired legionnaires' disease [ ] . legionella urine antigen testing will often be positive on the first day of illness and remain positive for several weeks [ ] . molecular testing of lower respiratory tract specimens can also be used to identify both legionella pneumophila and legionella species by pcr [ ] . preferred therapies for immunocompromised patients with legionnaires' disease include levofloxacin and azithromycin [ ] [ ] [ ] . tigecycline is a third generation, intravenous glycylcycline and minocycline derivative that inhibits bacterial protein synthesis by binding to bacterial s ribosomal subunits [ ] . prior in vitro and animal model studies have shown that tigecycline achieves high intracellular concentrations [ ] . however, demonstrated clinical effectiveness of tigecycline in the treatment of community-acquired pneumonia in humans with legionnaires' disease remains limited. two prior case reports describe successful use of tigecycline in the treatment of immunocompromised patients with legionellosis; however, fluoroquinolones were used as initial therapy in both of these cases and tigecycline was later added to their antimicrobial regimen [ ] [ ] . a recently published case series describes eight patients with legionnaires' disease who were switched to tigecycline, often due to worsening sepsis and/or respiratory status, following initial exposure to macrolide and/or fluoroquinolone therapy (median of three days) [ ] . all but one of these eight patients received combination therapy with tigecycline plus either levofloxacin or azithromycin as part of their treatment regimen once tigecycline was added. furthermore, the one patient in this case series who received days of tigecycline monotherapy had received eight days of azithromycin prior to switching therapy. thus, it is difficult to ascertain whether clinical improvement in these cases was due to the addition of tigecycline or post-antibiotic effect and delayed response from fluoroquinolone/macrolide therapy. integrated results from two randomized controlled trials showed comparable cure rates between tigecycline and levofloxacin in the treatment of hospitalized patients with community-acquired pneumonia, of which a small proportion were diagnosed with legionnaires' disease in each treatment arm [ ] . while the integrated results of these two randomized controlled trials support the early use of tigecycline as empiric treatment of community-acquired pneumonia, one of these trials permitted switching to oral levofloxacin following at least three days of intravenous therapy if evidence of clinical improvement. current evidence, albeit limited, suggests that tigecycline may be added as combination therapy in severe cases of legionnaires' disease. this case, however, demonstrates that tigecycline can be effective as a second-line treatment option for legionnaires' disease in the setting of allergies to traditional mainstays of therapy. in , the food and drug administration (fda) approved a new boxed warning about the higher risk of death among patients receiving tigecycline compared with other antibiotics, particularly apparent for hospital-acquired pneumonia and ventilator-associated pneumonia [ ] . while both the fda and health canada have approved tigecycline for treatment of community-acquired bacterial pneumonia, complicated skin and soft tissue infections, and complicated intra-abdominal infections, its use should be reserved for situations when alternative treatments are not suitable [ ] [ ] . legionnaires' disease is a rare cause of community-acquired pneumonia but can be associated with significant morbidity and mortality, especially amongst immunocompromised individuals. although the evidence regarding the use of tigecycline in treating legionnaires' disease is limited, this case report provides evidence supporting the use of tigecycline as a second-line therapeutic option in select cases where fluoroquinolone or macrolide therapy may be contraindicated. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. legionnaires' disease and pontiac fever . mandell, douglas, and bennett's principles and practice of infectious diseases legionella and legionnaires' disease: years of investigation treatment strategies for legionella infection principles and practice of infectious diseases activities of tigecycline (gar- ) against legionella pneumophila in vitro and in guinea pigs with legionella pneumophila pneumonia a case of legionellesis pneumonia verified by isolation of legionella pneumophila serogroup from bronchoalveolar lavage fluid treated with levofloxacine and tigecycline disseminated legionella pneumophila infection in an immunocompromised patient with tigecycline tigecycline as a second-line agent for legionnaires' disease in severely ill patients. open forum infect dis integrated results of phase studies comparing tigecycline and levofloxacin in community-acquired pneumonia the role of tigecycline in the treatment of infections in light of the new black box warning epidemiologist with the north dakota department of health in providing details pertaining to this outbreak of legionellosis. key: cord- -ipnt g i authors: khan, adeel a; ata, fateen; munir, waqar; yousaf, zohaib title: fluid replacement versus fluid restriction in covid- associated hyponatremia date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ipnt g i hyponatremia is one of the most frequently observed electrolyte abnormalities in coronavirus disease (covid- ). literature describes syndrome of inappropriate anti diuretic hormone (siadh) as the mechanism of hyponatremia in covid- requiring fluid restriction for management. however, it is important to rule out other etiologies of hyponatremia in such cases keeping in mind the effect of an alternate etiology on patient management and outcome. we present a case of hypovolemic hyponatremia in a patient with covid- , which unlike siadh, required fluid replacement early in the disease course for its correction. a -year-old filipino gentleman presented with a three-week history of diarrhea and symptomatic hyponatremia. there was no history of fever or respiratory symptoms. physical examination revealed a dehydrated and confused middle-aged gentleman. labs revealed lymphopenia, thrombocytopenia, and severe hyponatremia ( mmol/l). blood cultures and stool workup were negative. severe acute respiratory syndrome coronavirus (sars-cov- ) nasopharyngeal swab was positive. hyponatremia workup excluded siadh. the patient had hypovolemic hyponatremia due to gastrointestinal (gi) losses and was managed with saline infusion for correction of hyponatremia with improvement in his clinical status. hyponatremia in covid- is not only secondary to siadh but can also be due to other etiologies. hypovolemic hyponatremia should be distinguished from siadh as these conditions employ different management strategies, and early diagnosis and management of hypovolemic hyponatremia affects morbidity and mortality. hyponatremia has been reported in patients with lower respiratory tract infections and can be hypervolemic, euvolemic, or hypovolemic, with different underlying pathophysiological mechanisms [ ] . the severe acute respiratory syndrome coronavirus (sars-cov- ) infection has been recently reported to manifest as hyponatremia secondary to syndrome of inappropriate anti diuretic hormone (siadh ) [ ] [ ] [ ] [ ] [ ] . however, hyponatremia can be due to other etiologies as well. with the prevalence of gastrointestinal (gi) symptoms in coronavirus disease (covid- ), there is a possibility of hypovolemic hyponatremia secondary to gi loss [ ] . a timely clinical judgment based on etiology guides the management strategy. a -year-old filipino gentleman, known hypertensive, presented with a one-day history of confusion, fatigue, and two episodes of vomiting. this presentation was accompanied by generalized abdominal pain and nonbloody diarrhea of three weeks' duration. there was no history of fever or respiratory symptoms. vital signs were within normal limits. physical examination revealed a dehydrated middle-aged gentleman, inconsistently oriented to time, place, and person, with no focal neurological deficit. the rest of the physical examination was unremarkable. initial labs revealed lymphopenia, thrombocytopenia, and severe hyponatremia ( mmol/l). the patient was managed in the medical icu, where he received hypertonic saline ml thrice, followed by normal saline infusion of l, with a close serum sodium monitoring. the initial working diagnosis was of gastroenteritis due to an infectious etiology. blood and stool workup did not detect any common bacterial, viral, or parasitic pathogen. the sars-cov- nasopharyngeal swab was sent for polymerase chain reaction (pcr), which came back positive. apart from fluid replacement, the patient was managed conservatively. hyponatremia workup excluded siadh and was secondary to gi loss ( table ) . timely determination of the etiology of hyponatremia led to successful but gradual improvement in the symptoms and sodium level. the patient improved and was discharged in a stable condition. covid- is caused by sars-cov- . the mode of transmission is person to person, primarily via respiratory droplets. the most common symptoms are respiratory, but gi symptoms have also been reported [ ] . hyponatremia is associated with covid- [ ] [ ] . yousaf et al. described the mechanism of hyponatremia in covid- secondary to siadh as being multifactorial, including increased interleukin- (il- ) levels stimulating antidiuretic hormone (adh) release [ ] . in the case series, all three patients recovered with fluid restriction. however, it is essential to consider other possible etiologies as a cause of hyponatremia in covid- . measuring the osmolality of serum and urine is essential in the management of hyponatremia. a normal or high serum osmolality would indicate pseudohyponatremia. once a low serum osmolality affirms the diagnosis of true hyponatremia, urine osmolality is needed to distinguish between siadh and other causes. sodium excretion in urine is a marker of the volume status. however, during initial decision making, clinical judgement of volume status is paramount to prevent any delay in treatment. volume status would be the deciding factor between fluid conservative and fluid replacement strategy. erroneous treatment leads to increased morbidity, intensive care admissions, and increased duration of stay [ ] [ ] . also, inappropriate fluid resuscitation is associated with increased pulmonary complications in covid- [ , [ ] [ ] . our patient was hypovolemic based on a suggestive history and clinical examination. hyponatremia workup was sent and fluid replacement was started afterwards awaiting results. the workup showed he was appropriately treated as hypovolemic hyponatremia with iv fluid replacement. hypovolemic hyponatremia has a higher mortality rate than hyponatremia associated with siadh [ ] . therefore, caution should be exercised before attributing every hyponatremia in covid- to siadh. an early clinical judgement should consider the volume status of the covid- patients with hyponatremia to decide between fluid restriction and isotonic fluid replacement. hyponatremia in covid- is not only secondary to siadh but can also be due to other etiologies. it is critical to establish the cause of hyponatremia early in the disease course to guide initial management. hypovolemic hyponatremia should be distinguished from siadh as these conditions employ different management strategies, and the management affects morbidity and mortality. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. inflammation and hyponatremia: an underrecognized condition? clinical features, laboratory characteristics, and outcomes of patients hospitalized with coronavirus disease (covid- ): early report from the united states. diagnosis (berl). il- , and sars-cov- (covid- ) infection: may all fit together endocrinology in the time of covid- : management of hyponatraemia and diabetes insipidus covid- associated siadh; a clue in the times of pandemic! covid- presenting with diarrhoea and hyponatraemia clinical characteristics and differential clinical diagnosis of novel coronavirus disease (covid- ) electrolyte imbalances in patients with severe coronavirus disease (covid- ) moderate hyponatremia is associated with increased risk of mortality: evidence from a meta-analysis effect of early correction of hyponatremia on neurological outcome in traumatic brain injury patients diagnosis and treatment of hyponatremia: compilation of the guidelines critical care brigham and women's hospital covid- clinical guidelines mortality rates are lower in siad, than in hypervolaemic or hypovolaemic hyponatraemia: results of a prospective observational study key: cord- -kxfj ziu authors: dimaria, christina n; lee, byeori; fischer, robert; eiger, glenn title: cognitive bias in the covid- pandemic date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: kxfj ziu cognitive bias plays a significant role in medical errors. in the pandemic of corona virus disease- (covid- ), recognizing and creating strategies to minimize these biases is crucial to optimize medical care for our patients. in this article we present a case of a -year-old male with decreased appetite, subjective fears, dry cough, and confusion. the report illustrates the concept of cognitive bias during a pandemic and discusses strategies to ameliorate them. cognitive bias includes a variety of unconscious influences, heuristics, and behaviors which aid our decision making [ ] . these shortcuts can be helpful in clinical decision making, but they can also lead to medical errors. a study by graber et al. found that % of diagnostic errors in internal medicine practice are related to cognitive factors [ ] . recognizing and creating strategies to minimize these biases is crucial to optimize medical care for our patients. we describe a case of a -year-old male with decreased appetite, subjective fears, dry cough, and confusion presenting during the corona virus disease- (covid- ) pandemic. to our knowledge there are no case reports or studies focusing on the role of cognitive biases during a pandemic or strategies to overcome them. a -year-old male presented with decreased appetite, fatigue, and confusion for four days. his wife reported worsening disorientation and drowsiness for one day prompting her to bring him to the hospital. other symptoms included subjective fever and dry cough. he lived at home with his wife and grandchildren and was independent in activities of daily living at baseline. he had hypertension and hyperlipidemia. the patient had no recent travel or sick contacts. his medications included spironolactone, hydrochlorothiazide, losartan, and nifedipine. he had no smoking, alcohol, or drug use history. vital signs on admission included blood pressure / mmhg, oxygen saturation of % on room air, heart rate bpm, and temperature degrees celsius. he had no neck stiffness, no focal neurological deficits, and was alert and oriented to his name. the rest of the physical findings were unremarkable. chest x-ray showed no acute disease. noncontrast cranial ct was negative. serum sodium was meq/l, potassium . meq/l, creatinine . mg/dl, wbc , per microliter with a neutrophil predominance of %. a nasal swab was negative for influenza and respiratory syncytial virus (rsv) by polymerase chain reaction (pcr). a nasal swab for covid- pcr was obtained and the patient was admitted to the covid general medicine floor for "covid rule out." while awaiting the covid test result, the patient was followed clinically. minimal additional testing was performed. his mental status continued to wax and wane for the next six days, with delirium worsening when his fever was high. no specialty services were consulted. eventually, covid- testing returned positive and he was treated with symptomatic management. this case brings into question how we approach medical decision making during the covid- pandemic. although our patient was eventually diagnosed with covid- , there were alternative diagnoses that should have been considered including but not limited to a central nervous system (cns) infection or vasculitis, seizures, hypercapnia, hiv, or uncontrolled hyperthyroidism. the primary bias illustrated by our case is premature closure. premature closure is a cognitive error in which the physician fails to consider reasonable alternatives after an initial diagnosis is suspected [ ] . given the increasing prevalence of covid- , it is hard not to focus on this diagnosis when evaluating a patient. after the patient was admitted to the medicine floor, minimal further testing was done as it was thought "prematurely" that the patient had covid- . another cognitive bias demonstrated by this case is availability bias --the mental shortcut that relies on likelihood or frequency of a disease to construct a differential diagnosis [ ] . currently there are , , confirmed cases of covid- in the united states [ ] . the likelihood of our patient having covid- is high, yet other diseases have not vanished, and other diagnoses are still possible. on review of the case, the presenting symptoms were vague, yet we focused on dry cough and fever to lead us to a diagnosis of covid- . other symptoms and other physical findings were overlooked. this is an example of anchoring bias. the final bias observed in our case is framing bias, the influence of how information is presented on medical decision making [ ] . this bias occurs at many levels; admission from the ed, medical rounds presentations, handoffs, and signouts. in this case, the general medicine team was called for an admission for "covid rule out." and this was also the term used for handoffs and signouts. we believe this wording may oversimplify the patient's disease state and focus only on covid- . yes, in the end, the patient was found to have covid- , but what if after six days the test came back negative? would we have then recognized the biases that affected our medical decision making? could we have provided better and safer medical care? recognition and strategies to prevent cognitive biases, especially during a pandemic, are crucial to optimize medical care for our patients. it would facilitate more efficient diagnosis of non-covid- diseases which would allow for earlier discharges and free up hospital beds. for this reason, we suggest some guiding principles to prevent cognitive bias errors during the covid- pandemic. three alternative diagnoses should be routinely sought for patients with suspected covid- infection. after making sure the patient is screened appropriately for infection control and placed on the proper isolation, it is important to think about common pre-covid- diseases. in addition, covid- positivity does not rule out other diseases. our patients are complicated and can have multiple diagnoses. common things will always be common, and we are learning that this is still the case during a pandemic. after brainstorming differential diagnoses, take a time-out as a team. ask what else besides covid- can this be? as a team, review the patient's initial symptoms, vital signs, labs and synthesize this with new data or findings found while the patient has been on the floor. during this time out consider how likely covid- is for the patient and if potentially a positive test could be a false positive. we, physicians, are a team in this fight against covid- . resources on many levels are stretched thin. for this reason, we think it would be beneficial to involve specialists. even if they are working via telemedicine, discussing the case with experienced specialists may provide further insight. although cognitive biases are known contributors to cognitive errors, we still are not sure of all the ways they play into medical decision making during this covid- pandemic. by dissecting this case we feel we were able to illustrate the concept of cognitive bias, how it influences our medical care, and suggest a few strategies to overcome them. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. a cognitive forcing tool to mitigate cognitive bias-a randomised control trial diagnostic error in internal medicine the pitfalls of premature closure: clinical decision-making in a case of aortic dissection judgment under uncertainty: heuristics and biases covid- map -johns hopkins coronavirus resource center influence of framing on medical decision making key: cord- -fktc q authors: tahir, shumaila; tahir, syeda anjala; bin arif, taha; majid, bushra; majid, zainab; malik, farheen; ahmed, ashfaque; memon, arslan; ahmed, jawad title: epidemiological and clinical features of sars-cov- : a retrospective study from east karachi, pakistan date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: fktc q background severe acute respiratory syndrome coronavirus (sars-cov- ) has spread to almost every country on the globe, and each country is reporting the symptomatic presentation of their patients to give better insight into the various clinical presentations of sars-cov- . however, the epidemiological literature from pakistan is scanty. methods we retrospectively analyzed data from patients who were residents of east karachi and tested positive for sars-cov- between february to april , . patients' demographics, symptoms, travel and contact history, and outcomes were recorded. all statistical analysis was performed using the statistical package for the social sciences (spss) version (ibm spss statistics for windows, ibm corp, armonk, ny). results most of the patients were male ( . %), the majority ( . %) belonging to the - to -year age group. most of the patients ( . %) were residents of gulshan iqbal. a total of . % of the patients were admitted to the hospital, and . % of patients expired. the three most common presenting symptoms were fever ( . %), cough ( . %), and flu ( . %). the majority of patients ( . %) gave a history of contact with sars-cov- patients. conclusion the number of sars-cov- cases is rapidly increasing in karachi, pakistan. there is a need to educate the population about the most common sign and symptoms of the virus so that individuals can identify these symptoms and get themselves tested. the concerned authorities should devise an adequate and effective plan to flatten the infectivity curve. in december , several locals in wuhan, china presented to the hospital with respiratory symptoms due to a novel pathogen. the pathogen was identified and named as severe acute respiratory syndrome coronavirus (sars-cov- ). sars-cov- is classified as a type of rna virus, a member of the coronavirus family, and belongs to the "beta" genus. other members of the same genus include sars-cov- and middle east respiratory syndrome coronavirus (mers-cov) [ ] [ ] [ ] . the possible origin of sars-cov- from bats could be elucidated by its similarity ( % identical) to two other sars-like covs derived from bats (bat-sl-covzc and bat-sl-covzxc ) [ , ] . since its origin, the virus has spread all over the world, affecting nearly every continent and triggering an international public health emergency in its wake. on march , the world health organization (who) declared coronavirus disease of (covid- ) a pandemic. according to the most recent who covid- situation reports (dated may , ) , a total of , , individuals have been infected, with , confirmed deaths [ ] . in the eastern mediterranean region, pakistan has the third-highest number of cases after iran ( , cases) and saudia arabia ( , cases). pakistan has , cases ( , in sindh, , in punjab, , in khyber pakhtunkhwa, , in baluchistan, in gilgit-baltistan and azad kashmir) with deaths as of may , [ ] . the rampant nature of sars-cov- is due to its high infectivity. the virus can be transmitted from human to human through physical contact, respiratory droplets produced by coughing, or sneezing [ ] . recently, vertical transmission through the mother to the newborn has also been postulated [ ] . sars-cov, mers-cov, and the recently identified sars-cov- all cause respiratory symptoms. the main clinical manifestations of sar-cov- range from mild asymptomatic disease to lifethreatening complications. initially, the patient presents with cough, fever, dyspnea, and fatigue. other less common complaints may include diarrhea, headache, and the production of sputum. the disease can progress to cause pneumonia, leukopenia, and lymphopenia [ ] . severe complications may occur, such as acute respiratory distress syndrome (ards), rnaaemia, acute cardiac injury (aci), secondary infection, heart failure (hf), and multiple organ failure requiring intensive care unit (icu) admissions [ , ] . since its spread in pakistan, the government has taken drastic measures for control and prevention of the further spread of covid- , including quarantine of suspected individuals carrying the disease and improvement in diagnostic and treatment procedures. nonetheless, the already scarce resources of the healthcare system of pakistan have been stretched thin. the primary aim of this retrospective observational study was to report the epidemiological features and statistics of individuals infected with covid- from february to april from east karachi, pakistan, and contribute towards an accurate collection of figures from the country. we also aimed to study the age groups, modes of transmission, and durations and details of symptoms, among other variables, to understand this wide-spreading disease better and work effectively towards prevention and suitable management plans. we carried out a retrospective cross-sectional analysis of the infected population of east karachi (consisting of two towns, gulshan iqbal and jamshed). all records that were found to be positive for the covid- virus were analyzed, including cases that presented to the hospitals with screening facilities along with cases traced by the rapid response team of the district's covid- control room for the 'at home' suspects, cases and contacts. the data was collected from the daily notifications given to the surveillance line list and updated by the district health office, control room, which included data from the first case, from february to april , . the individuals of east karachi were filtered via screening criteria for suspected cases, due to the high cost and lack of testing kits, which evaluated the epidemiological history and clinical manifestations. the first part of criteria comprised the following four points: ( ) travel history from a high-risk area within days before the disease onset ( ) history of contact with individuals with sars-cov- (positive nat result) within days before the disease onset ( ) history of contact with individuals with fever or respiratory symptoms in the high-risk area within days before the disease onset ( ) disease clustering (two or more cases of fever and/or respiratory symptoms at home/school/office etc.). the clinical manifestations as part of the criteria are as mentioned: ( ) fever and/or respiratory symptom ( ) significant findings on ct imaging ( ) levels of white blood cell count normal or decreased. nasopharyngeal swabs were obtained from individuals with high suspicion for the covid- , which were tested using polymerase chain reaction (pcr) to confirm the diagnosis. the suspected or confirmed cases were clinically classified as asymptomatic, mild, moderate, severe, and critical, according to the national institute of health, pakistan guidelines and are defined below in table [ ]. asymptomatic nasopharyngeal rt-pcr positive for covid- without any symptoms mild presence of symptoms consistent with covid- such as fever, fatigue, cough (with or without sputum production), anorexia, malaise, muscle pain, sore throat, dyspnea, nasal congestion, or headache without any hemodynamic compromise, need for oxygen or chest x-ray findings moderate hypoxia (oxygen saturation ≤ %) or mild infiltrate on cxr persistent high-grade fever for over three days . signs of shock: delayed capillary refill; cold, clammy peripheries; mottled skin; systolic bp less than or less than mmhg of baseline in hypertensive; urine output < . ml/kg/hr rt-pcr (reverse transcription-polymerase chain reaction); cxr (chest x-ray); curb- score (confusion, uremia, respiratory rate, bp, age ≥ years); qsofa (quick sequential organ failure assessment) score; pao (partial pressure of arterial oxygen); fio (percentage of inspired oxygen); paco (partial pressure of carbon dioxide in arterial blood); jvp (jugular venous pressure); bp (blood pressure) data in the above table adapted from [ ]. due to the lack of resources, including the availability of health workers, personal protective equipment (ppe), and adequate isolation spaces in hospitals, it was proposed to manage asymptomatic and mild cases via home isolation. in contrast, moderate, severe, and critical cases were admitted to a hospital facility. a patient was labeled as recovered upon testing negative for covid- on two separate samples after contracting the disease. patients who tested positive for the infection and succumbed to the disease were classified as "expired", contributing to the mortality rate. the criteria mentioned above and guidelines were evolved and developed over time, the main framework being consistent with all cases. all statistical analysis was performed using the statistical package for the social sciences (spss) version (ibm spss statistics for windows, ibm corp, armonk, ny). for the assessment of qualitative variables, frequencies and percentages were used. we analyzed the data of covid- patients in our study. the majority of the study participants were male (n= , . %). additionally, the majority of participants were also young ( to years [n= , . %]; to years [n= , . %]). all participants came from two towns in east karachi, with more than half belonging to gulshan iqbal (n= , . %), as represented in table . options data collection was started from february , , and one case was reported that day. during the month of march, cases were reported, while cases were reported till april , , as is illustrated by figure . the differing status of our study participants, all of whom were positive for covid- , were categorized into four groups. the groups included participants who had recovered, expired, sent into isolation at home, and admitted to the hospital, as shown in table . most of the patients presented with at least one symptom (n= , . %), whereas only . % (n= ) were asymptomatic. these symptoms varied and the most common that were experienced were fever (n= , . %), cough (n= , . %), flu (n= , . %), and body ache (n= , . %). the least common symptoms witnessed were nausea (n= , . %), headache (n= , . %), chest pain (n= , . %), decreased appetite (n= , . %), and lower respiratory tract infection (lrti) (n= , . %). the symptoms are listed below in table . frequency (%) the vast majority of the patients (n= , . %) had been exposed to the virus from a person who was covid- positive. others had a positive travel history or had attended a big religious congregation ( table ) . [ ] . with a rapid increase in the number of cases and a fragile economy, the country was put under a nationwide lockdown on april , . although pakistan was expecting , cases of covid- by april , the number remained less than half of the presumption [ ] . the government of pakistan has been taking necessary measures to control the outbreak and facilitate its people. many hospitals across the country are working to combat the deadly outbreak of covid- . early case detection, contact tracing, risk communication, social distancing, isolation and quarantine, and introduction of covid- relief funds to receive donations for the welfare of people are other significant measures taken by the country [ ] . our study primarily highlights the scenario of covid- cases in the east district of karachi, pakistan. on analyzing the demographic profile of patients, males were found to be affected twice as much ( . %) as females ( . %). this is significantly higher than a study from wuhan, china, which indicated that % of patients with covid- were males [ ] . similarly, another study of patients from wuhan found that . % were males [ ] . gender is a significant risk factor of severity and mortality in patients with covid- . according to a retrospective study by jin et al., men tended to develop more severe disease. although men and women had similar susceptibility, men were more prone to dying and accounted for approximately . times that of women in the deceased patients [ ] . covid- can lead to hospitalization and even death in young and middle-aged adults. it has caused the most severe health issues for adults over the age of , with higher fatality over the age of . comorbidities like diabetes, hypertension, heart diseases, or other chronic illnesses can cause more intense manifestations and complications in the disease. besides, older adults are more susceptible to infection due to a gradual loss of resilience of the immune system. almost a quarter ( . %) of italy's population is over years where a significantly higher number of covid- cases and deaths were reported with case fatality rate (cfr) of . % in - years, . % in > years, and . % deaths occurring in adults aged years and greater [ ] . in contrast, approximately . % population of pakistan falls in - years age group. our study reported a higher incidence of infection in - years depicting that age structure is a significant risk factor for incidence and mortality rates of covid- . according to the who covid- situation report, a total of , confirmed cases and , deaths were reported across the globe till march , . these figures are approximately nine times greater than the statistics recorded on february , . by the end of march, pakistan had , confirmed cases with recoveries and deaths [ ] . about cases were reported in march from the eastern towns of karachi, as demonstrated by our study. the global cases increased dramatically to around , , confirmed cases by april , . pakistan crossed a critical mark of the outbreak in the country as the total number of cases surged to about , on april with an immediate increase in death rate ( deaths) secondary to covid- [ ] . however, our study recorded an approximately three-fold increase in the cases in east karachi with the death of individuals. out of cases, more than half ( %) were sent to home isolation, and % recovered while . % were admitted to the hospital for supportive care. the rising covid- cases pose a challenge to pakistan's crumbling healthcare system. fragile economy, lack of availability of personal protective equipment for healthcare providers, inadequate quarantine and testing facilities, and periodic ease in lockdown are the principal reasons for the drastic rise in cases [ ] . clinical presentations of covid- range from asymptomatic or mild symptoms to complicated illness and/or mortality. common symptoms include fever, cough, and shortness of breath, malaise, and respiratory distress. according to the centers for disease control and prevention (cdc), cough and shortness of breath with at least two accessory symptoms (fever, chills, sore throat, muscle pain, headache, and new loss of taste or smell) may indicate covid- . it can also present as gastrointestinal complaints like nausea, vomiting, anorexia, and diarrhea [ ] . symptoms may develop two days to two weeks following exposure to the virus. a pooled analysis of covid- cases from january to february , , reported a mean incubation of . days. out of confirmed cases, . % of individuals developed symptoms within . days [ ] . the majority of patients in our study presented with a single complaint. fever ( . %) was the predominant symptom, followed by cough ( . %), flu ( . %), and body ache ( . %). these findings coincide with an initial report by huang et al., which specified fever ( %) as the most common clinical finding, followed by cough ( %) and myalgia ( %) [ ] . asymptomatic infections have been reported, for example, by chan et al., but the exact incidence is unknown [ ] . our study found individuals with no symptoms of covid- . some unusual symptoms included abdominal pain, vomiting, arthralgia, drowsiness, diarrhea, headache, and anorexia. clinicians evaluating patients with fever and acute respiratory disease should obtain details regarding travel history or exposure to an individual who recently returned from a country experiencing active local transmission [ ] . furthermore, the cdc has proposed contact tracing as a part of a multipronged approach to fighting the covid- pandemic [ ] . patients with suspected covid- should be immediately reported to the healthcare provider and the local or state health department. candidates with fever, symptoms of lower respiratory illness, and a travel history to wuhan, china or other countries with uncontrolled covid- cases or who have been in contact with an individual suspected of covid- or with laboratory-confirmed covid- in the preceding days should be isolated and tested for the infection promptly [ ] . one of the preventive measures proposed by who for protection from the spread of covid- is the maintenance of an adequate distance of m ( feet) from others and avoiding crowded places [ ] . about . % of patients in our study contracted the disease from individuals with an existing infection, with a minority of patients reporting a history of travel to covid- endemic states or attending religious congregations. the easing of the lockdown across pakistan resulted in , new cases and new deaths in one day; experts say if social distancing and isolation are not practiced by the overwhelming majority of the population, pakistan would likely experience massive fatalities soon [ ] . our study has a few limitations. first, it includes all covid- cases from only one district (i.e., east karachi), pakistan. a survey with a large sample size from multiple towns of the city can reflect more accurate statistical figures regarding the epidemiological and clinical features of covid- . furthermore, the duration of the study was only two months. detailed analysis of the clinical features, laboratory findings, complications, and prognostic indicators is recommended to get a better insight into the infection and its associated entities, which can help the state to think of possible strategies to combat the pandemic. a previous study from karachi has depicted poor knowledge regarding the maintenance of adequate hygiene among healthcare providers [ ] . apart from maintaining social distancing, it is recommended to practice all necessary preventive measures like frequent cleansing of hands with running water or a sanitizer, covering coughs and sneezes with disposable tissues or clothing, and avoiding excessive touching of eyes and nose or unprotected contact with animals. sars-cov- is infecting the population of karachi rapidly, resulting in an exponential increase in the number of cases. the descriptive analysis of the epidemiological data in our study showed a large majority contracting the virus through contact with an already infected person and highlights the significance of following the guidelines of maintaining social distancing. the public, government, and health authorities of pakistan urgently need to realize their responsibilities and devise efficient plans to curb further spread of the disease, keeping in mind the limited resources and grave health outcomes. human subjects: consent was obtained by all participants in this study. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. a novel coronavirus from patients with pneumonia in china genomic characterisation and epidemiology of novel coronavirus: implications for virus origins and receptor binding cardiac manifestations of coronavirus disease (covid- ): a comprehensive review world health organization: novel coronavirus (covid- ) situation reports covid- health advisory platform by ministry of national health services regulations and coordination world health organization: modes of transmission of virus causing covid- : implications for ipc precaution recommendations -scientific brief possible vertical transmission of sars-cov- from an infected mother to her newborn clinical features of patients infected with novel coronavirus in wuhan, china. lancet. pm imran urges pakistanis to be steadfast in their faith amid covid- crisis covid- outbreak: current scenario of pakistan early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia clinical characteristics of patients infected with sars-cov- in wuhan gender differences in patients with covid- : focus on severity and mortality. front public health demographic science aids in understanding the spread and fatality rates of covid- centers for disease control and prevention: symptoms of coronavirus the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application a familial cluster of pneumonia associated with the novel coronavirus indicating person-to-person transmission: a study of a family cluster evaluating and testing persons for coronavirus disease (covid- ) case investigation and contact tracing: part of a multipronged approach to fight the covid- pandemic world health organization: coronavirus disease (covid- ) advice for the public pakistan eases nationwide lockdown even as coronavirus cases rise compliance and knowledge of healthcare workers regarding hand hygiene and use of disinfectants: a study based in karachi key: cord- -d z m l authors: chenna, avantika; konala, venu madhav; gayam, vijay; naramala, srikanth; adapa, sreedhar title: coronavirus disease (covid- ) in a renal transplant patient date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: d z m l coronavirus disease (covid- ) has resulted in significant morbidity and mortality worldwide. transplant patients are particularly at a higher risk of contracting covid- because of their immunosuppressed state, and they have the propensity to develop opportunistic infections. the pre-immunosuppressed state, along with other existing comorbidities, can influence the outcomes of covid- in transplant patients. we describe a case of a renal transplant patient who developed covid- . real-time nucleic acid testing (nat) should be done in deceased and living donors. the most common management strategy is the modification of immunosuppression along with current experimental strategies for covid- . the pandemic of coronavirus disease (covid- ) is a public health emergency caused by the novel coronavirus, which is also termed as severe acute respiratory syndrome coronavirus (sars-cov- ). transplant patients are particularly at a higher risk of contracting covid- because of their immunosuppressed state, and they have the propensity to develop opportunistic infections [ ] . the pre-immunosuppressed state, along with other existing comorbidities, can influence the outcomes of covid- in transplant patients. here, we describe a case of a renal transplant patient who developed covid- and, unfortunately, died from the infection despite all medical management. a -year-old african american male presented with fever, cough, and weakness for two weeks duration. the patient denied having any chest pain, shortness of breath, nausea, vomiting, or diarrhea. the patient denied any travel history, contact with any person tested positive for covid- , or attending any public gatherings. the patient was admitted to the hospital two weeks before the presentation for left lower extremity superficial femoral artery angioplasty and could have likely got exposed to covid- . past medical history included end-stage renal disease (esrd) secondary to diabetic nephropathy and underwent deceased donor kidney transplant in , hypertension, diabetes mellitus, peripheral vascular disease status post right above knee amputation (aka). the patient was taking tacrolimus mg twice a day, mycophenolate mofetil (mmf) mg twice a day, and prednisone mg daily for maintenance immunosuppression. other home medications included simvastatin mg daily, lisinopril mg po daily, insulin humalog sliding scale before meals, insulin levemir units daily, clopidogrel mg po daily, and gabapentin mg po daily. on presentation, the patient was febrile with . celsius, pulse rate beats per minute, blood pressure / mm hg, respiratory rate breaths per minute, and oxygen saturation % on room air. physical examination was significant for a patient in respiratory distress with decreased breath sounds on bibasilar lung fields. the rest of the physical examination was unremarkable. the labs were summarized in table . the patient's baseline creatinine was . gm/dl with sub-nephrotic range proteinuria on the labs done three months ago. reference the chest x-ray revealed cardiomegaly with bilateral lung infiltrates (figure ) . computed tomography (ct) of the chest without contrast revealed prominent multifocal pneumonia and multiple ground-glass airspace opacities throughout all lung fields ( figure ). the patient was started on treatment with hydroxychloroquine, azithromycin, and ceftriaxone for suspected covid- and pneumonia. electrocardiogram (ekg) was done every hours to monitor the qtc interval. all ekgs showed a normal qtc interval (figures - ) . the mmf, prednisone, and lisinopril were held, tacrolimus was continued at a home dose, and the patient was started on methylprednisolone mg every eight hours. tacrolimus was stopped within hours, as the patient continued febrile and hypotensive. the patient was started on norepinephrine for hypotension and required continued escalation of treatment with three pressors. the patient also developed intermittent episodes of acute kidney injury, which was managed with intravenous fluids and diuretics as needed but never needed dialysis. the respiratory status deteriorated over the hospital course, progressing to acute respiratory distress syndrome requiring intubation and ventilation with % fraction of inspired oxygen (fio ) and high positive end-expiratory pressure. unfortunately, the patient developed asystole and died despite resuscitative efforts days into hospital admission. covid- is a rapidly evolving disease with a high transmission rate and has changed our lives in an unprecedented way. the transplant patients are a special group that needs collaborative effort amid this global health crisis. the viral load and mortality were higher in transplant recipients infected with prior coronavirus outbreaks [ ] . the illness from covid- in renal transplant recipients ranged from mild to severe, and few patients presented with atypical symptoms [ , ] . there were no reported instances that covid- was spread through organ donation [ ] . the detection of sars-cov- in blood and organs ascertains that transmission through organ donation is a possibility [ ] . the transplant societies have issued guidance worldwide on screening the donors and recipients to decrease the spread [ ] . real-time nucleic acid testing (nat) should be done in deceased and living donors [ ] . taking universal precautions and appropriate personal protective equipment (ppe) should be used to decrease the risk of transmission during organ procurement [ ] . the transplant surgeries should be postponed if there is known exposure. the decision to proceed with transplant surgery should be individualized based on the risk and benefits of proceeding with transplantation and the introduction of immunosuppression. the transplant recipients and the care team members should follow the same precautions as the general public in the event of exposure or development of symptoms. management is challenging because there is no proven drug therapy and the experience is based on a few studies. the common practice is to modify immunosuppression by holding mycophenolate mofetil/azathioprine and adjusting the dose of calcineurin inhibitors (cnis), such as tacrolimus, in our patient [ ] . in a study by the university of washington with patients ( renal transplant patients), % have a reduction in immunosuppression antimetabolite, held in almost all patients [ ] . drug interactions should be paid close attention to as reported by bartiromo [ ] . higher-dose steroids were used, which can be associated with delayed viral clearance [ ] . transplant patients constitute a population more vulnerable to develop covid- because of their immunosuppressed state and higher risk for opportunistic infections. management includes the modification of immunosuppression with anti-metabolite held in most patients. prevention is the key, as there is no proven treatment or vaccine available. we advise caution while using high-dose steroids, as it can be associated with delayed viral clearance. novel coronavirus- (covid- ) in the immunocompromised transplant recipient: #flatteningthecurve covid- : a global transplant perspective on successfully navigating a pandemic case report of covid- in a kidney transplant recipient: does immunosuppression alter the clinical presentation? ebola virus disease: implications for solid organ transplantation university of washington covid- in solid organ transplantation case report series study group threatening drug-drug interaction in a kidney transplant patient with coronavirus disease (covid- ) prolonged shedding of human coronavirus in hematopoietic cell transplant recipients: risk factors and viral genome evolution human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -ij u v authors: amaratunga, eluwana a; corwin, douglas s; moran, lynn; snyder, richard title: bradycardia in patients with covid- : a calm before the storm? date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ij u v cardiac manifestations of coronavirus disease (covid- ), including arrhythmia, have been described in the literature. however, to our knowledge, association of covid- with bradycardia has not been reported. this case study describes sinus bradycardia as a potential manifestation of covid- . this is a retrospective case series of four patients with laboratory-confirmed severe acute respiratory syndrome coronavirus (sars-cov- ) infection, admitted to st. luke’s university health network icu between march and april . medical records of these patients were reviewed using the epic electronic health record system. demographic, clinical, laboratory, and treatment data were reviewed against periods of bradycardia in each patient. the patient group comprised two males and two females. two patients had pre-existing cardiovascular (cv) comorbidities but no history of arrythmias. heart rates ranged between and beats/min on admission. the lowest rates during bradycardia were between and beats/min. the onset of sinus bradycardia in patients , , and were day nine, , and five of illness, respectively. patient had three episodes of bradycardia, starting on day of illness. patients’ bradycardia episodes lasted one to days. during bradycardia, maximum body temperatures ranged between . and . degree fahrenheit. patients , , and required vasopressors to maintain mean arterial pressure > mmhg during episodes. all four patients were on propofol at some point during bradycardia with patients , , and also receiving dexmedetomidine. there was no consistent correlation of these medications with bradycardia. electrocardiogram (ecg) findings included sinus bradycardia. prolonged qtc interval observed in patient on admission improved during bradycardia. transient sinus bradycardia is a possible manifestation of covid- and is important for close cv surveillance. etiology can be multifactorial, but severe hypoxia, inflammatory damage of cardiac pacemaker cells, and exaggerated response to medications are possible triggers. high levels of pro-inflammatory cytokines may act directly on the sinoatrial (sa) node contributing to the development of bradycardia. this may be a warning sign of the onset of a serious cytokine storm. an increased awareness of possible exaggerated bradycardia response is important to consider with the use of empiric medications which have arrhythmogenic effects. in december , the first coronavirus disease patient was reported in wuhan, china. since then, the severe acute respiratory syndrome-coronavirus (sars-cov- ) has rapidly spread reaching pandemic status within a few months. while ongoing research efforts are providing a vast amount of information, there is much regarding this novel coronavirus that remains unknown. cardiac manifestations of covid- have been reported with a higher prevalence described in patients admitted to icus [ ] [ ] . he et al. reported two patients with covid- with different electrocardiographic (ecg) manifestations [ ] . the first patient was a previously healthy -year-old female who demonstrated a transient s q t finding on the day of tracheal intubation, followed by reversible nearly complete atrioventricular (av) block. a simultaneous echocardiogram performed demonstrated findings of elevated pulmonary artery pressure. the other patient reported was a -year-old male with a history of hypertension and type diabetes, who required veno-venous extracorporeal membrane oxygenation (vv-ecmo) for severe hypoxia, without significant improvement in his oxygenation. the ecg findings in this patient included st segment elevation accompanied by multifocal ventricular tachycardia, with an increase in levels of cardiac troponin i (ctni) [ ] . acute cardiac injury (elevation of ctni above th percentile upper reference limit) is the most commonly reported cardiac complication in covid- , affecting approximately %- % of all patients with covid- [ ] . other reported clinical manifestations include acute coronary events, acute left ventricular (lv) systolic dysfunction, acute congestive heart failure, and cardiac arrhythmias [ ] [ ] [ ] . a study involving patients infected with covid- in wuhan, china, demonstrated cardiogenic shock, arrhythmia, and acute cardiac injury to be among common complications; . %, . %, . % respectively [ ] . the incidence of arrhythmia was higher in patients admitted to the icu compared to those who were not [ ] . bradycardia is another cardiac manifestation of covid- that has not been previously reported in the medical literature. this clinical sign was noted in several patients receiving care in our icu. while there have been a few studies regarding the development of tachy-and bradyarrhythmias in patients with covid- , the specific nature of the dysrhythmias was not reported [ , ] . a recent publication stated that tachycardia might be a common arrhythmia in patients with covid- [ ] .to the best of our knowledge, and in review of medical literature, this is the first time that there has been an association with covid- and bradycardia. this is a retrospective case series involving four patients admitted to st. luke's university health network -anderson campus icu between march and april . all four patients were confirmed positive for covid- pneumonia with severe acute hypoxic respiratory failure requiring intubation and mechanical ventilation. a positive confirmation of covid- was determined by the detection of sars-cov- in polymerase chain reaction (pcr) of nasopharyngeal specimens. the epic electronic health record system was used to review medical records of each patients' hospital course. patient demographics, comorbidities, presenting day of illness since symptom onset, admission heart rate, duration of illness at intubation, duration of illness at onset of bradycardia, vital signs [blood pressure, mean arterial pressure (map), oxygen saturation, respiratory rate, temperature], laboratory studies (including ctni, ferritin, c-reactive protein, d-dimer, fibrinogen), as well as medications and dose adjustments were investigated and compared against episodes of bradycardia. the ecgs acquired on admission and during bradycardic episodes were reviewed to further characterize the bradycardia. electronic cardiac monitoring was reviewed as well. baseline characteristics of patients ( ) ( ) ( ) ( ) at hospital admission are presented in table . their ages were , , , and years, respectively. two patients were of male gender and the other two female. patients and had no documented cardiovascular (cv) comorbidities. patients and had underlying coronary artery disease (cad), hypertension (htn), and hyperlipidemia (hl). none had previous history of either brady-or tachy-arrhythmias. their heart rates on admission ranged between and beats/min. they presented to the hospital more than five days since symptom onset and required intubation and ventilation within one day of admission due to acute hypoxic respiratory failure. patient developed sinus bradycardia on day nine of illness (day one of hospital admission) and patient on day five of illness (day one of hospital admission). their bradycardia lasted for hours. patient developed bradycardia on day of her illness (four days into admission) and persisted for four days until spontaneous resolution. patient had multiple episodes of bradycardia; days - (four days into admission), days - , and days - of illness. patients' maximum body temperatures (tmax) ranged between . and . degree fahrenheit during bradycardic episodes. patients maintained map > mmhg during bradycardia, however, some required vasopressors. all patients except patient were on either norepinephrine or vasopressin since admission. norepinephrine infusion in patient was increased two hours after onset of bradycardia to maintain a map > mmhg. afterward, her infusion rate was gradually decreased, and discontinued two days after bradycardia resolution. patient was started on norepinephrine two hours prior to bradycardic episode, however, she did not require continuation of the medication. therefore, infusion was discontinued within the first hour of bradycardia onset. norepinephrine was re-started on day two of bradycardia due to low map and weaned off following bradycardia resolution. patient was started on norepinephrine and vasopressin two days prior to onset of bradycardia. vasopressin was continued at the same dose during first bradycardia episode, through day one of the second bradycardia episode. his norepinephrine was at mcg/min three hours before onset of bradycardia, and it was gradually weaned off on day one of bradycardia. he did not require dose increase of norepinephrine in subsequent bradycardic episodes. patient maintained map > mmhg during bradycardia without requiring vasopressors. all four patients were on propofol at one point during bradycardia. patients , , and were also given dexmedetomidine. figure summarizes propofol and dexmedetomidine infusions relative to first onset of bradycardia. patient was started on propofol and dexmedetomidine infusions two hours prior to bradycardia onset. dexmedetomidine was discontinued five hours into bradycardia while propofol was continued at a lower rate. propofol was continued following bradycardia resolution and further increments of propofol dosage did not result in bradycardia. patient was on a varying combination of fentanyl, propofol, and hydromorphone for over three days prior to onset of bradycardia. the patient was started on dexmedetomidine a day into the episode and continued infusion following the resolution of bradycardia. seven days after resolution of bradycardia, dexmedetomidine and propofol were re-initiated without the onset of bradycardia. propofol infusion was initiated two hours prior to bradycardia onset in patient . while propofol rate was gradually decreased, the patient continued to receive infusion following bradycardia resolution. later initiation of dexmedetomidine did not induce bradycardia. patient was on continuous propofol infusion for three days prior to onset of bradycardia. during the three episodes of bradycardia, there were changes to propofol dosage, with increments of rates in the interim periods. propofol was continued at the same rate following resolution of the last bradycardia episode. azithromycin and hydroxychloroquine were initiated on the day of admission in patients , , and . patient only received hydroxychloroquine as she had a corrected qt interval (qtc) of milliseconds (ms) on the day of admission. patients and developed bradycardia on day one and two of azithromycin and hydroxychloroquine combination treatment. patient developed bradycardia on day five of hydroxychloroquine therapy, and continued to be bradycardic following discontinuation of the medication. patient was noted to have bradycardia for two days while on azithromycin and hydroxychloroquine combination. this patient subsequently developed further episodes of bradycardia while off of these medications. while two patients' home medications included anti-hypertensives (i.e. lisinopril, losartan, atenolol), all home anti-hypertensives including beta-blockers were held on admission. initial ecgs on admission showed normal sinus rhythm, with a heart rate ranging between and beats/min. no arrhythmias were noted. patient did have a prolonged qtc of ms which persisted, but improved to ms during the bradycardic episodes. all patients had normal sinus rhythm during episodes of bradycardia (i.e. sinus bradycardia). as previously described, acute myocardial injury was thought to be the most common cardiac manifestation in covid- patients and potential for developing cardiac arrhythmias has been noted in a few studies. to our knowledge, the development of sinus bradycardia has not been described in patients with covid- thus far. our case series included four patients; two males and two females. two patients had preexisting cv comorbidities including hypertension, coronary artery disease, and hyperlipidemia. all four patients developed sinus bradycardia during their icu stay despite their cv state prior to admission. their lowest pulse rates were , , , and beats/min in patients - respectively. bradycardia severity did not appear to be related to their pre-existing cardiac conditions. however, pre-existing cv disease and/or development of acute cardiac injury have been associated with significantly worse outcome in covid patients [ , , [ ] [ ] . the development of sinus bradycardia ranged from day four to day of their hospitalization. this was transient with spontaneous resolution occurring within hours to four days. limited data are available on time course of development of cardiac manifestations in this infection. a study performed in china shows that increase in cardiac troponin i (ctni) in fatal cases started around days into their illness [ ] . reviewing our patients' ctni values, all patients had ctni < . during bradycardia. severe acute respiratory syndrome coronavirus (sars-cov) is another major viral respiratory tract infection which is of the same family of sars-cov- , with a major outbreak in . the pathological features in covid- were found to resemble closely with those seen in disease seen with sars-cov [ ] . although not the most common manifestation, significant sinus bradycardia was seen in . % of sars-cov patients, with a prevalence of . %, . %, and . % in first, second, and third week of hospitalization, respectively. this was noted to be transient [ , ] , as seen in our patients. with onset of bradycardia ranging between four and days of illness in these patients, time course for the development of bradycardia cannot be established at this point. more research requiring a larger sample size may help establish this. relative bradycardia is the term used to describe the mechanism where there is dissociation between pulse and temperature [ ] . this has been reported in many infectious diseases including typhoid fever, legionnaires' disease, psittacosis, typhus, leptospirosis, malaria, babesiosis, and dengue fever [ ] [ ] . we noted that during the bradycardia episodes our patients' body temperatures had readings that went above degree fahrenheit. although the term 'relative bradycardia' is used with body temperatures above degree fahrenheit [ ] , we believe this is still a significant finding due to the degree of bradycardia in our patients. this is an important finding to recognize as it provides insight to potential mechanisms of the disease process. the pathogenesis of relative bradycardia is poorly understood, but release of inflammatory cytokines, increased vagal tone, and direct pathogenic effect on the myocardium are few of the proposed mechanisms [ ] . a group of researchers hypothesized that "relative bradycardia is the central mechanism reflecting and influenced potentially by the direct pathogenic effect on the sinoatrial node as well as cross-talk between the autonomic nervous system and immune system". they further stated that cardiac pacemaker cells may be a target for inflammatory cytokines resulting in a change in heart rate dynamics or their responsiveness to neurotransmitters during systemic inflammation [ ] . this is particularly interesting because recent studies show evidence of severe deterioration in some patients with covid- being closely related to the cytokine storm [ ] . development of bradycardia may be a manifestation of this stage of the illness, implying the possible 'calm before the storm' in these patients. in a mouse model, it was noted that mice with bradyarrhythmia had increased levels of pro-inflammatory cytokines, including interleukin (il)- , il- , il- , and tumor necrosis factor alpha (tnf-α) [ ] . the etiology of cardiac manifestations in covid- patients seems to be multifactorial, which includes direct viral myocardial damage, hypoxia, hypotension, enhanced inflammatory status, angiotensin-converting enzyme (ace )-receptor downregulation, drug toxicity, and endogenous catecholamine adrenergic status [ , ] . direct myocardial injury from viral involvement of cardiomyocytes and the effect of systemic inflammation are thought to be the most common mechanisms responsible for cardiac injury [ , [ ] [ ] . ecg changes in the severe stages of covid- have been attributed to possible hypoxia and inflammatory damage incurred by the virus [ ] . our four patients had severe acute hypoxic respiratory failure, requiring intubation within hours of hospital admission. their inflammatory markers (ferritin, c-reactive protein, d-dimer, ldh, and fibrinogen) were elevated throughout bradycardic episodes which may imply a possible immunological damage leading to initial bradycardia. the inflammatory cytokines released during the stage of overwhelming immune response, acting on the cardiac pacemaker cells could possibly contribute to bradycardia. it may be that the high levels of pro-inflammatory cytokines, including il- directly act on the sinoatrial (sa) node [ ] . as all four patients developed bradycardia over six days into their illness, the time course falls within the timeline for onset of cytokine storm. this would be an interesting finding as it may be a sign of worsening inflammatory reactions or a prediction of cytokine storm. one may argue while all patients had elevated inflammatory markers during bradycardia, these did not appear to worsen on days following bradycardia episodes. in fact, in most patients, the inflammatory markers showed mild improvement. this may be due to early initiation of methyl-prednisone with or without tocilizumab in all patients, preventing severe inflammation. as mentioned above, the pulse-temperature dissociation could imply a possible direct pathogenic effect on the sa node. a case report published in january , reports sinus bradycardia on day seven of a patient with h n infection. this was noted to be suggestive of "progressive involvement of conducting tissue and severity of disease, culminating into a fatal outcome" [ ] . the group of researchers has also suggested that "in the terminal phase, sa node and av node affection was preferentially more than the inter-nodal connecting pathways, bundle branch, or purkinje fibers". azithromycin and hydroxychloroquine are often used in the management protocol in covid- patients who are hospitalized. these medications, especially when given together, are known to cause atrial and ventricular arrhythmias, and qtc prolongation [ , ] . while patient had initial prolongation of qtc prior to initiation of hydroxychloroquine, this improved while on the medication, and at the onset of bradycardia. all other patients developed bradycardia while on azithromycin and hydroxychloroquine combination, but had normal qtc intervals throughout bradycardia. we do not feel that the cause of bradycardia in our patients was due to medication-related qtc prolongation. of note is that patients were on continuous infusion of propofol with or without dexmedetomidine during bradycardia episodes. while onset of bradycardia could have been related to initiation of propofol in patients and , other patients were on propofol infusion three days prior to their episodes. further, continuation, reinitiation, or rate increments of propofol or dexmedetomidine infusions after bradycardia resolution did not cause bradycardia. while there is always a chance of these medications inducing bradycardia, a clear correlation could not be found. there is also a potential for an exaggerated response of medication induced bradycardia in these patients, especially considering the severity of bradycardia. while cardiac manifestations have been reported and are now a recognized complication of covid- pneumonia, transient sinus bradycardia has not been well described. sars-cov- viral infection appears to induce a transient sinus bradycardia, as noted in some patients with covid- . while etiology could be multifactorial, severe hypoxia, damage of cardiac pacemaker cells from inflammatory cytokines, and exaggerated response to medications are possible triggers. we believe it is important to know about the potential development of transient sinus bradycardia as a part of disease sequalae and for close cv surveillance of patients. a special consideration should be made in patients with inherited arrhythmia syndromes. it is particularly important to consider this to be a possible warning sign of a serious cytokine storm onset. as there are many medications being used empirically in patients, there is a need for increased awareness of possible drug interactions and close monitoring due to potential effects on av conduction, qtc interval prolongation as well as worsening bradycardia. bradycardia could be a possible predictor of worse outcome of covid- as well. further studies are needed to evaluate the prevalence of bradycardia occurring in covid- patients, prognostic outcome in those who develop bradycardia, and long-term cardiac sequelae in survivors which is too early to assess at this point. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china. jama. current data on the cardiovascular effects of covid- characteristic electrocardiographic manifestations in patients with covid- cardiovascular disease and covid- cardiovascular considerations for patients, health care workers, and health systems during the covid- pandemic the science underlying covid- : implications for the cardiovascular system cardiac and arrhythmic complications in patients with covid- an acute respiratory infection runs into the most common noncommunicable epidemic-covid- and cardiovascular diseases cardiac manifestations of coronavirus (covid- ) . statpearls cardiovascular implications of fatal outcomes of patients with coronavirus disease (covid- ) clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study pathological findings of covid- associated with acute respiratory distress syndrome cardiovascular complications of severe acute respiratory syndrome proposed mechanisms of relative bradycardia dengue and relative bradycardia the diagnostic significance of relative bradycardia in infectious disease the clinical significance of relative bradycardia the pathogenesis and treatment of the `cytokine storm' in covid- cytokine profile of the blood in mice with normal and abnormal heart rhythm cardiac conduction system affection in a case of swine flu key: cord- -ck hcu authors: chahrour, mohamad; assi, sahar; bejjani, michael; nasrallah, ali a; salhab, hamza; fares, mohamad; khachfe, hussein h title: a bibliometric analysis of covid- research activity: a call for increased output date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ck hcu background: the novel coronavirus disease (covid- ) has impacted many countries across all inhabited continents, and is now considered a global pandemic, due to its high rate of infectivity. research related to this disease is pivotal for assessing pathogenic characteristics and formulating therapeutic strategies. the aim of this paper is to explore the activity and trends of covid- research since its outbreak in december . methods: we explored the pubmed database and the world health organization (who) database for publications pertaining to covid- since december up until march , . only relevant observational and interventional studies were included in our study. data on covid- incidence were extracted from the who situation reports. research output was assessed with respect to gross domestic product (gdp) and population of each country. results: only publications met our inclusion criteria. these articles came from different countries, constituting % of all affected countries. china produced the greatest number of publications with publications ( %). with respect to continental research activity, asian countries had the highest research activity with original publications ( %). in terms of publications per million persons (ppmps), singapore had the highest number of publications with . ppmps. in terms of publications per billion-dollar gdp, mauritius ranked first with . . conclusion: covid- is a major disease that has impacted international public health on a global level. observational studies and therapeutic trials pertaining to covid- are essential for assessing pathogenic characteristics and developing novel treatment options. the capital of the chinese province hebei, wuhan city, has witnessed starting the st of december , the emergence of a new lower respiratory tract disease [ ] . chinese scientists were able to find the virus resulting in the epidemic, which was identified as the severe acute respiratory syndrome coronavirus (sars-cov- ), later identified as the covid- [ ] . in , march , the world health organization (who) has declared covid- to be a pandemic, with the virus infecting more than , persons in countries as of the th of march [ ] [ ] . between january and march , worldwide efforts have been focused on dealing with this emerging pandemic [ ] . the high infectivity rate of the virus has been a problem in countries where healthcare facilities became saturated and not able to accommodate patients [ ] . casefatality rate among covid- confirmed cases is estimated to be between . % and . % with the majority of deaths typically occurring among the elderly (age > years), immunocompromised, or those with multiple comorbidities such as cardiovascular disease [ ] [ ] . until now, the who's and the us centers for disease control and prevention's (cdc) directives for the management of covid- have been limited to infection control and symptomatic management of patients. no antiviral drugs or vaccines are available for the coronavirus [ ] . physicians are using different antivirals and anti-inflammatory agents based on expert opinion, as well as case series, and prospective and randomized trials reported from all over the world [ ] . that mentioned, research done on covid- is of major importance for both the containment of the disease and the treatment of the patients [ ] . reports from countries with big numbers of confirmed cases would delineate risk factors, clinical features as well as treatment strategies for patients with covid- [ ] . this paper aims at exploring the activity and trend of covid- research worldwide since its outbreak in december . the pubmed database of the national center for biotechnology information (ncbi) and who database were used to find the publications related to this study. in pubmed, publications were identified by searching for the terms "novel coronavirus ," "coronavirus ," "covid ," and "covid " in the search field. all publications between december and march , were included. data were also extracted from the who database of publications on covid- , which is collected from bibliographic databases, table of contents of relevant journals, and other relevant scientific articles. pubmed publications were cross-referenced to the ones found in the who spreadsheet on covid- publications. all the relevant articles not present on pubmed were then added to our database. news reports that were present in the who database were identified by two reviewers, and were removed from our final database. four reviewers (from the authors) looked at the publications. the corresponding author's country of origin was identified. the publication type was identified and only original articles and case reports were included in our study. the types of studies included basic science studies, epidemiological studies, randomized control trials, prospective trials, retrospective studies, and case series and reports. descriptive analysis was done to report the number and type of articles from each country. the number of articles in each country was then compared to its number of confirmed cases to identify countries where more publications are needed. data from the who health emergency dashboard novel covid- situation reports were extracted, from its initiation (january , ) up until the most recent one (march , ) [ ] . this information was used to compare research output per total number of cases in the country. to avoid bias, we divided the total number of publications by million persons in the country and by billion us dollar of gdp. our search yielded publications between december , and march , . after removing duplicates, news articles, and articles not related to the topic as deemed by two independent reviewers, we selected publications for our analysis. of these, only publications ( %) met our inclusion criteria ( figure ) . the main type of study was "case series" with ( %) publications. there were only five randomized control trials (rcts) among the original articles group accounting for around . %. the studies came from different countries ( in terms of publications per million person (ppmps), singapore ranked first with . ppmps, followed by mauritius with . ppmps ( table ). in terms of publications per billion-dollar gdp, mauritius ranked first with . , followed by honduras with . ( table ). covid- has arguably been the main focus of medical and scientific institutions around the globe for the past few months, and that is evident by the release of publications pertaining to it since december , . nevertheless, only around % of those constitute observational and interventional studies. china alone has contributed over % of the publications, followed by the united states with publications, or almost % of the total. for a topic of the utmost medical importance, we may expect to have a larger number of original publications; including but not limited to randomized trials and case series. with the rapid spread of covid- around the globe, healthcare systems and experts were required to mount a rapid response as well. as clinical interventions and contingency planning rose in priority [ ] , the time and effort needed to write and successfully publish articles became of secondary importance during the acute stages of the pandemic [ ] . over the course of history, humanity has faced a plethora of deadly diseases. from smallpox and the bubonic plague, to aids and ebola, the human race is no stranger to global pandemics [ ] [ ] [ ] . as medicine and science advanced, pandemics became less frequent and mortality rates better controlled. the scientific community may be geared towards developing potential vaccines and treatments rather than dedicating valuable time towards observational studies [ ] . conducting rcts is a lengthy process and publishing results may require several weeks to months; hence, the low volume of therapy-directed research when compared to observational studies is reasonable at this stage [ ] . the countries with the largest number of cases are china, italy, iran, spain, and germany in descending order. considering the fact that china houses over . million licensed physicians, and is the birthplace of the current pandemic [ ] , it is not surprising that the majority of relevant publications are attributed to chinese institutions. however, it is notable that italy and iran have produced a combined total of only studies, even though they account for almost % of all reported cases. a reason for this may be the strain on the healthcare systems in these said countries; as medical professionals race to keep up with the increasing number of reported cases. looking at the volume of annual research output per country of , it was found that italy and iran ranked th and th respectively in medical research output, with a combined number of studies close to , [ ] . this further indicates that the research shortage is not due to a lack of research culture or proper academic institutions, but rather due to the overstrain of healthcare facilities and physicians in the face of the rapid disease outbreak. consequently, patient healthcare constituted a priority over publishing observational studies and case reports. of the current countries with or more reported covid- cases, we notice that only five countries have published or more articles. with limited knowledge of this novel virus, the value of case-series and observational studies in countries with a large number of cases should not be underestimated; hence, medical institutions should be contacted and encouraged to publish their findings. population-level data can be a valuable tool for designing medical management algorithms and guidelines. as history can attest to, humanity has been surviving epidemics with improved outcomes. this is largely due to our most important line of defense, information. the quicker quality information can be gathered about a newly arising disease, the earlier scientific experts and researchers would be able to procure novel treatments, and ideally, cures. this information begins with early-outbreak case reports and observational studies, where the basic characteristics of the novel disease are documented, and hence, awareness can be raised [ ] . furthermore, randomized controlled trials of currently available antivirals and/or immune modifiers may procure valuable data, useful for treating severe cases and limiting morbidity. in what appears to be an arms-race between pathogens and the medical community, the importance of observational and interventional research cannot be understated [ ] [ ] [ ] . in the covid- era, evidence-based medicine can generate evidence-based survival. thus, we recommend increasing research output, from all countries involved with the disease, to better understand its pathogenic characteristics and help find proper therapeutic modalities. to the best of our knowledge, this is the first bibliometric analysis to study the worldwide covid- research output. nevertheless, there are some limitations in our study. even though we made use of both pubmed and the who databases, there still might be publications that were not in our scope. we were also dependent on the indexing of the databases used, as is the case in any other bibliometric study. the outbreak of covid- has caused a major threat to the international community and has raised significant public health concerns. the wide spread of this disease, along with its high rate of infectivity has incited a global demand for relevant research that can help describe the clinical and pathogenic characteristics of this illness. observational studies related to covid- can help describe the symptomatology of the disease, assess the efficiency of diagnostic tools, and establish proper management guidelines. therapeutic trials can help discover novel treatments and come up with new curative options. raising these concerns is essential for increasing the global research output pertaining to covid- . the epidemiology and pathogenesis of coronavirus disease (covid- ) outbreak severe acute respiratory syndrome-related coronavirus: the species and its viruses -a statement of the coronavirus study group world health organization declares global emergency: a review of the novel coronavirus (covid- ) an epidemiological study on covid- : a rapidly spreading disease. cureus the novel coronavirus originating in wuhan, china: challenges for global health governance the response of milan's emergency medical system to the covid- outbreak in italy case-fatality risk estimates for covid- calculated by using a lag time for fatality clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study the origin, transmission and clinical therapies on coronavirus disease (covid- ) outbreak -an update on the status care for critically ill patients with covid- an invited commentary on "world health organization declares global emergency: a review of the novel coronavirus (covid- )": emergency or new reality? clinical characteristics of coronavirus disease in china who health emergency dashboard novel coronavirus disease (covid- ) situation reports conducting clinical trials in outbreak settings: points to consider how to write a scientific article integrating clinical research into epidemic response: the ebola experience the deadly coronaviruses: the sars pandemic and the novel coronavirus epidemic in china the third plague pandemic in europe vaccines as epidemic insurance a commentary on randomized clinical trials: how to produce them with a good level of evidence number of licensed doctors in china from research output by country importance of observational studies in clinical practice conflict medicine in the arab world . handbook of healthcare in the arab world sports medicine in the arab world . handbook of healthcare in the arab world academic medicine and the development of future leaders in healthcare. handbook of healthcare in the arab world human subjects: all authors have confirmed that this study did not involve human participants or tissue. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- - usyb nn authors: baek, woong kee; sohn, soo-yeon; mahgoub, ahmed; hage, robert title: a comprehensive review of severe acute respiratory syndrome coronavirus date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: usyb nn severe acute respiratory syndrome-coronavirus (sars-cov- ), the virus strain that causes coronavirus disease (covid- ), was first identified in wuhan, china in december . it spread to several countries across continents and infected more than one million people within three months. while there is no consensus on the treatment of the disease yet, understanding the virus and its transmission is a cardinal priority. sars-cov- can be transmitted through bodily fluid. upon inoculation, the surface enzyme angiotensin-converting enzyme (ace ) acts as a receptor protein for viral entry. the mean incubation period is . days, and infected individuals can exhibit a variety of symptoms from fever, cough, dyspnea, and respiratory failure to even multiorgan failure. given the current situation, it is of paramount importance to understand the virus as thoroughly as possible. in this review, we discuss the background, epidemiology, possible pathophysiology, clinical presentation, and diagnostic studies related to sars-cov- infection. we also elaborate on the current research and evidence on treatment options and vaccine development based on the literature. values can be obtained once the epidemic is over. as the number of disease cases changes rapidly, conducting a precise epidemiological study is challenging. the complete reference genome sequence data of sars-cov- was made available in december , and the sequence data and variations have been updated at genbank [ ] . sars-cov- is . % identical to a bat cov ratg and shares . % of its identity with sars-cov, suggesting the bat as the most likely natural host of the virus. however, it is suspected that the zoonotic infection took place via an unknown intermediate host [ ] . the molecular protein responsible for the entry of sars-cov- into human host cells is angiotensinconverting enzyme (ace ) [ ] . this protein is widely found in different organs such as the lung, kidney, heart, and endothelial tissue. the main functions of ace are the downregulation of the renin-angiotensinsystem (ras), balancing the overdrive of ras mediated response and the renal, gastrointestinal absorption of amino acids [ ] . it also acts as a means of clathrin-mediated internalization of viruses such as sars coronavirus [ ] . recent studies have revealed that ace interacts with transmembrane protease, serine (tmprss ), which is responsible for the s protein activation of sars-cov- , just as in sars coronavirus [ , , ] . s protein of the viral structure interacts with surface ace enzyme, which leads to the internalization of the viral material. as the viral rna is released into the host cytoplasm, the viral translation process takes place using the host cellular machinery [ ] . the viral replicase gene of the single-stranded rna is translated to produce key proteins such as rnadependent rna polymerase (rdrp), rna helicase, and other non-structural proteins, which will serve as replicase-transcriptase complex (rtc) [ , ] . further to rtc translation, subsequent viral rna synthesis takes place using rdrp through a complementary strand as an intermediate. the translation products of the viral sub-genomic rna are further processed, and this results in a series of viral structural s, e, n, and m proteins. they are subsequently used in the assembly process with viral genomic rna, which is then released [ ] . upon viral infection, the immune system responds mainly in three ways. at the early phase of the infection, an innate immune response deploys myeloid lineage cells, natural killer (nk) cells, and epithelial cells, which, upon activation, will secrete proinflammatory cytokines and chemotactic factors. these include but not limited to interleukins (il) - , - , - , - , - , - , tumor necrosis factors (tnf), granulocytemacrophage (gm)-, granulocyte (g)-, macrophage colony-stimulating factors (m-csf), and interferongamma (ifn-ɣ) , , . these cytokines act to induce specific cells, including nk and dendritic cells [ ] . dendritic cells of the respiratory system can be directly and indirectly activated upon viral respiratory infection. epithelial cells release il- and then gm-csf to recruit dendritic cells and secrete il- to support paracrine regeneration [ ] . in the lung, type ii pneumocytes (t p) also participate during the immune response: t p produces surfactant, which is composed of phospholipids (mainly phosphatidylcholine and phosphatidylglycerol), lipid (cholesterol), and surfactant protein a, b, c, d. the surfactant a and d pair with viruses to promote the action of macrophages [ ] . an effective early phase defense mechanism depends on phagocytic cell interaction with antigens directly using pattern recognition receptors (prr) and pathogen-associated molecular patterns (pamp) or indirectly via opsonins. the adaptive immune response, especially the arm of t cell maturation, is in majority through an increase in il- , followed later by a cd +th cell response and cd +t-cell-mediated cytotoxic response. through the process of autophagy, harmful and damaged cellular components are metabolically degraded [ ] . autophagy also plays an important role in modulating the innate and adaptive responses during a viral infection as any pathogenetic steps of viral infection from its entry, fusion, and to the interference of cellular homeostasis can disrupt the immune-protective mechanism [ ] . a similar early innate response is seen in sars-cov- -infected patients who present with initial cardinal symptoms such as fever and malaise. yet, their clinical sequelae and the response to the treatment are different from any respiratory diseases known today. the increase in the body temperature seems to be due to the production of proinflammatory cytokines such as il- , - , - , - , - , and tnfs from first responders such as monocytes, damaged local endothelial cells, and neutrophils. while macrophages promote the local inflammatory response with the release of chemotactic factors, the paracrine response of the endothelial cells and pneumocytes enhances the expression of adhesion molecules such as intercellular adhesion molecule (icam- ) on t p. e-selectin and vascular cell adhesion molecule (vcam) facilitate the migration of white blood cells. it is suspected that the acute respiratory distress syndrome (ards)-like picture in sars-cov- -infected patients is precipitated and worsened by the excess monocytes in response to gm-csf, which is released by rapidly activated cd +t-cell lineage [ ] . the progression to ards-like presentation is driven by three main factors: the local inflammatory response by neutrophils inducing local damage; the releasing of proteinaceous cellular debris in the alveolar space; and locally-acting mediators such as endothelin- , phospholipase a- , and angiotensin- making the local vessel more permeable. the damage to type i pneumocytes impedes local gas exchange while damage to type ii pneumocytes results in decreased surfactant production. the surfactant has an important function in reducing the surface tension of alveoli. as more t p are lost, the surface tension of the alveoli increases, which leads to the collapse of the alveolar cavity. furthermore, the alveolar cavity is filled with the proteinaceous cellular debris from the inflammatory reactions and the exudate from the increase in vascular permeability, which translates into the pulmonary edema-like picture in patients. the infection spreads to the adjacent alveoli through the pores of kohn, infecting adjacent alveolar cavities. these events explain the progression of lung involvement, dyspnea, and shortness of breath. yet, ards-like presentation with sars-cov- infection is atypical as the patients who fit into the berlin definition do not show similar lung compliance and shunt fraction as a typical ards patient [ ] . sars-cov- -infected patients have shown a rise of cytokines during their disease course, notably, il- , - , - , - , - , tnf-α, g-csf, interferon-gamma-inducible protein (ip), monocyte chemoattractant protein (mcp ), and macrophage inflammatory protein alpha (mip a), between day - of disease onset, which corresponded to the disease severity of the patients [ , , ] . patients with mild symptoms presented with an elevation of cytokines within the reference ranges, while severe patients showed markedly elevated levels [ ] . as for the ifn-ɣ, there are mixed findings [ , ] . zhou et al. have considered the high ifn-ɣ and gm-csf by th cells and gm-csf by cd +t-cells as the possible cause of the hyper-inflammatory reaction, as nk cells and b-cells were not found to relate with these features [ ] . given that monocytes respond to gm-csf as expected, sars-cov- -infected patients had higher cd +cd + monocytes than normal healthy individuals [ , ] . these monocytes promote the secretion of gm-csf and il- , both of which are surged in severely ill patients, overfeeding the inflammatory response, and suggesting the relationship among gm-csf, il- , monocytes, and th cells, which explains the cytokine storm [ , , ] . a recent study of sars-cov has shown that t-cell dysfunction along with the decrease in type i ifn is related to t-cell exhaustion [ ] . yet, the relationship between the clinical severity of sars-cov- -infected patients and t-cell exhaustion is still unknown. mehta p et al. have reported that the cytokine profile and the trend of the inflammatory markers of sars-cov- -infected patients present similarly to the secondary hemophagocytic lymphohistiocytosis (shlh), whose severe clinical presentation is related to the cytokine storm [ ] . further study is needed to verify if the severe presentation and poor prognosis are related to any of these aforementioned findings. a spectrum of symptoms is observed in sars-cov- -infected patients. the degree of the severity of the disease experienced by a diverse population is very different as well. while the majority of patients experience cardinal and respiratory symptoms, a minority of the population also presents with gastrointestinal symptoms such as diarrhea, nausea, and vomiting. the most commonly reported symptoms are fever, dry cough, and fatigue followed by myalgia, chest tightness/pain, sore throat, shortness of breath, dyspnea, and rhinorrhea (tables , ) [ , [ ] [ ] [ ] [ ] . liu et al. have reported that the severity of atypical pneumonia correlated with an increase in different criteria such as sequential organ failure assessment (sofa), acute physiologic assessment and chronic health evaluation ii (apache ii), and curb (the acronym for criterion assessing the risk of patients presenting with respiratory diseases) [ ] . wang et al.'s study found a similar tendency among sars-cov- infected patients [ ] . the progression of atypical pneumonia and respiratory failure were reported as sequelae of this disease with other severe complications such as multiple organ failure, sepsis, and death. the correlation may suggest poor prognosis; however, a meta-analysis is required to support this. the level of il- is also suggested as being associated with a severe presentation of respiratory symptoms, possibly related to the cytokine storm [ , ] . in addition, onder et al. have shown a significant case fatality in relation to the increase in the age of patients [ ] . on the other side of the spectrum, although uncommon, neurological symptoms have been reported, suggesting neurologic deficits can be associated with sars-cov- infection. zhao et al. have reported a case of a possible association with guillain-barré syndrome (gbs), where a -year-old woman acutely developed symmetric lower extremity weakness eight days before the onset of fever and respiratory symptoms [ ] . another case, a post-infectious acute hemorrhagic necrotizing encephalopathy, was reported in a patient who had a three-day history of altered mental status with cough and fever [ ] . however, it is difficult to conclude if sars-cov- infection is associated with these specific diagnoses added based simply on two individual case reports. more data and studies are needed to elucidate this relationship and risk population. there is no identified pathognomonic clinical presentation of sars-cov- infection. at the initial phase of the epidemic, high clinical suspicion was related to the presence of fever, malaise, respiratory or gastrointestinal symptoms along with a recent travel history to wuhan, china, or physical contact with people at high risk, which were used to determine if further investigations were indicated. as the pandemic progressed and the chains of spreads took root within many local communities, more emphasis was put on the importance of diagnostic studies rather than clinical presentation. wang et al. have stratified the sars-cov- -infected patients' presentation according to the symptom severity ( table ) [ ] . mild mild symptoms including fever, fatigue + absence of radiographic feature + absence of pneumonia-like symptom [ ] moderate fever + respiratory symptoms + presence of radiographic features [ ] severe dyspnea, respiration rate of > /min or o saturation of < % or p a o /f i o of < mmhg [ ] critical respiratory failure or septic shock or multiple organ failure [ ] sars-cov- : severe acute respiratory syndrome coronavirus ; pao : partial pressure of oxygen; fio : fraction of inspired oxygen many non-specific inflammatory markers, including c-reactive protein (crp), erythrocyte sedimentation rate (esr), and ferritin are elevated in sars-cov- -infected patients [ , ] . other laboratory findings include elevated procalcitonin, decreased total lymphocytes count, prolonged prothrombin time (ptt), elevated d-dimer, alanine transaminase (alt), aspartate transaminase (ast), blood urea nitrogen (bun), creatinine (cr), lactate dehydrogenase (ldh), and creatine kinase (ck), which were generally found to be more pronounced in patients admitted to the intensive care unit (icu) [ ] . patients in the icu had high levels of cytokines such as il - , - , - , tnfα, g-csf, and mip a [ ] . critically ill patients and nonsurvivors had high levels of neutrophils, d-dimer, ferritin, bun, and cr, suggesting a possible pathological etiology related to a poor prognosis [ ] . laboratory tests for diagnosing sars-cov- include nucleic acid amplification tests (naat) such as realtime reverse-transcriptase polymerase chain reaction (rt-pcr), serological testing such as enzyme-linked immunosorbent assay (elisa), and viral sequencing [ ] . each diagnostic method has its own advantages and disadvantages. currently, rt-pcr is most favored for its practicality, time efficiency, and cost factor [ ] . radiographic features are usually absent in mild cases of sars-cov- infection. common early-stage ct findings up to day four after symptom onset have shown numerous focal 'ground-glass opacities' in the majority of patients [ ] . between day - , lung involvement worsened with increasing consolidation in several lobes of both lungs. these pulmonary pathologies started to improve after day but a complete resolution was hardly achieved even after days [ ] . other manifestations included vascular thickening, halo-or air bronchogram sign, and pleural effusion, although these have been rarely encountered [ , ] . ultrasound (us) images have supported ct findings confirming thickened pleural lines and the location of lesions [ , ] . us shows b lines in the early stage and in mild infections with the alveolar interstitial syndrome as the disease progresses [ ] . there is no consensus yet on how to treat sars-cov- -infected patients who present with a wide spectrum of clinical symptoms and severity. the current use of hydroxychloroquine is based on the knowledge of minimizing the viral entry into the host cell and impeding viral replication by disrupting the assembly and release of the virus [ ] . mukherjee et al. have reported a favorable outcome in a -year-old patient who had multifocal atypical pneumonia and treated with hydroxychloroquine [ ] . a recent non-randomized clinical trial in france, without a control group, has shown a positive result of the use of hydroxychloroquine with azithromycin in sars-cov- -infected patients, leading to a faster resolution of symptoms in the majority of patients [ ] . an adenosine analog, remdesivir (gs ), acts as a nucleotide analog that halts the transcription process of viral rna [ ] . holshue et al. have reported successful treatment with remdesivir of the first sars-cov- -infected patient in the united states [ ] . wang et al. have reported positive effects of remdesivir and chloroquine in a study using infected cells [ ] . however, not all studies are in favor of the use of these drugs. a small pilot study of patients in china found no statistically significant difference in the remission of the disease between the hydroxychloroquine treatment group and the control [ ] . lopinavir and ritonavir, novel protease inhibitors that are used to treat hiv infection, are other medications proposed to treat sars-cov- infection. cao et al. found through a randomized, controlled trial of patients that the lopinavir-ritonavir treated group did not show a statistically significant difference in the mortality, hazard ratio, and viral load as compared to patients who had standard care [ ] . given that many antiviral treatments are related to severe side effect profiles, a precautious determination of the right dosage and appropriate targets should be determined through clinical trials. structural proteins such as glycoprotein or spike protein are important targets of antiviral vaccine development. given that the genomic sequence of the amino acid can be used for homology remodeling, it may, theoretically, assist in identifying molecules with possible antiviral properties [ ] . yet, the high potential of spontaneous mutation associated with the genetic properties of the coronavirus, such as a high recombination ability and the presence of splicing sites and more than rna modification sites may pose challenges to this as it can promote changes of target tissue specificity and antiviral sensitivity [ ] . in addition to the presence of ace , an important serine protease, tmprss is used in s protein priming. this process is shown to play an important role in viral entry by mediating viral envelope fusion with the cell membrane into the host cell and, hence, is related to infectivity [ ] . for this reason, hoffmann et al. proposed a serine tmprss protease inhibitor, camostat mesylate, for its potential benefit [ ] . however, this needs further studies as sars, another subset of coronavirus, can enter host cells via an alternative pathway using endosome when the key proteases are lacking [ ] . with the absence of a treatment of choice, preventive measures are the most effective way to minimize the spread of infection. the infection primarily spreads via respiratory secretions and droplets, direct contact by touching contaminated surfaces, and/or indirectly via fomites. transmission can occur from both symptomatic and asymptomatic patients, before symptom onset. infected droplets can spread - m and can deposit on surfaces where they remain for a period of time. the degeneration of infectious material is accelerated by common disinfectants like sodium hypochlorite and hydrogen peroxide. some studies have also indicated this virus to be present in stool and contaminated water supplies, suggesting possible transmission via the fecal-oral route [ ] . currently, preventive measures include the appropriate use of personal protective equipment (ppe), social distancing, and hand-washing. it is hard to predict where this infection can lead. with a relatively high number of reproducibility, a long incubation period, and possible transmissibility even during an asymptomatic period, sars-cov- has infected over . million people worldwide as of april , , less than four months after its first identification at the end of december [ ] . being an enveloped positive-sense single-stranded rna virus, its mutation rate is higher than the dna counterparts that use host replication machinery. as the number of infected people increases, different selection pressures can derive an emergence of variant strain and/or the survival of the fittest. tang et al. have reported two different strains of sars-cov- : l and s subtypes, with s subtype being the ancestral one. however, the progenic l subtype presents higher transmissibility [ ] . in addition, a recent chinese case report has described a patient shedding virus for days, which is unusually longer as compared to the median duration of days [ ] . this suggests that the variation of genotype is still emerging and that mutations can occur anytime in the future. the pathophysiology behind the peripheral leukopenia in severe patients is not fully understood. many viruses are known to interfere with t-cell activation, maturation, or programmed cell death. recent research has shown that mers-cov, another coronavirus, acts to promote the intrinsic and extrinsic pathway of tcell apoptosis, thereby decreasing the t-cell population [ ] . cd +t-cells are crucial in promoting humoral immunity and b-cell activation. the loss of th , th , and th populations implies a decrease in the efficacy of mounting the adaptive immune response. interestingly, the patient population who had severe symptomatic presentation showed more pronounced leukopenia, especially during the early phase (four to six days after disease onset) of the disease course, with an increase in cytokines (original research article to support this idea [ ] . more studies are needed in the future to elucidate the pathogenesis behind the peripheral cytopenia and immune dysregulation. a minority of patients on remission presented back with clinical symptoms of the disease relapse or reactivation between - days after discharge [ ] . chen et al. have reported a case of recurrence of viral rna after two consecutive days of negative tests [ ] . ye et al. have reported a rate of reactivation as high as % in their study, but their patients' clinical presentation was not as critical as the initial infection [ ] . the reactivations were confirmed using positive rt-pcr. the study suggested that the reactivation is associated with the degree of the immune status of the patients, the genotypic factor of the virus, and the baseline viral load. it also pointed out that all patients with reactivations were treated with antiviral medication such as oseltamivir or arbidol [ ] . although the clinical presentation and sequelae are not as severe in the patients with reactivation, there is still a risk of droplet-transmission to others upon discharge, and hence can pose a public health concern if ignored. it will be necessary to educate the patients on the possibility of reactivation and encourage a -day self-isolation to minimize contact with others while reporting to the appropriate healthcare agency if symptoms recur. sars-cov- infection or covid- is a highly transmissible novel zoonotic infection with high case fatality rates. the transmission of infection from both asymptomatic and symptomatic patients and its relatively long incubation period make it even harder to control its spread. unfortunately, there is no consensus on how to treat this infectious disease yet. more studies and data are needed. a good understanding of the disease transmission, its genetics, pathophysiology, clinical presentation, prognostic factors, diagnostic studies, and preventive measures are of prime importance in making clinical decisions and designing research projects for best treatment while responding to minimize the threat to people. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. 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protein of the sars-cov- shows protein ligand interaction with an aza-peptide and a noncovalent lead inhibitor with possible antiviral properties (in press) the architecture of sars-cov- transcriptome (epub ahead of print) a review of coronavirus disease- (covid- ) on the origin and continuing evolution of sars-cov- (epub ahead of print) a special case of covid- with long duration of viral shedding for days (in press) middle east respiratory syndrome coronavirus efficiently infects human primary t lymphocytes and activates the extrinsic and intrinsic apoptosis pathways elevated exhaustion levels and reduced functional diversity of t cells in peripheral blood may predict severe progression in covid- patients clinical characteristics of severe acute respiratory syndrome coronavirus reactivation recurrence of positive sars-cov- rna in covid- : a case report key: cord- - sgxiilt authors: cruz salcedo, elis m; rodriguez, lyd-marie; patel, jay; seevaratnam, andrew r title: use of dexmedetomidine in early prone positioning combined with high-flow nasal cannula and non-invasive positive pressure ventilation in a covid- positive patient date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: sgxiilt as the covid- pandemic continues to manifest in our society, we still lack evidence-based treatment guidelines. current treatment for covid- pneumonia has been modeled from currently established guidelines such as that of acute respiratory distress syndrome (ards). covid- pneumonia, also known as sars-cov- , is characterized by severe hypoxia and near-normal respiratory system compliance with a time-related presentation. dexmedetomidine is a centrally acting alpha- receptor agonist that promotes sedative and anxiolytic effects without the risk of respiratory depression and can provide cooperative or semi-rousable sedation. patients who are developing ards secondary to covid- pneumonia have been treated with self-proning intervals in combination with supplementation of oxygenation via high-flow nasal cannula (hfnc) or non-invasive positive pressure ventilation (nippv); however, a few patients have poor tolerance to the devices, leading to poor compliance and eventual worsening respiratory symptoms leading to intubation. in the current case report, we detail how a patient was able to successfully be self-proned with proper tolerance to hfnc and nippv while using dexmedetomidine, leading to discharge without the need for further oxygen supplementation at home. as the covid- pandemic continues to manifest among our society, we still lack evidencebased treatment guidelines. to this day, a wide array of treatment modalities have been used, recorded, and disseminated amongst health care providers detailing their management and results. current treatment for covid- pneumonia has been modeled from currently established guidelines such as that of acute respiratory distress syndrome (ards). communication between physicians who have been directly involved in the care of covid- positive patients has been key to establish and tailor current management recommendations by focusing on different theories of pathophysiology affecting the lungs. covid- pneumonia, also known as sars-cov- , is characterized by severe hypoxia and near-normal respiratory system compliance, with a time-related presentation. two phenotypes have been identified and been described as type l and type h [ ] . both presentations differ in pathophysiology, particularly as type l can evolve into type h, ultimately meeting the berlin criteria of ards [ ] . different treatments have been proposed per pathophysiology type. for the initial stages of type l, an increase in the fraction of inspired oxygen (fio ) administered with non-invasive ventilation methods, such as high-flow nasal cannula (hfnc) has improved the clinical outcome of some patients [ ] . it has also been noted that for these patients, prone positioning decreases intubation rates and improves outcomes for those developing ards [ ] [ ] . this combination of early prone positioning combined with non-invasive options of ventilation may have an association with a reduced intubation rate and prevention of transition to phenotype h [ ] . dexmedetomidine is a centrally acting sedative and anxiolytic, which may promote relief of anxiety from dyspnea and promote adherence to respiratory support from hfnc and nippv [ ] . our case details a patient with covid- pneumonia who was successfully managed with awake self-proning while using dexmedetomidine in combination with hfnc and noninvasive positive pressure ventilation (nippv) during the beginning stages of the disease in order to promote increased adherence to proning cycles and oxygen support equipment, to prevent endotracheal intubation. a -year-old, non-smoker caucasian female with a history of asthma, hypothyroidism, hypertension, and right breast cancer currently on remission, presented with complaints of worsening fatigue, myalgia, productive cough of clear sputum, and ℉ temperature that began one week prior to presentation. there was no travel history but the patient had a positive history of contact with a close relative with similar symptoms. on presentation, she was afebrile, with a heart rate of beats per minute, respiratory rate of breaths per minute, and oxygen saturation at room air of %. the examination was remarkable for diminished breath sounds bilaterally. laboratory studies showed a leukocyte count of , cells/µl with a normal differential and a coagulation panel within normal limits. further laboratory marker results for lactate dehydrogenase (ldh), erythrocyte sedimentation rate (esr), c-reactive protein (crp), procalcitonin, interleukin (il- ), ferritin, and d-dimer are detailed in figure . chest x-ray showed bilateral lung infiltrates and a venous doppler ultrasound for deep vein thrombosis was negative. severe sepsis criteria were met on admission, with evidence of end-organ damage and elevated troponin i of . ng/ml and a creatinine level at . mg/dl from a baseline of . mg/dl. the patient was started on azithromycin mg intravenous (iv) once daily and ceftriaxone , mg iv once daily in addition to fluid resuscitation pending covid- pcr results. final blood cultures and the influenza test were negative, however, the covid- pcr test was positive. initial hypoxemia resolved with oxygen supplementation with a l oxygen nasal cannula but progressively worsened requiring supplementation with a % fio . arterial blood gas at that time showed acute hypoxic respiratory failure, prompting an escalation of treatment to hfnc and transferring the patient into the medical icu. hydroxychloroquine mg once daily, methylprednisolone mg every eight hours, and enoxaparin mg/kg subcutaneous twice daily were added to the medical regimen. a repeat chest x-ray showed progressive worsening of bilateral infiltrates. considering worsening hypoxemia, intermittent self-proning was instituted with alternating hfnc and nippv. dexmedetomidine was initiated to assist with self-proning tolerance. proning sessions lasted an average of four hours alternating between supine and prone positions. ceftriaxone was discontinued and cefepime , mg every eight hours was initiated. the patient also received one unit of convalescent plasma. experimental therapies with tocilizumab and remdesivir were attempted but were unable to be provided. she completed a five-day course of azithromycin and a -day course of hydroxychloroquine. slow interval improvement on images ( figure ) and in the clinical presentation was noted, resulting in improvement of oxygenation and eventual discharge home without requirement for oxygen supplementation following a -day hospital stay. to the best of our knowledge, this is one of the few cases reported in the united states of treatment with awake self-proning combined with hfnc and nippv, with the use of dexmedetomidine. prior studies have demonstrated how hfnc is associated with improved survival rate among patients with acute hypoxemic respiratory failure when compared to standard oxygen or noninvasive ventilation; and it is associated with an increased degree of comfort, a reduction in the severity of dyspnea, and a decreased respiratory rate [ ] . prior studies have shown how prone positioning has a mortality reduction and improved oxygenation when applied early and for prolonged time periods in patients with severe ards [ ] . unlike proning intubated patients with ards, self-proning is less labor-intensive and poses a lower occupational hazard risk to nursing staff since patients are able to conduct this themselves. there is evidence that the aforementioned strategy resulted in the discharge of a covid- patient without requiring intubation in ontario, canada [ ] . additionally, a case series report of patients from a new york city hospital hypothesized an association between proning patients with covid- and improvement in oxygen saturation [ ] . the addition of dexmedetomidine sedation was essential to our management with self-proning, as it allowed adherence to treatment. dexmedetomidine is a centrally acting, presynaptic selective alpha- adrenoreceptor agonist that inhibits the release of norepinephrine from synaptic vesicles, which promotes analgesic, anxiolytic and sedative properties [ ] . by including the use of dexmedetomidine for patients using hfnc or nippv, it helped promote compliance and comfort during supine-prone rotation cycles and allowed improved tolerance to an otherwise previously oxygen support-naïve patient. additionally, isolation measures for covid- positive patients place them at a higher risk tier for anxiety, both from dyspnea-associated anxiety and isolation anxiety from strict distancing requirements in order to prevent further dissemination of the disease. this case further contributes to the current literature, aiming to increase recognition and to incite further investigations on potential modalities of treatment of covid- pneumonia, with a special emphasis on reducing intubation rates, reducing mortality, patient comfort, and preservation of resources. dexmedetomidine is a centrally acting alpha- receptor agonist that promoted sedative and anxiolytic effects without depressing the respiratory system. in patients who require increments of oxygen supplementation without the need for endotracheal intubation and/or those who present with the inability to tolerate hfnc or nippv, experience anxiety associated with dyspnea, or are unable to be compliant with self-proning, dexmedetomidine may be used effectively to assist with compliance and tolerance. patients who are able to tolerate selfproning treatment in combination with hfnc and nippv may experience improvement in oxygenation, leading to clinical improvement and discharge home without oxygen requirements. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. covid- does not lead to a "typical" acute respiratory distress syndrome early self-proning in awake, non-intubated patients in the emergency department: a single ed's experience during the covid- pandemic efficacy and safety of early prone positioning combined with hfnc or niv in moderate to severe ards: a multi-center prospective cohort study pubchem compound summary for cid high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure a comprehensive review of prone position in ards . respir care patient self-proning with high-flow nasal cannula improves oxygenation in covid- pneumonia this research was supported (in whole or in part) by hca healthcare and/or an hca healthcare affiliated entity. the views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of hca healthcare or any of its affiliated entities. key: cord- -xew ar e authors: eperjesiova, bianka; hart, eric; shokr, mohamed; sinha, prabhat; ferguson, gary t title: spontaneous pneumomediastinum/pneumothorax in patients with covid- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: xew ar e no spontaneous air leak case series have been described in the severe acute respiratory syndrome coronavirus (sars-cov- ) patient population thus far. we described seven spontaneous air leak cases we found in our coronavirus disease (covid- ) positive -patient cohort. five out of seven patients eventually required mechanical ventilation, and one of these patients died. all of our patients who demonstrated radiological air leaks after intubation died. no other precipitating factors offered in the literature thus far played a role in our patient population. we presume that acute lung injury leading to sars-cov- with associated acute respiratory distress syndrome (ards) predisposes patients to this rare complication. spontaneous air leak is the travel of free air following distended ruptured alveoli via peribronchovascular sheaths into the mediastinum or the pleural space [ ] . it can occur in the setting of obstructive or restrictive lung disease exacerbation, although it has been observed in hyperventilation states such as infections, vomiting, diabetic ketoacidosis, athletic activities, or inhalational drug abuse [ ] . air leak in hospitalized severe acute respiratory syndrome coronavirus (sars-cov- ) patients has been sparsely published as case reports, however, the presence of non-invasive ventilation and positive airway pressure were reported prior to this finding [ ] [ ] . additionally, there is no reported incidence found in the literature. studies of a severe acute respiratory syndrome with sars did identify air leak as a frequent complication, often with no relation to intubation or positive pressure ventilation [ ] [ ] [ ] [ ] [ ] . our institution cared for coronavirus disease or covid- (sars-cov- ) patients between march and april , . of these, we found cases of air leak; three traumatic/post-procedure, post-intubation/mechanical ventilation, and seven spontaneous (five cases of pneumomediastinum and two isolated pneumothorax). the demographic, clinical, laboratory, and imaging data of the seven patients who developed a spontaneous air leak are provided in table . (figure - a) . the patient was treated medically, and no mechanical ventilation was required. her hospital course was complicated by a bleeding duodenal ulcer, ischemic stroke, and fungemia. fourteen days later, ct showed a resolution of pneumomediastinum (figure - b) . she was discharged to subacute care. similarly for patient , ct was performed (figure - a, b ). the patient was treated medically, and no mechanical ventilation was required. her hospital course was complicated by a bleeding duodenal ulcer, ischemic stroke, and fungemia. fourteen days later, ct showed the resolution of pneumomediastinum (figure - b) . she was discharged to subacute care. radiological evidence of spontaneous air leak was found in seven patients (incidence . %) with event onset ± days (mean±sd) from covid- symptom onset and ± days (mean±sd) from admission. our cohort had no gastrointestinal/thoracic/vascular procedures or chest compressions during hospitalization. five out of seven patients required intubation, but all pneumomediastinum/pneumothorax events occurred before intubation. no difference in age, gender, body mass index, or medical histories as compared to other covid- patients was noted except for three out of seven patients having an obstructive lung disease. one out of seven spontaneous air leak patients expired. five out of six discharged patients had resolution of their air leak. all patients with an air leak after intubation expired. ct chest of patient number from our series, who expired, is depicted in figure - a pre-intubation, with progression in figure - b post-intubation. we presume that covid- infection leading to acute lung injury with associated ards might be associated with a spontaneous air leak, and further investigations are warranted to delineate mechanisms and impact on outcomes. human subjects: consent was obtained by all participants in this study. ascension providence hospital institutional review board issued approval - . in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. spontaneous pneumomediastinum in patients with severe acute respiratory syndrome spontaneous pneumomediastinum: analysis of consecutive adult patients spontaneous pneumomediastinum: a probable unusual complication of coronavirus disease (covid- ) pneumonia mediastinal emphysema, giant bulla, and pneumothorax developed during the course of covid- pneumonia high-resolution ct findings in patients with severe acute respiratory syndrome: a pattern-based approach key: cord- -z r vnku authors: downes, simon r; lykina, tatiana title: closing the gap in global neurosurgical education via online conference: a pre-covid survey date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: z r vnku introduction a reliable network for peer review and feedback can lead to an increase in knowledge and improving patient care. as opportunities to participate in online continuing medical education (cme) increase, there is a reduction in the worldwide knowledge gap often due to a lack of resources to attend conferences and advanced training in person. methods a total of participants completed a -item anonymous online questionnaire to assess how their knowledge and applied practical skills improved by participating in online conferences, and whether this education modality adequately addresses challenges for countries with limited access to conferences or training. results while an overall positive response toward this mode of neurosurgical education was expected, interesting insights were gained from the short-answer section, demonstrating a direct influence on clinical practice through online conference participation. conclusion while limited in size, the study results support the expectation of a positive attitude toward neurosurgical e-learning, which translates directly to improving patient care and lessening the worldwide gap in neurosurgical education. physicians have numerous opportunities to update their clinical and academic knowledge by reading journals and attending training and conferences. however, physicians' busy schedules present practical challenges for continuing medical education (cme) to improve medical knowledge and clinical skills. consider, for example, a community-based physician with limited resources for traveling to an out-of-state conference who must instead rely on traditional forms of learning. as a result, this individual may not be as connected and proficient as colleagues located in large cities [ ] . even in the face of a pandemic with social distancing, learning must continue. online conferencing and training overcomes geographical distance, and following the lockdowns due to coronavirus disease (covid- ), in-person conferencing will never be the same. although online cme is relatively new, numerous studies have pointed to its efficacy by evaluating measurements of its effectiveness over time [ ] [ ] [ ] [ ] [ ] [ ] [ ] . moreover, there are expanding opportunities to connect physicians around the world utilizing various online platforms for neurosurgical education, such as live courses and webinars offered by the american association of neurological surgeons. while the advent of online neurosurgical education is difficult to ascertain, various web conferencing platforms have hosted education and communication between medical practitioners [ ] [ ] [ ] [ ] . therefore, it is important to point out that while participants of this study utilized one online platform as a source of online neurosurgical education, this platform may not be representative of all online neurosurgical education. although anecdotal evidence from neurosurgeons who have attended online conferences or presentations points to promising results, questions remain regarding the extent to which neurosurgeons benefit from online cme and whether it can supplant traveling to live conferences, particularly for those living in countries with limited access to advanced neurosurgical education. thus, this study addresses the following research questions: . do neurosurgeons think that their knowledge and practical skills improve as a result of participation in online conferences? . do neurosurgeons think that virtual neurosurgical education can provide opportunities when there is limited access to conferences or advanced training? this study aims to understand the impact online neurosurgical education has on individual neurosurgeons, and also whether having access to online training and conferences will lessen the gap in global neurosurgery education. to explore the research questions, a multi-level questionnaire was created to measure attitudes toward the effectiveness of online learning through a combination of multiple-choice questions, likert-scale questions, and a short answer fill-in section. furthermore, demographic questions were added to better understand the population that completed the questionnaire. accordingly, to design questionnaire items that had a reasonable level of reliability or validity, we based our items on related scales which have been published in the literature [ ] [ ] [ ] [ ] . in total, individuals representing countries participated in the questionnaire. among the top countries, ( . %) participants were from cameroon, ( . %) were from the u.s., and ( . %) each were from pakistan and the republic of the congo; see appendix for a complete list of countries. furthermore, participants ranged from to years of age, with the majority of participants between and ( . %). the next largest age group was to ( . %). we created an online invitation to complete a -item questionnaire. the questionnaire was anonymous, and no specific questions were related to stage of neurosurgery education or qualifications as a neurosurgeon. respondents filled out the questionnaire between january , and february , . to avoid selection bias, no incentive was offered to answer the questionnaire. descriptive statistics were used to highlight the differences in respondents' opinions. to gain an initial picture of participants' attitudes toward online conferences, the first item asked, 'what is your impression of online webinars/conferences?' most respondents ( . %) answered positively, indicating they consider online sessions to be highly educational and would like to have their training sessions online, while ( . %) did not consider online sessions to be useful and preferred to attend in person ( figure ). careful consideration is necessary here as these results apply to attitudes toward online education in general and not necessarily neurosurgical education. the second item, 'neurosurgical online education is a useful form of education', aimed to determine how neurosurgeons value this novel form of education ( figure ). most ( . %) strongly agreed or agreed ( . %) that neurosurgical education in this format is useful. the third item, 'virtual neurosurgical education can extend educational opportunities for all levels of neurosurgeons', considered whether a certain level of neurosurgical education is needed to derive a benefit from online sessions ( figure ) . here, the majority of respondents strongly agreed ( . %) or agreed ( . %), signifying the opinion that online neurosurgical education is suitable at all levels of neurosurgery training. next, item five, 'do you plan to attend other online neurosurgical education sessions?', focused on individual intention for future participation in online neurosurgical education ( figure ) . overall, . % answered that they definitely would, while . % answered they probably would attend other sessions. given there were no negative responses, this could indicate a general acceptance of this form of online medical education. item six, 'virtual neurosurgical education can help to unify international neurosurgical knowledge', had participants consider whether this form of education can fill the global gap in education, particularly for developing countries where there are limited resources and those who cannot attend conferences in person due to cost or logistics ( figure ). most respondents either strongly agreed ( . %) or agreed ( . %). the seventh item, 'virtual neurosurgical education enhances the performance level of neurosurgeons', shifts the focus to the practical implications of online neurosurgical education ( figure ). while the majority strongly agreed ( . %) or agreed ( . %), some were undecided ( . %). this presents an interesting question as to exactly what components of this form of education lead to an improvement of neurosurgical skills. item eight, 'e-learning should take a more prominent role in neurosurgical education', inquired as to whether present neurosurgical education should place a greater emphasis on online education (figure ) . although most participants answered with strongly agree ( . %) and agree ( . %), this is the first instance where there was some disagreement ( . %). the final item, 'can you give specific examples of what you learned that you are going to take back to your practice to benefit patients?', asked respondents to write a short answer to demonstrate how their learning translated directly to their clinical practice. figure is a word cloud depicting the most commonly occurring words by respondents, while appendix shows the variety of responses by participants. it is important to note again that the questionnaire did not ask respondents about their level of neurosurgical training. in this study, we investigated how the experience of attending online neurosurgical conferences and training affects knowledge and skills acquisition. the questionnaire results indicate that respondents generally had a positive attitude toward online conferences and training and found neurosurgical online education to be useful. also, respondents noted they would attend other online neurosurgical education sessions in the future. most respondents agreed that online neurosurgical education can be beneficial for all levels of neurosurgeons and can help unify international neurosurgical knowledge. however, although most indicated that neurosurgeons' performance level is enhanced by online neurosurgical education, not all agreed that e-learning should take a more prominent role in neurosurgical education. regarding the extent to which neurosurgeons believe online training will directly benefit patients, short-answer responses included improvement of surgical skills and approaches, better case management and decision-making for their clinical practice, and a clearer understanding of relevant anatomy and pathology. the results indicate that there is a not only a positive attitude toward online neurosurgical education and direct benefits for neurosurgeons' clinical practice, but also that neurosurgeons agree this form of education may have wide-reaching possibilities for sharing knowledge. despite the small sample size, participants spanned countries, suggesting an interest in online neurosurgical education on a global scale. however, a question arises as to whether practitioners-especially those in developing countries-who cannot afford to attend physical conferences may also face challenges in accessing online content such as live feeds, streaming, or group conferences. the first limitation of this study is that given the length and scope of the questionnaire, additional factors could be investigated before drawing further conclusions. a further limitation is the anonymous nature of the questionnaire. while anonymity can increase the response rate, respondents cannot be contacted for follow-up regarding their responses. moreover, this study could not determine the respondents' level of neurosurgical training. while one neurosurgical online education platform was targeted in this study, this may not be representative of the entire population of neurosurgeons. future studies should consider similar research questions but explore different methods, such as standardized scales to gauge the attitude of neurosurgeons toward online education. additionally, a broader measurement may be needed to better understand the impact online neurosurgical education has on reducing the global education gap, particularly in developing countries. people around the world are increasingly sharing medical knowledge via the internet in the wake of covid- . to stay connected and to continue learning, online conferences reduce geographic barriers and minimize the effects of social isolation. to expand medical knowledge and advance neurosurgical education, we must better understand the effectiveness and forms of online content delivery. this study points to a consensus that online neurosurgical conferences and training can contribute to closing the gap in global neurosurgical education. further studies should look deeper into the impact of online neurosurgical education to suggest improvements for neurosurgical educators and all online medical education. in particular, it would be valuable to explore a variety of modalities with which online education reaches neurosurgeons and also how neurosurgeons access that information. human subjects: consent was obtained by all participants in this study. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other impact of formal continuing medical education: do conferences, workshops, rounds, and other traditional continuing education activities change physician behavior or health care outcomes? does online learning work better than offline learning in undergraduate medical education? a systematic review and meta-analysis a review of evaluation outcomes of web-based continuing medical education internet-based medical education: a realist review of what works, for whom and in what circumstances comparison of the instructional efficacy of internetbased cme with live interactive cme workshops: a randomized controlled trial the impact of cme on physician performance and patient health outcomes: an updated synthesis of systematic reviews a controlled trial of the effectiveness of internet continuing medical education effectiveness of continuing medical education learners' acceptance of a webinar for continuing medical education closed facebook™ groups and cme credit: a new format for continuing medical education multidisciplinary approach and outcomes of tele-neurology: a review telesurgery: past, present, and future . cureus students' perception, attitudes, and readiness toward online learning in dental education in saudi arabia: a cohort study attitude and use of elearning university students' attitudes towards e-learning: university of business & technology (ubt)-saudi arabia-jeddah: a case study a study of student's attitude towards virtual education in pakistan relationships: i am affiliated with an online neurosurgery training and conferencing platform called www.neurosurgical.tv. key: cord- -ev efm authors: fransawy alkomos, mina; aron, polina; laxina, ian; sanchez, jessimar; agnelli, michael title: covid- presenting as acute bilateral submassive pulmonary embolism in a young healthy female date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ev efm similar symptoms, signs, and laboratory abnormalities between coronavirus disease (covid- ) and pulmonary embolism (pe) creates a diagnostic challenge to every physician, and emerging data show an association between covid- , hypercoagulable state, and venous thromboembolism. we present a rare case of covid- presented as bilateral sub-massive pe. a -year-old covid- positive female with no significant past medical history presented with a dry cough and shortness of breath for three days. initial laboratory test showed elevated d-dimer, electrocardiogram (ekg) showed right axis deviation, right ventricular strain pattern, and s(i) q(iii) t(iii) pattern, and echocardiogram (echo) showed right ventricular dysfunction. those two bedside tests directed the urgency of chest ct angiography that showed bilateral sub-massive pe. since ekg finding of s(i) q(iii) t(iii) pattern and right ventricular strain, and echo finding of right ventricular dysfunction are well described in pe but not in covid- , these bedside diagnostic tools can help identify covid- patients with underlining pes. coronavirus disease (covid- ) (caused by the sars-cov- [severe acute respiratory syndrome coronavirus ] virus) was first reported in china in december of [ , ] . fever, dry cough, fatigue, shortness of breath, pleuritic chest pain, and elevated d-dimer were some of the commonly reported symptoms in two retrospective studies in china; these data overlap with pulmonary embolism (pe) clinical presentation and laboratory tests [ ] [ ] [ ] . electrocardiogram (ekg) and echocardiogram (echo) findings are uncommon but well reported in pe; however, they are not well reported in covid- cases [ , ] . since data is still emerging on covid- associated hypercoagulable status, venous thromboembolism, and pe [ ] [ ] [ ] , differentiating between covid- and pe based on clinical presentation and laboratory tests alone creates a diagnostic challenge for every clinician. with the aim of helping to develop a diagnostic algorithm, this case report points out the importance of utilizing ekg and echo in guiding the use of ct angiography (cta) in covid- patients suspected to have a pe. all patient information was de-identified. we present the case of a -year-old hispanic female with no significant past medical history who presented to the emergency department (ed) with a worsening dry cough and exertional shortness of breath of three days' duration. the patient presented to the ed a day prior with the same symptoms, and real-time reverse transcription-polymerase chain reaction assay for sars-cov- virus was collected, which later turned out to be positive. the patient was vitally stable and was sent home with instructions to return to the ed if the symptoms worsen. on the current presentation, the patient endorses progressive worsening of dry cough and shortness of breath on minimal exertion associated with generalized malaise and left-sided sharp chest pain that is aggravated by cough and deep inspiration. the patient denies fever, nasal congestion, sore throat, hemoptysis, recent travel, lower limb edema, recent surgery, immobilization, trauma, or hormonal therapy. however, the patient reported a family history of provoked deep venous thrombosis in her grandfather secondary to immobilization. on presentation, the patient had a body mass index of , was afebrile, and demonstrated normal blood pressure. the patient was hypoxic, saturating % on room air that improved to % on two liters nasal cannula, had a respiratory rate of breaths per minute, and was also tachycardic at beats per minute. her physical examination was remarkable for scattered crackles in bilateral lungs, with no lower limb edema or any other acute findings. laboratory tests were significant for a ddimer of . (normal range ≤ . μg/dl), elevated white blood cell count with neutrophilia and lymphopenia, elevated c-reactive protein, procalcitonin, and interleukin- , and negative factor v leiden ( table ) . white blood cell count, x /mm ekg showed sinus tachycardia with right axis deviation, right ventricular strain pattern (t wave inversion in the right pericardial leads v -v ), and s i q iii t iii (figure ). based on the ekg, echo findings, and the elevated d-dimer, the decision was made to perform cta of the chest. the test showed bilateral pe extending from the main pulmonary arteries into the segmental and peripheral branches (figure ). the patient was admitted to a negative pressure room, received intravenous tissue plasminogen activator (tpa), and was started on anticoagulation with heparin, azithromycin, and ceftriaxone for coverage of covid- associated pneumonia and community-acquired pneumonia. the patient was happy about the clinical progression of the condition and remained hemodynamically stable. the patient was discharged home after five days on non-vitamin k antagonist oral anticoagulants (noacs) to be continued for six months. covid- data are emerging daily. so far, infected patients were reported to have close symptoms of pe, including shortness of breath and pleuritic chest pain, as well as close laboratory abnormalities such as high d-dimer [ ] [ ] [ ] . covid- patients were also reported to be at risk of acute kidney injury; therefore cta in these patients is not encouraged [ , ] . ekg findings in pe are uncommon (less than %) but well reported as s i q iii t iii pattern, right ventricular strain, and new incomplete right bundle branch block [ ] . also, echo findings of right ventricular dysfunction were found in - % out of , patients diagnosed with pe [ ] . therefore, bedside test as ekg and echo can help to identify covid- patients with more likely associated pe. being conscious of the potential overlapping symptoms and laboratory abnormalities between covid- and pulmonary embolism are important for every clinician, as emerging data showed an association between covid- , hypercoagulable state, and venous thromboembolism. it will be harmful to perform a ct angiography on every covid- patients as they have a higher risk of acute kidney injury. therefore, utilizing a bedside diagnostic test like ekg and echo can help guide the need for cta to diagnose pe in covid- patients. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china. jama. clinical characteristics of coronavirus disease in china clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease prognostic value of the ecg on admission in patients with acute major pulmonary embolism findings from -lead electrocardiography that predict circulatory shock from pulmonary embolism: systematic review and meta-analysis acute pulmonary embolism and covid- pneumonia: a random association covid- pneumonia with hemoptysis: acute segmental pulmonary emboli associated with novel coronavirus infection covid- complicated by acute pulmonary embolism prognostic value of echocardiography and spiral computed tomography in patients with pulmonary embolism key: cord- - z tb ll authors: veerabathini, bala c; manthani, kaushik; gandhi, sandeep title: an unusual case of moraxella osleonsis bacteremia in an immunocompetent patient with sars-cov- infection date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: z tb ll moraxella osleonsis (m.osleonsis ) is an organism that rarely presents with bacteremia in immunocompetent patients. we report a case of an immunocompetent -year-old male with a recent sars-cov- infection that developed m.osleonsis bacteremia. we believe that sars-cov- infection may have played a role in developing m.osleonsis bacteremia in this patient and may be one of the first reported cases of such bacteremia in a covid- patient. the species moraxella osleonsis (m.osleonsis), first described in the literature in , consists of aerobic gram-negative oxidase-positive coccobacilli. in humans, species of the m.osleonsis were found to be inhabitants of the upper respiratory tract [ ] . this bacterium has been found in healthy adults' nasopharynx, nose, and oropharynx [ ] [ ] [ ] . however, individual reports of infection by this bacterium are rare and, as a result, m.osleonsis has been rarely studied for its clinical significance [ ] . it has been reported to cause the following infections: septic arthritis, vaginitis, endocarditis, bacteremia, meningitis, and sinusitis [ ] [ ] [ ] . the current coronavirus disease pandemic caused by the severe acute respiratory syndrome coronavirus (sars-cov- ) has emerged to be a cause for many ailments in humans. it is primarily known to affect the respiratory system but also causes cardiovascular disease, renal failure, and sequelae of a hypercoagulable state [ ] [ ] [ ] . being the first novel virus to have affected the human race in recent history, various mechanisms have been recently proposed to explain its effects. while the specific mechanisms are not fully understood, it is becoming more evident that a sars-cov- infection may be making humans more susceptible to various systemic diseases, including the possibility of causing rare bacteremia. a -year-old male with a past medical history of crohn's disease, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, bipolar disorder, and chronic back pain presented to the hospital with lethargy and vomiting. he had cough, nausea, vomiting and chronic back pain, but he denied chills, headaches, sore throat, diarrhea, loss of taste or smell, shortness of breath and muscle aches. of note, he had a recent hospitalization for covid- pneumonia two months prior where he was treated with ten days of hydroxychloroquine and he appeared well-nourished, cooperative, and in no acute distress. he was conscious, alert and oriented to person, place and time, but seemed lethargic. the physical exam was significant for poor dentition but otherwise unremarkable, including a benign abdominal exam and a nonfocal neurological examination. initial vitals are listed in table and pertinent lab results on admission are listed in table . covid- pcr test was positive for antigen and covid- igg antibody test was positive as well. urine toxicology was positive for benzodiazepines and cannabinoids. his initial infectious disease workup on day one was negative. on day two, one blood culture became positive for m.osleonsis and streptococcus species (salivarius, vestibularis). he was started on gram of intravenous ceftriaxone daily for days, and repeat blood cultures on day four revealed no growth. the following imaging studies were done. a chest x-ray showed no acute cardiopulmonary disease findings ( figure ) . ct of the chest showed mild right apical paraseptal and centrilobular emphysematous change and dependent atelectatic changes at lung bases ( figure ) . ct of the brain showed no acute intracranial hemorrhage or mass effect from vasogenic edema (figure ) . transthoracic echocardiogram showed no vegetations with a left ventricular ejection fraction of % ( figure ). leftwards facing red arrow shows the emphysematous changes. as mentioned, he continued intravenous ceftriaxone throughout his hospital stay. valproic acid was restarted on day three once the valproic acid level was therapeutic. his encephalopathy improved drastically over time and the patient was discharged on day six. on discharge, he was prescribed an eighth-day course of intravenous ceftriaxone for completion of the antibiotic regimen. dental evaluation, infectious disease, and psychiatry appointments were scheduled for outpatient follow-ups. polypharmacy and medication side effects are an important consideration when developing differentials for patient symptoms. this patient was taking several potent psychiatric medications, including valproic acid, clonazepam, trazodone, and olanzapine, which can cause lethargy, encephalopathy, and vomiting [ ] [ ] [ ] . despite normal kidney and liver function tests, hyperammonemia was present in this patient due to supratherapeutic valproic acid levels. symptoms of valproic acid toxicity can result in central nervous system depression, respiratory depression, metabolic abnormalities, nausea, vomiting, diarrhea, miosis, agitation, tremors, and myoclonus. symptoms of hyperammonemia can include vomiting, ataxia, behavioral changes, lethargy, somnolence, and coma [ ] . beyond medication-related encephalopathy, other etiologies were sought, including bacteremia, which was ultimately positive for rare bacteria: m.osleonsis. from to , the centers for disease control and prevention has received isolates that were later identified as m.osleonsis. the isolates consisted of specimens mostly from blood, cerebrospinal fluid, ear, nose, throat, urine, and genital secretions [ ] . as our patient was found to have poor dentition upon physical exam, this may be the site of entry for m.osleonsis bacteremia. while he did have lethargy, nausea, and vomiting, he did not present with other signs and symptoms that may present in bacteremia such as fever, chills, tachypnea, tachycardia, or increased white blood cell (wbc) count. this may be due to effective cephalosporin treatment in its early stages. [ ] [ ] [ ] [ ] . according to a study in wuhan, china, patients in the intensive care unit who were confirmed to have covid- pneumonia had considerably decreased cd + and cd + t cell levels [ , ] . another study also found decreased absolute numbers of t lymphocytes (cd + t cells, and cd + t cells) in both mild and severe cases of covid- pneumonia, but to a higher degree in the severe cases. cd + t cells and b cells were noted to be decreased with an increase in the cd +/cd + ratio in treated covid- patients and were associated with poor treatment outcome [ ] . cd + and cd + t cells play a crucial role in immune response against viral infections and may play a role in vaccine design and long-term immunity. cd + t cells release interferons (infγ), perforin, and granzymes to eliminate viruses, while cd + helper t cells enhance cd + cells and b cells to help them clear the viral pathogen [ ] [ ] ] . in a recent case report, this is illustrated in a covid- patient with diabetes mellitus, methicillin-sensitive staphylococcus aureus (mssa) bacteremia and osteomyelitis [ ] . cd + and cd + t cell functional exhaustion may explain the reason why the patient in that case report presented with recurrent bacteremia and multi-organ infection. despite aggressive antibiotic therapy, the patient remained with bacteremia and developed endocarditis with subsequent aortic root abscess [ ] . leukopenia was present in our patient which may be indicative of depleted t cells. unfortunately, the cd +/cd + t cell levels were not obtained for our patient, but it may suggest a way that sars-cov- infection could result in an immunosuppressed state and result in rare bacteremia, especially given that the patient was not taking any immunosuppressant medications or having immunocompromising conditions such as cancer or diabetes. current therapeutic treatments for covid- have included immune regulation and developing antibodies for vaccines. regulatory t cells (tregs) offer another alternative therapy. tregs are believed to be from the same lineage as cd + cells and may possibly be reduced in patients with covid- . tregs play a role in regulating or suppressing other cells in the immune system. according to current literature, the level of peripheral tregs is significantly reduced in severely affected covid- patients compared to mild disease. it has been hypothesized that tregs migrate to the lungs during tissue injury and cause peripheral reduction. reduction in the levels of tregs in the periphery could be associated with an overactive immune system, and in turn damaged lungs, in severely ill covid- patients. one team of scientists has proposed that cd +cd +foxp + regulatory t cell-based therapies may be beneficial. ex vivo transplantation of polyclonal tregs as well as allogeneic hla-matched umbilical cord-derived tregs have shown some positive results in covid- patients [ ] . particularly, two critically ill men with coronavirus who were treated with tregs from umbilical cord blood showed clinical improvements soon after their first infusion with tregs, to the point that they were able to be eventually extubated with subsequent tracheostomies in place [ ] . based on the currently published data, this is the first reported case of m.osleonsis bacteremia in a covid- positive patient. m.osleonsis has been shown to affect immunocompromised patients including those with lung cancer or kidney transplants, but rarely presents with bacteremia in immunocompetent patients. this raises the question of whether the presence of a recent sars-cov- infection (or the presence of current covid- antigen positivity) creates an immunocompromised state that predisposes patients to bacteremia. more studies will need to be done in order to understand those specific mechanisms of covid- that allow for bacterial translocation into circulation and developing bacteremia. current therapies for covid- have varied, and further understanding of t cell regulation in covid- patients may provide more robust treatments in the future. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. infection due to moraxella osloensis: case report and review of the literature distribution of species of moraxella and moraxella-like organisms in the nasopharynx of healthy human adults oxidase positive bacteria in the human nose incidence and species distribution, as diagnosed by 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and persistent cause of methicillin-sensitive staphylococcus aureus bacteremia characteristics of peripheral lymphocyte subset alteration in covid- pneumonia potential of regulatory t cellbased therapies in the management of severe covid- regulatory t cells tested in patients with covid- ards we would like to express our sincere gratitude to dr. andrew persits for providing guidance on the echocardiogram image. key: cord- -qmp tqtb authors: tahir, faryal; bin arif, taha; ahmed, jawad; malik, farheen; khalid, muhammad title: cardiac manifestations of coronavirus disease (covid- ): a comprehensive review date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: qmp tqtb since its origin in china, severe acute respiratory syndrome coronavirus (sars-cov- ) infection has become a pandemic and spread to countries. as coronavirus disease (covid- ) is a very rapidly emerging disease, organ-specific studies related to it have been reported. apart from respiratory findings, some studies have highlighted inflammatory consequences in the heart, kidney, and/or liver as well. cardiac involvement in covid- seems to be a result of an inflammatory storm in response to the infection. moreover, direct viral invasion of cardiomyocytes, as well as a myocardial injury due to oxidative stress, may account for acute cardiac injury in covid- . nevertheless, the mechanism of heart injury in covid- is not clear yet. however, multiple studies that highlight the clinical features, laboratory findings, and prognosis of acute myocardial injury (ami) in covid- -affected individuals have been published. in this review, we have summarized the findings of all those studies as well as the clinical features and management of cardiac injury discussed by some case reports. february , the coronavirus study group of the international committee on taxonomy of viruses named the new virus 'sars-cov- '. on march , the disease was declared a pandemic by the who [ ] . over the last three months, the disease has spread rapidly from cases to over . million cases worldwide [ ] . the basic reproduction number (r ) is an indicator of the transmissibility of a virus. it shows the expected number of new infections generated by an infected individual in a susceptible population. if r is more than , the number of new cases is likely to increase [ ] . the mean r for sars-cov- is . ( . - . ), which is comparable to sars, but the more widespread and rapid rise in the number of cases indicates higher transmissibility of sars-cov- [ ] . as covid- is a very rapidly emerging disease, new evidence and information are being reported daily. however, due to the emergence of such a large number of studies, disease-and organ-specific reviews are necessary to provide an updated and comprehensive summary of all literature for physicians who currently cannot spare their precious hours to go through vast online databases. hence, we searched pubmed, embase, scopus, google scholar, sciencedirect, wiley, and coronavirus collections of all major publishing groups to identify literature related to cardiac involvement in covid- . in this review, we summarize the cardiac manifestations of covid- and their prognoses. in december , people in wuhan, china, started visiting local hospitals with pneumonialike symptoms due to unknown causes. many of the index cases' history linked them to exposure to the huanan seafood wholesale market. china notified the who about the outbreak on december , , and closed the huanan market on january , , for cleaning and disinfection [ ] . on january , , scientists were able to isolate and identify the sequence of -ncov. all genome sequences from different patients were almost identical, indicating the recent emergence of disease in humans [ ] . since its origin in china, the sars-cov- infection has become a pandemic and spread to countries. according to the latest who covid- situation report (april , ), , , cases and a total of , deaths have been reported so far. an overwhelming number of , new deaths were reported in the last hours. the three countries with the highest number of cases (till april , ) are the united states, ( , ), spain ( , ), and italy ( , ) [ ] . an increase in percentage mortality over time has been observed in the who covid- status reports from january to april , ( figure ) [ ] . the x-axis shows the number of patients and y-axis shows the days covid- : coronavirus disease coronaviruses (covs) are a broad family of viruses that primarily affect the respiratory system. four genera of cov have been identified: alpha, beta, gamma, and delta. sars-cov- , a ribonucleic acid (rna) virus, belongs to subgenus sarbecovirus of the genus beta-cov. a total of six other covs that can infect humans have also been identified. other widely known members of the cov family that were identified earlier include sars-cov and the mers-cov, both belonging to the beta genus and capable of causing life-threatening respiratory infections. the other four are human coronavirus (hcov)- e, hcov-nl , hcov-hku , and hcov-oc , which cause milder disease [ , , ] . the gross structure of sars-cov- identified in patients in wuhan appeared spherical with some degree of pleomorphism on electron micrographs [ ] . the diameters of viral particles were between to nm and the size of spikes was about - nm, which appeared like a crown [ ] . the strain of sars-cov- is . kb [ ] . open reading frames (orfs) vary in number from - in the cov genome. the first orf has two-thirds of viral rna, which encodes for non-structural proteins and translates two polyproteins (pp a and pp b), while the structural and accessory proteins are encoded by other orfs. the four essential structural proteins include ( ) spike (s) glycoprotein, ( ) nucleocapsid (n) protein, ( ) matrix protein, and ( ) envelope (e) protein [ ] [ ] [ ] . sars-cov and mers-cov have genomes of . kb and . kb, respectively [ ] . the sars-cov- is more closely related to two sars-like covs derived from bats (bat-sl-covzc and bat-sl-covzxc ), with up to % similarity in identity, but distant from sars-cov and mers-cov (identity % and % respectively) [ , ] . this evidence suggests possible origin from bats [ ] . based on its origin and spread in the wuhan market, where there was an abundance of all sorts of animals, it is highly possible that covid- has a zoonotic origin and it transmitted to humans through an intermediate host [ ] . identification of sars-like covs in bats, which were similar to sars-cov- , shows the possibility that bats can be a reservoir host for its progenitor [ ] . it also indicates that mammals are likely to be a link between humans and covid- [ ] . based on recent research, there are two species of snake that could also be a possible reservoir for sars-cov- [ ] . however, no study has yet found any substantial evidence of a reservoir of sars-cov- other than birds and mammals. human-to-human transmission of sars-cov- is possible and accounts for the majority of cases now [ , , ] . sars-cov- is highly infective and transmission of the disease is through direct contact with an affected individual or through respiratory droplets produced by coughing or sneezing. there is recent evidence of possible vertical transmission from a mother to her newborn [ ] . a recent study by luo et al. has also shown that the virus is unlikely to be weakened in high temperatures and humidity and cluster transmission is possible even at conditions that were earlier thought to be unsuitable for viral transmission [ ] . the higher infectivity of sars-cov- can also be understood through its higher viability in the air as well as on different surfaces [ ] . sars-cov- can remain viable in air for more than three hours, and on plastic and steel for more than hours. on copper and cardboard, the viability of sars-cov- is less than four hours and hours, respectively [ ] . this high viability time period on different surfaces can lead to indirect transmission of sars-cov- to healthy individuals if they come into contact with objects used on covid- patients, such as stethoscope or thermometer [ ] . there have been no cases of fecal-oral transmission to date, and airborne transmission is possible in situations where there is aerosol production such as bronchoscopy, open suctioning, nebulization, tracheostomy, intubation, or cardiopulmonary resuscitation [ ] [ ] [ ] . aerosol generation from the fecal matter of affected individuals, such as by flushing toilets or treatment of excreta in rural areas, may cause viral spread [ ] . sars-cov- uses angiotensin-converting enzyme receptor (ace -r) for entry into the cells. s protein of the virus binds to ace -r. this binding causes a conformational change in s protein and leads to fusion of viral envelope with the host cell membrane, and sars-cov- rna is released into the host cell. genome rna is translated into polyproteins (pp a and pp b), which are further broken into proteinases. other viral proteins are produced by the translation of subgenomic messenger rna (mrna). in the endoplasmic reticulum (er) and golgi apparatus, the viral genome and proteins are assembled into virions. the newly formed virions are transferred to the cell membrane and released out of the cell [ ] . ace is found in the lower respiratory tract in humans, and the virus can be transmitted to the airway directly by respiratory droplets or touching of the nose after touching an infected surface [ , ] . initial clinical presentation of the disease is usually asymptomatic or mild with symptoms such as cough, sore throat, rhinorrhea, headache, fever, shortness of breath (sob), nausea, vomiting, diarrhea, and fatigue. in some patients, the disease can progress to pneumonia, respiratory failure, acute cardiac injury (aci), multi-organ failure (mof), and ultimately death [ , ] . a recently published study by huang et al. reported detailed symptoms of patients affected by covid- [ ] . symptoms at onset commonly included fever ( %), cough ( %), and myalgia/fatigue ( %). less common presenting symptoms were the production of sputum ( %), headache ( %), hemoptysis ( %), and diarrhea ( %). as the illness progressed, dyspnea, leukopenia, and lymphopenia developed in %, %, and % of the patients, respectively. all admitted patients developed pneumonia with bilateral pulmonary involvement (multiple consolidations and bilateral ground-glass opacity) visible on ct scan. a total of % of the admitted patients expired. complications developed by patients included acute respiratory distress syndrome (ards) ( %), rnaaemia ( %), aci ( %), secondary infection ( %), and complications requiring intensive care unit (icu) admissions ( %) [ ] . level of inflammatory chemokines and cytokines such as interleukin (il) -β, il ra, il , il , il , il , basic fibroblast growth factor (bfgf ), granulocyte-colony stimulating factor (gcsf), granulocyte-macrophage colony-stimulating factor (gm-csf), interferon-gamma (ifnγ), interferon-inducible protein (ip ), monocyte chemoattractant protein- (mcp ), macrophage inflammatory proteins (mip) α, mip β, platelet-derived growth factor subunit b (pdgfb), tumor necrosis factor-alpha (tnfα), and vascular endothelial growth factor a (vegfa) were elevated in both icu and non-icu patients [ ] . pro-inflammatory cytokines, namely il , il , il , gcsf, ip , mcp , mip a, and tnfα, were only elevated in icu patients, suggesting a possible association with increased disease severity [ ] . covid- can lead to cardiac involvement and injury via the following possible mechanisms: ( ) indirect injury due to increased cytokines and immune-inflammatory response, ( ) direct invasion of cardiomyocytes by sars-cov- , and ( ) respiratory damage from the virus causing hypoxia leading to oxidative stress and injury to cardiomyocytes [ ] [ ] [ ] . these mechanisms are graphically represented in figure , which is adapted from [ ] . along with the presence of ace in the respiratory tract, it is also found in the heart, and sars-cov- can use ace to enter the cells [ , ] . the mechanism of heart injury in covid- is still not entirely clear, i.e., it is unclear as to whether binding of sars-cov- alters the expression of ace or causes abnormality in the regulation of the renin-angiotensinaldosterone system (raas) [ ] . however, multiple studies analyzing acute myocardial injury (ami) in covid- -affected individuals have been published. ami was detected by high levels of serum c-reactive protein (crp), creatine kinase (ck), and troponins. affected individuals often had a history of chronic diseases such as diabetes, chronic obstructive pulmonary disease (copd), hypertension, and coronary artery disease (cad). ami was also associated with a longer hospital stay [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . critically ill patients had a higher likelihood of myocardial injury, which was associated with poor outcomes and an increased risk of in-hospital mortality [ , , , ]. multiple studies that highlight the clinical features, laboratory findings, and prognosis of ami in covid- -affected individuals have been published so far. these studies are discussed below. in a single-center retrospective case series, wang et al. delineated the epidemiological and clinical characteristics of novel coronavirus-infected pneumonia (ncip) among consecutively hospitalized patients at zhongnan hospital, wuhan [ ] . epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected from january to , . the authors then compared the outcomes of critically ill and non-critically ill patients. among all the patients, . % (n= ) were male with a median age of years. comorbidities were found in . % (n= ) of the patients, among whom cardiovascular disease (cvd) was appreciated in . % (n= ). among all the icu-bound patients (n= ), % (n= ) were reported to have cardiovascular comorbidity. the median heart rate (hr) of all patients and those in the icu was found to be beats per minute (bpm) and bpm, respectively. similarly, the mean arterial pressure (map) of all patients and patients bound to icu was recorded as mmhg and mmhg, respectively. aci was appreciated in . % (n= ), . % (n= ), and % (n= ) in all, icu bound, and non-icu-bound (n= ) patients, respectively (p< . ). furthermore, arrhythmia was found in . % (n= ), . % (n= ), and . % (n= ) in all, icu-bound, and non-icu-bound patients, respectively (p< . ). to recapitulate, the authors established a mortality rate of . % [ ] . huang et al. investigated the clinical features of patients infected with -ncov in wuhan, china [ ] . out of a total hospital-admitted patients identified as having laboratoryconfirmed covid- , the majority (n= , %) were men and less than half had underlying comorbidities such as diabetes (n= , %), hypertension (n= , %), and cvd (n= , %). the median age was years. aci (n= , %) was the third most common complication in these patients after ards and rnaemia. out of patients admitted to icu, four ( %) had an aci and five died. the study concluded that severe respiratory illness with n-cov infection with deteriorating complications was associated with icu admission and a higher mortality rate [ ] . zhang et al. retrospectively evaluated the clinical characteristics of hospitalized patients who died of covid- from january to february , , in the renmin hospital, wuhan [ ] . in this study, the majority of the deceased patients were male ( . %, n= ), with a higher mortality rate found among older individuals. significantly, . % (n= ) of non-survivors were > years of age. a major bulk ( . %, n= ) of the deceased individuals had some existing comorbidity, and among them, . % (n= ) had heart disease. cardiac damage was found in % (n= ) of patients, while cardiac failure (cf) ( . %, n= ) was the third most common cause of death after acute respiratory failure (arf) ( . %, n= ) and sepsis syndrome/mof ( %, n= ). along with other abnormal laboratory findings, levels of crp (> u/l), cardiac troponin t (tnt, > . pg/ml), ck (> u/l), myoglobin (> μg/l), lactate dehydrogenase (ldh, > u/l) and creatine kinase myocardial band (ck-mb, > ng/ml) were found to be much higher in % (n= ), . % (n= ), . % (n= ), % (n= ), % (n= ), and % (n= ) of the deceased cases, respectively. the authors concluded that either the virus itself or the storm of released cytokines in its response might have aggravated damage to vital organs, including the heart [ ] . in a retrospective, single-center study of medical records, hui et al. investigated the correlation between clinical features and aci among patients affected with covid- pneumonia [ ] . in this study, records of consecutive cases of covid- ( males and females) from beijing youan hospital in china between january and february , , were studied, including two deaths. in view of the th guidance provided by the national health commission of china, . % (n= ), . % (n= ), . % (n= ), and . % (n= ) of the patients were labeled as light, mild, severe, and critical cases, respectively. the median age of the patients was found to be years, and adult males were found more prone to develop a severe infection. underlying comorbidities such as hypertension, cad, diabetes mellitus (dm) type , and tumor were found in . % (n= ) of the patients, while severe and critical cases were notably substantial in the cardiac-related chronic disease group. moreover, as compared to the normal value of troponin i (tni), a -fold increase in its peak value and a higher crp level ( mg/l) was recorded among critical patients, which translated into a higher risk of cardiac injury. atrial fibrillation (afib) with hr inclining up to bpm was recognized in . % (n= ) of patients; all of them were under critical category and eventually died. reduced epicardial adipose tissue (eat) density was shown on the ct scans of severe (- . hu) and critical (- . hu) cases, indicating cardiac inflammation. the authors concluded that patients under light and mild categories rarely exhibited cardiac injury, whereas it was found more commonly among severe and critical patients, where tachycardia, elevated levels of tni, and low eat density were regarded as the main risk factors. to intercept fatality among covid- patients, the authors suggested close monitoring of the cardiac functioning of all patients, especially the severe and critical ones, and to seek possible interventions for patients evincing features of abnormal cardiac injury [ ] . wu et al. conducted a single-center retrospective cohort study to explore whether heart injury occurs in covid- and if it aggravates mortality later [ ] . among patients with covid- , the mean age was . years (range: - years) and ( . %) were male. older patients and patients with comorbidity (especially hypertension) tended to have increased highsensitivity troponin i (hs-tni) levels on admission, and a high mortality rate was associated with high hs-tni on admission (≥ . pg/ml). further, it was noticed that high hs-tni levels were associated with increased inflammatory levels [neutrophils, il- , crp, procalcitonin (pct)] and decreased immune levels [lymphocytes, monocytes, cluster of differentiation (cd) +, and cd + t cells]. raised ck-mb levels tended to occur only in male patients and current smokers and were associated with higher mortality, increased inflammatory levels, and decreased lymphocytes. similarly, increased ldh and α-hydroxybutyrate dehydrogenase (α-hbdh) tended to occur in older and hypertensive patients and were associated with higher mortality rates, increased inflammatory, and decreased immune levels. subsequently, hs-tni (p= . ) and ldh levels (p= . ) on admission day were negatively correlated with survival days. hence, it was concluded that heart injury signs arise in covid- , especially in older patients, hypertensives, and male patients with current smoking habits. elevated levels of heart injury indicators are associated with higher mortality and shorter survival days. the authors suggested that covid- might attack the heart by inducing an inflammatory storm and patients with signs of heart injury must be identified primarily and carefully treated by cardiologists [ ] . to investigate the clinical characteristics and eventual prognosis of covid- patients with already existing cvd, peng et al. retrospectively analyzed patients who visited the union hospital (wuhan) from january to february , [ ] . depending on the clinical severity of the disease, all the patients were grouped into two categories: critical (n= ) and general (n= ). in comparison with the general group, lymphocyte count [ . × /l ( . [ ( - ) ] was found to be much lower in the same category. keeping in view either the critical and general groups or the survivor and non-survivor groups, medication with ace inhibitor and angiotensin receptor blocker (arb) did not impact the morbidity and mortality related to covid- in patients with any preexisting cardiac disease. hence, the authors concluded that a higher risk of mortality existed among covid- patients with already existing cardiac disease/s where fulminant inflammation, lactic acid accumulation, and thrombotic events are regarded as the main exacerbating factors [ ] . a cross-sectional study by chen et al. evaluated the cardiovascular damage in patients with covid- [ ] . a total of covid- cases were included from tongji hospital (wuhan) and the patients were divided into groups of mild cases (n= ) and critical care cases (n= ). age, hypersensitive crp (hs-crp), and serum creatinine levels of the patients were observed to be higher in critical care cases than in mild cases (all p< . ). critical care patients had a higher prevalence of males, elevated n-terminal pro-b-type natriuretic peptide (nt-probnp) and cardiac troponin i (ctni), hypertension, and coronary heart disease (chd) (all p< . ). elevated ctni [odds ratio (or): . , % ci: . - . , p= . ] and chd (or: . , % ci: . - . , p= . ) were found to be the independent risk factors of critical disease status according to multivariate logistic regression analysis. the authors concluded that covid- could significantly affect heart function and lead to myocardial injury. the two crucial independent determinants of clinical disease status in patients with covid- were the past medical history of chd and an increased level of ctni [ ] . xu et al. investigated the clinical characteristics and risk factors of ami in covid- patients [ ] . a total of consecutive laboratory-confirmed and hospitalized covid- patients were included in the study. out of ( . %) patients with cardiac complications, the majority (n= ) had elevated cardiac enzymes followed by diastolic dysfunction (n= ), tachycardia (n= ), electrocardiography abnormalities (n= ), and ami (n= ). all patients with ami were aged > years, and five of them also had two or more comorbidities (hypertension, diabetes, cvd, and copd). furthermore, it was noticed that the severity of novel coronavirus pneumonia (ncp) was higher in these patients than in patients with non-definite ami (p< . ). three of these ami patients died while two remained hospitalized in the icu. covid- patients with ami had higher mean systolic pressure than other groups (p< . ). according to multivariate analysis, the major risk factor for cardiac abnormalities in covid- patients were elevated crp levels (p< . , or: . ; % ci%: . - . ), ncp severity (p< . , or: . ; % ci: . - . ), and underlying comorbidities (p< . , or: . ; % ci: . - . ). the occurrence of hypertension was higher in the ami group (n= , . %). similarly, cvd was more frequently found in ami patients (n= , . %), all of whom had a history of cad with one having prior coronary artery bypass grafting (cabg). other comorbidities like diabetes and copd were found in all patients with a significant occurrence in ami patients (diabetes: n= ; copd: n= ) compared to other groups. about covid- patients exhibited elevated cardiac markers; out of them, ami and non-definite ami patients had higher cardiac markers than other groups (p< . ). d-dimer levels on admission were also elevated in the ami patients (median= . µg/ml) and patients with abnormal cardiac markers (median= . µg/ml), and were subsequently higher than those in patients with normal cardiac markers (median= . µg/ml; p< . ). among patients exhibiting echo abnormalities, a higher frequency was found in ami patients, manifesting as left ventricular (lv) wall thickening and diastolic dysfunction, left atrial enlargement, lv enlargement, and mitral, aortic and triple valve regurgitation [ ] . liu et al. conducted a single-center retrospective study to analyze the association of cardiovascular manifestations with in-hospital outcomes of covid- cases [ ] . case details of consecutive hospitalized health staff with confirmed covid- were collected at the central hospital of wuhan, china. the mean age of the population was . ± . years. about ( . %) cases had cardiovascular manifestation (cvm). patients with cvm had comparatively lower baseline lymphocyte count (p< . ), had more incidence of positive nucleic acid detection of throat swab (p= . ) and received more oxygen support (p< . ). similarly, the rate of in-hospital effects was significantly higher in the cvm group (p= . ). multivariate logistic regression analysis indicated that the coexistence of cvm and ncp was not independently associated with in-hospital adverse effects (or: . , % ci: . - . , p= . ). however, a tendency of significance was noticed in baseline lymphocyte count between the two groups in the model (or: . , % ci: . - . , p= . ) [ ] . he et al. analyzed the clinical characteristics of severe or critically ill patients with covid- and evaluated the impact of the complicated myocardial injury on the prognosis of these patients [ ] . fifty-four patients who met the criteria of severe or critical conditions of covid- were included in this retrospective study. the median age of patients was ; ( . %) patients had hypertension, ( . %) had diabetes, eight ( . %) had chd, and three ( . %) had previous cerebral infarction. it was noticed that ( . %) patients were complicated with myocardial injury and ( . %) patients died during the hospital stay. patients with myocardial injury had higher in-hospital mortality rates than those without myocardial injury (n= , . % with myocardial injury vs. n= , . % without myocardial injury, p= . ). moreover, patients with significant myocardial injury exhibited significantly higher levels of crp ( . ng/l vs. . ng/l) and nt-probnp ( . ng/l vs. . ng/l) than patients without myocardial injury (all p< . ). this study postulated that severe or critically ill covid- patients have a higher prevalence of myocardial injury, and these patients face a significantly higher risk of in-hospital mortality. hence, it is vital to monitor and manage the myocardial injury during hospitalization for severe or critically ill covid- patients [ ] . in another retrospective comparison of the clinical features of recovered versus deceased patients with covid- , deng et al. collected data from two hospitals in wuhan [ ] . out of the total enrolled covid- patients, died during hospitalization, whereas recovered. the median age was higher in the deceased group as compared to the recovered group ( years vs. years, p< . ). levels of creatinine ( . μmol/l vs. . μmol/l, p< . ) and crp ( . mg/l vs. . mg/l, p < . ) were found to be significantly higher in the deceased group versus the recovered one. complications were recorded to be higher among the deceased group in which aci ( . % vs. . %, p< . ) was found to be much higher as compared to the recovered group [ ] . to investigate the epidemiological and clinical features of patients infected with covid- and cardiac injury, liu et al. collected and analyzed data of medical records from january to february , [ ] . among patients from guangzhou eighth people's hospital, . % (n= ) had a cardiac injury. patients with cardiac injury were comparatively older than those without injury; the median age was found to be years. there was a male predominance among cardiac injury patients, as . % (n= / ) of them were male. hypertension ( . %, n= ) and chd ( %, n= ) were the most predominant comorbidities among individuals presenting with a cardiac injury. moreover, common symptoms of covid- like fever ( . %, n= ), cough ( . %, n= ), headache or fatigue ( . %, n= ), and dyspnea ( . %, n= ) without any complaints of chest pain and palpitations were appreciated in this group. patients who had cardiac injury showed relatively higher systolic blood pressure (bp) ( mmhg vs. mmhg), tni ( . ug/l vs. . ug/l), and bnp ( . pg/ml vs. . pg/ml) levels when compared with those without cardiac injury. nevertheless, the levels of crp were found to be raised among all patients with cardiac injury (n= / ). among all the enrolled patients, ards ( %, n= ) and severe pneumonia ( . %, n= ) were reported more commonly in cases with a cardiac injury, which complicated the disease. the authors concluded that cardiac injury can be commonly found among patients with covid- , where it worsens the clinical outcomes and, hence, should be regarded as a potential prognostic risk indicator [ ] . zhou et al. studied the clinical characteristics of myocardial injury in patients with covid- [ ] . a total of patients with covid- were included in this study who were further divided into two groups: patients with severe covid- (n= ) and those with very severe covid- (n= ). the median age was years in the severe covid- group and years in the very severe group. the authors noted significantly increased ctni ( . ng/l vs. . ng/l), ck ( u/l vs. u/l), α-hbdh ( u/l vs. u/l), and ldh ( u/l vs. u/l) in the very severe group as compared to the severe group. the percentage of very severe patients with elevated ctni levels was markedly higher as all eight patients with very severe disease exhibited increased ctni while only one patient with severe disease had raised ctni levels (p< . ). this study concluded that patients with very severe covid- have a higher percentage of increased ctni levels and their mortality rate can be improved by protecting them from myocardial injury [ ] . to explore the association between cardiac injury and mortality in patients with covid- , shi et al. conducted a single-center cohort study at renmin hospital of wuhan university, china [ ] . they included a total of hospitalized patients with covid- in the final analysis, with a median age of years. about patients ( . %) were declared to have a cardiac injury. in comparison with patients without cardiac injury, these individuals were older (p< . ), had more comorbidities such as hypertension (p< . ), had higher leukocyte counts (median: , ) and higher levels of crp (median: . ), pct (median: . ), ck-mb (median: . ), myohemoglobin (median: ), hs-tni (median: . ), nt-probnp (median: , ), aspartate aminotransferase (ast, median: ), and creatinine (median: . ), and had a higher proportion of multiple mottling and ground-glass opacity in radiographic findings ( . %). patients with cardiac injury required a greater proportion of non-invasive mechanical ventilation (p< . ) or invasive mechanical ventilation (p< . ). similarly, complications like ards (p< . ), acute kidney injury (aki, p< . ), electrolyte disturbances (p= . ), hypoproteinemia (p= . ), and coagulation disorders (p= . ) were higher in patients with a cardiac injury. a higher mortality rate (p< . ) was noticed in patients with cardiac injury ( . %) than those without cardiac injury ( . %). additionally, patients with cardiac injury were at a higher risk of death, both during the time from onset of symptoms (hr: . , % ci: . - . ) and from admission to endpoint (hr: . , % ci: . - . ) according to cox regression model. the study concluded that cardiac injury is a prevalent condition among hospitalized patients with covid- in wuhan, china, and it is associated with a higher risk of in-hospital mortality [ ] . in order to depict the clinical characteristics of deceased patients owing to covid- infection, chen et al. retrospectively evaluated a case series among a cohort of confirmed cases of covid- admitted to tongji hospital from january to february , [ ] . in comparison with the recovered cases, deceased patients were mostly male ( %, n= ) with a median age of years. among all those who died, chronic hypertension ( %, n= ) and other cardiovascular abnormalities ( %, n= ) were the predominant comorbidities. vital signs revealed higher median systolic bp ( mm hg), arterial pressure (≥ mm hg), and hr ( . bpm) among deceased patients. apart from other abnormal laboratory findings, considerably higher levels of crp, ck, ldh, ctni ( . pg/ml), and nt-probnp ( pg/ml) were appreciated among the deceased patients. moreover, eight deceased patients exhibited more than , pg/ml ctni whereas two of them had more than , pg/ml. the disease was more frequently complicated among the deceased patients with the occurrence of aci (n= / ) and hf (n= / ) in % and % of the individuals, respectively. it was also observed that individuals with cardiovascular comorbidity were more susceptible to the development of cardiac complications. however, cardiac injury and hf were still more common among deceased patients as compared to the recovered ones, regardless of any history of cardiac disease. the authors concluded that aci and hf were among the most common complications that affected the prognosis of critically ill patients [ ] . to evaluate the association of underlying cvd and myocardial injury with fatal outcomes in patients with covid- , guo et al. conducted a retrospective single-center study [ ] . a total of patients with confirmed covid- were selected, and their demographic data, laboratory findings, comorbidities, and treatments were analyzed regardless of elevation in tnt levels. overall, ( . %) patients had underlying cvd manifested as hypertension, chd, and cardiomyopathy, while ( . %) patients exhibited myocardial injury as indicated by elevated tnt levels. patients with cvd and elevated tnt levels had a higher mortality rate ( . %) than other groups, i.e., patients without underlying cvd and normal tnt ( . %), patients with underlying cvd and normal tnt ( . %), and patients without underlying cvd but elevated tnt ( . %). similarly, patients with underlying cvd were more likely to present with elevated tnt than those without cvd ( . % vs. . %). plasma tnt levels depicted a significantly positive linear correlation with plasma hs-crp (β= . , p< . ) and nt-probnp levels (β= . , p< . ). similarly, plasma tnt and nt-probnp levels elevated significantly during hospitalization (median: . for plasma tnt; median: , for plasma nt-probnb) and indicated impending death (median: . for serum tnt; median: , for serum nt-probnp) as compared with admission values (median: . for serum tnt; median: . for serum nt-probnp) in the patients who died. however, no significant changes in tnt and nt-probnp were observed in survivors. patients with elevated tnt developed frequent malignant arrhythmias and required more glucocorticoids ( . % vs. . %) and mechanical ventilation ( . % vs. . %) as compared to those with normal tnt levels. the mortality rate of patients with and without the usage of acei or arb was . % and . %, respectively. these observations concluded that there is a significant association between myocardial injury and fatal outcome of covid- while the patients with underlying cvd without myocardial injury have a relatively favorable prognosis [ ] . figure provides a summarized flowchart of all studies discussed above [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] ]. a few case reports have also depicted the distinctive involvement of the cardiovascular system in covid- infection. the first case to report the cvm of covid- was presented by zeng et al. [ ] . the article highlighted fulminant myocarditis as a complication of covid- in a year-old patient with no known comorbidity, who presented with fever, cough, dyspnea, and chest tightness. during hospitalization, myocardial enzymes showed elevated tni ( . g/l), myoglobin ( . ng/ml), and nt-probnp ( , pg/ml). electrocardiogram (ecg) showed sinus tachycardia with no st-segment elevation. however, an enlarged lv ( mm), diffuse myocardial dyskinesia along with low left ventricular ejection fraction (lvef, %), pulmonary hypertension ( mmhg), and decreased inferior vena cava (ivc) collapse rate were noticed on bedside echocardiography. severe pneumonia, ards, fulminant myocarditis, and multiple organ dysfunction syndrome (mods) were considered as differentials. there was no improvement in the patient's condition with supportive treatment. the ventricular septum thickened to mm, and il- increased by . pg/ml. extracorporeal membrane oxygenation (ecmo) was used to reduce the cardiopulmonary burden, which showed a reduction in tni ( . g/l), nt-probnp ( pg/ml), and il- ( . pg/ml). the lvef gradually recovered to %, and the lv and wall regained their normal thickness after treatment [ ] . inciardi et al. highlighted cardiac involvement as a complication of covid- without symptoms and signs of interstitial pneumonia in a -year-old patient [ ] . ecg of this patient showed diffuse st elevation. elevated hs-tnt and nt-probnp levels were also detected. findings on chest radiography were normal. cardiac mri showed increased wall thickness with diffuse biventricular hypokinesis, predominantly in the apical segments, and severe lv dysfunction (lvef of %). short tau inversion recovery (stir) and t -mapping sequences depicted marked biventricular myocardial interstitial edema and a diffuse late gadolinium enhancement involving the entire biventricular wall. a circumferential pericardial effusion, especially around the right cardiac chambers, was also observed. these findings were consistent with acute myopericarditis, and the patient was treated with dobutamine, antiviral drugs, steroids, chloroquine, and medical treatment for hf, with progressive clinical and instrumental stabilization [ ] . similarly, bilateral pericardial and pleural effusion as a complication of covid- infection has been reported by albarello et al. [ ] . -ncov infection may also involve other organs like heart, vessels, liver, and kidney, as demonstrated by yao et al. [ ] . the minimal invasive autopsies in three covid- cases revealed degeneration and necrosis of parenchymal cells, the formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases in other organs and tissues, while no evidence of coronavirus infection was observed in these organs. the authors suggested conducting further studies to investigate the mechanism of underlying extra-pulmonary pathological changes of this disease [ ] . further, cui et al. highlighted multiple organ damage and rapid disease changes in a -day-old infant diagnosed with covid- pneumonia [ ] . laboratory investigations on the day of admission revealed mildly abnormal myocardial zymogens with altered liver function tests (lfts). with the deterioration of the patient's condition, an increase in tni ( . μg/l) was noticed, which indicated myocardial injury. intravenous sodium creatine phosphate was added to her regimen for the protection of her heart. later, the myocardial zymogen and liver function improved with supportive treatment, and the patient was discharged [ ] . a summary of all the important findings of the aforementioned case reports is given in table . female acute myocardial inflammation in a covid- patient who recovered from the influenza-like syndrome and developed fatigue and signs and symptoms of heart failure a week after upper respiratory tract symptoms albarello et al. [ ] we can conclude that aci is common in covid- , especially among adult males, where it is regarded as a potential prognostic risk indicator. higher levels of cytokines, il, cardiac injury markers such as troponin and ck, and crp are usually appreciated in these patients. consequently, myocarditis, ventricular dysfunction with or without pericardial effusion, and subsequently, hf cumulatively increase the mortality rate. hence, careful monitoring and immediate management plan to avoid or treat cardiac injuries are vital to achieving a decline in the number of deaths due to hf secondary to covid- . aci: acute cardiac injury; icu: intensive care unit; covid- : coronavirus disease ; chd: coronary heart disease; ctni: cardiac troponin i; cvms: cardiovascular manifestations; cvd: cardiovascular disease; acei: angiotensin-converting enzyme inhibitors; arbs: angiotensin receptor blockers; crp: c-reactive protein references . timeline of plague a novel coronavirus from patients with pneumonia in china covid- ) situation reports the reproductive number of covid- is higher compared to sars coronavirus genomic characterisation and epidemiology of novel coronavirus: implications for virus origins and receptor binding mers, sars and other coronaviruses as causes of pneumonia a new coronavirus associated with human respiratory disease in china from sars to mers, thrusting coronaviruses into the spotlight origin and evolution of pathogenic coronaviruses the origin, transmission and clinical therapies on coronavirus disease (covid- ) outbreak -an update on the status sars and mers: recent insights into emerging coronaviruses the proximal origin of sars-cov- the epidemiology and pathogenesis of coronavirus disease (covid- ) outbreak cross-species transmission of the newly identified coronavirus -ncov possible vertical transmission of sars-cov- from an infected mother to her newborn (epub ahead of print) possible transmission of severe acute respiratory syndrome coronavirus (sars-cov- who: modes of transmission of virus causing covid- : implications for ipc precaution recommendations -scientific brief covid- among medical personnel in the operating room (epub ahead of print) reducing hand recontamination of health workers during covid- (epub ahead of print) alert for sars-cov- infection caused by fecal aerosols in rural areas in china (epub ahead of print) covid- infection: origin, transmission, and characteristics of human coronaviruses epidemiological and clinical characteristics of cases of china: a descriptive study clinical features of patients infected with novel coronavirus in wuhan, china. lancet. epidemiologic features and clinical course of patients infected with sars-cov- in singapore (epub ahead of print) pathological findings of covid- associated with acute respiratory distress syndrome the cardiovascular burden of coronavirus disease (covid- ) with a focus on congenital heart disease ace receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china. jama. clinical characteristics of death cases with covid- (in press). medrxiv. , accessed clinical and radiographic features of cardiac injury in patients with novel coronavirus pneumonia (in press). medrxiv. , accessed heart injury signs are associated with higher and earlier mortality in coronavirus disease clinical characteristics and outcomes of cardiovascular disease patients infected by -ncov. 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(article in chinese) a -day-old female infant infected with covid : presenting with pneumonia, liver injury, and heart damage (epub ahead of print) in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. inciardi et al. [ ] key: cord- -p okfa b authors: flores, gabriel; kumar, jay i; pressman, elliot; sack, jayson; alikhani, puya title: spontaneous brainstem hemorrhagic stroke in the setting of novel coronavirus disease – a case report date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: p okfa b coronavirus disease (covid- ) is caused by severe acute respiratory syndrome coronavirus (sars-cov- ) and has become a global pandemic. this disease has been shown to affect various organ systems, including the cerebrovascular system with sequelae still not completely uncovered. we present an unusual case of extensive brainstem intraparenchymal hemorrhage in a patient with covid- to caution readers of this possible complication in patients positive for covid- . in this report, we outline the clinical presentation of a -year-old male who developed severe coughing and sneezing before presenting to the emergency department with confusion, somnolence, and respiratory distress. ct head without contrast revealed extensive pontine and midbrain hemorrhage with intraventricular extension and early hydrocephalus. neurological examination revealed pinpoint, minimally reactive pupils, withdrawal to painful stimuli in the right hemibody, left hemibody paresis, and intact left corneal, cough, and gag reflexes. mri and mra brain revealed no evidence of an underlying vascular lesion. over the next two days, the patient had worsening multiorgan failure and hypoxemia without intracranial hypertension. he remained too unstable to undergo cerebral angiogram. on hospital day four, his neurological examination deteriorated to quadriparesis and only cough and gag reflexes remaining intact after which his family opted for comfort measures only. in summary, a potential increased risk of intracerebral hemorrhage adds to the complexity of management of patients with covid- . this is especially true in those who have violent sneezing or coughing, or those who are on anticoagulation or antiplatelet therapy. since initial reports in december from wuhan, china, the coronavirus disease (covid- ) caused by severe acute respiratory syndrome coronavirus two (sars-cov- ) has become a global pandemic. while primarily a respiratory disease, sars-cov- is also known to affect multiple disparate organ systems, including the cerebrovascular system, however, this is typically in the setting of an ischemic event [ ] . some case reports have been published so far about hemorrhages in the cerebrovascular system in the setting of other risk factors, however to our knowledge, there are no reports on patients with hemorrhage in the absence of risk factors [ ] [ ] [ ] [ ] [ ] [ ] [ ] . we present a unique case of extensive brainstem intraparenchymal hemorrhage in a patient with covid- to caution readers of this possible complication during this pandemic, even in patients without prior risk factors for hemorrhage. our patient is a -year-old male with past medical history of obesity, hypertension, and type two diabetes mellitus who developed severe coughing and sneezing before presenting to the emergency department with confusion, somnolence, and respiratory distress. he was hypertensive ( / mmhg) with tachycardia and oxygen saturation (sao ) of %. he was intubated for respiratory protection. a ct head without contrast revealed extensive pontine and midbrain hemorrhage with intraventricular extension into the third and fourth ventricles with early hydrocephalus (figure ) . he underwent emergent transfer to our tertiary center for neurosurgical evaluation. neurological examination revealed pinpoint, minimally reactive pupils, withdrawal to painful stimuli in the right hemibody, left hemibody paresis, and intact left corneal, cough, and gag reflexes (glasgow coma scale eyes one, verbal zero, motor four). an external ventricular drain was placed with an opening intracranial pressure (icp) of mmhg. a chest radiograph revealed bilateral pulmonary congestion, infiltrates, and cardiomegaly. sao remained at % on % o . chest radiograph revealed bilateral pulmonary congestion, infiltrates, and cardiomegaly. initial labs were notable for elevated inflammatory markers and d-dimer. per our hospital's covid- protocol, the patient was placed in a negative pressure room, and a sar-cov- rapid polymerase chain reaction (pcr) test returned positive. exposed personnel followed the hospital's exposure protocol for testing and self-isolation in accordance with centers for disease control recommendations. mri brain with and without contrast and mra brain without contrast revealed no evidence of an underlying vascular lesion ( figure ). on hospital day two, the patient had worsening respiratory distress with multi-organ failure. the patient did not qualify for remdesivir or convalescent plasma treatment by the hospital's protocol. over the next two days, the patient had worsening multiorgan failure and hypoxemia without intracranial hypertension. he remained too unstable to undergo cerebral angiogram for further evaluation. on hospital day four, his neurological examination deteriorated to a glasgow coma scale of three with only cough and gag reflexes remaining intact. the family was counseled and opted for comfort measures only. this report demonstrates the potential for intracranial hemorrhage in patients with covid- despite no apparent bleeding diathesis. the strength of this report lies in its novelty and in our patient's lack of previously associated risk factors or provocative factors for intracranial hemorrhage such as hypertensive emergency, anti-coagulation medication use, or anti-platelet medication use, though our patient was obese and had diagnosed diabetes mellitus. the main limitation in this report was our inability to obtain a diagnostic cerebral angiogram to further evaluate the patient's vascular pathology. neurological complications are not uncommon in patients with covid- [ ] . due to concern for systemic small vessel thrombosis, many covid- patients have been anti-coagulated, increasing risk of cerebral hemorrhage [ ] . another study reported intracerebral hemorrhage in patients ( were on anticoagulation, three on antiplatelets, two with thrombocytopenia and one with idiopathic systemic hemorrhage) [ ] . intracerebral hemorrhage without a bleeding diathesis has been reported only rarely in covid- patients [ ] . one was a -year-old man who did not receive anticoagulants and had normal platelet levels [ ] . another patient was a -year-old woman who had been revived from a cardiac arrest prior to hospitalization [ ] . a third patient was reported in a series of covid- patients from wuhan [ ] , and five more were reported in a series of covid- patients in italy [ ] . the pathogenesis of intracerebral hemorrhage in our patient is unclear. severe cough was reported to cause cerebral hemorrhage in patients with whooping cough as early as [ ] . the sars-cov- virus has been demonstrated to bind angiotensin converting enzyme two (ace ) on endothelial surfaces [ ] . this binding inhibits the local protective function of ace and likely compromises endothelial integrity [ ] . it is possible that a sudden rise in icp caused by violent coughing and sneezing could have disrupted the alreadycompromised vascular endothelium, causing cerebral hemorrhage. increased risk of intracerebral hemorrhage adds to the complexity of management of patients with covid- . clinicians should be aware that in patients with covid- , especially in those who have additional violent sneezing or coughing, that they be additionally predisposed to intracerebral hemorrhage. our report details such a case in a patient not on any anticoagulation or antiplatelet therapy, however, the risk is likely even higher in patients also on anticoagulation or antiplatelet therapy. we believe this additional risk is due to the virus's ability to bind to angiotensin converting enzyme two on endothelial surfaces. human subjects: consent was obtained by all participants in this study. university of south florida institutional review board issued approval n/a. case reports of patients or less are not required to seek irb or patient approval as long as no identifying information is present in the article. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. neurologic manifestations of hospitalized patients with coronavirus disease in wuhan, china high risk of thrombosis in patients with severe sars-cov- infection: a multicenter prospective cohort study hemorrhagic stroke and anticoagulation in covid- covid- and cerebral hemorrhage: proposed mechanisms (in press) covid- and intracerebral haemorrhage: causative or coincidental novel coronavirus disease and subarachnoid hemorrhage: a case report neuroradiological features in covid- patients: first evidence in a complex scenario (in press) aphasia and cerebral haemorrhage complicating whooping-cough sars-cov- cell entry depends on ace and tmprss and is blocked by a clinically proven protease inhibitor angiotensin converting enzyme : sars-cov- receptor and regulator of the renin-angiotensin system key: cord- -hox m mv authors: anderi, emilyn; sherman, latoya; saymuah, sara; ayers, eric; kromrei, heidi t title: learning communities engage medical students: a covid- virtual conversation series date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: hox m mv context challenges to medical education have been pervasive during the covid- pandemic, and medical students, in particular, have faced numerous obstacles as a result. one of the greatest losses for medical students was the inability to gather with their peers and a lost sense of community. the learning community (lc) program at wayne state university school of medicine (wsu som) expanded our offerings through the use of the zoom platform to increase a sense of connectedness among medical students. the first initiative of its kind at wsu som, the virtual conversation series enabled students to share their pandemic challenges while also connecting with physicians on the covid- frontlines. students were offered eight online sessions with physicians and residents who were able to share insight regarding ( ) how to succeed as a medical student on rotation during covid- , ( ) potential implications of the pandemic on residency applications, ( ) the utility of telemedicine, ( ) tips for patient encounters, and ( ) realities of serving as a physician during a global health crisis. methods residents and clinical physicians on the covid- frontlines participated in -minute discussions with wsu som students through zoom. electronic qualtrics surveys were distributed to medical student attendees of the virtual conversation series and responses were received via likert scale, open text, and ranking questions. results qualtrics results demonstrated % of medical students (n= ) reported they learned new information about the covid- pandemic from the perspective of physicians. additionally, % of medical students described the virtual conversation series as ‘extremely useful’. conclusion the virtual conversation series emphasizing different medical aspects of covid- provided a unique benefit to medical students’ understanding of the current landscape of healthcare, the anticipation of their future roles as physicians, connectedness with their community, and opportunity to practice flexibility as they begin to apply online learning with real-world situations in the health system. qualtrics results demonstrated % of medical students (n= ) reported they learned new information about the covid- pandemic from the perspective of physicians. additionally, % of medical students described the virtual conversation series as 'extremely useful'. the virtual conversation series emphasizing different medical aspects of covid- provided a unique benefit to medical students' understanding of the current landscape of healthcare, the anticipation of their future roles as physicians, connectedness with their community, and opportunity to practice flexibility as they begin to apply online learning with real-world situations in the health system. remote learning has emerged to the forefront of academic content delivery, posing a unique challenge to building community and rapport among peers in academic programs. over the past few years, medical schools have been moving away from the traditional lecture-style education model and moving towards more small-group learning experiences, as well as experiential learning activities [ ] . instructional strategies such as case-based learning sessions, laboratory sessions, and earlier clinical encounters are expanding. as the covid- pandemic evolved and social distancing measures were put into place, medical students faced numerous obstacles relating to their education such as the inability to gather with peers, lost sense of community, inadequate opportunities to practice crucial clinical skills, uncertainties of their roles in rotations, as well as individually grappling with virtual delivery of rigorous and difficult academic content while in quarantine [ , ] . the loss of these collective experiences poses a huge threat to the unity of the student body that medical schools and students have worked so hard to build. there are numerous examples of schools utilizing virtual teleconferencing platforms to increase engagement during the covid- pandemic [ , ] . faculty members adjusted their lectures for both pre-clerkship and clerkship curriculum to allow for optimal delivery over an online platform. many small-group case-based learning sessions are being facilitated online, and some schools have even been successful at providing clinical skills instructional experiences virtually [ ] . the ramifications of social distancing measures and pause in medical education have also taken a toll on medical student's psychological wellbeing. cao et al. utilized the -item generalized anxiety disorder scale (gad- ) to assess the mental health of medical students in china during the covid- outbreak [ ] . it was found that . % of medical students experienced anxiety and of these students, . %, . %, and . % of students experienced severe, moderate, and mild levels of anxiety, respectively. students identified that much of their anxiety was due to stressors such as economic hardships, changes to daily life, and academic delays; whereas students who had strong social support reported lower levels of anxiety. medical schools have been exploring the implementation of different strategies to help cope with the mental and emotional issues faced by medical students during this pandemic. the shiraz university of medical sciences developed a social media platform to offer peer mentoring services to medical students [ ] . their platform provided the opportunity for senior medical students to act as peer mentors to junior medical students and assist them in coping with the anxiety and stress brought on by the covid- pandemic. not only did students report satisfaction with the program and a significant impact on their mental wellbeing, but it also provided them with an opportunity for professional growth. prior to the pandemic, maintaining a sense of support and community amongst medical students has always been a challenge faced by schools across the country. wayne state university school of medicine (wsu som) has worked at encouraging the engagement of students through the introduction of learning communities (lcs). here, students are divided into one of eight lcs, each with - students per class year, and each with a student elected to serve as an lc coordinator (lcc) for each medical class. working with the lc program manager, lccs take on the duty of encouraging students within his/her cohort to engage students through mentorship, social and unifying activities, scholarship, and community service. as the covid- pandemic evolved, the lccs were inspired to find creative ways to maintain connections with their peers and community members. the lc program at wsu som expanded their programming to increase the sense of connectedness among the student body and promote integral exposure to the realities of covid- for medical students through a virtual conversation series. to our knowledge, this is the first initiative of its kind, which enabled students in the som to share their experiences during a pandemic while simultaneously connecting with physicians on the covid- frontlines. although many medical students have volunteered in the fight against covid- , they do not know what to expect in their roles as future physicians in the constantly evolving health care landscape. herein, we discuss the topics offered through this virtual conversation series, and their effectiveness in promoting student engagement during the covid- pandemic. the virtual conversation series initiative involved lccs individually reaching out to an array of residents and clinical physicians selected from the network of office of student affairs director of mentoring and student engagement. essential frontline physicians were handpicked based on specialty and range of experience. lccs contacted each physician by email, with an invitation to co-host a virtual conversation alongside a second or third-year medical student lcc facilitator. the physicians immediately began accepting the invitations by scheduling the virtual conversations over the first three-weeks of april . social media announcements and email invitations were then sent to the lc members by their respective lccs. details regarding the eight -minute virtual conversations included the name of the hosting lc and physician, conversation topic, date and time, as well as the zoom link to join. conversation topics included ( ) utilizing telemedicine, ( ) serving on the frontlines from a resident's perspective, ( ) physician experience managing a pandemic versus natural disasters, ( ) being an intern in the medical intensive care unit (micu), ( ) leading community resources, ( ) leading and rounding, ( ) an epidemiologist's perspective, and ( ) unique barriers faced by homeless and lesbian, gay, bisexual, transgender and queer or questioning (lgbtq)+ adolescents during the pandemic. the decision to use zoom as the platform for the series was based on the rapid transformation to online learning and the preference to continue the uninterrupted duties and engagement of the lcs. zoom was the chosen platform for the series as students were familiar with the interface and had regularly utilized it during the transition to remote learning through wsu som. a survey link was emailed to the attendees within one hour of concluding the conversations to collect the data needed to measure the series objectives. afterwards, a composite of all the surveys was used to qualitatively analyze the data. the virtual conversation series primarily aimed to inform the wsu som medical students who are anticipating their new roles serving on the frontlines. a likert scale ( =extremely dissatisfied, =slightly dissatisfied, =neither satisfied/dissatisfied, =slightly satisfied, =extremely satisfied), open text, and ranking questions (extremely useful, very useful, useful, somewhat useful, not at all useful) were used to collect response. a likert scale and ranking questions were used to standardize responses for comparison, and open text responses were included to illicit more specific feedback from attendees. without utilizing identifying information, evidence was gathered using the qualtrics survey tool to evaluate each of the presentations. wsu som used the survey responses to identify, measure, and appropriately address shortcomings, introduce specific covid- pandemic-related curriculum, and prepare students, faculty, and staff accordingly. the eight lcs hosted a unique student experience through the virtual conversation series. one hundred percent of the respondents (n= ) from each conversation of the series reported that the presentations were useful, with open text responses demonstrating % of students felt the topics directly covered student experiences in clinical rotations during a global health crisis, as well as student futures as physicians in the covid- landscape. students interacted with and questioned the panelists about health systems' preparedness and vigorously changing safety protocols, the roles of medical students during the global health crisis, and more. when asked to rate the usefulness of the virtual conversation series, % of medical students selected 'extremely useful' and % selected 'very useful'. % of medical students selected 'not at all useful' (figure ). qualitative text analysis was performed by two individual researchers, and any relevant discrepancies were discussed and resolved. results of the analysis identified new information medical students learned through the virtual conversation series categorized according to the following: ( ) reflections on patient experiences, ( ) resource shortages, ( ) medical student roles during the covid- pandemic, ( ) covid- perspectives from frontliners, ( ) mental health exacerbations of clinical providers during the pandemic, and ( ) the impact of covid- on lgbtq+ populations. % of medical students reported they learned something new about the covid- pandemic from the perspective of frontliners (figure ). when asked, "how satisfied are you with zoom for this type of online session?" responses indicated the use of zoom as a platform for the series was highly received by a wide margin. six percent of the attendees were extremely dissatisfied with the platform but did not state why. four percent of students were neither satisfied nor dissatisfied. contrarily, % of the responses ranged from slightly satisfied to extremely satisfied ( figure ). students were also asked for suggestions of future topics in the interest of another installment of the virtual conversation series. twenty-one students responded with suggestions among which % reported wanting to hear more about physicians' perspectives from the front lines of the covid- pandemic, % were interested in hearing more about managing covid- patients, and % hoped to learn more about the roles of medical students and residents during this time. the remaining % were interested in various topics such as managing mental health as a patient care provider, the health system's preparedness for the pandemic, and financial management as a physician. the virtual conversation series was influenced by covid- to bring awareness of the realities of the pandemic to wsu som lc medical students. the objective was to provide peer connectedness while educating students on the medical concerns surrounding the pandemic by using residents and physicians to engage directly with students. conversation topics included ( ) utilizing telemedicine, ( ) serving on the frontlines from a resident's perspective, ( ) physician experience managing a pandemic versus natural disasters, ( ) being an intern in the micu, ( ) leading community resources, ( ) leading and rounding, ( ) an epidemiologist's perspective, and ( ) unique barriers faced by homeless and lgbtq+ adolescents during the pandemic. students were asked "what did you learn about the covid- pandemic that you didn't already know?", and two individual researchers performed qualitative text analysis to identify response themes. results indicated topics such as mental health and burnout concerns affecting inexperienced residents, intensive care units (icus) quickly meeting capacity, the importance and rationale behind telemedicine, and adaptation and preparedness for pandemics are similar to that of natural disasters. the virtual conversation series feedback survey was used to measure and appropriately address shortcomings, introduce specific pandemic related curriculum, and prepare students, faculty, and staff accordingly. limitations include student sample size; although there was a total of participants, only students responded to the survey. however, the majority of students who responded agreed on the utility and importance of the initiative. the virtual conversations series allowed the wsu som lc program to provide an opportunity for engagement and mentorship of students while promoting and following social distancing measures. many students were able to network with the presenting residents and physicians and proposed topics for future installments of the series. the majority of student responses indicated that future directions of the virtual conversation series should focus on medical student concerns and questions regarding the covid- pandemic such as managing covid- patients and the roles of medical students and residents during this time. the virtual conversation series provided a unique benefit to medical students' exposure of the realities of covid- , the current landscape of healthcare, anticipation of their future roles as physicians, connectedness with their community, and opportunity to practice flexibility as they begin to apply online learning to real-world situations in the health system. medical students who are training to serve in their roles as frontliners have been provided with an opportunity to connect with their peers already on the frontlines, which has bolstered their preparation. with a desire for expansion of the topics presented in this virtual conversation series, as well as other topics that pertain to medical students' professional development, it is recommended this initiative be incorporated into a more longitudinal component of the medical school curriculum to increase student connectedness with their peers through lcs and physician colleagues. is lecture dead? a preliminary study of medical student' evaluation of teaching methods in the preclinical curriculum medical student education in the time of covid- the role of medical students during the covid- pandemic daily medical education for confined students during covid- pandemic: a simple videoconference solution ophthalmic clinical skills teaching in the time of covid- : a crisis and opportunity the psychological impact of the covid- epidemic on college students in china peer mentoring for medical students during covid- pandemic via a social media platform we would like to acknowledge the help of the wayne warrior learning community student coordinators, as well as the residents and physician panelists who made this opportunity possible. human subjects: consent was obtained by all participants in this study. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -ev nx h authors: cancarevic, ivan; tathineni, praveena; malik, bilal haider title: coronavirus disease (covid- ) in cancer patients date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ev nx h the coronavirus disease (covid- ), caused by severe acute respiratory syndrome coronavirus (sars-cov- ), has become the most talked-about clinical entity in early . as an infection that spreads easily and has a significant mortality rate, it has caused global panic rarely seen before. many of the measures taken by governments worldwide will have long-lasting impacts on the wellbeing of the population at large. it has been widely reported that the most vulnerable patients have been most negatively affected by sars-cov- (covid- ). in this study, we have tried to search the currently available data on the outcomes of infected cancer patients. most of the data points to the very challenging nature of treating such patients. their overall outcomes seem to be worse than in the general population, and it may be difficult to differentiate which potential complications are a result of the primary oncologic disease versus the infection. management presents its own set of challenges, including but not limited to, deciding whether postponing cancer treatment until the infection resolves is going to benefit the patient and how to organize all aspects of patient care when social contact is as limited as it is for patients newly diagnosed with covid- . we believe that as more data becomes available, it is going to be necessary to publish detailed guidelines on how to approach this unique clinical challenge. the coronavirus disease , caused by severe acute respiratory syndrome coronavirus (sars-cov- ), was first described in wuhan, china, in december [ ] . after severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov), sars-cov- is the third highly pathogenic and transmissible coronavirus [ ] . since december, the virus has spread globally and has led to the implementation of some of the most serious policies around the world. on january , it was declared a public health emergency by the world health organization (who) [ ] . since then, we have seen a number of consequences that have impacted people's lives. on march, the united states restricted the entry of european citizens into the country [ ] . since then, multiple countries have suspended all but essential travel and strongly advised their own citizens against overseas travel [ ] . the economic impact has also been huge. financial markets have been severely impacted, putting people's financial wellness at risk [ ] . the incubation period is not notably longer than for other viruses in the same family [ ] . however, the fact that people have been required to stay in isolation for days has had a severe psychological impact on many affected individuals [ ] . the most common clinical presentation is that of a mild upper respiratory tract infection, although a number of patients develop progressive respiratory failure [ ] . cough, fever, and fatigue are the most frequently reported presenting symptoms, evident in the vast majority of cases, followed by expectoration, myalgia, and gastrointestinal symptoms [ ] [ ] [ ] . the most common co-morbidities of patients diagnosed with covid- were hypertension and diabetes mellitus, while respiratory co-morbidities were comparably rare [ ] [ ] [ ] . chest x-rays showed evidence of bilateral ground-glass or patchy opacities in almost % of patients, while leukopenia and, to a lesser extent, eosinopenia were frequently reported laboratory findings [ ] [ ] [ ] . severe disease was associated with elevated levels of c-reactive protein, d-dimer, and procalcitonin [ ] . the risk of intensive care unit (icu) admission and death was significantly higher in older individuals and those with co-morbidities and the development of end-organ damage (acute respiratory distress syndrome, acute kidney injury, cardiac injury) [ ] . many treatment regimens have been attempted, without a clear strategy being developed at the time of this writing. empiric antivirals, antibiotics, corticosteroids have been frequently used [ ] . the purpose of this article is to analyze the impact of covid- infection on patients with malignant co-morbidities. considering the increased severity of the disease in those patients, their social, psychological and physical limitations and the number of such patients in the society, we strongly believe that it is essential to get a clearer understanding of the unique challenges in protecting some of the most vulnerable members of the society during this outbreak. cancer patients have weaker immune systems compared to the general population, both due to the disease itself as well as the treatment. as such, morbidity and mortality of any serious infections would be expected to be high among cancer patients. liang et al. found that the prevalence of cancer among patients infected with sars-cov- (covid- ) was higher than in the general population [ ] . one percent of the covid- cases had a history of cancer when compared to . % of the chinese population [ ] . lung was the most common primary site with / patients having lung cancer [ ] . colorectal ( / ), breast ( / ), and bladder ( / ) cancer were reported more than once, while lymphoma, papillary thyroid cancer renal cell carcinoma, and adrenal carcinoma were reported once [ ] . compared to other patients with confirmed covid- infections, cancer patients were, on average older, more likely to be smokers, and had more severe baseline ct findings while having similar baseline x-ray findings, symptoms, and other co-morbidities [ ] . they also reported that the outcomes (including the likelihood of icu admission) of such patients were, on average worse when compared to those without a malignant co-morbidity ( % versus %) [ ] . those who underwent surgical resections or chemotherapy within the past month were also found to be more likely to die or require icu admission ( out of versus out of ) [ ] . xia et al., however, raised a few concerns about the findings in the study published by liang et al. [ ] . they believe that the sample size of only cancer patients infected with sars-cov- is too small and also that liang et al. failed to account for possible confounders, including smoking/chronic obstructive pulmonary disease (copd) history which is an independent risk factor for worse outcomes in covid- infections [ ] [ ] . diagnostically, covid- infections complicate the diagnosis of lung infiltrates in cancer patients [ ] . overall, it is clear that the recent outbreak significantly affects cancer patients. the association between malignant co-morbidity and mortality from covid- is less clear. smoking status and other systemic, especially pulmonary co-morbidities, potentially skew the mortality rate. also, the widespread presence of another condition that presents with lung infiltrates adds to the difficulty of accurately diagnosing and treating those patients. we would encourage clinicians to keep reporting any new cases so that a larger systematic review can be done, and possible confounders, especially smoking and other lung diseases, can be addressed. cancer patients are known to be prone to developing psychiatric disease, including anxiety and depression. as such, mental health care is an important aspect of treating patients suffering from malignant disorders. considering the importance of social contacts for cancer patients, the quarantine requirements for patients suspected of contracting sars-cov- could further complicate their situation. kotronoulas et al. found that emotional support and reassurance were the most prominent needs of colorectal cancer patients regardless of the disease stage of the treatment phase [ ] . faller et al. reported that psycho-oncologic interventions were associated with effects on emotional distress and quality of life with longer interventions yielding longer-lasting results [ ] . the study was limited by small-sample bias and low-quality reporting in some of the studies analyzed [ ] . moore et al. discovered that the impact of social isolation on cancer survival was significant (hr= . p= . ), even when accounted for the fact that patients receiving no therapy were more likely to be socially isolated [ ] . multiple studies suggest that the outcomes of cancer patients are dependent on their social infrastructure [ ] [ ] [ ] . nowadays, psychological support is becoming an integral part of comprehensive cancer management [ ] . with the number of people in isolation rising due to the sars-cov- outbreak, it is reasonable to assume that the issue of social isolation is going to become more prominent, which is especially worrisome for cancer patients. recently, there have been news reports on quarantined patients in spain being found 'dead and abandoned,' which provides valuable insight into the scale of the problem [ ] . it seems evident that hospitals and practitioners should work on developing systems to help cancer patients maintain as much social contact as possible throughout the outbreak. psychological interventions through phone and video calls may prove to be an essential part of the management of such patients. managing cancer patients during the covid- outbreak presents multiple unique challenges. the amount of time cancer patients spend at hospitals, the hospital schedule changes, and the necessity of administering chemotherapy and radiotherapy, which weaken the immune system, all increase the difficulty of properly treating those patients. as liang et al. pointed out, cancer history, surgery, and chemotherapy all significantly contributed to adverse outcomes [ ] . a possible problem with the study is that the number of patients was low [ ] . interestingly, lung cancer did not appear to be more hazardous than other forms of cancer [ ] . yu et al. stressed the importance of adequate protection for health workers during abdominal surgeries [ ] . also, they believed that the laparoscopic approach was preferable over the traditional approach [ ] . once a cancer patient is diagnosed with covid- , it is debatable whether cancer treatment should be continued while the patient is recovering from the infection [ ] [ ] . zhang et al. reported a case of a lung cancer patient whose osimertinib treatment was continued throughout the infection due to his stable clinical condition, and the patient made a complete recovery and was discharged [ ] . yang et al. point out that generally, anti-covid- therapy should be either combined with cancer therapy or administered prior to it [ ] . they recommend that integrative cancer therapies that involve close contact with patients are forbidden or only permitted in rare circumstances [ ] . despite the relative scarcity of the available data due to the novelty of the sars-cov- , it remains clear that the majority of experts recommend focusing on infection management over cancer management. if new studies show that there is a significant association between chemotherapy-or radiotherapy-induced immunosuppression and adverse outcomes of covid- patients, a short delay in administering them would likely be beneficial in order to improve the odds of surviving the acute infection. however, it should be noted that most of the currently available articles used the data from liang et al. and as xia et al. pointed out, there are multiple issues with that study [ ] [ ] . we would strongly encourage clinicians to keep reporting any cases of cancer patients infected with sars-cov- , their management, and the outcome in order to further our understanding of this complex issue. the outbreak of covid- has caused global panic rarely seen before and reaching management decisions has been difficult due to the scarcity of available data on the disease and the lack of clearly known risk factors for adverse outcomes. the currently available evidence seems to suggest that there is a correlation between cancer and covid- as cancer prevalence among the infected patients seems higher than in the general population, with lung being the most frequent site. since most of the affected individuals have few symptoms of the infection, it poses a diagnostic challenge to determine the exact etiology of lung infiltrates in cancer patients. smoking and other chronic conditions could be confounders that need to be addressed. lack of social interactions is another problem facing cancer patients at the time of the sars-cov- outbreak as social isolation is the most important infection prevention measure. finally, a challenge worth pointing out is the issue of delaying cancer treatment, especially in patients with mild cases of covid- . the currently available evidence suggests that oncologic therapies may be acceptable in those with mild infections. that being said, it is still impossible to tell whether patients would benefit from it, and the additional risk to healthcare workers could make such practice more hazardous than delaying cancer treatment until the infection resolves. we believe that it is essential that clinicians keep reporting cases of covid- in patients with malignant co-morbidities. more detailed guidelines will be necessary to determine the priorities in treating those patients. does sars-cov- has a longer incubation period than sars and mers? emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus : biology and therapeutic options severe acute respiratory syndrome coronavirus (sars-cov- ) and coronavirus disease- (covid- ): the epidemic and the challenges proclamation-suspension of entry as immigrants and nonimmigrants of certain additional persons who pose a risk of transmitting novel coronavirus coronavirus travel updates: which countries have restrictions and fco warnings in place fed anounces more loans as investor alarm persists coronavirus: concerns rise over mental health impact of isolation epidemiologic features and clinical course of patients infected with sars-cov- in singapore clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centered, retrospective, observational study clinical characteristics of patients infected with sars-cov- in wuhan clinical findings in a group of patients infected with the novel coronavirus (sars-cov- ) outside of wuhan, china: retrospective case series cancer patients in sars-cov- infection: a nationwide analysis in china risk of covid- for cancer patients clinical characteristics of coronavirus disease in china the differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of the novel coronavirus disease a systematic review of the supportive care needs of people living with and beyond cancer of the colon and/or rectum effects of psycho-oncologic interventions on emotional distress and quality of life in adult patients with cancer: systematic review and meta-analysis social isolation: impact on treatment and survival in patients with advanced cancer advancing psychosocial care in cancer patients spanish army finds care home residents 'dead and abandoned several suggestion of operation for colorectal cancer under the outbreak of corona virus disease in china the treatment and outcome of a lung cancer patient infected with sars-cov- challenges and countermeasures of integrative cancer therapy in the epidemic of covid- in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -ffgd ets authors: albalawi, hani b title: covid- : precautionary guidelines for ophthalmologists date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ffgd ets several coronaviruses can infect humans, and the globally endemic human coronaviruses, hcov- e (human coronavirus e), hcov-nl (human coronavirus nl ), and others, tend to cause mild respiratory diseases. the zoonotic middle east respiratory syndrome coronavirus (mers-cov) and severe acute respiratory syndrome coronavirus type (sars-cov- ) have high fatality rates. in december , the world health organization (who) was notified by chinese authorities about an outbreak of pneumonia before the causative organism was identified in january as a novel coronavirus family. the who refers to the virus as coronavirus disease (covid- ). within several weeks, the outbreak has become an emergency, and many countries have since been affected. the method of transmission is not yet fully known but is thought to be mainly respiratory. healthcare providers, particularly ophthalmologists, are at high risk of a covid- infection through unprotected contact with eye secretions during routine ophthalmic examinations that involve the use of direct ophthalmoscopy and slit-lamp examinations, which are usually performed in a setting that allows for close doctor-patient contact. in light of these, specific measures are needed from an ophthalmic point of view to control the covid- outbreak and to protect health care providers. a -year-old ophthalmologist, dr. li wenliang, was the first to raise the alarm about a cluster of severe acute respiratory syndrome (sars)-like pneumonia cases late december at wuhan city, china. regrettably, that warning was not taken seriously. following that, dr. li returned to work and, unfortunately, contracted the virus from an asymptomatic glaucoma patient in early january. later on, dr. li passed away, leaving behind a child and a wife, who is pregnant, and opened the doors and discussions about the risk of infection among ophthalmologists. a survey study by nair and colleagues reported that the majority of ophthalmologists in india ( . %) felt that ophthalmologists were potentially at a higher risk of contracting covid- as compared to other specialties while examining patients [ ] . in fact, ophthalmologists are at high risk of contracting the covid- virus through unprotected eye contact with secretions during routine ophthalmic examinations with direct ophthalmoscopy and slit-lamp examinations, which are usually performed in a setting that has close doctor-patient contact. on december , , the who was notified by china about an outbreak of pneumonia with an initially unknown etiology in wuhan city in hubei province. in january , the causative organism was identified as a novel member of the coronavirus family. initially tentatively named novel coronavirus ( -ncov) and named sars-cov-type by the international committee of taxonomy of viruses (ictv), this virus is the cause of the disease named coronavirus disease . to date, covid- has already confirmed to have affected over , , people and caused over , deaths worldwide, spanning countries in south east asia, europe, north america, australia, and the middle east and led to huge public health challenges [ ] . the transmission route of covid- is not yet fully known but it is thought to be mainly respiratory. it is even more overwhelming that many infected persons showed no apparent respiratory symptoms and presented with non-respiratory manifestations, including conjunctivitis in the ocular tissue [ ] and diarrhea in the gastrointestinal system [ ] . covid- may spread through the eye's mucous membrane via indirect contact with droplets. the variable presentation of the disease makes transmission via contact, especially for health care providers like ophthalmologists, possible. since the outbreak, more than , healthcare professionals having been infected, with deaths, including one ophthalmologist. multiple comprehensive recommendations by the american academy of ophthalmology (aao) [ ] and a well-designed study from hong kong [ ] were announced helping ophthalmologists for safe practices. however, it is the responsibility of global organizations to review daily evidence and provide instructions and uniform guidelines. this paper aimed to provide an evidence-based approach, although this may not be applicable to all institutes and is not a proven medico-legal recommendation. subsequent information about the nature of covid- may change these recommendations in the future. in light of these, specific measures are needed from an ophthalmic point of view to control the covid- outbreak and to protect health care providers. because of the disease's contagiousness and way of spread, it is better and safe to keep nonurgent patients away from the hospital during the pandemic period. the priority should be on how to reduce the risk of covid- virus transmission from human to human and the rate of new case development. then, we "flatten the curve" and not overwhelm the health services and limited supply of hospital beds, intensive care unit (icu) beds, ventilators, and others. second, direct all disposable medical supplies and focus them on hospitals where they are most needed [ ] . therefore, all non-urgent routine follow-up and surgeries like mild nonproliferative diabetic retinopathy or routine scheduled cataract surgery should be postponed. it is even better if patients can be sent text messages or called to discuss the need to reschedule their appointment or a public announcement to cancel all routine follow-up visits and surgeries, in order to minimize all non-urgent cases coming to the eye clinic or hospital [ ] . a three-stage control measure to reduce the transmission of the virus in the ophthalmology department in hong kong was based on text messaging to reschedule refill visits [ ] ; a triage to identify patients with fever, conjunctivitis, and respiratory symptoms; asking those who recently traveled to areas infected with the virus to postpone their ophthalmology visits for days; and the avoidance of micro-aerosol generating procedures, nasal endoscopy, and operations under general anesthesia. in addition, infection control was provided to the environment and health personnel. always keep in mind that the main goal during this pandemic is to protect yourself and your patient, preserve all health services to stop its spread, and prevent the health system from being compromised. it is safer to divide patients who attend eye clinics or have ophthalmology complaints into three groups: low risk, medium risk, and high risk ( table ) [ ] . ophthalmology clinics that see patients should be equipped with screening stations before entry to the waiting area and must take a detailed history about any respiratory illnesses, fever, recent return from high-risk areas, or contact with family members recently back from one of the countries battling a covid- outbreak [ ] . this way, every patient can be classified as low, medium, or high risk. this should be coupled with nurse-directed triage protocols to determine if an appointment is necessary or if the patient can reschedule and be sent home to ensure safe triage and isolation of patients presenting with covid- symptoms or other respiratory infections. those at low risk can be attended to with standard precautions. medium-risk patients with non-urgent ophthalmic problems should be asked to return home and reschedule their appointment [ ] . high-risk patients with a non-urgent ophthalmic problem should be sent to the emergency room (er) immediately and local health authorities notified. medium-risk patients with urgent ophthalmic problems should be put in the examination lane immediately in order to decrease the time spent at the clinic. the patient, the ophthalmologist, and all health care personnel should wear surgical masks, gowns, gloves, and eye protection. in case of any planned procedure that results in an aerosolized virus, an n mask should be worn. highrisk or covid- positive patients with urgent ophthalmic problems can be seen but after following local hospital guidelines and precautions for treating patients with covid- or that of the centers for disease control and prevention (cdc) such as using an n mask, eye protection, and gowns ( figure ) [ ] . standard precautions for every patient should be followed, including using a breath shield during a slit-lamp exam or any clear plastic barrier to block the transfer of breaths between the patient and the doctor ( ) . ophthalmologists should tell their patients that they will speak as little as possible during the slit-lamp examination and request that the patients also refrain from talking. they should always use protection for the mouth, nose, and eyes when caring for patients potentially infected with covid- . they should also keep the waiting room as empty as possible and advise seated patients to remain at least two meters (around feet) from one another [ ] . as much as is prudent, they should reduce the visits of the most vulnerable patients. patients with or suspected to have covid- should be cared for in a single-person room with the door closed. limited points of entry to the facility is strongly recommended too. before opening a routine clinic, checklist criteria that aim at safe opening should be available. complying with local governmental guidance, these guidelines should be closely reviewed and followed. making a plan and pre-opening planning will be critically important to the success of your practice reopening, including an assessment of your personal protective equipment (ppe) needs and alternatives such as cloth masks, eye protection, and others [ ] . evaluate the clinics to determine what kinds of surfaces and materials make up that area, as most surfaces just need normal, routine cleaning; however, frequently touched surfaces like doorknobs will need to be cleaned with soap and water and then disinfected using united states environmental protection agency (epa)-approved disinfectant. if a disinfectant is unavailable, you can use one-third cup of bleach added to gallon of water or % alcohol solutions to disinfect. make sure all slit-lamps are equipped with a breath shield ( figure ) . it is better that staff who do not need to be physically present in the office stay at home and work remotely. even more, consider bringing employees back in stages, at different parts of the day, or working on alternative days. start with a few outpatients visits a day and work on a modified schedule to avoid high volume or density. unless necessary, ask patients to attend alone, keep the waiting room as empty as possible, and advise seated patients to remain at least two meters (around feet) from one another, consider another option to wait in the clinic by asking patients to wait in their car or outside and text or calling when the appointment is ready. remove magazines, brochures, remote controls, and other shared items from waiting and exam rooms. follow u.s. centers for disease control and prevention (cdc) guidance, which requires all individuals who visit the office to wear a cloth face covering. this should be explained to patients and other visitors before they arrive at the clinic. prioritize seniors above years, those with chronic diseases like diabetes mellitus, and patients on chemotherapy to be seen and leave the clinic early. the availability of screening stations before entry to the waiting area should also continue to pick up any suspected cases and then deal with them as high-risk patients. after seeing every patient, standard cleaning and disinfection should apply to all patient care, regardless of the suspected or confirmed infection status of the patient [ ] . wear single-use gloves when cleaning and disinfecting surfaces. all ophthalmic instruments, including slitlamps, tonometer, and contact lenses, and all places the patient touched should be disinfected. standard hand hygiene is critical, including frequent hand wash with soap and water for at least seconds before and after seeing patients [ ] . if soap and water are not readily available, use a hand sanitizer that contains at least % alcohol [ ] . the virus causing covid- is an enveloped virus, making it very susceptible to the same alcohol-and bleach-based disinfectants that ophthalmologists commonly use to disinfect ophthalmic instruments and office furniture. some methods recommended by the cdc to disinfect and destroy the covid- virus include alcohol solutions with at least % alcohol and diluted bleach. however, the united states environmental protection agency (epa) shared a list of antimicrobial products like stepan company (northfield, illinois) products (disinfectant spray) that are expected to be effective against covid- [ ] . the importance of disinfecting ophthalmic examination instruments to minimize cross-infections and protect ophthalmic medical staff is clear. there are a wide range of disinfectants available that can be used to disinfect surfaces. kampf et al. found that some members of the coronavirus family -sars and middle east respiratory syndrome (mers) -can persist on surfaces like metal, glass, or plastic for up to nine days but can be efficiently inactivated by surface disinfection with %- % ethanol, . % hydrogen peroxide, or . % sodium hypochlorite within one minute. other biocidal agents, such as . % to . % benzalkonium chloride or . % chlorhexidine digluconate, are less effective [ ] . severe acute respiratory syndrome coronavirus type (sars-cov- ), also known as covid- virus, is a species of the coronavirus family that infects humans, bats, and certain other mammals. in fact, bats are a major reservoir of many strains of sars-related coronaviruses, and several strains have been identified in palm civets, which were likely ancestors of sars-cov- . cross-species transmission (cst), also called host jump, or spillover, is the ability of a foreign virus, once introduced into a new host species, to infect that individual and spread throughout the new host population, as has happened with swine flu, sars-cov- , and now covid- [ ] . it is a member of the genus betacoronavirus and subgenus sarbecoronavirus and is an enveloped positive-sense single-stranded rna virus that enters its host cell by binding to the angiotensin-converting enzyme receptor (ace ) receptor [ ] . human to human transmission occurs with close contact with an infected person. this primarily occurs when an infected person coughs or sneezes and produces respiratory droplets that spread like other respiratory pathogens. these droplets can settle in the mouth or nasal mucosa and lungs of people who inhale the air [ ] . however, it is widely agreed that the clinical picture varies from a simple respiratory infection, which presents with symptoms such as a runny nose, sore throat, fever, and coughing to more complicated findings like septic shock [ ] . similar to sars-cov and mers-cov, which caused epidemics in the past years, the usual first symptoms are commonly defined as fever, cough, and shortness of breath. in patients with covid- virus infection, chest pain, confusion, and nausea-vomiting were noted in addition to previous findings [ ] . x-ray and thorax ct imaging of patients with covid- showed unilateral or bilateral involvement compatible with viral pneumonia. reported complications include acute heart damage, acute respiratory distress syndrome (ards), secondary infections, pneumothorax, and some patients with other comorbidity exhibited more severe symptoms and even death [ ] . the diagnosis of covid- infection is based on history, including detailed contact and travel history aided by laboratory testing. viral infection laboratory testing methods are important, including serology tests and viral culture. the most commonly used diagnostic methods are molecular methods, such as reverse transcription-polymerase chain reaction (rt-pcr) or real-time pcr by using a respiratory sample as the oropharyngeal swab, sputum, or bronchoalveolar lavage. unfortunately, the covid- virus not only affects the respiratory tracts, it also may manifest in other regions like the gastrointestinal tract and ocular tissues, as conjunctivitis has been reported during this outbreak and conjunctival secretions yielded positive rt-pcr results [ ] . this suggests that covid- can infect the conjunctiva and cause conjunctivitis, and virus particles are present in ocular secretions. indeed, there is also evidence that some coronavirus family can occasionally cause conjunctivitis in humans. in fact, human coronavirus nl (hcov-nl ) was first identified in a baby with bronchiolitis and conjunctivitis. in cases of children with confirmed hcov-nl infections, % had conjunctivitis [ ] . clinical entities, such as conjunctivitis, anterior uveitis, retinitis, and optic neuritis, have been seen in animal models [ ] . one of the affected healthcare workers reported his experience of the disease. despite being fully dressed in a protective suit and n respirator, he was still infected by the virus, with the first symptom being unilateral conjunctivitis, followed by fever. in spite of the controversy about the eye as the possible means of transmitting disease, qing et al. posit that the virus enters the tear duct through droplets, which may pass through the nasolacrimal ducts and then into the respiratory tract [ ] . combined with all this information, we assert that healthcare professionals should use eye protection when in close contact with patients. at the time of the pandemic, with limited information, no treatment for covid- , and no vaccine as yet, we will need to stay highly cautious to recognize the possible non-respiratory early manifestations of covid- infection, including the consideration of viral conjunctivitis as a possible presentation. healthcare professionals, including ophthalmologists, should take the full recommended measures and precautions to protect themselves and their patients and stop the spread of the infection. effect of covid- related lockdown on ophthalmic practice and patient care in india: results of a survey -ncov transmission through the ocular surface must not be ignored epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study important coronavirus updates for ophthalmologists . (american academy of ophthalmology stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from hong kong coronavirus (covid- ) outbreak: what the department of endoscopy should know covid- : a physician practice guide to reopening list n: disinfectants for use against sars-cov- (covid- ) persistence of coronaviruses on inanimate surfaces and its inactivation with biocidal agents wildlife and emerging zoonotic diseases: the biology, circumstances and consequences of cross-species transmission. current topics in microbiology and immunology isolation and characterization of a bat sars-like coronavirus that uses the ace receptor the epidemic of -novel-coronavirus ( -ncov) pneumonia and insights for emerging infectious diseases in the future gastrointestinal infection could be new focus for coronavirus diagnosis. cureus. epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study clinical features of patients infected with novel evaluation of coronavirus in tears and conjunctival secretions of patients with sars-cov- infection human coronavirus nl , france . emerg infect dis can the coronavirus disease (covid- ) affect the eyes? a review of coronaviruses and ocular implications in humans and animals the possibility of covid- transmission from eye to nose human subjects: all authors have confirmed that this study did not involve human participants or tissue. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -i azljq authors: lakshman, harini; athwal, pal satyajit singh; gondi, anitha; dhillon, sandaljit; towfiq, basim a title: a case of adult-onset still's disease with positive antinuclear antibodies date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: i azljq adult-onset still's disease (aosd) is a rare inflammatory disorder involving multiple systems. it can present a wide range of symptoms like maculopapular rash, fever, and arthralgia, which may overlap with many other disorders, making it difficult to diagnose. unknown etiology and no diagnostic tests further make it complex to establish the diagnosis of aosd. we report the case of a -year-old female who presented with persistent rash, joint pain, and fever, along with positive antinuclear antibodies (ana), diagnosed with this condition. the patient improved with corticosteroids and the plan is to start disease-modifying antirheumatic drugs (dmards) after tapering off steroids. in , george frederic still first described juvenile idiopathic arthritis (jia) in children, followed by bywaters who later on defined adult-onset still's disease (aosd) [ ] [ ] . aosd is a rare autoimmune condition with unknown etiology. clinically, it presents as a maculopapular rash, fever, arthralgia, leukocytosis, and raised acute phase reactants. it is a diagnosis of exclusion, and differentials include a wide range of infectious, autoimmune, neoplastic pathologies. yamaguchi's criteria can be used to diagnose after the exclusion of other disorders [ ] . there is no diagnostic lab test though serum ferritin can be used for monitoring and consideration for aosd [ ] . non-steroidal anti-inflammatory drugs (nsaids), corticosteroids, and rheumatological agents are the mainstay of treatment [ ] . we report a case of aosd diagnosed on the basis of the yamaguchi criterion and weakly positive antinuclear antibodies (ana). a -year-old female with a past medical history significant for protein c deficiency and a history of pulmonary embolism comes with an urticarial rash associated with arthralgia. she did not have any history of fever or joint pain at that time. the episode started recently and was associated with high fever and significant joint pain and stiffness. she was seen in urgent care and treated with prednisone mg. her rash remained stable but she still had swelling and tenderness of bilateral knee and ankle joints and bilateral wrist and elbow joints. she was seen for the same complaints in the emergency department. an x-ray of the bilateral knee was unremarkable; she was given morphine for pain and was sent for follow-up in the clinic. meanwhile, suspecting a broad differential of autoimmune etiology, workup was done, including complete blood count, basic metabolic profile, liver function test, urine analysis, erythrocyte sedimentation rate (esr), c-reactive protein (crp), ana, complements, rheumatoid factor, hepatitis panel, human acquired immunodeficiency virus (hiv) rapid antigen test, and blood cultures. she was admitted to the hospital for increasing pain and fever of f. her white blood cell (wbc) count at that time was . , with a neutrophilic predominance and significant bandemia; the liver function test was abnormal. bone marrow biopsy was not performed because of no lab or physical findings of any hematological malignancy. suspecting infectious etiology she was started on broad-spectrum antibiotics, vancomycin, and cefepime. her blood cultures and urine cultures were negative. suspecting infectious endocarditis, echo was done, which was again negative for vegetations, with preserved ejection fraction and normal valves and wall motion. with the given amount of tachycardia, she was also having an elevation of d-dimer. computed tomography (ct) chest with contrast was done, pulmonary embolism (pe) was ruled out, and the lungs were unremarkable for any pathology. she still had persisting spiking fevers every day and with each spike of fever, she had a worsening rash and joint pains. the rash was papulosquamous and present over extremities more than axial as shown in figure and and , respectively. lactic acid was normal. ana titers were : speckled pattern and the c , c , and c complements and c q levels were normal. thyroid-stimulating hormone (tsh) was normal. the x-ray of the knee joints was unremarkable. she had a troponin elevation of . , for which cardiac cath. was done, which showed clean coronaries. with all the infectious and autoimmune diseases ruled out, ferritin and transferrin were done, suspecting still's disease since she had temperature spikes, associated rashes, and mild troponin and ana elevation, ferritin was significantly elevated at , and transferrin was . with the clinical findings, four major criteria, and one minor yamaguchi criteria along with the ferritin value, she was diagnosed to have adult-onset still's disease and started on high-dose steroids when her rashes and joint pains decreased. she was given methylprednisolone mg for three days and sent home with prednisone mg. on follow-up after a week, she reported decreased symptoms. a plan was made to continue steroids for six to eight weeks and start on dmards after tapering the steroids. little is known about the etiological factors and pathophysiology of this rare autoimmune condition. elevated levels of tumor necrosis factor-alpha (tnf-α), interleukin (il)- , and il- are associated with asos [ ] . asos has bimodal peaks: one in - years and the other one between and years, however, this patient was diagnosed at years of age [ ] . patients with aosd typically present with fever, rash, arthralgia, fever exceeding . f, and sore throat, as seen in this case, though sore throat was absent. the rash is typically nonpruritic and maculopapular and was seen distributed over the extremities in this case. the urticarial rash is a typical feature seen in asod, which was also present in this case. apart from a sore throat, there was no lymphadenopathy, splenomegaly, or nervous system involvement, which might also be seen in case of asod [ ] . the diagnosis of asod is based on yamaguchi's criteria ( table ) , requiring five or more criteria, including two or more major criteria, yielding . % sensitivity and . % specificity and hyperferritinemia, along with the exclusion of other disorders [ ] . yamaguchi's criteria or more criteria are required, of whom or more must be major. major criteria- this case was diagnosed with four major criteria and one minor criterion, along with a ferritin level of , . ana in this patient was positive, with a titer of / without any feature or other antibodies for sle. it is very rare to have positive ana with asod, and the diagnosis of asod should not be excluded based on the rheumatoid factor (rf) or ana [ ] [ ] . the treatment of aosd includes nsaids. patients who fail to respond to treatment should be started on dmards such as methotrexate. biological agents are reserved for refractory cases, as rituximab was used in a case resulting in favorable outcomes [ ] . on a form of chronic joint disease in children still's disease in the adult preliminary criteria for classification of adult still's disease evaluation of serum ferritin as a marker for adult still's disease activity proinflammatory cytokine profiles in sera and pathological tissues of patients with active untreated adult onset still's disease interleukin- as a diagnostic marker of adult-onset still's disease in older patients: a case report and review of the literature adult-onset still's disease: a case report sore throat and hyperferritinemia adult still's disease despite the presence of positive antinuclear antibodies diagnostic challenge: a report of two adult-onset still's disease cases successful treatment of refractory adult onset still's disease with rituximab aosd is a rare disease that is very challenging to diagnose. the lack of diagnostic tests and symptoms mimicking other diseases pose a major challenge for a physician in diagnosing aosd. through this case, we want to focus on the fact that asod should not be excluded in case of the presence of ana and should be kept within the differentials in a patient presenting with fever, arthralgia, and rash. human subjects: consent was obtained by all participants in this study. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -rsu xviv authors: zhang, qian; shan, khine s; gopisetti, neethu; yoon, thomas; iqbal, iqra title: a mysterious paratracheal mass: parathyroid carcinoma date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: rsu xviv parathyroid carcinoma is a rare cause of primary hyperparathyroidism. we detail a -years-old gentleman who was otherwise healthy presented to the hospital due to acute encephalopathy. he was subsequently found to have parathyroid carcinoma as the cause of the acute encephalopathy with impressive serum calcium and parathyroid hormone levels. the parathyroid carcinoma was later surgically resected with the diagnosis confirmed via pathology specimen. the patient was safely discharged from the hospital with recommendations of close routine outpatient followup. parathyroid carcinoma is a rare cause of primary hyperparathyroidism [ ] . it is accountable for less than one percent of all sporadic primary hyperparathyroidism [ ] . according to a systemic review conducted from - by ruda et al., parathyroid carcinoma accounted for . % of cases out of the total study population of , patients [ ] . the diagnosis of parathyroid carcinoma is often made status post resection of the tumor. it is important to recognize parathyroid carcinoma in the early phases as a prompt aggressive surgical approach is essential for the treatment of the disease [ ] . the patient was a -years-old gentleman with no pertinent past medical history presented to the emergency department (ed) due to altered mentation. he was found to be confused, acting strangely in his home by his neighbor that prompted the urgent ed visit. initial laboratory findings: temperature . ° f, blood pressure / mmhg, respiratory rate breaths per minute, heart rate beats per minute, and oxygen saturation % on room air. the patient was alert and oriented to self and unable to follow verbal commands. laboratory findings showed a negative urine drug screen, white blood cells of . k/ul with neutrophilic predominance along with lactic acid of . meq/l, and negative severe acute respiratory syndrome coronavirus (sars-cov- ). arterial blood gas finding was otherwise unremarkable. the initial serum calcium was found to be . mg/dl with parathyroid hormone (pth) of . pg/ml. the endocrinologist recommended intravenous fluids, calcitonin, cinacalcet, and pamidronate for hypercalcemia treatment. a computerized tomography (ct) scan of the head was negative for acute intracranial abnormalities. the chest x-ray was unremarkable for inflammatory processes. there were concerns of sepsis given acute encephalopathy along with lactic acidosis despite otherwise being hemodynamically stable. he was subsequently treated empirically with vancomycin, ceftriaxone, ampicillin, obtained cultures, and admitted into the medical intensive care unit (micu) for further evaluation. he remained stable overnight. on the second day of hospitalization, the patient remained disoriented, confused, and restless in the setting of hemodynamic stability. the differential diagnosis included meningoencephalitis as nuchal rigidity was found on physical examination. lumbar puncture and magnetic resonance imaging of the brain was not performed as the patient was agitated. dexamethasone was added to the treatment regimen. the patient remained in the micu overnight. on the third day of hospitalization, he became more agitated on top of confusion and restlessness. the empirical antibiotics were discontinued as there was a low clinical suspicion of an infectious process given normalization of lactic acid and negative culture data. serum calcium level had improved from . mg/dl to . mg/dl after receiving the hypercalcemia treatment. pth continued to trend upwards from . pg/ml to . pg/ml. there was a strong clinical suspicion that the acute encephalopathy was related to metabolic derangement due to severe hypercalcemia. he remained hemodynamically stable overnight. on days - of hospitalization, the patient became more lucid as serum calcium level had normalized to . mg/dl with treatment. ct of the chest, abdomen, and pelvis was ordered as there was a strong concern for underlying malignancy given the severe hypercalcemia with elevated pth. ct discovered a x mm mass located at the right retroclavicular location that indented and deviated the trachea to the left side ( figure ). no other abnormal masses were discovered in the rest of the imaging study. the paratracheal mass was subsequently surgically resected and sent for pathology evaluation. a x mm mass located at the right retroclavicular location that indented and deviated the trachea to the left side. on day of hospitalization, the patient recovered well after the surgery with stable hemodynamics, adequate pain control without surgical complications. his mentation had completely returned to normal as he was alert and oriented. postoperative serum calcium level was . mg/dl with pth of . pg/ml. serum calcium levels were trended for the next couple of days to ensure there were no signs of hungry bone syndrome. he was started on calcium carbonate mg daily. the patient remained to have normal serum calcium levels with elevated pth levels for the next few days. there were no physical examination findings of paresthesias or perioral numbness. surgical pathology findings revealed parathyroid carcinoma. he was subsequently discharged with mg of calcium tablets twice a day. he was recommended to have close follow up in the outpatient setting for the continuation of care. acutely altered mentation is one of the common reasons that require hospitalization. an acute cognitive impairment or delirium is often associated with an underlying illness [ ] . there are multiple etiologies that may contribute to acute delirium. in a prospective study conducted in elderly patients by francis et al., it was discovered that common risk factors such as abnormal electrolytes, dementia, fever or hypothermia, medication side effects, and azotemia were associated with delirium [ ] . our patient, an otherwise healthy individual with no pertinent medical history, was suddenly found to be delirious by his neighbor. he had received extensive workup in the medical intensive care unit to rule out potential causes that may explain his acute encephalopathy. there were initial concerns that his acute delirium could be contributed by an infectious process as he was treated with empirical broad-spectrum antibiotics. later on, dexamethasone was added to his treatment regimen as there was a positive neurological finding of nuchal rigidity to cover for acute meningoencephalitis. however, these differential diagnoses were soon eliminated, as hypercalcemia was the cause of the delirium. primary hyperparathyroidism is mostly caused by a solitary benign adenoma (from to %). nevertheless, other causes include double adenomata (from to %), diffuse or nodular hyperplasia (from to %), or parathyroid carcinoma (< %) [ ] . severe hypercalcemia is defined as serum calcium > mg/dl. it is often associated with severe clinical symptoms, including stupor, confusion, lethargy, and coma [ ] . the first step in managing hypercalcemia is to confirm the result of hypercalcemia via total calcium corrected for albumin. the degree of hypercalcemia could serve as an indicator of the possible underlying etiology once the value is confirmed. serum calcium of greater than . mg/dl is unusual for hyperparathyroidism, whereas it is a strong suspicion for underlying malignancy [ ] . parathyroid carcinoma's important clinical manifestations are related to various factors such as the age, serum calcium level, and the parathyroid hormone level. according to data obtained from a retrospective study conducted by quinn et al. at a tertiary referral center that investigated , patients who were referred for surgical evaluation, patients were later found to have papillary carcinoma [ ] . parathyroid carcinoma patients had larger tumor sizes, higher mean serum calcium and pth levels, and also had a higher incidence for hypercalcemic crisis comparing to patients with atypical adenomas. furthermore, the mean serum calcium and pth levels were . mg/dl and pg/ml, respectively [ ] . interestingly, our patient had an impressive initial serum calcium level of . mg/dl along with pth level that peaked at . pg/ml. we opted to perform a ct scan of the chest, abdomen, and pelvis as there was a strong suspicion of malignancy in order to evaluate for anatomical staging as well as pre-operative planning. based on findings from a retrospective review of patients with parathyroid carcinoma from the national cancer database from to by asare et al., it was discovered that the age of the patients, tumor size, and sex had an impact on the five and years overall survival rate of the patients [ ] . the primary treatment for parathyroid carcinoma is surgical resection, as it offers the greatest chance for potential cure [ ] . however, it is advised that the serum calcium levels should be controlled prior to surgery as our patient's hypercalcemia was normalized after being treated with intravenous fluids, calcitonin, cinacalcet, and pamidronate. moreover, adjuvant radiation therapy did not show an absolute survival benefit, whereas other forms of treatment, including chemotherapy and bio-modifying agents, currently remain unproven and experimental. unfortunately, re-operative surgery should be considered if there is a reoccurrence of malignancy or persistent carcinoma induced hypercalcemia [ ] . it was noted that % of the patients were cured after the initial surgical resection, % of the patients had a reoccurrence that required reoperation, and % of the patients experienced a short and aggressive clinical course [ ] . parathyroid carcinoma is a rare but potentially fatal cause of primary hyperparathyroidism. it is crucial to have prompt surgical evaluation after initial medical stabilization of the patient that often requires intensive care unit level of care. close follow-up is essential as patients could develop complications or reoccurrence of the malignancy after the initial surgical resection. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. parathyroid carcinoma: update and guidelines for management a systematic review of the diagnosis and treatment of primary hyperparathyroidism from to . otolaryngol head neck surg a: acute confusion a prospective study of delirium in hospitalized elderly primary hyperparathyroidism in the s. choice of surgical procedures for this disease understanding hypercalcemia. its metabolic basis, signs, and symptoms differential diagnosis of hypercalcemia modern experience with aggressive parathyroid tumors in a high-volume parathyroid carcinoma: an update on treatment outcomes and prognostic factors from the national cancer data base (ncdb) parathyroid carcinoma: a review . head neck surgical treatment of parathyroid carcinoma (review) key: cord- -yemg ds authors: jameel, tahir; baig, mukhtiar; gazzaz, zohair j title: persistence of reverse transcription-polymerase chain reaction (rt-pcr) positivity in covid- recovered patients: a call for revised hospital discharge criteria date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: yemg ds in the world scenario, the advent of covid- has halted every aspect of life. it influenced every field of life, including the economy, and revealed the inadequacies in all nations' healthcare systems, from the most developed to the underdeveloped countries. there is a debate about the timing of antibodies production and detection during the disease. what is the significance of reverse transcription-polymerase chain reaction (rt-pcr) viral ribonucleic acid (rna) in symptom resolving period? in the present manuscript, we have evaluated these points. the covid- pandemic has adversely affected the world scenario. it has influenced every area of life, caused the loss of precious lives, and altered social, mental, and psychological wellbeing and global gross domestic product (gdp) [ ] . however, this pandemic also brought the opportunity to improve our healthcare facilities. the diagnosis of covid- depends on clinical presentation and essential investigations. the gold standard test remains the reverse transcription-polymerase chain reaction (rt-pcr) assay for the detection of viral ribonucleic acid (rna) in oropharynx or nasopharynx. we have assessed rt-pcr and antibodies assay utility in covid- patients in this brief review. we searched the national library of medicine (pubmed) by using the search term "rt-pcr test in covid- patients," and "antibodies test in covid- patients," and found , and , results, respectively. we narrowed our search by removing duplicate articles and abstracts, we downloaded full-text articles and selected only those articles that showed post-discharge viral rna positivity. the emergence of covid- has flipped the world upside down. soon after its onset, the covid- was isolated and recognized via real-time rt-pcr. its incubation period is around three to nine days ( figure ). in around % of cases, the transmission of covid- occurs before the symptomatic phase. about % of rt-pcr positive patients remain asymptomatic [ ] . on recovery, symptoms disappear in almost ten days, but pharyngeal and oropharyngeal viral shedding is continued till around - days. the clearance of fecal shedding takes a longer time to resolve than the throat sample in almost %- % of patients [ ] . that's why patients are advised to observe strict hygienic measures, especially after using the toilet. the hospital discharge criteria for covid- patients upon recovery includes the absence of respiratory symptoms, afebrile for the last three days, radiological improvement of chest exudates (by x-ray or ct scan), and two upper respiratory tract samples negative for viral rna in rt-pcr assay, collected at the interval of at least hours. in the case of asymptomatic patients, the rt-pcr should be documented negative after days [ ] . several researchers have reported that sometimes after satisfying all criteria of discharge from hospital or quarantine, patients continued to be rt-pcr positive for the next few days/weeks [ ] [ ] [ ] [ ] [ ] ( table ) . there are certain possibilities, one being that rt-pcr can detect the presence of viral rna irrespective of its virulence. during viral infections, the immunological system of the body produced specific antibodies against the infecting strain. the initial response is the production of immunoglobulin m (igm), which can be detected up to three days of infection. after this, a highly specific igg response can be observed. it plays a major role against the virus and is associated with signs of recovery. it also provides immune memory, and the person is resistant against the specific strain of the infecting virus [ ] . in the majority of covid- patients, the identification of igm provides evidence of acute infection. in contrast, igg specific to the virus strain protects the individual from succeeding reinfection and can be used in the form of immune serum therapy to serious patients. over time igm concentrations fall, and igg remains high and exponential rise is seen in the case of reinfection [ ] . it has been observed that viral rna is present for a comparatively longer time in patients with comorbidities and were receiving glucocorticoids [ ] . there is a need to revaluate the discharge criteria of covid- patients as most of the patients have to wait because of rt-pcr finding. instead, if we take the help of igg antibody levels by sensitive techniques like enzyme-linked immunosorbent assay (elisa), igg's rising titers in a convalescent patient are diagnostic of recovery from the disease. who, in the latest newsletter "criteria for releasing covid- patients from insolation," advised not to keep on waiting for rt-pcr to become negative; instead, the decision should be based on clinical and essential laboratory investigation like the presence of neutralizing antibodies. as in the presence of neutralizing antibodies, a nonsymptomatic person cannot transmit the disease to others [ ]. the number of cases of covid- has increased so much that now the previously laid criteria of quarantine and admission in the hospital are being revised the world over because of the scarcity of resources as compared to the number of patients. when the covid- patient recovers, the discharge criteria from the hospital are meticulous, and the patient may wait a long time to be released from isolation because of the positive rt-pcr assay. alternatively, if we use sensitive techniques such as eliza to measure igg antibody levels, the rising igg titers (neutralizing antibodies) in a convalescent patient diagnose the disease's recovery. the doctor-patient relationship is centered around the well-being and safety of our patients. at the same time, we should make sure that our patients do not create coronavirus disease (covid- ) pandemic and economic impact clinical characteristics of asymptomatic infections with covid- screened among close contacts in nanjing persistence and clearance of viral rna in novel coronavirus disease rehabilitation patients positive rt-pcr test results in patients recovered from covid- post-discharge surveillance and positive virus detection in two medical staff recovered from coronavirus disease (covid- ), china a case series of recurrent viral rna positivity in recovered covid- chinese patients characteristics of pediatric sars-cov- infection and potential evidence for persistent fecal viral shedding igm in microbial infections: taken for granted world health organization: clinical management of severe acute respiratory infection when novel coronavirus (ncov) infection is suspected world health organization: criteria for releasing covid- patients from isolation, scientific brief key: cord- -g ro pbb authors: terrigno, vittorio r; tan, jian liang; singh, devinder; sabir, sajjad a title: right atrial thrombus in a patient with covid- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: g ro pbb coronavirus disease (covid- ) is a worldwide pandemic. evidence suggests a strong association between covid- and pro-thrombotic states. we report our experience in managing a patient with covid- complicated by a right atrial thrombus. we highlight the successful use of half-dose anticoagulation in the treatment of right atrial thrombus in a patient with covid- . to our knowledge, this is a first reported case of right atrial thrombus in a covid- patient who was treated successfully with half-dose anticoagulation. coronavirus disease (covid- ) is a dangerous infectious disease that can affect multiple organ systems. while no definitive treatment has been established, it is apparent that early diagnosis is essential for the initiation of supportive measures and treatment with the end goal of preventing rapid respiratory collapse. hypercoagulable states as well as the many complications that can be associated with an increased state of coagulation have been strongly associated with this disease. it is important that the medical community continues to discuss and examine the appropriate preventative and therapeutic interventions to combat this specific aspect of this disease course. a -year-old woman with asthma and hypertension presented to the emergency room with a one-week history of dyspnea. she had an exposure to an individual who tested positive for severe acute respiratory syndrome coronavirus (sars-cov- ). on examination, she was able to speak in full sentences. her oxygenation saturation was % on room air, which improved to % with a non-rebreather facemask. wheezing and diminished breath sounds were present on lung auscultation. her respiratory status declined with an increased work of breathing within minutes of her presentation, which prompted endotracheal intubation. her intubation course was complicated due to significant laryngeal edema and a brief episode of pulseless ventricular tachycardia with return of spontaneous circulation after three cycles of chest compressions. she required intravenous (iv) norepinephrine to achieve a mean arterial pressure of mm hg. laboratory tests demonstrated lymphopenia and abnormal biomarkers (creatinine of . mg/dl, procalcitonin of . ng/ml, c-reactive protein of mg/dl, d-dimer of . ug/ml, lactate dehydrogenase of , u/l, ferritin of , ng/ml, and lactate of . mmol/l). her initial high-sensitivity troponin was ng/l and peaked at mg/l. postcardiac arrest transthoracic echocardiogram (tte) revealed reduced biventricular systolic function and a mobile echo dense mass in the right atrium (ra) (figures , and videos , ). she was eventually taken off of iv norepinephrine on hospital day and showed some clinical signs of improvement. however, despite receiving hydroxychloroquine, azithromycin, and lopinavir/ritonavir, her respiratory status once again worsened. her family decided to proceed with a compassionate extubation due to worsening of her covid- illness and she expired on hospital day . due to hospital protocol during the covid- pandemic and the family's wish, prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia incidence of thrombotic complications in critically ill icu patients with covid- covid- and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: jacc state-ofthe-art review in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. autopsy was not performed. in a retrospective single center study of covid- icu patients from china, % ( / ) of the patients developed venous thromboembolism (vte). these patients had an elevated ddimer, similar to our patient. none of the patients had received vte prophylaxis [ ] . in another three-center retrospective study of covid- icu patients from the netherlands, the authors reported % incidence of thrombotic complications. all patients received standard thromboprophylaxis. of note, the diagnostic testing was only carried out in patients with a suspicion of thrombotic complications [ ] . therefore, the true incidence is likely higher.our case supports the need to think of initiating therapeutic anticoagulation early in the course of critically ill patients with covid- . in a publication by an international collaborative of clinicians and investigators, a majority of the panel members recommended prophylactic dose anticoagulation, but a minority supported considering even intermediate to therapeutic dose anticoagulation [ ] . in addition to this, our case also highlights the use of half-dose anticoagulation therapy to treat a right atrial thrombus. patients with covid- may need prone positioning, which makes monitoring for bleeding difficult and frequent neurological checks difficult. in addition to this, patients with other bleeding risks may not be able to receive full-dose anticoagulation. to our knowledge, this is the first reported case of right atrial thrombus in a covid- patient that resolved with a half dose of thrombolytic therapy. our case report highlights the continued need for the consideration of early anticoagulation in patients with covid- . numerous studies have shown a direct correlation between hypercoagulable states and covid- infection. we highlight the ability to treat a right atrial thrombus in a patient with covid- with half-dose anticoagulation. this may be beneficial in patients with covid- who require prone positioning and frequent neurological checks as well as for covid- patients who are at higher risk when receiving thrombolytic therapy. human subjects: consent was obtained by all participants in this study. irb cooper university hospital issued approval n/a. the patient in our case report is deceased and we were unable to reach her next of kin for consent. we contacted our irb department requesting an approval letter, but it was deemed that our case report does not meet the definition of a human subject per cfr . (f) and would not fall under the irb purview. we took great care to ensure that we did not include any identifiable patient health information in our case report. . key: cord- -ds uw y authors: ahmed, jawad; malik, farheen; bin arif, taha; majid, zainab; chaudhary, muhammad a; ahmad, junaid; malik, mehreen; khan, taj m; khalid, muhammad title: availability of personal protective equipment (ppe) among us and pakistani doctors in covid- pandemic date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ds uw y background the coronavirus disease (covid- ) pandemic has put an excessive strain on healthcare systems across the globe, causing a shortage of personal protective equipment (ppe). ppe is a precious commodity for health personnel to protect them against infections. we investigated the availability of ppe among doctors in the united states (us) and pakistan. methods a cross-sectional study, including doctors from the us and pakistan, was carried out from april to may , . an online self-administered questionnaire was distributed to doctors working in hospitals in the us and pakistan after a small pilot study. all analysis was done using statistical package for social science (spss) version . (ibm corp., armonk, ny). results after informed consent, doctors ( . % from pakistan and . % from the us) were included in the analysis. the majority of the participants were females ( . %), and the mean age of the participants was . ± . years. most doctors ( . %) were from medicine and allied fields. among the participants, . % of doctors from the us reported having access to masks/n respirators, . % to gloves, . % to face-shields or goggles, and . % to full-suit/gown. whereas, doctors in pakistan reported to have poor availability of ppe with only . % having access to masks/n respirator, . % to gloves, . % to face-shields or goggles, and . % to full-suit/gown. the reuse of ppe was reported by . % and . % physicians from the us and pakistan, respectively. more doctors from pakistan ( . %) reported that they had been forced to work without ppe compared to doctors in the us ( . %). conclusion there is a lack of different forms of ppe in the us and pakistan. doctors from both countries reported that they had been forced to work without ppe. compared to the us, more doctors from pakistan reported having faced discrimination in receiving ppe. after informed consent, doctors ( . % from pakistan and . % from the us) were included in the analysis. the majority of the participants were females ( . %), and the mean age of the participants was . ± . years. most doctors ( . %) were from medicine and allied fields. among the participants, . % of doctors from the us reported having access to masks/n respirators, . % to gloves, . % to face-shields or goggles, and . % to fullsuit/gown. whereas, doctors in pakistan reported to have poor availability of ppe with only . % having access to masks/n respirator, . % to gloves, . % to face-shields or goggles, and . % to full-suit/gown. the reuse of ppe was reported by . % and . % physicians from the us and pakistan, respectively. more doctors from pakistan ( . %) reported that they had been forced to work without ppe compared to doctors in the us ( . %). there is a lack of different forms of ppe in the us and pakistan. doctors from both countries reported that they had been forced to work without ppe. compared to the us, more doctors from pakistan reported having faced discrimination in receiving ppe. the novel coronavirus, initially originating from the hubei province of china, has spread to nearly every continent, overwhelming and straining even the most sophisticated healthcare systems [ ] . the severe acute respiratory syndrome coronavirus (sars-cov- ) is transmitted through inhalation or contact with infectious droplets. it may be asymptomatic early on in the course or present with mild respiratory symptoms, headache, fever, fatigue, nausea, vomiting, in addition to some reports describing hematological and cardiac involvement [ ] . healthcare workers (hcws) or individuals who tend to coronavirus disease patients are at highest risk of contracting the infection. the prevention of the spread of infection to and from medical personnel solely lies in the effective use of personal protective equipment (ppe), including gloves, face masks, airpurifying respirators, goggles, face shields, respirators, and gowns. the rampant nature of covid- has created a shortage of ppe in high demand areas. the abrupt increase in the demand for ppe has to be met with an accelerated manufacturing and supply of ppe. many healthcare systems are failing to provide ppe due to financial or time constraints. there have been multiple reports of hcws protesting about the lack of appropriate ppe, and instances of doctors and other healthcare staff being forced into working without this precious commodity [ , ] . the healthcare system of the united states (us) is known all over the world for its innovative and highly specialized patient care. the us spends a significant amount ( . %) of the country's gross domestic product (gdp) on health care, which is far more on health care as a percentage of its economy than any other developed nation [ ] . nonetheless, the us has the highest number of cases ( , , cases and , deaths; may , ) of covid- , and despite being the pinnacle of modern medicine, the healthcare system is strained and stretched to its very limits [ ] . as expected, the situation in developing countries, with weaker healthcare infrastructure, is even direr. the covid- pandemic was confirmed to have reached pakistan on february , [ ] . in pakistan, , cases have been reported with deaths till may , [ ] . consequently, the already struggling health care system of pakistan is not equipped for large pouring in of potentially infectious patients seeking testing and care [ ] . resources are stretched thin, and the number of hcws being infected is rising every day. in this context, we sought to examine the availability of ppe in pakistan (a resource-constraint country) and the us (resource-rich country) as well as draw a comparison between the two in terms of availability, discrimination in distribution and perceived reasons for the shortage of ppe. a cross-sectional study was carried out among doctors in the us and pakistan using convenience sampling. the study duration was from april to may , . a self-administered questionnaire was made using google forms and was distributed to doctors in the us and pakistan via emails and social media platforms. the bias of receiving irrelevant (non-doctors) responses was reduced by posting the questionnaire on doctor/physician-only groups. the credibility of social media groups was ensured that they only admit licensed doctors after confirming their registration numbers and affiliations. the inclusion criteria consisted of three points, ( ) a practicing doctor, ( ) work in a hospital, and ( ) currently working in pakistan or the us. responses of doctors working in private clinics were excluded from the study. explanation of the study's aim, as well as the informed consent form was present at the start of the questionnaire, permitting us to collect the data. a structured questionnaire consisting of four major parts was designed by authors (see appendices section). the initial draft of the questionnaire was sent to multiple senior doctors for evaluation, and all appropriate suggestions were incorporated in the questionnaire. the first part consisted of a brief explanation of the study, informed consent statement, and demographic variables such as country name, age, gender, the specialty of work, and hospital type (private or public). the second part consisted of questions to assess the availability of different forms of ppe, including n respirator, masks, gloves, eye protection (goggles or face shield), and full-suit/gown. the third part consisted of questions to assess any discrimination in ppe distribution, perceived reasons for its shortage, the extent of reuse of ppe, and to identify if doctors had been forced to work without ppe. the last part consisted of questions about the likelihood of quitting the job if adequate ppe was not provided and feelings of doctors working in the pandemic situation. in total, the questionnaire consisted of items. a small pilot study was carried out among doctors from each country (pakistan and the us) to ensure that no ambiguity exists in the questionnaire. recent contact with covid- patients was defined as a contact within the last three days of filling the questionnaire. all the data were entered and analyzed through statistical package for the social sciences software (spss version . ; ibm corporation, armonk, ny, us). results were drawn through descriptive statistics, and means with standard deviation were presented for continuous variables such as age and amount of money spent on purchasing ppe. categorical variables were reported as frequencies with percentages. chi-squared and independent sample t-tests were used to find statistical significance, and a p-value of < . was considered significant for all analyses. a total of doctors ( ; . % males) from both countries ( . %; n = from pakistan and . %; n = from the us) were included in the analysis. the mean age of participants was . ± . years, and most of the respondents ( . %; n = ) were from medicine and allied fields. the demographics of the participants are noted in table ppe availability was reported significantly more (p < . ) among doctors in the us than doctors in pakistan. in the us, . % (n = ) doctors reported having access to all forms of ppes (including n respirators/masks, gloves, gowns/full-suits, and face-shields or goggles) in their hospitals, whereas only . % (n = ) of doctors in pakistan reported having this privilege. among the participants, . % (n = ) of doctors from the us reported having access to masks/n respirator, . % (n = ) to gloves, . % (n = ) to face-shields or goggles, and . % (n = ) to full-suit/gown. in contrast, doctors in pakistan reported to have poor availability of ppe with only . % (n = ) having access to masks/n respirator, . % (n = ) to gloves, . % (n = ) to face-shields or goggles, and . % (n = ) to full-suit/gown. more than half ( . %; n = ) of n respirator users in the us reported to have size-fitted masks, whereas only a quarter ( . %; n = ) of participants from pakistan reported sizefitting for their n respirator in pakistan. in our analysis, . % (n = ) and . % (n = ) doctors from the us and pakistan reported reusing ppe, respectively. the details of the frequency of reusing ppe for the us and pakistan are graphically presented in figure . chi-squared test and independent sample t-test were used to find statistical significance between the variables. in the absence of ppe, significantly higher (p < . ) number of doctors in pakistan ( . %; n = ) reported to have kept working in contrast to doctors form the us ( . %; n = ). moreover, a significantly higher (p < . ) number of doctors from pakistan ( . %; n = ) reported that they had been "bullied into working" without ppe as opposed to the us doctors ( . %; n = ). shortage of supply ( . %; n = ) and inadequate/poor distribution management ( . %; n = ) were reported as the most common reasons for the lack of ppe ( table ). other reasons reported by doctors from the us and pakistan are given in figure . a total of ( . %) doctors, with ( . %) from pakistan and ( . %) from the us reported that they would "likely quit" their job and ( . %) doctors (the us = ; pakistan = ) proclaimed that they would "definitely quit" if they do not receive proper ppe in the future ( table ) . almost three-fourth ( %; n = ) doctors from pakistan and . % (n = ) from the us reported that hcws in their hospitals had been infected by covid- . half of the respondents from the us ( . %; n = ) and pakistan ( . %; n = ) expressed that they felt scared working in a pandemic situation ( table ) . almost one-third ( . %; n = ) doctors from pakistan and one-fourth ( %; n = ) doctors from the us reported that they felt purposeful and proud of themselves for working in the pandemic (figure ). the summarized results of the study and responses of doctors from both countries are presented in table and table . chi-squared test and independent sample t-test were used to find statistical significance between the variables. one of the most substantial strategies to protect both patients and hcws from transmittable pathogens is the adequate use of ppe. in our study, the availability of ppe was reported to be better among the us doctors as compared to pakistani doctors. more doctors in pakistan faced discrimination in receiving ppe, and the reuse of ppe was reported by the doctors from both countries. according to the world health organization (who), the essential supplies of ppe include gowns, gloves, masks or respirators, goggles, face shields, head cover, and rubber boots. since covid- is primarily transmitted by contact or droplet and its definite cure has not been discovered yet, the only significant and emotive subject for the hcws is ppe. the types of protection required to combat the specific mode of transmission include ( ) gloves and aprons as contact precautions, ( ) gloves, aprons, fluid-resistant surgical masks with or without eye protection (goggles or a visor) for droplet transmissions, and ( ) gloves, fluid repellant longsleeved gowns, eye protection, and filtering facepiece / (ffp / ) mask or n respirator during aerosol-generating procedures [ ] . our study population comprised of doctors from two countries having a vastly different landscape of healthcare and helped us in comparing the difficulties faced by both countries in the face of a pandemic. a comparison of ppe availability in the us and pakistan with reports from the uk is shown in table . our results are consistent with reports from the uk that some protective equipment such as gowns/full-suits and eye protection are scarce [ ] . almost three-quarters of the doctors from pakistan reported that they were not size fitted for their n respirator. these results are alarming as the improper fitting of the n respirator reduces its efficacy and can make doctors susceptible to infection [ ] . in our study, doctors from the us reported to have comparatively better access to ppes, however, they too, are struggling to maintain adequate ppe supply in light of the overwhelming influx of cases, and are not out of danger to get infected. for the worst-hit cities like new york and san francisco, donations were called for from the locals, to ease the state of desperation [ ] . the strategic national stockpile (sns), which was responsible for making ppes available during epidemics of ebola virus and h n influenza, is currently making an effort to balance between a quick distribution and restocking [ ] . part of the problem could be attributed to the unpreparedness of the authorities despite multiple warnings of a possible influenza pandemic in the near future [ ] . furthermore, the us had decreased its production of masks, gowns, and gloves and hugely relied on imports from countries like china [ ] . in our study, more than one-third of the doctors from pakistan ( %) reported reusing one ppe for more than one week, while most of the doctors in the us ( %) reported reusing one ppe for two days. in times of extreme shortages and the rapidly increasing cases, the health and safety executive (hse) recently issued guidance that recommended reusing ppes, which followed a skeptical response by the hcws of england [ ] . the guidance stated reusing water-resistant equipment and promoted the use of sealable bags for storage, whereas washable gowns or similar long-sleeved articles of clothing were advised as replacements for medical gowns [ ] . in literature, several methods of disinfection have been described, which include the use of hydrogen peroxide vapors, ultraviolet (uv) radiation, moist heat, dry heat, and ozone gas, with hydrogen peroxide vapors being the most widely suggested technique [ ] . reuse of ffp after appropriate measures has been considered a suitable alternative; however, it is uncertain to state the same for surgical masks [ ] . although our study reported that a large majority of physicians from the us and pakistan reusing their pieces of equipment, the exact method of decontamination being administered is beyond the scope of this study and needs further evaluation. the dire shortage of protective gear does not seem to be the only concern of hcws worldwide as the biased distribution and supply further add to the trouble. analysis of our data showed that doctors from pakistan faced greater discrimination in receiving ppe, with one of the main reasons being lack of seniority in position, which is surprising since a large workforce in tertiary care hospitals comprises of junior training doctors. our study showed that . % and . % of doctors from pakistan and the us, respectively, were forced to work without ppe. when compared to the reports from the uk, where % of doctors felt pressurized to work despite inadequate ppe, our figures are lower, but they cannot be ignored [ ] . news of doctor being arrested for demanding ppe in pakistan has also been reported [ ] . several factors have contributed to the shortage of ppes on a global scale. one reason is the psychological 'fear of uncertainty' among masses, giving rise to panic buying and hoarding of masks and gloves along with other essential products. in the current era of globalization, the supply of any product is dependent on its demand; however, with the advent of this sudden calamity, the demand has escalated multiple folds in a short duration, leaving the suppliers struggling to keep up. disruption in the supply and demand graph has resulted in a higher equilibrium price, and certain opportunists are trading the life-saving essentials at staggering rates. another major aspect contributing to the crisis is the travel/export restrictions halting china's trade, which produces and supplies nearly % of the worldwide face masks along with other types of safety equipment [ ] . the shortage of supplies on a global scale has not only rendered several nations to improvise and innovate but also highlighted the significance of national self-dependency. who, at the beginning of march , advised the relevant industries and governments to ramp up the manufacturing of ppes by % to curb the ever-increasing demand [ ] . regardless of the efforts of several non-governmental organizations (ngos) in pakistan to distribute ppes among doctors and donation of supplies from china as a gesture of goodwill, the level of protection of pakistan's hcws is nowhere near satisfactory. in the us, however, the role of ngos in contributing to ppe supply or healthcare system is limited, the reason being the notable difference in the socioeconomic status and spendings of both countries on their respective health budgets. even before the pandemic, the government-run tertiary-care hospitals of pakistan highly relied on the interventions from ngos and overseas donors, with the dependency increasing now more than ever. the majority of doctors in our study reported being scared of the current situation and feared that they might transmit the infection to their loved ones. the feeling is synchronous among doctors globally, particularly emergency room physicians, working in direct contact with the infected patients, and performing the intubation [ ] . the fear of infecting loved ones was responded positively by the vast majority of both pakistani and the us doctors, with . % and . % responses, respectively. the figure is comparatively greater than that found in a survey performed by royal college of physicians (rcp), stating that % of respondents worrying about spreading the disease to family members [ ] . almost % of participants of our study, from the us and pakistan, described feeling scared while working in a global pandemic. the study from rcp reported similar data, with % of their respondents feeling concerned about working in the current situation [ ] . the fear among hcws is real and justified as the infectivity and mortality due to covid- is increasing every day. similarly, a study on the effect of the sars outbreak ( - ) on hcws described a significant sense of threat to life, vulnerability, along with the somatic and cognitive impact [ ] . in our study, about ( %) pakistani participants felt like quitting their job due to lack of ppe, which was higher than the response from the us doctors, ( . %) of which responded affirmatively. however, this figure is not in line with a study from greece published during the a/h n influenza pandemic in , where only . % of hcws reported opting for leave to avoid contracting the virus [ ] . even a recent article from the same country (greece) reported the willingness of hcws to work during the current pandemic to be unaffected [ ] . the readiness to work, in turn, may be dependent on the socioeconomic status of a state, the trust of its service workers on government, and the severity of the situation. other factors may include but are not limited to gender, childcare responsibilities, personal safety, and protective measures [ ] . in our study, % of doctors from pakistan and . % from the us reported that hcws in their hospitals had been infected with covid- . in china, an estimated , hcws were infected, and expired due to "insufficient protective equipment" [ ] . these statistics are alarming, for the war against covid- is yet to be over. as the number of infected/dead hcw rises, the anxiety and reluctance of other hcws to work will also increase [ ] . the general public should be made aware of the fact that ppe is crucial for hcws on the frontline and n respirators, full-suits/gowns or eye protection are not required for daily life uses. it is suggested to introduce a proper surveillance system for the distribution of ppe among doctors in a healthcare setting. social media spreading unauthentic information and promoting black marketing to escalate prices should be banned. the shortage of ppe can cripple the healthcare system. as more healthcare personnel will get infected with covid- , the workforce fighting against pandemic will decrease. a recent study conducted in a resourcelimited setting found that ward assistants have not been adequately educated about hygiene protocols [ ] . educating ward assistants is equally important regarding the proper use of hand disinfectants and ppe, so they do not act as a vector for transmitting infections to healthy patients in this time of covid- pandemic. alternative methods for the conservation of these limited and indispensable commodities need to be employed. at present, some healthcare systems are disinfecting or reprocessing ppes using appropriate techniques reported by who or using telemedicine tools for performing medical exams as a form of electronic-ppe [ , ] . furthermore, recommendations of reprocessing n respirators using hydrogen peroxide vapors or uv light have surfaced. although resourceful, these methods lack standardized protocols, and the efficacy of the disinfection process is still uncertain [ ] . our study is limited by its online-survey nature, small sample size, and reporting bias, as some responses may be driven by personal emotions of doctors. to conclude, there is a shortage of ppe in hospitals of the us and pakistan due to covid- and doctors are feeling scared working without adequate protection in the pandemic situation. some doctors even reported that they are likely to quit their job if they do not receive proper ppe in the future. adequate ppe is crucial in the battle against covid- , and radical steps need to be taken by hospital administrations and governments to make ppe more accessible to doctors and other hcws. there is a need to educate the general population regarding ppe usage and make them realize that doctors and other hcws are the ones that need them the most. further research is required on this topic that includes other healthcare personnel, and a need to study the opinion of the general population regarding ppe usage is suggested. availability of personal protective equipment (ppe) is a pressing issue for doctors working in covid- pandemic. the study aims to assess the availability of ppe to all doctors currently working. the data will be kept confidential and no names and institution details are required. if you meet the following criteria, only then please fill the form ( ) are a practicing doctor, ( ) work in a hospital (if you work in a private clinic you are ineligible to fill the questionnaire), and ( ) working in pakistan or united states. by filling the questionnaire you agree to be part of the study and agree to provide information to the best of your knowledge. the study data will be used for publication in any journal. thank you for taking part in the study. your response has been recorded. human subjects: consent was obtained by all participants in this study. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. covid- : the crisis of personal protective equipment in the us cardiac manifestations of coronavirus disease (covid- ): a comprehensive review. cureus. healthcare workers protest for vital protection equipment doctors lacking ppe "bullied" into treating covid- patients world health organization: united states of america world health organization: novel coronavirus (covid- ) situation reports drugs ther perspect. personal protective equipment during the covid- pandemic -a narrative review comparing the protective performances of types of n filtering facepiece respirators during chest compressions: a randomized simulation study why america ran out of protective masks -and what can be done about it rimmer a: covid- : experts question guidance to reuse ppe disposable masks: disinfection and sterilization for reuse, and non-certified manufacturing, in the face of shortages during the covid- pandemic pakistan doctors beaten by police as they despair of 'untreatable' pandemic china makes them, but has been hoarding them world health organization: shortage of personal protective equipment endangering health workers worldwide as coronavirus spreads, doctors fear for themselves -and their families nearly half of doctors fear for their health -survey psychological impact of severe acute respiratory syndrome on health workers in a tertiary hospital general hospital staff worries, perceived sufficiency of information and associated psychological distress during the a/h n influenza pandemic covid- pandemic and its impact on mental health of healthcare professionals healthcare workers' willingness to work during an influenza pandemic: a systematic review and meta-analysis. influenza other respir viruses what hospitals and health care workers need to fight coronavirus protecting health care workers during the covid- outbreak: lessons from taiwan's sars response (epub only) compliance and knowledge of healthcare workers regarding hand hygiene and use of disinfectants: a study based in karachi world health organization: rational use of personal protective equipment for coronavirus disease ( covid- ) and considerations during severe shortages electronic personal protective equipment: a strategy to protect emergency department providers in the age of covid- key: cord- -b c txut authors: neeki, michael m; dong, fanglong; archambeau, benjamin; cerda, melinda; ratliff, sireyia; goff, alan; roloff, kristina; tran, louis title: san bernardino county youth opioid response: improving access to evidence-based medical treatment for opioid use disorder date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: b c txut opioid use disorder (oud) and related overdose deaths have become a crisis of epidemic proportions in the united states. in , over million people age years or older misused opioids.substance use is also correlated with increased physical and mental health disorders, and developmental challenges among youths. medication-assisted treatment (mat) has been reported to reduce mortality, opioid use, and human immunodeficiency virus and hepatitis c virus transmission while increasing treatment retention in adults. the san bernardino county youth opioid response (sbcyor) program was formed to explore best practices for youths at risk of opioid use disorders and/or overdose. sbcyor is a coalition of professionals in healthcare, behavioral health, public education, law enforcement, emergency medical services (ems) agencies, and juvenile detention centers throughout san bernardino county, california. sbcyor focuses on high-risk and addicted individuals between the ages of to years in san bernardino county’s correctional system. it utilizes a strategy of collaboration, prevention, risk mitigation, medication, psychological treatment, and community outreach. this study aimed to evaluate the implementation and progress of sbcyor. the rate of opioid use and dependency has increased to the point of being a major public health priority in the united states over the last decade. in , the national survey on drug use and health (nsduh) reported that . million people aged years or older have misused opioids [ ] . the associated medical and social complications related to opioid use disorders (ouds) have also grown proportionately. addiction disorders strain public resources, emergency departments (eds), and correctional institutions. in , california providers issued more than . million prescriptions for opiates despite the , documented opiaterelated deaths [ ] . the opioid addiction epidemic continues to pose an ongoing threat to the health of americans. the youth populations (aged - years) are particularly vulnerable and have also been affected by the opioid crisis. youths may lack prefrontal cortical function leading to behavior inhibition and risk aversion [ ] . this contributes to a more substantial addiction pathology. in , more than , died from drug overdoses, making it the leading cause of injury-related deaths in adolescents and young adults in the united states [ ] . youths also have more serious mental illnesses, depression, and suicidality with a strong correlation to substance abuse [ ] . high risk sexual behaviors in this population also lead to sexually transmitted infections and/or unintended pregnancy. almost nine in pregnancies in adults with oud are unintended, and it is prudent to anticipate similar prevalence among youths [ ] . the office of the surgeon general has stated that medication-assisted treatment (mat) combined with psychosocial therapy and community-based recovery support is the gold standard for treating opioid addiction [ ] . however, youths may be excluded from these addiction treatment programs, as many programs are geared toward adults. feder et al. reported that only . % of adolescents received mat, as compared to . % of adults [ ] . additionally, youths may experience greater barriers in accessing care such as lack of insurance, reliable transportation and parental notification concerns [ ] . these barriers are magnified in youths with low socioeconomic status, in part due to complexities in health insurance coverage and access to safe treatment for drug dependence. in , orgera and tolbert suggested that patients with medicaid coverage were more than . times likely to receive treatment for oud than uninsured patients [ ] . even among commercially insured youths, only % received mat for oud [ ] . treatment strategies for oud are complex and multifactorial. recent emphasis on mat in conjunction with cognitive behavioral therapy (cbt) has shown to be effective in treating oud in adults [ ] . although not well studied among adolescents and young adults, clinical experience has not identified any age-specific safety concerns. matson et al. demonstrated that continued outpatient therapy with buprenorphine/naloxone (suboxone) achieved a high rate of long-term sobriety among adolescents and young adults [ ] . the american academy of pediatrics has recommended that pediatricians consider mat for adolescents with oud [ ] . the san bernardino county youth opioid response (sbcyor) program was formed to help mitigate the spread of oud, increase access to mat and reduce the risk of overdose for the youth populations. the program is a part of the california youth opioid response (yor california) project. sbcyor is a coalition of professionals in healthcare, behavioral health, public education, law enforcement, emergency medical services (ems) agencies, and juvenile detention centers throughout the county. it focuses on high-risk and addicted individuals between the ages of to years in san bernardino county's correctional system. the program utilizes a strategy of collaboration, prevention, risk mitigation, medication, psychological treatment, and community outreach. its goal is to integrate the county's available resources into a continuum of care to enable the youths of the community to grow into productive members of society, free of the burden of opioid use exposure, disorder and associated risks. the objective of this study is to evaluate the implementation and sustainability of the sbcyor program and its effects in the community to date. this is a prospective observational study of youths aged to years identified through san bernardino county's correctional, educational, and healthcare systems. data were extracted from the electronic health records (ehr) of the county's department of probation, the sheriff's department, and arrowhead regional medical center (armc), a county owned and operated safety net hospital. san bernardino county (sbc) is the largest geographic county in the united states with a diverse population of . million people. according to the census data, the racial makeup of sbc was . % latino, . % white, and . % african american [ ] . the county has a large proportion of low socioeconomic status individuals. approximately % of the population lives below the poverty level, and more than a quarter of the population is younger than years old [ ] . patients enrolled in the program were tracked and results from data were reported to yor california, in compliance with state and federal regulations. this study was approved by the armc institutional review board. eligibility for inclusion in this study was between age to years with a reported history of opioid use, the presence of opioid on a screening drug test, physical signs of drug use, or evidence of overdose or withdrawal. physical signs of drug use included the presence of track marks, lethargy, flu-like symptoms, unexplained somnolence or respiratory depression. a clinical opiate withdrawal scale (cows) score was used to assess the degree of opioid withdrawal. exclusion criteria was age less than or greater than years, refusal of enrollment, hypersensitivity to recommended medication, inability to obtain consent, active withdrawal from alcohol or benzodiazepine, or medical frailty. medical frailty was determined by an attending emergency physician in consultation with other subspecialties, after a thorough evaluation of the patient's medical history and present illness. examples of medical fragility include decompensated heart failure, severe liver disease, or poorly controlled psychosis. the program required participating providers to obtain an x waiver. the x waivered providers received extensive training and education in key aspects of mat including identification of individuals who may benefit from treatment, safe and appropriate use of federal drug administration-approved medications, strategies for communicating and educating patients and their families, and coordinating care with other community infrastructure. sbcyor implemented its community outreach program in phases ( after a thorough situation analysis, sbcyor agreed to focus on four primary objectives to guide design and implementation of the program. these four primary objectives were: to decrease the morbidity and mortality in the target population to increase access to effective treatment including medication assisted treatment to decrease the stigma associated with oud within the community to improve continuity of care for the target population to achieve these goals, sbcyor reached out and connected with the community, healthcare providers, and county agencies. team members attended community events, gathered and shared information and resources, and provided education for families to recognize addiction as a chronic medical condition, the signs and symptoms of oud. emphasis was placed on reducing exposure to opioid use and prevention of overdose. because oud in youth can begin with appropriately prescribed opiates, health care providers were educated about risk mitigation for patients and household members. mitigation efforts also included education and access to naloxone (the reversal agent for an opiate overdose). the coalition also explored the formation of a referral network, connecting patients to the existing resources for behavioral counseling services and mat within the community and the county. sbcyor established treatment protocols and safe prescribing practices amongst youths with oud, allowing x waivered providers to initiate mat by prescribing buprenorphine/naloxone. the x waivered providers also assessed youths at risk for oud, and performed interventions deemed appropriate. leadership of the program connected with established oud treatment programs such as the california bridge (ca-bridge) project, an initiative which developed hospitals' emergency departments into primary access points for treating acute symptoms of oud. sbcyor integrated with ca-bridge's established network, coordinated by armc, to help transition youths to outpatient-based mat clinics for continued therapy. sbcyor collaborated with local and county agencies to form a coalition. these agencies included school district leadership, law enforcement, ems, correctional facilities, behavioral health centers, and hospitals. specifically, sbcyor connected with the county's department of probation, department of behavioral health, the sheriff's department, armc, and the inland empire opioid crisis coalition (ieocc). site champions within each organization were identified and enrolled into the effort. once the coalition was established, these agencies were invited to actively participate in planning, refining, and eventual implementation of the program. sbcyor also reached out to community resources such as the local harm reduction coalition and mat clinics of the california hub and spoke system (ca h&ss) who also became key partners. the program officially launched on august , . the coalition provided site-specific training and technical assistance for healthcare providers in the detention facilities that would have encounters with the target population. screening assessment tools were created for nursing staff in the detention centers to streamline the process for appropriate referrals and treatment. figure presents the detailed triage algorithms. these screening assessment tools were instrumental in identifying and enrolling individuals who would potentially benefit from the program. sbcyor facilitated access to emergency departments and outpatient treatment centers for mat therapy. in addition, the program has an ongoing series of community outreach initiatives, including public service announcements, community events, and on-site teaching to increase and maintain community awareness and involvement. the program has also embraced technology in its efforts with the use of remote health screening and social media. designated case managers and substance use navigators (suns) helped guide patients through the complexities of the healthcare system, addressing their specific needs. they connected patients to outpatient mat centers based on specific needs such as insurance coverage, transportation, and appropriate referrals for comorbid conditions. the sun is expected to play a significant role in a patient's recovery, facilitating social support to help with living situations and dealing with external stressors. most importantly, the sun provided the patient with a constant point of contact whenever needed. all eligible youths identified by the county health staff within the probation and sheriff's departments detention centers were tracked. similarly, information on all youths who received mat through arrowhead regional medical center (armc) were collected. data collection was reported by providers and tabulated by the sun. providers were able to notify the sun through phone calls, hipaa compliant emails, or the consult function of the electronic record. once the patient was released from a facility, the sun followed the youth via individualized home visits, phone calls or video telehealth visits. data were collected and reviewed weekly by the program director and steering committee. a more detailed analysis of the compiled data was performed monthly and quarterly. based on the observations and findings of these analyses, the program was continually refined accordingly. the goal was to identify areas of need for immediate attention and/or resources diversion. while the sbcyor program was created through grant funding from the substance abuse and mental health services administration response to the opioid epidemic, it was important to institutionalize practices and partnerships to gain financial independence with the goal of becoming less reliant on future grant funds. thus, the program focused on embedding best practices and workflows at an organizational level to be integrated into funding systems of each coalition partner. the mat program in each institution is now integrated into the standard medical services provided by physicians and advanced providers and has become part of standard practice. after initial preparation and coordination with the grant originating organization, california institute for behavioral health solutions (cibhs), implementation of the sbcyor program was initiated in august . the core operations team was formed and members were assigned roles and responsibilities. a timeline was created with goals and milestones established. the core team set out to secure site champions at contributory facilities. these facilities included california university of science and medicine (cusm) and its affiliated hospital, armc, along with west valley detention center, sbc juvenile detention center, and local school districts as target sites. a website and online social media presence were created to announce the launch of the program and give a point of contact for the community. over the next three months, policies and procedures were created and the medical staff at participating institutions were trained. the program implementation was piloted in the juvenile detention center and later expanded to the adult detention center. by october , % of the healthcare staff in the detention centers received training on oud and mat. the educational team members also reached out to train other county's facilities and programs, such as halfway houses, public schools, and law enforcement agencies. in december , an agreement with local probation leadership was reached to include the opioid use disorder and naloxone (narcan) training into the permanent training protocol for the probation academy program. the program trains - new officers per year. narcan training was incorporated into standard departmental training for all officers, with additional officers trained per year. in order to reach the largest audience, sbcyor is working with the local school districts to bring the educational teams to junior high and high schools. . %) and received treatment ( ; . %) both increased from q to q . in total, % ( / ) of patients referred for evaluation were successfully enrolled into treatment. the decrease in total screens from q to q is thought to be a consequence of the current covid- pandemic. during q , california governor gavin newsome issued stay-at-home orders to mitigate the spread of the sars-cov- , the coronavirus that is responsible for covid- . the crime rates in sbc saw a subsequent drop when compared to [ ] . this likely affected the number of individuals being sent to correctional facilities. despite the decrease in total youths screened, the total number of patients referred for evaluation ( ; . %) and treatment ( ; . %) both increased from q to q . data collection became more detailed as the program grew and developed. by q , sbcyor was able to tabulate and evaluate demographic data for all patients who were enrolled into the system. table presents detailed demographic data. among the youths who were screened, a significant majority were males ( . %, n = ) and in the - years age group ( . %, n = ). more than half were hispanic or latino ( . %, n = ), followed by black or african american ( . %, n = ) and white ( . %, n = ). despite preparation for treatment of pregnant youths within this program, we did not receive a referral for pregnancy during the study period. opioid use disorders are chronic conditions with substantial personal and societal costs [ ] . the pathophysiology of opioid use disorder is well understood. morgan and christie have demonstrated that opioid tolerance may develop rapidly, even after limited use [ ] . susceptible individuals will therefore experience more pain and discomfort than normal when the opioid effect is removed. this can lead to recreational misuse, and addiction in people who use opioid medications chronically [ ] . substance use disorder is a medical condition with structural and chemical brain changes [ ] . dugosh et al. have concluded that behavioral therapy alone is not effective in maintaining abstinence in patients with oud [ ] . medication-assisted treatment (mat) has been effective and is currently the gold standard for treating oud [ ] . current clinical evidence indicates that the risk of relapsing increased when pharmacotherapy is discontinued. therefore, treatment should be individualized to each patient without a set time for discontinuation of pharmacotherapy [ , ] . subramaniam et al. demonstrated that youths suffering from oud commonly have multiple comorbidities, including polysubstance abuse, psychiatric disorders, hepatitis c infection, a history of high-risk sexual and criminal behaviors [ ] . they are at high risk for sexually transmitted infections and unintended pregnancies. pregnancy in women with ouds is associated with adverse outcomes such as fetal growth restriction, preterm labor, stillbirth, and neonatal abstinence syndrome (nas) [ ] . these patients are best managed by a multidisciplinary team that utilizes mat and additional counseling and preparation for nas [ ] . unfortunately, pregnant women referred from criminal justice agencies for treatment of ouds receive evidence-based therapies less often than those referred from other sources [ ] . sbcyor aims to reduce health care disparities among pregnant youths in sbc with oud by including maternal fetal medicine physicians as part of the collaborative team. as a result, integrated contraceptive services, access to long-acting reversible contraceptive methods, and access to abortion services as well as comprehensive longitudinal care for the continued pregnancy were incorporated into the sbcyor program to ensure comprehensive treatment and health equity amongst participants. opioid use disorder also places a significant burden of cost on society affecting health care, social service, and justice systems. a strong effort must be made to target this group early with both preventative and therapeutic options in order to mitigate downstream effects. people affected by oud are often ashamed of their problem. they fear social stigma associated with drug use, and implications with law enforcement involvement [ ] . this problem may be amplified in the youth population because of relative social and cognitive immaturity. as a result, many at risk or affected youths are not identified until they have downstream complications such as an overdose and/or incarceration. by then, addiction may have already profoundly and negatively impacted their lives. it is a challenge to encourage youths who are in the earlier stages of opioid dependence to self-identify and seek treatment. therefore, future directions of the sbcyor program may include screening for at-risk youths at all public education institutions. to this end, sbcyor is currently engaging the san bernardino school district in a pilot project to identify opportunities for collaboration. historically, substance use disorder treatment of any kind, nationally and statewide, has been offered under the substance abuse prevention and treatment block grant. multiple public systems have responded to growing community needs resulting in diverse and uncoordinated approaches. discrete system and programming responses has resulted in an inability to share data. this lack of data sharing has been a significant barrier to forming a coordinated effort in developing a continuity of care for these patients. previous efforts at forming a centralized database in san bernardino county for all partners have been limited, and often lacking vital elements of the patient's health history, such as medication, dosage, and response to treatment. this adversely impacts the delivery of care as the patient moves along the spectrum of recovery [ , ] . while confidentiality regulations present challenges, these can be overcome with interagency cooperation and patient informed consent. the response to the opioid crisis must be broad in its scope in order to be effective. it must incorporate medication therapy, evidence-based practices, and solutions to psychosocial components unique to each individual [ ] . sbcyor plans to enroll its coalition partners in developing a centralized and hipaa compliant regional data sharing system, which will allow a multidisciplinary team to properly develop and coordinate an effective care plan. this crisis affects more than just the individuals who misuse opioid medications and illicit drugs. repercussions of this crisis reverberate throughout the entire community. the stigma surrounding oud and deficits in current treatment strategies must be addressed. among the youth population, oud is a growing concern. any strategy will need to understand the systemic barriers and be sensitive to unique attributes of this population. without a cultural transformation of the system, no recovery program can be successful long-term. actions to address the crisis requires the endorsement from the community and coordination from multiple agencies and organizations. without active support from the county organizations, public schools, law enforcement agencies, local fire departments, social services and department of behavioral health, it would be impossible to reach affected youths and provide them with essential and ongoing care. as such, sbcyor has successfully brought together community stakeholders, especially public service entities on the frontlines of the epidemic. together, community partners can disseminate information, provide support, offer an alternative to drug use, and participate in therapeutic interventions. consideration must be given to local, state, and federal regulations to this socially sensitive field of medicine. the greatest challenge moving forward for continued implementation of programs such as sbcyor is securing the commitment of agencies to the implementation of best practices. procuring on-going funding is necessary; however, much can be achieved by system, organizational, practitioner commitment to change. there has been significant financial, government, and community support to initiate this campaign, but to this point, further funding beyond the first year of implementation has not been secured. additionally, in light of a new challenge in response to the covid- pandemic, the coalition plans to utilize telemedicine and other available technologies in an effort to prevent delay in screening, care and treatment. ultimately, the organizational will, innovations, and pathways must be established for continued funding without dependence on grants. this may be achieved by refining the logistics, bringing more oud awareness, and government and community buy-in. opioid use disorder is a chronic condition with substantial health, economic and social costs. sbcyor was created as a coalition to help fill a gap in the national effort to address the opioid use crisis in sbc. it specifically targets youths aged - years in sbc suffering from oud. early results of sbcyor suggested that the coalition has enrolled youths in mat programs and provided an integrated response, showing promising results, and has successfully partnered with community stakeholders. future systematic implementation of various clinical and administrative integration strategies is needed in order to ensure a better continuum of care and success of this program. human subjects: consent was obtained by all participants in this study. arrowhead regional medical center-irb issued approval - . animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: this study was funded by a grant from california institute for behavioral health solutions, california youth opioid response services. michael m. neeki is the program director. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. substance abuse and mental health services administration: key substance use and mental health indicators in the united states: results from the national survey on drug use and health california opioid overdose surveillance dashboard adolescent tuning of association cortex in human structural brain networks drug overdose deaths in the united states clinical characteristics of treatment-seeking adolescents with opioid versus cannabis/alcohol use disorders. drug alcohol dependence prescription opioid misuse associated with risk behaviors among adolescents office of the surgeon general: facing addiction in america: the surgeon general's spotlight on opioids medication-assisted treatment for adolescents in specialty treatment for opioid use disorder healthcare barriers and utilization among adolescents and young adults accessing services for homeless and runaway youth the opioid epidemic and medicaid's role in facilitating access to treatment trends in receipt of buprenorphine and naltrexone for opioid use disorder among adolescents and young adults primary care management of opioid use disorders: abstinence, methadone, or buprenorphine-naloxone? a retrospective study of retention of opioid-dependent adolescents and young adults in an outpatient buprenorphine/naloxone clinic committee on substance use and prevention: medication-assisted treatment of adolescents with opioid use disorders non-violent crime drops in san bernardino during coronavirus lockdown a systematic review of health economic models of opioid agonist therapies in maintenance treatment of non-prescription opioid dependence analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human the use of psychosocial interventions in conjunction with medications for the treatment of opioid addiction opioid use disorder: medical treatment options treatment of opioid-dependent adolescents and young adults with buprenorphine committee on obstetric practice: opioid use and opioid use disorder in pregnancy expanding contraception access for women with opioid-use disorder: a qualitative study of opportunities and challenges (preprint) medications for opioid use disorder among pregnant women referred by criminal justice agencies before and after medicaid expansion: a retrospective study of admissions to treatment centers in the united states social stigma toward persons with prescription opioid use disorder: associations with public support for punitive and public health-oriented policies implementing key strategies for successful network integration in the quebec substance-use disorders programme improving information sharing for youth in foster care treatment outcomes of a combined cognitive behavior therapy and pharmacotherapy for a sample of women with and without substance abuse histories on an acute psychiatric unit: do therapeutic alliance and motivation matter? we acknowledge the efforts of elizabeth stanley-salazar mph, and deborah werner, ma, pmp, for their guidance and support. we are grateful to the yorca, sbcyor coalition members for their help throughout the program implementation. additionally, we would like to send a key: cord- -n iscmr authors: solaimanzadeh, isaac title: nifedipine and amlodipine are associated with improved mortality and decreased risk for intubation and mechanical ventilation in elderly patients hospitalized for covid- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: n iscmr dihydropyridine calcium channel blockers (ccb) are typically used agents in the clinical management of hypertension. yet, they have also been utilized in the treatment of various pulmonary disorders with vasoconstriction. severe acute respiratory syndrome coronavirus (sars-cov- ) has been implicated in the development of vasoconstrictive, proinflammatory, and pro-oxidative effects. a retrospective review was conducted on ccb use in hospitalized patients in search of any difference in outcomes related to specific endpoints: survival to discharge and progression of disease leading to intubation and mechanical ventilation. the electronic medical records for all patients that tested positive for sars-cov- that were at or above the age of and that expired or survived to discharge from a community hospital in brooklyn, ny, between the start of the public health crisis due to the viral disease up until april , , were included. of the patients that were identified, survived until discharge and expired. seven patients from the expired group were excluded since they died within one day of presentation to the hospital. five patients were excluded from the expired group since their age was above that of the eldest patient in the survival group ( years old). with patients left, were found to have been administered either amlodipine or nifedipine (ccb group) and were not (no-ccb group). patients treated with a ccb were significantly more likely to survive than those not treated with a ccb: ( %) survived and expired in the ccb group vs. six ( . %) that survived and ( . %) that expired in the no-ccb treatment group (p<. ; p= . ). ccb patients were also significantly less likely to undergo intubation and mechanical ventilation. only one patient ( . %) was intubated in the ccb group whereas ( . %) were intubated in the no-ccb treatment group (p<. ; p= . ). nifedipine and amlodipine were found to be associated with significantly improved mortality and a decreased risk for intubation and mechanical ventilation in elderly patients hospitalized with covid- . further clinical studies are warranted. including either nifedipine or amlodipine in medication regimens for elderly patients with hypertension hospitalized for covid- may be considered. of the patients that were identified, survived until discharge and expired. seven patients from the expired group were excluded since they died within one day of presentation to the hospital. five patients were excluded from the expired group since their age was above that of the eldest patient in the survival group ( years old). with patients left, were found to have been administered either amlodipine or nifedipine (ccb group) and were not (no-ccb group). patients treated with a ccb were significantly more likely to survive than those not treated with a ccb: ( %) survived and expired in the ccb group vs. six ( . %) that survived and ( . %) that expired in the no-ccb treatment group (p<. ; p= . ). ccb patients were also significantly less likely to undergo intubation and mechanical ventilation. only one patient ( . %) was intubated in the ccb group whereas ( . %) were intubated in the no-ccb treatment group (p<. ; p= . ). nifedipine and amlodipine were found to be associated with significantly improved mortality and a decreased risk for intubation and mechanical ventilation in elderly patients hospitalized with covid- . further clinical studies are warranted. including either nifedipine or amlodipine in medication regimens for elderly patients with hypertension hospitalized for covid- may be considered. nifedipine and amlodipine are dihydropyridine calcium channel blockers (ccbs) regularly used to treat hypertension. yet, both medications have been utilized in the treatment of various pulmonary disorders with vasoconstriction as well. severe acute respiratory syndrome coronavirus (sars-cov- ) has been described to use the angiotensin-converting enzyme (ace ) receptor for entry into target cells expressed by the epithelial cells of the lung, leading to vasoconstrictive, proinflammatory, and pro-oxidative effects [ ] . this vasoconstriction may play a role in the pathogenesis of the disease. dysregulation or loss of hypoxic pulmonary vasoconstriction is suspected in coronavirus disease (covid- ) as well [ ] [ ] . a retrospective review of patients on either nifedipine or amlodipine was conducted in search of any difference in outcomes, including survival to discharge and progression of disease leading to intubation and mechanical ventilation. patients in this population were prescribed either of these medications for the treatment of hypertension. yet, reviewing outcomes in this context may reveal a benefit for the treatment of covid- as well. it is important to note the difference between dihydropyridine calcium channel blockers and non-dihydropyridines, as physiologic effects are likely not the same [ ] . whenever this article refers to a ccb, it is referring specifically and only to either nifedipine or amlodipine. nifedipine was found to increase pulmonary vasodilation without decreasing arterial oxygenation or causing systemic hypotension in patients that suffer pulmonary hypertension from a chronic airflow limitation [ ] . in tandem, amlodipine taken orally also produces acute pulmonary vasodilatation in patients with pulmonary hypertension [ ] . furthermore, amlodipine was also found to be an effective pulmonary vasodilator in patients with chronic obstructive pulmonary disease (copd) with pulmonary hypertension [ ] . in addition to being a safe and effective pulmonary vasodilator in these patients, it was also shown that amlodipine leads to an improvement in the right heart function [ ] . during hypoxia, nifedipine significantly reduces pulmonary vascular resistance at both rest and exercise and inhibits hypoxic pulmonary vasoconstriction in patients with copd [ ] . in the same study, it was also found to substantially increase oxygen delivery during both rest and exercise. moreover, in patients with normal pulmonary artery pressures, nifedipine was shown to attenuate hypoxia-induced increases in pulmonary artery pressure and acutely dilates the constricted vascular bed associated with hypoxia in patients with copd [ ] . although modulated via the endothelium, the core mechanism of hypoxic pulmonary vasoconstriction is in the smooth muscle cell [ ] . the reversal of vasoconstriction with the use of dihydropyridine calcium channel blockers may be a method to improve outcomes in covid- . nifedipine was previously observed to shift the pulmonary pressure-flow relationship to the right and increase the dispersion of blood flow distribution at rest and during exercisestrongly suggesting the release of hypoxic pulmonary vasoconstriction [ ] . in light of this, the concomitant use of either nifedipine or amlodipine in patients hospitalized with covid- was reviewed. again, patients herein were treated with the calcium channel blockers for hypertension. yet, this review sought to discover if a mortality benefit could be revealed in an acute illness requiring hospitalization for covid- . a retrospective review of electronic medical records for all patients admitted to a community hospital who tested positive for sars-cov- , who were at or above the age of , and who either expired or survived to discharge from hospital between the start of the public health crisis due to the viral disease (earliest admission date of a patient that tested positive at this hospital: february , ) and april , . it is important to note that only patients with a final disposition on the day of study conclusion were included and that many more patients still hospitalized were not included in this review. the two groups were: ( ) treated with either nifedipine or amlodipine as part of the ccb group or ( ) not treated with either amlodipine or nifedipine as part of the no-ccb group. being "on" either of these medications required that they received more than one dose. all patients in both groups were managed by a clinical team wherein antibiotics were administered in addition to hydroxychloroquine depending on patient consent and/or qtc prolongation status. patient outcomes were assessed for survival to discharge or signed out independently against medical advice (ama) and expiration. also looked at as a secondary outcome was the need for intubation and mechanical ventilation. clinical co-morbidities were reviewed in addition to demographic and clinical data. results were analyzed for statistical significance with the use of software available on these web pages: https://www.socscistatistics.com/tests/chisquare/default .aspx and https://www.socscistatistics.com/tests/fisher/default .aspx. the chi-square test and fisher exact test calculator for a x contingency table were utilized for a statistical significance limit of p<. except where indicated. to check for any significance between groups for factors that were continuous variables, the standard deviation was derived from the following website enlisted for statistical dispersion: http://www.alcula.com/calculators/statistics/dispersion/. thereafter, the following website was utilized to calculate the comparison of means: https://www.medcalc.org/calc/comparison_of_means.php. a total of patients were identified. of these, survived until discharge and expired. one patient signed out against medical advice (ama) and this was included in the survival group. seven patients from the expired group were excluded since they died within one day of presentation to hospital and the time frame of clinical deterioration limited potential therapeutic interventions. in order to attempt to age match the case and control groups, five patients were excluded from the expired group since their age was above the eldest patient in the survival group ( years old). for the record, of these, only one was on a ccb and four were not on a ccb. with patients left, were found to not have been treated with either nifedipine or amlodipine and were found to have been prescribed and taking either nifedipine or amlodipine during the course of hospitalization. demographic data are outlined in table in patients treated with a ccb, ( %) survived and expired, whereas only six ( . %) survived and ( . %) expired in the no-ccb treatment group (p<. ; p= . , see table ). considering this from a different perspective, % ( / ) of patients that survived and that were successfully discharged from the hospital were on a ccb, whereas % ( / ) of patients that expired were not on a ccb ( figure ). blocker. patients treated with a ccb were significantly less likely to have undergone intubation and mechanical ventilation. since only one patient ( . %) in the ccb group was intubated and mechanically ventilated and ( . %) were not, whereas ( . %) were intubated and mechanically ventilated and ( . %) were not in the no-ccb treatment group (p<. ; p= . , see table and figure ). other sample medications administered were not significantly different between groups (see table ). broad-spectrum antibiotics could be qualified with various medication regimens such as ceftriaxone in combination with azithromycin or doxycycline, vancomycin and meropenem, etc. intravenous fluid comprised all patients that were administered at a minimum of ml/hr at some point during the course of hospitalization. steroid use included any type such as methylprednisolone, dexamethasone, or hydrocortisone. several other factors, including vital signs and laboratory findings at initial presentation, were compared between groups as well ( table ) . some patients did not have specific laboratory tests drawn; the number of patients included is indicated. also, the first recorded pulse oximetry measure in many patients from both groups include levels obtained after immediate placement of oxygen supplementation was already initiated. these results reveal that dihydropyridine calcium channel blocker (nifedipine or amlodipine) usage is associated with significantly improved mortality in elderly patients hospitalized for covid- . they also reveal that ccb usage is associated with a significantly decreased risk for intubation and mechanical ventilation. this study reveals the possible benefits of nifedipine and amlodipine in patients hospitalized with covid- . larger clinical studies are warranted. for those that already have hypertension and present to hospital with elevated blood pressure, assuming no contraindications exist, it may be fair to give preference to a ccb as first-line therapy for concomitant benefit. further studies of other potential therapies that function as vasodilators in the pulmonary arterial flow should be pursued as well. clinical data comparisons between groups at the time of presentation were significant for differences in systolic as well as mean arterial blood pressure. this may indicate higher levels of hypotension or at least a lack of elevated blood pressure measures in the no-ccb group at presentation and/or foreshadow treatment with a ccb anti-hypertensive medication. differences in erythrocyte sedimentation rate, d-dimer, and lactate dehydrogenase may reflect a disparate severity of disease upon presentation. however, on the other hand, this reasoning may be countered since results between levels of lactic acid, c-reactive protein, b-type natriuretic peptide, and interleukin- were not significantly different, in addition to no significant difference between hemoglobin and glomerular filtration rate (gfr). it is not known if patients were taking a ccb at home or not. this may be another avenue to explore with consideration to decipher if the severity of disease expression is diminished or halted by ccb medication -prior to virus exposure. future studies may investigate different patient populations. moreover, ccb treatment, while monitoring blood pressure closely in patients that are suffering from covid- , and that do not have underlying hypertension, may be envisaged. blood pressure is generally not hypotensive in many hospitalized patients suffering from covid - and can even be higher in patients in the intensive care unit (icu) [ ] . the limitations of this study may be inherent in the small sample size, possible confounding factors not otherwise accounted for, and even selection bias as part of prior clinical decisionmaking to treat hypertension with a ccb or not. therefore, larger and more rigorous studies should be pursued. prospective studies may be considered as well. large health systems may be in a unique position to help advance knowledge on this subject matter by conducting a more robust retrospective review. if clinical researchers therein would peruse electronic medical records (emr) for similar outcomes, as described in this paper, that can aid in gaining a better understanding of the role that ccbs may have in mitigating disease. particular attention may be paid, where possible, on patient adherence to outpatient medication regimens prior to acute hospitalization. for example, if the rates of hospitalization for patients that were adherent to ccbs were decreased, that might indicate preventative benefits. this could potentially explain significant differences of clinical data at the initial presentation described above, but this remains to be investigated. with the current emr technology available at some institutions, this may be investigated rapidly. results obtained may yield benefits for thousands of patients across the country and throughout the world that have not yet fallen ill but remain at risk for contracting this disease. the need for mechanical ventilation likely represents the continuum of progression of the disease. it can be regarded as an intervention aimed at curtailing a trajectory towards mortality. however, mechanical ventilation should not be considered an all-encompassing treatment option for patients with covid- . in a recent study, amongst patients intubated, only ( . %) were discharged alive, with . % that died and over % still in hospital [ ] . avoiding intubation with the utilization of potential countermeasures, such as with ccbs and other vasodilators described below, can be considered and evaluated since they may aid in the achievement of improved outcomes. when precisely during the course of the illness (early vs. late) these medications may be most effective may also be examined. furthermore, perhaps beneficial effects of ccbs and other vasodilators described below can be extended to patients that are already mechanically ventilated. clinical studies may investigate if successful weaning from mechanical ventilation is promoted by the use of vasodilators. therefore, it is incumbent upon the medical community to exert their best efforts, on behalf of the many patients at risk, and pursue further evaluation as part of efforts to enhance clinical interventions that compel augmentation. this data provides an impetus to explore different approaches to the treatment of patients with covid- . focusing on vasodilatory agents may allow for an alternative treatment strategy. herein, improved flow via the alveolar-capillary unit may be achieved. with improved flow, impediments to oxygenation, including inflammation and vasoconstriction, may be better negotiated. furthermore, blood transit improvement as a result of vasodilation may potentially offset clot formation. lastly, fluid accumulation or edema that can inhibit oxygenation may be collectively reduced as well. altogether, the improved flow may attenuate the precipitous progression of the disease. virchow's triad highlights three aspects compromising blood flow: stasis, hypercoagulability, and endothelial injury. all three may be occurring in advanced covid- . yet, the progression to severe disease consisting of an inability to oxygenate may be the endpoint of a gradual process. in other words, flow (or micro-perfusion) via the alveolar-capillary unit may be slowly but surely decreasing as a result of a vicious cycle wherein inflammation secondary to viral injury begets hypercoagulability as well as the impedance of blood flow. clot formation certainly lulls or wholly undermines segments of previously oxygenating pathways passing through the alveolar-capillary unit. moreover, inflammation by itself, enhanced by the recruitment of cytokines, leukocytes, and the whole gamut of caustic endogenous mechanisms, may further render viable tissue non-functional. additionally, with inflammation comes fluid or edema formation -this also compromises oxygen diffusion. on top of all this exists the innate disposition or tendency for hypoxic pulmonary vasoconstriction [ ] . perhaps, vascular inflammation also contributes to elicit reactive vasoconstriction independently. altogether, a microvascular process may be occurring over numerous alveolar-capillary units, which yields a macro result. in sum, with increasing hypoxia and respiratory failure, the following challenges are faced and each promotes the other perhaps in sequence but not necessarily: ( ) viral injury provoking inflammation, ( ) recruitment of an immune response, ( ) fluid accumulation, ( ) vasoconstriction or compromised vascular flow, and ( ) hypercoagulability and clot formation. multi-faceted challenges are faced in various clinical cases. however, the ultimate development of clot formation may not be applicable to many, if not most, patients upon presentation. these patients must be distinguished as not being in a category wherein the precipitous decline just described has already been realized. this is especially early on in the illness, since some may be managed, improve, and recover with supplemental oxygen and conservative fluid management or gentle fluid restriction alone. herein, a vasodilator can be utilized from the outset since inflammation has not been prolonged, whereby flow via the alveolar-arterial complex is still consistent and clot formation likely has not already developed. however, in patients that have had prolonged symptoms, a consistent deterioration of oxygen saturation and/or hypoxemia should be evaluated with the consciousness that all five challenges may have already been established and taken form. other patients maybe somewhere in between. this being said, consideration of other vasodilatory agents should be pursued. these may include phosphodiesterase inhibitors sildenafil and tadalafil, as well as acetazolamide among others. for example, sildenafil was shown to increase exercise capacity during severe hypoxia, as well as reduce hypoxic pulmonary hypertension at rest and during exercise while maintaining gas exchange and systemic blood pressure [ ] . the same study also revealed that it yields an increased maximum workload and maximum cardiac output compared with the placebo. beyond this, phosphodiesterase inhibitors have the added benefit of improved renal perfusion and gfr -a valuable commodity as kidney disease is associated with the in-hospital death of patients with covid- [ , ] . also, when not administered with nitrates, sildenafil use resulting in hypotension, orthostatic hypotension, and syncope were found to be less than % [ ] [ ] . tadalafil once daily was found to improved exercise capacity and reduced time to clinical worsening in patients suffering from pulmonary arterial hypertension (pah); offering an alternative to sildenafil as well [ ] . finally, combining tadalafil with acetazolamide, rather than taking acetazolamide alone, can be an even more effective method for the prevention of some conditions [ ] . dosing of sildenafil is less restrictive in cases of compromised renal function. acetazolamide also attenuates hypoxic pulmonary vasoconstriction but has the added benefit of increasing minute ventilation and oxygenation [ ] [ ] [ ] . acetazolamide, however, requires close monitoring of arterial blood gases, prior to and following use, as treatment is contraindicated in metabolic acidosis; a condition that it can spur. however, some of the adverse effects of acetazolamide can be avoided by reducing the dose to compensate for age-related reductions in renal drug clearance [ ] . in any case, the addition of sodium bicarbonate can be utilized to counteract an acid tide and may be administered repeatedly in an alternating fashion with acetazolamide [ ] . acetazolamide also acts to inhibit carbonic anhydrase in vascular smooth muscle and this mechanism may be achieved by means of ph changes therein [ ] . clinical status and work of breathing must also be monitored closely. patients that are already on a ventilator may also stand to benefit most from acetazolamide, as the control of various parameters may be adjusted for the optimization of therapy. an additional asset of acetazolamide includes diuresis of fluids -many, if not most, patients have significant crackles present on auscultation, and this likely hinders oxygenation as well (the latter is a clinical observation) [ ] . thus, acetazolamide can provide a triple benefit: diuresis of fluid/pulmonary edema, improved ventilation, and reversal of pulmonary vasoconstriction. there is a caveat to all of this. that is, improvement of oxygenation and ventilation can only be pursued if clot formation does not exist or is previously adequately treated. a recent study found that an incidence of thrombotic complications is up to % of icu patients with covid- [ ] . this must be addressed as well. for example, in patients that are early stage and without markedly elevated d-dimers, preferably younger and not elderly, wherein crackles are grossly apparent on auscultation, the use of a vasodilator such as acetazolamide or a ccb may potentially stave off intubation independently. however, in an elderly patient, with markedly elevated d-dimers and little to no crackles with clear air movement on auscultation, it may be ineffective as alveolar-capillary units that are already clotted may harbor a formidable barrier towards improvement. therefore, treatment with anti-coagulation prior to vasodilator therapy should be considered in these patients. treating any clots or microclots first may allow for the effective flow once vasodilator therapy is implemented. the vasodilatory agents mentioned in this article may enhance clinical outcomes in patients suffering from covid- . yet, they should be accompanied with considerations for anticoagulation and anti-inflammatory agents as well, not to mention antibiotics for the prevention of co-infection and anti-virals that may also contribute towards resolution. since adding a vasodilatory agent in a patient that has had prolonged disease and may have already developed a clot or microclots may not suffice. anti-coagulation, whether in prophylactic or treatment doses, may aid in reducing clot formation or extension. therefore, combining regimens particularly in elderly patients and/or those that have had a prolonged course may be prudent. if anti-coagulation is administered, certainly close monitoring for any signs of bleeding must be implemented. nonetheless, some patients may recover without anticoagulation as well, and clinical acumen is necessary in all circumstances. fluids are an important subject matter that must be appreciated within the context of overall management, although it certainly deserves further assessment beyond this article. generally, in patients that have stable blood pressure, no significant clinical signs of dehydration, and crackles on auscultation, conservative fluid management seems to be best. ground-glass opacities present on imaging may be reflective of fluid collection as well. in these cases, avoiding intravenous fluid hydration and relegating to oral fluid intake as needed may decrease the risk of excess fluid accrual in the lungs. this approach is not feasible in many clinical situations such as where co-morbid diabetic ketoacidosis, severe dehydration, hypernatremia, or rhabdomyolysis occurs. nonetheless, oxygenation impedance as a result of edema formation is still worth taking into account in clinical management over an extended course of hospitalization. on the other hand, patients that are dehydrated from the outset or were previously on anti-coagulation prior to presentation and perhaps taking a ccb may have relatively clear sounding lungs on auscultation -this is a clinical observation. those previously taking anti-coagulation and/or a ccb might possibly be less prone to fluid accumulation given preemptive counters to the impedance of flow and clot formation. this may be analogous to a pipe wherein, if flow is preserved, fluid may pass without interference. however, if it is clogged then certainly running more water will rebound and not successfully traverse the pipe without backing up or collecting proximally. in the former, where significant interference is not present, fluid may be a boon to expedite the clearance of inflammation. in the latter, where viral triggers of inflammation, down the five-step theoretical pathogenesis described above, have already exerted influence, it may worsen clinical status. the "pipe" analogy should be further qualified since, in our case, vascular channels may not be intact, as endothelial injury and capillary permeability are both likely. moreover, inflammation in itself is prone to fluid accumulation as seen in patients with bowel wall edema following surgery, ascites in cancer, or serositis. yet, while abdominal fluid accumulation may be a cause for significant discomfort, even mild pulmonary edema development may swiftly compromise oxygenation. finally, the use of steroids in severe cases and potentially in all hospitalized patients may aid in alleviating inflammation but, certainly, this is under investigation. with the concomitant use of vasodilators and anti-coagulation, the benefits of steroid use in covid- may become more apparent. all in all, in severe cases, early utilization of one or more vasodilator agent(s), anti-coagulation, steroids, and a diuretic (if no contraindications exist, preferably acetazolamide, given the additional benefits mentioned above), in addition to antibiotics and potential antivirals may be one protocol pathway to consider ( table ). therapeutic interventions herein reflect the five-step progressive course outlined above. patients that are otherwise stable but requiring oxygen supplementation to maintain a stable saturation level may improve with a vasodilator such as nifedipine or amlodipine (maximizing the dose to achieve ideal blood pressure may be of interest), prophylactic anti-coagulation, steroids, antibiotics and antiviral therapy alone without the use of a diuretic agent. yet, if the clinical disease progresses and suspicion of need for invasive ventilation emerges, a diuretic such as acetazolamide may be considered. in ventilated patients, acetazolamide may be a key to promote weaning as described above. frequent and repeated doses of acetazolamide may be necessary since the inflammatory effects of the viral provocation, as well as capillary permeability, will not vanish instantaneously and following a brief course of treatment reaccumulation of fluid may materialize. therefore, consistent perseverance may be a successful strategy to quell the buildup of fluid, maintain vasodilation, and allow for conquest over time. indeed, all vasodilation agents may exert their benefit over a gradual time course. just like the decline of patients succumbing to covid- occurs over an extended time course of worsening pathogenesis, so too the vasodilation agents may mitigate the same pathogenic process over an extended course of the viral illness. in other words, treating for just two days may not suffice even though some clinical improvement is observed. stopping at that point may incur a rebound in status. rather, a course of treatment at least five to seven days and up to two to three weeks in severe cases may be best. it is worth noting that a relatively minor subset of patients, tending to be elderly and frail, has been observed to have disproportionately cold hands and feet relative to their extremities and the rest of their body. additionally, they may be markedly sleepy and difficult to arouse. a pulse oximeter may fail to retrieve a saturation level when placed on their fingers and may yield a result only after being placed on their forehead. this may reflect an underlying lack of perfusion to extremities and conserving mechanisms for blood distribution. these patients are extremely ill and, although they may have stable vital signs, may be at risk for rapid deterioration. similar treatment may ensue, but with compromised oral intake, intravenous fluid hydration may be needed; this may be best conducted at a gentle, gradual, and consistent rate. this subgroup should be recognized as possibly being part of a separate group of patients with an advanced illness that may require special attention. any clinician that has encountered patient presentations on a covid unit, icu, or emergency department is aware that presentations of covid- are disparate and each individual case is different. nonetheless, while correcting any concomitant disturbance (e.g. renal failure, hyperosmolar syndrome, hypernatremia, etc.), bearing in mind the central role of pulmonary deterioration in overall clinical demise is crucial. ultimately, morbidity and mortality in covid- may be a result of a failure to accommodate the pathogenic sequelae of toxic viral provocation rather than an immunologic deficiency. therefore, aiding in the adaptation and negotiation of a physiologic response to the transient viral insult may effectively mitigate disease burden and promote improved outcomes. altogether, implementing a strategy that optimizes flow via the alveolar-capillary unit may be a progressive path forward. in this small retrospective review, dihydropyridine ccbs were found to be significantly associated with improved mortality, as well as a decreased risk for intubation and mechanical ventilation in elderly patients hospitalized with covid- . larger clinical studies are warranted. future studies may also elucidate results in different patient populations and possibly reveal benefits even in mechanically ventilated patients. consideration of treatment with a ccb in patients who are suffering from covid- and that do not have underlying hypertension may be studied as well. other potential therapies that function as vasodilators in pulmonary arterial flow should be pursued. potential benefits may outweigh the risks of including nifedipine or amlodipine in the treatment regimens of elderly patients with hypertension hospitalized with covid- . human subjects: consent was obtained by all participants in this study. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. covid- ) infection and renin angiotensin system blockers to a "typical" acute respiratory distress syndrome covid- pneumonia: ards or not comparative effects of nifedipine, verapamil, and diltiazem on experimental 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obstructive pulmonary disease clinical features of patients infected with novel coronavirus in wuhan, china. lancet. presenting characteristics, comorbidities, and outcomes among patients hospitalized with covid- in the new york city area hypoxic pulmonary vasoconstriction sildenafil increased exercise capacity during hypoxia at low altitudes and at mount everest base camp: a randomized, double-blind, placebo-controlled crossover trial sildenafil improves renal function in patients with pulmonary arterial hypertension caution on kidney dysfunctions of covid- patients use of sildenafil (viagra) in patients with cardiovascular disease overall cardiovascular profile of sildenafil citrate tadalafil for the treatment of pulmonary arterial hypertension tadalafil and acetazolamide versus acetazolamide for the prevention of severe high-altitude illness acetazolamide reduces hypoxic pulmonary vasoconstriction in humans acute mountain sickness and acetazolamide: clinical efficacy and effect on ventilation acetazolamide improves oxygenation in patients with respiratory failure and metabolic alkalosis acetazolamide blood concentrations are excessive in the elderly: propensity for acidosis and relationship to renal function the alternating use of an alkalizing salt and acetazolamide in the management of cystine and uric acid stones vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action acetazolamide: a forgotten diuretic agent incidence of thrombotic complications in critically ill icu patients with covid- the authors would like to thank dr. baoying lin-chen, director of infection control at interfaith, and the industrious members of her team who have helped prepare parts of the database utilized to conduct this review. key: cord- -mzez v d authors: elsayed, sarah m; reddy, mithun k; murthy, pooja m; gupta, ishita; valiuskyte, monika; sánchez, diana f; diaz, mark anthony title: the possibility and cause of relapse after previously recovering from covid- : a systematic review date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: mzez v d the severe acute respiratory distress syndrome coronavirus- (sars-cov- ) is a novel coronavirus that is believed to be mainly transmitted via droplet and contact transmission. while research is focusing on epidemiology, transmission, vaccine development, and therapeutics for coronavirus disease (covid- ), there is a possibility of disease relapse. there are reports of patients who tested positive for sars-cov- after clinical recovery and initial clearance of the virus. objective this systematic review aims to identify the trends of covid- relapse, the effects of co-morbidities on it, and associated mortality rates. methods we conducted a systematic search during march and april for research articles on the relapse of covid- using two primary databases, pubmed and embase. results a total of eligible studies were screened of which (case reports) were eligible for data extraction. the earliest to report relapse was after two days of discharge and the latest was days after discharge. the mean number of days to relapse was days and the median number was seven days. there was incomplete information about comorbidities. no mortalities were reported at the time of the study. sars-cov- is a novel coronavirus that was first identified in wuhan, china, at the end of . this virus causes a respiratory illness named covid- (referring to the year ) and has grown to be a global pandemic as declared by the world health organization (who) in march . currently, the virus is believed to be transmitted via droplets and contact transmission although speculations about airborne transmission exist [ ] . while research is focusing on the epidemiology, transmission, vaccine development, and therapeutics for covid- , there remain gaps in our understanding of the natural history of this disease. one of those gaps is the possibility of disease relapse. there have been reports of patients who tested positive for sars-cov- after clinical recovery and initial documented clearance of the virus. multiple explanations could exist, including disease relapse or reinfection. being able to identify and accurately define disease relapse is of utmost importance, as this will allow researchers to recognize whether reinfection exists, which would have major implications on efforts to prevent infection. recurrence or recrudescence refers to the reappearance of symptoms in survivors due to the persistence of the virus at immunologically segregated body sites [ ] . reinfection refers to survivors being susceptible to acquiring new infections after recovery. patients reinfected with a strain determined to be of a different genotype or subtype than the previous strain they were infected with can easily be identified using genotyping assays. however, when reinfection with a similar strain of the same subtype occurs, phylogenetic analysis is required to distinguish reinfection from a virologic relapse [ ] . disease relapse has seldom been reported and there is no current consensus on its definition. in the quest to better understand the natural history of covid- , this systematic review of published evidence aims to identify the trends of covid- relapse, the effects of co-morbidities on its relapse incidence, and relapse-associated mortality rates. we conducted a systematic search during march and april for research articles on the relapse of covid- . two primary databases were used, pubmed and embase. the search strategy used the keywords covid-relapse, relapse covid, recurrence covid , and corona relapse and was comprehensive with the cross-checking of reference lists from the articles retrieved. the preferred reporting items for systematic reviews and meta-analysis (prisma) guidelines were used. this study is registered with the prospero protocol (registration: crd ). we identified , abstracts via a literature search, of which full-text articles were reviewed ( figure ). of these, publications met the inclusion criteria for the final evaluation. a total of articles were excluded, as they were not relevant to the aim of our study and did not contain any information on the relapse of covid- . the publications included covid- positive patient data and the relapse of disease was confirmed by pcr; the full text was available for these publications. articles that included lab studies were excluded. each publication was reviewed by two reviewers independently, and disagreements were discussed amongst all reviewers and resolved via consensus. figure illustrates the preferred reporting items for systematic reviews and meta-analyses: the prisma statement [ ] . data were collected in the following categories when available: study design; study country; patient demographics; clinical signs and symptoms; laboratory findings; imaging studies; dynamics of the oropharyngeal swab test; treatment of the first presentation; the clinical picture of relapse; day of a positive result after confirmed negative we tabulated the data using microsoft excel ( , microsoft corp, redmond, wa). the data that were included in these tables were checked for accuracy by all authors. statistical analysis was done by authors. this study did not require institutional review board (irb) approval as data was obtained from already available databases, and patients were not directly involved. two authors independently assessed the risk of bias of each study included. the authors resolved disagreements by consensus, and a third author was consulted to resolve disagreements if necessary. a total of eligible studies were screened, of which (case reports) were eligible for data extraction. the study reports a total of patients ( females and males), all from china, who tested positive for covid- . all of them met the symptoms and testing criteria for discharge, which are: (i) afebrile for at least three consecutive days, (ii) improvement in respiratory symptoms, (iii) improvement in chest imaging studies, computed tomography (ct), or x-ray, and (iv) two negative reverse transcription-polymerase chain reaction (pcr-rt) tests hours apart [ ] . all of them were sent for precautionary quarantine for days, as knowledge about the nature of the virus was not established yet. there is no information about home disinfection before discharge. the cases reported a relapse, the earliest report was after two days of discharge and the latest was days after discharge. the mean number of days to relapse was days and the median number was seven days. the patients were mostly females and less than years old. six patients presented with symptoms ( . %) and five were asymptomatic ( . %). the most common symptoms with which relapsed patients presented were fever and fatigue ( . %). coronaviruses are enveloped ribonucleic acid (rna) viruses that can cause multiple system disorders in the human body. six types of coronaviruses are known to infect humans. two of them cause acute respiratory distress syndrome (ards) -the severe acute respiratory syndrome coronavirus (sars-cov), which caused an outbreak in in china, and the middle east respiratory syndrome coronavirus (mers-cov) that caused an outbreak in the middle east in . the novel sars-cov is a betacoronavirus that also causes ards and can be transmitted between humans. sars-cov uses the angiotensin-converting enzyme (ace) receptor as a receptor for cell invasion. this is a similar mechanism to sars-cov [ ] . the typical presentation of sars-cov infection is fever, dry cough, dyspnea, fatigue, and lymphopenia [ ] . in late april, the centers for disease control and prevention (cdc) announced that a new loss of taste or smell, headache, muscle pain, sore throat, and repeated shaking with chills can be associated with sars-cov . it might result in severe acute respiratory syndrome (sars) and even death in severe cases [ ] . the general population is susceptible to sars-cov- as the main ways of transmission are respiratory droplets and contact. sars-cov- infected individuals are the primary source of infection in humans even if they are asymptomatic carriers [ ] . many patients have associated comorbidities [ ] . in china, by the end of february, , patients were discharged from hospitals after meeting the set discharge criteria. fourteen percent of the discharged patients showed positive nucleic acid re-examination or regained fever within one week [ ] . in this study, we reviewed published reports of such patients in an attempt to better understand this phenomenon. after a comprehensive review of the available literature, we identified adult patients, all reported in china, who tested positive after being discharged and were thought to be recovering. table outlines the patients' demographics and the initial clinical presentation. of the patients, five were males ( . %) and six were females ( . %). six ( . %) were less than years old and five ( . %) were older than years old, including one patient older than years old ( . %). one patient ( . %) had a past medical history of resolved tuberculosis, four ( . %) had no comorbidities such as hypertension, diabetes, kidney disease, liver disease, cardiac disease, or immunosuppression. there is no data about the comorbidities of the remaining six patients ( . %). nine of the patients had an initial presentation with fever ( . %) and eight had shortness of breath ( . %). all of them were rt-pcr positive. ten patients ( . %) had ct findings of ground-glass opacities or lobar infiltrates at the time of presentation while one ( . %) had no ct findings at all. all the patients were admitted for isolation and treatment in hospitals. all patients received empiric antiviral therapy either with the neuraminidase inhibitor oseltamivir or with the membrane infusion inhibitor umifenovir along with an empiric antibacterial, most commonly a fluoroquinolone. • age more than years old ( %) • diabetes ( %) • hypertension ( %) • renal disease ( %) • liver disease ( %) • cardiac disease ( %) • pulmonary disease ( . %) • immunosuppression ( . %) [ ] . it is proven that corticosteroids are beneficial in the treatment of acute respiratory distress syndrome (ards). also, it is believed to prevent the progression of severe covid- pneumonia to ards by suppressing the pro-inflammatory response and the cytokine storms if administered at five to seven days of onset [ ] . this resulted in earlier fever recovery ( days vs. days, p = . ) as well as quicker improvement in spo ( days vs. . days p = . ) [ ] . one-hundred percent ( %) of these patients met the pre-set criteria for discharge (mentioned earlier) [ ] . after discharge, all cases were kept under surveillance and quarantined at home for at least days; all cases had an rt-pcr oropharyngeal swab test for sars-cov- every day or every other day, at least five times [ ] . this study highlights the possibility of covid- relapse. the patients reported were mostly females and less than years old. the common presentations of the relapse are asymptomatic presentation, fever, or fever associated with fatigue within days of discharge, although . % of cases reported after days up to days [ ] . we could not provide a correlation between the severity of the first presentation or comorbidities with the relapse. thirty-six point four percent ( . %) of the patients received corticosteroids, which suggests a potential link with the relapse that requires further studies [ ] . there is no data about hospital readmission or treatment received for the relapse. no mortalities were reported in the patients included in our study. there are possible explanations that require further studies. as the most common comorbidity of covid- patients, diabetes, and hypertension may affect the prognosis of the disease [ ] . we need more data if this could affect the possibility of getting a relapse. age, immune status, underlying lung disease, and the severity of the sars-cov infection could all affect the elimination of the virus [ ] . furthermore, the cell entry receptor for covid- is the angiotensin-converting enzyme- (ace- ) receptor, which is mainly located on type pneumocytes rather than in the upper respiratory tract, which could occasionally lead to false-negative results for oropharyngeal or nasopharyngeal swab tests due to the lower viral load in these specimens [ , , ] . so, an important question is whether individuals upon recovery are prone to repeat infection. but, unfortunately, until now, it is an unresolved question. several studies in the last four decades have shown that infections with the four endemic coronaviruses ( e, oc , nl , and hku) are common in the general population. natural re-infections with the same virus type have been documented previously, in which repeated infections with oc and e were recorded by serological testing. subsequent infections were separated by at least eight months, though study participants were tested every four months. in most cases, re-infection occurred, though it could present with mild symptoms and a shortened duration of shedding [ ] . the development of immunity to a pathogen through natural infection is a multistep process that typically takes place over one to two weeks. the body responds to a viral infection immediately, with a non-specific innate response in which macrophages, neutrophils, and dendritic cells slow the progress of the virus and may even prevent it from causing symptoms. this non-specific response is followed by an adaptive response where the body makes antibodies that specifically bind to the virus. these antibodies are proteins called immunoglobulins. the body also makes t-cells that recognize and eliminate other cells infected with the virus. this is called cellular immunity. this combined adaptive response may clear the virus from the body, and if the response is strong enough, may prevent progression to severe illness or re-infection by the same virus. this process is often measured by the presence of antibodies in the blood [ ] [ ] [ ] [ ] [ ] [ ] [ ] . most of these studies show that people who have recovered from infection have antibodies to the virus [ ] [ ] [ ] . tests to detect antibody responses to covid- in the population will be critical to support the development of vaccines and to add to our understanding of the extent of infection among people who are not identified through active case finding and surveillance efforts, the attack rate in the population, and the infection fatality rate. for clinical diagnosis, however, such tests have limited utility because they cannot quickly diagnose acute infection to inform actions needed to determine the course of treatment [ ] . fang et al. did a study in february , which compared the sensitivity of chest ct with that of rt-pcr. their case series had patients and they found that the sensitivity of ct for covid- infection was % as compared to rt-pcr sensitivity of % with p < . . their study showed that the ct scan was more sensitive for covid- [ ] . considering this, it is possible that the rt-pcr tests that were negative in our patients on discharge could have been a false negative. the role of chest ct in the evaluation of possible relapses needs to be further explored. new research is directed to develop effective neutralizing antibodies (nabs) for covid- to be used as prophylactic and therapeutic agents to treat its infection and control its spread. in vitro studies showed that a mix comprising antibodies specific for rbd and specific regions in the s protein from sars-cov can crossreact and neutralize those of sars-cov- . this theoretically can improve the breadth and potency of nabs against the virus. also, human sera from recovered patients can be used to treat covid- , but still, studies are needed to make sure it is not a source of infection and to identify its effect on the immune response [ ] . our study has some limitations. these include the small sample size with all the reported patients being adults, incomplete reporting of comorbidities in the included studies in this systematic review, and the absence of reports about relapses outside china. in the end, it is not clear whether these included reports represent a true relapse, prolonged shedding of the virus, or represent false-negative results on discharge. the effect of immunosuppressive therapy given for severe cases on the potential for relapse needs to be further explored. based on this, a broader and larger study is necessary to further investigate the causes of the relapse. according to a recent scientific brief by the world health organization (who), there is no evidence that the patients who recovered from covid- are immune from a second attack. the exact reason for that requires further studies to determine if it is a relapse or reinfection of the virus has not been completely eradicated from the body. it is unclear if the immune system develops neutralizing antibodies against a covid- infection and if corticosteroid administration hinders their development. also, we need to further know if the individual in the second attack is as contagious as the first one even if they develop neutralizing antibodies. until then, it should be assumed that recovered cases are still at risk of reinfection. accordingly, infection prevention guidelines set by the cdc and who should remain in practice. human subjects: all authors have confirmed that this study did not involve human participants or tissue. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. personal protective equipment during the coronavirus disease (covid) pandemic -a narrative review accessed relapse or reinfection after failing hepatitis c direct acting antiviral treatment: unravelled by phylogenetic analysis the prisma group: preferred reporting items for systematic reviews and meta-analyses: the prisma statement positive result of sars-cov- in sputum from a cured patient with covid- clinical characteristics of severe acute respiratory syndrome coronavirus reactivation recurrence of positive sars-cov- rna in covid- : a case report national health commission of the people's republic of china analysis of the causes of "relapse" and treatment strategies of patients with novel 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assay to detect sars-cov- seroconversion in humans accessed world health organization. country & technical guidance -coronavirus disease (covid- ) sensitivity of chest ct for covid- : comparison to neutralizing antibodies against sars-cov- and other human coronaviruses key: cord- -picpuzvo authors: salazar, rafael; hallo, alejandro; vasquez, sebastian; reinthaller, steffy; echeverria, juan title: decreased mortality in patients with severe bronchospasm associated with sars-cov- : an alternative to invasive mechanical ventilation date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: picpuzvo the number of patients with acute episodes of severe bronchospasm needing intubation and ventilatory support has increased rapidly during the severe acute respiratory syndrome coronavirus (sars-cov- ) coronavirus disease (covid- ) pandemic. although medical consensus upholds the use of ventilatory support in this pathology, its survival benefits remain unclear. to improve the outcomes and survival rates, a bundle of early respiratory therapy with a pharmacological rescue regimen was provided to four patients with bronchospasm secondary to covid- . this therapeutic approach successfully delayed the need for invasive mechanical ventilation for hours and decreased the mortality rate in all cases. during the coronavirus disease (covid- ) pandemic, the number of patients with bronchospasm requiring mechanical ventilation has increased considerably. the sudden increase in patients needing intubation represents an unprecedented challenge due to limited availability of equipment in poorly prepared health systems [ ] and the lack of evidence to support its longterm benefits. according to lai, . % of patients with severe acute respiratory syndrome coronavirus (sars-cov- ) develop acute respiratory distress syndrome (ards) and % require invasive mechanical ventilation (imv) [ ] . poor response to imv leads to a mortality rate of . % at hours and % in the following days in intensive care unit (icu) stay [ ] . the increased mortality in critically ill patients [ ] , compared with the relatively low mortality rate in the general population [ ] , has prompted the scientific community to design new therapeutic approaches. global concern about the pandemic has indeed fueled research for treatments to fight the infection; however, to date, there is no standardized treatment [ ] and the process to develop a successful treatment might take months [ ] . we presented four cases in which we used early respiratory therapy and pharmacological approach to successfully address acute episodes of bronchospasm delaying the use of invasive mechanical ventilation hours after the acute episode. a -year-old male, covid- -positive confirmed with polymerase chain reaction (pcr) assay patient with no significant past medical history came to the emergency room (er) complaining of respiratory distress. the patient was admitted under suspicion of bronchospasm with preserved acid-base balance [ph: . (normal range = . - . ), partial pressure of carbon dioxide (paco ): mmhg (normal range = - mmhg), partial pressure of oxygen (pao ): mmhg (normal range = - mmhg)], fraction of inspired oxygen (fio ) of (normal range = > %), pao /fio was (normal range = > ), and oxygen saturation of % associated with sars-cov- complicated with acute respiratory distress syndrome (ards). on admission, the chest x-ray showed bilateral ground-glass pattern, radiographic assessment of lung edema (rale) score ( figure ) [ ] . the patient scored on the sequential organ failure assessment (sofa) score and on the acute physiology and chronic health evaluation (apache) score ( table ) . anteroposterior chest x-ray at the time of acute bronchospasm with radiographic assessment of lung edema (rale) score the initial management comprised placing the patient in the prone position and administering oxygen at high flow through a non-rebreather mask with flow between and liters per minute until reaching % fio . additionally, respiratory therapy consisting of deep inspiration with an inspiratory hold technique was implemented. epinephrine and magnesium sulfate were administered as a bronchodilator regimen ( table ) . ipratropium bromide puff every minutes for one hour followed by once every hours a -year-old male covid- -positive patient with no significant past medical history came to the er complaining of respiratory distress. the patient was admitted due to suspected bronchospasm associated with sars-cov- and later diagnosed with ards. on admission, laboratory and imaging tests showed bilateral ground-glass pattern on chest x-ray and a rale score of ( figure ) anteroposterior chest x-ray at the time of acute bronchospasm with radiographic assessment of lung edema (rale) score the patient was placed in the prone position and oxygenated at high flow with a non-rebreather mask with flow between and liters per minute until reaching % fio . additionally, respiratory therapy consisting of deep inspiration with an inspiratory hold technique was started. epinephrine and magnesium sulfate were administered as a bronchodilator regimen ( table ) . a -year-old female patient with morbid obesity was admitted to our hospital due to the risk of covid- related complications. the chest x-ray showed bilateral ground-glass pattern, rale score was (figure ) [ ] . sofa score was and apache score was ( table ) . anteroposterior chest x-ray at the time of acute bronchospasm with radiographic assessment of lung edema (rale) score the patient was placed in the prone position and oxygenated at high flow with a non-rebreather mask with flow between and liters per minute until reaching % fio . additionally, respiratory therapy consisting of deep inspiration with an inspiratory hold technique was started. epinephrine and magnesium sulfate were administered as a bronchodilator regimen ( table ) . a -year-old male covid- positive patient with no significant past medical history came to the er due to respiratory distress. chest x-ray showed bilateral ground-glass pattern, rale score ( figure ) [ ] . the sofa score was and apache score was ( table ) . the patient was diagnosed with ards. anteroposterior chest x-ray at the time of acute bronchospasm with radiographic assessment of lung edema (rale) score as part of the therapeutic approach, the patient was placed in a prone position with a non-rebreather mask with high flow oxygen between and liters per minute until reaching % fio . respiratory therapy consisting of deep inspiration with an inspiratory hold technique was started. also, epinephrine and magnesium sulfate were administered as a bronchodilator regimen ( table ). a consensus for acute bronchospasm associated with sars-cov- infection is the use of mechanical ventilation [ ] ; however, zareifopoulos warns of the lack of evidence about the long-term benefits in patients on imv [ ] . to improve ventilatory mechanics and ultimately postpone the need for imv due to acute bronchospasm in patients diagnosed with covid- , we put in place a therapeutic approach consisting of early respiratory therapy and pharmacological bronchospasm rescue approach. the patients were placed in a prone position during the treatment of the acute episode of bronchospasm. as per, this maneuver could improve pao /fio improving the oxygenation and ultimately postponing the need for mechanical intubation [ ] . theoretically, greater homogeneity in ventilation decreases ventral alveolar distention or dorsal collapse [ ] . concomitantly, early respiratory therapy using deep inspiration with an inspiratory hold technique was initiated. in this technique, the patient is asked to perform a forced expiration followed by deep inspiration which is held for five to seven seconds. the technique was repeated for four cycles of five breaths every hour to improve ventilation and the mobilization of secretions. although lazzeri reports the risk of superinfections as a possible complication of respiratory therapy in patients positive for sars-cov- , this event did not occur in our patients [ ] . the patients in our study developed their initial episode of severe bronchospasm, based on clinical signs and laboratory tests, at different times of their hospitalization. the events were successfully controlled through the implementation of pharmacologically preventive and rescue therapy for bronchospasm with ipratropium bromide, adrenaline, and magnesium sulfate according to the guidelines for asthma and chronic obstructive pulmonary disease ( table ) [ ] [ ] [ ] . due to the favorable evolution of the patients ( % improvement in respiratory function values in the first four hours compared with the baseline) this therapeutic regime was maintained until the acute presentation resolved. it is worth mentioning that clinical improvement didn't correlate with radiological improvement. as all patients showed remarkable improvement in ventilatory effort evidenced by the use of accessory musculature, oxygen saturation, and kirby index (pao /fio ), they were discharged from icu and continued management in the medical floors. we remark the importance of this case report in the management of patients with severe bronchospasm associated with covid- as the patients who underwent this therapeutic approach didn't require mechanical ventilation within hours after the acute event. by deferring the use of invasive mechanical ventilation, we have significantly decreased the mortality of patients with ards secondary to sars-cov- admitted to the intensive care unit in our hospital. the therapeutic bundle of early respiratory therapy, consisting of deep inspiration with inspiratory hold, and pharmacological bronchospasm rescue decreased the need for invasive mechanical ventilation in patients with bronchospasm associated with sars-cov- and reduced the mortality rate. we suggest further research studies to standardized this management and implementation of guidelines. human subjects: consent was obtained by all participants in this study. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. perspective from ecuador, the second country with more confirmed cases of south america: a review. cureus. severe acute respiratory syndrome coronavirus (sars-cov- ) and coronavirus disease- (covid- ): the epidemic and the challenges emergency tracheal intubation in patients with covid- in wuhan, china: lessons learnt and international expert recommendations intubation and mechanical ventilation of patients with covid- : what should we tell them world health organization declares global emergency: a review of the novel coronavirus (covid- ) perspectives on monoclonal antibody therapy as potential therapeutic intervention for coronavirus disease- (covid- ) frequency and distribution of chest radiographic findings in covid- positive patients covid- pandemic and non invasive respiratory management: every goliath needs a david. an evidence based evaluation of problems respiratory management in severe acute respiratory syndrome coronavirus infection respiratory physiotherapy in patients with covid- infection in acute setting: a position paper of the italian association of respiratory physiotherapists (arir). monaldi arch chest dis management of asthma: the current us and european guidelines new guidelines for acute copd exacerbations acute exacerbation of copd key: cord- -ujsqshjg authors: dexter, franklin; epstein, richard h; shi, pengyi title: forecasting the probability that each surgical case will either be ambulatory or the patient will remain in the hospital overnight versus having a length of stay of two or more days date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ujsqshjg when the hospital census is high, perioperative medical directors or operating room (or) managers sometimes need to review with surgical departments as to which surgical cases scheduled to be performed within the next three days may need to be postponed. although distributions of hospital length of stay (los) are highly skewed, a surprisingly effective summary measure is the percentage of patients previously undergoing the same category of procedure as that scheduled whose los was zero or one day. we evaluated how to forecast each hospital's percentage of cases with los of < days, segmented by category of surgical procedure. the large teaching hospital studied included several inpatient adult surgical suites, an ambulatory surgery center, and a pediatric surgical suite. we included , cases in a training dataset to predict , cases in a test dataset. for each category of procedure, we calculated the cumulative count of cases among quarters, from the most recent quarter, second most recent quarter, and so forth up to the quarter resulting in at least cases. if every quarter combined had fewer than cases for a given category of procedure, we included all cases for that category. for each combination of category and quarter, we used the cumulative counts of cases and cases with los of < days, excluding the current quarter. then, for each category of procedure, and for each of the preceding quarters included for the category, we used the cumulative counts to calculate the asymptotic standard error (se) for the proportion of cases with los of < days. if all preceding quarters combined provided a sample size such that the estimated se for the proportion exceeded . %, we included all preceding quarters. the observed absolute percentage error was . % (se: . %). this error was nearly -fold smaller than the percentage of cases to which it would be used (i.e., . % versus . % with los of < days). the principal weakness of the forecasting methodology was a small bias caused by a progressive reduction in the overall los over time. however, this bias is unlikely to be important for predicting cases’ los when the hospital census is high. when performing these time series calculations quarterly, a reasonable approach is to perform calculations of both case counts and ses for each category of procedure. we recommend using the fewest historical quarters, starting with the most recent quarter, either with at least cases or an estimated asymptotic se for the estimated percentage no greater than . %. applying our methodology with local los data will allow or managers to estimate the number of patients on the elective or schedule each day who will be hospitalized for longer than overnight, facilitating communication and decision-making with surgical departments when census considerations constrain the ability to run a full surgical schedule. in scenarios where hospital census is high, perioperative medical directors or operating room (or) managers may sometimes need to review with surgical departments as to which surgical cases scheduled to be performed within the next three days may need to be postponed, if clinically appropriate. this scenario has arisen at hospitals in regions with large increases in admissions due to coronavirus disease (covid- ) and hospital administrative or governmental mandates to reserve available beds for such patients. previously, we examined summary measures for hospital length of stay (los), as could be used to guide the or manager when deciding which cases may need to be postponed [ , ] . distributions of los are highly skewed, complicating the decision-making process. we used data from all hospitals and ambulatory surgery centers in florida to study all surgical cases that included at least one major therapeutic procedure, with procedures classified using clinical classifications software (ccs) from the agency for healthcare research and quality (ahrq) [ , ] . the first summary measure compared was the percentage of patients previously undergoing the same category of procedure as that scheduled whose hospital los was zero (i.e., ambulatory surgery) or one day (i.e., overnight stay) [ , ] . the percentage of cases with los of < days, being a single number, is simple to compute and easy to understand. the second set of summary measures compared were the mean and standard deviation of los for each category of procedure [ , ] . student's t-test with unequal variances is robust to deviations from a normal or lognormal distribution [ ] . however, for interpreting los, only considering the mean is insufficient because standard deviations differ markedly among procedures [ ] . consideration of both the mean and the standard deviation can be too challenging to be practical to assist decision-making related to case postponement. the third measure compared was the probability that a patient undergoing one category of procedure would have a smaller los than a patient undergoing another category [ , ] . that probability is the area under the receiver operating characteristic curve, calculated by the wilcoxon-mann-whitney test. although this approach is distribution-free, it does not summarize each case as needed by the or manager; rather, it provides pairwise comparisons among all cases [ , ] . the statistical power to compare cases of different categories of procedures was at least as large by comparing percentages of patients with los of < days than versus student's t-test with unequal variances or wilcoxon-mann-whitney test [ ] . we recommended applying the first measure because it is the easiest of the three to implement and interpret [ , ] . one application of our finding is for bed management during the covid- pandemic when the hospital census is high and the number of beds available for elective admissions is being rationed [ ] . the or manager will have many issues in addition to los to consider with surgical departments when determining which cases to postpone, including, but not limited to, the patients' medical conditions, their residential locations and travel times to the hospital, and surgeons' availability. the implication of our results is that when balancing multiple competing objectives and making decisions for scores or hundreds of cases per week, the manager and surgeons can include in the deliberation of which cases to postpone the simple statistic of whether there is a high probability that the patient will remain in the hospital for two days or longer. although the mode or median of the los for a given procedure may be known, this is insufficient to provide information about the tails of the distribution (i.e., the outliers) necessary for decision-making. for example, at the hospital studied, most patients undergoing nephrectomy had a los of two days (i.e., the mode was two days), and % of the patients had a los of ≤ days (i.e., median was two days), but % had a los of ≥ days. the or manager contributes to the assurance of enough bed capacity for medical patients requiring admission (e.g., with respiratory failure from covid- ). in practice, applying our scientific results [ , ] would require that the hospital estimates for each category of procedure the percentage of cases that have los of < days. for example, the preceding cases could be used for each category of procedure, and the percentage of those cases with los of < days calculated. this forecasting is a time series prediction problem. the advantage of using n = is that the cases will be recent, thereby reflecting current discharge practices. alternatively, the last cases could be used. the advantage of using n = is that the percentage of the cases with los of < days will be estimated more accurately. however, such thresholds are arbitrary. alternatively, for each category of procedure, the smallest number of preceding cases possible could be used for which the standard error (se) of each percentage estimate is less than some threshold (e.g., . %). the advantage of an approach based on the se is that to estimate the percentage of cases with los of < days, many fewer cases are needed to estimate the percentage within approximately . % when the raw percentage is approximately % than when the raw percentage is close to %. a further advantage is that consideration of the se balances the desire to use the most recent cases (i.e., favoring current practice), and the desire to obtain greater precision (i.e., larger sample size). in this study, we analyzed five years of data from a large teaching hospital to compare methods of estimating the percentages of cases with los of < days for each category of procedures. the university of iowa institutional review board determined on september , , that this project (no. ) does not meet the regulatory definition of human subjects research since it involved the analysis of previously collected and de-identified data. table shows the progressive process of selecting cases for the training and testing datasets. the surgical cases were performed in the main adult surgical suites, the ambulatory surgery center, or the pediatric suite ors at the studied hospital, all located within a five-minute indoor walk of one another [ ] . the cases were limited to those that were elective, defined by the organization as the surgeon having specified that the patient could wait safely at least three days for surgery (i.e., from friday to monday). the start date, october , , was selected because that was the change date in the united states when all inpatient procedures were required to be coded using the international classification of diseases version procedure coding system (icd- -pcs). we therefore only needed to use the ccs categories obtained from icd- -pcs and for current procedural terminology (cpt) codes [ , ] . the last date of cases was june , , the end of the last full quarter in before data analysis. los was estimated with discharge data through august . there were four-week periods available for testing during the final year. table shows that the distribution of included cases among surgical specialties was similar between the two periods. the sample sizes are explained in table for assigning a ccs category to each case, the vast majority of cases had only one procedure, or when more than one procedure was performed during the case, all procedures performed were of the same category. when a case included more than one procedure and the procedures mapped to more than one ccs category, we used data from the state of florida [ ] . for each ccs category of major therapeutic procedures, we have previously used the percentage of patients in florida in who had los of < days [ ] . the ccs assigned to the case at the study hospital was the ccs with the smallest percentage of patients with los of < days [ ] . the most common of the observed ccs categories are listed in table . all estimation for cases performed during each quarter corresponding to the test dataset was done based on the los percentages from cases performed before the start of that quarter ( table ) . we applied this approach because we expect that many hospitals would not update computer tables more frequently than on a quarterly basis. for example, estimates of the percentage of cases with los of < days for all cases in the th quarter were forecast using workdays in one or more of the preceding quarters. from each quarter, the data used were the count of elective cases for each of the categories and the count of such cases with los of < days. estimation for each quarter proceeded as described below. for each category of procedure, we calculated the cumulative count of cases among quarters, from the most recent quarter, second most recent quarter, and so forth up to the quarter resulting in at least cases. if all preceding quarters combined had fewer than cases, we included all previous cases. among the observed ccs categories of procedure, there were with fewer than cases in total. the choice of cases was based on the results as described in the below paragraphs. for each combination of category and quarter, we used the cumulative counts of cases and cases with los of < days, excluding the current quarter. for each category of procedures, and for each of the preceding quarters included for the category, we used the cumulative counts to calculate the asymptotic se for the proportion of cases with los of < days. that equaled the square root of three terms: the proportion multiplied by the quantity one minus the proportion then divided by the count of cases among the included preceding quarters. if all preceding quarters combined provided a sample size such that the estimated se for the proportion exceeded . %, we included the cases from all preceding quarters. for each combination of the category of procedure and quarter, we determined the smallest number of preceding quarters needed to be included for the preceding count of cases to be at least . we also determined the smallest number of preceding quarters needed to be included for the estimated se of the proportion to be ≤ . %. we used whichever of the two that permitted the use of fewer preceding quarters of data. as noted in the legend of table , there were n = included four-week periods during the final year, comprising the test dataset. for each of the four-week periods, we calculated the count of elective cases, the count of elective cases for each of the categories of procedures, as well as the count of such cases with los of < days for each of the categories. applying the training dataset as described in the preceding section, we also had for each case performed during the training dataset a forecasted probability that the case would have los of < days. we summed the forecasted probabilities to give an estimate for the count of cases with los of < days during the period. we summed the forecasted probabilities because the expected value of the sum of independent bernoulli trials equals the sum of the individual probabilities. the quality of the estimates was calculated for each four-week period. for each period, the observed percentage of cases with los of < days was subtracted from the estimated percentage of cases with los of < days. the absolute value of the difference was taken. the sample mean and sample se of the mean of the absolute values were calculated among the periods. all statistical inference was performed using two-sided one-group student's t-tests based on the sample size of n = independent four-week periods. data are reported as mean (se) except for data from florida [ ] , which were reported as percentages and se. the studied hospital averaged [ ] elective cases per workday. among all hospitals and ambulatory surgery centers in florida, . % ( . %) of cases had los of zero or one day [ ] . at the studied hospital, the percentage was . % ( . %) (i.e., no different from that in florida, p = . ). thus, we believe these findings can be generalized, even though the data in this study are from a single large teaching hospital. we varied the threshold sample size in increments of historical cases and the threshold se of the percentage of cases with los of zero or one day in increments of . %. the minimum observed absolute percentage error was . % ( . %), achieved by using the minimum number of quarters of the year of data providing for either a minimum of historical cases or a maximum . % se (see materials & methods). table shows that there were multiple, near-equivalent, and suitable choices for optimal parameter choices. the means are reported with the standard errors (ses) of the means among the test period of n = four-week periods (see table ). the parameter values described in the section materials & methods and used in table are noted with an asterisk. the negative numbers for bias in the third column show that the historical data (i.e., from the training period) underestimated the percentages of cases with los < days during the test period. this indicates that, overall, the studied hospital's los was declining progressively over time there were ccs categories of procedure with at least one case among the test periods. for each category, we calculated among all periods the absolute difference between the estimated and the actual count of cases with los of zero or one day. we calculated the contribution of each category to the mean. our primary result was that an average absolute percentage error of only . % can be achieved for the percentage probability of patients having los of < days. this error is nearly -fold smaller than the percentage of cases to which it would be used (i.e., . % versus . %). furthermore, tables , show that most of this small bias was caused by progressive reductions in the overall los over time (i.e., there was a consistent underestimation of the percentages of cases with los of < days). for the application of predicting cases' los when the census is high, such underestimation would be preferred because it is conservative. in other words, the number of patients staying in the hospital for ≥ days would be slightly less than predicted. one limitation of our study is that we used data from one large teaching hospital. however, there was no difference in its percentage los of < days than among all hospitals and ambulatory surgery centers in florida. thus, we believe these findings can be generalized. a second limitation is that we used two criteria for selecting historical quarters of training data for each category of procedure, while there are other potential predictive models (e.g., linear changes in percentages over time). however, we doubt that this is important. table shows that there were multiple, nearly equivalent choices for the optimal parameter choices. what matters is that our conceptual strategy worked well, with the precise value of the parameters being of minimal importance. when estimating percentages of cases with los of < days, a decision needs to be made as to how much historical data to use. including too many cases would increase the predictive error because of reductions in los over time for many procedures. including too few cases would increase the predictive error because of imprecision (i.e., wide prediction intervals). in this study, we show that when performing these time series calculations quarterly, a reasonable approach is to perform calculations of both case counts and ses for each category of procedure. we recommend using the fewest historical quarters, starting with the most recent quarter, either with at least cases or an estimated asymptotic se for the estimated percentage no greater than . %. the application of our methodology with local los data will enable or managers to estimate the number of patients on the elective or schedule each day who will be hospitalized for longer than overnight, thereby facilitating communication and decision-making with surgical departments when census considerations hamper the ability to run a full surgical schedule. human subjects: all authors have confirmed that this study did not involve human participants or tissue. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. monte carlo simulations comparing fisher exact test and unequal variances t test for analysis of differences between groups in brief hospital lengths of stay policy implications for the covid- pandemic in light of most patients (≥ %) spending at most one night at the hospital after elective, major therapeutic procedures clinical classifications software (ccs) for icd- -pcs (beta version clinical classifications software for services and procedures a review of analysis and sample size calculation considerations for wilcoxon tests wilcoxon-mann-whitney test for data that are not normally distributed many us hospital-affiliated freestanding ambulatory surgery centers are located on hospital campuses, relevant to interpretation of studies involving ambulatory surgery key: cord- -po zolo authors: inoue, gen; uchida, kentaro; fukushima, kensuke; uchiyama, katsufumi; nakazawa, toshiyuki; aikawa, jun; matsuura, terumasa; miyagi, masayuki; takahira, naonobu; takaso, masashi title: experience of an orthopaedic surgery department early during the covid- outbreak in japan including real-time polymerase chain reaction assay results for sars-cov- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: po zolo introduction the coronavirus disease (covid- ) epidemic beginning december in china has now become a worldwide pandemic. with the need to develop an approach to manage orthopaedic surgeries, we aimed to evaluate the most current data on all the surgical cases in our department including the results of the reverse-transcriptase polymerase chain reaction (rt-pcr) assay for infection with severe acute respiratory syndrome coronavirus (sars-cov- ). methods the monthly number of surgical cases from were reviewed, and compared the numbers of surgical cases both in elective and emergency surgery during the pandemic with the pre-pandemic period. the results of rt-pcr for sars-cov- in orthopaedic surgery cases from may to june , , and clinical signs/symptoms, and laboratory data of consecutive cases within a month from may were also evaluated. results the mean monthly number of surgeries from january to may was significantly lower than the mean number in ( . vs . , respectively, p= . ). the proportion of emergency surgeries in all surgeries performed in may was . %, which is significantly more than the mean rate of . % in (p= . ). hip arthroplasties and spine surgeries showed the greatest reduction, at greater than % and %, respectively. although none of the patients were positive for sars-cov- , . % showed signs/symptoms typical of covid- . the most frequent signs/symptoms were production of nasal mucus ( . %), followed by dry cough ( . %); and fatigue, headache, and dizziness ( . % each). the incidence of abnormal values, which are commonly noted in covid- patients, were eosinopaenia . %; lymphopaenia . %; thrombocytopaenia . %; and elevated prothrombin time . %. conclusions our results show that our rt-pcr negative patients showed signs/symptoms and abnormal laboratory values typical of covid- , indicating surgeons should be aware of these abnormalities in patients and the need to rule out covid- before proceeding with surgery. an epidemic of coronavirus disease caused by infection with the severe acute respiratory syndrome coronavirus (sars-cov- ), began in december in wuhan, china. by the end of february , hundreds of imported and resulting secondary cases were reported in several countries, and currently the pandemic is spreading rapidly across the globe, with more than million infections and more than , deaths worldwide, and on march , , the world health organization (who) declared the outbreak of this novel virus a pandemic [ ] . in japan, the first patient with covid- , with a history of travel to wuhan, was identified in our city in kanagawa prefecture on january , . up to february , covid- cases were detected in all of japan, in addition to the patients with covid- from the diamond princess cruise ship, which was anchored in the port of yokohama in kanagawa from february to march . according to a report on the diamond princess, among the , tested travelers, asymptomatic individuals were positive for sars- cov- by reverse-transcriptase polymerase-chain-reaction (rt-pcr) by february, , ; and the proportion of the confirmed cases that were asymptomatic increased from . % to . % within a week from february [ ] . it is notable that sars-cov- infections appear to have been transmitted during its incubation in the index patient, in whom the illness was brief and nonspecific [ ] . the fact that asymptomatic persons are potential sources of the infection may warrant a reassessment of the transmission dynamics of the current outbreak [ ] . the japanese government declared a state of emergency for japanese metropolitan areas, including our prefecture, regarding covid- on april . citizens in our prefecture were requested to "stay home" and refrain from going out except in cases of necessity, until may , when the state of emergency for metropolitan areas was cancelled. our institution is a critical care medical centre with , beds, which is one of biggest university hospitals in kanagawa inside the metropolitan area. we accept emergency patients including covid- from secondary medical area covering , , population within the area of km . starting in april , our institution officially decided to postpone elective orthopaedic surgeries without urgent necessity, which was consistent with the statement on triage from the japanese orthopaedic association (joa). that statement followed the guidance of the united states center for medicare & medicaid services (cms), which specified that surgeons should perform "essential" surgical procedures only and postpone or cancel "nonessential" surgery [ ] . in addition, because of the long incubation period and asymptomatic spread of covid- , our institution decided to perform real-time rt-pcr for sars-cov- , principally for all patients who required surgery. based on these backgrounds, situation related with orthopaedic surgeries completely changed during this duration. in this study, we reviewed all the surgical cases performed during the covid- pandemic from january to june, in our department. we compared the number and content of surgical cases performed during this period with the cases performed during the previous four years. we also examined the results of pt-pcr for sars-cov- , which was principally performed for all the surgical candidates in our department beginning may , and investigated their laboratory test results before surgery, their clinical signs and symptoms, which were reported to be related with covid- . this study was approved by our institutional review board. we reviewed the monthly number of new outpatients introduced as surgical candidates and surgical cases from january to june , and compared the pre-pandemic numbers with the intra-pandemic numbers of surgical cases both in elective and emergency surgery. we also investigated the relationship between the number of surgical cases and time table of the events related to covid- worldwide and in japan ( figure ). additionally, from january to june , , all surgical cases were reviewed, and the number of cases with frequently performed surgical methods occurring every month, and we compared the trend of change in surgical volume for each method. we undertook a retrospective review of clinical signs and symptoms in consecutive patients who underwent surgery performed by orthopaedic surgeons for one month from may to june , in our department. may , was the date for when rt-pcr was first used to test specimens for sars-cov- , which were taken two days before surgery from every patient needing general anesthesia for their procedure. upon admission, each patient was questioned about the presence of the following signs/symptoms typical for covid- the week before surgery: fever > . ℃, dry cough, fatigue, sore throat, dyspnoea, chest pain, nasal congestion, nasal mucus, smell impairment, taste impairment, headache, dizziness, diarrhoea, abdominal pain, nausea, and vomiting [ ] [ ] [ ] [ ] . the incidence of these signs/symptoms was investigated, regardless of the rt-pcr results. the occurrence of signs/symptoms associated with covid- during their hospital stay and the necessity of additional rt-pcr testing were also investigated. all patients were admitted to our institution two days before surgery and signed informed consent for rt-pcr testing. a nasopharyngeal swab was used to obtain a sample for testing by the -ncov real-time rt-pcr assay. samples were tested for sars-cov- with the nucleic acid detection kits which were recommended by national institute of infectious diseases in tokyo. all samples were processed at the gene testing room in kitasato university hospital. the real-time rt-pcr was performed by a one-step method using a sars-cov- kit according to the protocol " -ncov ver. . and . " both published in march by the national institute of infectious diseases [ ] . primer and probe were designed to detect n and n genes, produced by nihon gene research laboratories inc. (sendai, japan). blood tests were performed before admission, and the following laboratory data were reviewed: white blood cell (wbc) count; percentages of neutrophils, lymphocytes, and monocytes; platelet count; activated partial thromboplastin time (aptt); prothrombin time (pt); levels of d-dimer; albumin, total protein, alanine aminotransferase (alt); aspartate aminotransferase (ast); blood urea nitrogen (bun); and c-reactive protein (crp); hemoglobin (hb) a c; and estimated glomerular filtration rate (egfr). these laboratory data obtained from patients whose surgery was performed from may to june was analyzed. statistical package for social sciences (spss) statistics version (ibm corp., armonk, ny, usa) was used for statistical analysis. demographics were presented by mean and standard deviation (sd) or median and interquartile range (iqr), as appropriate. categorical variables are presented as numbers and percentages. the number of cases were compared by the unpaired t-test, and a p-value < . was considered statistically significant. figure depicts the tendency in number of new outpatients to come to our clinic as surgical candidates per month. the number started decreasing in january and gradually decreased until april, and increased again in may. figure among environmental change in society as described in figure , the number of elective surgeries gradually decreased from january, and decreased drastically in may. on the other hand, emergency surgery decreased gently from january to february, and did not change drastically until the end of june. the mean number of total monthly surgical cases significantly decreased from january to april than ( . ± . vs . ± . , p= . ). compared with , the reduction rate of elective surgery in may was . %, which was obvious compared with the rate of emergency surgery as was . %. the proportion of emergency surgery in all surgery under general anesthesia was significantly higher in may compared with the proportion in ( . % vs . %, p= . ). figure shows the overall detail of the decreased numbers of representative surgical methods. hip arthroplasty and spine surgery showed the most drastic change. hip arthroplasty decreased by % in march, and continue decreasing by more than % in may. spine surgery decreased by more than % in march, and showed a sudden decrease of % on may. arthroscopy and knee arthroplasty decreased in april by % compared with pre-pandemic. hand surgery decreased gradually, and fracture fixation did not change obviously throughout these six months. in january, the first covid- patient in japan was reported in our city, and citizens in our city started to hesitate to visit local medical institutes, resulting in gradual decrease of reference to our hospital. a total of patients receiving general anaesthesia underwent orthopaedic surgery after the initiation of rt-pcr testing until the end of june. during this period, one patient undergoing emergency surgery was not tested, based on the decision of the anaesthesiologist; because of the need for urgent procedures performed by several surgeons, without the rt-pcr testing at the later timing. a total of patients were then tested by the rt-pcr assay, and none of the patients were positive for sars-cov- . the results of laboratory tests performed just before surgery are shown in table . the mean wbc was . × /l. a total of six patients had leucocytosis (> . × /l), had neutrophilic granulocytosis (> . %), three had lymphocytosis (> . %), and had monocytosis. one patient showed leukopenia with a wbc of . × /l, and no patient showed lymphopenia. the platelet count was higher than the normal range in three patients ( . , . , and . × /l). blood coagulation assays showed prolonged aptt in three patients, and one patient each had a spinal metastasis from lung cancer, multiple fractures due to a fall, and secondary to warfarin before undergoing hip arthroplasty. the pt was prolonged in five patients, including two patients with spinal metastasis. abnormal d-dimer levels were seen in patients including four with mg/l, two with mg/l, and one with mg/l. fifteen ( . %) of patients had low albumin levels, and seven ( . %) had low total protein levels because of their preoperative poor condition. all patients did not show severe liver or renal dysfunction. two patients with lung cancer or multiple fractures due to a traffic accident showed a crp level higher than μmol/l. the covid- pandemic has changed all aspect of "normal" orthopaedic surgery in one of biggest university hospitals in kanagawa prefecture, the capital area of japan. during this period of the state of emergency, the kanagawa prefecture reported that the weekly number of new patients, diagnosed with covid- (excluding those associated with the diamond princess cruise ship) increased to a maximum of new patients from april to , and thereafter decreased gradually after the state of emergency declaration ( figure ) . in our department, we only performed less than % of surgery under general anesthesia in may, compared with the previous years. during this pandemic period, hip arthroplasty and spinal surgery decreased the most by % and % at maximum, followed by arthroscopy and hand surgery. the main reason of the decrease of elective surgeries from january was decrease of introduced surgical candidates from january to march, when patients started to hesitate to go to local clinics. additionally, the petition of the prefecture not to go out without necessity and emergency, declaration of state of emergency, and the policy of our hospital to postpone elective orthopaedic surgeries without urgent necessity facilitated the intensive decrease from april to may (figure ). because we accepted cases needing immediate surgery (e.g., multiple trauma, open fracture, rapidly progressing myelopathy, spinal metastasis, and pyogenic spondylitis), the cases of fracture fixation did not change throughout this period, and the emergency surgery decreased gently compared with elective surgery. on may , japanese government cancelled the declaration of state of emergency, and on june , our institution cancelled restriction of surgical procedures, and the number of procedures recovered to about % of the total number of cases compared with previous years. bar graph: new patients, line graph: cumulative number of patients. during this pandemic period, japanese citizens were required to stay home and avoid going out for unnecessary or nonurgent purposes; and to avoid the "three cs": closed spaces with poor ventilation, crowded places with many people nearby, and close-contact settings such as close-range conversations. additionally, our city was the first place where a covid- patient was diagnosed in japan. as a result of patient factors, the number of patients coming to the outpatient clinic as surgical candidates decreased gradually from january, and decreased drastically after the mandate by the governor not to go out without necessity and emergency at the end of march. additionally, the joa published guidance for triage for the postponement of nonessential orthopaedic surgery. the government mandates and guidance on surgery led our department to suppress the number of surgeries performed by our department from the middle of march to the end of june, apart from patients' factor. in the united states, over , hip and knee arthroplasty were estimated canceled each week during restrictions established because of the covid- pandemic [ ] . a large cohort study of . million residents in hong kong reported that orthopaedic surgeries were reduced by . %, and elective joint replacements and ligament reconstructions were decreased by % and %, respectively [ ] . the number of surgeries in our institute reduced by % in hip arthroplasty and by % in total. content of surgical methods should vary depending on the characteristics of each institute, and the reduction rate was consistent to the previous report. rt-pcr was positive for sars-cov- in % of our consecutive cases from may until june . keio university hospital in tokyo started to perform the -ncov real-time rt-pcr assay at their outpatient clinic on april for all patients who needed admission. their press release reported the incidence of rt-pcr positivity in asymptomatic patients every week from april thereafter. the highest incidence of rt-pcr positivity was . % (five of patients) during the week of april to [ ] . in new york city, rt-pcr assays of nasopharyngeal swab specimens from patients undergoing routine testing for sars-cov- prior to their planned orthopaedic surgical procedure showed a positivity rate of . %. a total of . % of the positive specimens were from asymptomatic patients [ ] . these results suggest that there are unknown numbers of asymptomatic patients who could be potential sources of an outbreak of covid- in any hospital elsewhere. the rates of asymptomatic individuals might vary between regions or types of hospitals and our results could not be consistent in another region even in japan. in japan, some experts thought that the indications for rt-pcr testing were too narrow, and the daily number of people tested was too low, resulting in an inaccurate number of individuals with covid- . indeed, the rate of rt-pcr testing in japan has been reported to be . per , people, which is the th lowest among countries participating in the organization for economic co-operation and development (oecd) [ ] . however, the data from the tokyo metropolitan government showed that the actual positive rate also decreased from . % on april to . % on may , and did not increase to higher than . % up until june [ ] . these epidemiologic data from kanagawa and tokyo suggest that the first wave of covid- might have peaked in the metropolitan area in early june. in covid- patients with pneumonia and abnormal findings on chest computed tomography, the reported signs/symptoms at onset included fever ( %), cough ( %), myalgia or fatigue ( %), sputum production ( %), headache ( %), haemoptysis ( %), and diarrhoea ( %); and after a median time of eight days from the onset of illness, dyspnoea developed in % of patients [ ] . the other report showed that impairment of smell or taste was often the first apparent symptom, with a prevalence of . % in mildly symptomatic patients, but that it rarely was the only symptom of sars-cov- infections [ ] . schneider et al. evaluated orthopaedic healthcare workers exposed to one patient who became positive for sars-cov- infection one week after admission, and reported that the rt-pcr assays were negative for all healthcare workers, although ( %) manifested clinical signs/symptoms suggestive of covid- , including cough ( . %), sore throat ( . %), nasal congestion ( . %), dyspnoea ( . %), fever ( . %), headache, and myalgias ( . %) [ ] . in our study, although pt-pcr testing was negative for all consecutive patients, several signs/symptoms were noted, including nasal mucus ( . %), cough ( . %), fatigue ( . %), headache ( . %), dizziness ( . %), nasal congestion ( . %), and diarrhoea ( . %). a few patients also reported sore throat, nausea, fever, chest pain, dyspnoea, abdominal pain, and smell impairment. these symptoms are not specific to covid- and have been confirmed to occur in patients undergoing orthopaedic surgery at various frequencies. there are several papers that revealed the characteristics of laboratory data of covid- patients. among patients with covid- related pneumonia, % had leukopenia (wbc less than × /l) and % of patients had lymphopenia (lymphocyte count less than . × /l) [ ] . [ ] . in this study, only one patient ( -year-old man) with multiple myeloma showed leukopenia (wbc . × /l), and the mean d-dimer level of patients was relatively higher ( . ± . mg/l). in our patients, only the incidence of elevated d-dimer levels ( . %) was similar which might be caused by various patients' backgrounds including severe general condition, but the other parameters were lower than those of the covid- patients noted in the literature review. our results suggest that abnormal values in laboratory data themselves were not specific for covid- , but surgeons should always be aware of the possibility of abnormal laboratory data that are uncommon in the usual clinical setting of orthopaedic surgery to rule out covid- patients. now, at the end of june, the time of this writing, the weekly number of new covid- patients in kanagawa prefecture seems to be under control ( figure ), but citizens were allowed to move across prefectures and increasing tendency are noted, with several clusters in tokyo. also, the cases of orthopaedic surgery were increasing now. we will continue rt-pcr testing for sars-cov- , in preparation for the second wave of infections that should arrive in the near future, trying to resume adequate orthopaedic surgeries. further evidence of experiences related with covid- is essential to establish the appropriate medical system to produce the orthopaedic surgery properly in this era of coexistence with the covid- . our results show that, in , the number of elective surgeries gradually decreased from january until may, but emergency surgery decreased gently from january to february, and did not change drastically until the end of june in our hospital. although none of the patients were positive for sars-cov- during the first wave of covid- in our department, . % of the patients showed signs/symptoms typical of covid- , indicating surgeons should be aware of these abnormalities in patients and the need to rule out covid- before proceeding with surgery. human subjects: consent was obtained by all participants in this study. institutional review board for observation and epidemiological study issued approval b - . this study was approved by our institutional review board. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. world health organization (who) coronavirus disease (covid- ) situation reports estimating the asymptomatic proportion of coronavirus disease (covid- ) cases on board the diamond princess cruise ship china coronavirus: six questions scientists are asking transmission of -ncov infection from an asymptomatic contact in germany a review of state guidelines for elective orthopaedic procedures during thecovid- outbreak clinical manifestations and evidence of neurological involvement in novel coronavirus sars-cov- : a systematic review and meta-analysis clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china. jama. a pneumonia outbreak associated with a new coronavirus of probable bat origin epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study national institute of infectious diseases report effect of covid- hip and knee arthroplasty surgical volume in the united states impact of covid- on orthopaedic and trauma service an epidemiological study keio university hospital information about coronavirus disease universal testing for covid- in essential orthopaedic surgery reveals a high percentage of asymptomatic infections organization for economic co-operation and development (oecd) policy responses to coronavirus (covid- ) tokyo metropolitan government covid- information website clinical features of patients infected with novel coronavirus in wuhan, china. lancet. alterations in smell or taste in mildly symptomatic outpatients with sars-cov- infection assessing the spreading potential of an undetected case of covid- in orthopaedic surgery epidemiology and clinical features of covid- : a review of current literature we are grateful to ms. aya nishiyama and ms. mamiko noshita from kitasato university hospital for sincere support for data collection and analysis in this study. key: cord- - ghjewxc authors: douedi, steven; alshami, abbas; costanzo, eric title: extracorporeal membrane oxygenation as treatment of severe covid- infection: a case report date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ghjewxc novel coronavirus (covid- ) is a severe respiratory infection leading to acute respiratory distress syndrome (ards) accounting for thousands of cases and deaths across the world. several alternatives in treatment options have been assessed and used in this patient population. however, when mechanical ventilation and prone positioning are unsuccessful, venovenous extracorporeal membrane oxygenation (vv-ecmo) may be used. we present a case of a -year-old female, with no significant medical history and no recent history of exposure to sick contacts, presented to the emergency department (ed) with fever, severe shortness of breath, and flu-like symptoms with a positive covid- test. ultimately, she worsened on mechanical ventilation and prone positioning and required vv-ecmo. the use of vv-ecmo in covid- infected patients is still controversial. while some studies have shown a high mortality rate despite aggressive treatment, such as in our case, the lack of large sample size studies and treatment alternatives places healthcare providers against a wall without options in patients with severe refractory ards due to covid- . the novel coronavirus (covid- ) is a respiratory tract infection that has resulted in a pandemic, infecting more than , , humans and claiming the lives of over , in less than six months [ ] . the disease classically results in hypoxemic respiratory failure requiring oxygen supplementation using low and high delivery systems, as well as mechanical ventilation. however, when all these measures fail, options become very limited. one of these potential alternatives is the extracorporeal membrane oxygenation (ecmo). evidence on ecmo in covid- patients remains controversial, as the immunological side effects of ecmo can further compromise the already debilitated immune system fighting covid- [ ] . we report a case of a covid- -positive patient who was managed with ecmo after no response to mechanical ventilation and prone positioning. a -year-old female with no significant medical history and no recent history of travel or exposure to sick contacts presented to the emergency department (ed) with a worsening dry cough, shortness of breath, and chest tightness, followed by fever, chills, and myalgias for four days duration. other reported symptoms included a mild sore throat and watery diarrhea. vital signs on admission were a temperature of . °fahrenheit (measured orally), a heart rate of beats per minute, a blood pressure of / mm hg, respiratory rate of breaths per minute, and oxygen saturation of % on room air ( % on liters nasal cannula). physical examination was pertinent for ill appearance and rhonchi over the left lung base. blood tests showed a white blood cell count of . cells/mm , lymphopenia of cells/mm , hemoglobin of . g/dl, potassium of . meq/l, aspartate aminotransferase (ast) of iu/l, alanine aminotransferase (alt) of iu/l, lactate of . mmol/l, and procalcitonin . ng/ml. polymerase chain reaction (pcr) tests for influenza a and b, metapneumovirus, adenovirus, parainfluenza, respiratory syncytial virus, and coronaviruses hku , nl , e, and oc were all negative. given the current pandemic, covid- was suspected, and a nasal swab was sent to be tested. a computed tomography scan of the chest was obtained and showed bilateral infiltrates ( figure ). bilateral diffuse scattered patchy ground-glass opacities throughout the lungs with more geographic mixed ground-glass and consolidative opacities in the lingular and superior segment of the left lower lobe extending to the posterior left lower lobe. mild to moderate patchy scattered ground-glass opacities were seen in the right lower lobe, as well as a perihilar right upper lobe with areas of peripheral ground-glass opacities the patient was started empirically on intravenous (iv) vancomycin, piperacillin-tazobactam, azithromycin, and hydroxychloroquine. over a one-day period, the patient's respiratory status progressively deteriorated, and she was subsequently intubated. on the following day, the covid- test came back positive, and the patient was continued on mg daily of hydroxychloroquine and mg twice daily of azithromycin. she was also started on high-dose vitamin c at a rate of grams iv twice daily, and mg of zinc sulfate via orogastric tube once daily. despite aggressive management, she developed severe acute respiratory distress syndrome (ards) and was requiring higher mechanical ventilation settings ( % fraction of inspired oxygen and of positive end-expiratory pressure). the decision was also made to begin prone positioning of the patient for hours a day for a ratio of arterial oxygen partial pressure to fractional inspired oxygen (p/f ratio) of < . liver enzymes continued to trend up (ast and alt ), and the patient developed acute kidney injury due to decreased organ perfusion. she was started on levophed for hemodynamic stability and to maintain a mean arterial pressure > . she was also given one dose ( mg/kilogram body weight) of tocilizumab, an anti-interleukin- receptor monoclonal antibody, in order to help control her cytokine storm. despite this, she continued to decompensate, and the patient was started on continuous venovenous hemodialysis (cvvhd) for renal failure and on venovenous extracorporeal membrane oxygenation (vv-ecmo). prior to vv-ecmo, an echocardiogram was performed which showed an ejection fraction of % - %, moderate pulmonary hypertension, and grade (mild) diastolic dysfunction. two days after starting vv-ecmo, the patient lymphocyte count was cells/mm , white blood cell count was . cells/mm , fibrinogen level < , and d-dimer , . she was started on lovenox, mg/kg, due to a severely elevated d-dimer; however, her platelet count decreased by greater than %, and she was switched to argatroban. heparininduced thrombocytopenia (hit) panel was sent and returned negative, but she remained on argatroban for anticoagulation due to the significant drop in her platelet count on heparin products. she began to develop ischemia in her fingers and toes bilaterally but was continued on levophed for hemodynamic stability and vv-ecmo. four days after the initiation of vv-ecmo, the patient developed an asystole rhythm and ultimately passed away. extracorporeal membrane oxygenation (ecmo) has remarkably progressed over recent years and became a reliable tool in severe cardiac and pulmonary dysfunction [ ] [ ] . venovenous ecmo (vv-ecmo) can be considered in patients with a pf ratio of - mm hg, murray score > , and a ph of < . on arterial blood glass [ ] . vv-ecmo allows deoxygenated blood to be pulled from the right atrium through a cannula allowing it to pass through an oxygenator and heat exchanger before being pumped back into the right atrium through another cannula [ , ] . there are no relative contraindications to vv-ecmo as the decision is made on a case-by-case basis; however, the patient's age and comorbidities must be taken into consideration and an echocardiogram should be performed prior to initiation to evaluate for right or left ventricular failure to confirm the nature of pulmonary failure [ , ] . complications of vv-ecmo include bleeding, infection, air embolism, heparin-induced thrombocytopenia (hit), and catheter/machine-associated dysfunction [ ] . despite these complications, some studies have shown that vv-ecmo significantly improves survival in severe acute respiratory failure, including patients with influenza a (h n )-related acute respiratory distress disease [ ] [ ] [ ] . vaquer et al. reported that % of patients who received vv-ecmo were successfully discharged from the hospital despite severe refractory ards [ ] . the use of ecmo in covid- patients is still controversial and has mixed results. li et al. reported seven covid- infected patients with p/f ratios < on vv-ecmo and was able to successfully wean three patients thus far; however, they had a mortality rate of % [ ] . yang et al. had similar results where five of six patients receiving ecmo for covid- infection died [ ] . it was found that a decreased lymphocyte count was associated with poor outcomes and death from covid- infections [ , ] . in our case presented, our patient did not respond to mechanical ventilation. due to a lack of alternatives, her young age, and no comorbidities, vv-ecmo was considered in our patient with severe ards (p/f ratio < ) due to the covid- infection. ultimately, her lymphocyte count was cells/mm and she did not respond to vv-ecmo and passed away. while most studies lack a significant sample size, this case adds to the concern on the use of ecmo in covid- patients. in patients with severe ards unresponsive to mechanical ventilation, prone positioning, and other alternatives, the need for further studies and understanding the role of ecmo in respiratory failure need to be assessed. vv-ecmo use in patients with severe refractory ards due to covid- infections is still controversial. while some studies have shown a high mortality rate despite aggressive treatment, such as in our case, they lack sufficient sample sizes. due to limited alternatives and treatment options for patients with severe refractory ards, studies evaluating the use of ecmo in covid- are desperately needed. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. covid- ) outbreak covid- , ecmo, and lymphopenia: a word of caution veno-venous extracorporeal membrane oxygenation: cannulation techniques extra corporeal membrane oxygenation (ecmo) review of a lifesaving technology venovenous extracorporeal membrane oxygenation in intractable pulmonary insufficiency: practical issues and future directions extracorporeal membrane oxygenation rescue for h n acute respiratory distress syndrome: equipoise regained systematic review and meta-analysis of complications and mortality of veno-venous extracorporeal membrane oxygenation for refractory acute respiratory distress syndrome. ann intensive care extracorporeal membrane oxygenation for coronavirus disease clinical predictors of mortality due to covid- based on an analysis of data of patients from wuhan, china key: cord- -hmy ovuq authors: mittal, abhinav; forte, michael; leonard, rachel; sangani, rahul; sharma, sunil title: refractory acute respiratory distress syndrome secondary to covid- successfully extubated to average volume-assured pressure support non-invasive ventilator date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: hmy ovuq coronavirus disease (covid- ) is a respiratory illness caused by the highly infectious novel sars-cov- coronavirus spread by droplet transmission. consequently, the use of respiratory devices that may potentially promote aerosolization like non-invasive positive pressure ventilation (nippv) for diseases such as obstructive sleep apnea (osa), advanced chronic obstructive lung disease, pulmonary hypertension (ph), and neuromuscular respiratory disease has been called into question. we present a case of a patient with history of osa and ph convalescing from refractory acute respiratory distress syndrome (ards) secondary to covid- who was successfully extubated to average volume-assured pressure support (avaps). a -year-old male with medical history notable for osa on nippv, ph, and hypertension presented with respiratory failure secondary to covid- confirmed on polymerase chain reaction (pcr) test. his respiratory status worsened leading to ards requiring intubation. he was initially extubated to high flow nasal cannula (hfnc) due to hospital policy to avoid nippv due to concerns of viral dissemination. he did not tolerate hfnc and required re-intubation for prolonged period. he was then medically optimized for a second attempt and extubated two days later to avaps with an anti-viral filter and negative pressure room with a goal of optimizing his critical illness myopathy and pre-existing osa and ph. he tolerated extubation well, and over the next five days was weaned from alternating avaps/hfnc to eventually requiring two liters nasal cannula in the day and avaps mode at night. this case highlights a potential therapeutic option for patients with severe respiratory failure secondary to covid- . this patient’s pre-existing comorbidities of osa and ph markedly increased his risk for extubation failure on hfnc. the use of avaps after his second extubation attempt helped ensure ventilation and oxygenation non-invasively. covid- can lead to prolonged dependence on mechanical ventilation. this pandemic has the potential to create medical resource scarcities, especially in rural areas where ventilators and trained personnel are already in short supply. by using avaps mode, this patient was able to rehabilitate his myopathy and participate in intermittent weaning of hfnc to ultimately simple nasal cannula. avaps is useful tool to facilitate extubation, as it allows non-invasive support of respiratory dynamics, particularly in those with co-morbidities such as osa and ph. further, larger scale studies are needed to determine its exact role during the covid- pandemic. a -year-old male with medical history notable for osa on nippv, ph, and hypertension presented with respiratory failure secondary to covid- confirmed on polymerase chain reaction (pcr) test. his respiratory status worsened leading to ards requiring intubation. he was initially extubated to high flow nasal cannula (hfnc) due to hospital policy to avoid nippv due to concerns of viral dissemination. he did not tolerate hfnc and required re-intubation for prolonged period. he was then medically optimized for a second attempt and extubated two days later to avaps with an anti-viral filter and negative pressure room with a goal of optimizing his critical illness myopathy and pre-existing osa and ph. he tolerated extubation well, and over the next five days was weaned from alternating avaps/hfnc to eventually requiring two liters nasal cannula in the day and avaps mode at night. this case highlights a potential therapeutic option for patients with severe respiratory failure secondary to covid- . this patient's pre-existing comorbidities of osa and ph markedly increased his risk for extubation failure on hfnc. the use of avaps after his second extubation attempt helped ensure ventilation and oxygenation non-invasively. covid- can lead to prolonged dependence on mechanical ventilation. this pandemic has the potential to create medical resource scarcities, especially in rural areas where ventilators and trained personnel are already in short supply. by using avaps mode, this patient was able to rehabilitate his myopathy and participate in intermittent weaning of hfnc to ultimately simple nasal cannula. avaps is useful tool to facilitate extubation, as it allows non-invasive support of respiratory dynamics, particularly in those with co-morbidities such as osa and ph. further, larger scale studies are needed to determine its exact role during the covid- pandemic. the management of coronavirus disease (covid- ) patients with hypoxemic respiratory failure is challenging due to high infectious potential of novel sars-cov- , presentation heterogeneity, severity of disease manifestation, finite supply of ventilators, and limited evidence-based practices [ , ] . given uncertainties regarding modes of transmission and risk of aerosolization of this novel virus, the use of non-invasive positive pressure ventilation (nippv) has been called into question [ ] . however, there is currently little guidance on how clinicians should manage patients previously reliant on nippv for diseases such as obstructive sleep apnea (osa), advanced chronic obstructive lung disease, pulmonary hypertension (ph), and neuromuscular respiratory disease. not only are patients with these co-morbidities more likely to suffer more serious manifestations of covid- , but prolonged ventilation predisposes patients to neuromuscular weakness. strategic use of average volume-assured pressure support (avaps) mode of ventilation as a bridge in recovering covid- has the potential to facilitate earlier extubation, conserve traditional ventilators, and prevent re-intubation/tracheostomies. we present a case of a patient with history of osa and ph convalescing from refractory acute respiratory distress syndrome (ards) secondary to covid- who was successfully extubated to avaps. a -year-old male with medical history notable for osa on nippv, ph, and hypertension initially presented to an outside hospital due to hypoxia and dyspnea. a week prior, he was in great functional health and, in fact, was returning from a skiing trip requiring travel through two major us airports. initial workup demonstrated bilateral infiltrates on chest imaging ( figure ) and covid- polymerase chain reaction (pcr) test was positive. his respiratory status worsened leading to moderate ards with pao /fio (arterial oxygen partial pressure divided by fraction of inspired oxygen) ratio of prompting intubation, paralysis, and transfer to our tertiary care facility. his intensive care unit (icu) stay was complicated by ventilator-associated pneumonia, non-st elevation myocardial infarction (nstemi), delirium, and myopathy of critical illness. transthoracic echocardiography showed preserved left ventricular ejection fraction after nstemi and he was medically optimized over the next week. standard ards management helped to slowly improve his respiratory status, and on hospital day (day of intubation), he was extubated to high flow nasal cannula (hfnc) because hospital policy recommended avoidance of nippv. unfortunately, he failed the trial and required re-intubation. he was again medically optimized and two days later was on minimal ventilator settings and favorable weaning parameters. however, this time given our concerns for his critical illness acquired myopathy and to better address his pre-existing osa and ph, we gained institutional clearance to proceed with trial of extubation to avaps with an anti-viral filter and negative pressure room on intubation day . he tolerated extubation well and over the next five days was weaned from avaps/hfnc alternating to eventually requiring two liters nasal cannula in the day and avaps mode at night. this case highlights a potential therapeutic option for those patients with respiratory failure from covid- . this patient's pre-existing co-morbidities of osa and ph markedly increased his risk for extubation failure on the first attempt. while hfnc can potentially provide some positive end expiratory pressure, it is certainly inferior to nippv [ ] . the use of avaps allowed us to ensure ventilation and oxygenation in a similar manner to mechanical ventilation non-invasively. furthermore, by using avaps mode, the patient was able to rehabilitate his myopathy and participate in intermittent weaning of hfnc to ultimately simple nasal cannula. we continued avaps therapy nightly for treatment of his osa and ph. we believe a similar scheme of ventilator weaning would be helpful in other such patients. covid- is a respiratory illness leading to hypoxic respiratory failure with rates of about % including need for nippv in - % and intubation in - % [ ] . patients with severe covid- infections often have prolonged dependence on mechanical ventilation. prolonged duration of mechanical ventilation predisposes patients to critical illness neuropathy/myopathy sometimes referred to as "icu acquired weakness". icu-acquired weakness increases risk of in-icu, inhospital, and long-term mortality, along with duration of mechanical ventilation, and length of stay. it augments healthcare-related costs, increases likelihood of prolonged care in rehabilitation centers, and reduces physical function and quality of life in the long term [ ] . in such a circumstance, the need to consider long-term tracheostomy may be superseded by the risk of further aerosolization involved in directly manipulating the airway of a covid- positive patient. our use of non-invasive ventilation with avaps mode not only helped optimize this patient's co-morbidities, but also ultimately avoided tracheostomy. we believe the avaps mode was able to provide him sufficient ventilatory support which kept him extubated. liberation from mechanical ventilation allowed him to better participate in rehabilitation for a better prognosis. this mode of ventilation could potentially shorten intubation times and reduce risk of neuromuscular weakness. avaps is a relatively new mode of ventilation. avaps uses an internal algorithm to make changes in the pressure support supplied to achieve the target volume, but these changes are small and occur over minutes (typically - . cm water per minute). that is why it is not a good mode in acute setting with rapid respiratory rate -but as noted in our case -worked well in a recovering patient requiring a slow wean. the perceived advantage of avaps over bilevel positive airway pressure (bipap) includes maintaining volumes despite altered patient effort based on sleep stage or altered lung mechanics. a fixed pressure support setting is unlikely to compensate for these changes in resistance due to changing lung compliance, body position, and sleep. in a randomized trial, avaps delivered a lower mean ps for oxygenation and transcutaneous paco levels and promoted better adherence than bipap [ ] . avaps mode is typically used in patients with neuromuscular disorders, ohs and chronic obstructive pulmonary disease (copd). given the potential impact of this pandemic to exhaust medical resources like ventilators, discussions of possible salvage support strategies like synchronous mechanical ventilation of multiple patients with a single ventilator are gaining attention [ ] . such pandemic-related scarcities have serious ramifications in rural areas where ventilators and trained personnel are already in short supply. utilization of home ventilators with avaps mode as a means of stepping down ventilator support could be one option to allocate the more powerful/sophisticated ventilators to the sickest patients. given this successful extubation after nearly two weeks on the ventilator, this experience also lends credence to the possibility of using avaps and other nippv devices to support patients on minimal ventilator settings who need more time convalescing from their acute illness [ ] . this case highlights the potential utility of avaps as useful tool to facilitate extubation, with its ability to manage complex lung dynamics including muscular weakness inherent to prolonged ventilation. using avaps as a bridge facilitated successful extubation and avoided tracheostomy. this could further help liberate ventilators for more advanced ards patients. further, larger scale studies are needed to determine its exact role during the covid- pandemic. practical recommendations for critical care and anesthesiology teams caring for novel coronavirus ( -ncov) patients treatment for severe acute respiratory distress syndrome from covid- more awareness is needed for severe acute respiratory syndrome coronavirus transmission through exhaled air during non-invasive respiratory support: experience from china high-flow nasal cannula oxygen therapy in adults: physiological benefits, indications, clinical benefits, and adverse effects surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease (covid- ) van den berghe g: icu-acquired weakness average volume-assured pressure support in obesity hypoventilation: a randomized crossover trial optimizing ventilator use during the covid- pandemic . us public health service commissioned corps noninvasive ventilation to prevent respiratory failure after extubation in high-risk patients human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- - mvfiuwc authors: montenegro-villalobos, jiulliana; miranda-jiménez, brian; Ávila-aguero, maría l; ulloa-gutierrez, rolando title: subconjunctival acute bilateral hemorrhages due to kawasaki disease in a costa rican girl: an unusual clinical manifestation of the disease date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: mvfiuwc kawasaki disease is an acute systemic vasculitis and is the leading cause of acquired cardiac disease in children. among the ocular manifestations in these patients, bilateral non-suppurative conjunctival injection and uveitis are the most common. we describe a six-year-old costa rican girl with acute kawasaki disease who developed severe bilateral conjunctival injection with subsequent bilateral subconjunctival hemorrhages. for her ocular involvement, she was treated expectantly, and after six weeks there was complete resolution. to our knowledge, this is the first report from latin america and among the few in the literature of a child in whom severe bilateral subconjunctival hemorrhages occur as a manifestation of kawasaki disease. kawasaki disease (kd) is an acute systemic vasculitis and the leading cause of acquired cardiac disease in children, with approximately % of cases occurring in children in the first five years of age. among ocular manifestations in these patients, non-suppurative conjunctivitis and acute uveitis are the most common and both are usually self-limited [ ] . this report describes the presence of bilateral subconjunctival hemorrhages as an unusual manifestation of kd in a girl who was transferred to the only national pediatric tertiary referral and academic hospital of costa rica, which belongs to the network of hospitals of the caja costarricense de seguro social (ccss). maternal written informed consent and institutional authorization were obtained for the publication of this report. a six-year-old girl presented to a regional peripheral hospital with a six-day history of persistent fever, bilateral non-suppurative bulbar conjunctivitis, cheilitis, a non-tender cervical right-side . cm diameter lymphadenopathy, and diffuse abdominal pain. she had been treated during the last three days with oral amoxicillin/clavulanic acid for an upper respiratory infection but had no improvement. acute kd was clinically suspected because of persistent fever despite antibiotic and antipyretic treatment, oral mucositis, and strawberry tongue, and the girl was referred to our center for specialized management and treatment. upon direct admission to our pediatric infectious disease ward, temperature was . °c, heart rate /min, blood pressure / (mean arterial pressure [map] ) mmhg, pulse oximetry % saturation. non-suppurative bilateral conjunctivitis with limbar sparing (figure ) was documented, strawberry tongue, and right-side non-tender cervical lymphadenopathy, and looked acutely ill. laboratory findings showed complete blood count hemoglobin . g/dl, hematocrit . %, leukocytes/mm (neutrophils , lymphocytes, eosinophils), and , platelets/mm . c-reactive protein (cpr) was mg/dl (normal range < mg/dl), and biochemistry tests were normal. no sterile pyuria was documented. intravenous immunoglobulin (ivig) at g/kg on single infusion, and oral acetylsalicylic acid (asa) at mg/kg/d were initiated. the patient evolved satisfactorily with fever resolution over the next hours. however, one day after ivig infusion was completed, she developed extensive bilateral subconjunctival hemorrhages of temporal predominance (figures , ) , which increased in intensity during the following two days especially in the left eye. given this finding, an evaluation by pediatric ophthalmology was performed, a normal eye fundus was documented, anterior uveitis was ruled out, and conservative eye management was recommended. an echocardiogram during admission showed normal coronary arteries, with no abnormalities in function or structures of the heart. she was discharged on oral asa mg/kg/ day. on followup appointments, a second echocardiogram was normal eight weeks after. she had resolution of the hemorrhages after approximately six weeks and no visual sequelae have been documented so far. no peeling in hands or feet was described subsequently, neither thrombocytosis was found on her follow up complete blood count test. the third echocardiogram has been postponed due to the coronavirus disease (covid- ) pandemic. kawasaki disease is a systemic vasculitis of small and medium sized vessels. kd etiology is presumed to be infectious, however, a specific agent has not been identified and the etiology is multifactorial. complete (typical) kd diagnosis is clinical, based on the presence of fever persisting for at least five days and accompanied by four of five findings: changes in the extremities including hand and/or foot erythema or swelling during the acute stage and fingertip scaling over convalescence; polymorphous skin exanthema; bilateral conjunctivitis with no purulent discharge and classically with perilimbal sparing; oral mucositis including strawberry tongue; and cervical unilateral lymphadenopathy with a . cm or larger diameter. in some cases, patients do not fulfill the classic criteria for kawasaki disease and are classified as having incomplete (atypical) disease, this is more common in younger infants and older children. ocular complications in kawasaki disease usually occur during the acute and subacute phases, are usually transient, and resolve during the following months. the most common ocular feature is bilateral conjunctival injection, which is present in up to % of patients [ ] . ohno et al. in were among the first researchers to describe prospectively the ocular manifestations of kd patients, by using slit-lamp biomicroscopy, ophthalmoscopy, determination of visual acuity and tonometry whenever possible and follow them up frequently. in an analysis of children, they found bilateral conjunctival injection in ( %) patients, superficial punctate keratitis in / children ( %), vitreous opacities in / ( %), papilledema in / ( %), and subconjunctival hemorrhage in / ( %). except for subconjunctival hemorrhage, these symptoms were also bilateral. in a more recent publication of kd cases from brazil, alves et al. described the presence of ocular complications in . % of patients, being the most frequent complication anterior uveitis in , papilledema in one, and conjunctival hemorrhage in one, being this unilateral as well [ ] . in , al-abbadi et al. [ ] performed cytopathological tests by means of pap smear of the conjunctiva of patients with kawasaki disease in the acute stage, and after treatment with ivig. they found that in the acute stage of the disease there is a predominantly neutrophilic inflammatory infiltrate, which rapidly changes to mononuclear and resolves in the convalescent stage, and that similar changes occur at the peripheral blood level, which correlates with the histological changes. the presence of anterior uveitis in kd can manifest in up to to % of patients, is usually self-limited, and has even been proposed as an additional diagnostic tool for early disease recognition and its timely treatment [ , , ] . retinal ischemia may occur as vasculitis progresses; some authors suggest prompt evaluation by an ophthalmologist if ocular complications are suspected [ ] . gao et al. in reported a case of a girl with incomplete kd and reduced eye volume, cataracts, retinal detachment, choroid, and chorioretinal folds. besides ivig, she was treated with eye steroids and had total recovery within one month [ ] . more recently, suganuma et al. described a seven-year-old boy who developed retinal vasculitis with impairment of visual acuity, and also refer to the only three reports in the literature with long-term visual impairment due to kd [ ] . in our patient, despite the significant conjunctival affection, anterior uveitis was ruled out by ophthalmology, and this is consistent with previous reports in the literature that severe ocular complications can occur during kd in the absence of uveitis. expectant management was given, without the need to use any other treatment than ivig, and no topical steroids were used. in the vast majority of the literature, various complications of kd are described at the ocular level, both in the anterior and posterior segment, and unilateral subconjunctival hemorrhages have been described, but to the best of our knowledge, our patient represents the first case report in which bilateral subconjunctival hemorrhages manifest as a complication of kd, at least in latin america. kd has well-defined clinical criteria, but since it is a systemic disease, unusual manifestations can occur also. the real incidence of ocular complications and in particular subconjunctival hemorrhages among children with kd is unknown, as most descriptions in the literature are single case reports, small case series, or retrospective studies. prospective multicenter studies focusing on the ocular involvement and complications of children with kd are needed, particularly in latin america where there is a paucity of information on this disease. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. ocular manifestations of kawasaki's disease (mucocutaneous lymph node syndrome) prospective study of kawasaki disease complications: review of cases conjunctival changes in children with kawasaki disease: cytopathologic characterization conjunctival biopsy in patients with kawasaki disease usefulness of anterior uveitis as an additional tool for diagnosing incomplete kawasaki disease uveitis as an important ocular sign to help early diagnosis in kawasaki disease rare ocular manifestations in an -year-old girl with incomplete kawasaki disease: a case report a case of kawasaki disease complicated with retinal vasculitis key: cord- -qctfl r authors: monday, lea m; gaynier, anthony; berschback, madeline; gelovani, david; kwon, henry y; ilyas, sahrish; shaik, asra n; levine, diane l title: outcomes of an online virtual boot camp to prepare fourth-year medical students for a successful transition to internship date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: qctfl r introduction changes in medical education and health care delivery have limited the ability of fourth-year medical students to perform the role of an intern prior to graduating from medical school. to address this issue, many schools have instituted residency preparation courses (sometimes referred to as boot camps) particularly for students entering surgical fields. courses for students entering nonprocedural fields are less common and most assess increases in self-reported confidence without providing objective evidence of a gain in knowledge or skills improvement. materials and methods we used a plan, do, study, act (pdsa) model to develop and pilot cycle of a nonprocedural internship preparation elective in . feedback was used to refine the course and map sessions to core competencies outlined by the accreditation council of graduate medical education (acgme) for pdsa cycle . the curriculum was adapted for remote synchronous delivery due to the coronavirus pandemic in spring using a combination of didactic lectures containing embedded polls and case-based role play responses using a chat box. students completed anonymous surveys assessing self-perceived levels of confidence, as well as an objective comprehensive assessment after course completion. results a total of students participated in the course. pre-session confidence was lowest for transfusion medicine, handling pages from nursing while on call, and knowledge of the role of a chief resident. a statistically significant increase in median scores for self-reported knowledge or confidence was seen in all sessions. the percentage of students reporting that they were either confident or extremely confident also increased significantly after each session (p< . for all). all sessions analyzed were rated as useful or extremely useful by more than half of the students, and % of the students scored % or higher on the comprehensive course assessment. conclusions an online virtual synchronous boot camp increased students’ confidence in handling common topics encountered during residency and demonstrated an appropriate gain in knowledge using a comprehensive assessment. we were able to adapt our curriculum to a remote model and will likely keep several sessions in an online format in the future. the goal of medical schools is to prepare students to be doctors ready for postgraduate training in their field of choice. since the publication of flexner's x model in , undergraduate medical education (ume) curriculum has been divided into two phases: the preclinical phase, which is focused on pathophysiology and medical theory, and the clinical phase, which is focused on training in surgical and non-surgical fields. in the united states, the fourth year of medical school varies in content and structure to maximize student freedom to choose elective courses and non-clinical pursuits [ ] [ ] [ ] . ideally, students will have opportunities during clerkship to care for patients from admission until discharge and immersed in patient care as if they are already interns. however, the degree of student immersion and experience deviates from this ideal due to several factors. patient length of stay has shortened, procedures are increasingly outsourced to interventional subspecialists, patient handoffs are frequent, and care is generally more fragmented than decades ago [ ] . in addition, changes in medical education such as duty hour regulation and limited privileges within the electronic medical record (emr) reduce student autonomy. the degree of student experience with the emr varies. in one recent survey, fewer than % of students on their obstetrics clerkship had entered orders and less than half ( %) had written a history and physical note in the patient chart [ ] . in another large survey of around , graduating medical students, % had entered information of some type into the emr on their internal medicine clerkship or subinternship; however, % had never entered admission orders [ ] . yet students are expected to step into residency on july and care for patients, including night shifts and with varying degrees of supervision and support. these challenges result in increased stress for interns, educational difficulties for program directors, and, most importantly, potentially unsafe care for patients. in order to address the difficulties in the transition to internship, some medical schools have created capstone courses focused on communication, common problems, procedural skills, or some combination of topics for students entering internship. elective courses for students entering dentistry [ ] , surgery [ ] [ ] [ ] [ ] [ ] , and obstetrics and gynecology [ ] [ ] [ ] have been shown to increase confidence in procedural skills and communication. similar courses in non-surgical specialties are not as common; however, their numbers are increasing. boot camp experiences have been replicated in family medicine [ ] , pediatrics [ , ] , emergency medicine [ ] , and with students entering a mix of fields including internal medicine [ ] [ ] [ ] . a common result is an increase in the level of confidence or preparedness reported among students. in a meta-analysis, boot camps were shown to be an effective educational strategy to improve learners' clinical skills, knowledge, and confidence [ ] . medical students graduating in were removed from all direct patient care and in-person educational activities due to the coronavirus disease (covid- ) pandemic. unfortunately, this drastically altered the content and delivery of courses at medical schools throughout the united states, including internship preparation courses. remote delivery of one boot camp course has been briefly reported for students entering pediatric residency [ ] . as of may , there is no published work describing the logistics and results of executing a nonsurgical internship preparation course open to all medical students regardless of match specialty. we describe a one-month intensive course entitled, "internship boot camp", which was designed after a previous pilot and adapted to be delivered remotely during the covid- pandemic. this online virtual synchronous interactive elective was taught by faculty, residents, and near peers, with the goal of assisting fourth-year medical students with the transition to internship. the goals of this study were to determine the effectiveness of the internship boot camp on three measures: ( ) level of confidence about entering their internship, ( ) ability to develop a framework for responding to common challenges, and ( ) ability to demonstrate an appropriate gain in clinical knowledge using a comprehensive post-course assessment. here, we report the outcomes of a non-surgical intern preparatory course. faculty from the department of surgery at our institution had been offering a procedural boot camp focused on laparoscopic skills and knot tying since ; however, no such course existed for students entering nonprocedural fields. starting in spring , we developed and piloted a nonprocedural preparation elective utilizing pdsa (plan, do, study, act) methodology ( figure ). fifty-three students from the wayne state university school of medicine who matched into a variety of non-surgical residencies were offered an ungraded elective entitled, "intern boot camp." before developing the boot camp curriculum, a needs assessment (a systematic process for determining and addressing needs or "gaps" existing in the knowledge and skills of medical students) was conducted through a voluntary online survey. input was provided by clerkship directors, residency program directors, residents, recent graduates, and our graduating medical students. next, a targeted needs assessment was performed to determine specific deficiencies, and course sessions were created with specific goals and objectives to meet the deficiencies identified. for example, if program directors answered that new interns did not know how to write admission orders, the specific deficiencies were asked on the targeted needs assessment (such as not understanding order sets, or diet and activity orders). this course was approved by the curriculum management committee and added to the course catalog for april and may of . faculty, chief medical residents, and residents taught each session. oversight was provided by the course director. course content was delivered using a variety of modalities including a combination of didactic powerpoint lectures, procedures on lightly preserved cadavers, a session on how to teach and give effective feedback, and case-based role play for handling difficult conversations, medical emergencies, and simulated pages from nursing. lastly, students completed symptom-based modules (which covered common clinical scenarios encountered on call) through the wise-on-call program distributed by aquifer® on behalf of new york university (nyu) school of medicine [ ] . after the pilot, a post-course survey was conducted to evaluate students' self-assessed learning achieved through the course and to learn where improvement was needed. these data were taken into consideration while adjusting and creating the schedule for april . institutional review board approval was not obtained as students participated voluntarily, topics covered constituted routine education, and the assessment of the learners was part of the normal course evaluation process. in early , planning began to scale this activity up to approximately one half of the class for april , ( figure ), in preparation for delivery to all students by spring . student feedback was used to adjust session topics, and the curriculum was redeveloped so that content was divided into six interrelated domains based on the accreditation council for graduate medical education (acgme) core competencies: patient care, medical knowledge, practicebased learning and improvement, interpersonal communication skills, professionalism, and systems-based practice ( table ) [ ] . residents must be able to provide patient care that is compassionate, appropriate, and effective for the treatment of health problems and the promotion of health. residents must be able to demonstrate knowledge about established and evolving biomedical, clinical, and cognate (e.g. epidemiological and social-behavioral) sciences, and the application of this knowledge to patient care. practice-based learning and improvement residents must be able to investigate and evaluate their patient care practices, appraise and assimilate scientific evidence, and improve their patient care practices. interpersonal communication skills residents must be able to demonstrate interpersonal and communication skills that result in effective information exchange and teaming with patients, patients' families, and professional associates. residents must be able to demonstrate a commitment to carrying out professional responsibilities, adherence to ethical principles, and sensitivity to a diverse patient population. systems-based practice residents must be able to demonstrate an awareness of and responsiveness to the larger context and system of health care and the ability to effectively call on system resources to provide care that is of optimal value. the curriculum was also designed to reinforce the american academy of medical colleges (aamc) core entrustable professional activity's (epas) whenever possible [ ] . content was delivered in sessions ( mandatory and optional). detailed mapping of each boot camp session topic with a description and the corresponding acgme core competency is provided in table . with the onset of the covid- pandemic, all student face-to-face activities were furloughed on march , . the course was rapidly transformed in days to an entirely online curriculum. we adapted content for synchronous remote delivery using the canvas online learning management system (instructure®, salt lake city, ut, usa). synchronous sessions used a combination of didactic powerpoint presentations that were made interactive by adding facilitator polling, multiple-choice questions, and small group or individual writing exercises that were shared with the group through incorporation into the presentation or chat board. for example, students were given a mock patient sign out electronically and had to use this to respond to virtual pages from a nurse for a simulated night-on-call. students were asked to write a note about some of the overnight events, which were later de-identified and shared with the group for feedback during the "sign out" lecture. procedural training on cadavers was adapted to include an independent review of online procedure videos by students. training in pronouncing death on a recently deceased cadaver and calling his/her family was adapted to include an interactive session on pronouncing patient death and a reflective reading assignment. an "ask the interns" panel discussion was adapted by requesting students to email questions for review by three high functioning interns who then took turns answering them through video chat and the live message board. pertinent hot topics were added, including a session on telehealth and a covid- patient case discussion that included a rich discussion of end-of-life care and the ethics surrounding decision-making with limited resources. in addition to the synchronous remote sessions, students were required to submit written exercises with a focus on compassionate care, wellness, and self-reflection. students wrote a letter to members of the incoming class of medical students. additional independent study requirements included aquifer cases and online naloxone training. sessions were grouped so that students had a monday or friday free each week to facilitate their end-of-year personal tasks such as finalizing housing plans or pre-employment requirements for their upcoming residencies, which may be in different cities or states. four additional optional sessions were held, one about preparing a professional powerpoint and three focused on topics pertinent to the care of pediatric patients. for out of sessions, the facilitators created a voluntary pre-session survey through a secure online data collection tool. medical students were asked to rate their confidence and understanding of requisite knowledge points on the topic before these sessions. items were graded on a -point likert scale ( meaning confidence or knowledge was very poor, meaning neutral, and meaning very high). after delivery of each session, students were given a postsurvey with one additional question about whether they found the activity useful. a competency-based exam was administered at the conclusion of the course to assess the knowledge gained. two to three multiple-choice questions were written for each lecture session assessing student competency of objectives identified by the educator. the questions were each mapped to acgme core competencies and written with varying degrees of difficulty addressing knowledge, application, and problem-solving [ , ] . the resulting -question comprehensive assessment was completed by all students except for one who contracted covid- . after completing the comprehensive assessment, students were given a link to the correct responses. pre-/post-survey median scores were analyzed using the wilcoxon rank-sum test (mann-whitney u test) for unpaired non-parametric data. to categorically compare the percentages of students who answered positively about each session, responses in the likert scale were combined into a x contingency table (positive, neutral, or negative responses), and data were analyzed using the chi-square test. for example, the likert scale response categories of extremely confident and confident were combined into one, "positive" category. usefulness of sessions and post-test grades were analyzed with descriptive statistics. all tests were twotailed, with p < . as the significance level. statistical analysis was performed using ibm spss version (ibm corp., armonk, ny, usa). a total of students and instructors participated remotely. student learners had matched into a mix of non-surgical residency programs, with internal medicine, emergency medicine, family medicine, being most common. instructors included faculty, chief residents, and current interns. pre-surveys were completed by - students ( - %), and post-surveys were submitted by - students ( - %). pre-test confidence scores were lowest for the sessions on transfusion medicine, the nursing pager on call activity, and chief medical resident expectations, with less than % of students feeling confident or extremely confident in those topics. pre-session confidence scores were highest in teaching medical students and providing feedback ( % and % of students felt at least confident and comfortable, respectively). the percentages of students who answered that they were confident or extremely confident in the subject matter before and after each session are summarized in table . all synchronous sessions resulted in a measurable increase in the portion of students reporting confidence or extreme confidence in the subject matter. the largest increases in confidence (over % increase) were seen in the session about when go to your program director, chief medical resident expectations, and what do after a patient dies, followed by the session on using blood products ( % increase). all values are rounded to the nearest %. to compare the percentages of students who answered positively for each question, the response categories in the likert scale were combined into a x contingency table (positive, neutral, and negative), and data were analyzed using the chi-square test. median confidence scores before and after the sessions are presented in table . before the session, median scores were lowest regarding knowledge about the role of a chief resident, confidence writing admission orders independently, using blood products, and how to fill out a death certificate. baseline median confidence scores were highest for teaching medical students and knowledge about how to give students feedback. a measurable increase in numerical confidence or knowledge scores was demonstrated for all sessions, even if the median score did not change. figure . overall, all sessions analyzed were rated as useful or extremely useful by over half of the students ( - %). the top five most useful sessions were the sessions on clinical documentation, common clinical scenarios, the night-on-call nursing paging activity, and clinical reasoning, which were rated as useful or extremely useful by %, %, %, and %, respectively. only of the sessions received any feedback of "not useful at all", and in all cases it was fewer than % of students. the cumulative post-test was taken by of students. of the students, ( %) achieved a score of % or higher, ( . %) scored in the - % range, and scored %. students were asked to provide feedback comments and state whether they believed certain sessions could remain virtual; comments are summarized in table . positive comments i enjoyed that this course was online. this is a big transition time for us, and it was very convenient to be able to have this online. i am glad that this was online because it allowed me to go home and be with my family for the month. the interactive nature of being able to type comments at any point and have your comments be addressed and interacted with by other students was helpful. i felt much more engaged than i normally do during in-person lectures. mandatory attendance and the chat box made it very interactive. virtual boot camp made it easier and less tiring to attend lecture since i could do it from home, and there was still great participation from the students. chat allowed other students to clarify things while the instructor was speaking, so the instructor didn't need to answer more questions. excellent resource that i plan on reviewing again the days prior to starting residency. constructive comments i think it would have been helpful to have more clinically oriented courses in-person. anything that's super participation heavy should be done in person if possible, but lectures that are just lectures (with perhaps a poll here and there) are great to have online. if you kept these lectures online, i would suggest shortening/separating them if possible. as a student, it is hard to pay full attention online with multiple hour-long lectures. summarizing handouts would be helpful to carry forward into residency. positive feedback was related to the flexibility of an online course and utility of the chat box, which, as some students reported, allowed them to be more engaged than they had been in live lectures. constructive comments included the suggestion that sessions with a focus on patient care may be better achieved by a live session in coming years. positive feedback was related to the flexibility of an online course and utility of the chat box, which, as some students reported, allowed them to be more engaged than they had been in live lectures. constructive comments included the suggestion that sessions with a focus on patient care may be better achieved by a live session in coming years. student preferences for which sessions could continue remotely versus which would be better facilitated in person are shown in figure . for a majority of sessions, the percentage of students preferring a virtual format outnumbered those preferring an in-person session. the sessions most heavily focused on medical knowledge and patient care such as the clinical scenarios, sign-out activity, and night-on-call had the highest percentage of students preferring an in-person session. this study demonstrates that students who participated in this elective non-surgical boot camp felt more confident and knowledgeable about handling situations they may encounter as interns and demonstrated an objective gain in knowledge beyond self-reported levels. most of the teaching sessions were adapted to an online virtual synchronous format without difficulty, and feedback from students was overwhelmingly positive despite the change in format. had there been more time to prepare, pagers could have been given to students to make the night-on-call activity more realistic; however, despite the absence of a pager, this was one of the highestrated sessions. the course was well received with significant increases in student's perceptions of readiness and comfort in multiple domains, which were linked to acgme core competencies. facilitators volunteered their time to construct and deliver the course content, and students used their personal computers; therefore, no high-fidelity simulation manikins or costly equipment was required. although several studies on internship preparation courses have been published demonstrating increases in self-reported confidence, very few have included objective assessments such as the cumulative post-test included in our study. all students except for one achieved a score of above %, which would correlate with the score required to pass a national shelf examination. limitations of this remote activity include the fact it was a single-school study and that student's level of interest and engagement may have been related to not having any other residency preparation options given the covid- pandemic. the number of students who signed up for the course increased significantly in the seven days prior to the start of the course, which may reflect that. other limitations include those of analyzing participation in pre-and post-surveys when some of the students did not complete both for each session. lastly, it is a possibility that students who filled out their surveys were more engaged, and thus results were more likely to be positive. covid- has presented many challenges to students and educators in undergraduate medicine. now more than ever students need all the help they can and to feel more confident and prepared when they start internship on july . despite the challenges we encountered, synchronous remote delivery of this boot camp was successful, and we will likely continue to hold certain sessions remotely in the future. this may be more useful for students traveling to arrange for new living arrangements during residency. future work includes include scaling up to all students and obtaining more volunteer facilitators that would enable small group breakout sessions which may increase opportunities to interact. we plan to re-survey students after their first month of internship to re-evaluate their perceived usefulness of this course. overall, an online synchronous boot camp was rated as useful by students, helped them feel more confident about common topics encountered during residency, and demonstrated an appropriate gain in knowledge using a comprehensive post-course assessment. we were able to adapt our curriculum to a remote model and will likely keep several sessions in an online format in coming years based on positive feedback from students. human subjects: all authors have confirmed that this study did not involve human participants or tissue. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. course offerings in the fourth year of medical school: how u.s. medical schools are preparing students for internship what training is needed in the fourth year of medical school? views of residency program directors the fourth year of medical education: a literature review the impact of fragmentation of hospitalist care on length of stay medical student experiences with accessing and entering patient information in electronic health records during the obstetrics-gynecology clerkship electronic health record use in internal medicine clerkships and sub-internships for medical students graduating from to an innovative clinical skills "boot camp" for dental medicine residents a senior elective designed to prepare medical students for surgical residency senior medical student "boot camp" can result in increased self-confidence before starting surgery internships the effect and durability of a pregraduation boot camp on the confidence of senior medical student entering surgical residencies a surgical skills elective can improve student confidence prior to internship do preclinical background and clerkship experiences impact skills performance in an accelerated internship preparation course for senior medical students re-boot: simulation elective for medical students as preparation boot camp for obstetrics and gynecology residency improving the medical school-residency transition ob/gyn boot camp using high-fidelity human simulators: enhancing residents' perceived competency, confidence in taking a leadership role, and stress hardiness a brief boot camp for th-year medical students entering into pediatric and family medicine residencies a pediatric preintern boot camp: program development and evaluation informed by a conceptual framework a suggested emergency medicine boot camp curriculum for medical students based on the mapping of core entrustable professional activities to emergency medicine level milestones a -week simulated internship course helps prepare medical students for transition to residency improving the transition from medical school to internship -evaluation of a preparation for internship course the key role of a transition course in preparing medical students for internship effects of postgraduate medical education "boot camps" on clinical skills, knowledge, and confidence: a meta-analysis a remotely conducted pediatric boot camp for th year medical students the milestones guidebook. acgme core entrustable professional activities for entering residency: toolkits for the core epas education techniques for lifelong learning: writing multiple-choice questions for continuing medical education activities and self-assessment modules drs. monday and levine had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. key: cord- -hsqphc t authors: sandesh, ram; shahid, wajeeha; dev, kapeel; mandhan, nikeeta; shankar, prem; shaikh, anam; rizwan, amber title: impact of covid- on the mental health of healthcare professionals in pakistan date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: hsqphc t introduction as a result of the ongoing covid- pandemic, health care professionals (hdps) are facing immense strain due to the heavy load of cases. in many cases, they work increasingly long hours, often with limited resources and a dubious infrastructure. thus, it is important to check on the mental health of caregivers. methods and materials this cross-sectional study was conducted in may , at various hospitals in karachi, pakistan. all hcps posted in the covid- isolation wards were invited to participate and a total of completed this study. a carefully structured form was created, which included the depression anxiety stress scale- (dass- ). results the overall mean score of anxiety was . ± . , depression was . ± , and stress was . ± . . there were ( . %) participants who suffered from moderate to extremely severe depression, ( . %) participants who suffered from moderate to extremely severe anxiety, and ( . %) participants who reported moderate to extreme stress levels conclusions it is evident that there are a high number of healthcare workers affected by various psychological ailments such as anxiety, stress, and depression. it is important that the government take steps to ensure that hcps' mental health is regularly checked and that efforts are made to reduce their burdens. , also known as coronavirus disease, was first identified in wuhan, china, in late . it is a highly contagious disease with a rapidly rising incidence globally. the world health organisation (who) recognized it as a pandemic due to its widespread transmission [ ] . as is the standard procedure in such pandemics, a lockdown is usually enforced to limit the spread of the disease and reduce potentially new cases by maintaining social distancing in all public places [ ] . the general public undertakes such safety measures, but health care professionals (hcps) are unfortunately left exposed to deal with the many issues that arise due to this situation. firstly, due to a huge load of cases as a result of the pandemic, health care professionals face increasingly long work hours, often with limited resources and a dubious infrastructure [ ] . secondly, they face physical discomfort and sometimes even breathing difficulties while wearing personal protective equipment (ppe), which is essential to keep them safe from exposure to [ ] . another big problem faced by the hcps is that because little is known about the new virus/disease, and therefore, no established protocols or evidence-based clinical treatments are prevalent, many hcps feel unprepared to carry out their duties [ ] . and then there is a very valid fear of autoinoculation and the risk of spreading the virus to their family and friends [ ] [ ] . this fear leads hcps to isolate themselves from their families, alter their daily routines, and even reduce their social support system, all in the hopes of keeping everybody potentially safe from themselves [ ] . unsurprisingly, all these factors take a toll on the mental health of hcps. in , during the outbreak of severe acute respiratory syndrome (sars), - % of hcps suffered severe emotional problems and psychiatric symptoms both during and after the breakout [ ] . in , when the middle east respiratory syndrome (mers) emerged, also caused by a coronavirus, hcps suffered dysphoria and stress [ ] . many other studies have reported that mental health implications for professionals involved in healthcare during epidemics and pandemics are long-lasting. even after some time had transpired after such events, high levels of stress, anxiety, depression, and even post-traumatic stress disorder (ptsd) were observed in many cases [ ] [ ] . therefore, it is extremely important to identify the hcps who are at high risk of burnout and are more likely to suffer from anxiety, depression and stress in this pandemic, so that help can be provided where and when needed. it is also equally important to identify and address the factors responsible for this stress. in this study, we will establish the frequency of hcps affected by anxiety, depression, and stress, as well as determine the causative factors behind them. this cross-sectional study was conducted in may , at various hospitals of karachi, pakistan. all health care professionals (hcps) posted in the isolation wards for covid- were invited to participate. a total of hcps completed this study. a carefully structured form was created, which included the english version of the depression anxiety stress scale - (dass- ). dass- is a -item self-report validated tool designed to measure the three related negative emotional states, which are: depression, anxiety, and stress [ ] . the online form also included various reasons that hcps thought were predisposing factors for anxiety, stress, and depression. the participants could choose multiple reasons as applicable to themselves. the collected data were analyzed using spss version . (ibm corp, armonk, nj). mean and standard deviation (sd) were calculated for the scores of anxiety, stress, and depression. frequencies and percentages were calculated for the severity of dass- and reasons predisposing healthcare professionals to anxiety, stress, and depression. out of the health care professionals (hcps) who participated in this study, ( . %) were male, and ( . %) were female. the overall mean score of anxiety was . ± . , depression was . ± , and stress was . ± . . there were ( . %) participants who suffered from moderate to extremely severe depression, ( . %) participants who suffered from moderate to extremely severe anxiety, and ( . %) participants who reported moderate to extreme stress levels ( table ) . the study found that the most common reason for stress and anxiety among hcps treating covid- positive patients was the fear that they might infect their family members ( . %), followed by the fear of getting infected themselves ( . %). other reasons were: increased workload ( . %), lack of ppe ( . %), lack of security ( . %), and lack of awareness among the general population about covid- ( . %) ( the psychological response of hcps to an epidemic could be dependent on many factors which may cause anxiety and stress such as feeling vulnerable to infection, lack of control over the situation, the spread of the virus, health of their family, and being isolated [ ] . other factors may also contribute to stress and anxiety among hcps such as shortage of ppes, medicines, etc. and an increasing number of actual and suspected cases [ ] . these factors may contribute to various levels and severity of psychological pressure, which may lead to a feeling of loneliness and helplessness and may result in stress, anxiety, irritability, mental fatigue, and depression [ ] . in this study, a significant number of pakistani participants had anxiety, stress, and depression. around % of hcps were afraid for their family, and % of hcps feared that they might get covid- themselves. these figures can be compared to wuhan, where among hcps looking after covid- [ ] . factors such as improper infrastructure for patient care, lack of awareness among the masses, and poor compliance with safety measures can be accredited to this high prevalence of anxiety, depression, and stress in pakistan. another important thing to note is the persistence of mental health implications for healthcare workers. even after some time had passed after an epidemic, many studies reported that high levels of anxiety, depression, stress, and even ptsd were observed in many hcps [ ] . in addition, the hcps who are directly involved in the treatment of a highly contagious disease such as the covid- may suffer a stigma whereas, at the other end of the spectrum, this pandemic has led to hcps being given the 'superhero' status. on the one hand, this adds value and gratification to the job, but on the other, it puts more pressure on the workers, leaving no margin for error. due to the sensational character of this worldwide pandemic, the 'superhero' status is being reinforced by the media, promoting the need for emotional support, encouragement, and appreciation [ ] . in light of the results of this study, it is clear that an alarmingly high number of healthcare workers are the victims of mental health ill-effects caused by the covid- pandemic. it can be also seen that many of the factors due to which hcps suffer from these ill-effects can be potentially modified, for example, such as free provision of ppes to all healthcare workers, promoting general public awareness about covid- , and building better infrastructure to encourage lighter work hours can all be carried out by the government and thus have a positive impact on the mental health of hcps. in our study, high levels of anxiety, stress and depression among health care professionals were noted, which is a cause for concern. both the government and health care agencies are responsible for protecting the psychological well-being of health care communities all over the world and ensuring a healthy work environment. since there is a high prevalence of anxiety, depression, and stress among hcps treating covid- patients, it is imperative to invest resources to promote the mental health welfare of frontline professionals. human subjects: consent was obtained by all participants in this study. civil hospital, karachi issued approval ch/ / a. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. novel coronavirus ( -ncov) situation reports isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus ( -ncov) outbreak public responses to the novel coronavirus ( -ncov) in japan: mental health consequences and target populations mental health survey of medical staff in a tertiary infectious disease hospital for covid- the mental health of medical workers in wuhan, china dealing with the novel coronavirus timely mental health care for the novel coronavirus outbreak is urgently needed psychological impact of the mers outbreak on hospital workers and quarantined hemodialysis patients vicarious traumatisation in the general public, members, and non-members of medical teams aiding in covid- control pandemic fear" and covid- : mental health burden and strategies safarizadeh mm: stress, anxiety and depression among medical university students and its relationship with their level of happiness the psychological impact of severe acute respiratory syndrome outbreak on healthcare workers in emergency departments and how they cope severe acute respiratory syndrome (sars) and healthcare workers factors associated with mental health outcomes among health care workers exposed to coronavirus disease recomendações para o bem-estar emocional da equipe multidisciplinar durante a pandemia pelo sars-cov- key: cord- -uwicyuhk authors: hoilat, gilles j; durer, ceren; durer, seren; gupta, pratishtha title: percutaneous mechanical pulmonary thrombectomy in a patient with pulmonary embolism as a first presentation of covid- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: uwicyuhk there has been a high incidence of thromboembolic diseases in patients with coronavirus disease (covid- ) pneumonia. we present a case of a healthy -year-old male with no past medical history who presented with shortness of breath, tested positive for covid- , and was found to have a large acute saddle pulmonary embolism. since late , the world is facing a rapidly expanding pandemic of a lower respiratory infection caused by severe acute respiratory syndrome coronavirus (sars-cov- ) and causing a clinical syndrome entitled coronavirus disease . clinical symptoms of the virus are vague and can mimic any other respiratory infection. however, what distinguishes this virus from others is its significant association with thromboembolic diseases as well as its high mortality rate. recent findings revealed that patients with severe cases of covid who are admitted to the intensive care unit with respiratory failure had a predominant hypercoagulable state leading to thromboembolism [ ] . in fact, the infection causes dysfunction within the endothelium as well as an inflammatory state leading to increased thrombin formation and reduced fibrinolysis [ ] . we present a case of a healthy patient who presented to the hospital with dyspnea, was found to be covid- positive, and was diagnosed with an acute saddle pulmonary embolism. a -year-old male with no pertinent past medical history presented to the hospital with shortness of breath. he reports being tested positive for covid- as an outpatient. at the time, he complained of some mild dyspnea and a non-productive cough, and kept himself quarantined for a few days until his dyspnea worsened which prompted him to come to the emergency department. he endorsed a single episode of hemoptysis, one teaspoon worth. otherwise denied any fever, chills, nausea, vomiting, abdominal pain, and lower extremity tenderness or swelling. on examination, he was tachycardic with a heart rate of /minute, tachypneic with a respiratory rate of /minute, normotensive with a blood pressure of / mmhg, and his oxygen saturation was % on room air. he was tested with the covid- polymerase chain reaction and was found to be positive. laboratory results were significant for creatinine . mg/dl (normal range: . - . mg/dl), procalcitonin . ng/ml (normal range: < . ng/ml), ferritin ng/ml (normal range: - ng/ml), pro-brain natriuretic peptide (probnp) pg/ml (normal range : < pg/ml), creactive protein . mg/l (normal range: < . mg/l), and d-dimer > μg/ml (normal range: < . μg/ml). a chest x-ray did not show any acute disease process. electrocardiography (ekg) was performed and showed sinus tachycardia. a thoracic ct scan angiography (figure ) was performed showing large saddle embolism which extended into segmental branches in both lower lobes and the right middle lobe. there was also moderate peripheral non-enhancing consolidation seen at the left lung base posteriorly suggestive of a probable pulmonary infarct. he was diagnosed as having a submassive pulmonary embolism. the right ventricle (rv) was enlarged and was consistent with right-sided cardiac strain. a doppler ultrasound of both lower extremities was negative for any deep vein thrombosis. the patient was started on a heparin drip and was admitted to the general medicine department. he was then shortly transferred to the intensive care unit for higher-level care and airway protection due to multiple episodes of hemoptysis and worsening tachypnea. bedside echocardiogram performed by the cardiologist revealed a dilated rv consistent with the right heart strain. vascular surgeons were consulted and decided to proceed with mechanical embolectomy since there was increasing evidence supporting catheter-directed therapy for submassive pulmonary embolism, which may have a lower risk of bleeding compared to systemic thrombolysis. a mechanical embolectomy was performed, and a large thrombus was removed ( figure ) . a subsequent pulmonary arteriogram demonstrated resolution of the filling defects. postprocedure, the patient remained clinically stable. the patient was subsequently transitioned from a heparin drip to rivaroxaban mg twice a day for days followed by rivaroxaban mg daily and was discharged with a three-month follow-up. the covid- outbreak has been an exceptional universal public health challenge. as of mid-june , there are about . million cases worldwide with a death toll reaching , . a study conducted by guan et al. that included , patients revealed that the most common symptoms of patients with covid- were fever ( . %) and cough ( . ), while diarrhea only occurring in . % of the cases [ ] . pulmonary embolism and deep vein thrombosis have been reported in viral pneumonia caused by different viruses but not as frequently as in covid patients. one retrospective study performed by bompard et al. reported that out of patients who underwent ct pulmonary angiography, % of them were found to have acute pulmonary embolism [ ] . it has been hypothesized that the covid- induced thrombosis is partly due to the disease-specific hypercoagulable state and partly due to cytokine-mediated diffuse microvascular damage [ ] . the risk of pulmonary embolism can be further increased with obesity, advanced age, and immobilization in hospitals. covid- -related severe hypercoagulability in patients admitted to intensive care unit for acute respiratory failure coagulation and sepsis clinical characteristics of coronavirus disease in china pulmonary embolism in patients with covid- pneumonia clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study pulmonary embolism in patients with covid- : time to change the paradigm of computed tomography the incidence of acute pulmonary embolism in a patient with covid- remains unknown [ ] . however, the data available promote concerns about an increased incidence of thromboembolic diseases associated with the virus. our patient was a healthy male who presented with no risk factors for thromboembolic disease and no symptoms of viral pneumonia but still developed a large saddle embolism. given the large number of covid- patients seeking medical care and requiring hospitalization, patients with known covid- should receive a d-dimer test and if elevated on admission, ct pulmonary angiography should be considered since the incidence of thromboembolic diseases appears to be significantly higher in covid- . pulmonary embolism is a life-threatening but potentially treatable disease that requires a high index of suspicion and benefits from early intervention. human subjects: all authors have confirmed that this study did not involve human participants or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- - danzbqt authors: quadri, syed p; jain, nitesh k; brandon, brooke l; modi, harshit; bawaadam, hasnain title: an intriguing presentation of epstein-barr virus-associated hemophagocytic lymphohistiocytosis date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: danzbqt hemophagocytic lymphohistiocytosis (hlh) is an immune related clinical syndrome with protean manifestations, varying presentation, clinically complex, with diverse causes, and is an under-recognized entity which carries high morbidity and mortality. it is precipitated by an immunological trigger in a susceptible host resulting in immune activation and dysregulation leading to disruption of immune homeostasis, cytokine storm and multi-organ failure. we describe a case of epstein-barr virus (ebv) associated hlh with its typical diagnostic challenges and associated high mortality rate. certain diagnostic criteria and online tools may help to arrive at an earlier presumptive diagnosis which, in turn, may expedite treatment and lead to better clinical outcomes. hemophagocytic lymphohistiocytosis (hlh) is an extremely rare and potentially lifethreatening hematological disorder, characterized by clinical features of extreme inflammation and an unregulated immune system. it is precipitated by an immunological trigger in a susceptible host resulting in immune activation and dysregulation leading to disruption of immune homeostasis, cytokine storm and multi-organ failure. we describe a case of epstein-barr virus (ebv)-associated hlh with its typical diagnostic challenges and associated high mortality rate, but an early prompt diagnosis with appropriate treatment can lead to better outcomes. the objective of this clinical case report is to highlight the need for awareness and the complexity surrounding the diagnosis in an effort to lower subsequent morbidity and mortality. a -year-old caucasian male with no significant past medical history initially presented with severe fatigue, upper extremity joint pain, jaw pain, and new onset daily headaches. he was treated with a -day course of oral steroids for suspected temporomandibular joint dysfunction; this temporarily improved his symptoms. a few weeks later, his symptoms returned and he also developed daily high fevers with drenching night sweats. during this time, the patient was seen in the emergency room twice with dyspnea and cough and was treated for "presumed pneumonia" with broad spectrum oral antibiotics. he was eventually admitted to our hospital for failure of outpatient treatment of pneumonia. computed tomography scan of the thorax showed bilateral ground glass opacities, with no evidence of mediastinal lymphadenopathy ( figure ) . he was noted to have pancytopenia, cervical lymphadenopathy and parotid gland swelling. ebv polymerase chain reaction (pcr) was elevated to , copies per ml. ferritin was markedly elevated at , mcg/l; lactate dehydrogenase (ldh) was elevated to , u/l. he underwent parotid gland biopsy which was ebv-negative and demonstrated acute sialadenitis with necrosis. an extensive autoimmune, infectious and hematologic workup was equivocal. he was treated with broad spectrum iv antibiotics and high dose steroids. he remained afebrile for four days, and was ultimately discharged home on a two-week course of doxycycline, valacyclovir and fluconazole. his symptoms returned the following month with fevers, headaches and night sweats. the outpatient evaluation revealed a new non-tender, non-pruritic erythematous rash on his chest. bone marrow biopsy was obtained which revealed a hypocellular marrow with trilineage hematopoiesis (figure ), negative for dysplasia; moderate number of pelger-huet type neutrophils; single lymphoid aggregate with an unremarkable flow cytometric profile. subsequent positron emission tomography (pet)-scan demonstrated diffuse hypermetabolic lymphadenopathy in the mediastinum, upper abdomen and retroperitoneum, as well as pleural thickening and pulmonary hypermetabolic opacities. he was advised to obtain outpatient biopsy of the abdominal lymphadenopathy with interventional radiology, but he was unable to schedule it. the patient was readmitted to the hospital few days later due to continued weight loss and seizure-like activity at home. ct head was unremarkable. he was found to have elevated liver enzymes with aspartate aminotransferase (ast) of , u/l, alanine aminotransferase (alt) of u/l and alkaline phosphatase (alp) of u/l. liver biopsy revealed scattered acidophil bodies which can be seen in infections or drug-induced liver injury, rare ebv-positive cells but no evidence of fibrosis or lymphoproliferative disorder. he was once again found to have elevated ferritin of , mcg/l. high dose dexamethasone mg/day was started for treatment of presumed hlh, based on labs and clinical presentation ( table ) . chest x-ray showed right mid-lung opacity. the patient developed acute respiratory failure requiring intubation and mechanical ventilation. bronchoscopy with lavage revealed aspergillus species and he was started on appropriate anti-fungal treatment immediately. repeat bone marrow biopsy was performed due to pancytopenia and demonstrated changes consistent with hlh, with definitive evidence of hemophagocytosis. despite treatment, the patient continued to decline and developed rapid multi-organ failure. he was transitioned to comfort care and expired the same day. the major finding in the patient's autopsy was hemophagocytic histiocytosis with rare ebvpositivity noted in the bone marrow analysis, suggesting that the hlh was due to ebv infection. there was no evidence of any lymphoproliferative disorder. lung examination revealed acute aspergillus spp. pneumonia with left upper lobe abscess formation, likely related to his immunocompromised state in the setting of hlh. also discovered was multiorgan vasculitis, the significance of which is unclear. although there have been rare reported cases of hlh in the setting of vasculitis, the laboratory evidence of ebv infection and finding of rare ebv-positive cells in the bone marrow on autopsy and in the ante-mortem liver suggest that the hlh was related to ebv infection. the official cause of death in the patient was determined to be pulmonary aspergillosis with organizing pneumonia in the setting of hemophagocytic lymphohistiocytosis, likely secondary to epstein-barr virus infection. hlh is a rare life-threatening condition characterized by hyperinflammation and immune system dysregulation [ ] . it can occur in both familial and acquired forms [ ] . acquired hlh is associated with various infections including bacterial, viral, fungal and parasitic; autoimmune diseases including vasculitis, rheumatological disorders, malignancy, and acquired immune deficiency states including aids, and with drug use [ , ] . the basic pathophysiology in hlh is that the natural killer (nk) cells and cytotoxic tlymphocytes, which represent the innate and acquired immunity respectively, have altered cytotoxic function. this is coupled with excessive macrophage activation. the nk cells and lymphocytes are not able to eliminate the macrophages by perforin-mediated cytotoxicity. eventually there is a huge amount of cytokine release by all these above-mentioned immune cells resulting in excessive tissue damage across multiple organ systems [ , ] . toll like receptor activation of the immune system can also be another potential mechanism of hlh [ ] . it usually presents with fevers, hepatosplenomegaly, pancytopenia along with elevated liver enzymes, significant ferritin elevation and hypertriglyceridemia [ ] . ebv is the most common infection associated with acquired hlh [ ] . other viruses such as adenovirus and cytomegalovirus can also trigger hlh. infectious triggers cause immune activation. alternatively, immune deficiency can also trigger hlh such as hiv disease, malignancy, and certain rheumatological diseases [ ] . diagnosis of hlh is challenging and requires a high index of suspicion. it is not uncommon for patients to have had a prolonged or multiple hospitalizations associated with clinical decline in health status before the diagnosis is finally made. diagnostic criteria have been formulated as per the hlh- protocol which includes molecular, clinical and laboratory criteria [ ] . genetic testing should be performed in all suspected cases. the hlh- protocol has not been validated in adults in secondary hlh. also, it has practical difficulty in application as the various tests required for completion of the diagnostic protocol take time and are not rapidly available. in one study of patients, the clinical findings included in hlh- protocol were found to variably distributed in the patient population [ ] . the prevalence of low or absent nk cell function was %. prolonged fever was seen in % of the population, whereas depleted cell lines were seen in up to % cases. splenomegaly was seen in % of the cases. hypertriglyceridemia or hypofibrinogenemia were noted in % cases. elevated ferritin greater than mcg/l was found in % of the patients. in contrast, evidence of hemophagocytosis on bone marrow exam was only seen in about % of the study subjects, the least prevalent of the markers. markers of increased t cell activation such as elevated cd counts were seen in up to % of the patients. it is therefore to be noted that the characteristic finding of "hemophagocytosis" in the liver, lymph nodes or bone marrow is not necessary for diagnosis, however, its presence can aid in diagnosis. flow cytometry in a specialized laboratory can be very helpful with immunological markers [ ] . the h-score is a much more pragmatic and easier tool to apply by the patients' bed side and can help with rapid diagnosis and therefore help with treatment considerations, as timely intervention can help improve prognosis. an online calculator is also available for calculating the h-score [ , ] . hlh should be considered in the differential diagnosis of any patient presenting with unexplained fever, pancytopenia, hepatosplenomegaly, rash, lymphadenopathy, neurologic symptoms, liver function abnormalities and high serum ferritin. elevated ferritin due to macrophage activation is helpful in children but much less specific in adults. however, a very high elevation of ferritin and scd are very helpful in making the diagnosis. treatment should be initiated in a timely manner and consists of supportive care, treating the underlying triggers like infection, immunosuppressive agents, monoclonal antibodies, cytotoxic therapy and biological agents [ ] [ ] [ ] [ ] . hematopoietic stem cell transplant may be an option for definitive treatment of hlh in selected patients [ ] . delay in diagnosis is associated with poor prognosis due to multi-organ involvement. mortality rate remains high despite treatment, ranging from - % in ebv-associated hlh [ ] . given the current day pandemic, severe cases of covid- can act as hlh mimic, as the former manifests as severe sepsis with cytokine storm syndrome. this needs further elucidation and some therapies like il- inhibitor tocilizumab, which have been used for hlh/cytokine storm syndrome previously, are being tried as therapy for covid- [ ] . several academic institutions have employed the h-score mentioned above to guide therapeutic decisions on ilinhibitors. an h-score greater than confers a % probability of hlh and a score of less than confers a less than % probability of hlh [ , ] . our case highlights the importance of having a high index of suspicion for hlh in unusual presentations of febrile illness with pancytopenia, even in otherwise healthy individuals. it is possible that our patient could have benefited from earlier treatment with steroids or other appropriate agents, rather than later in the course of the disease. further research is needed to better understand the pathophysiology of hlh at a molecular level, which could lead to modification of existing treatment protocols and improve patient survival. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. hemophagocytic lymphohistiocytosis: when the immune system runs amok familial hemophagocytic lymphohistiocytosis reactive hemophagocytic syndrome in adult systemic disease: report of twenty-six cases and literature review hemophagocytic syndromes and infection pattern recognition receptors and inflammation hlh- : diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. pediatr blood cancer clinical features and treatment strategies of epstein-barr virus-associated hemophagocytic lymphohistiocytosis hemophagocytic lymphohistiocytosis: a review haemophagocytic lymphohistiocytosis in adult critical care chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the hlh- treatment protocol treatment of familial hemophagocytic lymphohistiocytosis with antithymocyte globulins, steroids, and cyclosporin a immunotherapy of familial hemophagocytic lymphohistiocytosis with antithymocyte globulins: a single-center retrospective report of patients requirement for etoposide in the treatment of epstein-barr virus-associated hemophagocytic lymphohistiocytosis haematopoietic stem cell transplantation in haemophagocytic lymphohistiocytosis poor outcomes of chronic active epstein-barr virus infection and hemophagocytic lymphohistiocytosis in non-japanese adult patients a study to evaluate the safety and efficacy of tocilizumab in patients with severe covid- pneumonia (covacta) development and validation of the hscore, a score for the diagnosis of reactive hemophagocytic syndrome performances of the h-score for diagnosis of hemophagocytic lymphohistiocytosis in adult and pediatric patients key: cord- -grzrkff authors: almutairi, abdulelah; alfaleh, mohammed; alasheikh, muath title: dermatological manifestations in patients with sars-cov- : a systematic review date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: grzrkff severe acute respiratory syndrome coronavirus (sars-cov- ) has been initially defined as a disease of the respiratory tract; however, with the increasing number of patients and announcing that the virus became a pandemic, new systemic clinical manifestations are observed, including dermatological manifestations. however, the identification and characteristics of these manifestations are still controversial. this review article aims to evaluate the medical literature and explore the dermatological clinical manifestations in patients with sars-cov- . the literature was reviewed through medline®, ovid, pubmed®, and embase®. searching terms included were a combination of "dermatological" or "skin" and "symptoms" or "manifestations" and "sars-cov- ". the following step was filtering the results to include only original research studies investigating the different types of skin and dermatological clinical manifestations in patients with sars-cov- . a total of studies were retrieved. following the exclusion of studies on animals and including only studies on humans, studies emerged. altogether, seven studies were identified as eligible, covering patients with sars-cov- who had dermatological symptoms. three studies were retrospective, two studies were prospective, and two studies were case series. different types of dermatological lesions can occur in patients with sars-cov- , most commonly erythema, urticaria, and varicella-like rash. dermatological manifestations with sars-cov- can be misdiagnosed with other conditions. further studies with robust design are needed. coronaviruses are defined as a class of viruses that commonly lead to mild to moderate respiratory tract infections [ ] . moreover, in the last few years, there were some mutations that occurred in coronaviruses leading to transmission from animals to humans [ ] . furthermore, the virulence of the virus has increased, leading to increased mortality. examples of these viruses are the middle east respiratory syndrome-related coronavirus (mers-cov), severe acute respiratory syndrome coronavirus (sars-cov), and the recently explored severe acute respiratory syndrome coronavirus (sars-cov- ) [ ] . sars-cov- virus has been primarily identified in wuhan city in china, in november [ ] . the transmission rate of the virus started to increase rapidly and progressively till being announced as a pandemic by the who in february [ ] . signs and symptoms of the new viral infection might range from an absence of symptoms to severe and sometimes, life-threatening condition [ ] . at the beginning of this wave of infection, it was thought that sars-cov- affects only the respiratory tract; however, with the increasing number of new cases globally, other systemic symptoms have been reported, which varied in severity [ ] . one of these systemic symptoms is dermatological manifestations [ ] . some patients with sars-cov- were observed to have some cutaneous symptoms such as urticaria spreading over the body, erythematous rash, skin vesicles, similar to chickenpox infection [ ] . these dermatological symptoms were commonly reported all over the body, particularly over the trunk [ ] . also, patients with sars-cov- complained of itching of varying severity. however, there is still a debate on these symptoms and whether there are other symptoms identified in patients with sars-cov- [ ] . our review aims to examine the current medical literature to explore the different types of dermatological clinical manifestations in patients with sars-cov- . this systematic review of the literature was performed in compliance with the preferred reporting items for systematic reviews and meta-analyses (prisma) checklist recommendations for systematic review and meta-analysis [ ] . this systematic review was carried out through searching electronic databases to include eligible studies in four databases, including medline®, pubmed®, ovid, and embase®. searching terms included "dermatological" or "skin" and "symptoms" or "manifestations" and "sars-cov- ". all the titles, as well as abstracts that emerged from this exploration, were reviewed completely to prevent missing any eligible studies. the results were then filtered to include only original research studies examining the different types of skin and dermatological clinical manifestations in patients with sars-cov- . additionally, all study designs from different countries were included. only studies written in the english language were listed as related studies, which can be further assessed in the second step. following this stage, the inclusion criteria to choose the studies that will be recognized in the systematic review were determined. abstracts were reviewed manually to determine the appropriate abstracts to be considered. the inclusion criteria included discussing enough data on the dermatological symptoms with sars-cov- . moreover, only studies done among adult patients were included. furthermore, references of the chosen studies were assessed to distinguish any related studies. lastly, the required data sets were collected from the final record of eligible studies and summarized. studies were eliminated in case of in vitro or animal involvement, overlapped or incomplete data, and unavailability of full-text studies or inappropriate study design. entire details on the search strategy are shown in figure . the first step included a preparatory review, a specially designed excel sheet was used for data extraction. chosen data from eligible studies were then reviewed through the excel sheet. any studies published by one research group examining alike variables were evaluated for any potential duplication. cochrane, a quality assessment tool, was used to evaluate the quality of the included clinical studies [ ] . data were then statistically expressed in terms of frequencies (number of cases) and percentages for categorical variables. mean, standard deviations, medians, and interquartile ratios were used to represent the numerical variables. all statistical calculations were performed by ibm spss version (statistical package for the social science; ibm corp, armonk, usa). after searching the abstracts and reviewing the eligibility criteria in identified potential abstracts, a total of seven studies [ ] [ ] [ ] [ ] [ ] [ ] [ ] were considered as eligible to be included in the present systematic review, covering a total of patients with sars-cov- who had dermatological symptoms in the form of skin lesions. out of the seven studies, two studies were prospective [ , ] , three studies were retrospective [ , , ] , and two studies were case series [ , ] . additionally, all the included studies considered the objective of describing the dermatological manifestations of patients with sars-cov- with varying severity levels in different countries. due to the scarcity of data and lack of experience with the newly identified virus, all study designs were included [ ] [ ] [ ] [ ] [ ] [ ] [ ] . furthermore, all the studies identified the types of dermatological manifestations in patients. erythema and urticaria were common in four studies [ , [ ] [ ] [ ] , varicella-like lesions were defined in three studies [ , , ] , while other types of rash were identified in four studies [ ] [ ] [ ] ] . the included studies are discussed in detail in table . thailand. one patient out of the patients had a skin rash with petechiae. because dengue is very common in thailand, petechiae rash is a frequent clinical manifestation in dengue. the patient had thrombocytopenia. dengue was misdiagnosed in the beginning. there was no image, and a biopsy is not routinely done for dengue diagnosis in thailand. the patient was initially misdiagnosed as dengue, which has led to a delayed diagnosis there is a chance that a patient with sars-cov- can primarily have a skin rash that can be misdiagnosed as another common disease. the novel sars-cov- virus was identified in late , with minimal knowledge and experience regarding its diagnosis and treatment until present [ ] . although the symptoms of sars-cov- are mainly affecting the respiratory tract, other systemic features have been identified [ ] . dermatological manifestations, such as urticaria, erythema and rash, were also identified in some patients with sars-cov- in different countries. however, the description of these manifestations and their correlation to sars-cov- is still controversial [ ] . the present review evaluated the description and characters of dermatological manifestations in patients with sars-cov- . it has been shown that different types of cutaneous lesions occur in patients with sars-cov- , even in patients with mild respiratory symptoms. hence, the misdiagnosis of dermatological lesions in sars-cov- is common. furthermore, the most frequent types of lesions were varicella-like rash and rash resembling recent viral infection, in addition to urticaria and erythema. it is worth noting that these lesions might be itching or non-itching and are usually mildly severe in most patients, resolving at the end of the course of infection. dermatological lesions can also develop at a later stage of the infection. erythema and urticaria in sars-cov- patients have been described in some studies. the most robust study design described dermatological manifestations in spanish sars-cov- patients. the study described the lesions as commonly occurring in the acral areas, with % having erythema in the form of pseudo-chilblain, which developed in later stages in the infection, and another % having urticaria lesions. also, the dermatological lesions related to sars-cov- were severe in the acral area, with less severe lesions in other parts. additionally, the maculopapular rash was also characteristic in spanish patients with a prevalence of % [ ] . another study that had a retrospective design reviewed patients and showed that dermatological lesions appeared at a later stage of the infection, with inflammatory lesions occurring in % of patients in the form of exanthema, chickenpox-like vesicles. additionally, the study identified that the remaining % of patients had vascular lesions in the form of porcelain-like macules, livedo, necrotic purpura, chilblain, and eruptive cherry angioma [ ] . another study from italy included patients in a retrospective design and demonstrated that . % of patients had cutaneous manifestations, with eight patients developed the dermatological symptoms at an earlier stage of the onset of the sars-cov- infection, while ten patients developed the lesions after hospitalization due to sars-cov- due to severe infection. importantly, there was no correlation between the occurrence of dermatological lesions and the severity of sars-cov- infection, where some patients had dermatological lesions without developing respiratory symptoms for sars-cov- . the study also highlighted that the lesions are resembling those occurring in common viral infections [ ] . this finding was also supported by a varicella-like rash observed by two studies [ , ] . it is worth to mention that other frequent conditions can misdiagnose dermatological lesions occurring in patients with sars-cov- . in thailand, one study described one out of sars-cov- patients who had a rash with petechiae that was misdiagnosed with dengue disease, especially with the absence of routine biopsy in this setting [ ] . the included studies also had some limitations; most of the included studies were performed in one center, which may affect the external validity of outcomes. also, the sample size in each study was relatively small, which could reduce the reliability of their outcomes. these limitations should be considered in future studies. finally, this is considered the first systematic review to identify the dermatological manifestations occurring in patients with the novel sars-cov- infection. this should be a guide for clinicians to prevent the misdiagnosis of these manifestations with other dermatological conditions. dermatological lesions are frequent in patients with sars-cov- , especially erythema, urticaria, and varicella-like rash. differential diagnosis should be thoroughly considered before deciding that the present rash is related to sars-cov- infections. till present, the rash is not correlated to the severity of sars-cov- infection, which needs to be confirmed with studies with more robust design and larger sample sizes. these findings should be considered by clinicians working with patients with sars-cov- in order not to misdiagnose the occurrence of dermatological lesions, which may delay therapy or increase the risk of complications. covid- : attacks the -beta chain of hemoglobin and captures the porphyrin to inhibit human heme metabolism (preprint) cutaneous manifestations in covid- : a new contribution urticarial eruption in covid- infection covid- pandemic and the skin-what should dermatologists know? (in press) comment on: cutaneous manifestations in covid- : a first perspective. safety concerns of clinical images and skin biopsies a dermatologic manifestation of covid- : transient livedo reticularis covid- in singapore-current experience: critical global issues that require attention and action alert for non-respiratory symptoms of coronavirus disease (covid- ) patients in epidemic period: a case report of familial cluster with three asymptomatic covid- patients (preprint) covid- can present with a rash and be mistaken for dengue": petechial rash in a patient with covid- infection dermatology staff participate in fight against covid- in china covid- and cutaneous manifestations the prisma statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration the cochrane collaboration's tool for assessing risk of bias in randomised trials classification of the cutaneous manifestations of covid- : a rapid prospective nationwide consensus study in spain with cases varicella-like exanthem as a specific covid- -associated skin manifestation: multicenter case series of patients chilblain-like lesions on feet and hands during the covid- pandemic vascular skin symptoms in covid- : a french observational study (preprint) a case of covid- presenting in clinical picture resembling chilblains disease. first report from the middle east cutaneous manifestations in covid- : a first perspective covid- can present with a rash and be mistaken for dengue in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -ibt mupq authors: suwanwongse, kulachanya; shabarek, nehad title: fatal outcome in a kidney-pancreas transplant recipient with covid- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ibt mupq severe acute respiratory syndrome coronavirus (sars-cov- ) is a highly contagious pathogen causing the novel coronavirus disease (covid- ), the ongoing unprecedented pandemic in . sars-cov- primarily targets the respiratory systems, so acute respiratory distress syndrome is the major cause of death. clinical courses of covid- are variable and unpredictable, while some epidemiologic and clinical factors have been found to have a negative impact on the disease prognosis. despite a growing report on clinical characteristics and prognosis of patients with covid- , the data in the special population, including transplant recipients, is still limited. herein we report on the clinical features and fatal outcome of covid- in a dual pancreas-kidney transplant recipient (with failure of the pancreas graft). our case illustrates the similarities and differences of the covid- disease course between transplant recipients and the general population. we proposed that the pre-existing t-cell dysfunction from the long-term use of immunosuppressive agents in organ transplant recipients adversely affects covid- prognosis and worsens covid- mortality. the novel coronavirus disease , caused by severe acute respiratory syndrome coronavirus (sars-cov- ), is one of the greatest pandemic challenges in the st century. since its first report in december , sars-cov- has rapidly spread worldwide resulting in over five million confirmed cases and almost , deaths [ ] . in general, transplant recipients are vulnerable to develop serious infections due to chronic medical-induced immunosuppressive states. however, impaired immune functions may paradoxically protect transplant patients from the hyper-inflammatory response to sars-cov- and thus dampen the disease severity. previous reports on the outcomes of covid- in transplant recipients showed contradictory results, in which the mortality rate ranges from % to % [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the diversity in covid- prognoses across each literature may be due to different baseline patient characteristics, including age, sex, and comorbidities, as well as various management strategies across institutions. herein we report our experience in treating covid- in a dual pancreas-kidney transplant recipient and discuss the current knowledge regarding covid- in transplant patients. we present the case of a -year-old male who received dual pancreas-kidney transplantation from a deceased donor years ago because of end-stage renal disease (esrd) due to diabetic nephropathy. he had pancreas graft failure and underwent second pancreas transplantation years ago with immediate graft failure from thrombosis and third pancreas transplantation years ago with failure of the graft a year later due to viral infection. he then decided not to have further attempts of pancreas transplantation. his maintenance immunosuppressive therapy included oral tacrolimus (tac) mg twice daily, mycophenolate mofetil (mmf) mg twice daily, and prednisone mg once daily. he reported medication compliance and was adherent to follow-up appointments. his baseline creatinine ranged . - . mg/dl over the past year. the decline in his renal function was due to diabetic nephropathy, which was diagnosed by renal biopsy. his most recent serum creatinine (cr), two months prior to the current admission, was . mg/dl. the patient also had insulin-dependent diabetes mellitus (recent hemoglobin a c . %), hypertension, and obesity (body mass index . kg/m ), for which he took losartan mg once daily, metoprolol succinate mg once daily, rosuvastatin mg once daily, and insulin regimens. he presented with worsening dyspnea for three days and reported subjective fever, dry cough, watery diarrhea, polydipsia, and polyuria. on initial evaluation, his temperature was . °f, blood pressure was / mmhg, heart rate was beats per minute, and respiratory rate was breaths per minute with oxygen saturation (spo ) of % on room air. he had dry mucous membranes and did not appear to use accessory respiratory muscles. his lung examination revealed rales in both lungs. his neurological examination was normal. chest x-ray (cxr) showed bilateral multifocal ground-glass appearances ( figure ). laboratory values are described in table . sars-cov- reverse transcriptase-polymerase chain reaction (rt-pcr) from the nasopharyngeal swab specimen was positive. he was diagnosed with diabetic ketoacidosis (dka) and covid- . due to a lack of a negative-pressure room in our institution, he was admitted to a regular patient room on the medicine floor, with droplet and contact precaution. the patient received the standard treatment of dka, including insulin drip, aggressive electrolytes replacement, and intravenous hydration. he received supplemental oxygen via nasal cannula ( l/min), and his spo was improved to %- %. hydroxychloroquine ( mg twice daily on the first day, and mg twice daily for the following four days) was administered for covid- treatment as per hospital protocol. assuming his immunocompromised status, the primary team decided to give antibiotics: oral doxycycline and intravenous ceftriaxone for possible secondary bacterial pneumonia. his tac was stopped. mmf and prednisone were continued with the same dosage. his blood pressure medications and statin were discontinued. on day , his cr worsened to . mg/dl, while his respiratory function remained stable. the primary team contacted his transplant center for possible transfer due to suspected acute graft rejection from discontinuation of tac. however, he was rejected due to a lack of patient beds. tac was re-started. the next day, the patient became more hypoxemic with a p:f ratio of . his spo was around % despite adjusted high ventilator setting: volume control -positive end-expiratory pressure (peep) value of mmhg and % fio . cxr showed worsening pneumonia and ards. he was started on the proning protocol, with mild improvement of spo to %- %. although his hypoxemia was likely from severe ards, the primary team decided to give enoxaparin to treat possible pulmonary embolism, assuming the medication risks were lower than benefits. on admission day , he acutely developed oliguria with urine output less than ml in eight hours. his creatinine was doubled to . mg/dl. his transplant center was contacted again, but there was still no bed available. the daily changes in his creatinine are demonstrated in figure . he received hemodialysis with total ultrafiltration of l. however, his conditions were progressively worsening and he eventually died on day . multiple blood and sputum cultures were done during hospital courses, which all revealed negative results. his cause of death was septic shock and multi-organ failure from severe covid- . sars-cov- uses angiotensin-converting enzyme (ace ) receptors to enter the host cells causing a spectrum of diseases ranging from flu-like illness, pneumonia to severe ards, septic shock, and death [ , ] . the uncontrolled hyper-inflammatory response to sars-cov- , rather than the own viral virulence, presumably underlies the covid- severity [ , ] . certain comorbidities, including hypertension, diabetes mellitus, and cardiovascular diseases, adversely impact covid- prognosis, probably due to the changes in the renin-angiotensin system (ras) or underlying chronic inflammatory states [ , ] . many research teams have been repurposing various anti-viral and immunomodulating agents to treat covid- . however, to date, no specific drugs have proven mortality benefits, and unfortunately, the best covid- management is supportive measures, which include the provision of supplemental oxygen, invasive ventilation, and extracorporeal membrane oxygenation [ ] . long-term immunosuppressive therapy in organ transplant recipients may alter clinical features and outcomes of covid- . however, considering our patient and previously published literature, transplant recipients with covid- did not show prominent differences in terms of clinical symptoms, laboratory values, and cxr findings [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . our patient had hypertension, diabetes mellitus, and obesity, which are identified as poor prognostic markers of covid- in the normal population [ , ] . whether these comorbidities negatively impact covid- in transplant recipients is not well-characterized, but most of the literature published so far and our case report suggest a similar result [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . recent evidence showed that the duration of organ transplantation correlates with covid- severity [ ] . our patient underwent dual kidney-pancreas transplantation for years, so he had unfavorable outcomes leading ultimately to death. whether the type and number of organ transplantation affect the covid- courses remains undetermined. the long-term use of immunosuppressive medications in organ transplant recipients is associated with the decrease in t-cell number and function; tac and mmf preferentially inhibit t-cell response. t-cell lymphocytopenia has also been found in patients with covid- and is correlated with the disease severity [ ] . whether the chronic t-cell suppression in organ transplant recipients attenuates the clinical course and severity of covid- remains unknown. recently, we reported the extremely high mortality rate of hiv patients with sars-cov- infection [ ] . t-cell impairment is the major characteristic of hiv-associated immunopathology. based on our observations, we propose that the previous medically induced t-cell impairment negatively affects covid- prognoses in the transplant recipients. further research exploring the role of t-cell lymphocytes in sars-cov- pathogenesis will be worthwhile. it is uncertain whether the immunosuppressive agents should be adjusted in transplant recipients who have been infected with sars-cov- . aberrant host-immune reactions characterized by hyper-inflammatory states and persistent cytokines releases likely contributed to covid- severity. severe covid- patients had considerably high serum proinflammatory cytokines, including tumor necrosis factor (tnf)-α, interleukin (il)- , and il- [ ] . abrupt discontinuation of immunosuppressive agents may lead to an exaggerated rebound inflammatory response to sars-cov- . a study from the netherlands found that immunosuppressive drug withdrawal worsened covid- mortality. however, in this report, immunosuppressive agents were discontinued in patients with severe disease, presumably with high mortality risks. the current expert opinion urges adjusting the immunosuppressive agents based on covid- severity. we have summarized the recommendations in surprisingly, on admission, our patient had an increase in the glomerular infiltration rate. this is likely due to the early phase of sepsis and acute kidney injury (aki). clinicians should be aware that patients may have lower serum cr during the early phase of aki. other common causes of the acute drop in cr include urinary tract obstruction and certain medication effects. the doubled rise of his cr level on day was likely due to septic shock and multi-organ failure. the patient was unlikely to have acute renal graft rejection from tac withdrawal as he had undergone transplantation for more than years and tac was discontinued for only a few days. the definitive diagnosis of acute renal graft rejection requires kidney biopsy. however, it was not done in our patient as the diagnosis would not change our management. the patient required hemodialysis as he had oliguric acute renal failure and suffered from severe covid- . we report a clinical course and lethal outcome of covid- in a transplant recipient. preexisting t-cell immune response deficits from long-term use of immunosuppressive agents may worsen the prognosis of covid- in transplant recipients. the optimal management of covid- in the post-transplant population remains unclear. the recent expert opinion recommended adjusting immunosuppressive agents based on covid- severity. there is an urgent need to develop the collaborative management guidelines of organ transplant recipients with covid- in the non-transplant centers to provide patients the best available care. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. coronavirus disease covid- in solid organ transplant recipients: a single center case series from spain successful recovery of covid- pneumonia in a renal transplant recipient with long-term immunosuppression covid- and kidney transplantation covid- in solid organ transplant recipients: initial report from the us epicenter covid- in long-term liver transplant patients: preliminary experience from an italian transplant centre in lombardy clinical outcomes and serologic response in solid organ transplant recipients with covid- : a case series from the united states covid- in solid organ transplant recipients: a single center experience covid- and liver transplantation: lessons learned from three reported cases genomic characterisation and epidemiology of novel coronavirus: implications for virus origins and receptor binding clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study complex immune dysregulation in covid- patients with severe respiratory failure dysregulation of immune response in patients with coronavirus risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease pneumonia in wuhan, china evidence based management guideline for the covid- pandemic -review article reply to "coronaviruses and immunosuppressed patients. the facts during the third epidemic suppressed t cell-mediated immunity in patients with covid- : a clinical retrospective study in wuhan clinical features and outcome of hiv/sars-cov- co-infected patients in the bronx how should i manage immunosuppression in a kidney transplant patient with covid- ? an era-edta descartes expert opinion key: cord- - dx q o authors: ashraf, muddasir; sajed, sulaiman title: seizures related to coronavirus disease (covid- ): case series and literature review date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: dx q o neurological manifestations are common in coronavirus disease (covid- ) patients. we present three cases of covid- patients with seizures. two patients had a history of seizures but very well controlled. they presented with seizure activity likely triggered by covid- . the third patient had no history of seizures and presented with new onset of seizure activity. all these patients were routinely screened for covid- on admission and tested positive on nasopharyngeal real-time reverse transcriptase-polymerase chain reaction (rrt-pcr). none of these patients had respiratory symptoms. electroencephalography (eeg) was abnormal in all three patients. all these patients recovered and were discharged in a stable condition. coronavirus disease (covid- ) started in wuhan china, a city in the hubei province, but soon became a pandemic. covid- is a reality now that we have to live with, and scientists worldwide continue to learn how it affects our bodies. it was initially thought to be a respiratory disease, but we soon realized that it is not true. covid- is a systemic disease that primarily affects the lungs but can affect other organs too. covid- causes many neurological manifestations, including stroke, headache, altered consciousness, encephalitis, anosmia, hypogeusia, guillain-barre syndrome, and seizures [ ] [ ] [ ] . these patients are usually sicker and in the intensive care unit but not in all cases [ ] . both patients with new-onset seizures and those with seizures with a previous history of seizures have been reported. some patients may have no respiratory symptoms at all, and their initial presentation may be neurological [ ] . patients with status epilepticus have also been reported [ ] . multiple mechanisms have been proposed, and further studies are needed to be conducted to understand it better. a -year-old male with a past medical history of dementia and seizures was brought by paramedics due to five episodes of witnessed generalized tonic-clonic seizures. the patient was post-ictal on arrival in the emergency and was slightly agitated later on. there was no reported history of tongue biting or loss of bladder or bowel incontinence. the patient was reportedly compliant with his antiseizure medications, which included oxcarbazepine and lacosamide. on physical examination, vital signs were stable. the patient was disoriented, agitated, and not following commands. the rest of the physical examination was unremarkable. labs, including complete blood count and basic metabolic panel, were unremarkable except mildly elevated white blood cell count of . x /ul. creatinine kinase levels were normal. real-time reverse transcriptase-polymerase chain reaction (rrt-pcr) for covid- came back positive. chest xray ( figure ) showed cardiomegaly, but no acute infiltrates. computed tomography (ct) of the head did not show any acute abnormalities. the patient was loaded with intravenous keppra® and admitted to the hospital. electroencephalography (eeg) (figure ) showed generalized sharps with slowing. the patient subsequently improved with his mentation back to the baseline. he did not have any further seizures. the patient was finally discharged with increased doses of oxcarbazepine and lacosamide. a -year-old male resident of a nursing home with a past medical history of hypertension, diabetes type , and dementia presented to the hospital with the symptoms of altered mental status. the patient started having generalized tonic-clonic seizures on arrival in the emergency room. the patient did not have any witnessed seizure activity in the nursing home but had fallen with face down on the floor. the patient did receive versed® by paramedics. the patient was unresponsive in the emergency room after the seizure. on physical examination, vitals were stable with no evidence of hypoxemia. the chest was clear to auscultation. the cardiovascular examination was unremarkable. the abdomen was soft and non-tender, and bowel sounds were positive. neurological examination was significant for unresponsiveness, with the patient only responding to painful stimuli. pupils were equal and reactive to light. initial workup in the emergency room was significant for leukocytosis, metabolic acidosis with lactic acid greater than mmol/l, and acute renal failure. labs are shown in table . rrt-pcr for covid- was positive. chest x-ray ( figure ) showed bibasilar small airspace disease. ct of the head was unremarkable for any acute abnormalities. magnetic resonance imaging (mri) of the brain was unremarkable as well. ct of the abdomen also showed no acute abnormalities. the patient was started on intravenous fluids and empiric intravenous antibiotics. ammonia levels were umol/l on admission, and the patient was started on lactulose through a nasogastric tube for hepatic encephalopathy. ultrasound liver did not show any evidence of liver disease. eeg (figure ) performed on admission did show left-sided sharps with background slowing. the patient was also loaded with intravenous keppra on arrival in the emergency room and later on continued during the hospital course. the patient did not have any further seizures during the hospital course. the patient made a remarkable recovery with no need for ventilation and recovered back to his baseline with the resolution of acidosis and renal failure. ammonia levels normalized as well. all other laboratory parameters also improved. the patient was finally discharged on oral keppra back to the extended care facility. a -year-old male resident of the nursing home with a past medical history of ischemic stroke with residual left-sided hemiparesis, seizure disorder, crohn's disease, hyperlipidemia, and dementia on aricept presented to the emergency room with generalized tonic-clonic seizures. the seizure was witnessed in the nursing home. the patient was post-ictal on arrival in the emergency room. the patient was also agitated afterward. the patient had no respiratory symptoms. on physical examination, vitals were stable. the neurological examination was significant for dysarthric speech and left-sided hemiparesis, and the patient was disoriented. the rest of the physical examination was unremarkable. labs, including complete blood count and comprehensive metabolic panel, were unremarkable. troponin, creatine phosphokinase, and c-reactive protein were within normal limits. rrt-pcr for covid- came back positive. chest x-ray ( figure ) showed focal consolidation in the medial right lung base. ct brain ( figure ) showed old right encephalomalacia with no acute abnormalities. eeg (figure ) showed slowing with right-sided sharps. the patient was loaded with intravenous keppra in the emergency room. the patient did not have any further episodes. the patient gradually improved and was finally discharged back to the nursing home with the same regimen of covid- is known to cause respiratory problems such as pneumonia. however, its role in causing seizures in patients is still under study. it is reported that covid- causes an inflammatory response, releasing inflammatory cytokines that play a role in acute seizures [ ] . previous studies show central nervous system (cns) infection from the severe acute respiratory syndrome coronavirus (sars-cov) infection from [ ] . as covid- is also a part of the coronavirus family, it would share a similar pathway to that of sars-cov. similar cases have arisen within patients with no history of seizures who develop a seizure [ , ] . however, a study in china with patients found that seizures were not occurring within these patients, attributing any seizures seen to acute stress or hypocalcemia [ ] . this study was conducted earlier in the year before covid- was labeled a pandemic, which could contribute to the lower incidences of seizures. another study contradicts the study conducted in china, showing the growing number of neurological complications associated with covid- [ ] . the development of headaches, encephalitis, strokes, and epileptic seizures are among the many neurological symptoms that are manifesting within covid- patients [ ] . elderly patients with chronic conditions or severe patients of covid- are at a higher risk of these neurological symptoms in the setting of these types of acute infections [ , ] . the genetic material of viruses can be found in nervous tissue samples [ ] . while subsequent studies need to be conducted to gain evidence of covid- spreading into the cns, mechanisms have been proposed as to how the virus spreads. a proposed mechanism is that the virus can move from the olfactory nerve to the cns [ ] . this can occur within the first seven days of infection as covid- quickly moves from the olfactory tract to the brain and cerebral spinal fluid [ ] . this would cause the release of cytokines by the host's immune system, leading to encephalitis. while the olfactory nerve propagation is possible within some coronaviruses, some can also penetrate the cns through the cribriform plate of the ethmoid [ ] . more studies are needed to be conducted to determine whether the propagation is done through this method. another proposed mechanism is the hematogenous spread of the viral particles within the cns [ ] . this would be possible through the circulating lymphocytes. after infection, the circulating lymphocytes traveling to the brain would infect it, causing the inflammatory response. covid- also has been seen to have a large affinity for angiotensinconverting enzyme (ace- ) [ ] . the viral attachment to ace- at the blood-brain barrier could be the source of viral encephalitis. these proposed mechanisms can explain how covid- spreads within the cns; however, the neurotropic pathogenic mechanism must be studied in further detail to understand the neurological effect covid- has. similar studies into the nipah virus, which also causes neurological symptoms identical to those found in covid- patients, along with research into sars can possibly reveal information as to how covid- spreads within the body [ ] . as covid- is now something that we have to live with, it is urgent that we must understand it more thoroughly to understand its pathogenesis. covid- can cause many neurological complications including seizures. not only can it worsen seizure control in the patients with previously well-controlled seizures, but it can also cause new-onset seizures in healthy patients. the new-onset seizures are generally present in sicker patients, as was the case in our patient. though there are many proposed mechanisms, further research will make our understanding of its pathophysiology better. frequent convulsive seizures in an adult patient with covid- : a case report covid- pandemic: a neurological perspective covid- presenting with seizures focal status epilepticus as unique clinical feature of covid- : a case report central nervous system manifestations of covid- : a systematic review new onset acute symptomatic seizure and risk factors in coronavirus disease : a retrospective multicenter study neurological complications of coronavirus disease neurologic manifestations of hospitalized patients with coronavirus disease nervous system involvement after infection with covid- and other coronaviruses explanation for covid- infection neurological damage and reactivations human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -ju vcalk authors: barbosa, daniel a. n.; de oliveira-souza, ricardo; gorgulho, alessandra; de salles, antonio title: upholding scientific duty amidst poisonous disinformation date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ju vcalk because of a recent politically-biased lancet editorial, the world’s opinion has been directed against the brazilian government over the rising numbers of covid- cases in the country. this is an example of reporting data without accounting for important covariates. epidemiological figures should always be corrected for population size. in fact, brazil is not even on the list of the countries with the highest number of deaths per , people. belgium, the united kingdom, and spain are the most affected countries in this regard. the disinformation presented by a renowned medical journal has ignited severe criticisms against a chief-of-state for not promoting a generalized lockdown in a country of continental size. as scientists, we have a duty to stress the caveats of science instead of fueling political attacks, and we should refrain from jumping to uninformed conclusions without considering well-analyzed data. moreover, while there is no evidence to endorse the efficacy of a generalized lockdown in socioeconomically vulnerable populations, it is undoubtedly associated with severe nationwide adverse effects. in a recent lancet editorial, the world's attention was directed toward the rising numbers of confirmed covid- cases and deaths in brazil [ ] . it highlighted some worrisome projections from studies by the imperial college, london [ ] . during the current global health crisis, articles in renowned medical journals have guided public policies and investments in healthcare [ ] . consequently, scientific information has gained the power to alleviate the suffering of societies; however, disinformation, on the other hand, causes suffering and ruins livelihoods [ ] . brazil is now the country with the second-highest total number of confirmed covid- cases and deaths [ ] . yet, as scientists, we cannot interpret this piece of raw data without accounting for covariates. brazil has the sixth largest population in the world; therefore, this raw number must be corrected by its population size. it turns out that brazil has never been among the large countries with the highest number of deaths per , people. that list is headed by belgium, the united kingdom, and spain [ ]. as of july , , brazil occupies the th spot in that list ( table ) . such a spurious manner of reporting public health data is completely unacceptable even by the lay media, let alone by a renowned scientific journal [ , , ]. the lancet focused on politics instead of a scientific analysis of the pandemic's status in brazil, an odd choice for a scientific publication. data not corrected for population size was used to build the claim that "perhaps the biggest threat to brazil's covid- response is its president ", and that "brazil's leadership has lost its moral compass, if it ever had one" [ ] . the editorial failed to provide scientific support, but rather echoed politically-biased ideas. the lancet's manifesto is merely a science-fueled attack against a chief-of-state for advising state governors to reopen the economy, and serves instead to encourage a policy of generalized lockdown, which is associated with severe nationwide adverse effects, i.e., increased poverty, conjugal crises, street criminality, depression, suicide, and substance abuse. calling the lockdown a "sensible measure" contrasts with fair criticisms against leaders embracing policies without sufficient evidence of their efficacy and safety. in fact, the universal lockdown adopted by brazilian mayors and state governors has not slowed down the growing raw number of covid- cases; instead, it has proven to be extremely harmful to several underserved communities [ ] . indeed, physical distancing and hygiene recommendations are impossible to follow in brazil's underserved communities, as pointed out by the same editorial [ ] . the forceful implementation of these measures has oppressed vulnerable populations, by instilling hunger and crime [ ] . it is irresponsible to use poorly analyzed data to accuse leaders, countries, and doctors working with the best of intentions to fight a pandemic that has caused immense misery even in the most developed countries. the use of disinformation to point fingers against those fighting in extremely difficult conditions against the same misery, covid- , for the benefit of their underserved people is inhuman and unfair, and the heroes of this pandemic deserve better. the lancet's editorial board should at least publish a note apologizing for these unfounded accusations and lack of sensibility [ , , ]. while we seek to serve the people with a scientific outlook and approaches, a pertinent question arises: when are our colleagues in the medical field going to stop delivering politically-biased disinformation? editorial (anonymous): covid- in brazil covid- : brazil now has third highest number of cases behind us and russia disinformation: former spy chief reveals secret strategies for undermining freedom, attacking religion, and promoting terrorism lockdown puts brazilian lives at risk in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -oxe chd authors: meza, jose l; triana, abel; de avila, ivan; del rio-pertuz, gaspar; viasus, diego title: diabetic ketoacidosis precipitated by covid- in patients without respiratory symptoms: case reports date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: oxe chd worse outcomes of coronavirus disease (covid- ) have been documented in older patients with comorbidities, especially in those with diabetes mellitus (dm). however, the clinical picture and risk factors of covid- in dm is still emerging. here, we report four cases of severe covid- patients with acute diabetic ketoacidosis (dka) without respiratory symptoms, with viral and bacterial coinfection, and poor clinical outcomes. higher monitoring of patients with dm and covid- is advised, as well as rapid and accurate diagnostic tests and treatment. in december , an acute respiratory illness of unknown origin occurred in wuhan, china. the causal microorganism, which was named severe acute respiratory syndrome coronavirus (sars-cov- ) [ ] , has spread worldwide causing a pandemic. the typical clinical manifestations include fever, dry cough, sore throat, myalgia, fatigue, headache, nausea, and diarrhea. however, new clinical features or complications have been reported such as neurological or cutaneous manifestations [ ] [ ] . diabetes mellitus (dm) has been one of the most common comorbidities associated with patients having coronavirus disease (covid- ) with a prevalence ranging from . % to % [ ] . patients with pre-existing dm seem to have a higher risk of developing severe metabolic complications, requiring icu admissions, and death [ ] . however, clinical picture and risk factors in dm are emerging and the diabetogenic characteristic of sars-cov- is still under investigation. in this report, we highlight the important issues related to four cases of severe covid- presenting with diabetic ketoacidosis (dka). this report was approved by the institutional review board. an -year-old female was admitted to the ed suffering from four days of polydipsia and high capillary blood glucose levels, two days of fever, somnolence, and a recent fall. she had a history of type diabetes mellitus (t dm). the physical examination revealed disorientation and drowsiness. at admission, plasma glucose and hemoglobin a c (hba c) were mg/dl and . %, respectively. acute kidney injury (aki) and dka were diagnosed based on blood chemistry ( table ) . a chest ct showed bilateral ground-glass opacity ( figure a ). on day two, a rapid decline of the respiratory status resulted in oxygen supplementation and mechanical ventilation. vasopressors were also started. on day five the patient required renal replacement therapy due to worsening aki and died. she was positive for adenovirus, influenza type b, and sars-cov- . an overweight -year-old male was admitted to the ed with days of weakness, polydipsia, polyuria, nausea, and vomiting. physical examination revealed somnolence, tachycardia, tachypnea, and kussmaul breathing. upon admission blood chemistry revealed plasma glucose of mg/dl, hba c of %, aki and dka criteria ( table ) . a chest ct showed bilateral peripheral ground-glass pattern ( figure b) . bicarbonate infusion was started due to refractory severe metabolic acidosis. respiratory status declined rapidly which led to the need for mechanical ventilation. on hospital day four, blood culture reported salmonella enteritis. due to refractory metabolic acidosis, renal replacement therapy was performed. the patient was progressively improving, extubated, and discharged on day . he was positive for influenza type a and sars-cov- . a -year-old male was admitted to the ed complaining of four days of diarrhea, vomiting, asthenia, and somnolence. he had a history of t dm and hypertension. physical examination revealed a disoriented patient with incoherent speech, tachycardia, tachypnea, and kussmaul breathing. upon admission, blood chemistry revealed plasma glucose of mg/dl, hba c of %, aki and dka criteria ( table ) . a chest ct showed a crazy-paving pattern consolidation ( figure c) . on hospital day two, oxygen supplementation was started, and blood cultures showed staphylococcus hominis. on hospital day three, the patient developed psychomotor agitation and a rapid decline in respiratory status which derived in mechanical ventilation and died on this day. he was positive for sars-cov- . a -year-old male presented to the ed with one day of general weakness, associated with high blood glucose levels. he had a history of t dm. physical examination revealed tachycardia and hypertension. upon admission, plasma glucose was mg/dl, aki and dka criteria were documented in blood chemistry ( table ) . a chest x-ray reported bilateral radiopacity of the lungs ( figure d ). the patient developed altered mental status, acute respiratory distress which required mechanical ventilation. during the procedure, the patient underwent cardiac arrest. on hospital day four, the patient did not recover from respiratory failure and hemodynamic instability and died. he was positive for sars-cov- . information regarding clinical characteristics, complications, and outcomes of covid- is rapidly evolving as data continue to emerge throughout the world. the prevalence of dm in patients with moderate covid- is nearly %, being higher in severe patients ( %) [ ] . dm has been consistently associated with high morbidity and mortality in patients with covid- . in this regard, a meta-analysis documented that dm in patients with covid- is related with a two-fold increase in mortality as well as severe disease, as compared to nondiabetic patients [ ] . these case reports highlight important issues in dm patients with dka. first, we documented the variability of the clinical picture of covid- . we have recognized patients without respiratory symptoms with pulmonary infiltrates, with severe metabolic complication, and a rapid decline in the respiratory status leading to the need for mechanical ventilation. second, sars-cov- must be considered as a cause of metabolic decompensation in dm patients even in patients without respiratory symptoms. in this regard, adequate use of personal protective equipment should be considered in the attention of these patients until sars-cov- is ruled out. third, bacterial coinfection should be investigated in patients with dm decompensation secondary to covid- . the role of coinfection in prognosis required further studies. finally, dka precipitated by covid- is related to unpredicted worse outcomes. in the present case reports, the patients with pre-existing dm died and the patient with newly diagnosed dm progressed to aki that required renal replacement therapy as an outpatient treatment. therefore, dka during the covid- pandemic required rapid and accurate diagnosis tests and treatment. sars-cov- must be considered as a potential cause of metabolic decompensation in dm patients even in patients who do not have respiratory symptoms and adequate use of individual protective equipment should be considered in the attention of patients with dka until sars-cov- is ruled out. in addition, bacterial and viral coinfection should be investigated in patients with covid- and acute dka. clinical features of patients infected with novel coronavirus in wuhan, china. lancet. neurologic manifestations of hospitalized patients with coronavirus disease cutaneous manifestations in covid- : the experiences of barcelona and rome prevalence of diabetes mellitus in novel coronavirus: a meta-analysis is diabetes mellitus associated with mortality and severity of covid- ? a meta-analysis human subjects: consent was obtained by all participants in this study. comité de Ética en investigación de la división ciencias de la salud de la universidad del norte issued approval act no. -protocol: hun-inf-cetocovid- - . we obtained approval by the institutional review board and the research ethics committee of the universidad del norte, which allowed that informed consent was waived due to information was anonymized and obtained from clinical records. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -ur x fsa authors: bajwa, hamza; riaz, yumna; ammar, muhammad; farooq, soban; yousaf, amman title: the dilemma of renal involvement in covid- : a systematic review date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ur x fsa severe acute respiratory syndrome coronavirus (sars-cov- ), now known as coronavirus disease (covid- ), has posed a serious threat to global health since december . it has spread worldwide and is consuming healthcare resources rapidly. published literature suggests that people with advanced age and comorbidities are affected more severely. it is crucial to uncover the underlying pathogenesis of acute kidney insufficiency in covid- patients to understand better the reasoning behind the grave outcomes in these patients. in this review, we have included articles stating the prevalence and specific mortality rates of covid- patients with acute kidney insufficiency. our study included covid- positive patients, of whom ( %) developed acute kidney insufficiency and patients died, showing a mortality rate of %. patients with acute kidney insufficiency showed a more severe disease course, and these patients ended up more in intensive care units. particular attention should be paid to those with already established kidney disease, such as chronic kidney disease, or renal transplant recipients, as these patients are already on immunosuppressive therapy. our review focuses on the prevalence of acute kidney insufficiency in covid- patients and mortality rates in this subset of patients. the turn of the decade brought forth a new challenge for the entire world. this time the enemy was elusive, a minute particle made up of protein and nucleic acid. in december , coronavirus hit the world with its third major epidemic [ ] . starting from wuhan, in the hubei province of china, it spread to other countries and became a global problem within months. on february , , the world health organization (who) named this illness as coronavirus disease (covid- ) and later declared it a pandemic on march , [ ] . the western world has been most affected by this illness, with peaks noted in european countries and the united states (us). until may , , , , cases have been reported in the us, and , , cases globally, with , , patients recovered and , reported deaths worldwide [ ] . there is a wide range of clinical presentations of covid- -infected patients, varying from asymptomatic recovery to critical illness and death. classically, patients with covid- present with cough, fever, dyspnea, fatigue, and respiratory failure along with multiorgan damage in severe cases [ ] [ ] [ ] . the disease is highly contagious and spreads in cluster outbreaks. person-to-person contact via respiratory droplets is the primary mode of transmission. the fecal-oral route might be possible, while aerosol, tear, semen, and mother-to-fetus transmission are yet to be confirmed [ ] . there are several studies in the literature illustrating the possible mechanism of dissemination and multiorgan involvement in covid- patients. so far, diffuse alveolar damage and acute respiratory failure are the main features of severe covid- , but the data on the kidney's involvement is limited. initial reports from wuhan suggested that the prevalence of acute kidney injuries (aki) in covid- patients was quite low, ranging from - %; however, the subsequent analyses showed a relatively high aki burden of % [ ] . another chinese cohort study of patients with covid- revealed that only . % developed aki [ ] . while some studies have shown this association, data on the patients' mortality is limited. chen et al. reported an incidence rate of . % and the mortality rate of . % of aki in severe acute respiratory syndrome [ ] . nevertheless, a study on the association of renal injuries with covid- is warranted. our focus in this review is to analyze the published data on kidney injuries in covid- and mortality rates in these patients. a systematic search was done on pubmed, cochrane library, clinicaltrials.gov, and google scholar following preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines [ ] (figure ) the search was performed using mesh terms, "acute kidney injury" and "coronavirus". our search was not limited to any geographical area, and all relevant published articles in english or english translation from december to april , , were included in our study. we identified articles through systematic searches. out of these, five articles were analyzed and included in our review. these five articles had a pool of covid- positive patients. twenty-three patients already had chronic kidney disease (ckd), and seven patients were kidney transplant recipients (trx). out of total patients, ( %) developed aki after the acquisition of covid- . however, out of these patients died, showing a high mortality rate of %. out of patients who did not develop aki, patients died, and recovered (mortality rate= %). the results of individual studies are explained ( [ ], [ ] , [ ] [ ] [ ] cheng et al. enrolled covid- positive patients admitted in tongji hospital, wuhan, to study the prevalence of aki in covid- patients and to determine the association between abnormal kidney function markers and mortality in covid- patients. statistical analysis of the data showed an incidence of aki in . % of all enrolled patients and a much higher incidence ( . %) of aki in patients who already had elevated baseline serum creatinine levels at the time of admission. the analysis also revealed a higher incidence of in-hospital mortality ( . %) in covid- patients with raised baseline serum creatinine levels as compared to mortality ( . %) in those with normal baseline serum creatinine levels at the time of hospitalization. the review of medication data showed a higher trend of treatment with antiviral drugs (p = . ) and glucocorticoids (p = . our review comprehensively described the prevalence of acute kidney injury (aki) in covid- patients. the studies included were two prospective cohorts, one retrospective, and two case-series. the incidence of aki was high in patients with elevated baseline serum creatinine (cr). aki of higher than stage ii and cr > . mg/dl were associated with in-hospital death of covid- patients [ ] . the admission to intensive care units (icu) and mechanical ventilation requirements were also higher in patients with raised baseline cr regardless of covid- severity and general physical condition on admission. the aki patients have a higher mortality rate than patients with other comorbidities. it is observed to be more than the mortality rates of patients with cardiovascular pathologies ( %) [ ] . therefore, kidney functions should be monitored in patients with even mild respiratory symptoms, and particular attention must be given to those with altered kidney functions. various mechanisms have been proposed to explain how covid- infection causes acute kidney injury (aki). cytokine release syndrome (csr) offers a reasonable explanation for this association. crs can lead to aki by causing intrarenal inflammation, increased vascular permeability, volume depletion, and cardiomyopathy, leading to cardiorenal syndrome type . the syndrome includes systemic endothelial injury, which manifests clinically as pleural effusions, edema, intra-abdominal hypertension, third-space fluid loss, intravascular fluid depletion, and hypotension. interleukin (il- ) is a pro-inflammatory cytokine and has a major role in crs. the level of il- is markedly increased in covid- patients with acute respiratory distress syndrome (ards). the anti-il- monoclonal antibody tocilizumab is widely used to treat crs in many other medical conditions and is now being used empirically in severe covid- cases [ ] . the support for critically ill covid- patients with extracorporeal membrane oxygenation (ecmo), invasive mechanical ventilation, and continuous kidney replacement therapy (ckrt) also contributes to the generation of cytokine leading to increased chances of aki in critically ill patients. ards also results in additional damage to tubular cells in renal medulla by hypoxic injury [ , [ ] [ ] . the usual practice of fluid expansion in patients with shock may have a detrimental effect on kidneys, as it can worsen renal vein congestion, leading to renal compartment syndrome. a similar picture might be expected in covid- ; however, recent studies do not have this association. hyperkalemia, rhabdomyolysis, and metabolic acidosis can also occur in covid- patients and almost always are associated with hemodynamic instability. a recent study has encouraged the use of continuous renal replacement therapy (crrt) in these patients, with or without medium cut-off or high cut-off membranes [ ] . in extended icu stays, superimposed infections can cause septic shock. in a chinese study of patients, sepsis was present in of patients ( . %) with severe covid- [ ] . we can assume that septic aki may occur in such patients and act synergistically with other mechanisms of kidney injuries. in patients with suspected or confirmed gram-negative bacterial infections and an endotoxin activity assay result of . - . , the use of hemoperfusion with a cartridge containing polystyrene fibers functionalized with polymyxin-b provides effective endotoxin adsorption. the functionalized surface has sites that bind to endotoxin, reducing its plasma concentration [ ] . patients on hemodialysis seem to represent another target population for severe covid- disease. however, data does not suggest a variation from the general population until regular maintenance hemodialysis is provided. a study on this association showed out of maintenance hemodialysis patients contracted covid- , and none of them developed serious complications or died [ ] . renal transplant recipients (trx) are another group of susceptible populations because they are on chronic immunosuppression, making them more susceptible to pathogens and infections. these patients have a high trend of ending up in intensive care units (icu). an important consideration is how many patients will require renal replacement therapy or dialysis as the need for dialysis usually arises around the second week of infection, and about % of icu patients require dialysis [ ] . however, in our review, trx did not show complications related to covid- , and contrary to this, all five patients in the study conducted by zhang et al. survived, and none of them developed the severe disease [ ] . there is no need to lower immunosuppressive dose in trx with mild covid- symptoms, while drug adjustment is needed in those who develop acute respiratory distress syndrome or pneumonia [ , ] . early detection of renal derangements and treatment may improve the prognosis of covid- patients. therefore, to improve early detection of renal injuries, more frequent serum creatinine measurements should be performed. our review was limited regarding the number of articles. as it is still a new disease, data on the association of aki with covid- is limited. we could only include three articles directly revealing this association, the population in the other two articles was renal transplant recipient. we suggest more studies should be conducted on the prevalence and mortality of aki patients diagnosed with covid- . our study shows that the incidence rate of aki in covid- patients is around %, which is not alarming if we compare the incidence rate of other organ injuries, such as lungs and heart, in covid- . however, the alarming fact is the high mortality rate of % in these patients. these results demand that patients who are prone to developing aki should be given special attention, and kidney functions should be monitored frequently. in kidney transplant recipients and those with chronic kidney disease, the mortality rate is also low until aki develops. these results are from a limited data pool, and hence, we suggest conducting further studies involving a larger patient population to further evaluate this association. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. evidence that vitamin d supplementation could reduce risk of influenza and covid- infections and deaths kidney disease is associated with in-hospital death of patients with covid- latest upates on covid- stats identification of kidney transplant recipients with coronavirus disease prediction models for diagnosis and prognosis of covid- infection: systematic review and critical appraisal ct imaging changes of corona virus disease (covid- ): a multi-center study in southwest china covid- and kidney failure in the acute care setting: our experience from seattle kidney involvement in covid- and rationale for extracorporeal therapies preferred reporting items for systematic reviews and meta-analyses: the prisma statement clinical characteristics of deceased patients with coronavirus disease. : retrospective study covid- in kidney transplant recipients coronavirus disease infection does not result in acute kidney injury: an analysis of hospitalized patients from wuhan, china velissaris d: intubation and mechanical ventilation of patients with covid- : what should we tell them covid- : how a virus is turning the world upside down clinical characteristics of coronavirus disease in china covid- in hemodialysis patients: a report of cases the authors are grateful to dr. saad bajwa for his valuable critics to improve the quality of work. key: cord- -e n o p authors: ahmed, nishat; kamarul bahrin, muhammad hafiz; agha, adnan; deshmukh, anand title: sporadic fusobacterium bacteremia as an atypical cause of acute hepatitis in a young caucasian woman date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: e n o p fusobacterium species are gram-negative anaerobic non-spore-forming bacteria, which colonize mucous membranes in humans. over the recent decade, the significance of these organisms has been increasingly recognized. we describe a rare case of acute hepatitis, which was found to be likely due to fusobacterium nucleatum, grown on blood culture. in our case, the hepatitis caused by this microorganism resolved completely without any long-term sequelae to the liver, through conservative management namely intravenous antibiotics and supportive therapy only. this case highlights that early detection and prompt treatment in a case of acute hepatitis resulted in a good outcome. in addition, this case also illustrates that the differential diagnosis can be varied in cases of acute hepatitis. fusobacterium species are commensal to the oral cavity of humans and animals. they rarely cause problems in a healthy human being. in a retrospective study, based on the data obtained from a regional microbiology laboratory serving a population of . million people, over years, it was found that fusobacterium species, bacteremia in particular, is exceptionally rare with an annual incidence of only . cases/ , population [ ] . the two commonly reported species of fusobacterium are fusobacterium nucleatum and fusobacterium necrophorum, of which the latter is rarer. we report a case of acute hepatitis, associated with fusobacterium septicemia. fusobacterium can sometimes be associated with upper respiratory tract infections, which may spread to the internal jugular vein and cause thrombophlebitis. this is known as lemierre's disease. the mainstay of treatment is surgical drainage of any resulting secondary abscess and use of antibiotics [ ] . the commonly used antibiotics to treat fusobacterium infections are penicillins and metronidazole. in our patient, she was treated with piperacillin-tazobactam and metronidazole. a -year-old female patient presented with abdominal pain, nausea, and vomiting of one-week duration. she described an unremitting lower abdominal pain with pain intensity of / , located mainly in the suprapubic region, and was colicky in nature. she had a history of treated chlamydia infection two years ago. there was no history of any chronic illness, and her regular medications only included oral contraceptive pills. she worked in the food industry and did not go to work for the preceding weeks due to the covid- outbreak and the introduction of lockdown measures. on examination, she appeared jaundiced and demonstrated grade hepatic encephalopathy, as per the west haven score, as she was lethargic and minimally disoriented in time and place. she was very tender over the suprapubic region as well as moderately tender all over her abdomen without any rebound tenderness or rigidity. there was no ascites or stigmata of chronic liver disease. her observation parameters on admission were stable with a temperature of . -degree celsius, heart rate of beats per minute, respiratory rate of breaths per minute, blood pressure of / mmhg, and oxygen saturation of % on room air. interestingly, she was never pyrexial throughout her admission. speculum examination revealed brownish vaginal discharge and tenderness around the adnexa. cervical swab samples were sent to screen for gonorrhea and chlamydia, along with high vaginal swab for routine culture and sensitivity investigation. admission bloods are shown in table lactate level on the venous blood gas was initially . mmol/l and following intravenous (iv) fluid resuscitation, this improved to . mmol/l. she underwent ct imaging of the abdomen and pelvis which was later reported as normal, as it did not reveal any convincing etiology for her abdominal pain (figure ). further initial management included maintenance iv fluids, iv vitamin k milligrams once a day for three days, iv n-acetylcysteine (nac) infusion , milligrams over hours, iv piperacillin-tazobactam . grams thrice daily, alongside oral doxycycline milligrams twice daily, as there was a query of co-existing acute pelvic inflammatory disease (pid). early microbiology review raised a possibility of a fitz-hugh-curtis syndrome given her previous sexually transmitted disease (std) infection. however, this was invalidated as her screening tests for chlamydia and gonorrhea infection were subsequently negative. on day of admission, her blood cultures from the admission grew gram-negative bacteria in one of two of blood culture bottles and subsequent microbiobiolgy advice was to continue the same antibiotics. her urine culture was reported as negative. the advice from the microbiology team was to continue piperacillintazobactam and doxycycline. the microbiology team also requested that other intra-abdominal sources of infection, such as spontaneous bacterial peritonitis (sbp) or the upper urinary tract infection (uti), be investigated and considered in the differential diagnoses. however, these were deemed unlikely as the patient presented with no ascites and symptoms of uti were absent, in addition to the negative urine culture result. she was tested for viral and autoimmune hepatitis, which were all reported as negative. cytomegalovirus (cmv) and epstein-barr virus (ebv) igg assays were positive, but igm assays were negative suggesting no acute viral infection from these agents. covid- swab tests were negative on two separate occasions. fusobacterium nucleatum was later isolated in one of the two blood culture bottles with sensitivity to metronidazole. high vaginal swab result came back as heavy growth of mixed coliforms. the patient completed two-week course of iv antibiotics, consisting of tazobactam-piperacillin . grams thrice daily, in the first instance, which was subsequently changed to amoxicillin-clavulanate . grams thrice daily iv and metronidazole milligrams iv every eight hours. her liver function tests (lfts) improved gradually following the course of antibiotics as shown in table , her abdominal pain subsided, and she was discharged home. fusobacterium species colonize the mucous membranes of animals and humans and occasionally cause infections of oral cavity and head and neck. fusobacterium infections are relatively rare in the uk [ ] . hence, it is also referred to as the forgotten disease [ , ] . it has been reported that fusobacterium nucleatum is widely present in pregnancy complications, including premature birth and stillbirth [ ] , as well as intrauterine infections, including neonatal sepsis [ ] . other literature search of fusobacterium-related pathologies through medline revealed several case series, describing this microorganism as a common cause of lemierre's disease. this is a condition associated with anaerobic bacterial infection, starting as sore throat, progressing to severe systemic illness and formation of septic thrombophlebitis. metastasis to distant organs causing multi-organ failures may occur. gastrointestinal involvement of fusobacterium is often manifested as abscess collection or portal vein thrombosis [ ] . in some other cases, there has been an interest in the association of this bacterium with the development of colon cancer [ ] . in this case, the authors speculate that the source of her infection originated from the genital tract mucosa. the history of std and chronic vaginal discharge may have predisposed to the invasion of deeper tissues with this bacterium and subsequent hematogenous spread. fusobacterium nucleatum can invade the epithelial cells [ ] . adherence and invasion are essential mechanisms for colonization, dissemination, evasion of host defense, and induction of host responses [ ] . this is the viewpoint of the authors for the possible source of infection in this particular case; however, further studies will be required to show a link between female genital infection and bacteremia with this organism. incidence, risk factors, and outcomes of fusobacterium species bacteremia oxford handbook of infectious diseases and microbiology, e the forgotten disease: a case of lemierre's syndrome with distal extremity involvement clinical images. lemierre syndrome: the forgotten disease? comparative microbial analysis of paired amniotic fluid and cord blood from pregnancies complicated by preterm birth and early-onset neonatal sepsis fusobacterium nucleatum and adverse pregnancy outcomes: epidemiological and mechanistic evidence fusobacterium nucleatum bacteremia presenting with portal vein thrombosis: an abdominal lemierre syndrome? fusobacterium nucleatum positive colorectal cancer (review) interactions between periodontal bacteria and human oral epithelial cells: fusobacterium nucleatum adheres to and invades epithelial cells fusobacterium nucleatum: a commensal-turned pathogen sexually transmitted diseases. a practical guide for primary care this case highlights the rare incidence of acute hepatitis as a complication of fusobacterium nucleatum bacteremia, which was successfully treated with conservative management only. initially, potential diagnosis of fitz-hugh-curtis syndrome was raised. however, in fitz-hugh-curtis syndrome, the authors understand that the involvement of the liver parenchyma is minimal to none and it mainly affects the hepatic capsule [ ], causing hepatic-peritoneal adhesion. as a result, in fitz-hugh-curtis syndrome, lfts would typically be normal or minimally elevated [ ] . our case, on the other hand, presented with grossly deranged lfts, indicating an underlying liver parenchymal involvement. from this case, the authors would also like to highlight the importance of early initiation of antibiotics and fluids in the management of fusobacterium-related hepatitis, with close observation for development of any complications. acute hepatitis from bacterial infections such as fusobacterium can rarely happen, and the authors wish to raise the awareness of this condition. it is also important to consider sending blood cultures in a patient with abdominal pain and deranged lfts to diagnose this condition and initiate early antibiotic treatment. to the best of the authors' knowledge, this is a novel case where fusobacterium bacteremia was associated with acute hepatitis picture without abscess formation. human subjects: consent was obtained by all participants in this study. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- - javg m authors: kumar, jagdesh; katto, muhammad soughat; siddiqui, adeel a; sahito, badaruddin; jamil, muhammad; rasheed, nusrat; ali, maratib title: knowledge, attitude, and practices of healthcare workers regarding the use of face mask to limit the spread of the new coronavirus disease (covid- ) date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: javg m introduction many countries including pakistan are currently using face masks in their pandemic control plans. being highly prevalent, the correct use of these masks is particularly important, as an incorrect use and disposal may actually increase the rate of transmission. the purpose of this study was to investigate the knowledge, attitude, and practices of healthcare workers (hcws) in wearing a surgical face mask to limit the spread of the new coronavirus disease (covid- ). materials and methods this survey was conducted by interviewing hcws using a questionnaire consisting of the basic demographic characteristics, and the knowledge, attitude, and practices regarding the use of surgical face mask to limit the new covid- exposure. each correct answer was scored and each incorrect answer scored . the total number of questions was , and the final score was calculated and then labeled according to the percentage (out of ) of correct responses as good (> %), moderate ( - %), and poor (< %). results a total of participants with a mean age of . ± . years ( males and females) were included in the study. the overall final results were good in ( . %), moderate in ( . %), and poor in ( . %). around . % of participants knew about the correct method of wearing the masks, . % knew that there are three layers, % stated that the middle layer act as a filter media barrier, and . % knew the recommended maximum duration of wearing it. the majority ( . %) of participants knew that a cloth face mask is not much effective, around . % knew that used face mask cannot be re-used, and . % knew about the yellow-coded bag for disposal. conclusions knowledge, attitude, and practice of hcws regarding the use of face masks were found to be inadequate. studied hcws had a positive attitude but moderate-to-poor level of knowledge and practice regarding the use of face mask. hcws and general public awareness campaigns regarding the proper use of face mask by utilizing all social media available resources would be helpful during this pandemic. coronavirus disease (covid- ) is a respiratory illness caused by severe acute respiratory syndrome coronavirus (sars-cov- ), which first emerged in china in december , and has since spread to most countries around the world, resulting in the - coronavirus pandemic [ ] [ ] [ ] . the virus primarily spreads between people through respiratory droplets, which are produced when an infected person coughs or sneezes, or by touching contaminated surfaces or objects and then touching their own mouth, nose, or possibly their eyes. the risk of getting severe covid- is higher in health care workers (hcws) who are in close contact with confirmed covid- cases. the latest figures show thousands of hcws getting infected with a large percentage of them dying [ ] . in order to minimize risk, hcws are required to follow accepted infection control practices. aside from hand hygiene, one of the infection control measures is the routine use of a face mask. many countries including pakistan are currently using face masks in their pandemic plans. face mask works by providing a physical barrier between the mouth and nose of the wearer and potential contaminants in the immediate environment [ ] . in resource-limited settings, where the incidence of infectious disease is high and the environmental conditions of hospitals are often poor, hospitals may rely heavily on a face mask to protect medical staff against covid- and to prevent cross-contamination among patients and hcws. the use of a face mask among hcws is strongly recommended by the world health organization (who) and the centers for disease control and prevention (cdc) as a standard for transmission-based precaution [ , ] . moreover, the correct use of these masks is particularly important especially during this time when its use is becoming highly prevalent [ ] . the who states that incorrect use and disposal of this mask may actually increase the rate of transmission. if you wear a mask, then you must know how to use it and discard it properly [ ] . there is evidence that the hcws have inadequate knowledge and poor practice regarding the use of surgical mask [ ] . the purpose of this study was to investigate the knowledge, attitude, and practices of hcws in wearing a face mask particularly a standard surgical face mask to limit the spread of covid- . this cross-sectional community-based survey was conducted at the department of orthopedic surgery, dr. ruth k. m. pfau civil hospital, affiliated to dow university of health sciences, karachi, pakistan, in march (one month). the study participants were hcws, that is, consultant, medical officer, postgraduate trainee, house officer, and paramedical staff. a convenient sampling method was used and a sample size of was calculated, considering % precision, % confidence interval, and % as the correct practice of using face masks [ ] . keeping a minimum sample size of in mind, a total of patients were registered in the study duration. the study was conducted by interview using a semi-structured questionnaire. the questionnaire was developed with the help of previous literature on the proper use of surgical face mask and the guidelines of the centre for health protection and the cdc and consisted of two parts:( ) basic demographic characteristics (age, gender, job designation), and ( ) knowledge, attitude, and practices regarding the use of a face mask to limit covid- exposure [ , , ] . prior to the inception of the study, the nature and purpose of the study were explained to each respondent, and informed consent was obtained. for the convenience of analyses, each correct response in the knowledge category, good practice, or positive attitude was scored , and each incorrect response, bad practice, or negative attitude was scored . the total number of questions was , and the final score was calculated and then labeled according to the percentage (out of ) of correct responses as good (> %), moderate ( - %), and poor (< %). the information obtained from the participants was entered and analyzed using statistical package for the social sciences (sdss) statistics for windows, version . (ibm corp., armonk, ny, usa). mean with standard deviations were calculated for age and frequency with percentages for categorical variables. face masks are used as a protective barrier to reduce the risk of transmission of microorganisms between patients, hcws, and the environment [ ] . however, in order for face masks to provide effective protection, the hcws must have an intimate knowledge of wearing and disposing of those. in this study, . % of participants thought that they knew the proper steps of wearing a surgical face mask; however, only % obtained a good score by answering the procedural questions correctly. these results may be because of its simplest design, which leads many participants to mistakenly assume that they know the proper steps of wearing it. there was higher male participation in our study ( . %) compared with female participation ( %). this finding can be attributed to the higher male enrolment in our institution. in this study, . % of participants obtained an overall moderate-to-poor score regarding the correct usage of a surgical face mask. this low knowledge and practice may be because of recently circulating messages on social media claiming the proper way to wear the threelayered surgical mask, like "colored side facing out if you are sick, and the white side facing out if you want to 'stop the germs from getting in'". this is, however, false and misleading, according to nawhen, a columnist for medical mythbusters malaysia, a non-governmental organization that works to counter myths and inaccurate facts on medical matters; the correct way to wear a surgical mask is by wearing the colored side facing out independent of your health status. the outer colored layer is hydrophobic or is a fluid-repelling layer and its main function is to prevent germs from sticking to it, whereas the inner one is a hydrophilic layer that absorbs moisture from the air we breathe out. if you wear it the other way round, the moisture from the air will stick onto it, thus making it easier for germs to stay there. there is a middle layer that actually filters the microorganism [ ] . cloth mask, re-use of a surgical mask, and its extended use are commonly seen in pakistan during the extended outbreak of the covid- pandemic. it is highly unlikely for low-income countries that they will be able to provide disposable face masks for that extended period of time and may have to ration the use of these products. in this study, around . % hcws agreed that cloth mask is not as effective as a regular surgical mask and about . % knew that used surgical face mask cannot be re-used. around . % knew the correct maximum duration of using it. other studies also highlighted similar findings concluding that cloth mask, re-use, and extended use of mask makes it ineffective, still hcws are sometimes forced to do it due to the increasing shortage of these masks. we observed that wearing the same mask without removing it between patient encounters and disposing it properly at the end of the day is better than re-using it. still if re-using it due to shortage, it is better to fold the mask in such a way that the outer contaminated surface is held inward followed by storing it in a clean sealable paper bag or container [ ] [ ] [ ] . there is not enough evidence to prove that wearing a surgical mask protects every person from covid- . the who currently recommended that only hcws and people who are ill and those who are caring for the ill need to wear a mask to protect themselves from covid- . however, in low-income countries like pakistan, where the incidence of infectious disease is high and the hospital environmental conditions are often poor, our hcws rely almost entirely on a face mask to limit the spread of covid- [ ] . the who established a color-coded bin system for proper disposal of biomedical waste in hospitals [ ] . however, when it was asked from our participants, . % disposed it in the yellow-coded bag for disposal of face mask; this shows poor knowledge of hcws regarding the safe disposal of biomedical waste. some of the limitations of this study include the cross-sectional nature of study design limited to a single governmental hospital. further longitudinal studies should be carried out on a larger sample size, and both private and government hospitals should be included before the results could be generalized. moreover, different types of masks can be compared. knowledge, attitude, and practice of hcws regarding the use of surgical face masks were found to be inadequate. studied hcws had a positive attitude but moderate-to-poor level of knowledge and practice regarding the use of surgical face mask. hcws and general public awareness campaigns regarding the proper use of face mask by utilizing all social media available resources would be helpful during this pandemic. rd: features, evaluation and treatment coronavirus (covid- ). statpearls. statpearls publishing epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (covid- ) during the early outbreak period: a scoping review world health organization declares global emergency: a review of the novel coronavirus (covid- ) clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study use of face masks in a primary care outpatient setting in hong kong: knowledge, attitudes and practices. public health guideline for isolation precautions: preventing transmission of infectious agents in health care settings advice on the use of masks in the community, during home care and in healthcare settings in the context of the novel coronavirus ( -ncov) outbreak: interim guidance wearing face masks in public during the influenza season may reflect other positive hygiene practices in japan how effective are face masks in operation theatre? a time frame analysis and recommendations use mask properly knowledge, perceptions and practices of healthcare workers regarding the use of respiratory protection equipment at iran hospitals show your colours: only one way to wear surgical masks correctly, with the coloured side out use of cloth masks in the practice of infection controlevidence and policy gaps a cluster randomised trial of cloth masks compared kumar et al. cureus ( ): e . doi healthcare workers contamination by respiratory viruses on outer surface of medical masks used by hospital healthcare workers covid- ) advice for the public: when and how to use masks safe management of wastes from health-care activities human subjects: consent was obtained by all participants in this study. dow university of health sciences and dr. ruth k. m. pfau civil hospital issued approval ortho/duhs/ / . animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -p sz bj authors: kabashneh, sohaip; al-sagri, zaynab; alkassis, samer; shanah, layla; ali, hammad title: diabetic ketoacidosis complicated by a brain death date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: p sz bj diabetic ketoacidosis (dka) is a life-threatening complication of diabetes mellitus (dm). cerebral edema (ce) can complicate dka management. we report a patient with no significant medical history who presented with dka and a new-onset dm; she received the standard management with regular insulin and iv fluids, the management resulted in a rapid drop in serum osmolality, the patient`s mental status deteriorated and became nonresponsive, brain imaging confirmed ce, a few days later the patient was declared brain dead by neurology. this case highlights the importance of gradual correction of hyperosmolar conditions including hyperglycemia and urges all healthcare providers to closely trend glucose levels in the management of dka. diabetic ketoacidosis (dka) is an acute, life-threatening complication of diabetes mellitus (dm) occurring more commonly in type one dm. dka is characterized by elevated blood glucose, anion gap metabolic acidosis, and ketonemia [ ] [ ] [ ] . osmotic diuresis due to hyperglycemia leads to volume depletion and electrolyte imbalance which are the hallmark of the disease process [ ] . the backbone of management in dka consists of fluid resuscitation, electrolyte repletion, and hyperglycemia correction by insulin infusion. hypoglycemia and hypokalemia are the most common complications of the treatment of dka. however, cerebral edema (ce), although infrequent, can lead to devastating outcomes, especially in the younger population. we present a case of a young patient who presented with dka; her management was complicated by a rapid drop in plasma osmolality and subsequently developed ce and brain death. we present a -year-old female with no previous medical history who was brought to the hospital by her parents. two days prior she became nauseated and had one episode of emesis, then she became sleepy and subsequently became less responsive. on initial assessment, she was obtunded, had a temperature of . °c, a heart rate of beats per minute, a blood pressure of / mmhg, oxygen saturation of % on room air. on neurological assessment both pupils were three millimeters, equal and reactive to light, her eyes were open spontaneously, she was moving all her limbs spontaneously, but was not following command, she was also making incomprehensible sounds, not responding to questions. the examination of her lungs, heart, and abdomen was unremarkable. table ) . a urine drug screen was negative. infectious workup with chest x-ray, covid- nasal swab, urine analysis, urine culture, and blood culture were done but were unremarkable. she was started on an insulin drip and iv fluids for dka, in less than hours a repeat lab is done ( table ). later on the second day of admission, her mental status deteriorated further, she became none responsive, her glasgow coma scale (gcs) dropped to three and she was subsequently intubated for airway protection and her ventilator settings were set at a respiratory rate of breaths/minute, a tidal volume of ml, a fraction of inspired oxygen of %, and a positive end-expiratory pressure of five cm h o. ct scan of her brain was obtained quickly and showed changes consistent with ce ( figure ). neurology team was consulted, she had electroencephalography (eeg) done which showed moderate to severe degree of cerebral dysfunction consistent with metabolic/hypoxic encephalopathy, the waveforms were not epileptiform in nature. despite multiple interventions including lowering paco to - mmhg, hypertonic saline %, pentobarbital coma, and cooling the patient to °c ( °f), she did not show any signs of improvement. on the third day and fourth day of admission, her condition continued to worsen, and so on the fifth day and because she was not exhibiting response to painful stimuli, no brainstem reflexes, neurology proceeded with a brain death exam, which she had no arousal to voice or sternal rub, no withdrawal to painful stimuli, no cough response, gag or corneal reflexes, her pupils were dilated and fixed, nonreactive to light. symptomatic ce occurs in % of dka cases [ ] . however, subclinical edema occurs in almost half of dka patients and can be detected by brain imaging [ ] . the affected population is usually younger than years with most cases occurring in dka [ ] . the most common risk factors for developing ce are newly diagnosed dm, young age, first episode of dka, severity of dka, and administration of bicarbonate [ ] . symptoms develop within - hours of the initiation of treatment but may be present before the onset of management. the first manifestation is a headache, followed by lethargy and decreased arousal. seizures, incontinence, pupillary changes, bradycardia can develop with the worsening of edema. ce is a life-threatening complication, brain herniation is the leading cause of death in dka-associated ce, it has a mortality rate of %- % [ ] . cerebral edema develops when fluid moves from the extracellular to the intracellular compartment faster than the brain cells can adapt to increased intracellular volume [ ] . this can happen when there is rapid correction of hyperglycemia, leading to a sudden drop in serum osmolality. the pathophysiology of ce in hyperglycemic crises is not fully understood. the correction of hyperglycemia is usually accompanied by a concurrent rise in serum sodium, which ameliorates the rapid drop in serum osmolality if blood glucose is corrected isolation. another mechanism involves idiogenic osmoles, which are osmotically active substances produced within brain cells during periods of extracellular hyperosmolality to counteract the osmolar imbalance. these idiogenic osmoles have a slow clearance rate, resulting in high intracellular osmoles which can lead to the movement of extracellular fluid into the intracellular space [ ] . in order to reduce the risk of ce in high-risk patients, in the american diabetes association (ada) recommended the following measures to reduce the risk of ce in high-risk patients [ ] : ) gradual replacement of sodium and water deficits in patients who are hyperosmolar. the usual fluid regimen with isotonic saline can be started at a rate of - ml/kg/h with a maximum of < ml/kg in the first two to three hours. ) avoidance of rapid reduction of plasma osmolarity, and a gradual decrease in serum glucose. dextrose should be added to the saline solution once the serum glucose levels have fallen to mg/dl in dka, the serum glucose should be maintained at - mg/dl until the patient's serum osmolality has normalized. there is limited data regarding the effectiveness of ce treatment in adults. recommendations depend on clinical judgment without scientific evidence. small series in children suggest benefit from prompt administration of mannitol ( . - g/kg) [ ] . some case reports suggest the use of hypertonic ( %) saline ( - ml/kg over minutes) as an alternative to mannitol [ ] [ ] . intubation may be indicated for airway protection, hyperventilation (pco < mmhg) in those patients has been associated with worse outcome, therefore, should be avoided unless necessary [ ] . diabetic ketoacidosis is associated with an increase in serum osmolality. the management typically includes insulin drip with a goal to decrease blood glucose and close the anion gap. rapid correction of blood glucose and serum osmolality can lead to ce, particularly in children and adolescents. slow correction and close monitoring of serum glucose and osmolality is essential to avoid such a devastating event. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared hyperglycemic crisis in adults: pathophysiology, presentation, pitfalls, and prevention euglycemic diabetic ketoacidosis: a review fatal cerebral edema in a young adult with diabetic ketoacidosis: blame the bicarbonate cerebral oedema in diabetic ketoacidosis in children cerebral edema in diabetic ketoacidosis -fluid shifts and shifting paradigms causes of death in children with insulin dependent diabetes - . arch dis childhood diabetic ketoacidosis in infants, children, and adolescents: a consensus statement from the american diabetes association overview of cerebral edema during correction of hyperglycemic crises hyperglycemic crises in adult patients with diabetes. diabetes care diabetic ketoacidosis with intracerebral complications use of hypertonic saline in the treatment of cerebral edema in diabetic ketoacidosis (dka) use of hypertonic saline for the treatment of altered mental status associated with diabetic ketoacidosis. pediatric crit care med factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- - js authors: rai, harpreet k; john, geevarghese; anton, maria title: atypical presentation of panhypopituitarism date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: js hypopituitarism is a rare disorder. hypopituitarism can present as a deficiency of individual anterior pituitary hormones (e.g., adrenocorticotropic hormone, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, prolactin, growth hormone) or posterior pituitary hormones (e.g., oxytocin, vasopressin) or as the deficiency of all these pituitary hormones, also known as panhypopituitarism. here, we discuss a -year-old man who presented with two episodes of unwitnessed syncope after an episode of vomiting. on admission, the patient was hypotensive to / mmhg, afebrile, and with a leukocyte count of . k/µl (reference range: . to . k/µl). ct scan of the head revealed a hyperdensity in the left intracranial internal carotid artery just proximal to the bifurcation, suggesting an artifact or presence of an embolus. additional findings included a sellar mass with calcifications and suprasellar extensions. the patient was admitted for further workup of syncope. other differential diagnoses included sepsis, stroke, cardiac arrhythmias, and pulmonary embolism. sepsis, stroke, and cardiac workup were negative for significant findings. the patient remained persistently hypotensive despite aggressive intravenous hydration, raising suspicion for an underlying endocrine disorder. mri of the brain was negative for stroke but again was significant for a sellar mass. additional workup showed a deficiency of all the anterior pituitary hormones likely secondary to mass effect. the patient was diagnosed with panhypopituitarism due to pituitary macroadenoma. there are fewer than , patients with hypopituitarism in the united states [ ] . the global incidence is estimated to be . cases per , patients per year [ ] . a study from northwestern spain conducted by regal et al. reported a prevalence of . cases per , population [ ] . damage to the anterior pituitary can be mild or severe, can present precipitously or insidiously, and can affect the secretion of one or more of its hormones. as a result, hypopituitarism has a wide range of clinical presentations. pituitary apoplexy, for example, presents with the rapid development of symptoms causing sudden impairment of adrenocorticotropic hormone (acth) secretion and, consequently, the sudden onset of cortisol deficiency symptoms. on the other hand, radiation damage to the pituitary takes time to present. clinical presentation can also vary, depending on the severity of the hormonal deficiency. the causes of hypopituitarism include pituitary tumor ( %), nonpituitary tumor ( %), or a nontumor cause ( %) [ ] . hypopituitarism can result from diseases of the pituitary gland or diseases of the hypothalamus. the diseases affecting the pituitary gland secretions include mass lesions, surgery, and radiation to treat mass lesions. hereditary hemochromatosis, hypophysitis (including lymphocytic, granulomatous, plasmacytic, and xanthomatous), pituitary infarction (sheehan syndrome), pituitary apoplexy, and pituitary infection are among the rare causes of this condition. we describe a patient who presented following a syncopal episode with a wide range of differential diagnoses based on initial laboratory results, clinical course, and workup, ultimately leading to the diagnosis of panhypopituitarism. a -year-old man with past medical history of hyperlipidemia presented to the ed following two episodes of unwitnessed syncope. the patient reported a sudden onset of nausea and vomiting prior to these episodes. he described a room-spinning sensation when he awoke associated with ringing in the ear. he regained consciousness within one to two minutes. while attempting to stand, he again lost consciousness. in the ed, the patient denied any symptoms. in the ed, his physical examination was significant for symptomatic orthostatic hypotension. vitals included blood pressure of / mmhg and a heart rate of beats/minute. the patient was afebrile. the patient's initial laboratory workup results are presented in table . his electrocardiogram showed normal sinus rhythm. his chest x-ray findings were unremarkable. a ct scan of the patient's head showed an apparent hyperdensity in the left intracranial internal carotid artery just proximal to the bifurcation, representing an artifact or the presence of an embolus. it also showed an apparent sellar mass with calcifications and suprasellar extension. a ct scan of the abdomen showed cholelithiasis and was negative for any acute pathology. the patient was admitted for further evaluation of syncope. sepsis was considered given his leukocytosis and hypotension. a ct scan of the head showing a questionable embolus was followed by a neurological evaluation to test for a possible stroke. the patient was admitted to a telemetry unit to rule out syncope due to cardiac arrhythmias. intravenous fluids were started to treat his hypotension. on the patient's second day of admission, the intensive care unit team was consulted for persistent hypotension. intravenous hydration was recommended along with a follow-up workup for sepsis and pulmonary embolism. a morning cortisol level was also ordered to rule out adrenal insufficiency. the patient was not started on antibiotics at that time as he remained afebrile, the leukocyte count normalized, and the blood culture showed no bacterial growth. a ct angiogram of his chest was significant for a small filling defect in a right upper lobe segmental pulmonary artery, compatible with pulmonary embolism. the patient was not started on therapeutic anticoagulation as a follow-up ventilation-perfusion scan showed low probability for pulmonary embolism. the patient underwent a cardiology evaluation for syncope and suspected underlying arrhythmia. telemetry monitoring was negative for significant cardiac arrhythmias. echocardiography showed an ejection fraction of %, normal diastolic function, and normal valves. the results of his neurological exam were benign, as the patient had no focal weakness and reflexes were normal. mri of the brain with contrast was negative for a stroke but was significant for an enhancing mass filling and expanding the sella turcica, measuring . cm caudally, . cm anteroposteriorly, and . cm transversely. it encroached on and elevated the optic chiasm (figures , ) . on the patient's third day after admission, his morning cortisol level was inappropriately low ( . µg/dl; reference range: . to . µg/dl). the endocrinology team was consulted over concerns for secondary adrenal insufficiency due to the sellar mass. a cosyntropin stimulation test showed maximum cortisol elevation to . µg/dl. table present the patient's hormone level results. he was diagnosed with central hypothyroidism, then panhypopituitarism due to the pituitary macroadenoma. the patient was started on hydrocortisone, -mg tablet in the morning and -mg tablet in the evening, along with levothyroxine, -mcg tablet once daily. the patient was discharged with recommendations for outpatient follow-up with the endocrinology team for continued monitoring of his pituitary hormone level deficiencies and sellar mass. outpatient ophthalmology follow-up was also recommended for visual field assessment, as the mass was causing elevation of the optic chiasm. finally, his care team recommended outpatient neurosurgery follow-up evaluation for possible surgical resection of the mass. the outpatient follow-up assessments were ultimately delayed due to the novel coronavirus disease (covid- ) pandemic. syncope is a common presenting symptom in the er, accounting for % to % of er visits and a hospitalization rate in approximately % of cases. the average length of stay for evaluation of syncope is . days [ ] . after reviewing the history, physical examination findings, and electrocardiogram, er physicians can determine the underlying diagnosis in approximately % of cases [ ] . patients admitted to the hospital for further workup of syncope usually undergo an extensive cardiac and neurological assessment. according to a study performed on patients with syncope, an etiology could not be identified in % of patients [ ] . the patient presented above was diagnosed with a sellar mass leading to hyposecretion of all the pituitary hormones. his symptoms were mainly related to acth deficiency (secondary adrenal insufficiency). symptoms of acth deficiency are exclusively related to cortisol deficiency. cortisol is necessary for peripheral vascular tone. in its most severe form, cortisol deficiency leads to death due to vascular collapse. milder symptoms of the same phenomenon include postural hypotension and tachycardia. an acth deficiency does not affect aldosterone secretion (which is present in primary adrenal insufficiency); therefore, it does not cause salt wasting, volume contraction, or hyperkalemia. hyponatremia can be present because cortisol deficiency can cause inappropriate secretion of antidiuretic hormone (vasopressin). our patient presented with normal electrolytes as mentioned in table , that is, he did not have signs of salt wasting or volume contraction. acth deficiency does not cause hyperpigmentation, which is a symptom of primary adrenal insufficiency due to a reflex increase in acth. the treatment of hypopituitarism is focused on the supplementation of the individual deficient hormones to restore the body's natural physiology. this provides relief of symptoms with minimal side effects. the patient was started on hydrocortisone and levothyroxine supplementation. outpatient endocrinology follow-up was recommended for continued hormone monitoring and testosterone replacement therapy. transsphenoidal surgery is the mainstay of treatment for most sellar masses and would be a potential therapy for this patient. however, due to the covid- pandemic, the outpatient follow-up has been delayed. syncope is a common presenting symptom in the er. postural hypotension and syncope are the most common presentations of secondary adrenal insufficiency and panhypopituitarism. evaluation of syncope rarely includes a thorough endocrine workup. in this case, endocrinology workup was started after neurological, cardiac, and septic evaluations were insignificant. clinicians should be mindful of considering endocrine causes as a differential for syncope at the time of presentation. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. prevalence and incidence of hypopituitarism in an adult caucasian population in northwestern spain syncope: epidemiology, etiology, and prognosis diagnosing syncope. part : value of history, physical examination, and electrocardiography. clinical efficacy assessment project of the american college of physicians evaluation and outcome of patients with syncope key: cord- -tqxvu pu authors: iqbal, phool; ata, fateen; rose, samman; chaudhry, hammad s; rahil, ali title: should we rely on screening tests for further management alone in polymerase chain reaction negative covid- patients? a case series date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: tqxvu pu since the declaration of coronavirus disease (covid- ) disease as a pandemic by the world health organization (who), it has been a challenge to the whole medical community. researchers and clinicians have been trying to explain and explore its mechanism and pathophysiology to get a better understanding of this disease, as it has exhausted the healthcare resources and has impacted human life in general. many tests have been developed including polymerase chain reaction (pcr) of the virus and rapid diagnostic testing in patients based on igm/igg serology. but owing to variable sensitivity and specificity of these tests, it has created a challenging situation to proceed with the further management plan. we are reporting a case series where we experienced the dilemma of diagnosing covid- disease in our patients and further plan of care. the coronavirus disease (covid- ) outbreak was declared a worldwide pandemic by the world health organization (who) on march [ ] . because this disease is new to the medical community, there have been challenges in diagnosing and treating its various clinical manifestations. currently, the ongoing research has resulted in many published research articles that can provide some insight, but the dilemma, related to the diagnostic testing for the virus and further management plans, prevails. the genexpert express system technology uses the polymerase chain reaction (pcr) to detect the severe acute respiratory syndrome-coronavirus- (sars-cov- ) obtained from nasopharyngeal swabs. herein, we report our experience with covid- patients who were tested multiple times using this system but were negative for the sars-cov- virus. however, improvement was observed in the clinical condition of the patients who were managed as per covid- protocol based upon the clinical signs and symptoms after correlating with diagnostic chest imaging studies. laboratory investigations were remarkable for lymphopenia, high d-dimer, c-reactive protein (crp), and ferritin. the infectious disease team advised testing with covid- serology (immunoglobulin (ig) m and igg antibodies through lateral flow assay), the results of which were positive, indicating recent infection. he was maintained on isolation protocols for covid- , and treatment was administered based on local guidelines. he improved during his hospital stay with no further clinical deterioration and was discharged home with follow-up in the outpatient department. a -year-old bangladeshi man with type diabetes presented to the hospital with a dry cough and fever lasting for four days. he initially sought treatment from a private hospital, where he received oral antibiotics. due to the worsening of his symptoms, he presented to the ed of our hospital. on clinical examination, he maintained oxygen saturation in room air but was in respiratory distress with mild tachypnea of - breaths per minute. his respiration system examination was unremarkable, although his cxr ( figure b) revealed basal nonhomogeneous opacities. laboratory investigations were significant for elevated inflammatory markers, specifically, crp, ferritin, and d-dimer. his blood cultures and pcr test for respiratory viruses (adenovirus, influenza viruses, par influenza viruses, rous sarcoma virus (rsv), human rhinovirus, enterovirus, and other coronaviruses, including middle east respiratory syndrome (mers) coronavirus and sars-cov- ), were negative. during the hospital stay, multiple nasopharyngeal swab samples were obtained, and pcr tests were performed to detect covid- on the swabs. five of the repeated tests were negative, and one was inconclusive. the infectious disease team was consulted and based upon his clinical presentation and previous investigations, the patient was maintained on the local management protocol for covid- infection. clinical improvement was noted, and then, he was discharged home without any complications. a -year-old nepalese man with no past medical history presented with fever, dry cough, and sore throat lasting for five days. upon presenting to the ed, he maintained normal oxygen saturation at room air, but hours later, he required l/min of oxygen through a nasal cannula to maintain his oxygen saturation above %. his body temperature was higher than °c. his cxr ( figure c) showed ill-defined opacity in the right middle and lower zones in the perihilar region. the complete respiratory viral panel (adenovirus, influenza viruses, par influenza viruses, rsv, human rhinovirus, enterovirus, and other coronaviruses, including mers coronavirus and sars-cov- nasopharyngeal swab) was negative. there was suspicion of mycobacterium tuberculosis infection based upon cxr findings, but his tb workup (acid-fast bacillus smear and quantiferon test) was negative. laboratory investigations were remarkable for high inflammatory markers, including crp and ferritin. the pcr test for covid- was performed four times from nasopharyngeal swabs. three of the test results were inconclusive, while one was negative. rapid serology (lateral flow assays) tests for igm and igg antibodies were positive and indicated recent infection. the infectious disease team was consulted, and based on his clinical picture, he was managed based upon covid- local treatment guidelines. he improved and did not require further oxygen supplementation. he was discharged home. a -year-old healthy indian man without any past medical history came to the hospital with a high-grade fever of more than °c and a dry cough lasting for seven days. the patient was maintaining saturation on room air. cxr showed bilaterally patchy consolidation at the bases ( figure d ). septic workup was performed, consisting of pcr for respiratory viruses (including covid- ) from a nasopharyngeal swab, blood cultures, tb workup, and urine culture. however, the results were unremarkable for any source of infection. his crp and ferritin levels were high. after two days, the patient required oxygen supplementation through a nasal cannula at - l/min. the infectious disease team was consulted, and the covid- pcr test was repeated four times. the first two samples were negative, the third sample was inconclusive, and the fourth sample turned out to be positive. he was managed using the covid- pneumonia local guidelines. his condition improved, and he did not require further oxygen. due to its highly contagious nature, sars-cov- has spread worldwide, and the covid- global pandemic has adversely affected the economy, healthcare resources, and social interactions. the disease primarily affects the pulmonary system and may cause fever, cough, anosmia, loss of taste, and shortness of breath that may develop sufficient severity so that endotracheal intubation is required. other various atypical presentations include diarrhea and hyponatremia [ ] [ ] . healthcare professionals across the world have been tailoring their diagnostic approach and treatment according to the local requirements and available limited evidence. the dilemma of a diagnosis based on less sensitive and specific tests or atypical presentations may cause complications due to delay in the management of covid- patients. the reverse transcription-pcr (rt-pcr) test for covid- is the most widely used method for screening purposes [ ] . although the sensitivity of this test is considered to be up to %, large-scale testing can lead to an increase in the number of false-negative cases, which contributes to further spreading of the virus in the community [ ] [ ] . in one study, the sensitivity of the rt-pcr test for patients was found to be highly variable, with % for bronchoalveolar lavage, % for sputum, % for nasal swabs, and only % for throat swabs. moreover, the accuracy also depends upon certain other factors such as the stage of the disease, degree of viral multiplication or clearance, and if multiple genes are being tested [ ] . other tests currently used for suggestive covid- infection are the rapid antibody detection test, ct of the chest, and biomarkers in the blood [ , [ ] [ ] . serology with rapid antibody detection has recently been introduced to estimate the immunity against covid- infection, but the time course and accuracy of serology tests are still under investigation [ ] . ct of the chest has been widely used due to typical changes related to covid- infection that occur, (i.e., peripheral ground-glass opacities seen in the lungs) [ ] . however, falsenegative ct scan rates vary in the literature, ranging from % to % in rt-pcr-positive patients [ ] . artesi et al. highlighted this point in their study, where they assessed multiple rt-pcr methods and concluded that methods targeting a single genome could be unreliable [ ] . one of their studied mutations was in the e gene. while using the cobas® system (f. hoffman-la roche ag, basel, switzerland) for studying the reverse transcription of eight samples, it was found that they were negative for e gene reverse transcription but positive for orf ab reverse transcription. four samples were retested by targeting the rdrp and e genes via the taqman fast virus -step master mix (thermo fisher scientific, waltham, ma) sars-cov- , which was described by corman et al. [ ] . other tests currently used for suggestive covid- infection are the rapid antibody detection test, chest ct examination, and biomarkers in the blood [ , [ ] [ ] . serology with rapid antibody detection has recently been introduced to estimate the immunity against covid- infection, but the time course and accuracy of serology tests are still under investigation [ ] . chest ct has been widely used as well, due to typical changes related to covid- infection; however, false-negative ct scan rates vary in the literature, ranging from % to % in rt-pcr-positive patients [ ] . therefore, the lack of a clear-cut gold standard test for covid- infection creates a challenge for the medical community [ ] . the idea of a pretest probability can be applied here. pretest probability is high when a patient exhibits typical symptoms such as cough, fever, shortness of breath, history of exposure, and when a patient originates from a geographical location with a high prevalence of the disease [ ] . moreover, biomarkers such as crp, ferritin, lymphocyte counts, lactate dehydrogenase, and n-terminal pro b-type natriuretic peptide, along with radiological findings in cxr or features such as unilateral or bilateral pneumonia, ground-glass opacities, or consolidations in a chest ct scan, can suggest covid- infection even in such patients where rt-pcr alone is negative [ ] . there have been inconsistencies in the guidelines for treating patients with covid- . hydroxychloroquine, a drug used to treat malaria and systemic diseases such as rheumatoid arthritis and systemic lupus erythematosus, was effective in inhibiting the growth of the virus in in-vitro studies. early data supported its role in the management of covid- pneumonia [ ] . however, it was associated with an increase in inpatient hospital mortality [ ] . anti-retroviral drugs, specifically, lopinavir and ritonavir, were also used for the treatment of covid- infection [ ] . later, cattaneo et al. found them to be ineffective in a prospective randomized, open-label trial [ ] . as the pandemic progressed, in vitro experimentation led to the use of several drugs or their combination, including chloroquine, hydroxychloroquine, azithromycin, ribavirin, favipiravir, and interferons. however, promising results in improving survival have currently been obtained only with remdesivir and steroids, particularly dexamethasone [ ] . in critical cases of covid- , where the patients exhibit hypoxia and high inflammatory markers, tocilizumab and convalescent plasma have also been used in combination with other drugs. however, as of june , there is no licensed medication for covid- treatment [ ] . there have been numerous cases in our center, where the rt-pcr test for sars-cov- was performed multiple times, and the results were inconclusive repeatedly. nevertheless, if the overall clinical picture concerning signs and symptoms is consistent with a probable viral respiratory infection, and laboratory tests indicate inflammation, then this is suggestive of sars-cov- infection. in these patients, acute symptoms of upper respiratory tract infection, such as sore throat, fever, shortness of breath, and myalgia, were suggestive of sars-cov- infection. high crp, high ferritin, and d-dimer were measured in all patients, while lymphopenia was observed in one of the patients ( table ) . although these are nonspecific findings, in the current literature, these findings are very likely to suggest sars-cov- infection [ ]. we also performed septic and tb workups to rule out secondary infections that can present in the same manner. the results were unremarkable. however, cxr of all patients revealed bilateral nonhomologous opacities involving different zones of the lung field, which has been recently described in association with covid- [ ] , as shown in figure . based on the patients' signs and symptoms, they were managed with isolation protocols and local guidelines. they improved within the covid- recovery period based on mild to moderate pneumonia with no further deterioration during their hospital stay, and this further consolidated our diagnosis [ ] . positive covid- rt-pcr indicates confirm covid- case, but in our case , the patient did not test positive for rt-pcr and therefore labeled and managed as "probable covid- " due to the clinical picture and suggestive radiological imaging correlating with the infection [ ] . on the other hand, the patients did not undergo ct scan imaging which is more sensitive than cxr. the rationale behind this is, that the cxr of all the patients was remarkable of unilateral/bilateral nonhomogenous opacities which is also attributed to covid- [ ] . and the laboratory findings were also suggestive. serological testing is also helpful to suggest covid- infection, however, it can be false-negative in an asymptomatic patient or who has been recently exposed but still, the body immune response did not develop sufficient detectable antibodies. in our cases, the patients were symptomatic, and positive serology testing indicates exposure and symptoms onset of more than five days [ ] . such cases can be easily missed in this pandemic state if a proper clinical and correlating investigational approach is lacking leading to unnecessary exposure to frontline health workers. currently, a single test that can accurately detect sars-cov- infection does not exist. there are high falsenegative rates even on repeated tests. there is a risk that sars-cov- will be spread in the hospital and community settings when false-negative test results are obtained. in such a situation, we should apply the idea of pretest probability based on the patient's history, clinical signs and symptoms, suggestive biomarkers in the blood, and radiological imaging. hence, after a literature review and taking into account our experience, we have proposed an algorithm to identify patients with high clinical suspicion of covid- and to treat the patient for covid- despite negative rt-pcr results ( figure ) [ ] . however, there is a need for larger-scale clinical studies to validate this pathway and establish it as a recommendation. rt-pcr, reverse transcription-polymerase chain reaction; crp, c-reactive protein. the covid- pandemic is a challenging global situation with various amounts of false-negative testing that occurs during the process of diagnosis. therefore, we recommend that a structured approach based on previous studies and evidence should be used rather than one testing modality if there is high clinical suspicion of sars-cov- infection. human subjects: consent was obtained by all participants in this study. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. an overview of covid- covid- presenting with diarrhoea and hyponatraemia covid- testing a composite reference standard for covid- diagnostic accuracy studies: a roadmap interpreting a covid- test result managing high clinical suspicion covid- inpatients with negative rt-pcr: a pragmatic and limited role for thoracic ct serology testing in the covid- pandemic response clinical characteristics of asymptomatic infections with covid- screened among close contacts in nanjing a recurrent mutation at position , of sars-cov- is associated with failure of the e-gene qrt-pcr utilized in a commercial dual-target diagnostic assay detection of novel coronavirus ( -ncov) by real-time rt-pcr. eurosurveillance. breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of covid- associated pneumonia in clinical studies covid- : who halts hydroxychloroquine trial to review links with increased mortality risk does lopinavir really inhibit sars-cov- ? diagnosis and treatment of coronavirus disease (covid- ): laboratory, pcr, and chest ct imaging findings effects of age and sex on recovery from covid- : analysis of israeli patients key: cord- -xx xbjqu authors: malik, talia title: covid- and the efficacy of different types of respiratory protective equipment used by health care providers in a health care setting date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: xx xbjqu coronavirus, the virus that caused the global pandemic at the beginning of and affected millions across the globe, presented as an enormous challenge to health care providers around the world. with increasing numbers of infected patients presenting daily, health care workers are struggling to take effective measures to protect themselves from transmission against the highly contagious coronavirus. this case helps us understand the implications of coronavirus-infected patients on the health care providers directly responsible for the management of these patients and the relative efficacy of different types of respiratory protective equipment mainly n masks and surgical masks in preventing the spread of infection among those at the front lines providing care. the coronavirus (covid- ) was declared a global pandemic by world health organization (who) on march , after it was known to originate from wuhan, china, and resulted in more than , confirmed cases around the world at the time [ , ] . very little is known about its effect among those responsible for its management and treatment, primarily the doctors, nurses, and the first responders. the coronavirus causes an acute respiratory infection that is transmitted by contact and droplet routes. the use of personnel protective equipment (ppe), such as surgical gloves, face masks, eye protection, and regular hand washing, is known to limit the spread of the virus, but little is known about the relative efficacy of n masks over the regular surgical masks in preventing the transmission of the virus among health care workers (hcws). this aspect of identifying the superior type of respiratory protective equipment (rpe) is of significant importance in order to provide maximal protection to hcws, prevent medical equipment shortages, and to lessen the burden on manufacturers and suppliers of this equipment. both types of face masks are known to prevent the transmission of respiratory particles; however, the n masks are thought to have a superior efficacy by filtering out very small particles. in spite of having many benefits, the n masks have certain limitations and it is important to understand if the benefits outweigh the risks when compared to surgical masks. this case helps us better understand the efficacy and benefits of different types of rpe used by hcws during the management of patients infected with the coronavirus. a -year-old woman with a history of diabetes mellitus was admitted to the intensive care unit (icu) in early march for severe shortness of breath. she had recently returned from a trip to iran and was suspected to have been in contact with people infected with the coronavirus. on admission, she was given high-flow supplemental oxygen that slightly improved her shortness of breath; however, after a few hours, her respiratory status worsened and she was intubated and mechanically ventilated in the icu. the hcws who performed the aforementioned procedures used either the n mask or the surgical mask depending upon availability and personal preference. the patient's respiratory status gradually improved over a period of two days. in accordance with existing guidelines, the patient was extubated and shifted to the isolation ward for further management. three samples of nasopharyngeal swabs were obtained from the patient for three consecutive days for covid- testing and all came out positive for severe acute respiratory syndrome coronavirus (sars-cov- ) on polymerase chain reaction (pcr) assay. all the hcws exposed to the patient were isolated and quarantined for a period of days. information was obtained about the type of rpe used by each hcw during exposure to the patient. half of the hcws used surgical masks, whereas the rest used n masks as the rpe while performing procedures on the infected patient. during this period of quarantine, routine surveillance monitoring for cough, shortness of breath, and muscle aches was made. two samples of nasopharyngeal swabs were obtained from the hcws on the day of exposure and the last day of quarantine for covid testing via the pcr assay. each hcw remained asymptomatic and tested negative for covid on both tests. the coronavirus is known to spread through aerosolized particles. hcws are at an increased risk of being infected without proper ppe and protective measures. this case highlighted the importance of evaluating the efficacy of different rpe during a viral pandemic in protecting the hcws from the transmission of infection. none of the hcws who were exposed to the virus tested positive for covid- despite using the different types of rpe. this helps us in determining the relative efficacy of surgical masks and n masks over one another in preventing the transmission of the virus among hcws. it can also be deduced that both types of rpe offer equal protection to hcws from the virus; however, these findings need to be validated by well-designed large-scale studies. the observation made in this case report was also highlighted by a previous study which showed that n masks were not superior to surgical masks for preventing influenza infection among hcws [ ] . another study concluded that there was no significant difference between n mask and surgical masks in preventing the risk of transmission of respiratory infections from infected patients [ ] . although the above studies showed no significant difference in efficacy of both types of rpe, it is vital to understand that different infectious agents have different mechanisms of transmission and action, and hence large-scale randomized controlled trials (rcts) need to be conducted to better understand the particular pattern and characteristics of sars-cov that differentiate it from other respiratory infectious agents with similar features. the n mask is thought to be superior to the surgical masks. these masks are known to filter out % of small airborne particles including bacteria and viruses. they have been tested and approved by the national institute of occupational safety (nios); however, there are certain limitations to its use. since breathing while wearing the n mask is harder, it is not recommended for the elderly, claustrophobics, and individuals suffering from lung diseases as it may exacerbate their pre-existing conditions. these masks need to be properly fitted on the face every time to ensure that a proper seal is in place to provide maximal protection. the inability to form a proper seal does not provide adequate protection. this can be difficult to achieve in individuals with facial hair and in children. it can also inadvertently lead to frequent contact between the hands and the face while adjusting the mask, which further increases the risk of transmission. the tight seal also leads to the build-up of heat and humidity within the mask causing discomfort and difficulty in breathing. the duration and cost of manufacturing are longer and higher and during a pandemic, shortages of this equipment can result in avoidable exposure to hcws. during a pandemic or health crisis, hcws need to be able to access ppe readily in order to protect themselves, patients, and their contacts. interpretation of this case and the above studies helps us understand the need to urgently conduct large-scale rcts and incorporate the findings of these trials and studies to revise the existing guidelines regarding the use of rpe by hcws and possibly increase the usage of readily available surgical masks in favor of n masks for preventing covid- transmission. till the availability of any conclusive evidence, health care providers in direct contact with covid- cases should continue the use of n respirators as advocated by the current guidelines. although this case report helps us in determining the relative efficacy of different rpe in preventing covid- transmission, there is still a lot more that needs to be studied about the transmission and pathology of the coronavirus to introduce effective measures and equipment that will protect hcws in the future. the intricate details about the size and transmission of the virus still need to be studied in depth to figure out the best method of rpe that can be used to prevent its transmission. although this case report signifies that there is no superior protection offered by n masks in comparison to surgical masks, it has certain limitations and additional studies, particularly rcts need to be conducted in a health care setting to determine the effectiveness of different rpe, which may lead to the revision of existing policies and guidelines regarding the best ways to protect hcws from being infected with the coronavirus in the event of an exposure. human subjects: all authors have confirmed that this study did not involve human participants or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. clinical features of patients infected with novel coronavirus in wuhan, china journey of a thai taxi driver and novel coronavirus respect investigators: n respirators vs medical masks for preventing influenza among health care personnel: a randomized clinical trial effectiveness of n respirators versus surgical masks in protecting health care workers from acute respiratory infection: a systematic review and meta-analysis key: cord- -ffoiv ma authors: ranjit, eukesh; roxborough, john; davis, dean; sapra, amit; bhandari, priyanka title: clavicular osteomyelitis secondary to candida parapsilosis infection date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ffoiv ma candida parapsilosis osteomyelitis is a rare diagnosis. candidal infection can occur via hematogenous or local spread. a localized swelling around a bony structure should raise clinical suspicion. diagnosis is made by a combination of imaging modalities and biopsy. anecdotal case reports have been reported in medical literature and treatment guidelines are very limited. treatment modality includes a combination of surgical debridement and antifungal therapy. osteomyelitis is an inflammation of the bone secondary to infection. it is an old disease that has existed for at least million years, and the condition has been noted since the time of hippocrates [ ] . the majority of osteomyelitis cases are bacterial in etiology. fungal osteomyelitis is rare, with candida and aspergillus being the common agents [ ] . osteomyelitis with other rarer fungi such as blastomyces has been reported as well [ ] . in cases of candidal osteomyelitis, candida albicans is the most common causative agent with candida parapsilosis accounting for about % of the cases [ ] . management of candidal osteomyelitis with surgical debridement and antifungal therapy is recommended by the infectious disease society of america (idsa) based on anecdotal case reports and open-label series [ ] . also, osteomyelitis of the clavicle is a rare type of infection and usually results from hematogenous or traumatic spread [ ] . we present the case of a patient with multiple morbidities and history of sternal fracture that had been managed surgically three years prior to presentation. the patient presented with pain and swelling of the right upper chest, which was found to be caused by fungal clavicular infection with candida parapsilosis. a multidisciplinary team approach was adopted to diagnose and manage the case and address the patient's needs. a -year-old male presented to the primary care clinic with complaints of pain along his collar bone. the patient had a past medical history of diabetes mellitus type ii, morbid obesity (body mass index of . ), obstructive sleep apnea on bilevel positive airway pressure (bipap), chronic obstructive pulmonary disease (copd), major depressive disorder, fibromyalgia, hepatitis c secondary to intravenous drug use (ivdu), polysubstance abuse on suboxone maintenance therapy, anxiety disorder, closed body fracture of the sternum, and sternal osteomyelitis. three years before the current presentation, the patient had developed sternal osteomyelitis following a closed body fracture of the sternum after stumbling and falling onto the corner of a dresser in the middle of the night. the patient had undergone sternal wound debridement by cardiothoracic surgery (cts) and closure with re-advancement myocutaneous pectoralis flaps by plastic surgery at the time. wound cultures grew strep viridans and a few diphtheroids, which had been treated with antibiotics. when the patient was initially seen in the clinic, he endorsed vague pain, swelling, and minimal tenderness along the right collar bone for about two weeks ( figure ). no inciting event or trauma was reported. ultrasonography of the area was performed, which revealed a . x . x . cm heterogeneous soft tissue structure extending from the sternomanubrial joint ( figure ). mri of the chest was then ordered, which could not be completed due to insurance issues. an urgent outpatient ct of the chest was then ordered, which revealed right sternoclavicular septic joint with osteomyelitis at the head of the right clavicle's connection with the manubrium (figure ). the patient's primary care provider (pcp) recommended that he be admitted for further management. during admission, wbc count was elevated at . . comprehensive metabolic panel (cmp) was unremarkable. vancomycin and piperacillin/tazobactam were started empirically for osteomyelitis after blood cultures were drawn. ultrasound-guided aspiration of the sternoclavicular joint was performed by the interventional radiology team, yielding . ccs of thick purulent fluid. infectious disease (id), cts, and plastic surgery teams were consulted. the patient reported worsening anxiety secondary to hearing about covid- cases in the news and left against medical advice (ama). with the coordination of care between the inpatient team and pcp, multiple telephone conversations were conducted by the pcp, which resulted in the patient returning to inpatient service six days after he left. ultrasound-guided aspirate grew candida parapsilosis. the patient was started on intravenous fluconazole, and antibiotic coverage with daptomycin and piperacillin/tazobactam was initiated. the patient reported worsening right clavicular pain at the time of readmission. wbc count was elevated at . , and c-reactive protein (crp) was elevated at . . an mri of the right sternoclavicular joint was performed, which revealed right-sided sternoclavicular septic arthritis and osteomyelitis with associated periarticular abscess ( figure ). open incision and drainage of the right sternoclavicular joint was performed by the cts team, followed by sternal wound closure by the plastic surgery team. sternoclavicular joint aspirate culture revealed candida parapsilosis again, and a subclavicular tissue culture revealed staphylococcus aureus. intravenous fluconazole was continued for a week, after which it was transitioned to oral fluconazole. intravenous daptomycin was continued at the time of discharge for eight more weeks. candida parapsilosis, formerly known as monilia parapsilosis, is found in nature and as a human skin commensal organism. initially isolated in from a patient with diarrhea in peurto rico, it was thought to be nonpathogenic. however, in , this pathogen was found to be associated with endocarditis/sepsis in a patient with a history of ivdu [ ] . when considering osteomyelitis, the differential diagnosis includes common pathogens such as staphylococcus aureus. if the patient has certain risk factors such as sickle cell anemia or thalassemia, salmonella species are also considered [ ] . in the cases of patients similar to the one discussed here, with a history of ivdu, diabetes, morbid obesity, tobacco use, and previously closed injury resulting in osteomyelitis, the clinician should be aware of the increased risk of osteomyelitis. yingling et al. reported a case of candida parapsilosis in an immunocompromised hiv patient with a history of hardware implantation [ ] . although the patient was not hiv-positive, he did have underlying health conditions and had undergone treatments associated with fungal osteomyelitis and diabetes, and had a history of ivdu and broad-spectrum antibiotic use [ ] . other common risk factors for fungal infections, such as total parenteral nutrition and central venous catheters, were not present in this case. our case emphasizes the importance of maintaining a broad differential when assessing patients with septic arthritis/osteomyelitis. gamaletsou et al. noted that although fungal osteomyelitis remains rare, as many as % of rib osteomyelitis cases were due to fungal pathogens, and the incidence is increasing with the increasing number of susceptible hosts [ , ] . treatment strategies for candida parapsilosis osteomyelitis incorporate surgical debridement with antifungal chemotherapy [ ] . both candida albicans and parapsilosis are biofilmproducing pathogens, thus necessitating the debridement of the infected tissues to improve the chances of resolution [ ] . our patient was treated with extensive surgical debridement, intravenous daptomycin, and intravenous fluconazole as an inpatient and was eventually transitioned to oral fluconazole for outpatient treatment. at the time of this writing, he is continuing with the treatment. given the increasing prevalence of candida parapsilosis osteomyelitis, it is prudent for the family physician to understand this pathogen, commonly associated risk factors, and management techniques [ ] . our patient's case showcases the need for family physicians to be aware of candida species as a pathogen, particularly in higher-risk patients frequently encountered in our routine practice. candida parapsilosis involving clavicle is a rare form of osteomyelitis. the patient may present with vague swelling and discomfort on the upper chest. diagnosis involves initial imaging followed by a biopsy, and management includes surgical debridement and antifungal therapy. management with a multidisciplinary team approach is necessary. potential anxiety related to numerous procedures and prolonged course of antibiotics should be addressed. proper communication and transition of care between the inpatient team and pcp helps with issues of patient non-compliance and provides a better outcome for the patient. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. a history of osteomyelitis from the fungal osteomyelitis and septic arthritis a curious case of blastomyces osteomyelitis candida parapsilosis osteomyelitis clinical practice guidelines for the management candidiasis: update by the infectious diseases society of america post-traumatic osteomyelitis of the clavicle: a case report and review of literature candida parapsilosis, an emerging fungal pathogen salmonella osteomyelitis a rare case of candida parapsilosis osteomyelitis: a literature review and proposed treatment algorithm fungal arthritis candida osteomyelitis: analysis of pediatric and adult cases epidemiology of fungal osteomyelitis key: cord- -c cq x authors: ali, mohammed; mujahid, aisha; sherani, khalid; surani, salim title: st-elevation myocardial infarction in a -year-old male with covid- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: c cq x severe acute respiratory syndrome coronavirus (sars-cov- ) is a virus that led to a global public health emergency causing coronavirus disease (covid- ). it was initially identified in wuhan, china after causing significant respiratory illness. although respiratory symptoms are the most common presenting symptoms, it is now recognized that covid- encompasses multiple organ systems including the cardiovascular system. acute myocardial injury and st-elevation myocardial infarction (stemi) have now been associated with covid- . covid- patients with cardiovascular manifestations are at risk for increased severity of illness. here we present a case of a very young -year-old patient without any past history of hypertension, coronary artery disease, or any risk factors for coronary artery disease except obesity, who developed stemi while in the hospital. coronavirus is an enveloped positive sense rna virus belonging to the family coronaviridae. coronaviruses are widespread among birds and mammals. however, two subtypes (genera) of the subfamily orthocoronavirinae cause a significant disease in humans: alphacoronavirus and betacoronavirus [ ] . severe acute respiratory syndrome coronavirus (sars-cov- ) is a novel coronavirus with phylogenetic similarity to sars-cov. sars-cov- belongs to the betacoronavirus similar to sars-cov and middle east respiratory syndrome coronavirus (mers-cov), which are two related viruses that also caused significant epidemics with mortality rates of % and %, respectively [ , ] . in december in the city of wuhan in hubei province of china, officials identified a cluster of cases of respiratory infection of unknown etiology [ ] . this was later identified to be sars-cov- . the virus spread very rapidly through the city and subsequently out of the country to the rest of the world. the disease caused by the virus was subsequently termed coronavirus disease (covid- ) by the world health organization in february [ ] . it has since been declared a pandemic and has wreaked havoc around the world, leading to an unprecedented public health response on a global scale. the cluster of symptoms caused by the sars-cov- virus is similar to any viral pneumonia causing dyspnea, fever, cough, malaise, and myalgia. the most common reason for hospitalization by far is respiratory failure and in severe cases acute respiratory distress syndrome (ards). most cases are thought to be very mild not requiring hospitalization; however, of the hospitalized cases, there have been numerous cases of cardiac complications besides just respiratory illness. here we present a case of st-elevation myocardial infarction (stemi) in a very young -year-old african american patient who was admitted for respiratory , failure secondary to covid- . a -year-old obese african-american male with no significant past medical history presented to the emergency department (ed) with the complaint of dry non-productive cough, shortness of breath, and fever with a maximum temperature of . degrees fahrenheit prior to arrival. he reported visiting his sister in a different city who had tested positive for sars-cov- virus and was diagnosed with covid- . the patient stated shortly after he started having symptoms, which included shortness of breath, cough, nausea, vomiting, and diarrhea. these symptoms progressively became worse over the next eight days, and he now presented with significant dyspnea. upon presentation in the ed, he was immediately noted to be hypoxic with pulse oxymetry revealing oxygen saturation of % on room air. the rest of his vital signs were within normal limits. he was immediately placed on airborne precautions and started on supplemental oxygen via nasal canula receiving five liters per minute (lpm). a one-view chest x-ray was obtained, which revealed bilateral patchy infiltrates ( figure ). an electrocardiogram (ekg) was also obtained which was normal without st-segment changes ( figure ). initial laboratory workup revealed white blood cell count of . × /µl with . % lymphocytes and an absolute lymphocyte count of . × /µl. d-dimer was ng/ml. complete metabolic panel (cmp) revealed potassium of . mmol/l, blood urea nitrogen (bun) mg/dl, and creatinine . mg/dl. all were within normal limits besides potassium, which was supplemented in the ed. nasal swab for nucleic acid amplification of sars-cov- rna was positive. he was then admitted to the intensive care unit (icu) for close monitoring given his hypoxia and potential for deterioration. he was started on dexamethasone mg intravenous daily, azithromycin mg orally daily, vitamin c , mg every orally every six hours, zinc sulfate mg orally twice daily, vitamin d , iu orally daily, and thiamine mg orally twice daily. he was also initiated on weightbased low molecular weight heparin at mg/kg. remdesivir was unfortunately not available at this time for the patient. during the patient's first night, his oxygen requirements increased and he required lpm to maintain oxygen saturation around %. he was transfused two units of convalescent plasma on hospital day . on hospital day , he was requiring a nonrebreather mask (nrbm) to maintain the same saturation. an arterial blood gas (abg) was obtained that revealed ph of . , pco . mmhg, and po mmhg on % fio with nrbm . his respiratory status continued to worsen, and on hospital day he was placed on non-invasive ventilation on which he remained until the following night when his respiratory status further deteriorated requiring intubation and mechanical ventilation. a post-intubation chest x-ray was obtained (figure ) , which again revealed worsening infiltrates and also some subcutaneous emphysema in the soft tissues of the neck and bilateral apices. all his labs remained within normal limits except for d-dimer, which increased to ng/ml. he remained stable on the ventilator the following day, and abg on hospital day revealed ph . , pco . mmhg, and po . mmhg on the following settings: pressure control with respiratory rate of , inspiratory pressure of cmh o, and positive end-expiratory pressure (peep) of cmh o. the following morning on hospital day , it was noted by nursing staff that his rhythm had changed all of a sudden. a stat ekg (figure ) was obtained that revealed st depression in the inferior leads ii, iii, and avf. stat labs were also obtained, and cmp revealed acute renal failure with bun mg/dl and creatinine . mg/dl, both of which were normal the day prior. another rhythm change was observed on the telemetry monitor; therefore, a repeat ekg ( figure ) was obtained that revealed an acute stemi in the inferior and lateral leads. code stemi was called overhead, the heart catheterization lab was activated, and cardiology consulted. however, within a few minutes of activation, the patient went into cardiac arrest. advanced cardiac life support was then initiated, but unfortunately after aggressive resuscitation efforts the patient was pronounced dead. here we described a case of a young -year-old male with only history of obesity who initially presented with dyspnea due to covid- . he eventually suffered an stemi and unfortunately succumbed to this dreadful disease. it should be reported that, to the best of our knowledge, this was the youngest covid- patient reported to have suffered an stemi. since the start of the covid- pandemic, much has been learned about the disease process. however, much remains to be learned. the pathophysiology of the disease remains elusive. sars-cov- virus predominantly causes respiratory illness, such as respiratory failure, pneumonia, and ards. it is now increasingly clear however that there are cardiovascular complications, such as myocardial injury, arrhythmia, acute heart failure, and venous thromboembolism, involved with covid- that occur more frequently than previously thought [ ] . the extrapulmonary and systemic manifestations of covid- remain very poorly understood. in a recent cohort retrospective study consisting of patients, shi et al. reported that cardiac injury, as defined by serum cardiac enzyme, troponin i, above the th percentile upper reference limit, was present in . % of the patients [ ] . moreover, studies have shown that patients with pre-existing cardiovascular disease who are diagnosed with covid- have an increased risk of not only contracting the disease but also having a severe form of it or even death [ , ] . the pathophysiology of the cardiovascular injury in patients with covid- is not well understood. several mechanisms have been postulated by which sars-cov- can cause cardiovascular complications. sars-cov- infection occurs through receptor-mediated endocytosis triggered by binding of the viral spike protein to the angiotensin-converting enzyme (ace- ) receptor on the host cell. the ace- receptor is highly expressed in myocardial tissue, which may serve as a direct route of invasion for the virus into myocardial tissue causing disease [ ] . the virus can also cause systemic inflammation leading to cytokine storm, which can result in multiorgan system failure, including the cardiovascular system [ , ] . respiratory failure and the resulting hypoxemia can also lead to increasing demandsupply mismatch, thus leading to acute myocardial injury. sars-cov- is also widely thought to provoke a prothrombotic state leading to microthrombi formation, which can then embolize leading to acute ischemic event of the target end organ [ ] . this mechanism is what is thought to have occurred in our young patient. a recent retrospective analysis by stefanini et al. revealed that stemi was the presenting clinical manifestation in out of covid- patients who were diagnosed with an stemi. the rest had stemi during the course of the hospitalization. it should be noted that the mean age of these patients was ± years, ranging from to years [ ] . in % of the cases, a culprit lesion was not identified on coronary angiography. another case series published by bangalore et al. identified patients with covid- who had a stemi. the median age was years, ranging from to years. one-third of the patients did not have obstructive disease [ ] . the exact pathophysiological mechanisms of myocardial injury remains unclear; however, as mentioned microthrombi, cytokine storm, and hypoxic injury are thought to be the main means along with plaque rupture, coronary spasm, or direct endothelial or vascular injury. it was however noted that cardiovascular complications in patients with covid- led to a higher morbidity and mortality rate [ , [ ] [ ] [ ] . covid- has sparked a worldwide public health emergency and has led to significant morbidity and mortality globally. covid- has now been associated with increased cardiovascular injury and even more so in patients with severe disease. although the exact pathophysiology of cardiac injury remains a mystery, it is important to promptly recognize this manifestation. as our case illustrates young age, it may not preclude patients from cardiac injury resulting in significant morbidity and even death. di napoli r: features, evaluation and treatment coronavirus (covid- ) guide to understanding the novel coronavirus what we know so far: covid- current clinical knowledge and research situation report- catheterization laboratory considerations during the coronavirus (covid- ) pandemic: from the acc's interventional council and scai association of cardiac injury with mortality in hospitalized patients with covid- in wuhan, china cardiovascular considerations for patients, health care workers, and health systems during the covid- pandemic a review of acute myocardial injury in coronavirus disease emerging coronaviruses: genome structure, replication, and pathogenesis clinical features of patients infected with novel coronavirus in wuhan, china. lancet. st-elevation myocardial infarction in patients with covid- : clinical and angiographic outcomes st-segment elevation in patients with covid- : a case series cardiac involvement in a patient with coronavirus disease (covid- ) this research was supported (in whole or in part) by hca healthcare and/or an hca healthcare affiliated entity. the views expressed in this publication represent those of the authors and do not necessarily represent the official views of hca healthcare or any of its affiliated entities. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -xf bn cv authors: pata, ramakanth; kiani, roudabeh; ahmady, abolfazl; awad, vanessa m title: probability of covid- being the culprit in neurocognitive deception: a case series of incidental strokes in icu patients with covid- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: xf bn cv the coronavirus disease (covid- ) pandemic caused by the severe acute respiratory syndrome coronavirus (sars-cov- ) virus, originated in wuhan, china, and spread rapidly throughout the world, infecting millions and killing thousands. although some patients have mild or even asymptomatic responses to this infection, hospitalized patients present with symptoms such as fever, cough, and difficulty breathing. some patients have a severe response to the insult and experience rapid progression to acute respiratory distress and multiorgan failure. furthermore, many patients developed complications due to this infection. here, we present three patients who had strokes during their hospitalization for covid- pneumonia. in december , coronavirus disease (covid- ) quickly spread throughout the wuhan province of china and around the world, which led to the world health organization (who) declaring it as a pandemic on march , [ ] . covid- is caused by the sars-cov- virus, a zoonotic coronavirus linked to bats similar to the severe acute respiratory syndrome (sars) coronavirus and the middle east respiratory syndrome (mers) coronavirus [ ] . sars-cov- is transmitted through bodily fluids, such as respiratory droplets, and survives longer at lower temperatures (i.e., °c has higher survival than °c) [ ] . additionally, it has a high incubation period (average . and range of - days) [ ] , reproductive number (r ranged from . to . , with a mean of . ) [ ] , and reports have shown that the majority of patients are asymptomatic or have a mild response to the sars-cov- virus but release large amounts of viruses [ ] . these factors together caused this virus to spread rapidly and kill hundreds of thousands of patients, which is more than the sars pandemic in and the mers pandemic in combined [ ] . patients with covid- typically present with pyrexia, cough, and difficulty breathing. furthermore, some patients experience constitutional symptoms such as myalgia, arthralgia, chills, and/ or gastrointestinal (gi) symptoms (i.e., nausea, vomiting, and diarrhea) [ ] . in severe cases, patients experience severe insult to the lung tissue, causing acute respiratory distress syndrome. in addition to insults to the respiratory system, multiple complications in other systems have been reported in patients infected with covid- . these include, but are not limited to, acute kidney injury (aki) [ ] and cardiac injury [ ] . this case series demonstrates three incidences of stroke in three patients hospitalized for covid- pneumonia. on april , , a -year-old lady with a known medical history of diabetes mellites presented to the emergency department with altered mental status responsive to painful stimuli only. she was intubated due to a low glasgow coma scale (gcs) during which she had - ml hematemesis (arterial blood gas results in table ). she was found to be tachycardic and tachypneic, with elevated white blood cell (wbc /ul); subsequently, code sepsis was called. other laboratory findings showed blood glucose mg/dl, anion gap of , presence of ketones in urinalysis (ua), and creatinine . mg/dl. other laboratory findings on admission are shown in table additionally, the electrocardiogram showed sinus tachycardia with a corrected qt interval of ms (figure ) , and the head ct scan showed no acute intracranial abnormalities ( figure ). furthermore, a chest x-ray showed no acute pathologies (figure ) , and the covid- reverse transcriptase-polymerase chain reaction (rt-pct) was performed due to the recent outbreak of the sars-cov- virus, which came back positive. she was admitted for diabetic ketoacidosis with hyperglycemic hyperosmolar syndrome, metabolic encephalopathy, acute kidney injury secondary to hypotension, covid- pneumonia, and possible sepsis. she was given intravenous fluids, insulin drip, and antibiotics (vancomycin and meropenem) while on cardiac monitoring, and electrolyte levels were monitored (vitals presented in figures - ) . however, no anticoagulation was administered considering the hematemesis during intubation. on april , , the fecal occult blood test was negative and hemoglobin levels remained stable; therefore, she was put on lovenox® mg subcutaneous (sq) daily. a repeat of the head ct scan ordered on april , , due to altered mentation and showed a trace amount of acute subarachnoid hemorrhage products along the left superior frontal sulcus and suspected acute lacunar infarction in the posterior left periventricular white matter (figure ). on april , , a -year-old male with a known medical history of hypertension presented to the emergency department (ed) complaining of feeling sick for the past two weeks, having severe, persistent, and non-bloody diarrhea. additionally, he reported having some fever and chills, persistent dry cough, and worsening shortness of breath for the past few days. his initial chest x-ray was concerning for multilobar pneumonia with commonly reported imaging features of covid- pneumonia (figure ) , and his electrocardiogram showed sinus tachycardia with a corrected qt interval of ms (figure ). his oxygen saturation on room air was %; therefore, he was put on a rebreather mask. however, he developed respiratory distress causing his oxygen saturation to drop (table , figure , figure ). consequently, he was intubated and upgraded to the intensive care unit (on pressure-regulated volume control (prvc) with tidal volume ml, fio of %, positive end-expiratory pressure of mmhg (peep), and respiratory rate /min). additionally, covid- rt-pcr came back positive, and he was started on the following medications: hydroxychloroquine, azithromycin, (later replaced by doxycycline due to the qt interval), hydrocortisone mg (then replaced by methylprednisone mg), and heparin units q h for deep vein thrombosis (dvt) prophylaxis (later replaced with enoxaparin mg daily on april , ). he was put on cardiac monitoring in light of elevated troponin (troponin . ng/ml) and administration of hydroxychloroquine while electrolyte levels were monitored. other laboratory findings are shown in table . his kidney function deteriorated; therefore, he underwent hemodialysis (hd) on april , (blood urea nitrogen (bun)/cr: on admission / . ; pre-hd / . ; post-hd / . ). on april , , his temperature spiked to f˚ (figure ) , and his white blood cell (wbc) was elevated; consequently, blood culture (which grew staphylococcus hominis), transtracheal aspiration (tta), and urine analysis (ua; which grew candida albicans) was sent, and he was started on vancomycin and meropenem. these were discontinued on april , , and replaced with piperacillin/tazobactam . gm q h and fluconazole due to elevated liver function tests (lfts) ( table ). additionally, his potassium level was elevated to . mmol/l and glucose was mg/dl; therefore, he was treated with calcium gluconate and insulin. enoxaparin was held on april , , due to the presence of bloody secretion in the nasogastric tube (ngt). apixaban . mg twice a day was started on april , , after hemoglobin levels remained stable and the bloody secretions ceased. on april , , he was unresponsive to painful stimuli; therefore, a head ct was ordered, which showed a low-density area in the posterior right cerebral hemisphere with overlying subarachnoid hemorrhages representing a subacute infarction with associated hemorrhages in the absence of head trauma ( figure ). neurology consult advised the transfer of patients to a neurosurgery facility for further care. on april , , a -year-old african american male with a known medical history of diabetes and hypertension presented to the emergency department by paramedics for dry cough, three days of fatigue, and one day of shortness of breath. the patient denied any fever and night sweats. his chest x-ray showed cardiomegaly with pulmonary vascular congestion, small left pleural effusion, and bibasilar airspace disease. findings of secondary superimposed pneumonia due to congestive heart failure could not be excluded (figure ) . even though he was afebrile (figure ) , a sars-cov- rt-pct test was performed due to the recent outbreak of covid- , which came back positive. furthermore, the electrocardiogram showed sinus rhythm with ventricular premature beats and a corrected qt interval of ms (figure ) . his troponin was elevated ( . ng/ml), brain natriuretic peptide (bnp) was < pg/ml, and his o saturation was low ( %) (figure ) . consequently, he was admitted for cardiac and respiratory monitoring; he was put on a non-rebreather mask ( % oxygen), started on azithromycin ( mg intravenous (iv) daily), ceftriaxone ( gm iv daily), furosemide ( mg iv daily), methylprednisolone ( mg iv q h), and heparin for deep venous thrombosis (dvt) prophylaxis ( units q h sq). other laboratory findings are presented in table . on the fourth day of admission, he became hypotensive and was in respiratory distress; his blood pressure dropped to / mmhg, pulse was bpm, and respiratory rate was /min. he was intubated and put on mechanical ventilation (assisted control, tidal volume ml, respiratory rate /min, positive end-expiratory pressure (peep) , and fio %) and admitted to the icu (abg results in table ). he also developed aki ( / / bun . mg/dl and cr . mg/dl). on day , he had poor mentation even after sedation was held. a head ct was then ordered and reported focal area of hypodensity within the pons mainly along the left side, which indicated possible age-indeterminate infarction ( figure ) . methylprednisolone was held, and heparin was switched to apixaban ( mg po bid the pathophysiology of severe acute respiratory syndrome due to coronavirus (sars-cov- ), is the overproduction of early response proinflammatory cytokines, primarily tumor necrosis factor (tnf), interleukin- , and interleukin- β. the result is what has been described as a cytokine storm, leading to an increased risk of vascular hyperpermeability, multiorgan failure, and, in some cases, death [ ] [ ] . laboratory studies have confirmed "respiratory infections as triggers for acute myocardial infarction and stroke." data have already shown strokes triggered by respiratory infections such as the influenza virus and other confirmed respiratory viruses [ ] . the high concentrations of proinflammatory cytokines in severe covid- cases induce endothelial and mononuclear cell activation with the expression of tissue factor, ultimately causing the activation of coagulation and the production of thrombin. moreover, high levels of thrombosis and inflammatory serum markers, such as d-dimer, fibrinogen, and crp, have been seen in covid- patients. during the inflammatory process, concentrations of antithrombin iii, tissue factor pathway inhibitor, and the protein c system may decline, causing an imbalance in the anticoagulation system. the combination of these factors induces a pro-coagulation state and predisposes patients to microthrombosis and venous and arterial thromboembolism [ ] [ ] ] . furthermore, in a case series by kochi et al., five of six covid- patients with ischemic stroke showed the production of antiphospholipid antibodies (apl) [ ] . other case reports have also demonstrated evidence of coagulopathy and antiphospholipid antibodies in covid- patients who developed ischemic strokes. these findings suggest an additional avenue in which covid- can induce a hypercoagulable state and, consequently, ischemic stroke [ ] [ ] . multiple other reports have shown incidences of stroke in covid- patients. a retrospective study of data from the covid- outbreak in wuhan, china, revealed an approximately % incidence of stroke in hospitalized patients with covid- [ ] . other reports suggest a higher rate of cerebrovascular disease (mainly ischemic stroke) in severe covid- patients as compared to non-severe cases [ ] . additionally, case studies have shown large-vessel occlusion, with some in multiple territories [ ] . a case series by warren-gash et al. reported cases of covid- positive patients with large-vessel strokes in five patients younger than years of age [ ] . a comprehensive literature review on the clinical presentation, and management of the pandemic coronavirus disease (covid- ) unique epidemiological and clinical features of the emerging novel coronavirus pneumonia (covid- ) implicate special control measures the reproductive number of covid- is higher compared to sars coronavirus renal involvement and early prognosis in patients with covid- pneumonia cardiac and arrhythmic complications in patients with covid- covid- cytokine storm: the interplay between inflammation and coagulation the baffling case of ischemic stroke disappearance from the casualty department in the covid- era laboratory-confirmed respiratory infections as triggers for acute myocardial infarction and stroke: a self-controlled case series analysis of national linked datasets from scotland we propose that covid- infection influences the coagulation system, therefore, increasing the risk of stroke in patients, especially those with other risk factors for stroke such as hypertension and diabetes. additionally, we propose that careful monitoring and administration of anticoagulant therapies is necessary. further studies and trials are required to confirm these hypotheses. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -hgjv ot authors: mohamed, sherif; abo el-hassan, osama; rizk, magda; ismail, jumana h; baioumy, aml title: death due to cardiac arrest in a young female with highly suspected covid- : a case report date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: hgjv ot despite the common clinical presentations of the pandemic coronavirus disease of (covid- ) being well-known, there remain issues on its atypical or rare presentations. moreover, despite the known risk factors for severe covid- are cardiovascular disease, diabetes mellitus, hypertension, chronic lung disease, and advanced age, still younger patients suffer from this disease. herein, we present a case report of a -year-old female patient who was presented to the ed with cardiac arrest, then died within hours. first swab testing by reverse transcription-polymerase chain reaction (rt-pcr) came negative. however, she has typical ct features of covid- pneumonia, along with an echocardiographic picture of acute cor pulmonale. though it is rare, cardiac arrest can happen in young apparently healthy patients with covid- . as covid- patients are commonly having clotting disorders, endothelial and organ dysfunction, coagulopathy, and liable for pulmonary thromboembolism (pte), it is important to select those covid- patients who are at higher risk of pte, and practice ct pulmonary angiography (ctpa) for the diagnosis of pte, especially in case of significant increase of d-dimer values. despite the fact that common classical clinical presentations of the pandemic coronavirus disease of (covid- ) are well-known, there remain issues on its atypical or rare presentations. in a report to the united states centers for disease control and prevention (cdc) of over , confirmed covid- cases [ ] , the reported symptoms in descending order were as follows; cough ( %), fever (subjective or > . °f/ °c; %), myalgia ( %), headache ( %), and dyspnea ( %). less common symptoms included sore throat ( %), diarrhea ( %), nausea and/or vomiting ( %), and loss of smell or taste, abdominal pain, and rhinorrhea (< %) [ ] . severe covid- can occur in otherwise healthy individuals of any age, but it predominantly occurs in adults with advanced age or underlying medical comorbidities [ ] . recently, the cdc has created a list of certain comorbidities that have been associated with severe disease (defined as infection resulting in hospitalization, admission to the icu, intubation or mechanical ventilation, or death) [ ] . established risk factors include: cancer, chronic kidney disease, chronic obstructive pulmonary disease (copd), immunocompromised state from a solid organ transplant, obesity, serious cardiovascular disease, heart failure, coronary artery disease, cardiomyopathies, sickle cell disease, and type diabetes mellitus. herein, we present a case report of a -year-old female patient who presented to the ed with cardiac arrest and then died within hours. swab testing by reverse transcription-polymerase chain reaction (rt-pcr) came negative on the next day. however, she had typical ct features of covid- pneumonia. this atypical and severe presentation of covid- in a young patient could have significant impacts on diagnostic and therapeutic strategies of such patients. a -year-old egyptian female patient was brought by her husband to the ed in a state of cardiac arrest. cardio-pulmonary resuscitation (cpr) was immediately started and she revived after seven minutes. she was intubated and mechanically ventilated. history was taken from the husband that the patient is a nonsmoker, with two days history of cough and mild shortness of breath, with no fever. two hours before arrest she felt marked shortness of breath, chest tightness, then developed fainting attack with marked pallor and cold extremities. no history of close contact to covid- suspected or confirmed case in the last two weeks. no history of convulsions, vomiting, headache, or gastrointestinal symptoms. no past history of any chronic medical or pulmonary illnesses. after resuscitation, baseline clinical examination of the chest, heart abdomen was unremarkable, except for tachycardia. no clinical signs were suggestive of deep venous thrombosis (dvt) of the lower limbs. as the patient's symptoms were mainly respiratory --at the time of covid- pandemic --the resuscitating team decided to do urgent plain ct of the brain and chest before transferring the patient to the icu. ct brain was unremarkable, whereas surprisingly ct chest revealed extensive bilateral wide-spread, more peripherally situated parenchymal ground glass opacities (ggos) and consolidations in almost all lobes of both lungs ( figure ). at the icu, the patient was on mechanical ventilation, fio of %, with vital signs of blood pressure / mmhg, temperature . °c, respiratory rate of cycles/minute, and o saturation of %. the treating and icu teams decided ventilator strategy for acute respiratory distress syndrome (ards), prone positioning, iv vasopressors, septic workup, coagulation profile, and to do tracheal secretions swabbing for rt-pcr. her laboratory workup revealed normal total white blood count (wbc) with relative neutropenia and lymphocytosis, hemoglobin (hb) level of . g/dl, and normal platelet count. she had normal renal functions and electrolytes with double fold rising of liver enzymes. d-dimer was . ug/ml. serum testing for pregnancy (b-hcg) came negative. electrocardiography (ecg) revealed right ventricular strain and right bundle branch block (rbbb). bedside d echocardiography was carried out and revealed a picture of acute cor pulmonale ( figure ) . ejection fraction (ef) was %. despite all measures, the patient remained hypoxic and hypotensive for hours after intubation. then, she had a second cardiac arrest, and cpr was initiated; however, she did not revive and was declared dead after hours from her intubation. next day, the result of rt-pcr came negative for sars-cov- . a consent was obtained from the patient husband for publication of this case report. herein, we present a case report of a -year-old female who presented with cardiac arrest, with typical ct findings of covid- pneumonia, then died within hours. this atypical and severe presentation for covid- is strange and uncommon for many reasons: ( ) young age; ( ) female; ( ) apparently healthy with apparently good underlying cardiopulmonary reserve and no underlying risk factors of covid- or its severe form; ( ) rapid deterioration in few hours, up to death; and ( ) first sample was negative for sars-cov- by rt-pcr. unfortunately, there was no time for a second confirmatory sample. our current knowledge for clinical presentation of covid- is that % of infected individuals have mild symptoms, % have severe symptoms requiring hospitalization, while % become critically ill requiring mechanical ventilation. these differences in response are likely the result of degree of viral load, host immune response, age of the patient, and presence of co-morbidities [ ] . however, because the obligate receptor for the virus spike protein, human angiotensin converting enzyme (ace- ) is expressed in epithelial cells throughout the body, including the lungs, heart, kidney, and even the endothelium [ ] ; it is not surprising that %- % of patients with covid- infections have evidence of cardiac injury with elevated troponin [ ] . some patients with covid- infections die from cardiac arrest, likely as a result of a combination of primary cardiac involvement, or manifestation of systemic involvement such as severe hypoxia, multi-organ dysfunction syndrome, or systemic inflammatory response syndrome [ ] . acute pulmonary embolism (pe), reported in covid- patients, has been shown to be a cause of clinical deterioration in viral types of pneumonia, as well [ ] . patients with covid- often show clotting disorders, with organ dysfunction and coagulopathy, resulting in higher mortality [ ] . critical data came from the analysis of coagulation tests in samples collected on admission and during the hospital stay of covid- patients. nonsurvivors had significantly higher d-dimer and fibrinogen-degradation product (fdp) levels, and longer prothrombin time (pt) vs. survivors on admission [ ] . moreover, the clinical diagnosis of disseminated intravascular coagulation (dic) was observed in nonsurvivors during late stages of hospitalization [ ] . moreover, endothelial dysfunction is a key determinant in hypertension, thrombosis, and dic, which is common in patients with severe covid- [ ] . back to the clinical presentation of our case report, we thought that the patient had the diagnosis of severe covid- disease, despite that swab came negative. international guidelines have reported that a considerable number of patients could have false negative testing for sars-cov- , depending on the type of collected specimen [ ] . supporting this observation, recent studies had shown the diagnostic significance of ct chest in diagnosing covid- patients who had initial negative testing result(s) by rt-pcr [ ] . despite that the cause of death in this patient is not clear, we think that it is attributed to massive pe. this possibility is supported by the bedside echocardiographic findings and high d-dimer levels. unfortunately, time was not enough to carry out ct pulmonary angiography (ctpa) to confirm this diagnosis. recently, autopsy studies performed for covid- patients were shown. in patients who died from covid- -associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular t-cell infiltration. the lungs also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. histologic analysis of pulmonary vessels showed widespread thrombosis with microangiopathy [ ] . unfortunately, the patient's husband did not agree for post-mortem examination of our patient. lessons that could be learned from this case is that, it is important to select covid- patients at higher risk of pe, and practice ctpa for the diagnosis of pulmonary thromboembolism (pte) especially in case of significant increase of d-dimer values. anticoagulation could be a necessary therapy to control and reduce pro-thrombotic events, as well as to prevent pe, in patients with covid- [ ] . despite it is rare, cardiac arrest could happen in young apparently healthy patients with covid- . the clinicians dealing with suspected or confirmed covid- cases should always be alert. as covid- patients are commonly having clotting disorders, endothelial and organ dysfunction, coagulopathy, and liable for pte. we recommend that it is of crucial importance to select those covid- patients at higher risk of pte and practice ct pulmonary angiography for the diagnosis of pte, especially in case of significant increase of d-dimer values. if no clear contraindication(s), anticoagulation should be started early to control and reduce prothrombotic events in patients with covid- . human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. coronavirus disease case surveillance -united states covid- ): who is at increased risk for severe illness? -people of any age with underlying medical conditions people who are at higher risk for severe illness the science underlying covid- : implications for the cardiovascular system sars-cov- cell entry depends on ace and tmprss and is blocked by a clinically proven protease inhibitor association of cardiac injury with mortality in hospitalized patients with covid- in wuhan, china pulmonary embolism in covid- patients: awareness of an increased prevalence coagulopathy and antiphospholipid antibodies in patients with covid- abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia endothelial cell infection and endotheliitis in covid- infectious diseases society of america guidelines on the diagnosis of covid- chest ct for typical -ncov pneumonia: relationship to negative rt-pcr testing. radiology. pulmonary vascular endothelialitis, thrombosis, and angiogenesis in covid- key: cord- -pzatzadw authors: bellisario, alexandra; bourbeau, karissa; crespo, danielle a; deluzio, nicole; ferro, alexandra; sanchez, alexandra; jackson, tracy; kunath-tiburzi, gail; d'antoni, anthony v title: an observational study of vaping knowledge and perceptions in a sample of u.s. adults date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: pzatzadw background vaping is the use of e-cigarettes that contain inhalants such as nicotine, tetrahydrocannabinol, and cannabidiol. vaping is associated with e-cigarette or vaping product use associated lung injury (evali) and is a recognized public health crisis. despite rising numbers of hospitalizations due to evali, public knowledge and perceptions of the dangers of vaping require further investigation. objectives this exploratory study assessed knowledge and perceptions of vaping in u.s. adults. methods this study was approved by an ethical board, and informed consent was obtained from all participants. a cohort of u.s. adults was recruited by shared links on social media. participants completed an anonymous online survey that contained vaping knowledge and perceptions items. an a priori power analysis was conducted at % power and alpha = . . statistics were calculated using ibm spss statistics version (ibm corp., armonk, ny, usa). results a sample of (n = ) u.s. adults participated in the survey. the majority of participants ( . %) were females, and . % were between and years of age. over half ( . %) of participants were never asked about vaping use by a clinician at any visit, and . % agreed that vaping can reduce stress. of all participants, . % agreed that drinking alcohol makes someone more inclined to vape. significant positive spearman’s rho correlations were found between vaping and the use of cannabis, cocaine, ecstasy, hallucinogens, and inhalants (p < . ). conclusions we found a significant correlation between vaping and drug use. we also found that if the dangers of vaping are discussed by their health care providers, participants are more inclined to quit vaping. unfortunately, many physicians report that they avoid discussing vaping with their patients due to lack of vaping knowledge. our results illuminate the communication gap between patients and physicians. all clinicians need to counsel patients on the dangers of vaping, which might help prevent evali and related conditions. vaping is inhaling smoke from electronic cigarettes (e-cigarettes) that may contain nicotine, tetrahydrocannabinol, and cannabidiol [ ] . vaping is now recognized as a global public health crisis [ ] . vaping is associated with harmful conditions that include e-cigarette or vaping product use associated lung injury (evali) [ , ] . despite the rising numbers of hospitalizations due to evali [ ] , public knowledge and perceptions of the dangers of vaping are still not clear as the incidence of vaping continues to rise in children and young adults [ ] . using a murine model, pulmonary responses to e-cigarettes were assessed and it was found that mice exposed to e-cigarettes over only a two-week period produced significant increases in pulmonary oxidative stress and moderate macrophage-mediated inflammation compared to placebo (p < . ) [ ] . these authors concluded that e-cigarette vapor is a source of free radicals in which exposure can cause airway inflammation, oxidative stress, and suppresses bacterial clearance by alveolar macrophages [ ] . other researchers analyzed the tumorigenicity of e-cigarette smoke on lung and bladder tissue in mice [ ] . they found that . % of mice exposed to e-cigarette smoke developed lung tumors (adenocarcinomas) and . % developed urothelial hyperplasia in their urinary bladders [ ] . these data from basic science studies correlate with recent clinical findings. in the final analysis of their originally published case series, researchers stated that patients (n = ) in wisconsin and illinois were reported to their respective public health departments due to evali [ ] . the patients had bilateral infiltrates on chest imaging as a result of vaping. a total of % of the patients were hospitalized, % underwent intubation and mechanical ventilation, and two deaths were reported [ ] . a total of % of the patients reported having used tetrahydrocannabinol products in e-cigarette devices, although a wide variety of products and devices was reported [ ] . using a cross-sectional survey of , participants (n = , ), wills et al. [ ] found a significant association of e-cigarette use with chronic pulmonary disorder (p < . ). others recently analyzed bronchoalveolar lavage fluid from a convenient sample of patients (n = ) with evali to quantify the degree of toxicants and their chemical effects on lung tissue [ ] . these researchers found that vitamin e acetate was associated with evali [ ] . clearly, vaping is not an innocuous activity, and there exists a continued need to ascertain the perceptions of people who vape. such data can help drive evidence-based public health initiatives. vape products come in a variety of styles, and there are over , available flavors in the market [ ] [ ] [ ] . a cross-sectional survey in a large cohort (n = ) was carried out to examine the relationship between product characteristics and e-cigarette appeal [ ] . of participants that exclusively vaped, . % reported that the option of different flavors was the most attractive characteristic of using vapes that influenced their decision to begin vaping [ ] . these results suggest that people who have never vaped or smoked cigarettes may be vulnerable to e-cigarette flavor marketing strategies. allen et al. [ ] analyzed the contents of types of flavored e-cigarettes and found that diacetyl was detected above the laboratory limit of detection in of flavors (up to µg/e-cigarette), , -pentanedione was detected in of flavors (up to µg/e-cigarette), and acetoin was detected in of flavors (up to µg/e-cigarette). these data have driven lawmakers in some countries to ban flavored ecigarettes or restrict them from being sold to adolescents. rates of e-cigarette use among high school students in the united states have strikingly increased from . % in to . % in [ ] , and these data have been corroborated in more recent studies [ ] . in a qualitative study of young adults (n = ), researchers [ ] conducted focus groups and four main themes emerged: positive reinforcement, social benefits, negative effect reduction, and negative consequences. they found that many young adults were unsure of the negative consequences of vaping [ ] . vaping research is in its infancy, and there exist large gaps in the literature related to knowledge and perceptions of vaping among people of all ages. therefore, the purpose of this exploratory study is to assess public knowledge and perceptions of vaping by surveying a cohort of u.s. adults. the results can help clinicians provide effective vaping cessation strategies for their patients and drive evidence-based public health interventions. our three hypotheses are as follows: . there exists an association between knowledge of the chemicals found in vape pods and vape usage. . there exists a relationship between vaping and concomitant drug use. . there exists an inverse association between knowledge of the dangers of vaping and vape usage. the study protocol was fully approved by the wagner college, staten island, ny, usa. informed consent was obtained by all participants prior to their participation in the study. the design was an exploratory, observational study with a sample size of (n = ) participants. an a priori power analysis using g-power version . . . revealed that the minimum sample size need to achieve significance was participants at % power, effect size of . , at an alpha level of . [ , ] . because we did not find a published survey instrument that specifically aligned with the purpose of our study, we developed our own. the complexity of measuring perceptions related to vaping has been discussed in the literature [ ] . researchers have suggested that survey instruments be developed as e-cigarette products evolve [ ] . they summarized e-cigarette perception items from seven research groups, and we adapted some of our items from their summary [ ] . the survey instrument was first piloted on (n = ) participants so that the items and responses could be analyzed for inconsistencies and revised, if necessary. inconsistencies included the use of ambiguous terms or the lack of operational definitions for others. the wording of any items that appeared vague were was changed by consensus agreement among the authors. none of the data from these piloted participants were included in the final total sample. the final survey instrument included demographic items, as well as, vaping knowledge and perception items (see appendix). a likert scale was used for the knowledge and perception items. these items were paired (both positively and negatively worded items) but spaced from each other on the survey instrument. the purpose of these items was to evaluate acquiescence bias, which we did not find. the variables measured by the survey instrument are shown in table . the inclusion criteria were participants years or older, participants who vape or do not vape, and completed surveys. the exclusion criteria were participants less than years of age and incomplete surveys. all statistics were calculated using ibm spss statistics version (ibm corp., armonk, ny, usa). we distributed our electronic survey on a variety of social media websites using surveymonkey Ⓡ . these websites included facebook as a primary source due to its popularity and number of users. others included reddit, youtube, and instagram. a total sample of (n = ) u.s. adults participated. the internal consistency of our survey instrument was found to be moderately reliable (cronbach's alpha = . ). the gender and educational level of the sample are shown in table . most participants were females ( . %) between the ages of to years ( . %) and white/caucasian ( . %). figures and depict these data. table includes the medical and psychiatric diagnoses of the sample. less than half the sample ( . %) had never vaped, and the rest of the participants reported different frequencies of vaping ( figure ). data for current vape use among all participants can be found in figure . data for frequency of drug use among all participants can be found in table . figure includes data related to whether or not a participant has ever been asked about vaping usage by a health care provider. data for vaping perceptions and knowledge among all participants can be found in tables and , respectively. all data reported as n (%). in order to explore relationships between variables, spearman's rho correlation coefficient tests were used for all categorical data at an alpha level of . . this exploratory study helped fill the gap in the literature related to knowledge and perceptions of vaping among young u.s. adults. more significant correlations with perception statements were found than with knowledge statements. this suggests that perceptions of vaping risk play a critical role in the decision to engage in vaping. this finding lends support to our first hypothesis that an association exists between knowledge of the chemicals found in vape pods and vaping. whether or not such a perception changes as a person ages is unknown. over % of our sample fell between and years of age ( figure ). some reasons that incline adults to vape include ( ) belief that vaping reduces stress, ( ) belief that drinking alcohol makes people more inclined to vape, ( ) belief that the ingredients in a vape pod are safe to consume, and ( ) belief that smoking cigarettes is more dangerous than vaping. the lack of a significant finding between educational level and knowledge and perceptions of the dangers of vaping suggests that all adults need sound education regarding the dangers of vaping, irrespective of their educational backgrounds. the incidence of evali has increased and patients, with this acute condition acutely most often present with severe pulmonary consolidation with respiratory failure [ ] . based on our participants' responses, we found that if the dangers of vaping were discussed with them by their health care providers, they would be more inclined to quit vaping. this underscores how clinicians can influence vaping behavior changes in patients. such changes begin with candid conversations about the dangers of vaping between clinicians and patients. unfortunately, this may be easier said than done. hurst and conway [ ] conducted a qualitative study on physician attitudes about discussing vaping with patients and documenting vaping usage in the electronic medical record. many physicians believe that they lack medical knowledge needed to discuss vaping with patients and they rarely screen patients for vaping [ ] . in fact, one-third of the physicians in their sample did not hold strong objections to vaping [ ] . these data are sobering because they provide reasons why many clinicians avoid vaping conversations with patients. we found significant positive correlations between vaping and concomitant drug use that support our second hypothesis. there was a moderately strong positive correlation ( . ) between vaping and cannabis use (p = . ). weak positive correlations were found between vaping and cocaine use ( . ; p = . ), vaping and ecstasy use ( . ; p = . ), and vaping and inhalants ( . ; p = . ). our results align with other studies that have found an association between e-cigarettes and marijuana use in young adults [ ] . researchers found that youth who had used an e-cigarette were . times more likely to use marijuana compared to youth who had not used an e-cigarette [ ] . in a dutch cross-sectional survey, it was found that access to a variety of flavors is one of the most attractive characteristics prompting initial vape use [ ] . in our study, flavor was not found to be a significant factor influencing vape use. this suggests that recent legislation banning the sale of flavored cartridges may not be as effective as intended in deterring vaping [ ] . in our cohort, we found that participants who lack knowledge of the content and dangers of vaping are not only more likely to engage in vaping, but they also vape more frequently. this finding supports our third hypothesis that an inverse association exists between knowledge of the dangers of vaping and vape usage. we found a weak positive correlation between vape use and the belief that vaping reduces stress ( . , p = . ). our data support those of others [ ] who also reported that e-cigarette users believe that vaping reduces stress. this study provides a unique snapshot of the vaping landscape in a cohort of young u.s. adults. although unknown to us at the time, the data reported in this study were collected during the covid- pandemic [ ] . a future study during a non-pandemic time could be conducted and the data compared to ours. we were forced to close the study prematurely as new york city began to shut down. however, our sample size (n = ) exceeded the minimum identified by our a priori power analysis. a larger sample size could have resulted in more robust results. we do believe that our sample is representative of young, computer-literate u.s. adults. the fact that we were not permitted by the ethical review board to query respondents on their places of residence prevented us from generalizing our results to specific areas both within and outside the united states. our design was not immune to response bias inherent in survey instruments. furthermore, we were unable to answer any queries related to unfamiliar terminology on our survey because it was electronically distributed. however, as a result of piloting our survey, we did include operational definitions in simple language to help participants. we believe the internal validity of our study is robust. the homogeneity of our sample may weaken the external validity because the ethics board did not permit us to ask for the geographic locations of participants or their ip addresses. despite these limitations, our data can provide better direction for future studies on vaping knowledge and perceptions in adults. future studies can be designed to evaluate the efficacy of a vaping cessation "conversation protocol" for clinicians to help them engage in conversations about vaping with patients. analyzing factors that are most predictive of vaping cessation success would be useful in providing much needed patient education. future studies can also investigate the associations between vaping and drug use to see which drugs most influence a person's decision to vape. whether there exists a synergistic mechanism between the chemicals in vaping products and other drugs that make them more addictive in combination is currently unknown. undergraduate medical education should include comprehensive information on the pathophysiology and psychosocial factors of vaping. such a topic could be included within the neurology, psychiatry, and behavior courses. such a strategy would expose medical students to the fundamentals of vaping addiction. we also recommend screening for e-cigarettes use during every clinical encounter. complete survey instrument (demographic items, vaping knowledge items, and vaping perception items) used in the study protocol. • to which gender do you most closely identify with? ○ i vape - times a week. ○ i vape nearly every day. • which of the following statements do you most closely agree with? (current vape use.) ○ never ○ less than monthly (less than once a month per months) ○ monthly (once a month per months) ○ weekly ( - days per week) ○ daily ( days per week) • which of the following statements do you most closely agree with? click all that apply. vaping is less harmful than smoking cigarettes / vaping is more harmful than smoking cigarettes vaping will negatively affect a person's health over time / vaping will not negatively affect a person's health over time e-cigarette or vaping product use-associated lung injury world vaping update vitamin e acetate in bronchoalveolar-lavage fluid associated with evali a public health crisis: electronic cigarettes, vape, and juul. a. pediatrics exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice pulmonary illness related to e-cigarette use in illinois and wisconsin -final report e-cigarette use and respiratory disorder in an adult sample flavoring chemicals in e-cigarettes: diacetyl, , -pentanedione, and acetoin in a sample of products, including fruit-, candy-, and cocktail-flavored e-cigarettes an e-liquid flavor wheel: a shared vocabulary based on systematically reviewing e-liquid flavor classifications in literature comprehensive overview of common e-liquid ingredients and how they can be used to predict an e-liquid's flavour category e-liquid flavor preferences and individual factors related to vaping: a survey among dutch never-users, smokers, dual users, and exclusive vapers the rise of e-cigarettes, pod mod devices, and juul among youth: factors influencing use, health implications, and downstream effects vaping expectancies: a qualitative study among young adult nonusers, smokers, vapers, and dual users statistical power analyses using g*power . : tests for correlation and regression analyses power : a flexible statistical power analysis program for the social, behavioral, and biomedical sciences measuring perceptions related to e-cigarettes: important principles and next steps to enhance study validity exploring physician attitudes regarding electronic documentation of ecigarette use: a qualitative study association between electronic cigarette use and marijuana use among adolescents and young adults: a systematic review and meta-analysis regulations and policies regarding e-cigarettes preliminary estimate of excess mortality during the covid- outbreak we thank the anonymous participants who responded to our survey. a special thanks to michael j. flory, phd, who provided us with invaluable guidance. the news has affected my impression of vaping / the news has not affected my impression of vaping vaping is a health concern / vaping is not a health concern drinking alcohol makes a person more inclined to vape / drinking alcohol does not make a person more inclined to vape vaping makes one more socially acceptable to their friends / vaping does not make one more socially acceptable to their friends human subjects: consent was obtained by all participants in this study. human experimentation review board (wagner college) issued approval s - . the study protocol was fully approved by the wagner college (staten island, ny) human experimentation review board in january of . animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -l rocsk authors: akbar, aelia; iqbal, aqsa; gaziano, dominic; gasior, filip; zaidi, ayesha j; iqbal, anum; silva, abigail title: a cross-sectional survey on telemedicine use for doctor-patient communication date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: l rocsk introduction use of computers for doctor-patient communication is increasing. considering effective doctor-patient communication is important for good health outcomes. this study helps to determine the level of acceptance of telemedicine in general public and factors associated with it. methods: this survey with cross-sectional analysis comprised a brief survey with questions. the survey was distributed in public places to determine the opinions of the general public. results randomly selected participants completed the questionnaire. synchronous telemedicine was favored by young people ( % in the - age group vs . % of participants aged > years; p< . ), those with a higher education level ( . % of non-college-educated persons vs . % of college-educated persons; p< . ), and frequent computer users ( % who used a computer for less than two hours a month vs . % of those who used a computer more than hours a month; p= . ). asynchronous communication, like sending health information to doctors via a safe portal was acknowledged mostly by people who had used patient portals in the past ( . % vs . %; p= . ). use of patient portals was less among older users and senior citizens ( . % use in the age group > vs. . % in the age group - years vs. % in age group - years). receiving video education for specific health concerns was favored by those who used a computer frequently ( . % who used a computer more than two hours a month vs % who used a computer less than two hours a month; p = . ). conclusion telemedicine is generally favored, but physicians should be mindful about older people as they may not feel comfortable. step by step guidance should be provided especially to senior citizens for telemedicine and portal use. effective doctor-patient communication is important for history gathering, building trust, and patient compliance. studies have shown that effective communication between patient and physician is associated with positive health outcomes [ ] [ ] [ ] [ ] . telemedicine is the exchange of medical information through electronic devices between patients and physicians [ , ] . telemedicine may be used for asynchronous or synchronous doctor-patient communication [ ] . in asynchronous communication, the doctor and patient are not connected at the same time. for example, communication through emails, safe patient portals, interpretation of diagnostic tests and pre-visit completion of surveys by patients. synchronous communication refers to communication when the doctor and patient are connected at the same time, and is usually in the form of video conferencing [ ] . telemedicine increases access to care, saves travel time. and helps bring down costs. during the pandemic of covid- , telemedicine became an effective way to prevent the spread of infection without disrupting patients' access to health care. studies have shown increased access to healthcare and positive health outcomes when telemedicine was used for the management of chronic illnesses, like asthma in schools, and diabetes in rural areas [ , ] . the purpose of this study was to explore people's perspectives regarding the use of telemedicine for patient access to healthcare. our survey study took place from to in general public places like parks, bus stops, and convenience stores in the city of chicago, illinois. people aged years and older were eligible to participate. a written questionnaire was distributed among the people by anonymous study investigators and provided verbal consent to participate. respondents to the survey remained anonymous and therefore the study was exempt from irb approval. the individuals who completed the questionnaire did not receive any financial compensation. a research questionnaire consisting of questions was developed by the study investigators. we examined the general acceptance of doctor-patient online communication. we examined two scopes of doctor-patient interaction according to participants' characteristics, ( ) acceptance of synchronous telemedicine with doctor communicating directly via computer; and ( ) acceptance to asynchronous telemedicine, i.e., receiving health information from doctors on cellphone or computer, receiving appointment reminders on a cellphone, sending health information to the doctor through a safe portal, some health questions being answered before visiting the doctor, receiving wellness reminders through a computer, receiving video education from a doctor, and the doctor seeing and evaluating their patient's health information on an electronic health application. a brief verbal review of the study was provided to the people at public places by the study investigators. participants were randomly selected. those who verbally consented to participate were asked to fill out the anonymous paper survey questionnaire at the meeting place. the data was saved to an excel file. stata version (statacorp., college station, texas) was used to perform the statistical analysis. a descriptive analysis was obtained followed by bivariate analysis to detect a statistical association between the patient's independent variables and their standpoint (yes/no) on the acceptance of use of computer for communication with their doctor. a p-value of < . was considered statistically significant. chi-square test was used to compare the response of participants according to their characteristics. for data where the number of participants was less than seven, fisher's exact test was performed. there were patients who completed the questionnaire. the mean age of participants was . (sd . [sd: standard deviation) years with ages ranging from to years. approximately half of the participants were below the age of years, . % were - years and . % were years and older. out of the total number of participants, almost two-thirds ( . %) had attended college ( table ) . age (%) computer use pattern among study participants: the majority of participants who completed the survey used computer ( . %) and cellphones ( . %) in their everyday life. the percentage of participants who used computers to diagnose themselves was . %, and the percentage of those who used computers to research medical conditions was . %. majority of participants . % ( / ) used a computer for less than two hours a month. almost half ( . %) of participants had used a patient portal in the past ( table ) . the idea that it is useful when the doctor uses a computer to communicate directly with the patient / synchronous communication was shared by % of participants. the majority ( . %) were in favor of receiving the health information from their doctor on their cellphone and computer. the majority were in favor to receive appointment reminders ( . %) on their cellphones and receiving wellness reminders on their computer ( . %). the majority were comfortable in sharing their health information with their doctors through a safe portal ( . %) and favored the idea that some of their health questions could be answered before their visit to the doctor ( . %). participants also liked the idea to receive video education regarding their specific health concerns ( . %), and the use of health apps by the doctor to see and evaluate their health information ( . %) ( table ). would you find it useful if your doctor communicated with you directly through the computer? virtual patient-physician communication the patients' characteristics and computer usage affected their opinions towards virtual patient-physician communication (as shown in table ). younger patients and those with higher education level were in favor of the doctor communicating with them directly on the computer as compared to older patients and patients with lower education level, respectively % (in the age range of - vs . % aged years and older; p < . ) and . % (not college-educated vs . % of those who attended college). figure shows the percentage of participants who were in favor of synchronous doctor-patient communication according to age. hours of computer use also affected this opinion ( % who used the computer for less than two hours a month vs . % of those who used the computer more than hours a month; p < . ) with those who used a computer for more than two hours per day preferred synchronous communication ( table ). the use of a patient portal did not affect the opinion for the synchronous communication (p> . ). figure shows the use of patient portal according to age groups, and older age people were less likely to have used portal in the past ( . % use in age group and older vs. . % in those aged - years vs % in the - age group). figure shows the responses to asynchronous telemedicine according to prior use of patient portal in general public with mostly (> %) in favor of using it. table shows the responses of participants to questions on asynchronous communication according to age, education level, computer usage and prior use of patient portal. the participant age, education level, and use of computer and patient portal did not affect their opinion about receiving helpful health information from a doctor via computer, and the majority were in favor of it. the idea of receiving appointment reminders on cell-phone was mostly favored by those who used patient portal with statistical significance, but it was not affected by participants age, usage of computer or education level. only three participants out of total did not use cell phones so we did not analyze the opinion about receiving appointment reminders on cell phone according to cellphone usage. those who had not used a patient portal in the past were less likely to be comfortable sending health information to their doctors via a safe portal as compared to those who had used it in the past ( . % vs . %; p= . ). age, education level and frequency of computer use did not affect their attitudes about sending information through a safe portal. patient characteristics, computer use and prior use of patient portal did not affect their opinion about health questions being answered prior to their visit. the idea of receiving wellness reminders through a computer was favored by younger patients ( . % of - years of age vs . % of years of age; p< . ), with higher education level ( . % who attended college vs . % who did not attend college; p< . ), and those who had used patient portals in the past ( % vs . %; p < . ), but infrequent use of computers did not affect the idea of receiving wellness reminders through a computer (p > . ). the idea of receiving video education for specific health concerns was particularly favored by those who used computer frequently ( . % who used computer > hours vs % who used computer < hours a month; p = . ). age, education level and portal use did not affect this opinion. the opinion about use of health app by doctors to professionally evaluate health conditions did not differ by patient characteristics, frequency of computer use or use of patient portal, but it differed by education level. figure shows the use of patient portal according to age groups, and older age people were less likely to have used portal in the past ( . % use in respondents aged and older vs. . % in the - year age group vs % in those aged - years ). figure shows the responses to asynchronous telemedicine according to prior use of patient portals in general public with mostly (> %) in favor of using it. computers have become an integral part in clinical practice without detrimental effects on patient satisfaction [ ] . good patient-physician communication is important for healing [ ] . in this evolving era of medicine and communication, the purpose of our study was to inquire about the general public's perspectives about the use of telemedicine as well as suggest some methods for improvement. we found that majority of people were comfortable with their doctors communicating with them directly via computer, also known as synchronous telemedicine, a finding common to prior studies [ ] [ ] [ ] . however, previous studies did not analyze these opinions according to patient characteristics. in our study, younger age, higher educational attainment and computer usage were identified as strong indicators for acceptance of synchronous telemedicine. we evaluated general acceptance by participants to asynchronous telemedicine and provided some suggestions; using a patient portal, health concerns answered before a visit to doctor's clinic, receiving wellness reminders through the computer, receiving educational videos regarding specific health concerns, and use of health app by physicians for health evaluation. however, lack of prior use of a patient portal hampered the acceptance of this way of communication ( figure ) . patient portals allow patients to remain engaged in their healthcare decisions and easily communicate with their physicians. our study showed less use of patient portals by older adults (figure ) . the main barriers identified are lack of technology, health literacy and distrust of online devices by older patients [ ] [ ] . therefore, step by step guidance for the use of patient portals in this age group is necessary. we conducted the survey in general public and not just in physicians' clinics as there are many people who do not go to healthcare providers because of various reasons, such as lack of time and transportation. by conducting the survey in general public spaces, we were able to capture opinions of all types of people. another strength of this study is that we categorized the people's opinions according to age, education level, computer usage, prior use of patient portals, and evaluated their views about both asynchronous and synchronous telemedicine. however, our study was conducted before the onset of covid- pandemic during which telemedicine was the only way for most people to get their healthcare needs. it is likely to get more positive responses if the study is conducted during or after the pandemic and this opens door to future studies. our survey methods had several limitations as it was not specified for a particular group, and people with certain health problems could have answered differently as compared to those without any health problems. this opens doors to future studies to evaluate the acceptance of telemedicine on a case by case basis. for example, tele-neurology is widely accepted for mental health evaluation, refills of medicines, neurorehabilitation, outpatient consultation, as well as pediatric neurology [ ] . in conclusion, the use of computers for communicating with primary care physicians is generally accepted, however, clinicians should be mindful that older adults may not feel comfortable with synchronous telemedicine. people, especially older adults, should be encouraged to use computers and patient portals. human subjects: consent was obtained by all participants in this study. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. interacting with cancer patients: the significance of physicians' communication effective physician-patient communication and health outcomes: a review physician/patient communication: transmission of information and patient effects doctor-patient communication: a review telemedicine: a primer nursing care in telemedicine and telehealth across the world synchronous and asynchronous telemedicine effect of the school-based telemedicine enhanced asthma management (sb-team) program on asthma morbidity: a randomized clinical trial telemedicine in the management of type diabetes computers in the clinical encounter: a scoping review and thematic analysis how does communication heal? pathways linking clinician-patient communication to health outcomes effect of computer use on physician-patient communication using a validated instrument: patient perspective health information technology and physician-patient interactions: impact of computers on communication during outpatient primary care visits frankel r: health information technology and physician-patient interactions: impact of computers on communication during outpatient primary care visits facilitators and barriers of electronic health record patient portal adoption by older adults: a literature study. stud health technol inform characterizing the impact of health literacy, computer ability, patient demographics, and portal usage on patient satisfaction with a patient portal multidisciplinary approach and outcomes of tele-neurology: a review key: cord- -nidu om authors: erdinc, burak; raina, jilmil s title: spontaneous retroperitoneal bleed coincided with massive acute deep vein thrombosis as initial presentation of covid- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: nidu om severe acute respiratory syndrome coronavirus (sars-cov- ) is a novel coronavirus that has caused a global pandemic and unfortunately has caused a health crisis. when severe, coronavirus disease (covid- ) can manifest with bilateral pneumonia and hypoxemic respiratory failure but also can affect different organ systems. sars-cov- infection is known to cause a hypercoagulable state resulting in acute thrombotic events, including venous thromboembolism, acute myocardial infarction, acute stroke, acute limb ischemia, and clotting of ecmo (extracorporeal membrane oxygenation) and crrt (continuous renal replacement therapy) catheters. even though it commonly causes thrombotic complications, bleeding complications of covid- due to coagulopathy and use of anticoagulation are less commonly reported. we herein present a case of a patient with covid- complicated by spontaneous retroperitoneal bleeding and massive deep vein thrombosis (dvt), which was later complicated by compartment syndrome. to the best of our knowledge, coexistence of spontaneous bleeding with massive dvt has not been reported in the current literature. this case emphasizes that covid- induced hypercoagulable state can cause massive thrombosis, and patients might need anticoagulation therapy. however, clinicians should also consider the risk of hemorrhagic complications of the disease and be cautious when administering anticoagulant therapy in selected cases. a recent outbreak of novel coronavirus, severe acute respiratory syndrome coronavirus- (sars-cov- ), leading to severe pneumonia emerged in wuhan, hubei province, china. sars-cov- is an enveloped, non-segmented positive-sense rna virus belonging to the beta-coronaviridae family [ ] . according to the world health organization (who), there are more than million confirmed cases and , deaths from covid- globally. the most common presenting symptoms are fever, cough, fatigue, sore throat, diarrhea, headache, and loss of taste or smell. covid- may cause a severe inflammatory state leading to the disorder of hemostasis. it is also linked with various coagulation abnormalities, such as an increase in procoagulant factor levels, including fibrinogen, d-dimers, and factor viii that have been associated with higher mortality and increased risk of venous thromboembolism (vte). this combination of inflammation and thrombosis can be referred to as thromboinflammation or covid- associated coagulopathy. sepsis-induced coagulopathy and disseminated intravascular coagulopathy (dic) have been reported with severe disease, mainly in nonsurvivors. however, most patients with severe infection of sars-cov- develop thrombosis rather than bleeding, while bleeding is commonly seen in dic. severe covid- increases fibrinogen levels and factor viii activity which is not seen in patients with dic [ , ] . here we present a case of covid- infection that reports both thrombosis and bleeding. a -year-old female patient who had a past medical history of essential hypertension, morbid obesity, and surgical history of hysterectomy and cholecystectomy presented to brookdale university hospital and medical center emergency room (er) at the time of covid- pandemic peak in new york city with a new onset diffuse left lower extremity (lle) swelling, numbness, and pain along with back pain for the last hours. eleven days before presenting to the er, she called her primary care doctor (pcp) and spoke to him via telemedicine and told her that she started feeling very sick, had headache, fatigue, generalized muscle aches, body temperature of °f, sore throat, and cough. she also mentioned that she had lost her sense of smell or taste but denied any chest tightness or shortness of breath. her physician was concerned about sars-cov- infection and advised her to go to a clinic and get tested for it. however, she was scared of leaving her house and getting tested. on the initial physical exam in the er, the patient was awake, alert, and oriented but in mild respiratory distress. initial vital signs revealed a body temperature of . °f, blood pressure of / mmhg, heart rate of per minute, respiratory rate of per minute, oxygen saturation of % on room air which improved to % with supplemental oxygen therapy via non-rebreather mask, and a body mass index of kg/m . she had coarse breath sounds with increased respiratory effort, old midline laparotomy scar and benign abdomen, diffuse swelling and tenderness of her lle with decreased palpable pulses compared to right lower extremity. there was no discoloration or skin changes of the lle. initial chest x-ray (cxr) showed bilateral patchy pulmonary infiltrates concerning multilobar pneumonia that was later demonstrated with ct of the chest (figure ). a presumptive diagnosis of covid- was made, and a nasopharyngeal polymerase chain reaction (pcr) test was done that later confirmed the diagnosis of covid- . initial laboratory investigations are summarized in table , which revealed leukocytosis with neutrophil predominance, mild thrombocytopenia, microcytic anemia with high red cell distribution width (rdw), significantly elevated d-dimer level, acute kidney injury, lactic acidosis, and elevated inflammatory markers most likely secondary to severe sepsis due to covid- . ct angiogram (cta) of chest, abdomen, and pelvis with contrast was done to rule out pulmonary embolism (pe) in light of hypoxemic respiratory failure and markedly elevated ddimer, and also to investigate any source of bleeding that might cause an acute drop in hemoglobin, which ruled out pe but showed a large retroperitoneal hematoma in the left hemipelvis ( figure ). on the third day of admission, the patient's lle examination displayed significant edema and pain along with muscle weakness. compartments were tense but compressible in thigh and legs both. the patient underwent lle calf and thigh fasciotomy for lle compartment syndrome with inferior vena cava filtration and transferred to the surgical intensive care unit. the patient experienced significant rhabdomyolysis after fasciotomy with a maximum creatinine phosphokinase (cpk) level of , u/l which was complicated by acute renal failure and severe hyperkalemia (k level of . meq/l) requiring continuous renal replacement therapy (crrt). the patient had a cardiac arrest for six minutes on postop day and responded to resuscitation. during the remainder of the patient's hospital course, she received convalescent plasma as part of covid- treatment, required vasopressor support for septic shock from covid- , and started anticoagulation with enoxaparin and then heparin infusion after experiencing acute renal failure for treatment of dvt and hypercoagulable state. she had a worsening shock despite receiving multiple vasopressors. she was treated for septic shock empirically with meropenem and fluconazole for possible candidemia. even though she had persistent fever spikes and significantly elevated white blood cell counts with left shift, blood cultures did not grow any organisms but she had candida albicans in her sputum and urine cultures. her course was complicated with a second cardiac arrest on postop day . post cardiac arrest laboratory tests showed acute drop in hemoglobin from . to . and severe lactic acidosis with a ph of . . soon after, the patient had a third and fourth cardiac arrest without response to resuscitation efforts and died. patients with covid- have a high tendency to develop acute thrombotic events, including vte, acute stroke, acute myocardial infarction, and clotting of the ecmo (extracorporeal membrane oxygenation) and crrt catheters [ ] [ ] [ ] [ ] [ ] [ ] . autopsies of patients who died from covid- revealed severe endothelial injury, widespread thrombosis with microangiopathy and alveolar capillary microthrombi, and increased angiogenesis [ ] . these findings support the evidence of hypercoagulable state in patients with covid- . vte is commonly seen as a complication of hypercoagulable state in patients with covid- . when dvt is severe, it can compromise venous outflow from a limb and can cause significant limb swelling resulting in phlegmasia cerulea dolens (pcd). pcd caused by a massive dvt can further get complicated by compartment syndrome, which is a surgical emergency. compartment syndrome that develops with pcd is treated with fasciotomy as in our case. it is quite interesting that our patient presented with spontaneous retroperitoneal bleeding and also massive dvt causing compartment syndrome. to the best of our knowledge, spontaneous bleeding along with massive dvt has not been reported in the current literature, in patients with covid- . she did not receive any anticoagulation or had a trauma to the area prior to the ct scan, which makes this case an example of spontaneous bleeding. she also never had any prior history of thrombophilia, she was not on any oral contraceptives, and there were no other obvious factors that might be responsible for development of massive dvt. our patient initially had borderline low thrombocyte count, normal activated partial thromboplastin time (aptt, . seconds) with slightly increased prothrombin time (pt, . seconds), very high d-dimer ( , ng/ml ddu), high fibrinogen (> , mg/dl), and therefore, did not meet the diagnostic criteria for acute dic. even though patients who have severe covid- have a tendency to develop thrombotic complications, they also can less frequently have bleeding complications. a multicenter study reported the hemostatic manifestations, bleeding, and thrombotic complications of covid- patients [ ] . it showed a radiographically confirmed venous thromboembolic rate of . % ( . % in critically ill patients) with an overall thrombotic complication rate of . %. in contrast, the overall bleeding rate was . % ( . % in the critically ill patients), with a major bleeding rate of . % ( . % in the critically ill, including one fatal bleed). a meager rate of dic was noted in % of the critically ill patients. d-dimer levels were increased far out of proportion to any abnormalities in the pt/inr (international normalized ratio), aptt, fibrinogen level, or platelet count; these findings are uncharacteristic of dic as currently understood. therefore, coagulopathy in covid- is significantly different from severe sepsis from other causes. the remarkable combination of thrombocytopenia, prolonged pt, and elevated d-dimer can suggest dic, although it is different from dic seen in sepsis. in sepsis, thrombocytopenia is more profound, and d-dimer concentrations do not reach the high values observed in patients with covid- . according to the dic score of the international society on thrombosis and haemostasis, most patients with covid- would not be classified as dic. covid- post-mortem findings show typical microvascular platelet-rich thrombotic depositions in small vessels of the lungs and other organs. however, there are no signs of hemolysis or schistocytes in the blood film, and the platelet count is higher than would be expected in case of thrombotic microangiopathy. it is suggestive that coagulopathy associated with covid- is a combination of low-grade dic and localized pulmonary thrombotic microangiopathy [ ] . patients with severe covid- have a high tendency to develop hypercoagulable state and its acute thrombotic complications affecting different organ systems in critically ill patients. even though thrombotic events are frequently reported in patients with covid- , incidence of bleeding is far less common and it is usually associated with antiplatelet agents and anticoagulation. in addition, covid- coagulopathy is quite different from dic caused by severe sepsis of other causes. to the best of our knowledge, massive thrombosis along with spontaneous bleeding in patients with covid- has not been reported. we hope that this case report will contribute to our understanding of covid- related coagulopathy. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. a pneumonia outbreak associated with a new coronavirus of probable bat origin hypercoagulability of covid- patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis the procoagulant pattern of patients with covid- acute respiratory distress syndrome high incidence of venous thromboembolic events in anticoagulated severe covid- patients high risk of thrombosis in patients with severe sars-cov- infection: a multicenter prospective cohort study incidence of thrombotic complications in critically ill icu patients with covid- thrombosis in hospitalized patients with covid- in a new york city health system autopsy findings and venous thromboembolism in patients with covid- {epub ahead of print pulmonary vascular endothelialitis, thrombosis, and angiogenesis in covid- covid and coagulation: bleeding and thrombotic manifestations of sars-cov infection coagulation abnormalities and thrombosis in patients with key: cord- -ja wyr w authors: b k, anupama; chaudhuri, debanik title: a review of acute myocardial injury in coronavirus disease date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ja wyr w in december , an outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus (sars-cov- ), occurred in wuhan, hubei province, china, and it has spread rapidly across the world, causing the coronavirus disease (covid- ) pandemic. although sars-cov- infection predominantly results in pulmonary issues, accumulating evidence suggests the increased frequency of a variety of cardiovascular complications in patients with covid- . acute cardiac injury, defined as elevated cardiac troponin levels, is the most reported cardiac abnormality in covid- and strongly associated with mortality. in this article, we summarize the currently available data on the association of sars-cov- and covid- with acute myocardial injury. injury may be secondary to ischemic or nonischemic processes [ , ] . traditionally, elevated troponin concentrations have been considered equivalent to myocardial infarction. however, with improvements in troponin assays, elevated levels without overt symptoms or signs of myocardial ischemia are now more common; hence, the fourth universal definition of myocardial infarction considers myocardial injury to be a separate, unique entity [ ] . based on current evidence, a myocardial injury without overt ischemia represents approximately % of cases of abnormal troponin elevation [ ] . the differential diagnosis is broad in such cases. it can be recognized in the variety of cardiac such as acute heart failure, pulmonary embolism, myocarditis, cardiac surgery or procedures, cardiac arrhythmias, hypertension, stress-induced cardiomyopathy, or several non-cardiac conditions such as acute renal failure, sepsis, anemia, hypoxia, critical illness, drug-induced, rhabdomyolysis among others [ , ] . association of viral infections with myocardial injury has been well recognized, and the most common associations involve adenoviruses and enteroviruses such as coxsackie viruses [ ] . according to data from previous influenza virus and coronavirus epidemics, these viral infections have also been shown to cause myocardial injury, because cases of myocarditis have been described to be caused by both influenza and coronaviruses [ , ] . although sars-cov- infection predominantly causes pulmonary complications, such as pneumonia and ards, the disease has also been associated with a variety of cardiovascular complications, including acute myocardial injury, myocarditis, arrhythmia, heart failure, and venous thromboembolism [ ] . moreover, studies have shown that patients with covid- and preexisting cardiovascular disease (cvd) have an increased risk of acquiring the illness and subsequently having severe disease and death [ , ] . in a clinical bulletin issued by the american college of cardiology (acc), the overall case-fatality rate was . %, but the mortality reached . % in patients with underlying cvd [ ] . among various cardiac complications, acute cardiac injury with elevated cardiac biomarkers has been described in early studies from china on hospitalized patients with covid- . we discuss the prevalence, mechanism, clinical characteristics, management, and prognostic implications of sars-cov- -induced myocardial injury, according to current published research. sars-cov and mers may also result in cardiovascular complications, although most of the data are anecdotal, in the absence of systematic studies. although sars-cov infection is associated with some cardiovascular manifestations, there are no clear reported cases of myocarditis [ ] [ ] [ ] [ ] . however, in the saudi arabia outbreak, mers-cov was reported to cause acute myocarditis and heart failure ( table ) [ ] . first author and cohort size cardiovascular manifestation outcomes sars yu et al. [ ] (n= ) tachycardia ( %), hypotension ( %), bradycardia ( %), cardiomegaly ( %) and paroxysmal atrial fibrillation in only one patient transient pan et al. [ ] (n= ) cardiac arrest death li et al. [ ] (n= ) subclinical diastolic dysfunction without systolic impairment reversible on recovery peiris et al. [ ] (n= ) acute myocardial infarction cause of death in two of five fatal cases mers alhogbani [ ] (n= ) acute myocarditis and acute onset heart failure recovered acute cardiac injury has been reported to be highly prevalent in hospitalized patients with covid- ( the earliest single-center retrospective study conducted in china, involving hospitalized patients with covid- , detected acute cardiac injury in five ( %) patients. in the study, a diagnosis of acute cardiac injury was made if serum levels of cardiac biomarkers (troponin i) were above the th percentile upper reference limit, or new abnormalities were detected in electrocardiography (ecg) and echocardiography [ ] . since then, numerous retrospective studies reported an increased prevalence of myocardial injury in hospitalized patients with covid- , with a frequency between % and % [ , [ ] [ ] [ ] [ ] [ ] [ ] . the prevalence of cardiac injury increased with the severity of the disease ( however, data regarding troponin elevation in asymptomatic and mildly symptomatic, non-hospitalized patients are not available. the mechanism of cardiac injury among patients with covid- remains uncertain. the following potential mechanisms have been suggested. one potential mechanism is direct myocardial involvement mediated via angiotensin-converting enzyme (ace ) [ , ] . the betacoronaviruses can infect human hosts through ace , a membrane-bound protein expressed in many human cells, including vascular endothelia, renal tissue, cardiovascular tissue, and small intestinal epithelia. ace negatively regulates the renin-angiotensin system by inactivating angiotensin ii, and it is likely to protect against acute lung failure. a murine model has demonstrated that pulmonary infection with sars-cov also precipitates ace -dependent myocardial infarction. among humans, during the toronto sars outbreak, sars-cov viral rna was detected in % of autopsied hearts, thus raising the possibility of direct damage of cardiomyocytes by the virus [ ] . phylogenetic analysis has demonstrated that sars-cov- has a very similar receptor binding domain/motif to that of the sars coronavirus, thus suggesting that sars-cov- may use ace as a receptor to enter human cells and causes direct damage to the lung epithelia, thereby leading to pneumonia and ards. because ace is also highly expressed in the heart, covid- induced cardiac injury might potentially be mediated by ace , although whether sars-cov- binding alters ace expression or causes dysregulation of the renin-angiotensin-aldosterone system (raas) pathway remains unclear [ , , , ] . hence, one potential explanation for the higher likelihood of acquiring infection, and the increased risk of severe disease and adverse outcomes in patients with covid- with pre-existing cvd, maybe the elevated secretion of ace in these patients, thus making them more susceptible to direct viral damage to cardiac myocytes [ ] ; but, this has not yet been demonstrated in pathology studies. in a case report describing autopsy results for a -year-old man who died of covid- associated with ards, histologic examination of biopsied cardiac tissue showed rare interstitial mononuclear inflammatory infiltrates without substantial myocardial damage. however, the troponin level was not reported in the study [ ] . another suggested mechanism of covid- related cardiac involvement is an overwhelming immuneinflammatory response and cytokine storm [ , , ] . the hallmark of cytokine storm syndrome is an uncontrolled and dysfunctional immune response involving the continuous activation and proliferation of lymphocytes and macrophages [ ] . huang et al. have found that patients with covid- admitted to the intensive care unit have higher plasma levels of cytokines, including interleukins (il- , il- , il- , granulocyte-colony stimulating factor and igg-induced protein ), monocyte chemoattractant protein- , macrophage inflammatory protein -alpha, and tumor necrosis factor α [ ] . from a previous study of sars-cov infection and cardiovascular complications, subclinical diastolic left ventricular impairment appears to be common during acute sars infection and to be reversible after recovery, thus suggesting that left ventricular dysfunction in the acute phase might be associated with cytokine storm syndrome [ ] . several studies have shown that patients with covid- with myocardial injury show evidence of severe systemic inflammation, including elevated leukocyte and neutrophil counts, interleukin levels, c-reactive protein, procalcitonin, globulin, and biomarkers of myocardial injury and stress, such as creatine kinase and myoglobin and n-terminal pro-b-type natriuretic peptide (nt-probnp), thus linking myocardial injury to the severity of inflammation and subsequent ventricular dysfunction [ , , ] . similarly, in a case report of sars-cov induced fulminant myocarditis, the described patient had markedly elevated interleukin , thus suggesting that the presence of cytokine storms might have caused increased vascular wall permeability and myocardial edema, thus resulting in the observed thickening of the interventricular septum. because the myocarditis was transient, and recovery was enhanced with the use of continuous renal replacement therapy (crrt), myocardial injury can be considered to be associated with an excessive immune response mediated by viral infection [ ] . severe hypoxia due to acute lung injury and several systemic complications caused by the virus can result in oxidative stress and hence secondary myocardial injury due to increased myocardial oxygen demand [ , ] . for example in one study, there was a characteristic pattern of rise in cardiac troponin i over time. the troponin level was normal during admission, but subsequently increased in . % of patients especially in those who died. in those patients, the troponin level significantly increased in the week preceding the death coinciding with severe systemic disorders including multiple organ failure, severe electrolyte disturbances, management of ventilation or extracorporeal membrane oxygenation (ecmo), severe metabolic acidosis and coagulation dysfunction all of which can potentially lead to secondary myocardial injury due to increased oxidative stress on the heart [ ] . studies have demonstrated that patients with underlying cvd and other comorbid conditions are predisposed to myocardial injury during covid- ; the prevalence of hypertension among patients with cardiac injury has been reported to be as high as %- %, and that of coronary artery disease (cad) has been reported to be approximately %- % ( thus making the plaques prone to rupture. inflammation also causes endothelial dysfunction and increases the procoagulant activity of the blood, thereby contributing to the formation of occlusive thrombi over ruptured coronary plaques and predisposing patients to ischemic myocardial injury [ ] . there are several clinically diagnosed myocarditis cases in patients with covid- with supporting imaging ( in the study, among patients with covid , four ( . %) were clinically diagnosed with sars-cov- myocarditis based on the most updated diagnostic criteria for viral myocarditis [ ] . however, in a singlecenter retrospective study in admitted patients with confirmed covid- , the authors explored whether sars-cov- caused the myocarditis by performing at least one echocardiographic evaluation in all patients during hospitalization. a total of patients ( . %) presented with abnormalities suggestive of possible myocarditis with an elevation of troponin. the myocarditis diagnosis was based on findings of triple elevation in cardiac troponin i (> . ng/ml) plus abnormalities in echocardiography and/or ecg. the abnormalities in echocardiography were defined as a reduced left ventricular ejection fraction (lvef) (< %) or segmental wall motion abnormality or left ventricular wall thickening (> mm) and/or presence of pericardial effusion (≥ mm); the abnormalities in ecg were defined as st-segment elevation/st-t changes. the echocardiography did not show typical signs of myocarditis, as stated above, except for the presence of small pericardial effusion in some patients and nonspecific ecg manifestations, most commonly tachycardia, which was not typical for myocardial injury but was more suggestive of systemic causes. hence, the authors suggested that myocardial injury may be more likely to be a result of systemic consequences rather than direct damage by sars-cov- [ ] . uncertainties exist whether sars-cov- can directly cause cardiomyocyte infection as no biopsy-or autopsy-demonstrated sars-cov- localization within cardiomyocytes has been reported to date. in a study of covid- through post-mortem needle core biopsy of the lung, liver, and heart in four patients who died of covid- pneumonia, cardiac biopsy performed in two patients in whom cardiac troponin was elevated during hospital course showed only mild focal fibrosis and mild myocardial hypertrophy, which were probably associated with the underlying conditions, such as hypertension-associated myocardial hypertrophy and past ischemic injury; however, there was no evidence of inflammatory cellular infiltration to indicate myocarditis [ ] . tavazzi et al. have described the first case in which a biopsy demonstrated myocardial localization of viral particles suggestive of sars-cov- , in a patient presenting with cardiogenic shock [ ] . the clinical presentation was suggestive of fulminant myocarditis; however, the pathologic study demonstrated lowgrade myocardial inflammation without evidence of myocardial necrosis. given that the viral particles were observed in interstitial cytopathic macrophages and their surroundings, but not in cardiac myocytes, the authors could not infer viral cardiotropism and suggested that either a viremic phase or migration of infected macrophages from the lung is likely to occur in patients with covid- with non-ischemic acute myocardial injury [ ] . further investigations along with the histological demonstration of myocarditis (inflammatory lymphomonocytic infiltrates plus myocyte necrosis not typical of ischemia [ ] ) and identification of the viral genome in cardiac tissue will be required in the future to clarify the direct association of covid- with myocarditis. myocardial injury has been shown to present in three different patterns: . the most common pattern is mild troponin elevation (typically < th percentile of the upper reference limit), with a modest rise or fall on subsequent days, as frequently observed in patients without cardiac symptoms and those who survive after hospitalization [ , ] . . the second pattern is progressive, in which some patients have normal troponin levels or moderate troponin elevation during admission. however, the level progressively increases as the patients experience clinical deterioration with respiratory failure along with an increase in other biomarkers (e.g., interleukin- , ferritin, and lactate dehydrogenase) and usually occurs during the second week of hospitalization. this pattern is observed among non-survivors, and death occurs around a median of . days after symptom onset. one study has demonstrated that at four days after symptom onset, the median high sensitivity cardiac tni (hs-ctni) levels were . pg/ml in non-survivors vs. . pg/ml in survivors. during follow-up, the median hs-ctni among survivors did not change significantly ( . - . pg/ml), whereas it rose to . pg/ml on day , to . pg/ml on day , to . pg/ml on day and to . pg/ml on day in nonsurvivors [ , , ] . . the third pattern is early moderate troponin elevation (which may approach or exceed the th percentile upper reference limit) and, subsequently, fall over the course of illness; this pattern is usually seen in patients with clinically suspected myocarditis presenting predominantly with cardiac symptoms [ , , ] . studies have shown that patients with cardiac injury are more likely to be older (median age - years) than those without cardiac injury [ , , ] , and most patients present with typical symptoms of covid- like fever, cough, fatigue, and dyspnea. in a study of covid- patients, of whom had evidence of cardiac injury, no patients complained of chest pain or palpitations. the common symptoms at illness onset in both groups of patients with or without cardiac injury were similar and included fever, cough, headache, fatigue, and dyspnea [ ] . however, a minority of patients with cardiac injury might present with cardiac symptoms with or without respiratory symptoms. in another study, of ( . %) patients with myocardial injury presented with chest pain, compared with of ( . %) patients without cardiac injury (p< . ) [ ] . in a case report of myocarditis, the initial presenting symptom was chest pain and respiratory involvement, but an atypical presentation without respiratory symptoms was also described [ , ] . in terms of radiologic findings, bilateral and multiple mottling and ground-glass opacity are more prevalent in patients with than without cardiac injury [ ] . limited studies in which patients with cardiac injury underwent ecg have revealed ecg abnormalities such as t-wave depression and inversion, st-segment depression, and q waves [ ] . patients with clinically suspected myocarditis have been found to have stsegment elevations [ , ] . patients with cardiac injury and elevated troponin are more likely to be admitted to the intensive care unit and to develop complications including ards, malignant arrhythmias including ventricular tachycardia/ventricular fibrillation, acute coagulopathy, electrolyte disturbances, and acute kidney injury, and to receive mechanical ventilation, crrt, extracorporeal membrane oxygenation, and vasopressor therapy, thus further suggesting that cardiac injury might be associated with the clinical outcomes of covid- . the use of antibiotic treatment, glucocorticoids, and intravenous immunoglobulin treatment is also significantly higher in patients with cardiac injury than without cardiac injury [ , ] . studies have shown that cardiac injury is associated with higher mortality in patients with covid ( tables , [ ] . similarly, in another case series, even though patients with covid- with cardiac injury and underlying cvd had the highest mortality ( . %), patients with underlying cvd but normal tnt levels during the disease course had more favorable prognoses than patients with elevated tnt levels but no underlying cvd (mortality, . % vs. . %), thus indicating relatively favorable prognosis in patients with underlying cvd but without myocardial injury [ ] . these studies demonstrate that cardiac injury might be independently associated with an increased risk of mortality in patients with covid- . moreover, the mortality rate directly increases with the magnitude of the reference value of cardiac troponin. in a single-center, retrospective cohort study including patients with covid- in wuhan, china, conducted to explore whether heart injury occurred during covid- on admission and later increased mortality, approximately . % of patients had high-sensitivity cardiac troponin i (hs-tni) exceeding the clinical upper normal limit on admission. patients with high levels of hs-tni on admission had significantly higher mortality ( . %) than patients with moderate or low levels of hs-tni ( . % or . %). besides, hs-tni level on admission was significantly negatively correlated with the number of survival days (r=- . , p= . ) [ ] . a study by guo et al. showed that tnt and nt-probnp levels increased significantly during hospitalization in patients who ultimately died, whereas these dynamic changes in tnt or nt-probnp levels were not evident in survivors [ ] . based on a few studies, initial measurement of cardiac biomarkers immediately after hospitalization for sars-cov- infection and longitudinal monitoring during the hospital stay may aid in identifying a subset of patients who might progress to a poorer clinical condition. however, further evidence from more studies is required. a myocardial injury should be suspected in patients with covid- with troponin elevation or new abnormalities in ecg and could be related to type or type myocardial infarction, myocarditis, stressinduced cardiomyopathy or cytokine induced-myocardial injury [ , ] . the approach to evaluating myocardial injury in patients with known or suspected covid- should be based on balancing the benefits of further evaluation in changing the management strategy versus the potential risk of nosocomial spread of covid- infection [ , ] . as such, elevated troponin levels should not be considered as evidence of acute myocardial infarction, which is diagnosed based on symptoms and signs of ischemia and ecg changes [ ] . in a multicenter case series study form six hospitals in new york inpatients with confirmed covid- who had st-segment elevation on ecg with the elevation of cardiac enzymes, out of patients were classified as having noncoronary myocardial injury with no evidence of obstructive disease on coronary angiography and normal wall motion on echocardiography. eight patients received a clinical diagnosis of myocardial infarction. the median peak troponin level was higher in patients with myocardial infarction than in those with a clinical diagnosis of noncoronary myocardial injury [ ] . if the clinical presentation is suggestive of an acute coronary syndrome (acs), timely evaluation is required to determine the need for urgent intervention. in patients with covid- who have mild to moderate troponin elevation without symptoms and signs of acute heart failure, clinical monitoring may be performed without routine cardiac imaging until the recovery from the acute viral syndrome [ ] . for patients with clinical signs and symptoms of heart failure, echocardiography may be performed if the management strategy and prognosis would be likely to change with the diagnosis. the possible diagnosis in the patients with ventricular wall motion abnormalities, elevated troponin, and no acs include clinically suspected myocarditis or stress cardiomyopathy [ ] . as there is no established therapy for clinically suspected myocarditis, routine evaluation with cardiovascular magnetic resonance or endomyocardial biopsy in those cases is not recommended [ ] . as such, regardless of fulminant or non-fulminant presentation, american college of cardiology recommends against routine endomyocardial biopsy in patients with active covid- with abnormal cardiac enzymes as biopsy is unlikely to change immediate clinical management whether the etiology is due to myocarditis, cytokine-induced myocardial injury or type- myocardial infarction [ , ] . unfortunately, beyond guidelines for treating patients with ischemic myocardial injury, no consensus exists regarding the routine management of patients with covid- and myocardial injury. the management of myocardial injury focuses on identifying and treating the underlying cause and supportive care (including management of heart failure, therapy of arrhythmias, and avoidance of cardiotoxins) [ , ] . if the patient clinically deteriorates or develop hemodynamic instability, or has severely elevated or rapidly rising troponin, detailed evaluation, cardiology consultation and enrollment in clinical trials or experimental therapies like antiviral agents, anti-cytokines (il- inhibitors such as tocilizumab), the convalescent plasma may be considered on the case-by-case basis [ ] . although the use of steroids has not been recommended in the general treatment of covid- , some reports have described patients recovering from fulminant myocarditis with intravenous immunoglobulin and steroids. however, more studies will be needed to determine which patient would benefit from such therapies [ ] . for patients with refractory shock or ventricular arrhythmias secondary to fulminant myocarditis, early institution of mechanical support with ecmo can be considered as case reports with the successful rescue of such patients have been described [ ] . in general, as the presence of cvd and myocardial injury in covid- patients has been associated with more severe outcomes and increased mortality, triaging patients with covid- according to the presence of underlying cvd and evidence of myocardial injury for prioritized treatment strategies may be reasonable [ ] . finally, several therapies with potential cardiovascular side effects are currently being studied, and caution must be used when administering these therapies to patients with underlying cardiovascular disease. for example, preliminary clinical research has suggested the potential efficacy of hydroxychloroquine alone and in combination with azithromycin for treatment of covid- , but this is associated with qtc prolongation and risk of fatal arrhythmias, thus warranting regular monitoring of qtc [ ] . controversy remains concerning the use of acei/arb for covid- . some preclinical studies have suggested that raas inhibitors may increase ace (functional receptor for sars-cov- ) expression, raising concerns regarding safety in patients with covid- ; however, the data remain anecdotal, and no clinical studies have evaluated the effects of raas inhibitors in covid- . as such, several leading professional societies recommend continuation of raas inhibitors for patients who are at risk for, being evaluated for or currently have covid- , and are taking these medications to treat other conditions for which these agents are known to be beneficial, such as heart failure, or ischemic heart disease [ ] . most studies have been conducted on chinese cohorts, and thus the generalizability of the results to other countries, including the united states, remains to be determined. most studies have been single-centered retrospective studies with the enrollment of small numbers of patients. larger cohorts, multicenter and prospective studies should be planned. they should include assessment of detailed heart function related data, particularly ecg, echocardiography and possibly cardiovascular magnetic resonance imaging to determine myocardial function, and the etiology and mechanism of cardiac injury. most studies have not discussed why troponin was measured in the first place, and no data are available to support a different management strategy for patients with elevated troponin. studies must be planned to define whether adjunctive cardioprotective therapies, such as corticosteroids, immunosuppressants, antivirals agents, interferons and/or immunomodulatory therapy (immunoglobulins), may be advisable for patients with significant elevation of cardiac injury biomarkers. pathological examination of myocardial tissue of patients with covid- with definite myocardial injury will be needed to provide pathological evidence of the etiology of myocardial injury and establish covid- as a new etiological agent for myocarditis. in conclusion, covid- has been associated with an increased prevalence of acute cardiac injury, even more so in patients with severe disease. the presence of preexisting cardiovascular disease increases the risk of cardiac injury in patients with covid- . although the exact mechanism underlying the association of cardiac injury in patients with covid- remains unclear, direct virus-induced cardiomyocyte injury leading to viral myocarditis, systemic cytokine-mediated myocardial injury and hypoxia-induced myocardial oxidative stress have been suggested. the presence of myocardial injury is independently associated with mortality and may be a predictor of progression to severe disease and adverse clinical outcomes in patients with covid- . further studies are needed to elucidate the predominant etiology of myocardial injury in patients with covid- and to promote targeted treatment programs to improve patient prognosis. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. a novel coronavirus from patients with pneumonia in china clinical features of patients infected with novel coronavirus in wuhan, china. lancet. from sars to mers, thrusting coronaviruses into the spotlight genomic characterization of the novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting wuhan cardiovascular considerations for patients, health care workers, and health systems during the coronavirus disease (covid- ) pandemic 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coronavirus disease myocardial localization of coronavirus in covid- cardiogenic shock case description covid- myocarditis and severity factors: an adult cohort study pathological study of the novel coronavirus disease (covid- ) through postmortem core biopsies diagnosis of myocarditis covid- ): myocardial injury description and proposed management of the acute covid- cardiovascular syndrome st-segment elevation in patients with covid- -a case series hydroxychloroquine and azithromycin as a treatment of covid- : results of an open-label non-randomized clinical trial renin-angiotensinaldosterone system inhibitors in patients with covid- key: cord- -kuvnwdn authors: ikegami, saya; jitsuiki, kei; nagasawa, hiroki; nishio, ryota; yanagawa, youichi title: suspected virus-inducing severe acute respiratory distress syndrome treated by multimodal therapy including extracorporeal membrane oxygenation and immune modulation therapy date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: kuvnwdn a -year-old man who had been feeling general fatigue was found in an unconscious state on the same day. he had no remarkable medical history. on arrival at the hospital, his glasgow coma scale was e v m ; he had tachycardia and hypertension, was afebrile, and in a severe hypoxic state. his pao( )/fio( ) (p/f) was under , even with tracheal intubation with % oxygen. chest x-ray and ct revealed a bilateral ground-glass appearance with consolidation. cardiac echo initially showed hyper-dynamic wall motion. the main results of a blood analysis suggested an acute inflammatory reaction, rhabdomyolysis, and pancreatitis. the microscopic findings of sputum and a rapid test for bacterial and viral infections were all negative. as he showed deterioration of p/f, venovenous extracorporeal membrane oxygenation (ecmo) was started. he also showed hypotension and therefore underwent vasopressor and steroid administration. due to concerns of pneumonia, he received meropenem and azithromycin in addition to the infusion of γ-globulin and glycyrrhizin. the results of a covid- test, culture of sputum, and collagen disease test were all negative. the serum virus neutralization assay as a serological test for coxsackievirus b showed a four-fold increase in titer. the multimodal therapy mentioned above resulted in the improvement of his general condition, including acute respiratory distress syndrome (ards). in this report, we discuss the benefits of ecmo and immune modulation therapy in the treatment of severe ards. acute respiratory distress syndrome (ards) is a common cause of respiratory failure in critically ill patients and is defined by the acute onset of non-cardiogenic pulmonary edema, hypoxemia, and the need for mechanical ventilation [ ] [ ] [ ] [ ] . the pathology of ards is diffuse alveolar damage, such as the rapid development of capillary congestion, atelectasis, intraalveolar hemorrhaging, and alveolar edema, followed days later by hyaline-membrane formation, epithelial-cell hyperplasia, and interstitial edema [ ] . ards occurs most often in the setting of pneumonia, sepsis, aspiration of gastric contents, or severe trauma and is present in roughly % of all patients in intensive-care units worldwide [ ] . although much progress has been made in improving supportive care for ards, effective pharmacological therapies have not yet been identified, and mortality remains high at %- % in most studies [ ] . we report a case of suspected virus-inducing severe ards treated by multimodal therapy including extracorporeal membrane oxygenation (ecmo) and immune modulation therapy that led to a favorable outcome for the patient. a -year-old man felt generalized fatigue and took the day off from work. his son called him on the same day, but he did not respond. when the son visited his house, he found the patient unconscious and called an ambulance. he had no remarkable medical history. he was a neversmoker and drank g of ethanol per day. he worked as a truck driver and lived with his only son after his divorce. his work zone was not located in any of the districts that were reported to have covid- infections. when the emergency medical technicians checked him, he had a tonic convulsive posture with severe hypoxia, and he was transported to our hospital under bag-valve-mask ventilation with high-concentration oxygen. on arrival, his glasgow coma scale was e v m . a physical examination revealed the following findings: blood pressure of / mmhg; heart rate of beats per minute; a respiratory rate of breaths per minute; spo of % under room l per minute of oxygen; and body temperature of . °c. a venous route was immediately secured, followed by endotracheal intubation. an arterial gas analysis revealed the following findings: ph: . ; pco : . mmhg; po : . mmhg; base excess - . mmol/l; and lactate: mmol/l. electrocardiography revealed sinus tachycardia. a chest x-ray revealed a bilateral ground-glass appearance ( figure ). cardiac echo showed hyper-dynamic left-ventricular wall motion. whole-body ct revealed a bilateral ground-glass appearance in the ventral lung fields and bilateral consolidation in the dorsal lung fields ( figure ). the image shows a bilateral ground-glass appearance in the ventral lung fields (arrow) and bilateral consolidation in the dorsal lung fields (asterisks) the pancreas was normal. the main results of a blood analysis were as follows: wbc count: , /μl (neutrophil %, lymphocyte %, monocyte %); hemoglobin: . g/dl; platelet count: . × /μl; total protein: . g/dl; albumin: . g/dl; glucose: mg/dl; hba c: . %; total bilirubin: . mg/dl; aspartate aminotransferase: iu/l; alanine aminotransferase: iu/l; lactate dehydrogenase: , iu/l; blood urea nitrogen: . mg/dl; creatinine: . mg/dl; amylase: (pancreas %) iu/l; creatine phosphokinase (ck): , iu/l; sodium: meq/l; potassium: . meq/l; chloride: meq/l; brain natriuretic peptide: . pg/ml; c-reactive protein: . mg/dl: prothrombin time international normalized ratio: . ; activated partial thromboplastin time: . ( . ) seconds; fibrinogen: mg/dl; ddimer: . μg/ml; human immunodeficiency virus (hiv) antibody: negative; pneumococcal urinary antigen test: negative; legionella urinary antigen test: negative; rapid influenza diagnostic test: negative; microscopic finding of sputum: negative: and urine drug screening test: negative. later, β-d glucan, rheumatoid factor, and anti-neutrophil cytoplasmic antibody were all found to be negative. he received a tentative diagnosis of pneumonia of unknown causes accompanying severe ards, rhabdomyolysis, and pancreatitis. as he showed deterioration of pao [pao /fio (p/f) = ] and a murray score of . , he underwent mechanical ventilation under . fio and cmh o with positive end-expiratory pressure (peep) and received indwelling venovenous ecmo (mera centrifugal blood pump system has-cfp; mera nhp exelung nsh-r hpo- wh-c; senko medical instruments, tokyo, japan) with the right jugular vein (return side, fr) and right femoral vein (drainage side, fr) as the exit. as this event occurred during the night shift, we did not attempt supine therapy before introducing venovenous ecmo. he also showed hypotension and therefore underwent infusion of noradrenalin followed by vasopressin and mg of hydrocortisone. due to concerns of pneumonia, he received . g of meropenem and mg of azithromycin in addition to an infusion of g of γ-globulin and ml of glycyrrhizin as antibacterial and antivirus treatments respectively. after the induction of ecmo, the mode of mechanical ventilation was changed to a lung rest setting ( . fio and cmh o with peep). additional cardiac echo showed diffuse hypokinesis with a % ejection fraction, and troponin t became positive [ pg/ml (normal range: < pg/ml)] on the first hospital day, and so he was diagnosed with myocarditis as a complication. on the second day, his blood pressure increased, resulting in a reduction in the vasopressor administration. his p/f remained under . on the third day, inflammatory data remained high, and hence azithromycin was replaced with levofloxacin. however, this led to skin reddening and he was switched back to azithromycin. a complication of anemia, thrombocytopenia, and coagulopathy required blood transfusion. a polymerase chain reaction (pcr) test for covid- using sputum through the endotracheal tube without bronchoalveolar lavage (performed twice) and initial cultures of sputum, urine, and blood were all negative. on the fifth day, the inflammatory data remained moderate, and hence meropenem was replaced with linezolid and piperacillin/tazobactam. on the same day, in an attempt to withdraw ecmo, the mechanical ventilation setting was changed from to cmh o for peep and from . to . for fio . this resulted in the p/f increasing to over . after the circulation flow of ecmo was reduced from to l/minute, the p/f remained over ; hence ecmo was ceased, and the cannulations were removed (figure ). as the patient was thought to require long-term mechanical ventilation, he underwent tracheostomy on the eighth hospital day. sedative administration was ceased, and a negative water balance was targeted by limiting the infusion volume and the use of diuretics. he showed a transient decrease in his p/f by the formation of atelectasis due to bloody sputum; however, the average p/f improved day by day. on the th hospital day, his p/f exceeded under cmh o for peep and . fio ; hence mechanical ventilation was ceased (figure ). the patient was managed by extracorporeal membrane oxygenation and mechanical ventilation with the lung rest setting on the third day and was withdrawn from mechanical ventilation on the th day day (left) shows bilateral ground-glass appearances. day (middle) shows the deterioration of bilateral radiolucency. day (right) shows clear lung fields he recovered his ability to excrete sputum by himself, and tracheal cannulation was removed on the th hospital day. even after ceasing all drugs for lung and inflammation, his pneumonia, rhabdomyolysis, and pancreatitis did not recur. he was discharged on the nd day on foot. the troponin t level remained high ( pg/ml) even after the ck level normalized, so he was followed up as an outpatient. the serum virus neutralization assay performed as a serological test using pair serum samples with a more than two-week interval for coxsackievirus b showed a four-fold increase in titer (from x to x ). finally, the troponin t level returned to the normal range and showed no subsequent complications. risk factors of direct lung injury involving ards include pneumonia (bacterial, viral, fungal, or opportunistic), aspiration of gastric contents, pulmonary contusion, inhalation injury, and near-drowning, while those of indirect lung injury involving ards include sepsis (nonpulmonary source), non-thoracic trauma or hemorrhagic shock, pancreatitis, major burn injury, drug overdose, transfusion of blood products, cardiopulmonary bypass, reperfusion edema after lung transplantation, and embolectomy [ , ] . the risk factor in the present case was unspecified pneumonia, and an unspecified virus was considered the most likely cause based on the negative results of all cultures, β-d glucan, and rapid test for bacteria and influenza. concerning covid- , while an outbreak had been reported in tokyo at the time, our patient did not live in a covid- -infected district; in addition, two tests for covid- were negative, and ct showed subpleural sparing with a ground-glass appearance, which is not common for covid- . accordingly, the possibility of covid- -related pneumonia was considered to be low. based on our investigations for virus infection, we suspect that coxsackievirus b might have been the responsible virus. however, there are few reports concerning coxsackievirus b infection with pulmonary involvement, and there have been no reports of ards induced by coxsackievirus b [ ] . accordingly, this might be the first case report of severe ards in an adult induced by coxsackievirus b infection. as we did not perform a direct examination of a pulmonary specimen, the possibility of co-infection with multiple viruses or reactivation of coxsackievirus b cannot be excluded. there are two main treatments for ards: treating the main cause of ards or offering supportive therapy for the severely injured lungs. supportive therapy involves oxygen and mechanical ventilation. according to the berlin definition, severe ards requires mechanical ventilation with a high peep and a high concentration of oxygen. when conventional mechanical ventilation fails to improve the arterial oxygenation and/or eliminate carbon dioxide, ecmo is indicated. another indication is circulatory and/or cardiac failure. the conventional ventilation mode can cause ventilator-induced lung injury, such as volutrauma, atelectrauma, and/or biotrauma. in addition, the continuous inspiration of high-concentration oxygen can also injure the lungs. the induction of ecmo helps avoid such mechanical-and oxygen-induced lung injuries by using the lung rest setting, allowing patients time to recover from their lung injuries [ ] [ ] [ ] . as the present case also showed marked hypoxia despite mechanical ventilation with a high concentration of oxygen and high peep, ecmo was introduced, and the lung rest setting was selected. the severity of ards depends on the amount of etiologic substances with corresponding immune reactions, the duration of the appearance of specific immune cells, and the repertoire of specific immune cells that control the substances. therefore, treatment with systemic immune modulators (corticosteroids and/or intravenous immunoglobulin) as soon as possible may reduce aberrant immune responses in the early stage of ards [ ] . the results from clinical trials have often been controversial; however, the administration of steroids may shorten the duration of mechanical ventilation, duration of hospitalization, and improve oxygenation, probably because of the wide spectrum of potentially desirable effects, including antiinflammatory, antioxidant, pulmonary vasodilator, and anti-edematous [ , , ] . lee et al. noted that early systemic immune modulators (corticosteroids and/or intravenous immunoglobulin) along with antibiotics or antivirals could halt the progression of pneumonia and induce a rapid recovery of pulmonary lesions in patients with ards [ ] . furthermore, macrolides also induce a broad range of immunological mechanisms that result in immunomodulatory effects; hence macrolide therapy can also help reduce mortality in patients with ards [ ] . accordingly, the variety of supportive therapies offered for ards may explain the favorable outcome in the present case. viral pneumonia was thought to be the most likely cause of ards in the present case. respiratory viruses are a common cause of severe pneumonia and ards in adults [ , ] . initially, the present case was suspected of having covid- infection, but this diagnosis was not supported by pcr performed twice. the percentage of patients with ards for which no causative organism has been identified despite bronchoalveolar lavage or pcr testing remains high (> - %) [ ] . although antiviral therapy is available for some respiratory viral infections, most viruses do not have any specific treatment. one of the antivirus therapies used in the present case was glycyrrhizin. glycyrrhiza glabra roots contain glycyrrhizic acid (glycyrrhizin), which is effective against viruses [ ] . glycyrrhizin inhibits the growth and cytopathology of several unrelated dna and rna viruses while not affecting human cell activity or their ability to replicate [ ] . glycyrrhizin is therefore now applied in the treatment of a variety of viral infections [ ] . traditional chinese medicines such as glycyrrhizin may also be effective against covid- infection [ ] . in addition, macrolide and γ-globulin can also exert an antiviral effect [ ] . these unspecific antiviral therapies may be useful treatments for the main cause of ards, which may have resulted in the favorable outcome obtained in the present case. the present case showed pneumonia, pancreatitis, rhabdomyolysis, and myocarditis. the involvement of two pathogens (salmonella typhi and mycoplasma) that have been reported to accompany such complications was not found in the present case [ , ] . however, cases of pneumonia, rhabdomyolysis, myocarditis, and pancreatitis induced by coxsackievirus b have been reported [ ] [ ] . accordingly, this virus may have been the causative pathogen of these complications in the present case. we presented a case of suspected virus-inducing severe ards that was treated by multimodal therapy including ecmo and immune modulation therapy. the wide range of supportive therapies and unspecific antiviral therapies offered for ards may have resulted in the favorable outcome obtained in the present case. human subjects: consent was obtained by all participants in this study. the review board of juntendo shizuoka hospital issued approval . this case study was approved by the review board of juntendo shizuoka hospital. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: this work was supported in part by a grant-in-aid for special research in subsidies for ordinary expenses of private schools from the promotion and mutual aid corporation for private schools of japan. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. acute respiratory distress syndrome: the ikegami et al berlin definition acute respiratory distress syndrome definition, causes, and pathophysiology acute respiratory distress syndrome acute 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pancreatitis and polyneuropathy rhabdomyolysis associated with infection by mycoplasma pneumoniae: a case report tumor necrosis factor and coxsackie b rhabdomyolysis development of potential antiviral strategy against coxsackievirus b key: cord- - dqa dd authors: jain, mehr; kim, sonya t; xu, chenchen; li, heidi; rose, greg title: efficacy and use of cloth masks: a scoping review date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: dqa dd during the coronavirus disease (covid- ) pandemic, there has been a global shortage of personal protective equipment (ppe). in this setting, cloth masks may play an important role in limiting disease transmission; however, current literature on the use of cloth masks remains inconclusive. this review aims to integrate current studies and guidelines to determine the efficacy and use of cloth masks in healthcare settings and/or the community. evidence-based suggestions on the most effective use of cloth masks during a pandemic are presented. embase, medline, and google scholar were searched on march , , and updated on april , . studies reporting on the efficacy, usability, and accessibility of cloth masks were included. additionally, a search of guidelines and recommendations on cloth mask usage was conducted through published material by international and national public health agencies. nine articles were included in this review after full-text screening. the clinical efficacy of a face mask is determined by the filtration efficacy of the material, fit of the mask, and compliance to wearing the mask. household fabrics such as cotton t-shirts and towels have some filtration efficacy and therefore potential for droplet retention and protection against virus-containing particles. however, the percentage of penetration in cloth masks is higher than surgical masks or n respirators. cloth masks have limited inward protection in healthcare settings where viral exposure is high but may be beneficial for outward protection in low-risk settings and use by the general public where no other alternatives to medical masks are available. disposable surgical face masks (also termed procedure masks) and respirators are essential components of personal protective equipment (ppe) for preventing the transmission of infectious diseases. both the canadian and international guidelines highlight the importance of proper usage of ppe among frontline healthcare workers (hcws) during the current coronavirus disease (covid- ) pandemic [ ] [ ] [ ] [ ] . the shortage of ppe observed worldwide as a result of this pandemic places both hcws and patients at risk [ , ] . although guidelines from the world health organization (who) and centre for disease control and prevention (cdc) suggest various strategies to optimize the supply of ppe in healthcare settings [ , ] , there are limited data on alternatives to surgical masks. in these situations, d-printed respirators or community-sourced homemade cloth masks may be potential sources to meet demand in healthcare and community settings. cloth masks are defined as masks made of cloth or any other fabric that has been previously used to make masks, such as cotton, gauze, silk, or muslin [ ] . surgical masks are certified/rated medical ppe that are fluid-resistant and are effective to protect the wearer from large particles of respiratory secretions known as droplets. comparatively, respirators, which are also certified medical ppe and have a variety of ratings (of which n is the most commonly used in north america), are useful for user protection against small respiratory particles known as aerosols or droplet nuclei [ ] . in both cases, the primary reason these ppe are used in healthcare is the protection of the wearer or inward protection. however, there is an additional role of both surgical masks and respirators to retain respiratory particles in order to avoid spread to others, also known as outward protection. prior to the covid- pandemic, the usage of cloth masks in healthcare and the community is commonly observed in many asian countries, including china and vietnam [ , ] . during the severe acute respiratory syndrome (sars) outbreak in , there were reports of the usage of cotton cloth masks among hcws in china [ ] . in the current covid- pandemic, chinese recommendations on face mask use in community settings suggest that cloth masks could be used in a very low-risk population to prevent the spread of disease [ ] . in the western world, the use of cloth masks is rarely witnessed in healthcare settings due to the availability of surgical masks and respirators. in times of a global pandemic with limited resources, cloth masks may be useful in protecting hcws and retaining fluids and droplets in infected patients. however, there is a lack of comprehensive literature that summarizes the latest findings on the extended use and reusability of cloth masks [ ] along with limited guidance on its use during the covid- pandemic. this review aims to integrate current studies and guidelines to determine the efficacy of cloth masks as both inward and outward protective equipment and whether they can be used in healthcare settings and/or the community in light of the ppe shortage. furthermore, evidence-based suggestions are made on the most effective use of cloth masks during the times of pandemic. the search strategy was conducted on march , , using an open date search strategy. the search terms used were "masks", "respiratory protective device", "facemask" to capture articles studying face masks. the terms "cotton", "cloth", "homemade", "home made", "diy", "do it yourself", "t-shirt", "muslin", "gauze", "cheese cloth", "towel", "fabric", "tight woven" and "tight weave" were used to find articles related to cloth masks. the search strategy was employed on embase, medline, and google scholar. the search strategy was updated on april , . the titles and abstracts obtained from search strategies were screened by three reviewers (c.x., s.k., m.j.). discrepancies were resolved by discussion between the three reviewers. the same reviewers also completed the full-text review. the reference list of studies selected for the review was screened by one reviewer to gather additional articles. the study population comprised hcws and healthy volunteers. two studies, one observational and one rct, were conducted on hcw participants [ , ] . another three studies were conducted on healthy volunteers [ , , ] . of the nine studies, four used cotton cloth masks [ , , , ] , one used polyester masks [ ] , and four [ , , , ] compared different types of materials commonly found in a home as possible materials for homemade masks. the characteristics and results of each study are summarized in table three studies measured inward protection of cloth masks in human subjects [ , , ] . out of three studies, one rct showed that the cloth mask group had the highest rate of influenza-like illness compared to the medical mask group and control group and cautioned that cloth masks should not be recommended for hcws in high-risk settings [ ] . however, the results from this study are difficult to interpret as the control group was "standard practice", comprising individuals using both medical and cloth masks. one other study showed that homemade masks made of tea cloth provided protection during short-and long-term activities compared to no mask [ ] . ma et al. showed that while n respirators blocked . % avian influenza virus, cloth homemade masks and surgical masks were comparable ( . % and . %, respectively). these homemade masks used in the experiment were made from polyester and kitchen towels [ ] . three articles showed that cloth masks resulted in higher rates of infection or particle exposure as compared to surgical masks [ , , ] . three studies specifically measured outward protection either with human subjects [ , ] or by simulating expiration with an artificial head [ ] . in human subjects, both surgical and cloth masks were effective in controlling the number of microorganisms released into the environment when coughing, though surgical masks were more effective, especially with smaller particles [ ] . in an older study, quesnel showed that a cotton mask, which was not homemade, provided equivalent outward protection as two other surgical masks [ ] . in an experimental setup with an artificial head, cloth masks provided marginal outward protection [ ] . a few studies compared the filtration efficacy of various household materials [ , ] . one such study assessed pressure drop across different household materials to assess comfort of material when used in the masks along with filtration efficiency against microbial aerosols. davies et al. used both bacillus atrophaeus ( . - . um) and bacteriophage ms ( nm) to generate microbial aerosols for the simulation of particle challenge. they found pillowcases and % cotton t-shirts to be most suitable to construct more efficacious cloth masks compared to tea towels, vacuum cleaner bags, silk, and so on [ ] . another laboratory study evaluated the penetration of monodispersed nacl aerosol particles through cloth masks made of various materials (sweatshirts, t-shirts, towels, or scarves). the penetration of these masks was - % at nm in diameter and - % at - nm [ ] . assuming that sars-cov particles are of a similar size as sars-cov particles from the - outbreak ( - nm), these nanoparticles are in the relevant size range [ ] . studies that compared filtration efficacy of cloth masks to surgical masks or n respirators found that particle penetration was consistently higher in cloth masks [ , ] . another study showed no significant difference in the efficacy of surgical masks compared to wellconstructed reusable four-ply cotton muslin masks when testing micro-and nanoparticles together [ ] . higher compliance with cloth masks is seen in low-to middle-income countries and during pandemics due to the overall lack of ppe [ , , ] . during the h n pandemic, the majority of doctors and nurses used cloth masks (self-reported: . %) over medical masks across eight hospitals in beijing, china [ ] . another study reported that hcws showed equal compliance when wearing cloth as compared to medical masks ( %), where compliance was defined as wearing the mask more than % of the time [ ] . the main adverse events that decreased compliance were general discomfort and difficulty breathing, though adverse events were reported in both medical and cloth mask groups ( . % and . %, respectively) [ ] . in kathmandu, nepal, % of the general population surveyed were found to wear cloth masks on the streets to protect themselves against pollution [ ] . the fit of a mask is an important variable in determining its efficacy. it is considered an area of weakness for cloth masks. davies et al. used the wilcoxon sign rank test to assess the fit of surgical and cotton cloth masks. the participants underwent a variety of head and body movements while wearing the masks, and fit testing was also performed at rest. they determined the fit of surgical masks to be significantly superior (p < . ) than cotton cloth masks in all activities and at rest [ ] . some studies reported reusability and resulting contamination of cloth face masks; however, only one study quantified this. this study showed a negative linear trend between washing and drying cycles and filtration efficacy (r = . ). after the fourth wash and dry cycle, the efficacy of the mask had decreased by %. microscopic imaging of these masks after wash and dry cycles showed an increase in pore size, change in pore shape, and decrease in the number of microfibers in each pore after these cycles [ ] . there are no current guidelines or standardized protocols on the use or creation of cloth masks. the who presented interim guidelines in march in the context of the covid- pandemic stating that they do not recommend the use of cloth masks in healthcare settings, in the community, or at home [ ] . another set of recommendations from who published on april , , also stated that cloth masks are not appropriate for hcws. if cloth masks are used locally, the who highly encourages local authorities to assess the masks [ ] . the cdc suggests that hcws use homemade masks if certified face masks are not available. however, they state that these masks are not considered ppe. the cdc also recommends that homemade masks should be used with a face shield covering the entire face [ ] . furthermore, on april , , the cdc released recommendations asking the general population to wear cloth masks in areas where socially distancing is not possible [ ] . they also released tutorials on how to create these masks [ ] . to our knowledge, this is the first review to descriptively synthesize and evaluate the best available evidence on the efficacy of cloth masks, providing relevant and useful information that can guide public health guidelines during the current covid- pandemic. to date, there are little data to make definite recommendations as only one rct [ ] and a few observational studies [ , , ] have been conducted on this topic. when assessing the overall clinical efficacy of cloth masks compared to surgical masks, two factors must be considered: inward and outward protection. the general consensus of the included studies is that cloth masks confer some degree of inward and outward protection, but are less effective than surgical masks and n respirators [ , , , ] . the clinical efficacy of a face mask is determined by the filtration efficacy of the material, fit of the mask, and compliance to wearing the mask [ ] . filtration efficacy of a material is the ability to function in both inward and outward protective gear. in general, household fabrics such as cotton t-shirts and towels [ , ] have some filtration efficacy and were shown to have some protection against virus-containing particles. however, the percentage of penetration in cloth masks was higher than surgical masks or n respirators. one study, however, suggested that a reusable cloth mask can have the same filtration efficacy as a surgical mask ( . %) [ ] . surgical and cloth masks provide less outward protection partly due to the weaker seal around these masks. when pressurized droplets or aerosolized particles are released from the user (e.g., during a cough or sneeze), these particles have a higher likelihood of escaping from the sides than the front of the mask due to the mask's fit. cloth masks are inferior to surgical masks or n respirators when assessing the fit of the mask [ ] . there is greater opportunity for air leakage around the sides of a cloth mask than the other two mask types, which decreases its ability to contain particles released by the user. however, dato et al. showed a reasonable fit of their homemade mask in a letter to the editor of emerging infectious disease. they presented a protocol for homemade % cotton masks that yielded a fit factor up to (n respirators must have a fit factor of at least ). their homemade mask provided significant protection in an aerosol challenge. the recommended use of these masks was in situations where n respirators were unavailable [ ] . compliance of cloth masks does not differ from that of medical masks, indicating that homemade masks or masks of varying household fabrics are not any less comfortable. the main side effects were difficulty breathing and general discomfort, which were not unique to cloth masks [ ] . in fact, in low-to middle-income countries, compliance may be higher due to a lack of availability of surgical masks. a study was conducted on focus groups of doctors and nurses in vietnam to assess their compliance and opinions of face masks. the groups reported both cloth and medical masks to be comfortable to breathe through. surgical masks were found to be associated with words such as "safe" and "effective", whereas cloth masks were associated with "dirty" [ ] . given the variety of options available for different types of cloth masks, all that have shown comparable efficiency [ ] while also allowing users to exert their preference and pick a material more comfortable to them. of the various sources searched, guidelines on the use and efficacy of cloth masks were limited to the who and cdc's commentary on cloth masks not qualifying as ppe and the cdc's suggestion of the general population using homemade masks [ , , ] . the who and earlier cdc [ , ] guidelines focused on the usage of cloth masks as ppe to protect the user from the environment (inward protection) and did not address the use of cloth masks to contain droplets and secretions produced by infected individuals (outward protection). cloth masks showed some evidence of outward protection [ ] and filtration against microbial aerosols and nanoparticles [ ] [ ] [ ] , ] , albeit in varying degrees, depending on the material. as a result, the potential for outward protection of cloth masks in healthcare settings should be better assessed and addressed in international guidelines. there have been other guidelines posted on the websites of the who, cdc, and canadian government, which suggest that cloth masks can aid in covering the mouth and nose when coughing [ , , ] . wearing a mask as prophylactic protection against a cough serves as better source control compared to finding mouth coverings spontaneously as needed. it should be noted that cdc recommended disposing of materials sneezed into [ ] . cloth masks can be cleaned to address this point in the guidelines. the government of canada also recommended the use of cloth masks by the public in situations where social distancing is not possible and stated that homemade cloth masks are not a replacement for surgical masks [ ] . moreover, british columbia centre for disease control (bccdc) guidelines state that contaminated cloth can be cleaned with other pieces of clothing in a laundry machine. hot water ( - °c) with soap should be used to clean the laundry machine [ ] . many low-and middle-income use cloth masks in healthcare settings due to a lack of financial resources to support the wide use of surgical masks. recommendations regarding cloth mask use in vietnam, pakistan, and china include wearing them during low-risk activity (e.g., slashes of fluid or blood, bacterial infection) in the situation of the influenza season and a pandemic [ ] . therefore, cloth masks that are regulated may provide some protection against viruses and bacteria. another benefit of using cloth masks in healthcare or community settings is that the production of these masks can be outsourced to freelancers or volunteers in the community if a stringent and tested protocol is developed. for example, in the covid- pandemic, the lack of face masks and other ppe has been a global concern. michael garron hospital in toronto, canada, asked volunteers to create cloth masks at home for use in healthcare due to lack of face masks. the project has provided volunteers with a protocol to follow when making the mask, but whether this protocol has been studied is unknown [ ] . there is a tested protocol available through davies et al.'s research study. this group designed and studied a protocol for cotton cloth masks; however, this protocol was not widely implemented as an effort to standardize or certify commercially available cloth masks [ ] . moreover, the cdc has also released a tutorial on creating homemade cloth masks; however, the web article does not state if this protocol or recommended materials to make the mask have been tested [ ] . there are several strengths to this review. this review provides a unique detailed analysis of the various characteristics that contribute to droplet retention and mask efficacy, including the filtration efficacy of the material, fit of the mask, and compliance of the user. the strength of this review lies in its systematic search of multiple databases and search strategies developed and conducted in conjunction with a research librarian. moreover, international and national guidelines were collected to present the real-world implementation of existing research on cloth masks. there are also several limitations to consider. firstly, the scope of the recommendations presented in this review was limited by the lack of data available on cloth masks. only one rct has been conducted to date and few observational studies exist. included studies did not present a quantitative analysis of the filtration efficacy and penetration of materials commonly used in cloth masks or report on the number of layers of cloth material required for maximized benefit and comfort. this highlights important research questions that future high-quality studies should explore to increase our understanding of the efficacy and use of cloth masks. secondly, the heterogeneity of the included studies notably precluded a meta-analysis. future studies should focus on defining comparable outcomes. another limitation includes the fact that our search criteria limited our review to focus only on published studies. by not including grey literature, the review potentially misses out on other perspectives and information about the usage of cloth masks. future studies should investigate the effectiveness of masks in reducing travel velocities and distances of droplets and aerosols during expiration and coughing, which may reduce the transmission of covid- . secondly, studies should also investigate the ability of cloth masks to reduce virus transmission by preventing the user from touching their face or droplets from landing on naso-oral surfaces. lastly, to support the cdc recommendation of only using homemade masks in a healthcare setting if a face shield is worn [ ] , studies should investigate the efficacy of cloth masks used with d-printed face shields. both are easily producible in situations of ppe shortage such as the covid- pandemic, and if proven to provide adequate protection for hcw, they can be easily be produced in bulk by the general public. results from these studies may be used to guide recommendations on the use of cloth masks for the general public when social distancing measures are in place. to better understand the role that cloth masks play in pandemics and infectious control generally, further rcts must be conducted. however, a study by macintyre et al. highlights the ethical challenge in designing a rct for mask use, as hcws in the control group cannot be asked to wear a mask when working in high-risk situations [ ] . as this rct did not address outward protection, future studies should look at whether cloth masks worn by infected patients can protect the transmission of infection among hcws by retaining droplets and fluids. future studies should make evident whether they are studying inward or outward protection as this discrepancy was unclear in some studies. cloth masks are shown to have limited inward protection in healthcare settings where viral exposure is high but may be beneficial for outward protection in low-risk settings and use by the general public where no other alternatives to medical masks are available. during unprecedented times, such as the covid- pandemic, when some organizations like the cdc are suggesting the general population to use cloth masks in public settings, further studies on cloth masks are imperative. the current data are not enough to guide clinical decision-making. given that cloth masks are used when the supply of surgical masks is low, it is important to assess the true efficacy of cloth masks compared to not wearing any masks. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. care of the adult critically ill covid- patient covid- guidance: independent health facilities using personal protective equipment (ppe) rational use of personal protective equipment ( ppe) for coronavirus disease ( covid- ) : interim covid- : doctors still at "considerable risk" from lack of ppe, bma warns challenges to the system of reserve medical supplies for public health emergencies: reflections on the outbreak of the severe acute respiratory syndrome coronavirus (sars-cov- ) epidemic in china optimizing supply of ppe and other equipment during shortages use of cloth masks in the practice of infection controlevidence and policy gaps understanding the difference mask-wearing and respiratory infection in healthcare workers in beijing, china health care worker practices around face mask use in hospitals in hanoi, vietnam evaluation of control measures implemented in the severe acute respiratory syndrome outbreak in beijing rational use of face masks in the covid- pandemic covid- , shortages of masks and the use of cloth masks as a last resort optical microscopic study of surface morphology and filtering efficiency of face masks simple respiratory protection-evaluation of the filtration performance of cloth masks and common fabric materials against - nm size particles a study on the microbial filtration efficiency of surgical face masks--with special reference to the non-woven fabric mask the efficiency of surgical masks of varying design and composition potential utilities of mask-wearing and instant hand hygiene for fighting sars-cov- testing the efficacy of homemade masks: would they protect in an influenza pandemic? professional and home-made face masks reduce exposure to respiratory infections among the general population a novel coronavirus associated with severe acute respiratory syndrome advice on the use of masks in the context of covid- strategies for optimizing the supply of facemasks accessed simple respiratory mask: simple respiratory mask maclntyre cr : current practices and barriers to the use of facemasks and respirators among hospital-based health care workers in vietnam communication resources accessed examining the policies and guidelines around the use of masks and respirators by healthcare workers in china, pakistan and vietnam we need masks every week! use of masks to help slow the spread of covid- key: cord- -qm cik authors: ulloa, nicolas; cook, jessica m; smithson, shaun title: a clinical challenge in the emergency department: a case of klebsiella infective endocarditis presenting with splenic abscess date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: qm cik infective endocarditis (ie) is a serious bacterial infection of the endocardium and/or heart valves that carries considerable morbidity and mortality. often presenting with very non-specific symptoms, this disease presents many challenges to the emergency medicine practitioner. a -year-old male with no pertinent medical history presented to the emergency department complaining of shortness of breath. he stated that his symptoms had been persistent for the last three weeks and were associated with malaise and fatigue. ct of the abdomen/pelvis with iv contrast revealed a -cm hypodensity of the spleen concerning for abscess versus infarct. he denied any trauma or iv drug use. follow-up ultrasound was ordered, which characterized the hypodensity as a splenic abscess. an echocardiogram was recommended for possible ie, and cardiology was consulted. the transthoracic echocardiogram was performed on hospital day , which showed minimal mitral valve thickening with mild mitral regurgitation. the interventional radiology (ir) service was consulted for the splenic abscess in order to perform ct-guided drainage. an ir drain was successfully placed on hospital day . on the same day, blood cultures grew klebsiella pneumoniae. on hospital day , that patient was transferred to the icu for possible empyema formation with signs of respiratory distress. the patient underwent ct of the chest that showed the development of a left-sided effusion. the patient had also been persistently tachycardic and febrile, with high leukocytosis since admission and worsening respiratory status. transesophageal echocardiogram (tee) was scheduled but put on hold due to worsening respiratory status. repeat tee was scheduled five days later, which showed mitral regurgitation and increased size of the vegetation despite antibiotic therapy. two days later, he was scheduled for mitral valve repair. when reviewing our case, the patient had both common and uncommon aspects of splenic abscess or ie. first, despite having respiratory symptoms for two weeks, the primary reason he came to the hospital was due to the new onset of fevers. he was febrile, tachycardic, and with significant leukocytosis. he continued to have fevers despite antibiotic therapy and ir drainage of the abscess. with no history of iv drug use history, negative transthoracic echocardiography, lack of immunocompromising condition, and blood cultures with gram-negative rods, ie became less likely of a diagnosis. establishing the diagnosis of ie proved to be exceptionally complicated, especially in the setting of a covid- pandemic. the most notable challenge was having a high index of suspicion despite any risk factors. the patient was a previously healthy -year-old male with no medical problems. ie continues to be a clinical challenge for physicians, especially in the emergency department, due to the lack of diagnostic criteria such as positive blood cultures or vegetations visualized on echocardiographic studies. ie has a wide gamut of presentations with different levels of acuity. diagnosis is more straightforward when patients present with obvious risk factors, but, in many cases, such as this one, those risk factors may be absent. a high index of suspicion is required, especially in patients with additional findings such as splenic abscess, embolic phenomenon, focal neurologic deficit, mycotic aneurysm, decompensated heart failure, new murmurs, or pleural effusions. infective endocarditis (ie) is a serious bacterial infection of the endocardium and/or heart valves that carries considerable morbidity and mortality. often presenting with non-specific symptoms, such as fever, chills, fatigue, and shortness of breath, this disease presents several challenges to the physician in the emergency department (ed). patients may lack well-known risk factors such as intravenous drug use, previous history of ie, and prosthetic heart valves, which can make it more difficult to consider in the differential diagnosis, especially during the influenza season and novel coronavirus disease (covid- ) pandemic in which there is an abundance of patients presenting with flu-like illness. it is important for the emergency medicine (em) clinician to be aware of the multiple manifestations of ie on history and examination, especially in the absence of such risk factors. the foundation of establishing a diagnosis requires blood cultures and definitive echocardiographic findings, neither of which is considered during the patient's time in the ed. early consideration, recognition, and treatment of ie are crucial for improved outcomes. obtaining timely blood cultures and administering appropriate empiric antibiotics in the ed coupled with early transthoracic/transesophageal echocardiogram (tte/tee) are essential to guiding therapy once the patient is admitted to the hospital. a -year-old male with no pertinent medical history presented to the ed complaining of shortness of breath. he stated that his symptoms had been persistent for the last three weeks and he also reporting malaise and fatigue. he was seen at a different hospital previously for the same symptoms and was discharged home with an albuterol inhaler, with no improvement. a few days prior to arrival, his symptoms worsened and he started to experience subjective fevers, which led to his second ed visit. while in the ed, his vitals showed a low-grade fever of . °f, tachycardia ranging from - , a normal blood pressure of / , and oxygen saturation of %. the ed team pursued a diagnostic workup for suspected covid- . physical examination was notable for an ill-appearing and diaphoretic male. cardiac examination revealed tachycardia without any obvious murmurs. pulmonary examination was notable for tachypnea but otherwise clear to auscultation. the abdomen was soft and non-tender. his lab workup was notable for a leukocytosis of . x /l (normal range: . - . x /l) and elevation in his inflammatory markers. he had an initial c-reactive protein of . mg/dl (normal range: - . mg/dl), esr of mm/hr (normal range: - mm/hr), lactate dehydrogenase of units/l (normal range: - units/l), and d-dimer of , ng/ml (normal range: - ng/ml), which are all elevated. his lactic acid was within the normal range. of note, his troponin was moderately elevated at . ng/dl (normal range: . - . ng/dl). the chest x-ray was unremarkable and the computed tomography (ct) angiogram of the chest was negative for any infectious etiology, pulmonary embolism, or dissection. ct of the abdomen/pelvis with iv contrast revealed a -cm hypodensity within the spleen, concerning for abscess versus infarct ( figure ). he denied any trauma or iv drug use. follow-up ultrasound was ordered which characterized the hypodensity as a splenic abscess. the patient received a "sepsis bundle", which included the administration of iv fluids, ceftriaxone, and azithromycin to cover empirically for covid co-infection; blood cultures were drawn in the ed and he was subsequently admitted to the "covid rule-out" medical floor of the hospital. the patient tested negative for covid- within a few hours. the infectious disease service was consulted and adjusted the antibiotic regimen to vancomycin and piperacillin-tazobactam. an echocardiogram was recommended to rule out ie and the cardiology service was consulted. the tte was performed on hospital day , which showed minimal mitral valve thickening with mild mitral regurgitation. the interventional radiology (ir) service was consulted for the splenic abscess with plans to perform ct-guided drainage. an ir drain was successfully placed on hospital day . on the same day, blood cultures grew klebsiella pneumoniae. on hospital day , the patient was transferred to the icu due to respiratory distress and suspected new empyema formation. a ct of the chest was ordered at that time, which showed the development of a leftsided pleural effusion, as seen in figure . the patient had also been persistently tachycardic and febrile, with high leukocytosis and gradually worsening respiratory distress since admission. tee was scheduled but was postponed due to worsening respiratory status. at this point, the cardiothoracic surgery service was consulted. they scheduled the patient for left-sided lung decortication the following day. while still intubated from the procedure, the patient was scheduled for tee the following morning, which revealed ie of the mitral valve. findings were discussed with cardiothoracic surgery service that initially recommended medical management. repeat tee was scheduled five days later, which showed mitral regurgitation and increased size of the mitral vegetation despite aggressive antibiotic therapy. two days later, the patient was scheduled for mitral valve repair by ct surgery. postoperatively, the patient's tachycardia resolved, leukocytosis improved, and his temperature normalized. he continued to improve during his hospital stay and was discharged days later without complications. splenic abscess is a fairly uncommon disease. some data suggest it has an incidence as low as . - . % [ ] . there are a variety of etiologies in which a patient can develop a splenic abscess, but most commonly, after trauma, and in patients who are immunocompromised, it develops secondary to disseminated infection [ ] . it is important to note that up to % of ie cases are complicated by splenic abscess formation [ ] . a splenic abscess most commonly presents with various non-specific symptoms such as fever, abdominal pain, and chills; this can make the diagnosis difficult based on clinical presentation alone. it should also be considered in patients who have recurrent or persistent fevers despite adequate antibiotic regimen. fortunately, the increasing use and accuracy of ultrasonography and ct have aided in confirming the diagnosis. a review of the literature helps illuminate some of the more common presentations of splenic abscess. specifically, fever has been noted by some sources to be present in as high as . % of patients [ , ] . additionally, . - . % had abdominal pain and . - % had a leukocytosis [ , ] . of note, some data suggest that up to % of patients had left-sided pleural effusions that were noted on chest x-ray [ ] . in terms of microbiology, sources have mentioned that streptococcus viridans, staphylococcus aureus, and klebsiella pneumoniae tend to frequently be identified as the causative agents [ , ] . mortality is consistently cited at - % [ , ] . currently, there is no gold standard approach to the management of splenic abscesses. the three current modalities of treatment are iv antibiotics alone, percutaneous drainage, and splenectomy. the literature shows they have similar survival rates, and the recommendation is that treatment should vary on a case by case basis [ ] . when reviewing our case, the patient had both classic and subtle presentations of splenic abscess. despite having respiratory symptoms for two weeks, the primary reason he presented to the hospital was due to the onset of new fevers. he was febrile and tachycardic, with a significant leukocytosis. he continued to have fevers despite antibiotic therapy and ir drainage of the abscess. after the development of a left-sided pleural effusion and empyema formation, which has been well documented to co-exist with splenic abscesses, he required decortication of the left lung. despite these interventions, the patient remained febrile and tachycardic until he had the infected valve repaired. blood cultures were positive for klebsiella pneumoniae, which is uncommon but has been noted in the literature when reviewing splenic abscesses. despite this, he did not fit into any high-risk population. he denied any trauma preceding his symptoms. furthermore, he lacked any immunocompromising conditions such as hiv, end-stage renal disease, or diabetes. the patient was a previously healthy -year-old male with no hospitalizations prior to this one. he adamantly denied any drug use, which was confirmed by a negative urine drug screen. the absence of iv drug use history, negative tte, lack of immunocompromising condition, and blood cultures that grew gramnegative rods all pointed away from ie as the primary etiology. ie is an infection of the endothelial layer of the heart and can disseminate rapidly. this disease continues to be diagnostically challenging for em physicians to diagnose primarily due to a variety of presentations, breadth of acuity, and often absence of identifiable risk factors. the modified duke's criteria, as shown in figure , are the standard for which clinicians diagnose ie. recent literature updates demonstrate that these criteria have an % sensitivity in establishing a diagnosis [ ] . unfortunately, very few aspects can be readily applied in the ed. positive blood cultures and echocardiographic findings are the hallmark tests for diagnosing ie. while non-invasive bedside tte is somewhat sensitive if the vegetation is large, the blood culture results are not available when the patient is presenting acutely ill in the first few hours of their ed hospitalization. an article was written by delaney regarding ie in the ed in which she established guidelines to increase detection and determine who may benefit from hospitalization and further workup, specifically, febrile elderly patients in the absence of a clear source, patients with prolonged fever of more than two weeks without clear etiology, patients with evidence of vasculitis or embolization with a new murmur or change in old murmur, patients with fever plus known structural heart disease or recent instrumentation without a clear source, patients with fever and with cardiac prosthesis or any duration of malaise, vasculitis, or new murmur, and, finally, any febrile iv drug users [ ] . given the increasing prevalence of structural heart disease that is associated with aging, elderly patients with fever lasting more than two weeks should undergo workup that includes ie. additionally, they are more susceptible to bacterial illnesses. an individual with fevers longer than two weeks is unlikely to have a benign etiology and should be further evaluated. signs of vasculitis, embolization, and new murmurs should lead to an increased index of suspicion as they can be signs of acute pathology and disseminated infection. predisposing conditions such as structural heart disease, prosthetic heart valves, and iv drug use are significant risk factors for ie, and anyone with an associated fever without a clear source should be further evaluated [ ] . although quite dated, the article illustrates significant key features that can aid the em physician in considering ie. of note, other significant risk factors include previous diagnosis of ie, immunocompromised state, indwelling lines for venous access, and chronic kidney disease [ ] . echocardiography remains a critical element in diagnosing ie. tte tends to be the first image modality due to its convenience and non-invasiveness. despite this, the sensitivity of tte in diagnosing ie is merely % [ ] . there is a direct correlation between the size of the vegetation and the detection on tte. the literature demonstrates that tte has a sensitivity of %, %, and % for vegetations < mm, - mm, and > mm, respectively [ ] . although there is a lack of literature comparing pocus (point-of-care ultrasound) in the ed to a gold standard, it is reasonable to assume that sensitivities may be more variable than the standard of care tte, depending on the em providers proficiency with bedside ultrasound. any patient with a high degree of suspicion for ie and a negative tte should be followed up with a tee when possible, as they have a sensitivity of % [ ] . ie is associated with significant morbidity and mortality, making early diagnosis with appropriate therapy paramount. some studies have noted a -day mortality of % [ ] . a korean study compared the difference between early surgical intervention and conventional medical treatment, with primary outcomes being hospital death or embolic events within six weeks. the research showed a statistically significant difference between the two groups respectively ( % vs %) [ ] . the main difference is observed in the reduced embolic rates noted in the early surgery group [ ] . the study reinforces the importance of early intervention, which requires a timely diagnosis. when reviewing our case, establishing the diagnosis of ie proved to be exceptionally complicated, especially in the setting of the covid- pandemic. the most notable challenge was having a high index of suspicion for ie despite the lack of risk factors. the patient was a previously healthy -year-old male with no medical problems. he had no immunocompromising conditions, no congenital/structural heart defects, and normal dentition. of note, he adamantly denied drug use. on examination, he was ill-appearing, febrile, and tachycardic, with laboratories significant for high leukocytosis, elevation in inflammatory markers, and mild troponin elevation, which are non-specific. the key feature of the disease process was that ct of the abdomen/pelvis revealed an acute splenic abscess. in the absence of other risk factors for abscess, disseminated disease from ie had to be considered. even after a non-diagnostic tte, a follow-up tee would have ideally been performed next. unfortunately, the patient's respiratory status deteriorated after the development of a left-sided empyema, which delayed the procedure, diagnosis, and, ultimately, the treatment. the management of ie in the setting of an associated splenic abscess requires certain considerations. for example, some suggest splenectomy/drainage should take place before valve repair to prevent secondary infection [ ] . depending on the stability of the patient's condition, there is literature to suggest that splenectomy/drainage can occur simultaneously with valve repair as a one-stage process [ ] . our patient's course was complicated by ongoing fevers and tachycardia and the development of a left-sided empyema even after drainage of the splenic abscess, which delayed tee until after his lung decortication. his clinical picture began to improve after his mitral valve was repaired, and the remainder of his hospital course was uneventful. ie continues to be a clinical diagnostic challenge for physicians, especially in the ed, due to the lack of diagnostic criteria such as immediate positive blood cultures or ease of visualized vegetations on bedside echocardiographic studies. ie has a wide gamut of presentations with different levels of acuity. diagnosis is more straightforward when patients present with obvious risk factors, but, in many cases, such as this one, a high index of suspicion is required, especially in patients with additional findings such as splenic abscess, embolic phenomenon, focal neurologic deficit, mycotic aneurysm, decompensated heart failure, new murmurs, or pleural effusions. additionally, a contemporary scoring system/decision-making tool should be proposed and further studied to aid clinicians in earlier diagnosis, especially in the ed. ie carries significant mortality and would justify an aggressive push for performing tee early in the hospital course. protocols should be established to facilitate this process splenic abscess: a single institution study and review of the literature splenic abscess associated with infective endocarditis; case series splenic abscess: outcome and prognostic factors . coll physicians surg pak infective endocarditis: a contemporary update endocarditis in the emergency department diagnostic accuracy of transthoracic echocardiography to identify native valve infective endocarditis:a systematic review and meta-analysis early surgery versus conventional treatment for infective endocarditis human subjects: consent was obtained by all participants in this study. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -u z cpfk authors: gupta, ishita; reddy, mithun k; hussain, mir mehdi; murthy, pooja m; robert, chris a title: atypical neurological manifestations of covid- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: u z cpfk the novel coronavirus (sars-cov- ), belonging to a group of rna-enveloped viruses and believed to be transmitted by aerosol route, is a worldwide pandemic. many studies have described typical clinical manifestations such as fever, cough, fatigue, diarrhea, and nasal congestion. however, to our knowledge, there are minimal studies on the neurological manifestations in sars-cov- positive patients. our review aims to identify the various neurological manifestations in sars-cov- positive patients, which could be an added advantage in the early diagnosis and prevention of further complications of the nervous system. this study did not require ethical approval as data was obtained from already available databases, and patients were not directly involved. a total of eligible studies were screened and found eligible for data extraction (see table ). the study reports , covid- positive patients with males ( . %) and females ( . %) as seen in figure . the age range of the patients was six weeks to years, with a median age of years -almost all patients presented with neurological and non-neurological symptoms (see table ) [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the most common non-neurological symptoms were fever ( . %) and coughing ( . %). other non-neurological symptoms were diarrhea, anorexia, myalgia, sore throat, dyspnea, chest pain, fatigue, headache, arthralgia, nausea, and vomiting (see figure and table ) [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . among neurological symptoms, headaches were the most common [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . both central nervous system (cns) and peripheral nervous system (pns) symptoms were analyzed, and it was found that a higher number of patients had peripheral symptoms. headache was seen in patients and dizziness in patients; impaired consciousness and altered mental states were seen in patients [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . five patients also complained of neuralgia and two patients complained of paresthesia [ , , ] . gait abnormality was observed in one patient [ ] . guillain-barré syndrome (gbs) was the diagnosis in four cases (see table ) [ , , , ] . olfactory symptoms were present in patients and mainly included anosmia in patients [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . hyposomnia was seen in patients. ageusia was observed in patients and included loss of salty, sweet, sour, and bitter tastes [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . ocular symptoms were seen in patients and included conjunctivitis, including conjunctival hyperemia in three, chemosis in eight, epiphora in seven, and increased secretions in seven [ ] . one patient also presented with sensorineural hearing loss [ ] . one patient was found to be encephalopathic, nonverbal, and unable to follow any commands (see figure and table ) [ ] . the six-week preterm infant had a witnessed episode of sustained upward gaze associated with bilateral leg stiffening and decreased responsiveness lasting ten seconds with subsequent return to baseline and no hypoxia or vital signs change [ ] . our results show that there is a wide range of symptoms that a covid- patient can present with. hence, physicians must suspect covid- in those presenting with neurological symptoms as well. coronaviruses are a group of viruses that can involve and affect multiple organ systems. they can affect both humans and animals [ ] . the novel coronavirus sars-cov- is the causative agent of covid- . coronaviruses are a group of enveloped viruses [ ] . the alphacoronavirus and betacoronavirus infect mammals [ , ] . coronaviruses are spread mainly by the aerosol route. they can also be spread by feco-oral transmission and through fomites. human coronaviruses primarily target the epithelial cells of the respiratory epithelium, whereas the animal coronaviruses have their main affinity towards the epithelial cells of the digestive tract [ ] . three human coronaviruses produce symptoms that are severe: . severe acute respiratory syndrome coronavirus (sars-cov) . severe acute respiratory syndrome coronavirus (sars-cov- ) all the above three viruses belong to betacoronavirus [ ] . coronaviruses are primarily attracted to the respiratory epithelium [ ] . some studies provide evidence of neuronal involvement of sars-cov- . the nervous tissue expresses the ace- (angiotensin-converting enzyme- ) receptor, which has been detected over the glial and the neural tissues. sars-cov- has an affinity for the ace- receptors, thus making the nervous system a probable target of sars-cov- [ ] . sars-cov- being a new emergent virus, little is known about its mechanism of action. because of its genomic similarity with severe acute respiratory syndrome (sars-cov) and middle east respiratory syndrome (mers-cov), it is considered to mimic them [ ] . in the mediterranean sars-cov infection, the autopsy findings showed evidence of neural tissue involvement [ ] . the spread of sars-cov- through the cribriform plate, which is in close proximity to the olfactory region, has been demonstrated in patients affected with sars-cov- . sars-cov- can spread through two different pathways [ ] . the virus may enter the systemic circulation and enter the cerebral arteries through which it gains access to the brain. the endothelium of the capillaries also contains the ace- receptors [ ] . thus, the virus may get attracted to the ace- receptors and destroy the capillary endothelium, thus breaking the blood-brain barrier and entering the brain. the virus starts multiplying in the brain and can spread along the neural tissue due to the presence of ace- receptors and can cause neural damage without significant inflammation [ ] . the accessory pathway through which the sars-cov- can gain entry to the cns is through the cribriform plate as it is in close proximity to the olfactory bulb [ ] . after a comprehensive screening of the available literature, a total of eligible studies, which included mostly case series and case reports, were selected, and the patient data was assessed. the study reports a total of covid-positive patients, of which were males ( . %) and were females ( . %) as seen in figure . the age range of the patients was six weeks to years, with an average age of years as seen in table . the majority of patients in our study ( ) were european in origin [ , , ] . a wide variety of comorbidities such as asthma, hypertension, hypothyroidism, and diabetes mellitus were present. ground glass opacities were the most common radiological findings. the patients presented with a wide range of neurological and non-neurological symptoms, as summarized below. all patients were screened for covid- by oropharyngeal swab testing. table outlines the non-neurological symptoms of patients. the most common nonneurological symptoms include fever ( . %), cough ( . %), anorexia ( . %), myalgia ( . %), and diarrhea ( . %). other non-neurological symptoms were throat soreness, dyspnea, chest pain, fatigue, headache, arthralgia, nausea, and vomiting. chest pains, throat soreness, and dyspnea were seen in very few patients. table outlines the neurological manifestations of the patients in the study. both cns and pns symptoms were analyzed, and it was found that more patients had peripheral symptoms. the presentation of olfactory symptoms in sars-cov- -affected patients is due to the fact that the illness spreads through the cribriform plate, which is in close proximity to the olfactory region [ ] . gbs was diagnosed in four cases, but the outcomes were not specified [ , , , ] . one patient also presented with neurosensory hearing loss [ ] . this patient was cared for with standard respiratory care and recovery. there was no observation of a change of hearing loss in this case. auditory complication due to coronavirus is little mentioned in the literature [ ] . a -year-old male patient was found to be encephalopathic, nonverbal, and unable to follow any commands [ ] . considering the possibility of subclinical seizures due to an area of encephalomalacia and epileptiform discharges in the right temporal region, anti-epileptic medications were given prophylactically. the patient was treated empirically with vancomycin, meropenem, and acyclovir [ ] . a lumbar puncture did not indicate any evidence of central nervous system infection. due to his progression in symptomatology, he was then tested for covid- and found to be positive [ ] . the patient developed respiratory failure, required intubation, and was transferred to the icu. the patient was started on hydroxychloroquine and lopinavir/ritonavir and was continued on broad-spectrum antibiotics. the patient is critically ill with poor prognosis and currently remains in the icu [ ] . the six-week preterm infant had a witnessed episode of sustained upward gaze associated with bilateral leg stiffening and decreased responsiveness lasting ten seconds, with a subsequent return to baseline, and no hypoxia or vital signs change [ ] . a -year-old male patient from france with no significant comorbidities who was infected with sars-cov- presented with paresthesia in feet and hands, had a fever and cough for two days, and developed severe flaccid tetraparesis within three days [ ] . electrodiagnostic tests five days after neurological symptom onset showed a demyelinating pattern in accordance with gbs criteria. on needle examination, no rest-activity was observed [ ] . during muscle contraction, only one single motor unit was recorded with a firing rate up to hz in the right tibialis anterior, the right vastus lateralis, the left first interosseous, and the left deltoideus muscles. on cerebrospinal fluid (csf) analysis, the protein level was . g per liter, and the cell count was normal [ ] . anti-gangliosides antibodies were absent in the serum. our results show that there is a wide range of symptoms that can be presented by covid- patients. hence, physicians must suspect covid- in those presenting with neurological symptoms as well. this systematic review of the current literature on covid- provides insight into some of the atypical manifestations of the disease. with the pandemic continuing to unfold, research is the need of the hour. even with massive numbers of publications, gaps remain in the understanding of the natural history of the disease. further studies need to be undertaken in this regard. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. association of chemosensory dysfunction and covid- in patients presenting with influenza-like symptoms presentation of new onset anosmia during the covid- pandemic evidence of the covid- virus targeting the cns: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms neurological manifestations in covid- caused by sars-cov- identification of coronavirus isolated from a patient in korea with covid- . osong public health res perspect neurological complications of coronavirus disease olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (covid- ): a multicenter european study isolated sudden onset anosmia in covid- infection. a novel syndrome neurological manifestations of hospitalized patients with covid- in wuhan, china: a retrospective case series study self-reported olfactory and taste disorders in patients with severe acute respiratory coronavirus infection: a cross-sectional study a first case of meningitis/encephalitis associated with sars-coronavirus- covid- -associated acute hemorrhagic necrotizing encephalopathy: ct and mri features guillain-barre syndrome associated with sars-cov- infection: causality or coincidence sudden and complete olfactory loss function as a possible symptom of covid- hearing loss and covid- : a note characteristics of ocular findings of patients with coronavirus disease (covid- alterations in smell or taste in mildly symptomatic outpatients with sars-cov- infection covid- may induce guillain-barre syndrome guillain-barré syndrome following covid- : new infection, old complication neurologic manifestations in an infant with covid- meningoencephalitis without respiratory failure in a young female patient with covid- infection in downtown los angeles, early april concomitant neurological symptoms observed in a patient diagnosed with coronavirus disease acute-onset smell and taste disorders in the context of covid- : a pilot multicenter pcr-based case-control study guillain barre syndrome associated with covid- infection: a case report miller fisher syndrome and polyneuritis cranialis in covid- the springer index of viruses the springer index of viruses family -coronaviridae. virus taxonomy the neuroinvasive potential of sars-cov may play a role in the respiratory failure of covid- patients letter to the editor regarding the viewpoint "evidence of the covid- virus targeting the cns: tissue distribution, host-virus interaction, and proposed neurotropic mechanism key: cord- -jfpbkntx authors: parashar, bhupesh; chen, william c; herman, joseph m; potters, louis title: disease site-specific guidelines for curative radiation treatment during ‘limited surgery’ and ‘hospital avoidance’: a radiation oncology perspective from the epicenter of covid- pandemic date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: jfpbkntx the covid- pandemic has resulted in an unprecedented situation where the standard of care (soc) management for cancers has been altered significantly. patients with potentially curable cancers are at risk of not receiving timely soc multidisciplinary treatments, such as surgery, chemotherapy, radiation therapy, or combination treatments. hospital resources are in such high demand for covid- patients that procedures, such as surgery, dentistry, interventional radiology, and other ancillary services, are not available for cancer patients. our tertiary care center is considered the center of the epicenter in the usa. as a result, all non-emergent surgeries have been suspended in order to provide hospital beds and other resources for covid- patients. additionally, ambulatory efforts to avoid treatment-related morbidity are critical for keeping patients out of emergency departments and hospitals. in this review article, we discuss evidence-based radiation therapy approaches for curable cancer patients during the covid- pandemic. we focus on three scenarios of cancer care: ) radiation therapy as an alternative to surgery when immediate surgery is not possible, ) radiation therapy as a ‘bridge’ to surgery, and ) radiation options definitively or postoperatively, given the risk of hospitalization with high-dose chemotherapy. the main challenge faced during the coronavirus disease pandemic is the need to maintain access to proper cancer treatment. in order to achieve access, the staff providing those services must be safe, healthy, and available. the pandemic has resulted in an unforeseen and unprecedented situation where major hospitals and academic centers are overwhelmed with covid- patients, with limited access to standard of care (soc) cancer treatments. for example, most operations are being postponed in order to provide hospital capacity for covid- patients and also to reduce the risk of covid- infection in patients that undergo surgery for non-emergent clinical situations. amid this social and medical upheaval, there is concern and confusion regarding the best way to manage the treatment of potentially curable cancer patients. recommendations regarding palliative treatment for incurable cancer cases are published elsewhere [ ] [ ] . in this review, we discuss radiation therapy (rt) options for cancer patients in three settings: ) rt as an alternative to surgery when immediate surgery is not possible, ) rt as a 'bridge' to surgery and ), radiation options definitively or postoperatively, given the risk of hospitalization with high-dose chemotherapy. the proposed guidelines are evidence-based and are being successfully used in our major and the largest tertiary care academic health center in new york, the center of the epicenter. in general, cancer patients who may be at an increased risk of having more complications from covid- include those with uncontrolled diabetes, chronic lung infections, and patients currently on cancer treatments. in order to minimize the risk of exposure to covid- and maintain high-quality patient care with optimal disease outcomes, we have used the following principles to guide our institutional approach to cancer care: . when available, test cancer patients and staff for coronavirus infection and exposure . follow or create safety protocols to prevent infections for patients and staff . multidisciplinary discussion for each patient case (virtual or in-person with social distancing) . short-course hypofractionated rt is preferred when feasible . conservative (smaller) rt fields are preferred, if possible, to minimize rt-induced lymphopenia and reduce mucosal toxicity . consider enrollment into clinical trials to collect data and information on this cohort of patients. consider enrollment onto clinical trials if infected with the coronavirus. also, the following general recommendations should be considered while treating cancer patients with radiation during covid- : . aggressive and preemptive management of side effects includes early interventions, such as skin creams, anti-diarrheal, cough suppressant, antiinflammatory, and nutritional supplements radiation is considered immunosuppressive due to the sensitivity of lymphoid cells to radiation-induced cell death. however, given the focused nature of current external beam radiation therapy (ebrt) techniques, the quantitative effect of rt on the immune system is limited. in contrast, systemic treatments, such as chemotherapy, monoclonal antibodies, small molecule inhibitors, and immunotherapy, can result in substantial reductions in host immunity due to systemic effects on bone marrow and circulating blood cells [ ] . conformal ebrt results in limited exposure of healthy tissues to radiation for most sites. therefore, the clinically significant immune suppression caused by conformal radiation therapy, e.g., threedimensional conformal radiation therapy ( dcrt), intensity-modulated radiation therapy (imrt), and stereotactic body radiation therapy (sbrt), is limited when compared to chemotherapy, as commonly seen in clinical settings ( ) . in cases where patients are treated with large ebrt fields that include a significant amount of bone marrow, e.g., palliative rt to spine or pelvis, peripheral blood counts can be compromised [ ] . curative treatments should be prioritized based on the tumor site, histology, performance status, and stage. in general, the american society of clinical oncology (asco) and the american society of therapeutic radiation oncology (astro) guidelines suggest that specific non-emergent treatments for early-stage prostate and breast cancer should be delayed [ ] [ ] [ ] [ ] . in other cases, there are few recommendations related to the current covid situation. therefore, decisions regarding management should be based on a multidisciplinary discussion with the entire team and intended for the current covid- crisis (or future similar crises) when surgical treatments and chemotherapy are not readily available or are not preferred based on the patient's risk profile. the recommendations we propose are not always considered the soc during 'non-crisis' settings but are meant to maintain high-quality care and optimal disease outcomes for curative cases. the recommendations below assume surgery is not available or not recommended based on the patient's risk profile, and full-dose chemotherapy may be risky given systemic side effects and risk of patient hospitalization. in all situations where concurrent chemotherapy is a standard approach, it should be continued if the multidisciplinary team agrees that the risk of toxicity is low and the toxicities can be easily managed in an ambulatory setting without exposing the patients to unnecessary risks of hospitalization. if the risk of hospitalization is high, a different approach should be used: ) sequential chemotherapy and radiation, ) reduction of chemotherapy dose, ) use of a less toxic concurrent systemic or targeted therapy, or ) rt alone with an option of altered fractionation to compensate for lack of chemotherapy. head-and-neck cancers (hnc), most commonly squamous cell carcinoma (scc), are usually considered high-risk for local progression and need to be managed sooner than later. all decisions should be based on a multidisciplinary management approach. in patients who are considered candidates for rt alone, treatment may be started with a focus on hydration, minimizing the risk of hospitalization by excellent nutritional support and social support. pretreatment dental evaluation should be performed if possible but could be a challenge during the pandemic, given the lack of resources and risk of infections to patients and health care workers. patients should be made aware of the challenges of not performing proper dental evaluation before rt and the associated risk of osteonecrosis and worsening dentition. dental guards can be used to reduce electron scatter and reduce toxicity. older patients (> years old) who are unable to undergo surgery or concomitant chemoradiation for the advanced disease may be treated with hypofractionated rt or sbrt, - gy in five fractions delivered every other day. however, other fractionations are also reported to show acceptable results [ ] [ ] [ ] . rt plans should be conformal, keeping the mandible and dental dose as low as reasonably possible. in these situations, the gross tumor should be covered as a part of the primary planning target volume (ptv) and the elective nodal region avoided to minimize the risk of severe toxicity that may result in hospitalization. although rt should be completed in the shortest possible time, older patients that develop toxicities may need to be given a break from treatment rather than continuing and putting them at risk of hospitalization in a high-risk covid- patient-filled hospital. for human papillomavirus (hpv)-associated oropharyngeal cancer, rt alone is an option for early-stage disease ( gy in gy/fraction). for hpv-negative disease, concomitant chemo-rt should be standard of care, with modified chemotherapy/targeted dose regimens. if chemotherapy is not possible, rt alone (using altered fractionation, dose-escalation, or sbrt) may be appropriate [ ] . for laryngeal cancers (supraglottic, subglottic) and hypopharyngeal cancers, ebrt alone may be utilized ( gy in gy per fraction). for glottic cancers, rt to gy in fractions is the standard and should be followed [ ] . for nasopharyngeal cancers, rt with chemotherapy may be preferred given survival benefit seen in multiple studies compared to rt alone, although rt alone should be used if systemic therapy is risky and cannot be used ( gy in gy/fraction) [ ] . for parotid cancers, primary surgery is the preferred treatment. therefore, delaying treatment for a few weeks until surgery can be performed may be a reasonable approach. however, if the patient is unable to wait or the tumor is progressing, ebrt ( gy in gy/fraction) or sbrt ( - gy in five fractions) may be utilized [ ] . a similar rationale can be applied to other salivary gland cancers. oral cavity cancers are primarily managed with surgery, and efforts should be made to wait if surgery cannot be performed immediately. other options include induction chemotherapy, preoperative radiation, or definitive ebrt/sbrt. preoperative rt is a good option if surgery is being considered within four to six weeks after completion of rt ( gy in gy/fraction) [ ] . this rationale may be valid for the paranasal sinus tumor as well. for high-risk hnc post-resection, adjuvant rt alone may be preferred to chemoradiation to limit toxicity ( - gy in . - gy/fraction). for patients with multiple nodes, extracapsular extension (ece), and other high-risk features where adding chemotherapy is the standard [ ] , modified chemotherapy doses or less toxic regimens may be used in consultation with the medical oncology team. if adding chemotherapy puts the patient at risk of potential hospitalization, rt alone may be the preferred approach. astro/european society of therapeutic radiation oncology (estro) consensus practice recommendations for head and neck cancers during the covid- pandemic were recently published [ ] [ ] . small cell lung cancers are usually treated with a combination of chemotherapy and radiation to the thorax for limited-stage disease, followed by prophylactic cranial irradiation (pci). for extensive-stage disease, chemotherapy followed by thoracic rt and pci may be offered for those responding to chemotherapy [ ] . rt alone to the chest should be considered if chemotherapy is challenging. pci may be given for both limited-stage and extensive-stage disease. rt dose to the thorax may be - gy in . - gy once a day fraction for limited-stage cancer and gy in fractions to the thorax for the extensive-stage disease. the pci dose is gy in fractions [ ] . for patients with peripheral stage i/iia non-small cell lung cancer, sbrt may be an appropriate option. given a biopsy of the lesions may be challenging, sbrt without pathologic confirmation may be considered after a multidisciplinary discussion if a biopsy is not available or if the patient is at a high risk of complications from a biopsy. the national comprehensive cancer network (nccn) recommended sbrt dose options are listed below ( ) . options utilizing fewer fractions may be preferable to limit patient visits to the department ( table ) . rt: radiation therapy surgical resection is the soc, and radiation is offered postoperatively for high-risk categories. postoperative rt may be omitted for low-risk thymomas (e.g., stage i thymoma). for higherrisk thymomas, preoperative radiation may be used if surgical resection is not available at this time with an intention to operate within a few weeks of completing rt. chemotherapy may be added preoperatively or postoperatively for high-risk clinical presentations [ ] [ ] . as per the nccn, the adjuvant rt dose is to gy for negative margins, gy for microscopically-positive margins, and - gy for gross residual disease in conventional fractionation ( . - . gy/fraction) [ ] . for medically inoperable patients, a dose of - gy in . - gy/fraction is recommended. for patients unable to undergo surgery due to constrained resources from the pandemic, a preoperative rt/chemoradiation therapy (crt) approach can be used with - gy in conventional fractionation [ ] [ ] . if surgery or concurrent chemoradiation is a challenge, rt alone or induction chemotherapy may be an option [ ] . preoperative rt should be considered if surgery may become available in a few weeks once the covid-related risks diminish. limiting rt fields to the gross tumor, plus margins may reduce the risk of treatment-related toxicity. recommended rt doses [ ] : if surgery is not available, preoperative radiation can be utilized to delay surgical intervention. there are several studies showing a good pathological response to preoperative rt [ ] [ ] [ ] . this strategy may help reduce tumor burden and also serve as a bridge until surgery and chemotherapy become available. a chinese study evaluated preoperative rt to surgery alone and showed significant local control and survival benefit to adding preoperative rt [ ] . the rt dose in the study was gy in conventional fractionation to the cardia, lower segment of the esophagus, fundus, lesser curvature, and hepatogastric ligament. additional studies have shown the benefit of preoperative radiation with chemotherapy [ ] [ ] . preoperative radiation dose: - gy in . - gy per fraction postoperative rt: - . gy in . - gy per fraction [ ] pancreatic cancer standard fractionated chemoradiation has been shown to prevent local recurrence in the adjuvant setting and decrease local progression in the locally advanced setting [ ] [ ] . in patients with borderline resectable pancreas cancer, neoadjuvant chemotherapy and radiation have resulted in margin-negative resection rates and overall survival that is comparable to those patients who present with a resectable disease [ ] . while studies have shown similar outcomes when rt is given concurrently with gemcitabine or capecitabine, capecitabine results in a lower risk of neutropenia and immunosuppression and, therefore, should be preferred during the current pandemic [ ] . multiple single and multi-institutional studies have shown that sbrt given over three to five days in - and - gy fractions, respectively, results in survival outcomes that are similar to chemoradiation with less toxicity [ ] . if fiducial placement is challenging, pre-treatment images, such as magnetic resonance imaging (mri), computed tomography (ct) scan, or positron emission tomography-computed tomography (pet-ct), should be fused with a treatment planning scan. if possible, it is preferable to use shorter rt treatment delivery times by using manual breath-hold (with coaching) and abdominal compression as opposed to conebeam computed tomography (cbct) or mri as it can take longer to deliver the therapy. specifically, if there is no duodenal or stomach invasion, doses less than gy x or gy x can be given safely without fiducials or specialized imaging (mri). however, larger sbrt doses should not be delivered if there is bowel/stomach invasion, with or without either fiducial, image-guided radiation therapy (igrt), gating, and mr-guided rt [ ] . according to the nccn, for resectable preoperative chemoradiation, the following rt doses have been reported: gy in . gy fractions to - gy in . - . gy fractions [ ] . surgery may be performed four to eight weeks after rt. for resected pancreatic adenocarcinoma, the rt dose generally consists of - gy in . - . gy fractions to the tumor bed, surgical anastomoses (hepaticojejunostomy and gastrojejunostomy may be omitted if clinically appropriate), and adjacent lymph node basins, potentially followed by an additional - gy to the tumor bed, and anastomoses, if clinically appropriate [ ] . in rare occurrences, sbrt could be used in the adjuvant setting if there is a gross residual disease (r resection) that can be targeted based on anatomy or surgically placed clips and bowel is not in the field. for unresected pancreatic adenocarcinomas, a short course of sbrt is appropriate. nccn cites sbrt doses of three fractions (total dose: - gy) or five fractions (total dose: - gy) [ , ] . if chemotherapy and surgery are not possible or best avoided given the hospital's resources, rt may be used as a regimen for local control, although it is certainly not the standard [ ] . if resection has already been performed, rt may be directed to the tumor bed for high-risk diseases, such as t disease due to penetration to a fixed structure. for postoperative rt, - . gy can be delivered in . - gy per fraction. preoperative rt may be utilized as a bridge to the time surgery may be performed with concomitant chemotherapy, if possible (or without chemotherapy if the combination is risky), in - . gy in . - gy/fraction [ ] [ ] . if surgery is not being planned (given the pandemic) and abdominal malignancy is progressing, rt using either imrt or d may be utilized, making sure that abdominal organs at risk (oar) constraints are met. the use of sbrt in primary colon cancer has limited evidence. however, there is prospective evidence that has evaluated sbrt in abdominal metastasis [ ] . pelvic rt and vaginal brachytherapy are usually well-tolerated and can be used in the majority of patients without a need for hospitalization. endometrial cancers cancer be treated with ebrt and vaginal brachytherapy [ ] . as per the nccn recommendations, 'external-beam doses for a microscopic disease should be - gy in conventional fractionation ( . - gy/fraction). postoperatively, if there is a gross residual disease and the area(s) can be sufficiently localized, a boost can be added to a total dose of - gy, respecting normal tissue sensitivity. for neoadjuvant radiation, doses of - gy are typically used. one could consider adding one to two high-dose-rate (hdr) insertions to a total dose of - gy low-dose-rate (ldr) equivalent, to minimize the risk of positive or close margins at hysterectomy.' as per the nccn [ ] , for patients receiving postoperative hdr vaginal brachytherapy alone, regimens include gy x fractions prescribed to the vaginal surface, or gy x fractions or . gy x fractions prescribed to mm below the vaginal surface. the use of smaller fraction sizes may be considered to potentially further limit toxicity in selected cases. doses of - gy x - fractions are prescribed to the vaginal mucosa if hdr is used as a boost to external beam rt. for medically inoperable uterine cancer or patients where surgery cannot be performed, an eqd (equivalent dose in gy fraction) d of at least gy should be delivered to the uterus, cervix, and upper - cm of the vagina if brachytherapy alone is used and should be increased to gy for the combination of ebrt and brachytherapy. if an mri is used as part of planning, the target dose for the gross tumor volume (gtv) would be an eqd of ≥ gy [ ] . cervical cancer can be treated with reduced-dose chemotherapy, plus ebrt or ebrt alone. as per the nccn, patients with an intact cervix are typically treated with definitive ebrt to a dose of approximately gy ( - gy in conventional fractionation) followed by a brachytherapy boost. however, since brachytherapy for cervix cancer may be difficult, given the utilization of resources for covid- infections, an imrt or sbrt boost may be applied. sbrt does not usually replace brachytherapy. however, it may be an appropriate option if brachytherapy cannot be performed. the sbrt dose may be determined by published retrospective and phase i and ii data [ ] [ ] . for patients that are scheduled to undergo surgical resection and health system resources permit, preoperative short-course rt treatment may be preferred. the nccn recommends a short course of pelvic rt for t and m (if symptomatic or controlled systemic disease) rectal cancer. short-course radiation therapy ( gy in five fractions) with surgery within one week of completion of therapy or delayed six to eight weeks can also be considered for patients with stage t rectal cancer [ ] . another option for preoperative radiation is gy to the pelvis, followed by . gy in three fractions to the tumor with a cm margin. igrt is preferred in this setting to limit the dose to the adjacent bowel. for unresectable cancer, rt alone may be an option. dose as per the nccn is > gy in conventional fractionation. chemotherapy or systemic treatment may be added based on the risk of toxicity. standard treatment of anal cancer is concomitant chemoradiation. however, rt alone may be an acceptable option if adding chemotherapy may result in a higher risk of patients being hospitalized [ ] . rt dose options as per the nccn include the "shrinking field technique" with low-risk elective nodal ptv volume prescribed to . gy in . gy daily fractions [ ] . the high-risk elective nodal ptv is sequentially prescribed an additional . for patients that are elderly, some additional rt dose options have been published based on retrospective data, e.g., gy in fractions with concurrent -fluorouracil ( fu) [ ] , although this study included only a small number of patients and should not be considered a standard option. rt for primary and resected skin cancers can be delayed. however, if rt is indicated, use short courses and limit radiation to the mucosa. elective nodal radiation should be avoided unless strongly indicated. when using a large fractional dose, alternate day or less frequent rt treatment can be utilized. if surgery is not possible soon, primary rt can be utilized. for primary tumors less than cm, one can use gy in five fractions over two weeks [ ] . for a primary tumor > cm, - gy delivered over three to four weeks can be used [ ] . gy per fraction x (weekly) [ ] resected squamous cell/basal cell skin cancers gy in four weeks ( . gy/fraction) [ ] gy in fractions four days a week [ ] melanoma [ ] definitive cases: gy in five fractions over one week for < cm postoperative: gy in five fractions twice a week or every other day. soft tissue sarcomas can be treated with preoperative rt if surgery cannot be performed, given the coronavirus pandemic. if surgery has already been performed, postoperative rt can be delivered in high-risk pathology. brachytherapy may be difficult at this time and may need to be substituted by ebrt. most of the rt recommendations are based on extremity sarcomas, although the rationale can be applied to non-extremity sites. the nccn recommends the following rt doses that can be utilized during the covid- pandemic [ ] : besides, there are reports of using sbrt as a preoperative regimen (e.g., gy in five fractions) for sarcomas [ ] [ ] . during this covid- pandemic, hypofractionated regimens may be preferred to reduce patient visits and limit interactions. intermediate and high-risk patients can have combined androgen deprivation therapy ( table ) . at our institution, we commonly use . gy in five fractions for appropriately selected patients [ ] . usually, spaceoar® hydrogel (augmenix, inc., bedford, ma) and fiducial (or calypso®, varian medical systems, palo alto, ca) markers are placed before sbrt. however, given the pandemic and lack of resources, these placements can be done under local anesthesia or skipped. if omitted, daily cbct or onboard imaging is recommended during rt. surgical resection is the mainstay of treatment for this cancer. for patients that cannot undergo surgical resection, given the pandemic, sbrt may be used for unresected renal cancer. the studies utilizing sbrt for kidney cancer are shown in table . due to the covid- pandemic, if surgery and chemotherapy are not feasible, hypofractionated short course radiation schedules can be utilized for unresected bladder cancers. amestoy et al. found evidence that the use of hypofractionated rt showed reasonable outcomes [ ] . the nccn recommends conventional fractionation treating the whole bladder with or without pelvic nodes to . - . gy using conventional or accelerated hyperfractionation, followed by a boost to either the whole or partial bladder between - gy. reasonable alternatives to conventional fractionation include hypofractionated treatment of the whole bladder to gy in fractions or using simultaneous integrated boosts to sites of gross disease [ ] . the standard of care of primary high-grade brain gliomas is surgical resection followed by rt with concurrent temozolomide. given the ongoing pandemic, if resection is not possible, a multidisciplinary discussion should guide each patient's treatment. for resected cases, standard rt dose, based on the patient selection using a molecular profile, such as idh (isocitrate dehydrogenase) status, is gy in . - gy/fractions [ ] . if conventional fractionation is difficult to deliver, a decision needs to be made about an alternative regimen. the nccn recommends the following rt doses: a slightly lower dose, such as - . gy in . gy or gy in . gy fractions, can be applied when the tumor volume is substantial (gliomatosis), there is brainstem/spinal cord involvement, or for grade iii astrocytoma. if a boost volume is used, the initial phase of the rt plan will receive gy in gy fractions or - . gy in . gy fractions. the boost plan will typically then receive gy in gy fractions or - . gy in . gy fractions. in poorly performing patients or elderly patients, a hypofractionated accelerated course should be considered with the goal of completing the treatment in two to three weeks. typical fractionation schedules are gy/ fractions or . gy/ fractions. alternatively, a shorter fractionation schedule of gy/ fractions may be considered for elderly and frail patients with smaller tumors for whom a longer course of treatment would not be tolerable. these hypofractionated regimens should be considered if conventional fractionation is difficult or not possible [ ] . several hypofractionated regimens are published for unresected or recurrent meningioma. regimens include gy/ fractions, gy/ fractions, gy/ fractions, gy/ fractions, and gy/ fractions [ ] . these regimens are not validated in phase iii randomized trials but are published in one or more studies. recommendations regarding rt for breast cancer during this pandemic have recently been published by an international collaborative group [ ] . recommendations include the omission of rt in older patients with early-stage, low-risk breast cancer, using hypofractionated regimens (e.g., - gy in once weekly fractions over five weeks or gy in five daily fractions over one week as per the fast and fast forward trials, respectively), the omission of a boost in select patients, omission of nodal radiation in select patients, and using moderate hypofractionation for rt to the chest wall ( gy in fractions). one of the risks of adding rt postoperatively is radiation pneumonitis that may mimic covid- -induced pneumonia and this risk should be considered while planning rt. regarding radiation delivery, protocols need to be in place to streamline therapy staff. social distancing using technology, remote meetings, remote dosimetry, and personal protective equipment (ppe) are all techniques to enhance the safety of radiation personal [ ] . this unexpected pandemic has caused intense and widespread panic and anxiety worldwide. wellness sessions and techniques should be used to reduce stress among radiation staff and patients, with scheduled instructional sessions held in-person or online. staff should be made aware of available mental support resources within the institution. patients and staff alike need ready access to mental health services. before the start of rt, adequate imaging should be obtained for primary staging. it is preferable to obtain imaging at a facility that offers online image review to minimize handling of cds (compact discs) and other physical documents. during rt, one way to reduce exposure to staff and minimize the time of the patient in the department is to reduce the frequency of cbct imaging from daily to weekly cbct or weekly orthogonal films especially in circumstances where motion is minimal (brain lesions). resident education is crucial, and all efforts should be made to minimize disruption in their training. with the availability of online audio and video conferencing tools, didactic lectures should continue. online education makes it easier for many attendings and guest speakers to provide didactic instruction from local offices, thereby saving travel time and transportation/lodging expenses. peer review of plans and contours before the start of radiation can be done by remote login from each workstation and does result in 'safe distance' meetings. institutions and departments have to make sure that the quality of meetings is good, with minimum interruptions due to lack of audiovisual quality. otherwise, it defeats the purpose of the meeting and may necessitate a more risky in-person meeting. telemedicine has been used and should be increasingly used to reduce patient exposure. the patient-physician experience is enhanced if there is real-time two-way video and audio communication [ , ] . even without the video component, a telephonic consult, follow-up, or weekly evaluation using telemedicine is reasonable, given the easy availability of electronic records. in places where electronic medical records may not be available, it may be necessary to gather information over the phone from referring physicians and to access radiology and pathology records through other means. the current covid- pandemic represents an unprecedented era in healthcare with potential impacts upon cancer patients. the overriding goal of maintaining access to radiation therapy during the crisis is critical, given the opportunity for radiation therapy to be curative in many situations. the lack of access to surgery and some systemic therapies impacts the ability to provide current standards of care. nonetheless, in this review, we summarize treatment opportunities and supporting evidence that may be considered when access is limited. we must continue to care for patients during this time and reduce the potential stage migration and associated morbidity of delayed treatments. these treatment options are not to be considered a replacement of standard cancer care, but as potential alternatives when other resources are constrained. adapting palliative radiation therapy for bone metastases during the covid- pandemic: gemo position paper palliative radiotherapy for oncologic emergencies in the setting of covid- : approaches to balancing risks and benefits trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology analysis of weekly complete blood counts in patients receiving standard fractionated partial body radiation therapy guidelines to reduce hospitalization rates for patients receiving curative-intent radiation therapy during the covid- pandemic: report from a multicenter new york area institution practice recommendations for risk-adapted head and neck cancer radiotherapy during the covid- pandemic: an astro-estro consensus statement thoracic radiation therapy during covid- : provisional guidelines from a comprehensive cancer center within a pandemic epicenter management of locally advanced rectal cancer during the covid- pandemic: a necessary paradigm change at memorial sloan kettering cancer center long-term patientreported quality of life after stereotactic body radiation therapy for recurrent, previouslyirradiated head and neck cancer quality of life outcomes following organ-sparing sbrt in previously irradiated recurrent head and neck cancer randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of rtog study - covid- ) resources for the cancer care community induction chemoradiotherapy followed by resection for locally advanced masaoka stage iii and iva thymic tumors radiotherapy for thymic carcinoma: adjuvant, inductive, and definitive randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of adenocarcinoma of gastric cardia (agc)--report on patients study protocol of a randomized phase iii trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma: preact. bmc cancer neoadjuvant chemoradiotherapy or chemotherapy preoperative on outcomes of patients with locally advanced or irresecable gastric cancer (lagc) fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: -year analysis of the u.s. intergroup/rtog phase iii trial effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after months of gemcitabine with or without erlotinib: the lap randomized clinical trial alliance for clinical trials in oncology (alliance) trial a : preoperative extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas health-related quality of life in scalop, a randomized phase trial comparing chemoradiation therapy regimens in locally advanced pancreatic cancer phase multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma pancreas sbrt: who, what, when, where, and how… nccn guidelines insights: colon cancer, version outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer a phase i trial of preoperative eniluracil plus -fluorouracil and radiation for locally advanced or unresectable adenocarcinoma of the rectum and colon phase i trial of stereotactic mr-guided online adaptive radiation therapy (smart) for the treatment of oligometastatic or unresectable primary malignancies of the abdomen what is the evidence for the clinical value of sbrt in cancer of the cervix determining the recommended dose of stereotactic body radiotherapy boost in patients with cervical cancer who are unsuitable for intracavitary brachytherapy: a phase i dose-escalation study toxicity and survival of anal cancer patients treated with intensity-modulated radiation therapy proton beam radiotherapy for anal and rectal cancers sebag-montefiore d: effective treatment of anal cancer in the elderly with low-dose chemoradiotherapy radiation therapy of skin carcinomas: results of a hypofractionated irradiation schedule in cases followed more than years efficacy of a hypofractionated schedule in electron beam radiotherapy for epithelial skin cancer: analysis of cases preoperative radiosurgery for soft tissue sarcoma feasibility of using stereotactic body radiation therapy for unresectable soft tissue tumors of the trunk outcomes of a dose-escalated stereotactic body radiation phase trial for patients with low-and intermediate-risk prostate cancer stereotactic ablative body radiotherapy for inoperable primary kidney cancer: a prospective clinical trial single fraction radiosurgery for the treatment of renal tumors phase i dose-escalation study of stereotactic body radiotherapy (sbrt) for poor surgical candidates with localized renal cell carcinoma a phase dose-escalation study of robotic radiosurgery in inoperable primary renal cell carcinoma a prospective phase ii trial of using extracranial stereotactic radiotherapy in primary and metastatic renal cell carcinoma review of hypo-fractionated radiotherapy for localized muscle invasive bladder cancer hypofractionated stereotactic radiotherapy for patients with intracranial meningiomas: impact of radiotherapy regimen on local control international guidelines on radiation therapy for breast cancer during the covid- pandemic global telemedicine implementation and integration within health systems to fight the covid- pandemic: a call to action in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: joe herman declare(s) personal fees from medtronic consulting, consulting, pancan consulting. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -fgrvrlht authors: sule, harsh; kulkarni, miriam; sugalski, gregory; murano, tiffany title: maintenance of skill proficiency for emergency skills with and without adjuncts despite the use of level c personal protective equipment date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: fgrvrlht objective to determine the impact of level c personal protective equipment (ppe) on the time to perform intravenous (iv) cannulation and endotracheal intubation, both with and without the use of adjuncts. methods this prospective, case-control study of emergency medicine resident physicians was designed to assess the time taken by each subject to perform endotracheal intubation using both direct laryngoscopy (dl) and video laryngoscopy (vl), as well as peripheral iv cannulation both with and without ultrasound guidance and with and without ppe. results while median times were higher using vl as compared to dl, there was no significant difference between intubation with either dl or vl in subjects with and without level c ppe. similarly, no significant difference in time was found for intravenous cannulation in the ppe and no-ppe groups, both with and without ultrasound guidance. conclusions existing skill proficiency was maintained despite wearing ppe and there was no advantage with the addition of adjuncts such as video-assisted laryngoscopy and ultrasound-guided intravenous cannulation. a safe and cost-effective strategy might be to conduct basic, just-in-time ppe training to enhance familiarity with donning, doffing, and mobility, and couple this with the use of personnel who have maximal proficiency in the relevant emergency skill, instead of more expensive, continuous, skills-focused ppe training. the health crises related to ebola virus disease (evd) in and, currently, coronavirus disease (covid- ) highlighted a key challenge in caring for patients who have or may potentially have chemical-biological-radiological-nuclear (cbrn) exposures. although there are instances where healthcare is deferred until decontamination is complete or the risk of contamination eliminated, there are circumstances where aggressive airway management and hemodynamic stabilization is required with a significant risk of exposure to healthcare providers. given the high risk of contamination of front-line emergency medicine personnel, the use of appropriate personal protective equipment (ppe) is critical. there are generally two approaches to training exercises -focused training with periodic refresher courses or just-in-time training. the cost burden of preparing for high-risk, low-frequency events such as cbrn incidents is a significant challenge since it places a financial and personnel/time burden on hospitals [ ] [ ] [ ] . moreover, training exercises tend to focus on donning and doffing ppe, and not procedural competence while in ppe. in recent years, the use of adjunct devices, such as video laryngoscopy (vl) and ultrasound, has become instrumental in the daily practice of emergency medicine. conflicting evidence exists in the literature as to whether the use of ppe impedes the ability to simply successfully intubate, and this is further complicated by the impact of vl when using ppe [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . while there is also conflicting evidence regarding the impact of ultrasound on intravenous (iv) cannulation, there are no studies that address its use with ppe [ ] [ ] . our study is the first to examine these parameters while using both vl for intubation and ultrasound for intravenous cannulation. our primary objective was to determine the impact of level c ppe on the time to perform intravenous cannulation and endotracheal intubation, both with and without the use of adjuncts. we hypothesized that it would take longer to perform these key procedures while donned in ppe. the study was approved by the institutional review board of rutgers newark health sciences. this is a prospective, case-control study with self-matching that was performed in the extended treatment area (eta) of university hospital (newark, nj), which is part of the emergency department (ed) where all patients with suspected cbrn exposure are evaluated and treated. the subjects were emergency medicine (em) residents in our four-year residency program that had no previous training related to ppe used but were proficient in the technical skills being evaluated. each resident served as their own control. all study subjects were consented prior to participation. participants used ppe certified to provide the maximal level of protection to personnel responding to cbrn agents (level c). details of ppe, intravenous cannulation, and endotracheal intubation are shown in table . four stations were set up and fully equipped to perform the necessary tasks: two for intubation and two for intravenous access. study subjects were randomized into one of two groups with regard to the sequence of performing procedures, thereby attempting to limit any bias related to the order of procedures. group performed procedures first without ppe (standard hospital scrubs) and then with ppe, while group performed procedures first with ppe and then without ppe, as shown in figure . half of each em-year was assigned to each group. subjects donned and doffed ppe under the direction of experts in the appropriate protocols. each of the subjects was assigned to one of four procedure stations and rotated in sequence as described in table . upon conclusion of the study, each subject had attempted each skill twice; once while wearing ppe and once while wearing standard clothing. a iv iv+us dl vl iv iv+us dl vl b iv+us iv dl vl iv+us iv dl vl c iv iv+us vl dl iv iv+us vl dl d iv+us iv vl dl iv+us iv a iv iv+us dl vl iv iv+us dl vl b iv+us iv dl vl iv+us iv dl vl c iv iv+us vl dl iv iv+us vl dl d iv+us iv vl dl iv+us iv vl dl e dl vl iv iv+us dl vl iv iv+us f dl vl iv+us iv dl vl iv+us iv g vl dl iv iv+us vl dl iv iv+us h vl dl iv+us iv vl dl iv+us iv time to successful intubation was recorded for each subject. the procedure start time was recorded when the subject first touched the equipment for preparation. preparation for intubation included inserting the stylet into the endotracheal tube (ett), testing ett balloon inflation, and placing the macintosh blade onto the laryngoscope handle or the glidescope tm (verathon; seattle, wa) cover onto the light source. the procedure stop time was recorded when the endotracheal tube (ett) had been correctly inserted in the trachea with initial inflation of the lungs. time to successful iv cannulation was recorded for each subject. the procedure start time was recorded when the subject touched the equipment for preparation. preparation for this procedure included unwrapping the iv catheter from the package, cleaning the surface of the mannequin, placing ultrasound gel, and turning on the ultrasound machine. the procedure end time was recorded upon the successful initiation of a saline flush of the iv line to confirm proper placement. all procedure times were recorded in seconds (sec) by volunteers who had experience and knowledge of the skills evaluated. each subject's times were recorded on standardized data collection forms. no identifying information was recorded on the forms except for em year. at the conclusion of the study, all forms were collected by the primary investigator. the subjects were then debriefed and given an opportunity to convey their impressions regarding their performance in the skill stations. the shapiro wilk test was utilized to determine if the data fit a normal distribution model. given the small sample size, a two-tailed mann-whitney u test was used to compare the time to perform each procedure with and without ppe. significance was defined as an associated p-value of < . . sixteen of the total eligible em resident physicians participated in the study. nine residents were excused because of either scheduling conflicts or work-hour restrictions. resident participants in the study included two first-year residents (em- ), second-year residents (em- ), third-year residents (em- ) and fourth-year residents (em- ). one resident's data was excluded from the video laryngoscopy portion due to incomplete data collection. data for all four procedures were found to not fit the normal distribution model. therefore, median times with interquartile range (iqr) are reported below. when performance time was lower with ppe than without ppe, the time is reported as a negative value. the median time for each procedure with and without ppe is demonstrated in figure . our study showed that there was not a significant difference related to level c ppe use for endotracheal intubation with and without the use of adjuncts. median times were higher using video laryngoscopy as opposed to direct laryngoscopy, but there was no significant difference in the no-ppe and ppe sub-groups. this is not consistent with several studies where there was an increase in intubation time with the use of ppe. consistent with our data, macdonald et al., in a study of advanced and critical care paramedics, found no statistically significant difference in time to completion of intubation when comparing to a level c suit ( sec vs. sec) [ ] . in addition, wang et al. studied emergency physicians (residents) with and without level c ppe and found no difference in the mean time to successful endotracheal intubation ( . sec vs. . sec, p = . ) [ ] . most recently, adler et al. studied physicians and nurses with varying levels of ppe and found that there were no significant differences in tasks, including endotracheal intubation, except iv placement (median difference, . sec vs. sec, p< . ) [ ] . we chose to start the time of intubation at the moment the subjects began to prepare equipment for the procedure. therefore, it is difficult to compare the intubation times in this study with other studies where the start time was post-preparation or insertion of the laryngoscope. however, we felt strongly that this should be included since preparing equipment requires manual dexterity that is influenced by ppe, and in an emergency situation, this preparation will likely be done while donned. unfortunately, there is limited and somewhat conflicting literature that addresses the question regarding the appropriate time needed to successfully complete airway tasks by otherwise procedurally competent personnel while wearing ppe [ ] [ ] [ ] [ ] [ ] . in our study, the median times for successful intubation with dl and vl (including preparation for intubation), regardless of the use of ppe, were seconds and seconds, respectively. we feel that a time under one and half minutes for preparation and successful endotracheal intubation is an acceptable timeframe. similarly, our study showed no significant difference in time for iv cannulation in the no-ppe and the ppe groups, both with and without ultrasound guidance. although it was not a statistically significant finding, it was interesting that the median times for iv cannulation were faster with ppe than without ppe. castle et al. found an increase in the mean completion time of iv cannulation when wearing ppe level c ( . sec vs. . sec) [ ] . macdonald et al. found a statistically significant increase in completion time for iv cannulation when wearing ppe ( sec vs. sec, p < . ) [ ] . there has also been no previously established appropriate time for iv placement using ppe; however, the median time for iv cannulation with ultrasound using ppe was seconds. we feel that successful iv cannulation under two minutes is an appropriate time frame. however, our study has a few limitations. first, the participant group was small thereby making statistical analysis challenging. as a result, we were unable to parse out subtle differences in proficiency that might occur across varying training levels. second, we did not track the time taken for each individual stage of the procedure; that is, specific time for preparation, time from the insertion of the laryngoscope to passing the ett and lung inflation. this would have been beneficial in making a direct comparison of our results to existing literature. finally, while our participant group of trainees completed the procedures in what we consider an appropriate time frame, future studies should include a group of experienced clinicians so that a "gold standard" can be introduced for comparison. in this study, we demonstrate that there is no significant difference in completion time for any of the studied procedures with and without level c ppe, with no advantage related to the use of adjuncts such as ultrasound and video laryngoscopy. maintenance of existing skill proficiency while wearing ppe is a key finding and perhaps obviates the need for continuous, skills-focused ppe training. a safe and cost-effective strategy might be to conduct basic, justin-time ppe training for personnel who have maximal proficiency in the relevant emergency skill. human subjects: consent was obtained by all participants in this study. rutgers newark health sciences irb issued approval pro . the study was approved by the institutional review board of rutgers newark health sciences. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. world health organization: public health preparedness and response . public health response to biological and chemical weapons: who guidance occupational safety and health administration. personal protective equipment just-in-time training for high-risk lowvolume therapies: an approach to ensure patient safety antichemical protective gear prolongs time to successful airway management: a randomized, crossover study in humans practicality of performing medical procedures in chemical protective ensembles impact of chemical, biological, radiation, and nuclear personal protective equipment on the performance of low-and highdexterity airway and vascular access skills performance of resuscitation skills by paramedic personnel in chemical protective suits the effect of personal protective equipment on emergency airway management by emergency physicians: a mannequin study impact of personal protective equipment on the performance of emergency pediatric tasks comparison of the airtraq laryngoscope versus the conventional macintosh laryngoscope while wearing cbrn-ppe airtraq versus macintosh laryngoscope: a comparative study in tracheal intubation intubation efficiency and perceived ease of use of video laryngoscopy vs direct laryngoscopy while wearing hazmat ppe: a preliminary highfidelity mannequin study perceived difficulty and success rate of standard versus ultrasound-guided peripheral intravenous cannulation in a novice study group: a randomized crossover trial ultrasound-guided peripheral venous access: a systematic review of randomized-controlled trials the authors would like to acknowledge christine ramdin, phd, for her guidance with statistical analysis. key: cord- -fnsf qqm authors: yalcin bahat, pinar; aldikactioglu talmac, merve; bestel, ayşegul; topbas selcuki, nura f; aydın, zelal; polat, İbrahim title: micronutrients in covid- positive pregnancies date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: fnsf qqm pregnant women are considered among the high-risk population for covid- . therefore, research for methods of treatment and prevention of covid- positive pregnancies carries an importance. the aim of this study was to measure serum (oh)d, vitamin b , and zinc levels in covid- positive pregnant women to evaluate the role of these micronutrients in treatment and prevention. a total of covid- positive pregnant women who were hospitalized and treated at a tertiary clinic were included in this study. the mean serum (oh)d level was measured to be . ± . . the mean serum zinc level was . ± . , and the mean serum vitamin b level was . ± . . all these variables were significantly lower than the accepted cut-off values (p < . ). these low values might have contributed to a deficiency in their immune response and thus made these patients susceptible to covid- infection. supplementation of micronutrients during the pandemic could be beneficial during pregnancy for prevention. coronavirus family has long been a well-known source of infection causing diseases like common cold, severe acute respiratory syndrome (sars), and middle east respiratory syndrome (mers). novel coronavirus (sars-cov- ) is a newly discovered virus from the coronavirus family, which is the infection source of the covid- pandemic [ ]. covid- enters the host cells and triggers an immune response, which includes the production of proinflammatory cytokines, activation of t cells, cd , and cd + t cells [ ] . the severe forms of the disease leading to acute respiratory distress syndrome have been attributed to excessive production of proinflammatory cytokines also called 'cytokine storm' [ ] . since the outbreak, extensive research has been put into understanding the action mechanism of covid- in hope of finding a cure and a vaccine. however, there are still unknowns especially about the potential protective factors against the virus. vitamins and minerals, also known as micronutrients, are key factors in maintaining a healthy immune system and therefore are widely used as supplements for protection against bacterial and viral infections [ ] . zinc, hydroxyvitamin d ( (oh)d), and vitamin b belong to this family of micronutrients. zinc is an essential micronutrient that is involved in cell proliferation, differentiation, rna and dna synthesis [ ] , as well as cell structures and cell membrane stabilization [ ] . there is also strong evidence between zinc deficiency and several infectious diseases, such as malaria, hiv, tuberculosis, measles, and pneumonia. zinc is also involved in the modulation of the proinflammatory response by regulation of inflammatory cytokines and in controlling oxidative stress [ ] . similarly, (oh)d has anti-infective, antiinflammatory, and immunomodulant functions. it contributes to the maintenance of the cell's physical barrier integrity, enhanced activity of innate immunity through macrophages and monocytes, and t cells [ ] . lastly, vitamin b is a water-soluble vitamin. it is a cofactor in dna synthesis and is known to inhibit viral replication in the host cells [ ] . the aim of this study was to measure serum (oh)d, vitamin b , and zinc levels in covid- positive pregnant women to evaluate the role of these micronutrients in the prevention and to evaluate the possible cause between the blood levels of micronutrients and the covid- infection. this case-control study was conducted in a tertiary referral hospital between april and june . the study protocol was approved by the institution's ethics committee ( . . ) and registered to clinicaltrials.gov (nct ). written informed consent was obtained from all participants before their enrollment in the study. a total of covid- positive pregnant women were included in the study. pregnant women whose pcr test was positive for covid- , pregnancies older than eight weeks of gestation, and women who did not receive any antibacterial or antiviral treatment during the past three months or did not receive any (oh)d, vitamin b , and zinc supplements during their pregnancy were included in the study. women with known renal disease, rheumatic disease, diabetes mellitus type , acquired immune deficiency syndrome, and those using immunosuppressants were excluded. complicated pregnancies such as ectopic pregnancy, scar pregnancy, or hydatidiform mole were also excluded. a detailed medical history was obtained. all patients underwent a physical and obstetrical examination with ultrasound and received a thorax ct. in addition to routine blood tests, d-dimer levels and ferritin levels were also determined. gestational age was estimated based on the last menstrual period. if the date of the last menstruation was unknown, then crown-rump length (crl) was used for calculation. on the day of admission, blood samples were taken from a peripheral vein using one dry tube and one tube with ethylenediaminetetraacetic acid (edta). tubes were submitted to the hospital's central laboratory for determination of (oh)d, zinc, and vitamin b levels. quantitative determination of (oh)d was performed with competitive chemiluminescent immunoassay (clia) using liaison® oh vitamin d total assay (diasorin s. p. a., saluggia, italy). vitamin d deficiency was defined as serum vitamin d levels of less than ng/ml, insufficiency as - ng/ml, and sufficiency as - ng/ml according to recent clinical guidelines committee. recommended levels are higher than ng/ml for specific groups, such as in pregnant women. the mean of . ng/ml (sd: . ng/ml and an intra-control cv of . %) was the referred reproducible value to measure the (oh)d. for the same parameter, the intermediate precision was . ng/ml (sd: . ng/ml and an intra-control cv of . %) [ ] . access immunoassay system (© beckman coulter inc., brea, ca, usa) was used to quantitate serum vitamin b levels. a normal range of - pmol/l serum vitamin b was calculated with a % confidence interval [ ] . for zinc quantification, atomic absorption spectroscopy was used (perkinelmer® inc., waltham, ma, usa). current cut-off levels for zinc deficiency are < . μmol/l (afternoon, non-fasting) and for non-fasting women of reproductive age (aged - years; wra, < . μmol/l (morning) and < . μmol/l (afternoon)) [ ] . all calculations followed the best clinical practice. statistical package for social sciences . (ibm corp., armonk, ny, usa) was used for statistical analysis. descriptive statistical methods (mean, standard deviation, frequency) and their associated % confidence intervals of study variables were presented. one sample t-test was performed to evaluate the difference between accepted cut-off values and the means of our study groups regarding b , zinc, and (oh)d levels. p-value < . was considered for statistical significance. a total of covid- positive pregnant women were included in the study. the mean age was . ± . years. when pregnancies were divided into trimesters, it was observed that disease rate in our cohort increased with increasing trimester: . % (n = ) was in the first trimester, . % (n = ) were in the second trimester, and . % (n = ) were in the third trimester. the mean gravidity was . ± . , and the mean parity was . ± . (table ) . when thorax cts were evaluated, . % (n = ) did not reveal any pathology, . % (n = ) showed mild changes, and in . % (n = ) moderate and in . % (n = ) severe findings could be observed. majority of the patients in the study presented with mild to moderate ct findings. approximately . % were treated with hydroxychloroquine, whereas . % were monitored actively without any medical intervention. at the time of admission, the mean serum d-dimer level was . ± . and the ferritin level was . ± . . the mean duration of stay at the hospital was . ± . ( - ) ( table ) . while the minimum stay in the hospital was days and the maximum stay was days. the mean serum (oh)d level was measured to be . ± . . the mean serum zinc level was . ± . , and the mean serum vitamin b level was . ± . (table ). in one sample t-test analysis, all these variables were significantly lower than the accepted cut-off values (p-value < . ): (oh)d: , zinc: . , and b : . understanding the pathogenesis of sars-cov- has been challenging, and it has not yet been clarified. however, covid- affects the immune system in many different steps in the disease process [ ] . micronutrients are among these immune supplements, and their efficacy has already been shown with other viral infections [ ] . previous studies conducted with pregnant women and women in the postpartum period have shown the efficacy of micronutrients in fight against viral infections. especially, the inhibitory effects of (oh)d, vitamin b , and zinc, due to their safe use during pregnancy, on viral pathogenesis have already been shown. for example, in studies of h n prior to the finding of a vaccine, the protective effects of high levels of vitamin b on the newborns ingested through breast milk were observed [ ] . another study has shown that high levels of maternal serum (oh)d levels during pregnancy and lactation were associated with lower rates of acute respiratory infections of the newborns [ ] . additionally, it has been shown that serum zinc levels correlate positively with better immune response in pregnant women against infections [ ] . it is known that (oh)d plays an essential role in immune answer and its modulation [ , ] . in a study conducted by ilie et al., in countries that had a severe course of covid- such as spain, italy, and the united kingdom, mean serum (oh)d levels are low [ ] . another study showed that patients with high serum vitamin d levels sustained less lung damage. according to a study by alipio, lower rates of multiple organ failure were observed among patients with higher levels of serum (oh)d [ ] . from the existing evidence, it can be concluded that the suppression of viral replication by (oh)d is effective in the prevention and also responsible for a mild course of covid- [ ] . in our study, serum (oh)d levels of the covid- positive pregnant women were under the cutoff value. the reason for these low values could be pregnancy, less exposure to sunlight, and insufficient nutrition. the low levels of serum (oh)d, in accordance with the existing data, might have caused susceptibility to covid- . zinc plays an important role in the pathogenesis of viral infections. the correlation between serum zinc levels and the severity of infections has already been shown [ ] . anosmia, a common symptom of covid- , is also seen in zinc deficiency [ ] . in three women, included in the study, with very low levels of serum zinc, anosmia was among the symptoms. shittu and afolami advocated in their study that adding zinc supplements to the treatment regimen with chloroquine in covid- patients enhanced the antiviral action mechanism of the chloroquine and efficacy of the treatment [ ] . according to another study, it has been suggested that zinc could possess protective effects through reducing inflammation, improving mucociliary clearance, preventing ventilator-induced lung injury, and modulating antiviral and antibacterial immunity [ ] . therefore, zinc can be used both as preventative medication and adjuvant therapy of covid- . similar to the results with (oh)d, zinc levels were significantly low in our patient cohort, which might have played a negative effect on their immunity making these patients susceptible during the pandemic. in vivo studies of vitamin b have shown that vitamin b acts as a natural inhibitor of viral replication of the hepatitis c virus (hcv) [ ] . in another study, it was shown that vitamin b and folate levels affect the human papillomavirus methylation process and low serum levels increase malignancy [ ] . in our study, all serum vitamin b levels were significantly low can be making them more prone to covid- . there are several limitations to this study. first, there are difficulties in the measurement of serum (oh)d levels in pregnant women, which might have led to the lower levels observed in this study. additionally, a limited number of patients and a lack of a control group were further limitations. however, due to the need for cumulative data concerning the covid- pandemic, we believe that our results will be of importance for further studies on prevention and adjuvant therapy. the level of serum micronutrients in pregnant women with covid- was lower than the cut-off values. these low values might have contributed to a deficiency in their immune response and thus made these patients susceptible to covid- infection. supplementation of micronutrients during the pandemic could be beneficial during pregnancy for prevention. however, further studies are needed to show their effects on covid- infection. human subjects: consent was obtained by all participants in this study. kanuni sultan suleyman hospital issued approval kaek/ . . . registered to clinicaltrials.gov (nct ). . animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. zinc and the immune system coordination dynamics of zinc in proteins zinc and human disease . interrelations between essential metal ions and human diseases association between vitamin d supplementation and mortality: systematic review and meta-analysis association of serum vitamin b levels with stage of liver fibrosis and treatment outcome in patients with chronic hepatitis c virus genotype infection: a retrospective study vitamin d insufficiency a review of the cut-off points for the diagnosis of vitamin b deficiency in the general population determination of zinc status in humans: which indicator should we use? coronavirus infections and immune responses optimal nutritional status for a well-functioning immune system is an important factor to protect against viral infections vitamin b supplementation during pregnancy and postpartum improves b status of both mothers and infants but vaccine response in mothers only: a randomized clinical trial in bangladesh maternal vitamin d supplementation during pregnancy and lactation to prevent acute respiratory infections in infancy in dhaka, bangladesh (mdari trial): protocol for a prospective cohort study nested within a randomized controlled trial peculiarities of changes in indices of calcium and zinc trace elements and matrix metalloproteinase- in pregnant women with perinatal infections covid- and vitamin d-is there a link and an opportunity for intervention? spanish vitamin d and women's health research group: hypovitaminosis d during pregnancy: are we ready to recommend vitamin d supplementation? the role of vitamin d in the prevention of coronavirus disease infection and mortality vitamin d supplementation could possibly improve clinical outcomes of patients infected with coronavirus- (covid- optimisation of vitamin d status for enhanced immuno-protection against covid- re-establishment of olfactory and taste functions improving the efficacy of chloroquine and hydroxychloroquine against sars-cov- may require zinc additives-a better synergy for future covid- clinical trials zinc and respiratory tract infections: perspectives for covid- vitamin b supplementation improves rates of sustained viral response in patients chronically infected with hepatitis c virus folate and vitamin b may play a critical role in lowering the hpv methylation-associated risk of developing higher grades of cin the authors would like to thank assistant professor cihan kaya for his support and advice. key: cord- - v cg b authors: khaliq, maria; raja, riffat; khan, nasir; hanif, hina title: an analysis of high-resolution computed tomography chest manifestations of covid- patients in pakistan date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: v cg b objective the objective of the present study is to describe high-resolution ct (hrct) chest manifestations of coronavirus disease (covid- ) patients presenting to a tertiary healthcare facility in punjab, pakistan, and to analyze the distribution of the disease in lung fields. additionally, we assess the role of chest ct severity scoring (ct-ss) in determining the severity of pneumonia. methods in this cross-sectional descriptive study conducted from march , , to may , , confirmed covid- patients undergoing hrct scan in a tertiary care facility in punjab, pakistan were included. the hrct chest was performed on the patients using a standard protocol. each study was evaluated for the presence of ground-glass opacities (ggos), consolidation, mixed pattern, distribution, crazy paving, reverse halo sign, nodules, pleural effusion, and other findings. additionally, ct-ss was calculated by dividing each lung into zones. each zone was scored as , , and , representing no involvement, < % involvement, and > % involvement of one zone respectively (total score: - for each patient). the patients were classified into mild, moderate, and severe cases (mild: ct-ss of < , moderate: ct-ss of - , and severe: ct-ss of > ). results ggo was the most common finding, as seen in . % of the patients, followed by consolidations ( . %) and crazy paving ( . %). the majority of the patients showed the bilateral and peripheral distribution of the disease process. vascular dilatation and bronchiectasis were seen in patients; pleural effusions were observed in only two study patients, while no patient exhibited reverse halo sign or pulmonary nodules. the superior segment of lower lobes was the most commonly involved segment bilaterally. according to ct-ss, ( . %), six ( . %), and three ( . %) patients had mild, moderate, and severe disease respectively. conclusion the typical imaging findings of covid- on hrct are ggos with multilobe involvement and bilateral, peripheral, and basal predominance. ct-ss is helpful in categorizing pneumonia into mild, moderate, and severe types, thereby helping to identify patients with severe disease. this is particularly helpful in settings where fast triage is required. the global pandemic of coronavirus disease (covid - ) has been progressing rapidly and worsening around the world, and specialists in a wide variety of medical and diagnostic fields have been contributing their expertise regarding early diagnosis and management of the disease. reverse transcriptase-polymerase chain reaction (rt-pcr) test is considered the gold standard for diagnosing covid- [ ] . however, there are certain limitations to this test. it is time-consuming, is not readily available everywhere, and can also give false-negative results. moreover, studies have shown that it has a low sensitivity of - % [ , , ] . this low sensitivity is mainly attributed to low viral load and laboratory errors [ ] . because of the high number of false-negative results, repeat testing is often required. this is particularly challenging due to issues related to infrastructure and the availability of test kits. recent studies have shown that ct can be employed as a complement to rt-pcr for diagnosing covid- [ , ] . highresolution ct (hrct) of the chest is now commonly used not only in the diagnosis but also in monitoring the progression of covid- pneumonia. hrct chest has a sensitivity of - % in the diagnosis of covid- pneumonia [ , ] . however, experts still argue over the utility of ct as a diagnostic test for covid- pneumonia, and the role of ct in patients with covid- pneumonia is poorly understood. typical imaging features of covid- on ct chest include ground-glass opacities (ggos) and consolidation with bilateral and multilobe involvement and basal and peripheral predominance [ ] . however, most of the available literature on this topic is reported and published from far east [ , , ] . lung changes seen on ct chest are similar to those encountered in other viral types of pneumonia. therefore, it is argued that although ct chest is a sensitive modality to diagnose covid- pneumonia, it lacks the specificity. in this study, we describe the typical imaging features of covid- pneumonia on ct chest in patients presenting to a tertiary care hospital in punjab, pakistan, and analyze the distribution of the disease in lung fields. we also assess the role of chest ct severity scoring (ct-ss) in determining the severity of pneumonia. we believe our findings will help in the identification and management of patients with severe disease, especially in settings where fast triage is required. we opted for a cross-sectional descriptive study method. all patients with confirmed covid- infection who underwent an hrct scan of the chest at a tertiary healthcare facility in punjab, pakistan from march , , to may , , were included in the study. patients who were not willing to be a part of the study were excluded. after obtaining informed written consent, hrct chest scans were performed on the patients using the standard protocol. scans were performed with a multidetector ( ) toshiba aquilion ct scanner (canon medical systems corporation, Ōtawara, japan) with tube voltage and current set at kvp and ma respectively. each patient was scanned in a supine position, and lung fields from apices to bases were scanned in single breath-hold and -mm slice thickness. the images were analyzed at the workstation by two radiologists separately. each study was evaluated for the presence of ground-glass haze/opacities, consolidation or mixed pattern, distribution of opacities, i.e., central/peripheral/mixed pattern, crazy paving, reverse halo sign, nodules, pleural effusion, and other findings. ggo is defined as an area of increased attenuation where the underlying vessels are not obscured. consolidation is defined as an area of increased attenuation in which underlying vessels are obscured. the crazy paving pattern is defined as a geographical area of ground-glass haze with inter and intralobular septal thickening. the outer one-third of the lung was taken as peripheral while the remaining part of the lung was considered as central. additionally, the ct-ss was assessed for each patient. both lungs were divided into zones. each anatomical lung segment was considered as a single zone except in the left upper lobe where the apicoposterior segment was considered as apical and posterior, i.e., two separate zones. similarly, the posteromedial basal segment of the left lower lobe was considered as two separate zones, i.e., posterior basal and medial basal zones. the involvement of each zone was scored as , , and . a score of indicated no involvement, a score of indicated < % involvement of the zone and a score of indicated > % involvement of one zone. the total score ranged from - for each patient. according to the scores, the patients were classified into mild, moderate, and severe cases. mild disease indicated a score of < . moderate cases had scores of - and severe cases showed scores of > . data was entered and analyzed using spss statistics version . (ibm, armonk, ny) for manifestations and their percentages with reference to the parameters described above. the data was then compared with the available literature on this subject. a total of patients who underwent hrct of the chest fulfilled the inclusion criteria. among those, ( . %) were males and ( . %) were females. the average age of the study patients was . years. ggos were the most common finding, as seen in . % of the patients, followed by consolidations ( . %) and crazy paving ( . %) (figures , superior segment of the lower lobes was the most commonly involved segment bilaterally with involvement noted in patients in the right lung and patients in the left lung ( table ; figure ). the total ct-ss of these segments was and respectively ( table ). the secondmost commonly involved segment was the posterior basal segment in both lungs ( figure ). the total ct-ss for the right lung was , whereas it was for the left lung ( table ) . according to ct-ss, ( . %) patients had mild disease having the involvement of less than % of lung parenchyma. six ( . %) and three ( . %) patients had moderate and severe diseases, respectively ( table ) . since the outbreak of coronavirus in december , the population affected by the virus has been on the rise. the affected population may be asymptomatic in many cases. among symptomatic patients, the spectrum of the disease ranges from mild presentations to serious conditions such as severe acute respiratory syndrome (sars) [ , , ] . this disease burden and the consequent threat to public health are well-recognized by the world health organization (who) [ ] . multisystem involvement has been observed in covid- -positive patients with the respiratory system being the most common area to get affected [ ] . respiratory symptoms in the affected patients range from dry cough to respiratory distress [ , , ] . it is believed that damage to the alveolar epithelium is mainly responsible for acute respiratory distress syndrome (ards) seen in covid- , while the endothelium of blood vessels is less damaged, thereby resulting in a lesser amount of exudation. this explains the lesser involvement of other organ functions in covid- patients. the diagnostic hallmark of the disease is the reverse transcription-polymerase chain reaction (rt-pcr) test. it has been proven by multiple studies that the test has an overall sensitivity of - % [ , , ] . however, the test's sampling technique, longer waiting time, and lack of widespread availability have presented some challenges and limitations relating to its use for the prompt and efficient diagnosis of covid- . hence, the ct scan of the chest can play a pivotal role in the diagnosis and management of patients with covid- pneumonia. the present study showed that the predominant pulmonary parenchymal pattern for this disease is ground-glass haze/opacity followed by consolidation, as seen in . and . % of patients respectively. this is comparable to the other studies in the chinese population [ ] [ ] [ ] [ ] [ ] . a study by chung et al. showed that ground-glass opacification was the most frequently encountered imaging feature, as observed in % of the study population. the mixed pattern of both ggos and consolidations was detected in % of the population, compared to . % of the population in our study [ ] . the crazy paving pattern was noted in . % of our study population, which was comparable to a study by kanne et al., which showed crazy paving in % of the population [ ] . the reversed halo sign is defined as an area of central ggo with a surrounding rim of consolidation [ , ] . the reversed halo sign is seen in many conditions including cryptogenic organizing pneumonia, fungal infections, tuberculosis, sarcoidosis, and many other ailments [ ] . a study by zhao et al. has shown that the ct chest of . % of covid- patients exhibited these signs. moreover, according to that study, patients with moderate disease exhibited reversed halo sign more than those with severe disease ( . vs % respectively) [ ] . another study by jing et al. showed a reversed halo sign in . % of the patients [ ] . the findings of our study contrast with these results as they showed no reversed halo sign in any of the patients. this could be attributed to the fact that our study included a limited number of patients with moderate and severe disease. bilateral disease was seen in . % of patients, which is also comparable to other studies [ , , ] . it was observed that patients having unilateral disease ( . %) had mild disease and had mild or no symptoms, with the onset duration of symptoms never exceeding more than one week. similarly, the peripheral disease was seen in the majority of the patients ( . %). the mixed pattern of both peripheral and central disease was exhibited by . % of the patients, and a majority of these patients had either moderate or severe disease, and all of them had some respiratory symptoms. the scores noted for right and left lung in our study were also comparable with other studies [ ] . a study by yang et al. showed that the most commonly involved segments included posterior basal and superior segments of the lower lobes and posterior segments of the upper lobe [ ] . similar results were shown in our study where the most common segment involved was the superior segment of lower lobes, followed by posterior basal and lateral basal segments of the lower lobe. there are a few limitations to this study. firstly, the sample size was small, accounting for a small proportion of the total number of positive cases in pakistan. secondly, limited clinical and lab data were available due to the hectic workload in hospitals during this outbreak. thirdly, the course of the disease and outcomes in participants were not taken into account. based on our findings, the typical imaging findings of covid- pneumonia on hrct are ggos with multilobe involvement and bilateral, peripheral, and basal predominance. ct-ss is helpful in categorizing pneumonia into mild, moderate, and severe types, thereby enabling to identify patients with severe disease. this is particularly helpful in settings where fast triage is required. disclosures coronavirus infections and immune responses correlation of chest ct and rt-pcr testing in coronavirus disease (covid- ) in china; a report of cases chest ct findings in novel coronavirus ( -ncov) infections from wuhan, china: key points for the radiologist. radiology. ct imaging features of novel coronavirus ( -ncov). radiology. ct features of coronavirus disease (covid- ) pneumonia in patients in wuhan, china clinical features of patients infected with novel coronavirus in wuhan, china. lancet. ct imaging of the novel coronavirus ( -ncov) pneumonia . radiology. genomic characterization and epidemiology of novel coronavirus: implications for virus origins and receptor binding a novel coronavirus from patients with pneumonia in china world health organization: coronavirus disease (covid- ) outbreak a familial cluster of pneumonia associated with the novel coronavirus indicating person-to-person transmission: a study of a family cluster clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china. jama. clinical characteristics of coronavirus disease in china emerging novel coronavirus ( -ncov) pneumonia . radiology. covid- ): role of chest ct in diagnosis and management interpretation of ct signs of novel coronavirus (covid- ) pneumonia (epub ahead of print) the reversed halo sign in covid- pneumonia (preprint) . res square chest ct findings in coronavirus disease- (covid- ): relationship to duration of infection fleischner society: glossary of terms for thoracic imaging bronchiolitis obliterans with organizing pneumonia (boop), presenting as a ring-shaped opacity at hrct (the atoll sign). a case report the reversed halo sign: update and differential diagnosis chest ct severity score: an imaging tool for assessing severe covid- human subjects: consent was obtained by all participants in this study. institutional research forum, rawalpindi medical university issued approval /iref/rmu/ . ethical approval for the study was obtained from the institutional research forum, rawalpindi medical university. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- - gu ejul authors: moran, joseph v; godil, sara a; goldner, breanna; godil, kareem; aslam, jonaid title: post-extubation stridor complicating covid- -associated acute respiratory distress syndrome: a case series date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: gu ejul post-extubation stridor is a known complication of mechanical ventilation that affects a substantial number of all critical care patients and leads to increased morbidity and mortality. common risk factors for the development of post-extubation stridor include female gender, older age, and prolonged length of mechanical ventilation. there may be an increased incidence of post-extubation stridor in patients who require mechanical ventilation to manage the respiratory complications of covid- . in this case series, we analyzed nine patients from across our institution who were intubated to manage acute respiratory distress syndrome (ards) secondary to covid- and subsequently developed post-extubation stridor. the patients were predominantly females with prolonged intubations and multiple days of prone ventilation. while the patients in this case series possessed some of the well-described risk factors for post-extubation stridor, there may be risk factors specific to severe acute respiratory syndrome coronavirus (sars-cov- ) infection that make these patients more susceptible to the complication. the cuff leak test was performed on the majority of patients in the case series and did not successfully predict successful extubation in this population. our analysis suggests that prophylactic corticosteroids given in the - hours prior to elective extubation in female covid- patients who were intubated for more than six days with consecutive days of intermittent prone ventilation may be helpful in reducing the incidence of post-extubation stridor in this population. overall, this case series elucidates the need for exceptionally close monitoring of covid- patients upon extubation for the development of stridor. post-extubation stridor affects approximately % of all critically ill patients and is associated with re-intubation, prolonged duration of mechanical ventilation, and increased need for tracheostomy placement [ ] . patients who require mechanical ventilation to manage the complications of coronavirus disease (covid- ), caused by severe acute respiratory syndrome coronavirus (sars-cov- ), appear to have a substantial risk of their clinical course being complicated by post-extubation stridor [ ] . in this case series, we present nine patients who required mechanical ventilation for acute respiratory distress syndrome (ards) secondary to covid- and later developed post-extubation stridor. we will discuss the most common risk factors present in these patients, potential mechanisms for which sars-cov- makes patients more susceptible to post-extubation stridor, and potential treatment and prevention options. we identified nine patients from our institution who developed post-extubation stridor after intubation for ards secondary to covid- . during the interval that these patients were extubated, a total of covid- patients were extubated at our facility revealing an incidence of %. the patients were predominantly female with prolonged intubations and multiple days of prone ventilation. four patients received systemic steroids for an indication other than laryngeal edema during their initial intubation with the remainder not receiving systemic steroids until they developed post-extubation stridor. prior to their initial extubation, seven patients were noted to have a cuff leak. six patients were initially extubated to either high flow nasal cannula or noninvasive ventilation with one of these patients avoiding re-intubation. in total, eight patients required re-intubation with four ultimately requiring tracheostomy ( table ) . the patients presented in this case series possessed some of the well-described risk factors for the development of post-extubation stridor, specifically prolonged mechanical ventilation ( / were > days), obesity ( / had bmi > . ), and female gender ( / ) [ ] . there was concern that due to pre-existing obesity in many of the covid- patients, along with the use of enhanced personal protective equipment (ppe) for anesthesia teams that there would be an increased incidence of traumatic intubations, another common risk factor for post-extubation stridor [ ] . however, it is noteworthy that no traumatic intubations were reported among these patients by the intubating team at our institution. another interesting correlation was that all but one of the patients in this case series required consecutive days of intermittent proning. in the proning severe ards patients (proseva) trial, which randomized ards patients to intermittent proning, there was not a significant increase in post-extubation stridor reported in complications [ ] . it is not yet clear if this is also true for covid- patients who undergo proning and further analysis is needed to determine if proning is also a risk factor for post-extubation stridor in this population. there may be risk factors specific to covid- that increase the prevalence of post-extubation stridor in this population. during the interval that these nine patients were extubated, a total of covid- patients were extubated across our institution. this is notable considering that post-extubation stridor affects less than % of all critically ill patients [ ] . clinicians in smaller case series have noted considerable laryngeal edema and inflammation present upon intubation [ ] . while not yet described in sars-cov- , many of the other members of the coronavirus family have been associated with the development of laryngitis [ ] . a study analyzing the characteristics of a breakout of human coronavirus oc amongst patients revealed that . % developed laryngitis as a clinical symptom. if laryngitis occurs in a percentage of patients with covid- , this could help explain why these patients are at a seemingly higher risk of post-extubation stridor. seven of the patients were noted to have a qualitative cuff leak prior to extubation, with three of them having a documented quantitative cuff leak of %, %, and %, respectively. prior data correlate a successful extubation with a quantitative cuff leak of greater than %- % [ ] . however, at least one prior study suggested that the positive predictive value and sensitivity of the cuff leak test are quite low, making it a poor predictor of the presence of laryngeal edema in intubated patients. since this assessment may not provide an accurate evaluation of the presence of laryngeal edema or predict the occurrence of post-extubation stridor, some clinicians may prefer to avoid the cuff leak test in covid- patients altogether to reduce the risk of aerosolization of the virus. with the identification of potential risk factors, a focus can shift to proposed methods of prevention. while post-extubation stridor is often treated with systemic steroids and racemic epinephrine, the utility of prophylactic treatment prior to extubation with either agent has not been formally established. a meta-analysis on the use of prophylactic corticosteroid administration to decrease post-extubation stridor concluded that the administration of corticosteroids before elective extubation was associated with a significant reduction in the incidence of post-extubation stridor [ ] . only three of these patients were in the midst of a steroid course while being extubated, and amongst this group is the one patient who avoided re-intubation. therefore, it may be beneficial to prophylactically administer corticosteroids one to two days prior to an elective extubation for the dedicated purpose of reducing the risk of post-extubation stridor in select patients with covid- , particularly those with known risk factors. limitations of our study include the fact that our observations of stridor are mostly based on subjective assessments rather than objective findings of airway edema seen on direct visual inspection or imaging. additionally, there are a relatively small number of patients in our case series. post-extubation stridor in covid- patients is an important clinical entity that has not yet been described in detail in literature and warrants further study. this case series elucidates the need for close monitoring of covid- patients upon extubation for the development of stridor. contributing to an increased prevalence of this complication may be risk factors specific to covid- , with viral-induced laryngeal inflammation being a distinct possibility. the presence of a cuff leak did not predict successful extubation and may be deferred to minimize aerosolization of the virus. to mitigate the risk of post-extubation stridor, the use of prophylactic corticosteroids in the to hours leading up to extubation in females with a ventilator time greater than six days and who have required consecutive days of intermittent proning may be helpful. with mortality rates of covid- patients who require mechanical ventilation being exceptionally high, the reduction of any complication is paramount to the success of treating patients and reducing morbidity and mortality. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. cuff leak test for the diagnosis of post-extubation stridor: a multicenter evaluation study laryngeal oedema associated with covid- complicating airway management risk factors associated with prolonged intubation and laryngeal injury. otolaryngol head neck surg prone positioning in severe acute respiratory distress syndrome an outbreak of coronavirus oc respiratory infection in normandy, france the cuff leak test: does it "leak" any information prophylactic corticosteroids for prevention of postextubation stridor and reintubation in adults key: cord- -z q loy authors: ahmad, naim title: covid- modeling in saudi arabia using the modified susceptible-exposed-infectious-recovered (seir) model date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: z q loy the coronavirus disease (covid- ) pandemic has created unprecedented healthcare emergencies across the globe. the world health organization (who) has proposed social distancing (sd) as a prudent measure to contain the pandemic and, hence, governments have been enacting lockdowns of varied nature. these lockdowns, causing economic and social strain, warrant the development of quantitative models to optimally manage the pandemic. similarly, extensive testing aids in early detection and isolation, hence containing the spread of the pandemic. compartment epidemiology models have been used extensively in modeling such infectious diseases. this paper attempts to utilize the modified susceptible-exposed-infectious-recovered (seir) model incorporating the sd, testing, and infectiousness of exposed and infectious compartments to study the covid- pandemic in saudi arabia. saudi arabia has put restrictions on the movement of people in different phases to ascertain sd. time-dependent parameters based on the timeline of restrictions and testing in saudi arabia have been introduced to capture sd and testing. the arrived model has been validated through statistical tests. the [formula: see text] (r naught), basic reproduction number, value has ranged between . and . with an average of . and currently holds at . . in the absence of sd and testing measures, the model predicts the threshold herd immunity to be . % and [formula: see text] value as . . further, scenario analysis has been conducted for alleviating the sd measure. the results show that early lifting of all restrictions may undo all efforts in the containment of the covid- pandemic. the outcome of results will help policymakers and medical practitioners prepare better to manage the pandemic and lockdown. the current coronavirus disease (covid- ) pandemic has spread from the chinese city of wuhan. it mainly causes the common cold and could cause severe acute respiratory syndrome and may develop into fatal pneumonia [ ] . it transmits from person to person through direct and indirect contact, the fecal-oral route, and respiratory aerosolized droplets [ ] [ ] . it was first reported in wuhan in late december , and the first case in saudi arabia was reported on march , [ ] . as of in saudi arabia, there are a total of , confirmed cases, out of which , people have recovered and , died, leaving , active cases [ ] . the covid- pandemic has created restrictions on the movement of people and everyday activities, which is termed as social distancing (sd). as the world health organization (who) endorses physical distancing, wearing masks, washing hands with soap, and cleaning hands with alcohol-based hand rubs as some of the solutions to contain the pandemic until an effective drug or vaccine is available. this has resulted in lockdowns and severe strains on the economic activities and the mental and psychological well-being of many. therefore, to strike a balance between healthcare and economy, decision-makers need a quantitative model to predict the pandemic in order to ease lockdowns, resume economic activities, and protect the mental and psychological well-being of people. compartment epidemiology models have been widely used to quantify the trends of such infectious diseases. this study aims at using such a compartment epidemiology model to analyze the dynamics of the covid- epidemic in saudi arabia. the base compartment epidemiology model is susceptible-infectious-recovered (sir) [ ] and the extension of it is susceptible-exposed-infectious-recovered (seir). to study the dynamics of the covid- epidemic, several modified seir models have been used to incorporate various measures, especially social distancing, testing, public responses, and mobility restrictions [ , [ ] [ ] [ ] [ ] . the modified models have a large number of parameters that increase the complexity. incorporation of social distancing is essential and hubbs [ ] has used a single parameter to incorporate sd. further, as the measure of social distancing varies with time, hence, de falco et al. have introduced dynamic sd [ ] . dur-e-ahmad et al. [ ] incorporate the infectiousness among the exposed compartment similar to that of the infectious compartment as identified by he et al. [ ] . and berger et al. have modified the model with a testing parameter [ ] . the objective of this paper is to model the covid- pandemic in saudi arabia using seir, including sd, testing, and the infectiousness of exposed and infectious populations. for the simulation of the mathematical model, the python language has been used and results are validated with statistical analysis. further, the scenario analysis has been done to calculate threshold herd immunity and to study the effects of the alleviation of restrictions. the compartment epidemiology model seir divides the population of study into four compartments: susceptible , exposed , infectious , and recovered . the susceptible compartment represents a population that is prone to covid- , whereas the exposed population has acquired coronavirus but is asymptomatic. an infectious population has symptoms of coronavirus such as fever, cough, and fatigue and may infect the susceptible population. finally, the recovered compartment represents individuals that have either recovered or died. mathematically different compartments are governed by following differential equations ( ) ( ) ( ) ( ) . it is assumed that the total population ( ) remains fixed and recovered individuals remain immune to the disease during the study period. the parameter represents the average contact rate and and represent the inverse of the central measures of incubation period and infectious period. there is also one important index r naught, , known as the basic reproduction number that signifies the number of susceptible individuals that will get infected by an infectious individual. the value of needs to be less than one for a pandemic to die out. in the seir with sd model, one more parameter is introduced to represent sd that varies between (ideal isolation) and (no sd) [ ] . and in a dynamic sd case, the value of will vary with time based on the sd measure variations [ ] . similarly, dur-e-ahmad et al. have incorporated and to represent the relative infectiousness of exposed and infectious compartments, respectively [ ] . further, there are studies that have added parameter to represent testing [ ] . hence, a composite parameter to represent net measures is computed as , and mathematically, the positive part of this parameter ( ) is used, meaning for negative values, it will be zero. therefore, the mathematical formulation of the modified seir model adopted for the current study changes equations ( , ) as follows, whereas the equations ( , ) remain the same. the basic reproduction number ( ) is "defined as the expected number of secondary cases produced by a single (typical) infection in a completely susceptible population" [ ] . a nextgeneration matrix may be used to drive the equation of [ ] . using equations ( , ) , new functions and may be defined to represent the rate of new infections and the rate of transfer in and out of exposed and infectious compartments. therefore, the matrices and are defined, as shown in equations ( , ) . and the next generation matrix is defined as . the largest eigenvalue of (the spectral radius) gives , as given in equation ( ). there are a total of seven parameters , , , , , , and , and one derived parameter . and are disease-specific and calculated with incubation and infectious periods. signifies the contact rate and is modified by and accounting for social distancing and testing, respectively, or by net measures . and are modification parameters for the relative infectiousness of exposed and infectious populations. the incubation period ( ): the time period during which the exposed people become infectious and symptomatic is called the incubation period. the incubation period ranges between two and days [ ] . generally, the mid-value of days of the incubation period is considered but in the case of saudi arabia, the median incubation period is identified as six days [ ] . the inverse of the incubation period is known as the incubation rate. infectious period ( ): the time period during which an individual remains infectious and thereafter recovers or dies. this period is given between zero to days [ ] , three days or seven days [ ] , and . days [ ] . the inverse of the infectious period is known as the recovery rate. the value of this parameter has been taken within the acceptable range and in conjunction with model fitting in simulation. net measures ( ): the net measures ( ) is mathematically the positive part of the difference of social distancing ( ) and testing ( ). the social distancing ( ) measures are implemented differently by countries and vary with time. saudi arabia firstly suspended overseas umrah visitors on february , [ ] . the first case of covid- was detected on march , [ ] . thereafter, restrictions of a different nature were implemented such as curfews, classroom learning at schools and institutions, closure of private and public sectors, inter-city movements, hot-spot isolation, suspension of sports events, restrictions on public gatherings, prayers in masjids, suspension of domestic air and road transport, and others. the intensity of these measures was at the peak during march - , , for the eid festival by a hours nationwide curfew. after this relaxation period started in three phases, may - , , may -june , , and june , , onward. during the first phase, curfew was relaxed between am and pm, in the second phase, it was extended to pm, and in the third phase, it was relaxed completely. and all of the economic activities have been allowed with precautionary measures, such as face masks, sanitization, and physical distancing. but, still, international flights, overseas umrah, and school and colleges are closed and precautionary measures are being observed. based on these measures, a time-varying sd parameter has been defined, as shown in figure . the testing data for saudi arabia has been taken from the saudi ministry of health [ ] and the oxford covid- government response tracker [ ] and indexed between and to compute (figure ). both and values have been chosen to represent the sd restrictions and testing data in conjunction with model fitting in simulation. techniques [ ] . the value of is higher than the value of . the value of contact ratio ( ) is also estimated through optimizations techniques [ ] . the value of has been taken near and the values of and have been derived through simulation and optimization techniques. the model represented by ordinary differential equations ( , , , ) is utilized for the simulation of the pandemic in saudi arabia. coding was done in the python language [ ] in the environment of jupyter notebook [ ] . the equations were solved with the help of the function solve_ivp from the scipy.integrate sub-package. further, the minimize function from the scipy.optimize sub-package was used to minimize the difference between predicted and reported values of total cases to estimate and . the values of other parameters were given as defined previously such as . for the values of and , discrete events of sd and testing data were smoothed out slightly using the univariatespline function with a smoothing factor of . (figure ) . thereafter, the values of were computed from the smoothed values of and . the initial values for solving the ordinary differential equations were as follows (cases on first day), (assumed that five times individuals are exposed on first day), (recovered on first day) and , as the total population of saudi arabia is , , . the levene statistical tests were performed to validate model results against the epidemic reported data from the saudi ministry of health [ ] . the resultant model identified the values of and to be . and . by fitting the values of cumulative total cases against the reported cumulative total cases up to august , ( figure ) . the levene test (statistic= . , p-value= . ) shows that there is no significant difference between model values and reported values. further, in figure , it is evident that the model is fitting closely with the cumulative recovered cases as well. as the levene test (statistic= . , p-value= . ) confirms that there is no significant difference between model values and reported values. similarly, the cumulative active cases that include exposed and infectious populations fit closely and the levene test (statistic= . , p-value= . ) proves the same. the results of the simulation show a very significant model fitting, as all the three publicly reported data, such as total cases, recovered cases, and active cases, show no significant difference from the respective model values. the model results in the current scenario of restrictions and testings depict that there are multiple peaks for active cases (figure ) . it identifies two visible peaks in the period of days of neighborhood data settings to identify the local maxima. this pattern also closely resembles the reported data although the absolute values differ with the reported data within statistical non-significant limits. the value has ranged between . and . , with an average of . , and currently holds at . . as the current value of is less than one, the pandemic is expected to decline and the peak has already passed ( figure ). it is important to achieve herd immunity for the pandemic to decline in the absence of any measures. as of now, there is no proven vaccine for covid- , therefore, herd immunity can only be achieved when a substantial proportion of the population has recovered with the assumption that the recovered become immune to covid- . therefore, this scenario removes the sd and testing measures and recomputes the model results with the parameter values identified in the fitted model previously. the value has come out to be . and threshold herd immunity ( ) will be achieved at . % of the population ( figure ) . further, the pandemic will infect . % of the population by the end. further, the sd measures were varied for two possibilities and compared with the current measures (low-risk scenario). the first possibility is gradual full normalization by december , , and termed as a high-risk scenario. and the second possibility could be gradual partial normalization by june , , the expected date of vaccine (medium-risk scenario), whereas covid- testing is assumed to continue at the same level. the values of and for the above-mentioned three scenarios are shown in figure . the peak total active cases are , , , , and , , for low-risk, medium-risk, and high-risk scenarios, respectively ( figure ). these peak values are supposed to be achieved on the th day (july , ), th day (july , ), and th day (december , ) for the respective scenarios. in the low-risk scenario, the peak has already passed at a relatively very low value of , for active cases, the current scenario. in the second scenario of mediumrisk, the peak is flattened and delayed beyond the arrival of the expected vaccine date, although the peak value is almost . million of active cases, which is a huge number to be managed. the third scenario of high risk will bring a very high peak value of almost . million active cases before the end of this year and way before the expected vaccine date. this study has modeled the covid- pandemic using a modified version of the base compartment epidemiology model of seir. the modification was achieved by the introduction of four parameters accounting for the social distancing, testing, and infectiousness of exposed and infectious populations. the mathematical equations corresponding to the modified model were simulated in a python environment. the optimization technique was used to fit the model with reported cases by the varying contact rate and infectiousness of the exposed population. the remaining model parameters were chosen within the acceptable range and in conjunction with model fitting. the statistical analysis shows a good model fit, as the model results for total cases, recovered cases, and active cases have no significant difference with those of reported cases. as per model results, the peak has already passed and the pandemic is expected to decline with current measures in place. hence, the current measures have been proven to be very effective in saudi arabia. the model has been run on different scenarios for social distancing to predict the possible outcomes. the results indicate that early complete normalization efforts may undo the successful containment of the pandemic. therefore, the decision to alleviate restrictions has to be well worked with other mechanisms such as increasing the testing capacity and throughput and the availability of effective drugs and vaccines. nonetheless, due to unavoidable assumptions and the exponential nature of functions for all categories of cases, actual numbers may vary from the model results and care should be taken in interpreting the results. human subjects: all authors have confirmed that this study did not involve human participants or tissue. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. preparedness and response to covid- in saudi arabia: building on mers experience dynamics of sars-cov- outbreak in the kingdom of saudi arabia: a predictive model fecal transmission in covid- : a potential shedding route protection from covid- a contribution to the mathematical theory of epidemics transmission dynamics of the covid- outbreak and effectiveness of government interventions: a data-driven analysis an seir infectious disease model with testing and conditional quarantine outbreak dynamics of covid- in europe and the effect of travel restrictions transmission dynamics model of coronavirus covid- for the outbreak in most affected countries of the world coronavirus covid- spreading in italy: optimizing an epidemiological model with dynamic social distancing through differential evolution temporal dynamics in viral shedding and transmissibility of covid- notes on r perspectives on the basic reproductive ratio incubation period of novel coronavirus ( -ncov) infections among travellers from wuhan, china clinical characteristics of covid- in saudi arabia: a national retrospective study on a statistical transmission model in analysis of the early phase of covid- outbreak the effect of control strategies to reduce social mixing on outcomes of the covid- epidemic in wuhan, china: a modelling study seir and regression model based covid- outbreak predictions in india oxford covid- government response tracker the python language reference manual jupyter notebooks-a publishing format for reproducible computational workflows. positioning and power in academic publishing: players, agents and agendas. loizides f, schmidt b the author is thankful to king khalid university for all the support. key: cord- - s y kc authors: rajdev, kartikeya; lahan, shubham; klein, kate; piquette, craig a; thi, meilinh title: acute ischemic and hemorrhagic stroke in covid- : mounting evidence date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: s y kc the novel coronavirus disease of (covid- ) is caused by the binding of severe acute respiratory syndrome coronavirus- (sars-cov- ) to angiotensin-converting enzyme (ace ) receptors present on various locations such as the pulmonary alveolar epithelium and vascular endothelium. in covid- patients, the interaction of sars-cov- with these receptors in the cerebral blood vessels has been attributed to stroke. although the incidence of acute ischemic stroke is relatively low, ranging from % to %, the mortality associated with it is substantially high, reaching as high as %. this case series describes three distinct yet similar scenarios of covid- positive patients with several underlying comorbidities, wherein two of the patients presented to our hospital with sudden onset right-sided weakness, later diagnosed with ischemic stroke, and one patient who developed an acute intracerebral hemorrhage during his hospital stay. the patients were diagnosed with acute stroke as a complication of covid- infection. we also provide an insight into the possible mechanisms responsible for the life-threatening complication. physicians should have a low threshold for suspecting stroke in covid- patients, and close observation should be kept on such patients particularly those with clinical evidence of traditional risk factors. the novel coronavirus disease of (covid- ) caused by the severe acute respiratory syndrome coronavirus- (sars-cov- ) has infected more than million people causing more than , deaths worldwide as on august , [ ] . although the virus predominantly affects the lower respiratory tract, the extrapulmonary manifestations are not uncommon. the commonly involved systems are cardiovascular, gastrointestinal, hematological, hepatocellular, renal, and dermatological [ , ] . another equally concerning feature of covid- is the involvement of the central nervous system, which may vary from headaches, dizziness, hypogeusia, or encephalitis owing to direct viral invasion of neural tissue, to cerebrovascular disease or stroke [ , ] . the incidence of both acute ischemic stroke and hemorrhagic in covid- patients is reported to range from % to % [ ] [ ] [ ] [ ] [ ] [ ] . the acute brain infarction secondary to stroke is of particular importance because it not only substantially affects the prognosis of the patient but can also have long-term residual neurological deficits. in our case series, we present three relatively uncommon cases of covid- presenting with stroke. a -year-old woman with a past medical history of type-ii diabetes mellitus, chronic obstructive pulmonary disease (copd) on nocturnal l/min home oxygen, obstructive sleep apnea on bipap (bilevel positive airway pressure) at home, hypertension, and dyslipidemia was diagnosed with covid- infection eight days prior to her admission. she presented to the emergency department (ed) with a sudden onset of right-sided weakness and aphasia. the patient received thrombolysis therapy with tissue plasminogen activator (tpa) for ischemic stroke after a ct scan of the head was negative for hemorrhage. the patient was then transferred to our hospital for a higher level of care and evaluation for possible thrombectomy. in our ed, the patient had blood pressure (bp) and heart rate (hr) of / mmhg and beats/min, respectively, with % spo on l of oxygen through a nasal cannula. she was awake, alert, and following commands. a critical neurologic examination revealed severe global aphasia, dense right hemiparesis, and a left gaze preference, with an nih stroke score (nihss) of . her initial laboratory reports did not show any derangements. the patient underwent a ct angiogram of head and neck and ct perfusion scan of the brain, both of which did not reveal any major vessel occlusion or a perfusion defect. she was then admitted to the covid icu and was subsequently started on aspirin and statin, and intravenous medications to maintain systolic bp < / . she was also started on remdesivir for covid- related illness. mri of the brain was performed the next day that showed an acute/sub-acute infarct involving the left caudate nucleus and putamen ( figure ). on day of admission, she was observed to have worsening somnolence (nihss of ), for which another head ct scan was performed that did not reveal any new findings. over the course of the next three days, the patient continued to deteriorate with worsening lethargy and a progressive decline in her mental status. the patient was intubated for airway protection. despite appropriate treatment and mechanical ventilatory support, the patient's clinical condition continued to deteriorate. the patient's family was updated regarding her clinical prognosis, and after an adjudicated discussion, the patient's family decided that they no longer wish to subject her to further aggressive interventions, which were also in concordance with the patient's wishes. the following day she was compassionately extubated receiving comfort measures only. our patient expired six days into her hospital admission. a -year-old caucasian male with a past medical history of coronary artery disease with a two-vessel coronary artery bypass graft nine years ago, heart failure, hypertension, dyslipidemia, type diabetes mellitus, methamphetamine abuse, and tobacco abuse was brought to the ed after being found down at a friend's house. his last-known well time was the night prior to the presentation. the patient upon presentation was lethargic with severe aphasia with an hr of beats/min, bp of / mmhg, temperature of . °c, and oxygen saturation of % on room air. upon examination, he was noted to have right-sided hemiparesis, right-sided facial droop, expressive aphasia, severe dysarthria, and left gaze preference. while in the ed, the patient became more obtunded, requiring intubation for airway protection. the patient had a white blood cell count of , /µl, lactic acidosis of . mmol/l, and an elevated procalcitonin of . ng/ml. his chest x-ray showed bilateral patchy opacities. a ct angiogram of the head and neck revealed a moderate-sized subacute left middle cerebral artery (mca) branch infarct, which was primarily perisylvian with a corresponding perfusion defect (figure a) . there was no intracranial hemorrhage, mass effect, or any major vessel occlusion. the patient was not a candidate for thrombolysis and was started on aspirin and atorvastatin. his chest ct did not show pulmonary emboli but diffuse bilateral ground-glass consolidation ( figure ) . a nasopharyngeal swab for covid- pcr (polymerase chain reaction) was obtained, which came back negative. due to the concern for covid- pneumonia, a tracheal aspirate was sent for covid- pcr that returned positive. the patient was initiated on remdesivir and dexamethasone for covid- pneumonia. the pneumonia panel from tracheal aspirate showed methicillin-sensitive staphylococcus aureus, streptococcus agalactiae, and streptococcus pneumoniae for which he was initiated on appropriate antibiotics. his echocardiogram showed normal systolic function with an ejection fraction (ef) of %. mri of the brain showed an evolving moderate size subacute left mca branch infarct (figure b) . ekg did not reveal any cardiac arrhythmia. the patient improved from a respiratory standpoint and was extubated to high-flow nasal cannula on day of his hospital stay. the patient was awake, alert, and oriented; however, he continued to have right-sided hemiparesis and expressive aphasia. a -year-old hispanic male with a past medical history of hypertension and tobacco abuse presented to the ed with a two-day history of progressively worsening dyspnea and cough. his vitals upon presentation were as follows: hr of /min, bp of / mmhg, temperature of . °c, and spo of % on room air. he had a leukocyte count of , /µl, lactic acid level of . mmol/l, c-reactive protein of . mg/l, creatinine of . mg/dl, and an elevated procalcitonin of . ng/ml. ct scan of the chest showed bilateral nodular ground-glass opacities with a crazy-paving appearance. a nasopharyngeal swab for covid- pcr was positive. the patient was also initiated on antibiotics for concomitant bacterial pneumonia with a positive streptococcus pneumoniae urine antigen. his oxygen requirements gradually worsened requiring intubation on day of hospitalization and vasopressor support for shock. a pneumonia panel from tracheal aspirate detected streptococcus pneumoniae. he also developed worsening renal function requiring renal replacement therapy. the patient was noted to develop paraplegia on minimal sedation on day of hospitalization prompting a ct scan of the head, which showed a . -cm low-density area in the right occipital lobe consistent with a subacute ischemic stroke (figure a) . he was started on aspirin and atorvastatin. a transthoracic echocardiogram showed an ef of - % with no wall motion abnormalities. his mental status continued to deteriorate until he became unresponsive with bilaterally dilated pupils. a repeat ct scan of his head showed a new large . -cm right intraparenchymal hematoma with associated midline shift and transtentorial herniation with evidence of global hypoxic-ischemic injury and herniation-related infarction as well as scattered subarachnoid hemorrhage (figure b) . the patient was receiving subcutaneous heparin for deep vein thrombosis (dvt) prophylaxis but no therapeutic anticoagulation was given. in the best interest of the patient and in accordance with the patient's wishes, the family decided to transition his goals of care to comfort care only. the patient expired after a prolonged hospital stay of days. largely due to its multi-system involvement and a wide spectrum of clinical presentations, covid- continues to pose challenges affecting clinical prognosis, particularly among the elderly and those with underlying comorbidities, such as our patients. the clinical profiles of our patients are consistent with the findings of a recent meta-analysis by tan et al. who concluded that the mean duration of an acute ischemic stroke from the onset of covid- symptoms was ± days, with a mean age of . ± years [ ] . the precise mechanism responsible for causing acute ischemic stroke in covid- positive patients is currently unclear. however, proposed speculations suggest that the process may be multifactorial. the sars-cov- gains entry into the human body by attaching itself to the membrane-bound angiotensin-converting enzyme (ace ) receptors located on, but not limited to, pulmonary alveolar epithelial cells and vascular endothelium [ , ] . the viral interaction with ace receptors in blood vessels causes endothelial damage and induces a hyperimmune response: "cytokine storm" releasing inflammatory markers such as interleukin (il)- , il- , and tumor necrosis factor-alpha (tnf-a) that might predispose to stroke by causing vasculitis [ , , ] . moreover, covid- is also associated with hypercoagulability and hyperviscosity, which can immensely increase the risk of stroke [ , ] . lastly, the preexistence of traditional risk factors such as hypertension, dyslipidemia, diabetes, and atherosclerotic vascular disease (such as in our case) in the setting of extensive covid- infection may have a synergistic contribution in increasing patient predisposition to stroke by causing plaque disruption. the ace receptors also play a role in the pathogenesis of hemorrhagic stroke, wherein the downregulation of receptors coupled with elevated angiotensin ii and endothelial dysfunction in cerebral arteries increases bp, and thus the risk of hemorrhage [ ] . pre-existing hypertension is a potential risk factor for hemorrhagic stroke. stroke (both ischemic and hemorrhagic) occurring in the setting of covid- is reported to have a worse patient prognosis, with a substantially higher risk of in-hospital mortality [ ] . one study found that the risk of mortality among covid- patients with ischemic stroke was % [ ] . tan et al. also reported a similar finding in their meta-analysis, with a cumulative mortality risk of % [ ] . strategies that seem plausible in treating covid- patients with stroke include the use of tpa, but the role of other anticoagulants such as lowmolecular-weight heparin or unfractionated heparin is debatable and controversial. since sars-cov- binds to and depletes ace receptors, administration of exogenous ace in the form of human recombinant soluble ace (hrs ace ) might reduce the risk of acute stroke by replenishing ace in cerebral blood vessels [ , ] . interestingly, elevated serum levels of d-dimer, fibrinogen, and anti-phospholipid antibodies are implicated in covid- patients with ischemic stroke [ ] . periodic assaying of these biomarkers might help in identifying patients with increased stroke predisposition. workflow proposed by qureshi et al. seems promising as it lays down a step-by-step guide for the management of acute ischemic stroke for the physicians [ ] . another study involving patients with ischemic stroke reported that early intravenous thrombolysis and recanalization through mechanical thrombectomy had resulted in poor outcomes in their patient cohorts [ ] . moreover, stroke teams need to be extra cautious so as to minimize the risk of self-exposure with the proper use of protective equipment. both ischemic and hemorrhagic stroke are associated with covid- infection and carry a high risk of mortality. the ace receptors, circulating cytokines, and hypercoagulability are integral in the pathogenesis of stroke in covid- patients. further studies need to be conducted to understand the exact mechanism in covid- patients with stroke. however, treating physicians should have a low threshold for suspecting stroke in covid- patients, and close observation should be kept on such patients particularly those with clinical evidence of traditional risk factors. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities 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sars-cov- infections in engineered human tissues using clinical-grade soluble human ace management of acute ischemic stroke in patients with covid- infection: insights from an international panel treatment of acute ischemic stroke due to large vessel occlusion with covid- : experience from paris key: cord- - liu anc authors: elavia, nasha; sharma, nishant; li, si; wang, yichen; milekic, bojana title: an atypical presentation of acute pulmonary embolism with severe acute respiratory syndrome coronavirus (sars-cov- ) pneumonia date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: liu anc clinical presentation and severity of the severe acute respiratory syndrome coronavirus (sars-cov- ) varies greatly amongst patients, as supported by recent literature. this poses an ongoing challenge in the diagnostic and therapeutic approach for managing these patients. here, we would like to describe a case of acute bilateral pulmonary embolism (pe) presenting with atypical gastrointestinal symptoms in a patient with sars-cov- infection. this atypical presentation of pe is unique to our case and highlights the significance of a high index of clinical suspicion for sars-cov- and its associated thrombogenic effect, even in patients with atypical symptoms. although knowledge about the effects of the novel severe acute respiratory syndrome coronavirus (sars-cov- ) has been emerging, so far, the most commonly documented reason for hospitalization was respiratory distress [ ] . proinflammatory states, such as acute infections, were known to be associated with an increased risk of thromboembolic events. venous thromboembolism is an uncharacteristic complication of the sars-cov- , and only few descriptions of potential correlation exist in the literature [ ] . newly discovered atypical features of the sars-cov- infection continue to be frequently reported, while increasing clinician's awareness and mindfulness for uncommon presentations. here, we would like to describe a case of acute bilateral pulmonary embolism (pe) in a patient with sars-cov- pneumonia who mainly presented with gastrointestinal symptoms. a -year-old male with a past medical history notable for diabetes mellitus type , obstructive sleep apnea treated with nocturnal continuous positive airway pressure ventilation (cpap) and glaucoma presented to the emergency department with diarrhea and loss of appetite. the patient reported having four to five episodes of watery bowel movements per day, which started about seven days prior to admission. he denied any nausea, vomiting, abdominal pain, blood in stool, fever or any respiratory complaints of chest pain, shortness of breath or cough. social history was negative for smoking, recent travel, sick contact exposure, immobilization, hospitalization or recent antibiotic use. on presentation, he was tachypneic at breaths per , minute and hypoxic with an oxygen saturation of % while breathing ambient air. his physical exam revealed bilateral basilar rhonchi, but otherwise he did not appear in any acute respiratory distress. laboratory studies were notable for lymphopenia (absolute lymphocyte count . k/ul) along with significantly elevated lactate dehydrogenase ( u/l), ferritin ( , ng/ml) and c-reactive protein ( mg/l) levels. chest x-ray revealed bilateral airspace opacification as seen with sars-cov- . a nasopharyngeal swab for sars-cov- was positive. the pretest probability of pe calculated using the wells score was less than , which was unlikely for pe. bilateral lower extremity duplex was negative for deep venous thrombosis (dvt). d-dimer level was . ng/ml feu. in the light of significant discrepancy between severe hypoxia and the absence of respiratory symptoms or a respiratory viral syndrome, a pulmonary ct angiogram (cta) was performed, which confirmed acute bilateral pe extending from the distal right main pulmonary artery into all right lobes along with patchy ground-glass opacities consistent with sars-cov- pneumonia (figure ). axial image (a) and coronal image (b) demonstrating bilateral filling defects of the pulmonary artery (red arrows). the patient was admitted to a negative pressure room and started on anticoagulation with heparin. he was eventually discharged home on an oral novel anticoagulant and continuous oxygen at liters/minute via nasal cannula. the sars-cov- pandemic is challenging and, in many cases, an overwhelming situation for the medical community. research on the characteristics of this novel coronavirus is evolving every day as cases of sars-cov- continue to emerge with a multitude of clinical presentations. so far, fever is the most commonly reported symptom (approximately % of cases), followed by cough ( %), vomiting ( %) and diarrhea ( . %) [ ] . up to % of patients develop complications of severe interstitial pneumonia leading to acute respiratory distress syndrome (ards), multiorgan failure, disseminated intravascular coagulation and death [ ] . [ , ] . in contrast to our case, patients with suspected pe have been reported to have overlapping symptoms of sars-cov- [ ] . our patient however presented mainly with gastrointestinal symptoms, which have been reported with sars-cov- ; however, with significant hypoxia in the absence of a respiratory viral syndrome although with a low pretest probability for pe, we decided to further evaluate the patient for hypoxia. the presence of gastrointestinal symptoms and cardiopulmonary complications are reported in patients with sars-cov- ; however, the presence of gastrointestinal symptoms in sars-cov- complicated with pe in the absence of an overlapping respiratory viral syndrome makes our case unique. risk assessment scores and laboratory data are widely used to assist in clinical decision making; nevertheless, the importance of clinicians' degree of suspicion and mindfulness for atypical presentations and complications cannot be overstated, especially in a currently evolving disease like sars-cov- infection. at many centers across the united states, inflammatory marker levels are now routinely checked in sars-cov- patients. studies have shown that elevated d-dimer levels correlate with the severity of sars-cov- illness, poor prognosis, higher likelihood of admission to the intensive care unit (icu) and even death [ , ] . although our patient did not have symptoms of a viral respiratory syndrome, an elevated d-dimer level prompted us to do a chest cta. the decision was supported by the literature (algorithm by zuckier et al. published in april suggests obtaining a chest cta in sars-cov- patients with elevated d-dimer levels if there are no contraindications) [ ] . additionally, patients with severe sars-cov- disease, including those requiring invasive mechanical ventilation and intensive care, are known to have an increased risk of venous thrombosis [ ] . whether this thrombogenic phenomena is due to the virus itself or the acute inflammation in critically ill patients is not clear. as such, algorithms have been developed but the decision for therapeutic anticoagulation in sars-cov- patients at this time remains largely individualized, accounting for patient and physician factors. further studies are required to aid in developing evidence-based guidelines for therapeutic anticoagulation in patients with sars-cov- depending on patient characteristics and severity of the infection. cases of sars-cov- continue to emerge with atypical presentations such as the case highlighted here. therefore, it is important for all physicians (and particularly, the emergency department) to have a high clinical suspicion for both sars-cov- and venous thrombosis and include these in the differential diagnoses and early identification of the disease. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. acute pulmonary embolism and covid- pneumonia: a random association covid- complicated by acute pulmonary embolism clinical characteristics of coronavirus disease in china epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study analysis of deaths during the severe acute respiratory syndrome (sars) epidemic in singapore: challenges in determining a sars diagnosis anticoagulant treatment is associated with decreased mortality in severe coronavirus disease patients with coagulopathy diagnostic evaluation of pulmonary embolism during the covid- pandemic covid- complicated by acute pulmonary embolism and right-sided heart failure key: cord- -m vbkvju authors: torkian, pooya; ramezani, naghi; kiani, pejman; bax, michael r; akhlaghpoor, shahram title: common ct findings of novel coronavirus disease (covid- ): a case series date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: m vbkvju given the highly infectious nature of the coronavirus disease (covid- ) virus and the lack of proven specific therapeutic drugs and licensed vaccines effective against it, early diagnosis of the disease is of paramount importance. the common chest ct imaging of confirmed covid- cases is discussed here, which shows ground-glass opacity, crazy paving, and consolidation. in late december with the outbreak of coronavirus disease (covid- ) and an exponentially growing death toll in wuhan, china, a state of emergency was declared [ ] . iran, n subsequent epicenter of covid- , announced a total of deaths due to covid- as of march , [ ] . given the highly infectious nature of the virus and the lack of proven specific therapeutic drugs and licensed vaccines effective against covid- , early diagnosis of the disease is of paramount importance [ ] . as confirmed covid- cases are being diagnosed all over the world, radiologists are key to prompt clinical diagnosis and understanding of the common imaging manifestation of the disease as they may encounter suspected cases prior to other clinicians. the experience of affected countries shows that ct can play a pivotal role for pneumonia screening and diagnosis by producing fine specific details. the common chest ct imaging of confirmed covid- cases is reported here to aid prompt clinical diagnosis. ground-glass opacity (ggo) is frequently observed due to enhanced lung attenuation without obscuration of underlying vessels. in ggo, alveoli are partially filled with fluid which appears gray on ct images. the distribution of ggo lesions in covid- tends to be peripheral, bilateral, and along the pleura and bronchovascular bundles [ ] [ ] [ ] . a -year-old woman from the rasht provincial hospital presented three days after the onset of fever ( . °c), cough, and chills. she did not reveal any history of sick contacts in the family or underlying lung disease. unenhanced chest ct images at her presentation showed patchy illdefined ggos as an archetypal response to acute lung injury in the left and right lower lobes of the lung (figure ). a noncontrast-enhanced ct image of the lungs demonstrating bilateral patchy ill-defined groundglass opacities (ggos) in posterior segments of the lungs (a) and an inset magnified view of the lesion for better delineation at the location of ggo in the right lower lobe of the lung (b). following lung involvement in covid- , the thickened interlobular septa and intralobular lines laid over a background of ggo known as crazy paving can be observed. a -year-old man presented in our clinic with fever ( . °c), cough, dyspnea, and intermittent chest pain. in his physical examination, he exhibited coarse breath sounds during auscultation. axial thin-section unenhanced ct images obtained on march , show crazy paving mostly in the left and right lower lobes of the lung (figure ) . a noncontrast-enhanced ct image of the lungs demonstrating bilateral crazy paving in the posterior lobe of both lungs (a) and an inset magnified view of the lesion for better delineation at the location of crazy paving in the right lower lobe of the lung (b). consolidation is detected when underlying vessels and airways are obscured due to complete replacement of air with fluid. consolidation appears white on ct images. on march , , a -year-old man from the north of iran, one of the main epicenters of the covid- infection in the country, was referred to our center after the onset of fever ( . °c), nonproductive cough, muscle aches, and dyspnea. in his lung examination, coarse breath sounds were heard during auscultation. his transaxial unenhanced chest ct images show dense consolidation (figure ) . a noncontrast-enhanced ct image of the lungs showing consolidation in both lungs (a) and an inset magnified view of the lesion for better delineation at the location of consolidation in the right lower lobe of the lung (b). given the limited number of nucleic acid testing kits, such as real-time reverse transcriptase polymerase chain reaction (rrt-pcr) assays and the probability of false-negative rrt-pcr results, chest ct imaging as a noninvasive imaging modality can be a useful tool with high accuracy for early diagnosis of suspected covid- cases [ ] . for this purpose it is necessary to identify common imaging patterns of these cases. interestingly, fang et al. found that covid- rrt-pcr sensitivity may be as low as % compared to the % sensitivity of ct for covid- infection [ ] . due to the ease of access, wide availability, and rapid results of ct scanners compared to rrt-pcr kits, ct imaging is on the front line of covid- screening tools. up to the present time, most covid- cases have shown pure ggo and consolidative lesions in % of their early chest ct imaging [ , ] . as the infection advances, ct imaging will reveal other findings such as the crazy-paving pattern. when radiologists see the common chest imaging findings of this new strain of coronavirus, they can identify covid- cases in a timely manner based on the appropriate epidemiologic and demographic features. in so doing, prompt reasonable preventive action can be implemented to curtail the transmission of this enveloped positive-sense rna virus. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. china coronavirus: who declares international emergency as death toll exceeds covid- situation report laboratory diagnosis and monitoring the viral shedding of -ncov infections chest ct findings in novel coronavirus ( -ncov) infections from wuhan, china: key points for the radiologist. radiology. ct imaging features of novel coronavirus ( -ncov). radiology. emerging novel coronavirus ( -ncov) pneumonia use of chest ct in combination with negative rt-pcr assay for the novel coronavirus but high clinical suspicion sensitivity of chest ct for covid- : comparison to rt-pcr ct imaging of the novel coronavirus ( -ncov) pneumonia . radiology. key: cord- -p jl vie authors: asghar, muhammad sohaib; haider kazmi, syed j; khan, noman a; akram, mohammed; hassan, maira; rasheed, uzma; ahmed khan, salman title: poor prognostic biochemical markers predicting fatalities caused by covid- : a retrospective observational study from a developing country date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: p jl vie background and objectives infections with severe acute respiratory syndrome coronavirus (sars-cov- ) are rapidly spreading, posing a serious threat to the health of people worldwide, resulting in the world health organization officially declaring it a pandemic. there are several biochemical markers linked with predicting the severity of coronavirus disease. this study aims to identify the most effective predictive biomarker such as c-reactive protein (crp), ferritin, lactate dehydrogenase (ldh), procalcitonin (pct), and d-dimer, among others, in predicting the clinical outcome of the disease. materials and methods this study was conducted as a retrospective, observational, multi-centric study, including all admitted covid- positive patients only. the disease outcome was followed along with the hospital course of every patient at the time of analysis. baseline laboratory investigations of all patients were monitored both at admission and discharge. a comparative analysis was done between the survivors (n= ) and non-survivors (n= ). statistical analysis was conducted using ibm spss statistics for windows version (armonk, ny: ibm corp.). results of patients, . % were in the isolation ward, and . % were in the intensive care unit; . % of patients survived, while . % of patients died. the mean age of the study population was . ± . years with female patients significantly younger than male patients (p= . ) and to years being the most common age group (p= . ). among the survivors versus non-survivors of covid- , there were significant differences in total leukocyte count (p< . ), neutrophil count, (p< . ), lymphocyte count (p< . ), urea (p< . ), serum bicarbonate (p= . ), crp levels (p< . ), ldh (p= . ), and d-dimer (p< . ) at admission. at discharge, the laboratory values of non-surviving patients showed significant leukocytosis (p< . ), neutrophilia (p< . ), lymphocytopenia (p< . ), decreased monocytes (p< . ), elevated urea and creatinine (p< . ), hypernatremia (p< . ), decreased serum bicarbonate levels (p< . ), elevated crp level (p= . ), ldh (p< . ), ferritin (p= . ), and d-dimer (p< . ). among the recovered patients, the laboratory investigations at admission were significantly different from those at discharge like increased platelets (p= . ), lower neutrophil count (p= . ), higher lymphocyte count (p= . ), an improved creatinine (p= . ), higher sodium (p= . ), increased bicarbonate levels (p< . ), decreased crp levels (p< . ), and a lower ldh (p= . ). however, the laboratory values of non-surviving patients had shown a lower hemoglobin (p= . ), increased mean cell volume (p< . ), significantly increased total leukocyte count (p< . ), increased urea and creatinine (p< . ), hypernatremia (p< . ), increased bicarbonate (p= . ), elevated d-dimer levels (p= . ), and elevated pct (p= . ) on discharge. receiver operating characteristic analysis concluded ldh (area under the curve [auc]: . ), d-dimer (auc: . ), and pct (auc: . ) were superior biomarkers to ferritin (auc: . ) and crp (auc: . ) in predicting the fatality of covid- . conclusion inflammatory markers are a useful guide for predicting mortality, and the study results concluded that ldh, pct, d-dimer, crp, and ferritin were effective biomarkers. in december , a mysterious pneumonia-like syndrome was observed in wuhan, china [ ] . the causative virus was officially termed as the severe acute respiratory syndrome coronavirus (sars-cov- ), and the disease it caused was named coronavirus disease by the international committee on taxonomy of viruses [ ] . covid- is primarily a respiratory disease but can cause various non-respiratory manifestations, such as gastrointestinal, neurological, renal, and cardiovascular symptoms [ ] . the sars-cov- infection is rapidly spreading, posing a serious threat to the health of people worldwide, resulting in the world health organization officially declaring it a pandemic on march , . there are several biochemical markers linked with predicting the severity of coronavirus disease. ferritin, produced in inflammatory conditions of the body (infectious, malignant, hematologic, and rheumatologic), is an important acute phase reactant. microscopically, ferritin plays a defensive role within the body by limiting the supply of iron, due to which elevated serum ferritin levels can be seen in individuals with high pathogenic loads [ ] . ferritin not only limits the availability of iron to the pathogen but also regulates cytokine synthesis and release that are responsible for the cytokine (proinflammatory) storm [ ] . c-reactive protein (crp) is an acute-phase reactant that is synthesized by the liver in response to inflammation or infection. unlike most acute-phase proteins that undergo large variations in plasma levels (depending on the synthesis, consumption, and catabolism rates), plasma crp levels remain nearly constant. during acute inflammation, serum concentrations increase dramatically, making it a more accurate marker for sepsis [ ] . crp also contributes to the proinflammatory cycle by activating inflammatory cytokines in the body [ ] . crp and serum ferritin both play important roles in producing proinflammatory cytokines. interestingly, the principal finding of immunopathology in covid- is the cytokine storm. the virus replicates rapidly in the body's endothelial and epithelial cells, resulting in the immune system developing significant numbers of proinflammatory cytokines and chemokines [ ] . the severity of covid- resides in the development of large quantities of proinflammatory cytokines that can eventually contribute to acute respiratory distress syndrome (ards) and multiple organ failure (mof) [ ] . studies have shown that respiratory tract viral infections were associated with poor clinical outcomes due to the high rates of cytokines and chemokines released during the infection [ ] . severe covid- cases are progressing quickly to complications, such as ards, sepsis, septic shock, metabolic acidosis, coagulopathy, and mof [ , ] . a study that analyzed the clinical characteristics of deceased coronavirus patients identified sepsis, ards, respiratory failure, and heart failure as the most critical complications [ ] . due to its valuable role in the diagnosis and prognosis regarding sepsis, procalcitonin (pct) is widely considered to be the most useful marker of severe systemic inflammation. under normal circumstances, pct is produced in the c-cells of the parathyroid gland. however, the rise in pct seen during infectious states is believed to stem from neuroendocrine cells in the lungs and intestine. its release is mediated by proinflammatory cytokines, such as tumor necrosis factor-alpha and interleukin- . [ ] . studies found that pct levels were lower in seriously ill patients with viral infections and were much higher in bacterial infections [ ] . covid- patients with elevated levels of pct were associated with a five-fold greater risk of severe disease progression [ ] . it may be because secondary bacterial infections are also common in covid- pneumonia. severe sepsis patients also have associated high lactate dehydrogenase (ldh) levels. ldh is a cellular injury marker that shows the extent of damage to the tissue. failure of ldh levels to normalize within hours of the onset of sepsis is a strong predictor of patient mortality [ ] . during sepsis, there is an upregulation of tissue factor resulting in a downregulation of antithrombin and a subsequent increase in plasma thrombin. at the same time, the production of protein c decreases, and upregulation of type plasminogen activator inhibitor further inhibits fibrinolysis. collectively, all these changes induce a hypercoagulable state. increased coagulation and hypotension in sepsis can result in mof, which is the most severe and lifethreatening consequence of sepsis. a variety of molecules play important roles in the activation of the coagulation cascade. d-dimer is a sign of ongoing active fibrinolysis and, therefore, also of coagulation [ ] . d-dimer is a measure of the coagulation cascade and assesses the severity of the host response, which led it to play an important role in the risk stratification of patients with sepsis to improve clinical management. a study showed that the higher the d-dimer levels, the greater the risk of sepsis and septic shock for the patient [ ] . this study aims to identify the roles of these biomarkers (crp, ferritin, ldh, pct, and ddimer), among others, in predicting the severity and clinical outcome during the disease. the identification of an effective and predictive biomarker would thus help in risk stratifying the patients and overall improving the clinical management of patients with covid- , especially in the region. this study was conducted as a retrospective, observational, multi-centric study, including all the admitted covid- positive patients only. the outcome of the disease was followed along with the hospital course of every patient at the time of analysis. baseline laboratory investigations of all patients were monitored both at admission and discharge. the comparative analysis was done between the survivors (n= ) and non-survivors (n= ). the statistical analysis was conducted using ibm spss statistics for windows, version (armonk, ny: ibm corp.). all continuous variables were described as mean and standard deviation, and then compared using independent sample t-test and mann-whitney u test accordingly. receiver operating characteristic (roc) curves were used to determine the predictability of biochemical markers for the outcome of the disease. the youden index was used as a summary measure of cut-off values for area under the curve (auc). a p-value of < . was considered statistically significant. all the highly significant values of < . were rounded off as . . a total of covid- positive patients were included in the study with a mean age of . ± . years with female patients (mean age: . ± . ) significantly younger than male patients (mean age: . ± . ; p= . ). the most common age group was - years, with two-thirds of patients being males (p= . ). the majority of the patients were experiencing mild to moderate symptoms and were therefore admitted to the isolation ward ( . %), while the remaining . % were experiencing more severe disease and were admitted to the intensive care unit. the descriptive statistics of the study population are stated in table . the ongoing covid- contagion has spurred researchers to explore effective disease severity predictors that can aid in combating the sars-cov- virus. the main purpose of this research was to establish biomarkers that could accurately predict the severity of coronavirus disease, thereby guiding clinicians in the risk stratification and clinical management of the patients. our analysis showed that crp is significantly elevated as compared to the mild course of the disease in severe cases of covid- and was an important predictor of severity of the disease. this result is consistent with the findings of a review article that concluded that crp amounted to . % of patients infected with sars-cov- and was a crucial marker for predicting covid- prognosis and mortality in these patients [ ] . qin et al. also found a significant association in their study of increased crp and severe prognosis of the disease, but the values reported in the severe group of patients are about . times higher than ours; however, a ratio of . between the severe and non-severe groups was almost identical to our study, whereas the marker levels in the mild course of the disease are nearly identical to our levels in severe disease [ ] . in their research on the use of crp to predict disease prognosis, gao et al. have reached the same conclusion, with crp values reported being much higher than our analysis, although a ratio of : in the non-severe versus severe group was observed among the crp levels close to our ratio of . [ ] . a study undertaken in wuhan, china, that evaluated the clinical characteristics of covid- patients also found an important association of crp with severe disease prognosis. however, the levels of crp were much higher as compared to ours with a ratio of . between the severe and non-severe groups similar to our study [ ] . zheng et al. found that a mean value of . mg/l for crp was significant for a severe prognosis of the disease, which was higher than our mean of . mg/l [ ] . the conclusion reached by zheng et al. identifying crp as a significant marker for the severe manifestation of covid- is similar to ours; however, the ratio reported between severe and non-severe cases in their study is much higher compared to our study. their values of milder disease, along with another study, were similar to our findings [ , ] . our study showed that ldh is also significantly increased in patients experiencing a severe course of the disease compared to those with mild infections, thereby demonstrating its role as the most potential biomarker in predicting covid- severity. a study conducted in changsha also observed ldh as an important biomarker for disease severity [ ] . in that study, ldh were significantly elevated in patients with severe covid- ; however, their mean values were three times lower as compared to our reported findings. chen et al. also documented an association of elevated levels of ldh in patients with disease severity [ ] . their study's levels of ldh were two times lower in both the severe and moderate groups of patients as compared to ours, but their research, as well as ours, concluded a substantial association between ldh levels and disease severity. the significance of ferritin as a biomarker to monitor and predict disease severity as compared to crp and ldh was much lower in our study. this conclusion differs from what is reported by many other studies, most of them identifying serum ferritin to be a significant marker for the prediction of disease severity [ , ] . a study in wuhan, china, found a strong association of serum ferritin as a marker for the severe disease [ ] . the levels of serum ferritin in our study are three times higher from the study conducted in wuhan, in both surviving (mild-to-moderate) and non-surviving (severe) groups of patients. the levels of ferritin were much lower in that study compared to ours, but the association between the levels of ferritin and disease severity was closer to our study in terms of statistics, with our study reporting a p-value of . at admission compared to their p-value of . [ ] . our results also demonstrated the use of pct to be a significant biomarker of the disease, which is dissimilar to the conclusions reached by gao et al., where the authors did not find a significant association between pct and disease severity [ ] . on the contrary, several studies have reported a significant association in the elevated levels of pct and disease severity [ , ] . this association seen in our study between pct and its predictability of disease severity may be due to the higher rates of co-infection by bacteria and a high incidence of ventilatorassociated pneumonia. studies have shown the role of d-dimer as an effective predictor for mortality of covid- and thereby the severe course of the disease [ , ] . the values of d-dimer found in our study are significantly higher in both severe and non-severe patients when compared with the findings of other authors [ , ] . most of the studies conducted to explore the clinical features and the role of biomarkers in predicting the severity of covid- have found d-dimer to be an effective predictor, while some have associated it with increased mortality and ards [ , ] . our study concluded d-dimer to be the second most effective biomarker after ldh in predicting the mortality alongside pct, while crp and ferritin were lagging behind the above-mentioned biomarkers in predicting mortality. cardiac markers (trop i and pro-b-type natriuretic peptide) were not effective in predicting the severity or mortality in our study. also, serum fibrinogen had no role in predicting severity in our findings dissimilar to another study [ ] . roc curve analysis of the same study showed fibrinogen (auc: . ), which was much higher than our study, while crp (auc: . ) was much lower than our study [ ] . roc curve for d-dimer had similar sensitivity ( %) to predict severity at discharge in both the studies while our auc was slightly lower than their study [ ] . regarding the baseline laboratory investigations, increased tlc, neutrophil count, urea, creatinine, sodium, and decreased lymphocyte count were all associated with disease severity and mortalities in our study, a finding similar to many previously conducted research studies in the region [ ] . however, there were few limitations in our study, the major one being the confounding factor of various comorbidities that may be the cause of severe immune dysregulation in a certain group of patients. other than that, secondary bacterial infections and mof can also aggravate the immune dysregulation, which cannot be solely attributed to the viral agent being studied. we studied the effect of various biochemical markers in the prognosis of covid- and the order of effectiveness among the markers. our findings concluded that d-dimer, pct, and ldh were superior to serum ferritin and crp as an effective biomarker in predicting the fatality of covid- . we also could not establish significant associations of various other biomarkers in predicting the severity of coronavirus disease. acute kidney injury and hypernatremia were also proven fatal events during the hospital course in our study. such findings are crucial and can be used as guidelines when assessing the severity of the disease or treating patients in this region with the disease. human subjects: all authors have confirmed that this study did not involve human participants or tissue. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. virology, epidemiology, pathogenesis, and control of covid- covid- infection: origin, transmission, and characteristics of human coronaviruses clinical features of covid- hyperferritinemia and inflammation hyperferritinaemia: an iron sword of autoimmunity diagnosing sepsis: the role of laboratory medicine acute-phase proteins and other systemic responses to inflammation covid- pathophysiology: a review cytokine storms in infectious diseases c-reactive protein correlates with computed tomographic findings and predicts severe covid- early epidemiological characteristics and clinical features of critical and noncritical cases of covid- in chengdu clinical characteristics of deceased patients with coronavirus disease : retrospective study duque pinheiro i: procalcitonin as biomarker of infection: implications for evaluation and treatment biomarkers of inflammation and the etiology 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adult inpatients with covid- in wuhan, china: a retrospective cohort study clinical features and short-term outcomes of patients with covid- in wuhan clinical profiles, characteristics, and outcomes of the first admitted covid- patients in pakistan: a single-center retrospective study in a tertiary care hospital of karachi key: cord- -ffmo hm authors: siddiqui, raheel s; zirkiyeva, milana; saliaj, merjona title: onset of ketosis-prone diabetes in the setting of covid- infection date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ffmo hm diabetic ketoacidosis is typically associated with type i diabetes mellitus, but it can be associated with type ii diabetes mellitus under the conditions of extreme stress or as a presenting manifestation of ketosis-prone type ii diabetes mellitus. a -year-old prediabetic male presented to the emergency room with hyperglycemia six weeks after recovery from coronavirus disease (covid- ) pneumonia. laboratory results showed severe hyperglycemia, metabolic acidosis, positive ketones in urine and blood, and elevated fasting c- peptide level. covid- polymerase chain reaction (pcr) was negative, and immunoglobulin g (igg) antibodies were positive. the workup was completely unremarkable for acute infection. hemoglobin a c increased from . % to . % within six weeks. the mechanism by which covid- infection may trigger the onset of full-blown diabetes mellitus remains unknown. viral infection may cause the direct destruction of pancreatic beta cells or trigger the changes in the body that induce the state of insulin resistance. antibodies against severe acute respiratory syndrome coronavirus (sars-cov- ) infection may cross-react or interfere with the functioning of endogenous insulin. the association between type ii diabetes and covid- infections needs additional investigations to ascertain the exact mechanism by which covid- infection triggers the onset of full-blown diabetes mellitus. diabetes mellitus is categorized into type i and type ii. type i is an insulin-dependent diabetes mellitus and is associated with severe deficiency of insulin due to the destruction of pancreatic beta cells, whereas type ii diabetes is typically associated with increased insulin resistance, beta-cell exhaustion, and relative insulin deficiency [ ] . diabetic ketoacidosis is one of the most severe complications of diabetes mellitus and is typically associated with type i diabetes mellitus, but it can be seen with type ii diabetes mellitus under the conditions of extreme stress including infections, trauma, emergencies, and sometimes as a presenting manifestation of ketosis-prone type ii diabetes mellitus [ ] . several cases of patients infected with coronavirus disease (covid- ) presented with severe hyperglycemia along with ketoacidosis or hyperosmolar-hyperglycemic state during their acute phase of illness have been identified [ ] . in our case, the patient remained mildly hyperglycemic during the course of his covid- pneumonia; however, he presented with diabetic ketoacidosis six weeks after being discharged. a -year-old male with a past medical history of prediabetes was hospitalized and treated for acute hypoxemic respiratory failure secondary to covid- pneumonia. during that admission, blood sugar level remained below mg/dl even while the patient was being administered glucocorticoids. glucocorticoids were discontinued after five days of hospitalization. six weeks later, he was admitted for a severe hyperglycemic state of glucose level over mg/dl. symptoms reported included polyuria and polydipsia for one week. physical examination and vital signs were unremarkable except for a body mass index of . kg/m . initial labs revealed sodium of mmol/l (normal range: - mmol/l), chloride of mmol/l (normal range: - mmol/l), blood sugar of mg/dl (normal range: - mg/dl), bicarbonate of mmol/l (normal range: - mmol/l), ph of . (normal range: . - . ), anion gap of meq/l ( normal range: - meq/l), and lactate . of mmol/l (normal range: . - . mmol/l). serum and urine ketones were positive. covid- polymerase chain reaction (pcr) test was negative, whereas covid- immunoglobulin g (igg) antibodies titer was positive. urine and blood cultures were negative, and chest xray was negative for any pneumonia, as shown in figure . hemoglobin a c was found to be . % (normal range: - . %), whereas during the last admission with covid- pneumonia hemoglobin a c was found to be . %. labs further showed triglyceride level of , mg/dl (normal range: - mg/dl), fasting cpeptide level of . ng/ml (normal range: . - . ng/ml), and weakly positive glutamic acid decarboxylase antibodies. islet cell antibodies, insulin antibodies, and zinc transporter antibodies were negative. the patient was treated for diabetic ketoacidosis with insulin detemir as a basal insulin and insulin lispro as a bolus. the anion gap closed and blood sugar level showed improvement. the patient was later discharged on metformin and pioglitazone in addition to the basal-bolus insulin. the patient was followed for three weeks after the second discharge and reported fasting blood sugars in the range of to mg/dl with dietary modification, lifestyle changes, oral antidiabetics, and insulin ( figure the association between type ii diabetes mellitus and viral infections has not been strongly established in the literature. different viral infections including mumps, measles, echovirus, epstein-barr virus (ebv), and coxsackievirus have been traditionally associated with the onset of type i diabetes mellitus [ ] [ ] [ ] [ ] [ ] . in one study, three patients, who developed ketosis-prone diabetes mellitus immediately after documented viral infection with ebv or coxsackievirus and required insulin therapy on discharge, were followed for four to eight years; the first patient remained insulin-dependent throughout the life, the second one regained normal glucose tolerance, and the third one was being transitioned to oral antidiabetic medications [ ] . the study suggested that viral infections can trigger the onset of both type i and type ii diabetes mellitus. patients with covid- infection who presented with diabetic ketoacidosis or hyperosmolar hyperglycemic state during the acute phase of infection have been identified [ , ] . one retrospective study demonstrated that out of patients hospitalized with confirmed covid- infection, ( . %) patients presented with ketosis, whereas ( . %) patients presented with ketoacidosis. out of these five patients, three had established the diagnosis of diabetes and two were not previously diabetic [ ] . this shows that covid- infection causes physiological changes that induce ketosis irrespective of the presence or absence of diabetes. during the acute phase of infection, it is challenging to establish a cause and effect relationship between covid- infection and diabetes mellitus. this case is unique in that our patient with a history of prediabetes remained mildly hyperglycemic during acute phase of covid- infection, only to develop diabetes mellitus after the acute phase of viral infection. the rise in hemoglobin a c from . % to . % in just six weeks suggests that the blood sugar level trended up shortly after the first discharge from the hospital. the timeline for the onset of type ii diabetes mellitus coincides with the recovery from covid- infection. the mechanism by which covid- infection may have triggered the onset of full-blown type ii diabetes mellitus is yet to be understood. the viral infection may have caused the direct destruction of pancreatic beta cells [ ] or triggered the changes in the body that induced the state of insulin resistance. another hypothesis is that antibodies against severe acute respiratory syndrome coronavirus (sars-cov- ) infection may cross-react or interfere with the functioning of endogenous insulin. this warrants further investigations to explain the association between covid- infection and the onset of full-blown diabetes. we reported a case of a young male who developed full-blown ketosis-prone type ii diabetes mellitus status post-sars-cov- infection recovery. further studies are warranted to better understand the etiology and the pathophysiology of type ii diabetes mellitus secondary to covid- infection. human subjects: consent was obtained by all participants in this study. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. update on diagnosis, pathogenesis and management of ketosis-prone type diabetes mellitus. diabetes manag (lond) covid- infection may cause ketosis and ketoacidosis myocarditis with fulminant type diabetes mellitus diagnosed by cardiovascular magnetic resonance imaging: a case report a case of fulminant type diabetes associated with significant elevation of mumps titers various phenotypes of diabetes mellitus at ultimate outcome of acutely developed diabetic state induced by viral infection positive measles serology and new onset of type diabetes presented with bilateral facial paralysis: a case report a case of fulminant type diabetes mellitus accompanied by myocarditis diabetic ketoacidosis precipitated by covid- : a report of two cases and review of literature diabetes in covid- : prevalence, pathophysiology, prognosis and practical considerations key: cord- -jv lknl authors: ashraf, muddasir; sajed, sulaiman title: acute stroke in a young patient with coronavirus disease in the presence of patent foramen ovale date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: jv lknl we present an interesting case of acute ischemic stroke in a -year-old patient with coronavirus disease , who presented to the hospital initially with headache, vomiting, and right-sided numbness and tingling. the initial workup was negative, including computed tomography (ct) of the head without contrast and ct angiography of the head and neck with no acute abnormalities. the patient was diagnosed with migraine and discharged from the emergency department. the patient developed worsening symptoms at home in the form of increasing right-sided dysmetria and weakness, gait ataxia, and dysarthria, prompting her to return to the emergency room. magnetic resonance imaging of the brain was performed and was significant for right-sided acute ischemic cerebellar stroke, with also the involvement of the right cerebellar peduncle. echocardiogram with a bubble study demonstrated patent foramen ovale. the patient was treated with standard guidelines for stroke. novel coronavirus was identified in , and it rapidly reached pandemic proportions. the world health organization designated the disease caused by the severe acute respiratory syndrome coronavirus (sars-cov- ) as coronavirus disease (covid- ). there have been concerns that the virus causes hypercoagulability that leads to thromboembolic events. the pathogenesis of this tendency remains incompletely understood. one such consequence is the increased risk of stroke. unusually large numbers of stroke cases have been reported worldwide in young patients [ , ] , reinforcing our belief that covid- is a systemic disease that affects not only the lungs but also other vital organs. patients with an inherently increased risk of stroke such as patients with patent foramen ovale (pfo) or previous history of stroke, may be at higher risk of stroke with covid- . hence, the optimal management of these patients needs to be defined in terms of any necessary prophylaxis and treatment. a -year-old female patient with a past medical history of obesity, post-traumatic stress disorder, depression, and exercise-induced asthma presented to the emergency department with sudden onset of headache, vomiting, and right-sided numbness, and tingling. the patient underwent computed tomography (ct) angiography of the head and neck, which were unremarkable, and no vertebral artery dissection was seen. she was discharged with the diagnosis of migraine. she developed worsening of her symptoms at home, presenting again to the emergency department with increasing right-sided numbness, weakness, and dysarthria. vital signs were stable with no fever. the patient reported no respiratory symptoms and denied any recent head trauma or chiropractic neck manipulation. the neurological exam was significant for rightsided weakness, dysarthria, right-sided dysmetria, and gait ataxia. chest x-ray showed no acute infiltrates. magnetic resonance imaging (mri) of the brain showed an acute right cerebellar infarct with the involvement of the right cerebellar peduncle (figure ). magnetic resonance angiography of the head revealed narrowing of the right superior cerebellar artery ( figure ). an echocardiogram with a bubble study was performed, as well as a part of a stroke workup, which showed a pfo. the lower extremity venous doppler ultrasound was negative for deep venous thrombosis. the laboratory test results are shown in table . shows acute right cerebellar infarct figure : magnetic resonance angiography of the brain shows narrowing of right superior cerebellar artery the patient was screened for covid- with a nasopharyngeal reverse transcription polymerase chain reaction due to increased reports of stroke in young patients nationwide, and the test came back as positive, to our surprise. standard stroke treatments, including aspirin, clopidogrel, and high-intensity statins, were initiated for the patient. enoxaparin for deep venous thrombosis prophylaxis was also prescribed. covid- has been linked to an increased risk of venous thromboembolism and arterial thrombosis, including stroke in case series from different health centers and anecdotal reports. a single health system identified five cases of acute ischemic stroke associated with covid- over two weeks, with symptoms suggesting large-vessel occlusion; all patients were under years of age [ ] . before the pandemic, there were approximately . large vessel strokes per two-week interval in patients younger than years. in one of the series of intensive care unit (icu) patients, ischemic stroke was observed in three of (cumulative incidence, . %) [ ] . in another one of the series, cerebral ischemia was seen in three of [ ] . in the series that included non-icu inpatients, six ( %) underwent ischemic strokes, and an additional three in the icu underwent an ischemic stroke [ ] . the pathophysiology is not completely clear, but proposed mechanisms include endothelial inflammation, stasis, and increased procoagulant factors in the blood (hypercoagulability), consistent with virchow's triad. there is evidence of direct invasion of endothelial cells by sars-cov- . other sources of endothelial injury include intravascular catheters, mediators of acute systemic inflammatory response such as cytokines (e.g., interleukin- ), and other acutephase reactants [ ] . the contribution of complement-mediated endothelial injury has also been suggested [ ] . hyperviscosity was demonstrated in a series of fifteen critically ill patients in the icu [ ] . highly elevated levels of d-dimer have been noted as well, which correlates with disease activity. laboratory findings were characterized in a series of selected patients with severe covid- pneumonia (intubated) who were evaluated and also underwent standard coagulation testing and other assays, including von willebrand factor. the results showed normal or slightly prolonged prothrombin time (pt) and activated partial thromboplastin time (aptt), normal or increased platelet counts, increased fibrinogen, and increased d-dimer [ ] . early case series, including a series of consecutive patients from wuhan, china, suggested that thrombocytopenia and prolongation of the pt and aptt were more marked [ ] [ ] [ ] [ ] . it is not clear why these results differed somewhat from later findings of less severe pt and aptt prolongation. one possible explanation is that these patients were sicker, perhaps because earlier in the pandemic, the disease was not recognized as quickly, resulting in delays in patient presentation and treatment. another explanation for an isolated prolonged aptt is the presence of a lupus anticoagulant (la). two studies have found a high rate of la in patients with prolonged aptt ( of tested individuals ( %) and of tested individuals ( %)) [ , ] . the presence of an la may lead to an artifactual prolongation of the aptt but does not reflect an increased bleeding risk; patients with an la should receive anticoagulation if indicated. covid- hypercoagulability has been referred by some experts as a disseminated intravascular coagulation (dic)-like state, but the main difference is that covid- leads to thrombosis, unlike acute decompensated dic, which leads to bleeding due to consumption of clotting factors. the consumption of clotting factors is not the case with covid- , hence the increased levels of fibrinogen and factor viii activity that are seen in these patients [ ] . our patient had normal fibrinogen, platelet count, and aptt but elevated d-dimer, c-reactive protein, and ferritin. our patient also did not have any respiratory symptoms or chest x-ray abnormalities, but ct of the chest would have potentially revealed abnormal lung findings. this was not performed for our patient due to absent respiratory symptoms and to avoid unnecessary staff exposure. the interesting question that arises from this case is whether young patients with covid- have an increased risk of stroke in the presence of pfo, and should prophylactic anticoagulation be initiated to prevent stroke until these patients recover from their illness? if they present with acute stroke, should they be started on full anticoagulation to prevent recurrence or worsening of their stroke? prophylaxis is only possible if the patient had previously diagnosed pfo due to prior episodes of a transient ischemic event or stroke or due to some other indications. we did not make any such decisions without substantial evidence, given the paucity of data and potential for harm. we did start the patient on prophylactic enoxaparin sodium, which is the standard of care in stroke patients admitted to the hospital for deep venous thrombosis prophylaxis. it potentially has some anti-inflammatory properties as well. the number of patients with covid- who require treatment will most likely be increasing in the near future, not decreasing, and additional studies will be required to answer these questions. it has been observed that covid- causes an increased incidence of stroke in young patients. additional data are required to answer questions regarding the optimal management of these patients, especially in the subset of patients with inherently increased risk, such as patients with pfo, previous history of stroke, a recent history of transient ischemic attack, and asymptomatic but significant carotid disease. this case will hopefully lead to these studies and discussions to further advance our knowledge. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. large-vessel stroke as a presenting feature of covid- in the young incidence of thrombotic complications in critically ill icu patients with covid- high risk of thrombosis in patients with severe sars-cov- infection: a multicenter prospective cohort study venous and arterial thromboembolic complications in covid- patients admitted to an academic hospital in the factor viii acute phase response requires the participation of nfkappab and c/ebp complement associated microvascular injury and thrombosis in the pathogenesis of severe covid- infection: a report of five cases covid- -associated hyperviscosity: a link between inflammation and thrombophilia? hypercoagulability of covid- patients in the intensive care unit: a report of thromboelastography findings and other parameters of abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia exploring possible mechanisms for covid- induced thrombocytopenia: unanswered questions the versatile heparin in covid- anticoagulant treatment is associated with decreased mortality in severe coronavirus disease patients with coagulopathy lupus anticoagulant and abnormal coagulation tests in patients with covid- key: cord- -sz n a z authors: rehman, mahin; gondal, amlish; rehman, najeeb u title: atypical manifestation of covid- -induced myocarditis date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: sz n a z we present a case of a -year-old male who presented with chest pain without fever or respiratory symptoms. troponins were elevated and electrocardiogram (ecg) was inconclusive for st-elevation myocardial infarction (stemi). angiography revealed normal coronaries and the patient was found to be coronavirus disease (covid- ) positive; he was diagnosed with covid- myocarditis. with the global pandemic, more cases are emerging regarding myocardial injury induced by severe acute respiratory syndrome coronavirus (sars-cov- ) virus. although covid- manifests primarily as respiratory disease, few cases of cardiac injury without respiratory involvement or febrile illness have been reported. this case illustrates that covid- can present atypically and affect an isolated non-respiratory organ system. coronavirus disease (covid- ) (severe acute respiratory syndrome coronavirus [sars-cov- ]) not only affects the respiratory system but can involve dysfunction of other organ systems as well. there have been reports of myocardial injury occurring in patients who have tested positive for covid- with evidence of troponin leak and elevation, and these patients may initially present with a pseudoinfarct pattern [ ] . additionally, fever, cough, and respiratory distress were highly common symptoms noted in individuals who had myocardial injury associated with covid- [ ] . the sars-cov- virus is not known to be cardiotropic like other viruses such as the coxsackie virus. the virus attacks by attaching to the angiotensin-converting-enzyme- (ace ) receptor which is located in the lungs but also found on the heart and vessels; a cytokine release storm occurs due to an imbalance of t-cell activation with improper release of cytokines such as interleukin (il)- , il- and others, leading to the possibility of significant cellular damage [ ] . additionally, this severe immune system response may also result in plaque instability and ultimately lead to the development of an acute coronary syndrome (acs) [ ] . currently, there have been no reports confirming sars-cov- -induced viral myocarditis via histologic and viral genomic analysis through polymerase chain reaction (pcr); molecular proof and evidence are still needed via biopsy identifying the sars-cov- genome within myocytes. thus, these reports of covid- myocarditis are all clinical diagnoses. there was a case report that described a patient with covid- with regional wall motion abnormalities who had a biopsy consistent with lymphocytic myocarditis but histopathological and viral genomic polymerase chain reaction (pcr) analysis of the biopsy did not reveal the sars-cov- viral genome to be present within the myocytes [ ] . one case series of patients with covid- associated st-segment elevation on an electrocardiogram (ecg); myocardial infarction was diagnosed in eight of these individuals with the remaining being diagnosed with noncoronary myocardial injury [ ] . currently, there have been no covid- related reports of isolated myocardial injury without febrile illness and respiratory involvement. a -year-old kenyan male with no past medical history presented with midsternal chest pain. he had been residing within the usa for the last year and working as a long-distance truck driver. the patient described the pain as a heaviness which sometimes felt sharp and lasted several hours long. he had been experiencing this pain for two days and the pain usually started in the morning and worsened with exertion. on the day of presentation, he rated the pain out of on the severity scale and denied any symptoms of shortness of breath or pleuritic type chest discomfort associated with respiration. he was administered aspirin and sublingual nitroglycerin; the nitroglycerin did not relieve his chest pain and his presentation was worrisome for an st-elevation myocardial infarction (stemi). the patient was completely afebrile and vital signs were stable. physical examination only revealed some elicited pain with range of motion of his left arm. he denied any alcohol use, tobacco use, or illicit drug use and denied any family history of cardiac disease. his ecg showed to mm st elevations in lead i and avl, st depression in avr, mild j-point elevation, and t-wave inversion in leads ii, iii and avf ( figure ). his ecg was not entirely convincing of stemi and his troponins were found to be elevated at . ng/ml and eventually peaked to . ng/ml. he was taken urgently for cardiac catheterization and it revealed completely normal coronaries so no intervention was performed (figures a- b) . there was no evidence of myocardial bridging either. the red arrows in this ecg show to mm st elevations in lead i and avl, st depression in avr, mild j-point elevation and t-wave inversion in leads ii, iii and avf. given his profession of being a long-distance truck driver and traveling, he was tested via reverse transcription polymerase chain reaction (rt-pcr) for covid- (sars-cov- virus) and was found to be positive. subsequently, a ct scan was done to rule out pulmonary embolism as the cause of his chest pain since sars-cov- virus induces a hypercoagulable and thrombotic state in individuals [ ] . ct scan was negative for any pulmonary embolism and revealed clear lungs without any typical respiratory characteristics of covid- . this was followed up with a transthoracic echocardiography (tte) and it revealed no wall motion abnormalities and a completely normal ejection fraction at %- % and no evidence of pericarditis or pericardial effusion. the patient's blood work was consistent with biomarkers typically identified with covid- (sars-cov- ): his d-dimer was elevated at . mcg/ml, erythrocyte sedimentation rate (esr) elevated at mm/hr, lactate dehydrogenase (ldh) elevated at units/l, procalcitonin was negative at . ng/ml, c-reactive protein (crp) elevated at . mg/dl, creatine phosphokinase (cpk) elevated at units/l, amino-terminal pro-brain natriuretic peptide (nt-probnp) elevated at pg/ml, and mild to moderate liver enzyme elevation with aspartate aminotransferase (ast) elevated at units/l and alanine aminotransferase (alt) elevated at units/l [ ] . covid- is commonly associated with elevated ferritin levels since ferritin is an acute phase reactant but interestingly, in our patient, the ferritin was within normal limits at ng/ml [ ] . initially, stemi was at the top of the differential given that he had an equivocal ecg and worsening chest pain. with cardiac catheterization revealing normal coronary arteries and no lesion inducing stenosis, myocarditis became the top differential given that he had evidence of myocardial injury with the troponin leak. cardiac catheterization also ruled out any concern for myocardial bridging as the source of his chest pain. the patient was managed conservatively during his hospitalization. interestingly, after his cardiac catheterization, his chest pain resolved and the pain was well-controlled with acetaminophen alone. he was not on any medications prior to admission and was discharged in a stable condition with acetaminophen and non-steroidal anti-inflammatory drugs (nsaids) were avoided for the concern of exacerbating myocardial inflammation due to covid- . the patient is scheduled for follow-up with repeat serial tte to ensure that he is not developing heart failure with reduced ejection fraction or wall motion abnormalities. with this report, we aim to highlight an atypical presentation of covid- (sars-cov- )induced myocarditis as this patient was completely afebrile and had no respiratory symptoms, both of which are typical characteristics. current consensus around covid- -induced myocardial injury is to maintain conservative management especially in those without suspected acute coronary syndrome (acs) who have mild troponin elevation, as in our young patient. given that he is young, was recovering well, and did not present with acute heart failure, he was conservatively managed and carefully monitored without requiring further cardiac imaging such as magnetic resonance imaging (mri) as it would not have altered our management [ ] . with regards to not using nsaids in our patient, we erred on the side of caution. there was some concern about nsaids possibly exacerbating the covid- disease course early on in the pandemic but the world health organization (who) released a publication addressing this and concluding that there is no evidence of severe adverse effects in covid- patients treated with nsaids [ ] . thus, for future covid- patients, nsaids may be utilized should they be warranted. another major factor to consider with this case is the exposure of the cardiovascular team to sars-cov- virus without proper personal protective equipment (ppe) and appropriate precautions. he was taken urgently to the catheterization lab as there was concern for stemi and at that point, the disease was quite low on the differential since the patient did not have typical signs and symptoms of covid- . the european society of cardiology (esc) has released guidelines on how cardiovascular healthcare personnel can protect themselves [ ] . for percutaneous coronary intervention (pci), they recommend that for suspected and probable covid- positive patients, a disposable surgical cap, an n respirator, a disposable gown, disposable gloves, and eye goggles or face shield be utilized [ ] . again, our patient had no fever or respiratory symptoms of the disease, so it was very low on our differential and ultimately thorough protection was not worn. the cardiovascular team was tested for the virus as well and monitored for symptoms. the cardiac catheterization lab and equipment was thoroughly sanitized and disinfected; while the catheterization lab is not in use, ultraviolet light is left on for continuous disinfection. again, there have been no reports confirming the presence of sars-cov- viral genome in myocytes via endomyocardial biopsy showing lymphocytic infiltrate; once biopsy-proven invasion of myocardial cells by sars-cov- has been reported, then a new cardiotropic virus inducing myocarditis would be added to the literature. covid- -induced myocardial injury can present as a stemi or non-stemi (given the evidence of troponin leak) and without concurrent febrile illness or respiratory symptoms of the disease. conservative management with pain control is recommended with serial ttes on follow-up. nsaids may be utilized, should it be warranted as per the who, as there is no significant data indicating they exacerbate the disease course or induce harm to the patients. human subjects: consent was obtained by all participants in this study. not applicable issued approval not applicable. not applicable. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. association of cardiac injury with mortality in hospitalized patients with covid- in wuhan esc guidance for the diagnosis and management of cv disease during the covid- pandemic acute myocarditis presenting as a reverse tako-tsubo syndrome in a patient with sars-cov- respiratory infection st-segment elevation in patients with covid- -a case series autopsy findings and venous thromboembolism in patients with covid- covid- gone bad: a new character in the spectrum of the hyperferritinemic syndrome current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the european society of cardiology working group on myocardial and pericardial diseases the use of non-steroidal anti-inflammatory drugs (nsaids) in patients with covid- key: cord- -crfj adf authors: haider, asim; siddiqa, ayesha; ali, nisha; dhallu, manjeet title: covid- and the brain: acute encephalitis as a clinical manifestation date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: crfj adf central nervous system (cns) viral infections result in the clinical syndromes of aseptic meningitis or encephalitis. although the primary target of coronavirus disease (covid- ) is the respiratory system, it is increasingly being recognized as a neuropathogen. the hallmark clinical feature is altered mental status, ranging from mild confusion to deep coma. most patients with encephalopathy or encephalitis are critically ill. we present a case of covid- -related encephalitis who presented with acute delirium and new-onset seizures. the patient responded well to treatment with intravenous immunoglobulins and rituximab. coronavirus disease (covid- ) is a disease with a significantly broad spectrum of presentation and clinical syndromes. this novel infectious disease has been associated with acute respiratory distress syndrome (ards), thromboembolic syndrome, severe metabolic syndromes, severe acute tubular necrosis, electrolyte abnormalities, neurologic syndromes, and cardiac events, including myocarditis and arrhythmias [ ] [ ] [ ] . beijing ditan reported the first case of viral encephalitis associated with covid- in march . the researchers confirmed the presence of severe acute respiratory syndrome coronavirus (sars-cov- ) in the cerebrospinal fluid (csf) by genome sequencing [ ] . since then, clinicians and researchers worldwide have been observing more and more neurological manifestations of covid- . a -year-old male, with a medical history of benign prostatic hypertrophy, fatty liver disease, and hypertension, admitted to the hospital after experiencing multiple new-onset seizures followed by persistent confusion. as per the family, he experienced intermittent confusion and bizarre behavior like staring at the walls for two days before the onset of seizures. he was seen in his primary care provider's clinic four days before the onset of seizures and was in the usual state of health at that time. initial vital signs were: heart rate beats per minute, respiratory rate times per minute, temperature . °f, oxygen saturation % on room air, and blood pressure / mmhg. on physical examination, the patient was confused, not oriented to time, place, or person, and could not follow commands. however, he did not have any focal neurological deficits or neck rigidity. laboratory tests, including human immunodeficiency virus (hiv) antibodies, rapid plasma reagin (rpr), thyroid-stimulating hormone (tsh), vitamin b , and urine toxicology, were unremarkable. computed tomography (ct) scan of the head and ct angiogram of the brain and neck were negative. septic workup, including blood and urine cultures, were also negative. due to a persistent state of confusion, he underwent a lumbar puncture and was started empirically on antibiotics (vancomycin, acyclovir, ceftriaxone, and ampicillin) for meningitis treatment. he also received phenytoin mg three times per day for seizure prophylaxis. lumbar puncture showed an opening pressure of cm of h o, cerebrospinal fluid (csf) glucose level of mg/dl, protein level of mg/dl, and white blood cell (wbc) count of /mm . csf studies were negative for cultures (both bacterial and viral), cryptococcal antigen, and herpes simplex virus polymerase chain reaction (pcr) test ( table ) . the patient was noted to have a positive pcr assay for sars-cov- in the nasopharyngeal swab. autoimmune workup, including anti-n-methyl d-aspartate (nmda) receptor antibodies, anti-ro antibodies, anti-la antibodies, antineutrophil cytoplasmic antibodies (anca) antibodies, and anti-hu antibodies, were negative. blood tests, including lyme antibodies by western blot and varicella-zoster virus (vzv) pcr, were negative. initial electroencephalography (eeg) demonstrated the right temporal epileptiform activity. repeat eeg showed global cerebral dysfunction and severe toxic metabolic encephalopathy. magnetic resonance imaging (mri) brain without contrast showed small acute/subacute lacunar infarcts and a patchy area of t bright signals in the cortical and periventricular regions, concerning for cerebritis ( figure ). due to suspicion of covid- -related encephalitis, the patient received two doses of tocilizumab ( mg each) followed by intravenous (iv) immunoglobulin ( g/kg) for five days. the patient's mental status did not improve even after completing the treatment with tocilizumab and iv immunoglobulins. the decision was made to start the patient on rituximab. the patient received one dose of rituximab (one gram) with significant improvement in mental status. he became more calm and co-operative afterward. he was discharged to a nursing home. two months post-discharge, the patient was followed up and his mental status was much better; he was alert, oriented, and able to take care of his daily activities. although coronavirus's primary target is the respiratory tract, it is known to have neuroinvasive properties. however, the evidence on the central nervous system (cns) involvement and neurological manifestations of covid- is scarce and of low quality. a study that specifically investigated this issue documented that % of the hospitalized patients with a confirmed diagnosis of an acute respiratory syndrome from covid- infection had some neurological manifestations. neurological symptoms usually fall into one of three categories: cns symptoms or diseases (headache, dizziness, impaired consciousness, ataxia, acute cerebrovascular disease, and epilepsy), peripheral nervous system (pns) symptoms (hypogeusia, hyposmia, hypopsia, and neuralgia), and skeletal muscular symptoms [ ] . patients with severe symptoms are more likely to develop neurological symptoms than patients with mild or moderate disease [ ] . the exact mechanism by which covid- infects cns is not well-understood due to a lack of experimental data, but it is considered a mutation of the middle east respiratory syndrome (mers) virus and severe acute respiratory syndrome (sars) virus [ ] . the target receptor for these coronaviruses is the angiotensinconverting enzyme- (ace ) receptor. after attachment and internalization, viral ribonucleic acid (rna) is released into the cytoplasm, subsequently leading to translation and replication [ ] . the ace receptor is also found in the glial cells of the brain and spinal cord tissues. there are at least three proposed mechanisms through which coronaviruses can enter the cns: (a) retrograde transfer from the olfactory epithelium to the brain via cribriform plate, (b) damage to the blood-brain barrier during the viremia phase, and (c) transfer from peripheral nerve terminal to cns via synapse connected route [ ] . following cns invasion, neurological damage can occur via the following mechanisms: (a) immune-mediated damage in the setting of cytokine storm and (b) neuronal damage in the setting of significant hypoxia due to severe pneumonia and acute respiratory distress syndrome (ards) [ ] . the diagnosis of covid- -related encephalitis can be extremely challenging, as the definitive diagnosis of viral encephalitis largely depends on virus isolation from csf; this is difficult for covid- because sars-cov- dissemination is transient and its csf titer may be extremely low. most of the patients of covid- , who had encephalopathy and underwent eeg, showed nonspecific findings [ ] . two case series involving csf analysis data from patients reported that the csf had no white blood cells and the pcr assay for sars-cov- was negative in all the patients [ , ] . a spectrum of mri findings has been described in patients with covid- -related encephalopathy, including leptomeningeal enhancement, ischemic strokes, and cortical fluid-attenuated inversion recovery (flair) signals [ ] . isolated white matter microhemorrhages have also been described in patients with severe covid- -associated ards [ ] . the treatment of covid- -related encephalitis is mainly supportive. a variety of treatments, including high-dose iv steroids, iv immunoglobulin, and immunomodulators (e.g., rituximab), have been tried in various cases, with somewhat limited outcomes [ ] . neurological dysfunction may persist in many cases after the symptoms of acute illness have been resolved. in a case series, one-third of such patients were cognitively impaired at discharge [ ] . in our clinical experience, the patient is slowly improving to his baseline mental status. covid- is primarily a respiratory pathogen, but there is increasing evidence that it infects both the cns and pns. the absence of any specific findings on eeg, ct head, mri head, and csf analysis essentially makes it a disease of exclusion. the neurological manifestations of this virus are a rapidly evolving area but current evidence is limited. therefore, it is essential to collect reliable data on short-and long-term neurological manifestations worldwide. human subjects: consent was obtained by all participants in this study. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. clinical features of covid- in elderly patients: a comparison with young and middle-aged patients possible central nervous system infection by sars coronavirus nervous system involvement after infection with covid- and other coronaviruses first case of novel coronavirus disease with encephalitis neurological manifestations of hospitalized patients with covid- in wuhan, china: a retrospective case series study evidence of the covid- virus targeting the cns: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms covid- : consider cytokine storm syndromes and immunosuppression how to carry out and interpret eeg recordings in covid- patients in icu? brain mri findings in patients in the intensive care unit with covid- infection neurologic features in severe sars-cov- infection brain mri findings in severe covid- : a retrospective observational study sars-cov- -associated acute hemorrhagic, necrotizing encephalitis (ahne) presenting with cognitive impairment in a -year-old woman without comorbidities: a case report key: cord- -e rlbfin authors: pascual, king john; palosaari, andrew; ochoa, jacqueline; dreyer, claudia title: environmental health burdens and socioeconomic status in rhode island: using geographic information systems to examine health disparities in medical school date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: e rlbfin race and class are major predictors of health outcomes in the united states. health disparities among racial and low-income minorities often have environmental etiologies. using rhode island as a case study, we geocoded and visualized several environmental determinants of health via geographic information systems (gis) in the entire state and conducted a geospatial analysis to determine whether or not patterns existed along racial and class lines. the variables that we geocoded include elementary schools, fast food restaurants, superfund sites, and community parks. from a census tract level, we then analyzed the racial and income makeup of each geocoded site. we discovered that, on average, the worst-performing elementary schools, fast food restaurants, and superfund sites in rhode island were clustered in neighborhoods with a larger black population and lower household income. conversely, community parks and the best elementary schools in rhode island tended to be located near neighborhoods with a larger white population and higher household income. our results provide additional evidence for the pervasiveness of the unequal distribution of environmental health burdens between low-income, minority communities and affluent, predominantly white communities. this summer experiential student project demonstrates the feasibility of incorporating gis as a practical tool for learning health disparities material at a u.s. medical school. our study also highlights the value of digital technology and citizen science in helping the public recognize and understand the various environmental factors that perpetuate health disparities. the evidence in the scientific literature documenting the prevalence of racial and ethnic health disparities in the united states is profound. and yet between and , we only saw a modest increase in public awareness on the prevalence of health disparities [ ] . moreover, there seems to be public resistance to the notion that health inequality is heavily influenced by social and environmental factors. many americans believe that health disparities that affect low-income and minority communities are borne out primarily by personal choices, as opposed to structural and historical factors [ , ] . physician awareness and attitudes towards health disparities have also been a subject of concern. many physicians report not having sufficient knowledge and context of their patients' communities and the specific health barriers they face [ ] . while the majority of medical schools today include health disparities in their curriculum, many report that they do not feel satisfied with the quality of course offerings [ ] . furthermore, health disparities material, if not implemented well into medical school curriculum, can be met with negative attitudes by medical students [ ] . geography can help us understand and contextualize health and medicine in many ways. by having access to geographical data, we can analyze the onset, duration, and aftermath of diseases, which can, in turn, help public health advocates and policymakers create interventions that improve the health outcomes of their constituents. it should be no surprise then that "medical geography" has become a burgeoning area of research [ ] . in this article, we use geographic information systems (gis) to visualize the distribution of environmental health burdens in rhode island. specifically, we wanted to see if fast-food restaurants, superfund sites, failing schools, and community parks clustered in certain neighborhoods. we used rhode island as a case study due to its small size and the feasibility to conduct a statewide geospatial analysis. the limited number of health disparities research on rhode island also compelled us to use it for our study. our goal was to offer visual and concrete evidence of whether or not environmental health burdens disproportionately impact lowincome and minority communities. we utilized a digital tool (i.e. gis) that we believe has the potential to increase awareness of health disparities among healthcare professionals and the public at large. our study aims to continue the national discourse on health disparities by helping the public recognize how social and environmental burdens exist along class and racial lines. we hope that our findings could serve as an additional resource for public health advocates and policymakers, both in rhode island and around the country. geography serves as a medium where inequalities "may be passed on from one generation to the next via the environment of opportunities and services into which an individual is implanted at birth" [ ] . historically in the united states, low-income and racial minority communities have been subject to systematic discrimination. jim crow laws prohibited black students from attending schools with their peers. redlining has deprived communities of color generational wealth that their white counterparts now benefit from [ ] . decades of predatory marketing and advertisements by fast-food corporations such as mcdonald's and kfc have contributed to the obesity epidemic in black families [ ] . more recently, national discussions spearheaded by african-american communities in flint, michigan and native americans in north dakota bear witness to the ongoing issue of environmental injustice that predominantly affects low-income and racial minorities [ , ] . because geography has played an inherent role in the development and perpetuation of social inequality, gis can therefore be a practical tool for examining the intersections of socioeconomic status and environmental health burdens. geographic information systems is a visual and analytical tool with a multitude of applications. its users widely range from journalists and activists to marketing and advertising agencies [ ] [ ] [ ] . gis has been used to track human rights violations in uganda, document changes in population across the united states by race and ethnicity, and show locations of deforestations and mining concessions throughout the amazon rainforest in real-time [ ] [ ] [ ] . in public health research, the most common gis applications include disease surveillance, risk analysis, health access planning, and community health profiling [ ] . citizen science can be broadly defined as "the general public engagement in scientific research activities when citizens actively contribute to science either with their intellectual effort or surrounding knowledge or with their tools and resources" [ ] . central to citizen science is the mission to democratize data. initially, citizen science was predominantly seen in the natural sciences field but has been gradually embraced as a method of data collection in other fields such as economics, journalism, and political science. however, citizen science in public health can be argued as rare and didn't gain worldwide traction until the recent covid- pandemic. in this study, we utilize a multi-disciplinary approach that combines gis and citizen science to examine the distribution of environmental health burdens in rhode island using data from publicly available sources. addresses for local branches of kfc (n = ), mcdonald's (n = ), and taco bell (n = ) in rhode island were retrieved using company websites. locations of the top and bottom elementary schools in the state were collected based on data from www.schooldigger.com. public parks (n = ) with community playgrounds were identified from www.rifamilyguide.com. to identify facilities that release toxic substances and pollutants in rhode island, the u.s. environmental protection agency's envirofacts database was used, from which sites were randomly chosen for the study sample. the retrieved addresses were compiled in microsoft excel and geo-coded in arcmap using the nsrs stateplane coordinate system for rhode island. addresses that were not successfully geocoded initially and those that did not have a full street address were replaced by the closest address/intersection. a spatial join was then conducted between the geocoded point features and maps of census tracts containing american community survey (acs) data which was used to determine percent distribution of white population and average household income in surrounding neighborhoods. pearson correlations and independent sample t-tests were also used for analysis. the neighborhoods surrounding the bottom-ranked elementary schools had a lower average household income and percentage of white population than those surrounding the topperforming elementary schools in rhode island ( table ) . the difference was statistically significant with a p-value of less than . (α = . ). furthermore, the bottom-ranked elementary schools tended to be clustered in the providence county area compared to the topperforming elementary schools ( figure ). census tract neighborhoods within a two-mile radius of community playgrounds ( figure ) were . % white and had an average income of $ , . (figures , ) , which were . % and $ , . higher than the state average, respectively. the differences however were not statistically significant (p-value= . and p-value= . ). this study was primarily conducted by u.s. medical students as a summer experiential project to learn about health disparities and medical geography using a practical data analytics tool (i.e. geographic information systems). our findings reinforce the notion that lack of access to nutritious foods, multiple sources of environmental pollution, poor quality education, and lack of access to community parks disproportionately impact communities of color. for our first geospatial analysis, we specifically showed that the top-ranked elementary schools were mostly located in affluent and largely white neighborhoods, while the worst-ranked elementary schools were clustered in low-income and largely black neighborhoods. the associations were statistically significant (p< . ). this finding is concerning because quality of early childhood education has been shown to be a reliable predictor of health outcomes. students who attend high-quality schools, which often have comprehensive science and health curricula, have been shown to demonstrate higher levels of health literacy as adults [ ] . they are also more likely to be smarter consumers of medical information as well as stronger advocates of their own health when interacting with their physicians [ ] . we demonstrated the same pattern in race and class makeup of neighborhoods when looking at placements of community parks in rhode island. the communities that are within two miles of parks had higher household incomes and larger percentage of white residents compared to the state average. research shows that availability of green spaces has been linked to improved mental health and reduction in cardiovascular risk [ ] . considering the disproportionately high rates of chronic stress and diabetes in black and low-income patients, our data underscores the need for rhode island city planners to increase access to green spaces and community parks in low-income, minority neighborhoods. our subsequent geospatial analysis revealed associations between socioeconomic makeup of neighborhoods and placement of fast-food restaurants. on average, we discovered that household income increases as one travels farther from the address of a fast-food restaurant. while we did not directly examine the prevalence of food deserts, this finding aligns with the numerous studies documenting the high prevalence fast-food restaurants in black neighborhoods, which may help explain the obesity epidemic in these communities. in a geographical survey study, beaulac et al. documented that in areas with a high proportion of low-income or african american residents, there are fewer supermarkets or chain stores per capita when compared to more economically advantaged areas [ ] . the authors concluded that low-income, minority areas tend to have poor access to healthy food. studies also suggest that supermarkets may be intentionally avoiding such neighborhoods because of the lower purchasing power in these communities [ ] . perceptions that high crime and cultural norms will significantly hinder profit margins of supermarkets could be additional factors. that fast food is ingrained in the diet of african-americans can also be attributed to the intentional targeting of black communities by fast-food company advertisers [ ] . lastly, we conducted a geospatial analysis of superfund site locations and found that the neighborhoods in close proximity also tended to be more black and less affluent. this was not a surprising finding due to the well-documented historical data on the strategic placement of toxic facilities in minority and low-income neighborhoods [ ] . dating back to the s, politicians and urban planners have historically avoided white and affluent neighborhoods when planning for the construction of hazardous waste facilities such as landfills, industrial factories, and incinerators. one aim of our study is to offer yet another framework through which health disparities and environmental racism can be conceptualized. this study is the first to utilize gis to examine the relationship between community demographic data and the distribution of multiple sources of environmental health burden in rhode island. popick et al. used rhode island as a gis case study but only focused on access to care through proximity to bus lines and physician distribution by region and per capita [ ] . dong et al. also examined rhode island using gis as a tool [ ] . however, their focus was on food insecurity among adults who are on probation. other health-related gis studies on rhode island have involved an evaluation of flood-prone areas, nitrogen dioxide levels, and neighborhood walkability [ , ] . our study has limitations. first, we did not examine specific health conditions in rhode island. exploring the correlations between environmental health burdens and the prevalence of relevant illnesses like asthma and cardiovascular disease could lend more weight to the argument that gis research is critical for population health and can serve as a resource for health policy officials. second, our census tract dataset did not include asians, hispanics, and native-americans. future research on gis and health disparities, in general, should define "minority communities" in a way that it includes all communities of color. one unique strength in our study was the decision to use publicly available data (e.g. epa website, fast food online directories, schooldigger.com, google maps, rifamilyguide.com). doing so demonstrates the feasibility and value of conducting "citizen science" research, a growing field of interest in our current era of big-data. in addition to reaffirming the value of gis for urban planning and community health, we also believe that our study has practical implications for medical education and the national discourse on health disparities. as we mentioned earlier in this paper, it seems that a contingent of americans is resistant to the notion that health outcomes are significantly influenced by social and environmental forces that are historically rooted in classism and racism. moreover, physicians may be ill-equipped to provide culturally competent care to their patients due to their lack of knowledge or misperceptions about the fundamental causes of health disparities. given the death rate from the novel coronavirus among african-american and low-income patients, it should be no surprise if environmental racism and medical geography resurface as major topics of concern for american public health leaders and politicians. we thus recommend that digital platforms such as gis be used to visualize health disparities data in an accessible and interactive way. doing so may increase the public's awareness and level of engagement to learn more about the social and environmental factors that determine health outcomes and perhaps even spearhead citizen science projects themselves. we would also argue that gis combined with citizen science can be an engaging, innovative, and experiential modality to teach health disparities in medical school. if, for example, medical students are offered an opportunity to learn gis and practice citizen science, they would be better equipped to become public health advocates. not to mention, they will gain a technical skillset critical in a field that is relying more and more on healthcare innovation to improve patient outcomes on a population level. the data suggest that the locations of schools, fast food restaurants, superfund sites, and community parks are associated with the racial and economic makeup of their surrounding census tract neighborhoods. worst performing elementary schools, fast food restaurants, and toxic facilities were more likely to be surrounded by poorer and less white neighborhoods. in contrast, the best performing elementary schools and community parks were more likely to be placed in affluent and predominantly white neighborhoods. these findings are consistent with the literature on the relationship between systemic discrimination and health disparities. the results in this study may also help our current understanding of health disparities in rhode island and the united states as a whole. future studies should explore the link between specific health outcomes and environmental health burdens in rhode island. when defining "minority communities," studies should include asian, hispanic, and native american neighborhoods. identification of other potential etiological factors to health disparities should also be a subject of future gis research. lastly, incorporation of gis into health disparities curriculum or summer experiential projects during medical school presents a practical and engaging learning opportunity to conceptualize the racial, economic, and environmental determinants of health awareness of racial and ethnic health disparities has improved only modestly over a decade understanding public resistance to messages about health disparities promoting health equity and population health: how americans' views differ review: increasing awareness and education on health disparities for health care providers brown speights js: racial and ethnic health disparities curricula in us medical schools: a cera study disparities education: what do students want use of gis mapping as a public health tool-from cholera to cancer inequality and poverty: a marxist-geographic theory wealth inequality and accumulation the context for choice: health implications of targeted food and beverage marketing to african americans a case study of environmental injustice: the failure in flint mining and environmental health disparities in native american communities the diffusion of gis in journalism . lsu doctoral dissertations the map is not the territory: applying qualitative geographic information systems in the practice of activist archaeology geographic information systems in business genocide and giscience: integrating personal narratives and geographic information science to study human rights. the professional geographer geographic information systems and spatial data processing in demography: a maputopias: cartographies of communication, coordination and action-the cases of ushahidi and infoamazonia application of gis technology in public health: successes and challenges socientize consortium: green paper on citizen science. citizen science for europe addressing health literacy challenges with a cuttingedge infectious disease curriculum for the high school biology classroom promoting health literacy for children and adolescents residential green and blue space associated with better mental health: a pilot follow-up study in university students a systematic review of food deserts healthy food access in low-income highminority communities: a longitudinal assessment- - evaluating the impact of executive order . environ health perspect geographic access to care in rhode island through the use of gis food acquisition methods and correlates of food insecurity in adults on probation in rhode island using risk-based analysis and geographic information systems to assess flooding problems in an urban watershed in rhode island. environ manage walk score™ as a global estimate of neighborhood walkability in the united states. human subjects: all authors have confirmed that this study did not involve human participants or tissue. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -volbaipv authors: neupane, karun; ahmed, zahoor; pervez, hira; ashraf, rabia; majeed, aneela title: potential treatment options for covid- : a comprehensive review of global pharmacological development efforts date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: volbaipv coronavirus disease- (covid- ), first reported in china during december of , is caused by the severe acute respiratory syndrome coronavirus (sars-cov- ). infection later spread very rapidly around the globe with over , , cases reported, including more than , deaths reported across at least countries by june , . it was declared as a global pandemic by the world health organization (who) on march , . with the rapidly increasing number of positive cases and deaths, there is a dire need for effective treatment. an urgent unmet need led to the planning and opening of multiple drug development trials for treatment and vaccine development. in this article, we have compiled comprehensive data on many candidate drugs such as remdesivir, favipiravir, ribavirin, umifenovir, arbidol, lopinavir, ritonavir, baricitinib, hydroxychloroquine, nitazoxanide, azithromycin, baloxavir, oseltamivir, losartan, and tocilizumab. we have tabulated available data on various clinical trials testing various aspects of covid- therapeutics. themselves to better understand the virus and disease pathophysiology and develop effective drugs and preventive vaccines. while new treatment options are being sought out, one of the main areas of focus has been trying to repurpose the existing drugs to fight against covid- . several drugs are being tested in the trials, and the united states food and drugs administration (fda) has given emergency use authorization (eua) for remdesivir to treat covid- patients on may , [ ] . the clinical management of covid- patients is focused on alleviating clinical symptoms by general and symptom-specific supportive care [ ] . potential therapeutic options against covid- include molecules binding to the virus, inhibitors that can target specific enzymes involved in viral replication or viral transcription. small-molecule inhibitors can target helicase, essential proteases, or other proteins of the virus, and host cell protease inhibitor [ ] . based on the sequencing of the entire genome and the information coupled with protein structure modeling, the research community has been able to rapidly respond with a proposed list of antiviral agents with potential therapeutic efficacy in the treatment of covid- . the investigational drugs together with their potential mechanisms of actions and other specific characteristics are summarized in table . the % effective concentration (ec ) value of remdesivir against sars-cov- in vero e cells was . μm, which suggests that its working concentration is likely to be achieved in non-human primates [ ] . remdesivir is available for the treatment of ebola virus disease in humans and has shown promising results in animal models for mers-cov and sars-cov. therapeutic remdesivir treatment in mers-cov inoculated rhesus macaques resulted in the reduction in clinical signs, virus replication, and the absence of lung lesions in / remdesivirtreated animals along with the reduction in lesion severity in three additional animals. mers-cov has a close resemblance to sars-cov- and the drug is being studied for the treatment of covid- in china and the united states [ ] . results from a recent open-labeled, nonrandomized trial of remdesivir in covid- patients showed that after up to ten days of compassionate use of remdesivir, % of the cohort showed symptoms improvement with only % mortality rate at a median follow up of days. it is noteworthy to mention that ( %) patients were already on invasive ventilation before the initiation of the treatment, out of which patients were weaned off the invasive ventilation successfully following the treatment. the adverse effects with remdesivir ranged widely from increased liver enzymes ( %), diarrhea ( %), rash ( %) to more severe conditions being multiple organ failure ( %), septic shock ( %), hypotension ( %) and acute kidney injury ( %) [ ] . in a randomized controlled clinical trial of patients conducted by the national institute of allergy and infectious disease (niaid), remdesivir has shown the efficacy in the early results against advanced covid- (nct ). patients were randomized into the remdesivir group and placebo group. it was observed that remdesivir was better from the perspective of primary endpoint and time to recovery defined as being well enough for hospital discharge or returning to the normal activity level. preliminary results of this trial showed % faster time to recovery in those patients who received compassionate use of remdesivir as compared to placebo patients (p < . ). the median time to recovery was days for remdesivir group compared with days for placebo group. results were also significant in terms of survival benefit, with % mortality in remdesivir group as compared to . % in placebo group (p = . ) these results support the use of remdesivir for the patients who are hospitalized with covid- and require supplemental oxygen therapy [ ] . the american center for disease control (cdc) in a public document on its website, showed that three patients were treated with remdesivir via compassionate use protocol among the first patients confirmed to have covid- in the united states. all patients reportedly have recovered, but the few side effects like transient gastrointestinal symptoms and aminotransferase elevation were reported, and the authors were unable to weigh the efficacy of remdesivir because of no comparator and confounding treatments, including the concomitant use of corticosteroids in one patient [ ] . a recent update on the efficacy of rdv against covid- by gilead sciences also reported that more than , patients have now been treated with rdv through the expanded access programs [ ] . the ongoing clinical trials on remdesivir are given in table . [ ] . further studies are undergoing to test its efficacy. a fixed dose of the anti-hiv combination, lopinavir-ritonavir, is currently in clinical trials with arbidol or ribavirin but results are not yet available [ ] . favipiravir, which acts as an alternate substrate leading to lethal rna transversion mutations producing a nonviable viral phenotype, has also been recently approved for clinical trials in treating the covid- [ ] . the clinical trials on lopinavir and ritonavir are given in table . the use of corticosteroids for the treatment of coronavirus infections is controversial. while it reduces the immunological damage, viral rebound, and adverse events remain the major concerns [ ] . the use of corticosteroids in sars patients has been associated with increased viral load, while side effects like avascular necrosis (seen in % of patients in a cohort in hong kong) and opportunistic infections like aspergillosis have been reported [ ] . a significantly higher concentration of plasma viral rna concentration was reported in the second and third weeks of illness in patients treated with hydrocortisone (n= ) as compared to those receiving placebo (n= ; p= . ) [ ] . however, in another study, better results were seen in patients of sars-cov (n = ) treated with early high-dose steroids in combination with a quinolone (n= ) (zero deaths; meantime to discharge: . ± . ) vs other three treatment groups (n = , , ) (two or more deaths in each group; meantime to discharge: . ± . , . ± . , . ± . ). preliminary reports from the recovery (randomised evaluation of covid- therapy) trial (n= , received dexamethasone at a dose of mg once daily per oral/intravenous vs n= patients received usual care alone) showed that dexamethasone showed improved survival in covid- patients. among the patients receiving usual care alone, the days mortality in those requiring ventilation, requiring oxygen only, and in those not requiring any respiratory intervention was %, %, and %, respectively. even though no benefit was seen among the patients not requiring respiratory support (rate ratio . ; % confidence interval [ci] . - . ; p = . ), but in the ventilated patients with covid- , dexamethasone decreased the deaths by one-third (rate ratio . ; % ci . - . ; p = . ), and by one-fifth in the patients requiring oxygen only (rate ratio . ; % ci . - . ; p = . ). these results indicated that for the prevention of one death, eight patients requiring ventilation needed to treat while this number was in patients requiring oxygen only. these promising results mean the role of dexamethasone and possibly other steroids should be explored further for the treatment of covid- patients [ ] . the clinical trials on corticosteroids are given in table . baricitinib has anti-inflammatory action and possible ability to inhibit viral entry into the cells [ ] . it is a janus kinase (jak) inhibitor that binds to the cyclin g-associated kinase, a regulator of endocytosis. baricitinib in therapeutic dose (either as mg or mg once daily) is enough to inhibit ap -associated protein kinase (aak ), a regulator of the endocytosis process, which is implicated in the cellular viral entry process. baricitinib can disrupt aak causing the interruption of viral entry into the cell and intracellular assembly of virus particles, which makes it a potential drug for covid- [ ] . the clinical trials on jaks are given in table . nitazoxanide, an antiprotozoal drug, has antiviral potential against a wide range of viruses, including human and animal coronaviruses. it has also inhibited viral replication at a low-micro molar concentration in vero e cells, with half-maximal effective concentration (ec ) of . μm [ ] . ivermectin also acts as an anti-viral by inhibiting importin α/β and integrase proteins involved in viral replication [ ] . a single treatment with ivermectin has shown to reduce sars-cov- rna by ∼ -fold at hours in cell culture [ ] . plasma levels of interleukin- (il- ), il- , and il- were found to be higher in more sick patients and those admitted in the intensive care unit [ ] . tocilizumab is a recombinant humanized monoclonal antibody specific for the interleukin- (il- ) receptor and is used for the treatment of cytokine release syndrome. in a retrospective observational study involving twenty patients with severe or critical covid- , treatment with tocilizumab in addition to lopinavir, methylprednisolone, other symptom relievers, and oxygen therapy, resulted in body temperature of all the patients returning to normal on the first day of receiving tocilizumab and significant relief of clinical symptoms synchronously in the following days. after treatment, oxygen intake was lowered in / patients and one patient did not need oxygen therapy while ct scan lesions were absorbed in nineteen patients. no adverse events were reported during treatment with tocilizumab [ ] . ongoing clinical trials on tocilizumab are given in table . the use of convalescent plasma in severe acute respiratory infections (sari) has shown favorable results in the past, with the mortality rate reduced by % in those who received convalescent plasma among all viral etiologies such as sars coronavirus (sars-cov), spanish influenza a (h n ), avian influenza a(h n ), and influenza a (h n ). these studies did not report any major adverse events [ ] . covid- -specific plasma collected from five recovered sars-cov patients with age ranges from to , has shown positive results in a small case series of five critically ill patients diagnosed with covid- who were under mechanical ventilation, and had a high viral load despite receiving antivirals and methylprednisolone. among a total of five patients (age range: - ) who were treated with plasma, viral load reduction has been noted on the same day with continuous improvement over several days ( - days) followed by gradual resolution of symptoms. four out of five patients no longer required respiratory support on day nine post plasma transfusion and / patients were discharged home after hospital stay ranging from - days. hospitalization was continued for / patients with a total of days of hospital stay [ ] . similarly, the use of a high dose of intravenous immunoglobulin g (ivig) obtained from healthy donors' serum in patients (n = ) with the diagnosis of covid- severe type has also shown effective results. the fever subsided the very next day in two cases (age: and ) and the same day in the third patient (age ), accompanied by symptoms resolution over a couple of days with no adverse events reported. this indicates that the clinical outcome of patients with covid- can be improved if the disease progression is halted down by administering high dose ivig in a timely fashion [ ] . additional data and clinical trials on high dose ivig in covid- patients are warranted. the ongoing clinical trials are given in table . angiotensin-converting enzyme (ace ) is a binding site for sars-cov- . the binding of sars-cov- to ace leads to the downregulation of ace resulting in increased angiotensin production by angiotensin-converting enzyme (ace) as there is less ace to convert angiotensin to the vasodilator heptapeptide angiotensin - . this increased angiotensin causes increased angiotensin receptor (at r) stimulation resulting in increased pulmonary vascular permeability leading to lung injury. it has been hypothesized that at r antagonists like losartan increase ace expression and prevent lung injury in covid- patients [ ] . however, another hypothesis suggests that cellular entry of sars-cov- is facilitated by the up-regulation of ace caused by at r antagonist use and hence can be harmful in covid- patients. similarly, non-steroidal anti-inflammatory drugs (nsaids) like ibuprofen also acts by upregulating ace [ ] . ongoing clinical trials are given in table . the % effective concentration (ec ) value of chloroquine against the sars-cov- in vero e cells is . μm, which can be achieved clinically, as has already been demonstrated in the plasma of rheumatoid arthritis patients [ ] . in an open-label non-randomized clinical trial of hydroxychloroquine (hcq) (n = ), % of hcq treated patients (n= / ) were virologically cured vs . % in the control group (n= / ) (p = . ) at day six post inclusion while % patients treated with hcq plus azithromycin (n = / ) were virologically cured vs . % in patients receiving hcq alone (n = / ) [ ] . the limitations of this study were its small sample size, limited long-term outcome follow-up, and dropout of six patients from the study. hence a larger sample size study is essential to investigate and find out the efficacy of hcq in the treatment of covid- [ ] . however, in a recent study, hydroxychloroquine was not effective against coivd- patients and has been revoked from the emergency use against covid- patients due to safety concerns. ongoing clinical trials are given in table . collaborative global efforts are underway to control the covid- pandemic. many clinical trials are underway. these trials are different in study structure, the severity of the disease, the duration of the treatment, and the dosing of drugs in the target population. these trials are also different in the quality of the reported information. many studies are going in parallel, suggesting that the scientific community is working hard to come up with an effective treatment for covid- . few drugs like remdesivir and dexamethasone have demonstrated positive early results against covid- in clinical trials and their efficacy has also been observed in pre-clinical and clinical studies, but their use against covid- should be based on the severity of patient clinical status and ethical approval from randomized clinical trials. efficacy and safety data from further studies with larger sample size, blinded, randomized design, and longer follow-up are needed urgently. the epidemiological characteristics of an outbreak of novel coronavirus diseases (covid- ) in china isolation of -ncov from a stool specimen of a laboratoryconfirmed case of the coronavirus disease (covid- ) q&a: the novel coronavirus outbreak causing covid- features, evaluation and treatment coronavirus novel inhibitors of severe acute respiratory syndrome coronavirus entry that act by three distinct mechanisms anti-sars coronavirus agents: a patent review ( -present) remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus ( -ncov) in vitro prophylactic and therapeutic remdesivir (gs- ) treatment in the rhesus macaque model of mers-cov infection compassionate use of remdesivir for patients with severe covid- nih clinical trial shows remdesivir accelerates recovery from advanced covid- first patients with coronavirus disease (covid- ) in the united states comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against mers-cov a trial of lopinavir-ritonavir in adults hospitalized with severe covid- research and development on therapeutic agents and vaccines for covid- and related human coronavirus diseases a: more than clinical trials launch to test coronavirus treatments structural basis of influenza virus fusion inhibition by the antiviral drug arbidol dexamethasone reduces death in hospitalized patients with severe respiratory complications of covid- baricitinib as potential treatment for -ncov acute respiratory disease nuclear import and export inhibitors alter capsid protein distribution in mammalian cells and reduce venezuelan equine encephalitis virus replication the fda-approved drug ivermectin inhibits the replication of sars-cov- in vitro detection of novel coronavirus ( -ncov) by real-time rt-pcr effective treatment of severe covid- patients with tocilizumab the effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis a report of clinical diagnosis and treatment of nine cases of coronavirus disease high-dose intravenous immunoglobulin as a therapeutic option for deteriorating patients with coronavirus disease angiotensin receptor blockers as tentative sars-cov- therapeutics are patients with hypertension and diabetes mellitus at increased risk for covid- infection? covid- and treatment with nsaids and corticosteroids: should we be limiting their use in the clinical setting fatal aspergillosis in a patient with sars who was treated with corticosteroids effects of early corticosteroid treatment on plasma sarsassociated coronavirus rna concentrations in adult patients hydroxychloroquine and azithromycin as a treatment of covid- : results of an open-label non-randomized clinical trial treatment of q fever endocarditis: comparison of regimens containing doxycycline and ofloxacin or hydroxychloroquine in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -hva dasd authors: krawiec, conrad; myers, abigail title: remote assessment of video-recorded oral presentations centered on a virtual case-based module: a covid- feasibility study date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: hva dasd introduction the coronavirus disease (covid- ) pandemic has resulted in the suspension of our pediatric clerkship, which may result in medical student skill erosion due to lack of patient contact. our clerkship has developed and assessed the feasibility of implementing a video-recorded oral presentation assignment and formative assessment centered on virtual case-based modules. methods this retrospective study examined the feasibility of providing a remote formative assessment of third-year medical student video-recorded oral presentation submissions centered on virtual case-based modules over a one-week time period after pediatric clerkship suspension (march th to th, ). descriptive statistics were used to assess the video length and assessment scores of the oral presentations. results twelve subjects were included in this study. overall median assessment score [median score, ( th, th percentile)] was ( , ), described as “mostly on target” per the patient presentation rating tool. conclusion patient-related activities during the pediatric clerkship were halted during the covid- pandemic. this study demonstrated the possibility of remotely assessing oral presentation skills centered on virtual case-based modules using a patient presentation tool intended for non-virtual patients. this may prepare students for their clinical experiences when covid- restrictions are lifted. future studies are needed to determine if suspended clerkships should consider this approach. in , the coronavirus disease (covid- ) pandemic resulted in the unprecedented prolonged closure of educational institutions worldwide to curb the spread of the virus [ , ] . medical students were included in this group of learners per the guidance of the association of american medical colleges (aamc) [ ] . thus, our institution temporarily suspended the clinical portion of the pediatric clerkship. electronic resources exist to supplement the pediatric clerkship curriculum, thus key aspects can be taught remotely [ ] [ ] [ ] [ ] . one aspect that electronic sources lack, however, is patient contact. lack of patient contact results in the inability to practice clinical skills, including interviewing or orally presenting patients recently seen. these clinical skills are often assessed during the pediatric clerkship and students will often specifically receive feedback on these skills [ ] . they are also prioritized by some clerkships for the summative evaluation as students must develop these skills to demonstrate they can assess a patient and synthesize their medical knowledge [ ] . at our institution, we have instituted a remote learning curriculum for our third-year medical students starting at the end of april . when covid- restrictions are lifted, our students will undergo two weeks of patient contact time. because our students will not have been in a clinical environment for a prolonged time period, they may have difficulty transitioning [ ] . to minimize the impact this transition will have on our students, our pediatric clerkship has developed a video-recorded oral presentation assignment centered on a virtual case-based module with remote formative assessment. our goal was to enhance the development of this clinical skill remotely thereby allowing students to focus on clinical skill development in areas that cannot be achieved without patient contact (i.e., patient interviewing) when restrictions are lifted. the objective of this study is to demonstrate the feasibility of student video-recording an oral presentation centered on a virtual case-based module and having our attending faculty members provide a formative assessment. the study hypothesis is that it is feasible to assess and provide formative feedback on video-recorded oral presentations by pediatric attending faculty members using a patient presentation rating tool intended for non-virtual patients. this is a feasibility study requesting students to video-record an oral presentation centered on a virtual case-based module for formative assessment during a time period (march th, until march th, ) when pennsylvania state college of medicine third-year medical students were abruptly restricted from providing direct patient care during the pediatric clerkship. a retrospective review of faculty submitted formative assessments of the videorecorded oral presentations centered on virtual case-based modules was completed. this study was reviewed by our institution's review board and determined to be non-human research. third-year medical students -( ) part of our institution's traditional curriculum, ( ) rotated at the pediatric clerkship's primary site or off-campus affiliate sites during the first month of the academic year ( - ), ( ) were abruptly restricted from direct patient care due to the covid- pandemic, and ( ) completed a video-recorded oral presentation centered on a virtual case-based module -were included in this study. students who were part of the longitudinal integrated curriculum were excluded. the pediatric clerkship at our institution is a four-week rotation with the following clinical requirements: outpatient clinic, nursery, and inpatient service. on march th, third-year students were restricted from direct patient care, thus only three weeks of the clerkship was completed. the video-recorded oral presentation assignment was developed by a pediatric clerkship director experienced in inpatient medicine and an outpatient pediatrician. a patient presentation tool developed by lewin et al. was utilized for this assessment [ ] . using behavioral and verbal anchors, the patient presentation tool assesses various oral presentation sections including patient history, physical exam and diagnostic study results, summary statement, assessment and plan, clinical reasoning/synthesis of information, and general aspects (organization, speaking style) based on a -point scale ( being the highest) [ ] . overall assessment of presentation is based on a -point scale ( being the highest and described as "well above expectations"). eight faculty members were recruited to use this tool as they were assessing the video recordings. starting on march th, , the subjects were provided a remote learning curriculum and were notified of the video-recorded oral presentation assignment. they were informed that the pediatric clerkship will be graded pass/fail, that submission of a video-recorded oral presentation for formative assessment will be required, and was due on march th, . the subjects were instructed to ( ) video-record an oral presentation of either a patient they have seen during the course of the clerkship or after completing a virtual online case-based module through aquifer © (lebanon, new hampshire, usa) and ( ) upload the assignment via the instructure canvas (salt lake city, utah, usa) learning management system. students were given specific directions including the use of professional attire, limiting the video-recording to minutes, and requesting students to review the video prior to submission for clarity and organization. after receiving the video-recordings, the files were securely distributed through the canvas © learning management system among eight pediatric attending faculty volunteers who reviewed and provided formative assessment scores of the oral presentation. all completed assignments were collected using the instructure canvas learning management system. using the canvas learning management system, we extracted the following data: overall video-recorded oral presentation rating scores and video-recorded oral presentation scores divided by section as outlined by the patient presentation tool [ ] . if students elected to give an oral presentation based on a virtual case-based module, we asked students to complete the pediatric aquifer © case-based module , a -year-old male seen for a well-child visit [ ] . this case was chosen as it provides a robust history and physical examination, tasks the student to identify and prioritize problems uncovered during this visit, allows the student to apply a differential diagnosis when appropriate, formulate a management plan, and practice their organization skills during the oral presentation. we used descriptive statistics to assess the study population in terms of length of presentation, type of patient presented, and assessment scores based on the patient presentation tool [ ] . formative assessment of each oral presentation was reported in the median and interquartile range. twelve individual oral presentation videos centered on the virtual case-based module were included in this study. median video length [median time (mm:ss), ( th, th percentile)] was : ( : , : ). overall, median overall formative assessment score [median score, th, th percentile] of video-recorded oral presentation centered on virtual case-based modules was ( , ), described as "mostly on target" per the patient presentation tool [ ] . the lowest items scored were pertinent positives and negatives of the differential diagnosis [ ( , )] ( table ) . note: sections scored on a to scale, being the highest score patient presentation rating tool for oral case presentations [ ] . oral presentations are an essential clinical skill that facilitates physician to physician communication, improves efficiency on rounds, and enables individual as well as group learning [ ] . it also can be complex and time-consuming as students must use their medical knowledge and clinical reasoning skills to select the pertinent details to present from a patient's history, physical, diagnostic, and laboratory tests [ , ] . in this study, we hypothesized that video-recorded oral presentations centered on a virtual case-based module can undergo a formative assessment. this study successfully demonstrated that a formative assessment can be remotely provided for video-recorded presentations based on virtual casebased modules. these results imply that this form of assessment is possible, may prepare students for the eventual live clinical experience (with patient contact), and potentially optimize the transition period from covid- remote learning to a post-covid- clinical patient experience. to our knowledge, a pediatric clerkship has never been halted in this manner for a prolonged period due to a nationwide health emergency. because of this, our pediatric clerkship, like others across the united states was placed in an unprecedented situation, potentially placing our students at risk of achieving suboptimal competency in various clinical areas [ ] . novel approaches are necessary to ensure that our students, who were hastily restricted during their pediatric clerkship and future students that have yet to complete their pediatric clerkship, are adequately trained [ ] . our institution's current plans are for each clerkship to institute a remote learning curriculum and complete a two-week immersive clinical experience in each of the core clerkships. the remote learning curriculum will allow students to learn the basic concepts relevant for pediatrics and the two-week patient contact experience will allow students to apply their knowledge. when the two-week patient contact experience begins, however, the transition period may be difficult. students will not have seen a patient (possibly for months) and similar to transitioning from the pre-clerkship to clerkship years, students may be overwhelmed by clerkship logistics, expectations, and adjusting to the clinical culture [ ] . in all, students may be overwhelmed by this and the number of tasks they must complete in a short time period post-clerkship suspension, potentially limiting their clinical experience. thus, it is the clerkship's responsibility to ensure that students in a remote curriculum continue to be comparably trained and are provided as many similar clinical experiences as possible to ease the transition that will occur on clerkship reinstatement. while the pediatric clerkship is currently limited in allowing students to see patients during the remote learning experience, there are other ways that students can be robustly prepared for the clinical environment. the area that our clerkship elected to focus on is the oral presentation. if students are rigorously prepared to practice oral presentation skills using pediatric faculty members (that they will eventually present to), students may start to apply their communication, medical knowledge, and clinical reasoning skills earlier and potentially focus their clinical skills on other areas that they cannot easily achieve remotely (i.e., history taking and physical examination and providing live patient care) when they return to clerkship. students may also have a better understanding of their expectations, roles, and responsibilities of this skill for our clerkship and thus are better prepared to provide meaningful patient care and be effective team members sooner. in our study, we found that it is feasible for students to submit a video-recorded oral presentation centered on a virtual case-based module and recruit pediatric attending faculty members to assess and provide formative feedback. we also found that the overall median scores were "mostly on target" according to the patient presentation tool. the students who completed these assessments were the first students for the academic year, thus these results may indicate that these students developmentally require more practice. alternatively, these results may indicate that because these assessments are formative and the clerkship is now pass/fail, these students were given the feedback necessary to improve their skills. finally, students may not have received enough individual educational attention during the normal clinical workflow and thus were not given enough instruction. more studies are necessary to determine if these assessments are consistent. there were several limitations to this study. this includes its small sample size, the short intervention period, and the lack of randomization. the patient presentation rating tool intended for live patients was used without the opportunity to validate it for use in virtual casebased modules due to the haste in its implementation. future studies will be required to validate the tool for this purpose. student perception is also unknown regarding the effectiveness of this assessment technique, thus future qualitative studies are planned to determine this. our pediatric clerkship was suddenly curtailed during the covid- pandemic. the students were provided a remote learning curriculum to emphasize pediatric concepts but may not be able to demonstrate their clinical skills in communication, data synthesis, and patient assessment. our study demonstrated that it is possible to assess oral presentation skills centered on virtual case-based modules using a patient presentation rating tool intended for non-virtual patients and may potentially prepare students for their clinical experiences when covid- restrictions are lifted. future studies are needed to determine if suspended clerkships should consider this approach. human subjects: consent was obtained by all participants in this study. penn state college of medicine institutional review board issued approval study . the human subjects protection office determined that the proposed activity, as described in the above-referenced submission, does not meet the definition of human subject research as defined in cfr . (e) and/or (l). institutional review board (irb) review and approval is not required. please note: while irb review and approval is not required, you remain responsible for ensuring compliance with ferpa. if you have additional questions regarding ferpa regulations, please contact the office of the university registrar. the irb requires notification and review if there are any proposed changes to the activities described in the irb submission that may affect this determination. if changes are being considered and there are questions about whether irb review is needed, please contact the human subjects protection office. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. considering inequalities in the school closure response to covid- mitigate the effects of home confinement on children during the covid- outbreak guidance on medical students' participation in direct patient contact activities aquifer pediatrics (formerly clipp): a case-based virtual course blended learning educational format for third-year pediatrics clinical rotation degrees: planning a new pediatric clerkship curriculum competencies and objectives developing and implementing universal guidelines for oral patient presentation skills ready or not? expectations of faculty and medical students for clinical skills preparation for clerkships the patient presentation rating tool for oral case presentations covid- and medical education transition to clerkship courses: preparing students to enter the workplace the authors are grateful to our pediatric faculty, who took the time to assess our students during this stressful time. key: cord- -p v sl x authors: gubitosa, james c; xu, phoenix; ahmed, ahmed; pergament, kathleen title: covid- -associated acute limb ischemia in a patient on therapeutic anticoagulation date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: p v sl x coronavirus disease (covid- ), caused by severe acute respiratory syndrome coronavirus (sars-cov- ), has been found to cause multiple complications across several organ systems in patterns not typically observed in previous iterations of the virus. hemostatic mechanisms have been noted to be significantly altered in particular, resulting in a disseminated intravascular coagulation (dic)-like picture with elements of coagulopathy as well as hypercoagulability. a -year-old man with hypertension, hyperlipidemia, prior tobacco use, chronic kidney disease, and diabetes presented from a correctional facility with hypoxia. the diagnosis of covid- was confirmed. with his elevated d-dimer of > , ng/ml (reference: - ng/ml) in the setting of covid- and hypoxia, he was empirically started on therapeutic anticoagulation with enoxaparin. his oxygen requirements increased, mental status deteriorated, and platelets began falling, raising concern for heparin-induced thrombocytopenia versus dic. heparin products were discontinued in favor of a direct oral anticoagulant. he later became obtunded and unable to tolerate oral medications. fondaparinux was initiated. two days later, he was found to have acute limb ischemia of the right lower extremity. he underwent surgical thrombectomy but required an above-the-knee amputation the following day. shortly after he died secondary to hypoxic respiratory failure. this case highlights the derangement of hemostatic mechanisms seen prominently in covid- infection and raises questions as to appropriate anticoagulant choices to adequately prevent thrombosis. thorough physical exams should be performed on all patients with covid- , taking into account this documented hypercoagulability. further investigation is warranted into the use of heparin products as the anticoagulant of choice in these patients given observed deficiencies of antithrombin iii (atiii). coronavirus disease (covid- ), caused by severe acute respiratory syndrome coronavirus (sars-cov- ), has been found to cause multiple complications across several organ systems. hemostatic mechanisms have been noted to be significantly deranged, resulting in a disseminated intravascular coagulation (dic)-like picture with elements of coagulopathy as well as hypercoagulability present. in fact, the most common laboratory abnormalities seen in covid- -associated cases include an elevated prothrombin time and an elevated d-dimer [ ] [ ] [ ] . here, we report a case of a -year-old man who presented with acute hypoxic respiratory failure secondary to covid- . his hospital course was complicated by acute limb ischemia due to an acute occlusion of the right popliteal artery requiring eventual amputation of the limb, ultimately resulting in his death [ ] . a -year-old man with a history of hypertension, hyperlipidemia, prior tobacco abuse, stage chronic kidney disease (ckd), and diabetes presented from a correctional facility with progressive shortness of breath, cough, and fever for several days. these symptoms began insidiously and then rapidly worsened in the days prior to admission. many inmates from the same prison were known to be hospitalized with covid- . in the emergency department, he was found to be hypoxemic, saturating at % on room air that improved with oxygen via non-rebreather mask. the patient's chest x-ray demonstrated bilateral patchy opacities consistent with viral pneumonia (figure ) . ct of the chest with intravenous (iv) contrast further characterized the bilateral ground-glass opacities ( figure ). labs were notable for elevated inflammatory markers lactate dehydrogenase (ldh) , u/l (reference: - u/l), ferritin , ng/ml (reference: - ng/ml), and d-dimer > , ng/ml (reference: - ng/ml). lymphopenia was also present on complete blood count. the diagnosis of covid- was confirmed via nasal swab real-time polymerase chain reaction (rt-pcr). demonstrating diffuse ground-glass opacities in bilateral lung fields, most extensive in the bilateral lower lobes with mixed attenuation consolidations and accompanying traction bronchiectasis. therapeutic anticoagulation was empirically initiated with subcutaneous enoxaparin ( mg/kg twice daily) given the hypercoagulable state observed in many covid- patients with elevated d-dimer. enoxaparin was chosen based on the patient's still adequate creatinine clearance (crcl) of ml/min and the ease of dosing compared to heparin. three days after the first dose of enoxaparin, the patient's platelet count began to fall at a moderate pace, dropping from to x platelets/µl (reference: - x platelets/µl) by hospital day . at the same time, the patient's renal function began to worsen from a baseline creatinine of . - . mg/dl (reference: . - . mg/dl). urinalysis demonstrated mild proteinuria with mg/dl of protein detected (reference range: mg/dl) as well as large blood (reference range: negative). moreover, his fibrinogen levels fell below mg/dl (reference: - mg/dl), and mental status continued to deteriorate. dic was suspected given the patient's clinical findings, but heparin-induced thrombocytopenia (hit) could also not be ruled out. qualitative anti-heparin antibodies were sent and found to be positive. concern for hit was still low given the precipitation of thrombocytopenia within four days instead of the classic , and a low t score of . nonetheless, a serotonin-release assay (sra) was sent but would take several days to return. until the sra had returned, heparin products were avoided, and therapeutic anticoagulation cautiously continued with oral apixaban. while superinfection and sepsis-induced coagulopathy were considered, serial blood and urine cultures remained negative. over time, the patient's mental status continued to worsen, and he became unable to safely tolerate oral medications. a ct of the head was ordered but was unable to be performed in a timely manner due to significant strain upon the facility's scanners. a nasogastric tube was attempted but deemed unsafe as significant naso/oropharyngeal bleeding occurred upon manipulation. with no enteric access, therapeutic anticoagulation was instead switched to subcutaneous fondaparinux at a therapeutic renally calculated dose. the patient's mental status and renal function began to improve over the following days. his respiratory status also improved, as he was being transitioned to a nasal cannula from a non-rebreather. the sra also returned negative, effectively ruling out hit. however, two days after initiation of the fondaparinux, the patient complained of acute right leg cramps and was noted to have a cold right leg on follow-up neurological examination. the leg appeared dark, dusky, and dry distal to the knee compared to the left leg. the patient was unable to appreciate light touch, pressure, pain, or temperature sensation distal to the right knee, and had limited ability to move his toes. right dorsalis pedis pulses and posterior tibial pulses were absent on palpation and confirmed to be absent on evaluation with bedside doppler. labs at the time were significant for a persistently elevated d-dimer of > , ng/ml (reference: - ng/ml), partial thromboplastin time (ptt) seconds (reference: - . seconds), international normalized ratio (inr) . (reference: . - . ), platelets x /µl (reference: - x platelets/µl), and fibrinogen mg/dl (reference: - mg/dl). vascular surgery was emergently consulted for suspected acute limb ischemia, and the patient was started on an argatroban infusion with plans for emergent operative intervention. a perioperative ct angiogram of the chest and lower extremities demonstrated no pulmonary embolism but complete acute occlusion of the right popliteal artery at the level of the knee ( figure ). demonstrating acute occlusion of the right popliteal artery at the level of the distal femur/knee and patency of the left popliteal artery. bilateral popliteal arteries are indicated by yellow circles. the patient was taken for operative thrombectomy with four-compartment fasciotomy of the right lower extremity. during the procedure, the patient was found to have viable musculature within the superficial and deep posterior compartments but non-viable muscle in all other compartments. unfortunately, due to bleeding complications and worsening shock, the patient was taken for a right above-the-knee amputation the following day. following the procedure, the patient was unable to be extubated due to increased oxygen requirements. he was admitted to the surgical intensive care unit for the management of his mechanical ventilation as well as worsening shock requiring pressor support. the patient experienced cardiac arrest shortly afterwards and passed away despite resuscitative measures. during his hospitalization, the patient received covid- convalescent plasma twice, as well as tocilizumab. he was being considered for therapy with remdesivir just prior to his passing. this patient's clinical course is remarkable in that he experienced an acute arterial thromboembolic event while on therapeutic (albeit appropriately renally dosed) anticoagulation. it is unclear how our patient developed an acute arterial ischemic event while on a therapeutic dose of anticoagulation. although the patient was switched from multiple anticoagulants (enoxaparin to apixaban to fondaparinux), all doses were provided in a timely manner, with appropriate dosing, and without any gaps in anticoagulant coverage. in addition, the patient was not also taking any medications known to decrease the efficacy of fondaparinux and/or promote thrombosis. covid- has been found to affect almost every organ system and cause substantial morbidity and mortality. this patient experienced respiratory compromise as well as significant hematologic derangements resulting in a dic-like picture with rapid consumption of coagulation factors as well as hypercoagulability. these factors precipitated significant morbidity and mortality with the loss of a limb, followed by his death. it is possible that the cause of his acute arterial thrombosis was dic, but it is also possible that covid- contributed to his hypercoagulability by a yet unknown mechanism. the prevalence of these arterial and venous thromboses in covid- is well documented in the literature [ - , - ]. in a recent study of patients hospitalized with confirmed covid- , % experienced coagulopathy, and % of those experienced some form of venous or arterial thromboembolic event [ ] . a case series by gonzalez et al. described three cases of peripheral arterial thrombosis in covid- patients [ ] . a retrospective study of venous thromboembolism (vte) incidence in patients with covid- by llitjos et al. demonstrated that % (n = ) of those on prophylactic dose anticoagulation, and % (n = ) of those on therapeutic dose anticoagulation experienced vte [ ] . a case report by griffen et al. described an individual on therapeutic enoxaparin who also developed acute ischemia of the lower limb [ ] . the risk of thromboembolic events and the sheer magnitude of covid- -associated admissions have prompted many hospitals to establish novel protocols with which these individuals are provided anticoagulation at increased or even therapeutic doses compared to the more common prophylactic dose. the exact mechanism through which covid- promotes coagulopathy/hypercoagulability is still under investigation, as is the efficacy of these novel anticoagulation protocols. significant efforts have been made to identify the coagulopathic mechanism of covid- . patients hospitalized with severe covid- are subject to immobility that can commonly predispose to thrombosis. acute phase reactants, including cytokines such as interleukin- (il- ), are elevated and have been shown to cause endothelial damage and dysfunction, which can further predispose to thrombosis. vascular findings in several patients with severe covid- demonstrated endothelitis, with viral inclusion bodies seen under light microscopy in the endothelium of the specimens [ ] . skin and lung biopsies from five patients were examined in a separate study and found to have deposition of c b- , c d, and masp in their associated microvasculature with resultant microvascular damage. these findings were consistent with profound and generalized activation of both alternative and lectin-based complement pathways [ ] . one study of patients with confirmed covid- demonstrated a statistically significant relative deficiency of antithrombin iii (atiii) compared to control (p < . ) [ ] . atiii targets and inactivates proteases of the clotting cascade, namely factors x, ix, xi, xii, and most importantly factor ii, also known as thrombin. this inactivation leads to decreased coagulation. the anticoagulants heparin, enoxaparin, and the less commonly used fondaparinux potentiate atiii as their primary measure of promoting anticoagulation. individuals with hereditary or acquired atiii deficiency (as in the case of covid- patients) may thereby experience decreased efficacy of these anticoagulants. a more recent study analyzed whole blood samples of covid- patients using thromboelastography (teg). teg demonstrated decreased clotting time from the point of coagulation ignition to the appearance of the clot (decreased r-value), increased velocity of clot formation (decreased k-value and increased kangle), as well as increased values of clot maximum amplitude (ma). again, decreased atiii levels, as well as increased fibrinogen, d-dimer, factor viii, and von willebrand factor were observed. these values were all consistent with a hypercoagulable state [ ] . nephrotic syndrome is also known to cause an acquired atiii deficiency via renal protein loss, defined as - . g of urine protein in hours [ ] . our patient not only had pre-existing ckd, but also demonstrated mild proteinuria during his hospitalization, with a spot-urine protein of mg/dl (reference: mg/dl). had the patient not passed away, he may have benefitted from a -hour urine protein collection to diagnose nephrotic syndrome. no prior records were available to further characterize the severity and nature of his ckd. it is plausible that an atiii deficiency was precipitated by covid- -induced kidney injury/subsequent nephrotic syndrome, but this phenomenon has yet to be thoroughly investigated. it is also important to note that our patient had numerous risk factors for vascular disease, including hyperlipidemia, hypertension, diabetes, prior tobacco abuse, and his ckd. aortoiliac atherosclerotic disease was noted on the perioperative ct angiogram as well. it was known that his comorbidities were poorly controlled. outpatient blood pressure readings were approximately / mmhg on average, his hemoglobin a c was . % (reference: . %- . %), his low-density lipoprotein (ldl) was mg/dl (reference: - mg/dl), and his calculated -year atherosclerotic cardiovascular disease (ascvd) risk was . %. he had long struggled with blood pressure and glycemic control, and it is likely these contributed to his development of ckd. overall, his history paints the picture of a very unhealthy vascular state, one that may have predisposed to inflammation and thrombosis contributing to his mortality. at the time of composing this article, there are no established guidelines for preventing/managing "covid- -associated coagulopathy" or "cac" as it is sometimes called. a study of covid- patients demonstrated a statistically significant decrease in mortality ( . % experimental, . % control) in those receiving prophylactic doses of heparin and enoxaparin [ ] . however, given the persistently high mortality rate and incidence of thrombosis even while on prophylactic dose anticoagulation, organizations and institutions have developed novel protocols to determine if select patients should instead receive full-dose or therapeutic anticoagulation [ ] . the international society for thrombosis and hemostasis (isth) has developed an interim set of guidelines that recommends for as-usual prophylactic anticoagulation in hospitalized patients but consideration for therapeutic anticoagulation in patients who are deemed critically ill [ ] . many hospitals have taken further measures to gauge the risk of thrombosis, with most based off the d-dimer level. at these institutions, a significantly elevated d-dimer (at least > , mg/dl) calls for an automatic upgrade to therapeutic anticoagulation. this thought process is what lead to our patient being started on therapeutic anticoagulation. multiple studies are under way to thoroughly investigate the various sequelae of infection with covid- . for cac, research in molecular microbiology and biochemistry will be pivotal. with this information, we can more fully understand the molecular mechanics of how covid- causes this hypercoagulable state and intervene with the appropriate choice of anticoagulation to counterbalance the hematologic disruption caused by the virus. arterial thrombosis in coagulopathic states such as dic and cac has been cited in the literature; however, it is uncommon. arterial thrombosis occurring while a patient is on anticoagulation is even less common. in this patient, the presence of covid- and its associated derangement of hemostatic mechanisms cannot be ignored as a possible exacerbating factor of his thrombosis. there is a clear association between covid- and thrombotic events. moreover, with presentations of covid- being so novel, this case demonstrates the possibility that certain forms of anticoagulation, such as fondaparinux, could be inferior in preventing a thrombotic event. given the cited relative deficiency of atiii in cac and nephrotic syndrome, one can hypothesize that an acute arterial thrombosis may have been avoided if this patient was started on an argatroban infusion from the beginning of his hospital course, which would have provided therapeutic anticoagulation independent of atiii levels. further research is needed to assess the efficacy of and indications for the different anticoagulants in the setting of hypercoagulable states and elevated risk for thrombosis in the covid- infection. clinicians caring for covid- patients should be aware of this hypercoagulable state and take necessary measures to prevent and treat its occurrence. human subjects: consent was obtained by all participants in this study. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial incidence of thrombotic complications in critically ill icu patients with covid- covid- -related severe hypercoagulability in patients admitted to intensive care unit for acute respiratory failure clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china. jama. covid- associated acute limb ischemia in a patient on therapeutic anticoagulation: a case and literature review prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia high incidence of venous thromboembolic events in anticoagulated severe covid- patients acute peripheral arterial thrombosis in covid- . role of endothelial inflammation arterial thromboembolic complications in covid- in low-risk patients despite prophylaxis endothelial cell infection and endotheliitis in covid- complement associated microvascular injury and thrombosis in the pathogenesis of severe covid- infection: a report of five cases prominent changes in blood coagulation of patients with sars-cov- infection hypercoagulability of covid- patients in intensive care unit. a report of thromboelastography findings and other parameters of hemostasis acquired deficiency and urinary excretion of antithrombin iii in nephrotic syndrome anticoagulant treatment is associated with decreased mortality in severe coronavirus disease patients with coagulopathy coagulopathy in covid- : review and recommendations covid- and pulmonary embolism: frequently asked questions relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -ocvy ge authors: mehmood, maham a; patel, madanmohan; sanekommu, harshavardhan title: methicillin-resistant staphylococcus aureus: a very rare cause of meningitis date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ocvy ge community-acquired methicillin-resistant staphylococcus aureus (ca-mrsa) is mostly implicated in soft tissue and skin infections. cases with meningitis caused by ca-mrsa are rare. high index of suspicion should be kept for physicians as bacterial meningitis is a medical emergency and if untreated, has a high mortality rate. urgent steps need to be taken to determine the cause and implement therapy. here, we reported a case of a -year-old female with mrsa bacteremia and meningitis as confirmed by positive blood cultures and cerebrospinal fluid analysis; successfully managed with vancomycin and rifampin. staphylococcus aureus is rampant and a widely distributed microorganism. it is one of the most important pathogens of nosocomial and community-acquired infections. staph aureus causes a wide variety of diseases. the first methicillin-resistant staph aureus (mrsa) was discovered by jevons in the united kingdom and it is now seen worldwide. the clinical and bacteriological properties of community-acquired methicillin-resistant staphylococcus aureus (ca-mrsa) are different from those of hospital-acquired mrsa [ ] . despite its increasing distribution, meningitis continues to be associated with serious and occasionally fatal outcomes. treatment is difficult because of the critical location of these infections and the blood-brain barrier, which limits the penetration of systemically administered antibiotics to the site of infection [ ] . this paper emphasizes the need for early recognition and interventions as soon as meningitis is suspected, while identifying a case where synergistic effects of antibiotics are utilized to improve the penetration of antibiotic therapy for adequate treatment. a -year-old female with a medical history that includes hypertension and asthma presented to the ed with gradual onset altered mental sensorium of two days duration. she further endorsed active intravenous heroin usage and the last dose was on the day of arrival to the hospital. the patient partially responded to narcan en route to the hospital. on presentation, the patient was noted to be alert and oriented to self only, she was afebrile with temperature of . f, pulse /min respiratory rate /min, blood pressure / mm hg and oxygen saturation of % on room air. cardiovascular respiratory and gastrointestinal systems were reported normal, no focality and signs of meningism was noticed on neurological examination. pertinent laboratory findings included wbc . k/ul, hemoglobin . g/d, platelets k/ul erythrocyte sedimentation rate > mm/hr, c-reactive protein mg/l, hiv-negative, drug screen was positive for cannabis and opiates and chest x-ray revealed diffuse reticulonodular interstitial thickening, compatible with endobronchial infection versus atypical infectious process. all other labs including renal profile, liver function test and computed tomography (ct) of head were entirely normal. the patient was admitted to the floor for acute encephalopathy secondary to opiate overdose versus septic encephalopathy due to possible pneumonia (covid vs community-acquired). she was started on broad-spectrum antibiotics (vancomycin . g/twice a day, cefepime g/thrice a day, doxycycline mg/twice a day) and intravenous fluids. the clinical course of the patient was complicated with the development of high-grade fever, hypoxia and worsening of mentation and she was transferred to the critical care unit. acyclovir and ampicillin were added to the current regimen with a suspicion of meningoencephalitis. the blood culture grew gram-positive cocci which later turned out to be mrsa and pneumonia workup (sars-cov, mycoplasma, legionella, and streptococcus) was negative. seven days into her illness, the patient became completely oriented and mental status has improved, but remained persistently bacteremic and febrile despite being on vancomycin therapy. the patient and the family continued to refuse lumbar puncture. the transesophageal echocardiography did not reveal any vegetations and the heart function was normal otherwise. after rigorous counselling, patient agreed for lumbar puncture ( days into her illness) and the results were confirmatory for bacterial meningitis with gram stain positive for gram-positive cocci and bacterial antigen for staphylococcus aureus (as seen in table ). infectious disease specialty was called on board and treatment failure was considered by cause of subtherapeutic levels of vancomycin, hence the patient was loaded with vancomycin g and then kept on . g/twice a day and rifampin mg/twice a day was added for a synergistic effect. all other antibiotics were discontinued. at this point, the patient developed lower back pain, flank pain and dysuria. ct abdomen and pelvis and urine analysis were consistent with acute pyelonephritis and the patient was started on ceftriaxone. the symptoms improved, but the back pain remained. magnetic resonance imaging of the lumbar spine (mri ls) revealed posterior epidural phlegmon at l - , causing severe spinal stenosis. l and l spinous process edema also noted with t signal loss with reference to osteomyelitis (as seen in figure ) . neurosurgery was taken on board and the patient underwent bilateral l -l lumbar laminectomy, removal of epidural abscess and granulation tissue with decompression of the nerve root. aerobic cultures were also sent which were negative, most likely due to the patient being on antibiotics for a prolonged duration. fifteen days into her illness, the patient had the first negative blood culture, remained afebrile and improved clinically. the patient was discharged to short-term rehabilitation to complete a total of six weeks of vancomycin and two weeks of rifampin. the patient was followed up at a six-week interval, she remained afebrile with persistently negative blood cultures, and she had regained her physical strength as well and was successfully discharged home. community-acquired bacterial meningitis in adults in developed countries is largely attributed to: streptococcus pneumoniae, neisseria meningitidis, and listeria monocytogenes (primarily in patients over years of age, or those who have deficiencies in cell-mediated immunity) [ ] . meningitis caused by staph aureus is extremely rare, with an annual incidence of %- % [ ] . of these cases, more than % are associated with a neurosurgical intervention where the bacteria are introduced during procedures. the rest are due to spontaneous or community-acquired meningitis, most likely due to infection outside of the central nervous system (cns). to our knowledge, epidemiological data for mrsa meningitis has not been widely reported because of its rarity. the classic triad of acute bacterial meningitis consists of fever, nuchal rigidity, and a change in mental status, which occurs in % of patients. the most common clinical features include a severe headache ( %), fever greater than °c ( %), stiff neck ( %), a glasgow coma scale < ( %), and nausea ( %) [ ] . the clinical and laboratory findings of bacterial meningitis overlap with those of meningitis caused by viruses, mycobacteria, fungi, or protozoa [ ] . differentiation of these pathogens from bacterial meningitis requires careful examination of cerebrospinal fluid (csf) parameters, neuroimaging, when indicated, as well as consideration of any epidemiologic factors that would raise the possibility of specific bacterial or nonbacterial cns infections. initial investigations of suspected meningitis should include blood tests including a complete blood count with differential and platelet count and two aerobic blood cultures of appropriate volume (ideally, prior to the initiation of antimicrobial therapy). empiric therapy of broadspectrum antibiotics should be started immediately, without waiting for the lab results. serum electrolytes and glucose, blood urea nitrogen, and creatinine concentrations are helpful in determining the csf-to-blood glucose ratio. coagulation studies are indicated, especially if petechial or purpuric lesions are noted. blood cultures are often positive and can be useful in the event that csf cannot be obtained before the administration of antimicrobials. approximately % to % of patients with bacterial meningitis have positive blood cultures [ ] . every patient with suspected meningitis should have csf obtained unless a lumbar puncture (lp) is contraindicated [ ] . a computed tomographic (ct) of head scan is sometimes performed before lp to exclude a mass lesion or increased intracranial pressure, which rarely leads to cerebral herniation during subsequent csf removal [ ] . however, a screening ct scan is not necessary in the majority of patients and should not delay the initiation of antibiotics. the antibiotics should be preferably started after the blood cultures are drawn. the exact management for mrsa meningitis infection is still unknown and there are no current established guidelines for treatment. given significant rates of mrsa, vancomycin ( to mg/kg iv every to hours depending on) should be used as initial therapy when s. aureus is suspected or proven. the exact duration of therapy is based on clinical response and is mostly administered for to days [ , ] . the infectious diseases society of america has recommended two weeks of vancomycin therapy for mrsa meningitis. the major limitation of vancomycin therapy is its poor penetration into csf estimated penetration of % and % with uninflamed and inflamed meninges, respectively [ ] . in our literature research, we found out that rifampin may be beneficial as it achieves bactericidal concentrations in the csf, regardless of meningeal inflammation, and can be used as a form of treatment. the recommended dose was mg orally or iv once daily or to mg twice daily [ , ] . we implemented our research findings on our patient with positive outcomes and can safely recommend that rifampin can be added to vancomycin for a combined synergistic effect. in our research, we ascertained, that based upon some case reports and case series of patients with mrsa meningitis, alternatives to vancomycin include linezolid ( mg iv twice daily) [ ] , tmp-smx ( mg/kg of the trimethoprim component iv every to hours) [ ] and daptomycin ( to mg/kg iv once daily) usually combined with rifampin [ ] . further studies are needed to establish the benefit of these agents for the treatment of meningitis. patients with persistent bacteremia should be reevaluated for adequate therapy and other sources of infection, as seen in this patient. after repeated positive blood cultures, we evaluated the therapy and made changes accordingly. also, we followed up with the physical exam findings to determine a source of infection. this investigation led us to conduct an mri of the spine which revealed an epidural abscess. suspected seeding of bacteria from abscess leads to bacteremia and meningitis. we addressed the abscess as a possible source of infection through surgical intervention and the antibiotics. our case emphasizes the importance of keeping a high index of suspicion for mrsa meningitis and disseminated infection in iv drug users. mrsa meningitis is very rare and can be easily missed. we must emphasize the importance of thorough physical examination and clinical evaluation, particularly in patients with persistent bacteremia to identify the source of bacteremia. bacteria can seed any organ, and the consequences can be lethal and devastating. good clinical acumen, timely diagnosis, initiation of effective therapy and interventions can be lifesaving. human subjects: all authors have confirmed that this study did not involve human participants or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. invasive community-acquired methicillinresistant staphylococcus aureus in a japanese girl with disseminating multiple organ infection: a case report and review of japanese pediatric cases. case rep pediatr penetration of drugs through the blood-cerebrospinal fluid/bloodbrain barrier for treatment of central nervous system infections global etiology of bacterial meningitis: a systematic review and meta-analysis molecular epidemiology of methicillin-resistant staphylococcus aureus bloodstream isolates in urban detroit community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing etiology of aseptic meningitis and encephalitis in an adult population adult bacterial meningitis: earlier treatment and improved outcome following guideline revision promoting prompt lumbar puncture practice guidelines for the management of bacterial clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant staphylococcus aureus infections in adults and children vancomycin disposition and penetration into ventricular fluid of the central nervous system following intravenous therapy in patients with cerebrospinal devices penetration of rifampicin into the cerebrospinal fluid of adults with uninflamed meninges glycopeptide insensitive staphylococcus aureus subdural empyema treated with linezolid and rifampicin successful treatment of methicillin-resistant staphylococcus aureus meningitis with daptomycin key: cord- - fu lk authors: cohen, joseph paul; dao, lan; roth, karsten; morrison, paul; bengio, yoshua; abbasi, almas f; shen, beiyi; mahsa, hoshmand kochi; ghassemi, marzyeh; li, haifang; duong, tim title: predicting covid- pneumonia severity on chest x-ray with deep learning date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: fu lk introduction the need to streamline patient management for coronavirus disease- (covid- ) has become more pressing than ever. chest x-rays (cxrs) provide a non-invasive (potentially bedside) tool to monitor the progression of the disease. in this study, we present a severity score prediction model for covid- pneumonia for frontal chest x-ray images. such a tool can gauge the severity of covid- lung infections (and pneumonia in general) that can be used for escalation or de-escalation of care as well as monitoring treatment efficacy, especially in the icu. methods images from a public covid- database were scored retrospectively by three blinded experts in terms of the extent of lung involvement as well as the degree of opacity. a neural network model that was pre-trained on large (non-covid- ) chest x-ray datasets is used to construct features for covid- images which are predictive for our task. results this study finds that training a regression model on a subset of the outputs from this pre-trained chest x-ray model predicts our geographic extent score (range - ) with . mean absolute error (mae) and our lung opacity score (range - ) with . mae. conclusions these results indicate that our model’s ability to gauge the severity of covid- lung infections could be used for escalation or de-escalation of care as well as monitoring treatment efficacy, especially in the icu. to enable follow up work, we make our code, labels, and data available online. as the first countries explore deconfinement strategies [ ] , the death toll of coronavirus disease- (covid- ) keeps rising [ ] . the increased strain caused by the pandemic on healthcare systems worldwide has prompted many physicians to resort to new strategies and technologies. chest x-rays (cxrs) provide a non-invasive (potentially bedside) tool to monitor the progression of the disease [ , ] . as early as march , chinese hospitals used artificial intelligence (ai)-assisted computed tomography (ct) imaging analysis to screen covid- cases and streamline diagnosis [ ] . many teams have since launched ai initiatives to improve triaging of covid- patients (i.e., discharge, general admission, or icu care) and allocation of hospital resources (i.e., direct non-invasive ventilation to invasive ventilation) [ ] . while these recent tools exploit clinical data, practically deployable cxr-based predictive models remain lacking. in this work, we built and studied a model which predicts the severity of covid- pneumonia, based on cxrs, to be used as an assistive tool when managing patient care. the ability to gauge the severity of covid- lung infections can be used for escalation or de-escalation of care, especially in the icu. an automated tool can be applied to patients over time to objectively and quantitatively track disease progression and treatment response. we used a retrospective cohort of posteroanterior (pa) cxr images from a public covid- image data collection [ ] . while the dataset currently contains images, it only counted images at the time of the experiment, all of which were included in the study. all patients were reported as covid- positive by their physicians (most using rt-pcr) and sourced from many hospitals around the world from december to march . the images were de-identified prior to our use and there was no missing data. the ratio between male/female was / with an average age of ± . ( ± . for male and ± . for female). radiological scoring was performed by three blinded experts: two chest radiologists (each with at least years of experience) and a radiology resident. they staged disease severity using a score system [ ] , based on two types of scores (parameters): extent of lung involvement and degree of opacity. they were only presented with a single cxr image at a time without any clinical context of the patient. . the extent of lung involvement by ground glass opacity or consolidation for each lung (right lung and left lung separately) was scored as: = no involvement; = < % involvement; = %- % involvement; = %- % involvement; = > % involvement. the total extent score ranged from to (right lung and left lung together). . the degree of opacity for each lung (right lung and left lung separately) was scored as: = no opacity; = ground glass opacity; = consolidation; = white-out. the total opacity score ranged from to (right lung and left lung together). a spreadsheet was maintained to pair filenames with their respective scores. fleiss' kappa for inter-rater agreement was . for the opacity score and . for the extent score. -radiological society of north america (rsna) pneumonia detection challenge [ ] ; -chexpert dataset from stanford university [ ] ; -chestx-ray dataset from the national institute of health (nih) [ ] ; -chestx-ray dataset from the nih with labels from google [ ] ; -mimic-cxr dataset from massachusetts institute of technology (mit) [ ] ; -padchest dataset from the university of alicante [ ] ; -openi [ ] these seven datasets were manually aligned to each other on common radiological finding tasks in order to train a model using all datasets at once (atelectasis, consolidation, infiltration, pneumothorax, edema, emphysema, fibrosis, fibrosis, effusion, pneumonia, pleural thickening, cardiomegaly, nodule, mass, hernia, lung lesion, fracture, lung opacity, and enlarged cardiomediastinum). for example "pleural effusion" from one dataset is considered the same as "effusion" from another dataset in order to consider these labels equal. in total, , non-covid- images were used to train the model on these tasks. in this study, we used a densenet model [ ] from the torchxrayvision library [ , ] . densenet models have been shown to predict pneumonia well [ ] . images were resized to x pixels, utilizing a center crop if the aspect ratio was uneven, and the pixel values were scaled to (- , ) for the training. before even processing the covid- images, a pre-training step was performed using the seven datasets to train feature extraction layers and a task prediction layer ( figure ). this "pre-training" step was performed on a large set of data in order to construct general representations about lungs and other aspects of cxrs that we would have been unable to achieve on the small set of covid- images available. some of these representations are expected to be relevant to our downstream tasks. there are a few ways we can extract useful features from the pre-trained model as detailed in figure . the two dataset blocks show that covid- images were not used to train the neural network. the network diagram is split into three sections. the feature extraction layers are convolutional layers which transform the image into a dimensional vector which is called the intermediate network features. these features are then transformed using the task prediction layer (a sigmoid function for each task) into the outputs for each task. the different groupings of outputs used in this work are shown. similarly to the images from non-covid- datasets used for pre-training, each image from the covid- dataset was preprocessed (resized, center cropped, rescaled), then processed by the feature extraction layers and the task prediction layer of the network. the network was trained on existing datasets before the weights were frozen. covid- images were processed by the network to generate features used in place of the images. as was the case with images from the seven non-covid- datasets, the feature extraction layers produced a representation of the covid- images using a dimensional vector, then the fully connected task prediction layer produced outputs for each of the original tasks. we build models on the pre-sigmoid outputs. linear regression was performed to predict the aforementioned scores (extent of lung involvement and opacity) using these different sets of features in place of the image itself: -intermediate network features -the result of the convolutional layers applied to the image resulting in a dimensional vector which is passed to the task prediction layer; - outputs -each image was represented by the outputs (pre-sigmoid) from the pre-trained model; -four outputs -a hand picked subset of outputs (pre-sigmoid) were used containing radiological findings more frequent in pneumonia (lung opacity, pneumonia, infiltration, and consolidation); -lung opacity output -the single output (pre-sigmoid) for lung opacity was used because it was very related to this task. this feature was different from the opacity score that we would like to predict. for each experiment performed, the images covid- dataset was randomly split into a train and test set roughly / . multiple timepoints from the same patient were grouped together into the same split so that a patient did not span both sets. sampling was repeated throughout training in order to obtain a mean and standard deviation for each performance. as linear regression was used, there was no early stopping that had to be done to prevent the model from overfitting. therefore, the criterion for determining the final model was only the mean squared error (mse) on the training set. in order to ensure that the models are looking at reasonable aspects of the images [ ] [ ] [ ] , a saliency map is computed by computing the gradient of the output prediction with respect to the input image (if a pixel is changed, how much will it change the prediction). in order to smooth out the saliency map, it is blurred using a x gaussian kernel. keep in mind that these saliency maps have limitations and only offer a restricted view into why a model made a prediction [ , ] . the single "lung opacity" output as a feature yielded the best correlation ( . ), followed by four outputs (lung opacity, pneumonia, infiltration, and consolidation) parameters ( . ) ( table ). building a model on only a few outputs provides the best performance. the mean absolute error (mae) is useful to understand the error in units of the scores that are predicted while the mse helps to rank the different methods based on their furthest outliers. one possible reason that fewer features work best is that having fewer parameters prevents overfitting. some features could serve as proxy variables to confounding attributes such as sex or age and preventing these features from being used prevents the distraction from hurting generalization performance. hand selecting feature subsets which are intuitively related to this task imparts domain knowledge as a bias on the model which improves performance. thus, the top performing model (using the single "lung opacity" output as a feature) is used for the subsequent qualitative analysis. figure shows the top performing model's (using the single "lung opacity" output as a feature) predictions against the ground truth score (given by the blinded experts) on held out test data. majority of the data points fall close to the line of unity. the model overestimates scores between and and underestimates scores above . however, generally the predictions seem reasonable given the agreement of the raters. evaluation is on a hold out test set. the grey dashed line is a perfect prediction. red lines indicate error from a perfect prediction. r : coefficient of determination. in figure , we explore what the representation used by one of the best models looks at in order to identify signs of overfitting and to gain insights into the variation of the data. a t-distributed stochastic neighbor embedding (t-sne) [ ] is computed on all data (even those not scored) in order to project the features into a two-dimensional ( d) space. each cxr is represented by a point in a space where relationships to other points are preserved from the higher dimensional space. the cases of the survival group tend to cluster together as well as the cases of the deceased group. this clustering indicates that score predictions align with clinical outcomes. a spatial representation of pneumonia specific features (lung opacity, pneumonia, infiltration, and consolidation) when projected into dimensions ( d) using a t-distributed stochastic neighbor embedding (t-sne). in this d space, the high dimensional ( d) distances are preserved, specifically what is nearby. cxr images which have similar outputs are close to each other. features are extracted for all images in the dataset and the geographic extent prediction is shown for each image. the survival information available in the dataset represented by the shape of the marker. in figure , images are studied which were not seen by the model during training. for most of the results, the model is correctly looking at opaque regions of the lungs. figure b shows no signs of opacity and the model is focused on the heart and diaphragm, which is likely a sign that they are used as a color reference when determining what qualifies as opaque. in figure c and figure d , we see erroneous predictions. examples of correct (a,b) and incorrect (c,d) predictions by the model are shown with a saliency map generated by computing the gradient of the output prediction with respect to the input image and then blurred using a x gaussian kernel. the assigned and predicted scores for geographic extent are shown to the right. in the context of a pandemic and the urgency to contain the crisis, research has increased exponentially in order to alleviate the healthcare system's burden. however, many prediction models for diagnosis and prognosis of covid- infection are at high risk of bias and model overfitting as well as poorly reported, their alleged performance being likely optimistic [ ] . in order to prevent premature implementation in hospitals [ ] , tools must be robustly evaluated along several practical axes [ , ] . indeed, while some ai-assisted tools might be powerful, they do not replace clinical judgment and their diagnostic performance cannot be assessed or claimed without a proper clinical trial [ ] . existing work focuses on predicting severity from a variety of clinical indicators which include findings from chest imaging [ ] . models such as the one presented in this work can complement and improve triage decisions from cxr as opposed to ct [ ] . challenges in creating a predictive model involve labelling the data and achieving good interrater agreement as well as learning a representation which will generalize to new images when the number of labelled images is so low. in the case of building a predictive tool for covid- cxr images, the lack of a public database made it difficult to conduct large-scale robust evaluations. this small number of samples prevents proper cohort selection which is a limitation of this study and exposes our evaluation to sample bias. however, we use a model which was trained on a large dataset with related tasks which provided us with a robust unbiased covid- feature extractor and allows us to learn only two parameters for our best linear regression model. restricting the complexity of the learned model in this way reduces the possibility of overfitting. our evaluation could be improved if we were able to obtain new cohorts labelled with the same severity score to ascertain the generalization of our model. also, it is unknown if these radiographic scores of disease severity reflect actual functional or clinical outcomes as the open data do not have those data. we make the images, labels, model, and code public from this work so that other groups can perform follow-up evaluations. our model's ability to gauge the severity of covid- lung infections could be used for escalation or de-escalation of care as well as monitoring treatment efficacy, especially in the icu. the use of a score combining geographical extent and degree of opacity allows clinicians to compare cxr images with each other using a quantitative and objective measure. also, this can be done at scale for a large scale analysis. human subjects: consent was obtained by all participants in this study. comité d'éthique de la recherche en sciences et en santé (cerses) issued approval #cerses- - -d. data was collected from existing public sources such as research papers and online radiology sharing platforms. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: this research is based on work partially supported by the cifar ai and covid- catalyst grants. this funding does not pose a conflict of interest. it is funding for open academic research with no expected result or intellectual property expectations. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. children in spain allowed to play outdoors as country eases covid- lockdown records more than , coronavirus deaths in one day, global death toll reaches , chest radiographic and ct findings of the novel coronavirus disease (covid- ): analysis of nine patients treated in korea imaging profile of the covid- infection: radiologic findings and literature review a rapid advice 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examinations for distribution and retrieval torchxrayvision: a library of chest x-ray datasets and models on the limits of cross-domain generalization in automated x-ray prediction chexnet: radiologist-level pneumonia detection on chest x-rays with deep learning neural smithing: supervised learning in feedforward artificial neural networks. a variable generalization performance of a deep learning model to detect pneumonia in chest radiographs: a crosssectional study underwhelming generalization improvements from controlling feature attribution right for the right reasons: training differentiable models by constraining their explanations visualizing data using t-sne prediction models for diagnosis and prognosis of covid- infection: systematic review and critical appraisal hospitals are using ai to predict the decline of covid- patients -before knowing it works practical guidance on artificial intelligence for health-care data artificial intelligence versus clinicians: systematic review of design, reporting standards, and claims of deep learning studies clinical and chest radiography features determine patient outcomes in young and middle age adults with covid- the role of chest imaging in patient management during the covid- pandemic: a multinational consensus statement from the fleischner society this research is based on work partially supported by the cifar ai and covid- catalyst grants. this work utilized the supercomputing facilities managed by compute canada and calcul quebec. key: cord- -pzv dzow authors: massaad, elie; cherfan, patrick title: social media data analytics on telehealth during the covid- pandemic date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: pzv dzow introduction: physical distancing during the coronavirus covid- pandemic has brought telehealth to the forefront to keep up with patient care amidst an international crisis that is exhausting healthcare resources. understanding and managing health-related concerns resulting from physical distancing measures are of utmost importance. objectives: to describe and analyze the volume, content, and geospatial distribution of tweets associated with telehealth during the covid- pandemic. methods: we inquired twitter public data to access tweets related to telehealth from march , to april , . we analyzed tweets using natural language processing (nlp) and unsupervised learning methods. clustering analysis was performed to classify tweets. geographic tweet distribution was correlated with covid- confirmed cases in the united states. all analyses were carried on the google cloud computing service “google colab” using python libraries (python software foundation). results: a total of , tweets containing the term “telehealth” were retrieved. the most common terms appearing alongside ‘telehealth’ were “covid”, “health”, “care”, “services”, “patients”, and “pandemic”. mental health was the most common health-related topic that appeared in our search reflecting a high need for mental healthcare during the pandemic. similarly, medicare was the most common appearing health plan mirroring the accelerated access to telehealth and change in coverage policies. the geographic distribution of tweets related to telehealth and having a specific location within the united states (n= , ) was significantly associated with the number of confirmed covid- cases reported in each state (p< . ). conclusion: social media activity is an accurate reflection of disease burden during the covid- pandemic. widespread adoption of telehealth-favoring policies is necessary and mostly needed to address mental health problems that may arise in areas of high infection and death rates. the novel coronavirus outbreak that started in wuhan, china entered a new phase after the world health organization (who) officially declared it as a global pandemic on march , [ ] . this called out for urgent changes in the medical sector after presuming hospital- associated transmission in nearly % of infected health professionals and % of hospitalized patients [ ] . telehealth rapidly became a necessary technology to guarantee continuity of care amidst worldwide physical distancing policies, by allowing patients to receive medical care while minimizing the risk of exposure -a critical concern for the elderly and those with chronic conditions [ ] . as the pandemic remains ongoing, urgent action is required to support the digital transformation in healthcare and to understand the various concerns of patients needing care during this crisis [ ] . healthcare workers, patients, institutions, technology industries, and policymakers turned to social media to embrace this rapid shift in healthcare delivery. twitter (twitter, inc., san francisco, ca) has been considered among the best social media platforms for keeping its users on top of the most trending topics and in understanding consumers' opinions on health technology matters [ ] . for this reason, we planned to explore the data available on social media to better characterize the surge in telehealth during the covid- pandemic. our study aims to analyze the dynamics of social media data related to telehealth and understand the public activity to strategically optimize and accelerate the digital health transformation. this cross-sectional study was conducted from march , to april , . this study was exempted from the institutional review board at harvard medical school because the data used are publicly available. in this instance, a consent form was not necessary. this study followed the strengthening the reporting of observational studies in epidemiology (strobe) reporting guidelines. twitter is an online public social media platform that allows users to post -character posts. publicly posted "tweets" from march , to april , , were collected through the public streaming api (application programming interface). full-text tweets were preprocessed by converting the sentences to words (tokenization), removing unnecessary punctuations, tags, and stop words that do not have a specific semantic meaning (i.e. "the", "are"). we applied a stemming function with lexicon normalization to reduce related words to a common word root (i.e. connection, connected, connecting were reduced to "connect"). we isolated tweets with an identifiable location within the united states and constructed a density map. preprocessing was done using the natural language toolkit (nltk) on python . [ ] . descriptive analytics were performed to study the data collected. tweet characteristics included account median number and range of followers. generalized linear regression was performed to study the association between "telehealth" tweets and the number of confirmed covid- infections. statistical significance was set at p< . . unsupervised learning was performed using k-means clustering algorithms to classify tweets into topics. we used the elbow method to define the number of k dimensions where k depends on the number of topics. all data preprocessing, analysis, and visualization were performed on the google cloud computing service "google colab" (colab.research.google.com) using python . programming language (python software foundation; http://www.python.org). our search revealed that the word "telehealth" appeared in , posts on twitter from march , to april , . the retrieved twitter accounts had a median number of followers of (range - ). every post containing the word "telehealth" was retweeted with a median number of two times (range - ). the most common words apart from "telehealth" that appeared in these tweets were "covid", "health", "care", "services", "patients", "pandemic", "coronavirus", "healthcare", "access", "need". mental health was the most common health-related topic that appeared in our search. similarly, medicare was the most common appearing health policy-related topic mirroring the accelerated response to telehealth and the changes in coverage policies. unsupervised machine learning classification of tweets identified six clusters of tweets that contained words mostly related to: ( ) mental health services, ( ) digital health, ( ) policies and advocacies, ( ) hydroxychloroquine, ( ) technology, and ( ) general opinions. in the united states, our analysis showed that tweets were most commonly posted from our analysis revealed an association between the number of tweets related to telehealth posted in a certain state and the number of confirmed covid- cases in that particular state (p< . ) ( figure ). this variable distribution can also be visualized by comparing the density map with the number of tweets to that with the number of confirmed covid- cases in each state. social media platforms have proven to be very engaging with the public [ ] . data analysis of social media content has provided insight into political campaigns, media, healthcare, and daily events [ ] . in this study, we retrieved and analyzed public data available on twitter to investigate the rapid shift in telehealth adoption amidst the recent coronavirus covid- pandemics. our results highlighted the need for widespread implementation of digital health and the importance of favoring policy changes to unleash the power of this technology. interestingly, the number of tweets related to telehealth was associated with the number of covid- cases in each of the u.s. states. moreover, mental health appeared to be the most common health-related issue discussed online. this may refer to the significant effects on mental health in areas of high disease burden [ ] . in fact, efforts to implement telehealth were rapidly mobilized across the united states on many levels. healthcare plans and agencies provided regulatory relief and reimbursement policies to provide telehealth services during this public health emergency [ ] . major medicare and medicaid telehealth policy updates in the states with the highest reported coronavirus positive cases are summarized ( table ) . physical distancing and shelter-in-place orders are likely to result in considerable psychological distress, which prompts healthcare providers and organizations to ensure and sustain a pandemic workforce that addresses crisis-related health problems [ ] . new york -reimbursement for live video -some reimbursement for store-and-forward and home health services telehealth services have rapidly and largely transformed healthcare delivery in areas of high infection rates. in parallel, social media platforms became an immense source of information on day-to-day events and a reflection of social interactions and responses. in this study, we showed that such platforms can be used to assess the needs of our communities and to embrace the healthcare response, resilience, and preparedness during pandemics. nationwide efforts should focus on lifting provisions and scaling up resources to expand digital health implementation to address crisis-related sequelae. human subjects: all authors have confirmed that this study did not involve human participants or tissue. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. estimating clinical severity of covid- from the transmission dynamics in wuhan, china detection of sars-cov- in different types of clinical specimens covid- and healthcare's digital revolution digital mental health and covid- : using technology today to accelerate the curve on access and quality tomorrow twitter as a tool for health research: a systematic review natural language processing with python: analyzing text with the natural language toolkit heatmaply: an r package for creating interactive cluster heatmaps for online publishing social media and emergency preparedness in response to novel coronavirus us public concerns about the covid- pandemic from results of a survey given via social media addressing the covid- pandemic in populations with serious mental illness securing the safety net and protecting public health during a pandemic: medicaid's response to covid- ensuring and sustaining a pandemic workforce key: cord- -kcbxyhhh authors: eketunde, adenike o; mellacheruvu, sai priyanka; oreoluwa, philip title: a review of postmortem findings in patients with covid- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: kcbxyhhh multiple public health problems have been caused by various coronavirus strains over the last few years, such as the middle eastern respiratory syndrome (mers), severe acute respiratory syndrome (sars), and covid- . covid- , which is also known as coronavirus disease , was first detected in wuhan, china, and has significantly impacted people's health and lives. additionally, it has led to a pandemic, and the virus has spread to over countries worldwide. there is numerous information available regarding this virus. a detailed and extensive study of the morphological and histopathological findings will help understand and diagnose the disease. as it is a new disease, it is challenging to understand the mechanism of the action and disease pathology due to the limited availability of data from autopsies or biopsies. however, as the detailed mechanism of injury remains unclear, this paper aims to review the postmortem gross and histopathological findings of various organs that have been affected with coronavirus, focusing on the pulmonary, cardiac, and hematologic findings. this paper emphasizes the postmortem findings of the effect of the coronavirus disease on multiple organ systems. advance search of the keywords on pubmed was used, limiting the search to the last five years. the eligible article is narrowed based on relevance containing postmortem findings of the novel virus; covid- . a total of full-text articles were selected and used in the review of this paper. covid- is a pandemic that has affected a large percentage of the world's population. the total number of covid- cases worldwide as of july , , is over . million, which has led to over , deaths [ ] . these numbers are still rising. the severe acute respiratory syndrome coronavirus (sars-cov- ) virus originated in wuhan, china, and has spread rapidly across the world. people around the globe are following strict measures to contain the virus, and there is ongoing research into treatment for this fatal virus. the respiratory and immune systems are most affected by coronavirus strains. covid- is a novel coronavirus that has ribonucleic acid (rna) as nuclear material. it was declared a pandemic by the world health organization on march , [ ] . the sars-cov- virus has a similar genomic sequence, clinical manifestations, and biological behavior to sars-cov [ ] . the four major structural proteins are as follows: the spike surface glycoprotein, small envelope protein, matrix protein, and nucleocapsid protein. the spike protein binds to the host receptors via the receptor-binding domains of the angiotensin-converting enzyme (ace ) [ ] . the ace protein is also present in various human organs, including the respiratory system, gastrointestinal tract, liver, kidney, spleen, lymph nodes, bone marrow, and brain [ ] . sars-cov- is believed to be more virulent than sars-cov, as the virus affects various organ systems in the human body [ ] . our study provides a review of the postmortem findings of the above-mentioned organs (see the appendix), which will significantly improve the current understanding of the disease. there is a wide range of clinical spectrums of covid- , which ranges from the asymptomatic or paucisymptomatic forms to the conditions that are characterized by respiratory failure, which requires mechanical ventilation and admission to the intensive care unit. very severe cases can lead to multi-organ dysfunction syndrome (mods), which can result in sepsis or shock. the clinical manifestations have been divided into the following three categories based on the severity: this is an uncomplicated or mild illness. individuals show mild symptoms, such as a mild fever, dry cough, sore throat, nasal congestion, malaise, headache, or myalgias. this comprises % of the total cases, while some patients with moderate disease present with respiratory symptoms such as cough, shortness of breath, and tachypnea. no signs and symptoms of severe disease are present [ ] . this occurs in % of cases. the symptoms in these patients range from dyspnea, a respiratory rate of > , and a blood oxygen saturation of less than % [ ] . they present with severe pneumonia, acute respiratory distress syndrome, or sepsis. even in severe forms of disease fever can be moderate or absent [ ] . these patients present with respiratory failure, cardiac injury, septic shock, and/or mods, or multi-organ failure (mof). this comprises % of the total cases [ ] . the individuals who develop symptoms and/or are exposed to the virus are tested for covid- . a nasal swab is collected as a sample. during the analytic stage, real-time reverse transcription polymerase chain reaction (rt-pcr) is the molecular test of choice for the diagnosis of sars-cov- infections, whereas antibody-based tests were introduced as a supplemental tool. post-analytically, the results should be interpreted carefully with the help of both the molecular and serological findings [ ] . people across the world are practicing social and physical distancing to control the spread of this fatal virus. those who have been exposed to someone who is infected with the disease must be quarantined, and those who test positive and develop symptoms must isolate for days. according to a study conducted in china, the median incubation period for covid- was estimated to be . days with a % confidence interval with a range of . to . days. approximately . % of those who will develop symptoms will do so within . days with % ci, with a range of . to . days [ ] . the causes of death from covid- range from acute respiratory distress syndrome ( ; %), type i respiratory failure ( / ; %), sepsis ( ; %), acute cardiac injury ( / ; %), heart failure ( / ; %), alkalosis ( / ; %), hyperkalemia ( ; %), acute kidney injury ( ; %), and hypoxic encephalopathy ( ; %) [ ] . several studies have demonstrated how the covid- hyperinflammatory response is one of the primary causes of death that affects the heart vessels, liver, kidney, and other organs. macrophages are the major cells that are activated in response to an injury by supporting and activating the stem/progenitor cells, clearing the damaged tissue, remodeling the extracellular matrix to prepare the scaffolding for regeneration, and promoting angiogenesis [ ] [ ] [ ] . the bronchoalveolar fluid in patients with severe covid- has shown a large quantity of chemokine from the macrophages; this was also evident in the immunostaining of postmortem tissue from a covid- patient. the cd + lymph node, subcapsular, and splenic marginal zone macrophages expressed the sars-cov- entry receptor ace . they showed that these macrophages contained the sars-cov- nucleoprotein (np), although the small conditional rna (scrna)-seq analysis of human tissue failed to identify an ace expression on most tissue-resident macrophages [ ] . according to merad and martin's study, the hyper inflammation in severe covid- patients shared similarities with cytokine release syndromes, including macrophages activation syndrome. this leads to an increase in the production of cytokines, such as interleukin (il)- , il- and tumor necrosis factor (tnf), as well as inflammatory chemokines, including cc-chemokine ligand (ccl ), ccl and cxc-chemokine ligand (cxcl ), and the soluble form of the α-chain of the il- receptor. this then leads to the hypothesis of the dysregulated activation of the mononuclear phagocyte (mnp) compartment and contributes to the covid- -associated hyperinflammation [ ] . minimally invasive autopsies of three covid- patients in chongqing, china revealed damage to the alveolar structure with minor serous and fibrin exudation and hyaline membrane formation [ ] . the cells that were identified in the alveolar structure were mainly macrophages and monocytes. the other cells that were identified included multinucleated giant cells, lymphocytes, eosinophils, and neutrophils. the blood vessels of the alveolar septum were congested and edematous with monocyte and lymphocyte infiltration, mainly macrophages and monocytes [ ] . the findings show that the coronavirus particles in the bronchial epithelia and type ii alveolar epithelia and immunohistochemical staining were positive for the -ncov antigen, and the pcr analysis was positive for -ncov nucleic acid. the findings from the other organs showed degeneration and necrosis of the parenchyma cells and hyaline thrombus formation in the small blood vessels; however, there was no evidence of coronavirus infection in the cells [ ] . covid- has a % incidence of deep venous thrombosis, of which % of patients had pulmonary embolism as a direct cause of death [ ] . another autopsy of an -year-old woman in china who died of covid- , which took place five hours after her death, showed diffuse alveolar damage with a prominent hyaline membrane and inflammatory cells with prominent plasma cells in the alveolar septa. other observations included an interalveolar hemorrhage, vascular congestion, hyperplasia of type pneumocytes, and phagocytosis in the lungs, spleen, and lymph nodes. the glomeruli of both kidneys were marked by microthrombi, which suggests early signs of disseminated intravascular coagulation [ ] . like other viruses, coronavirus is associated with cardiomyopathy and myocarditis. infected patients may develop lymphocytic, eosinophilic, or giant cell/granulomatous myocardial inflammation, which results in infectious dilated cardiomyopathy [ ] . the myocardial damage from covid- that led to the death is about % and contributed to death in % of patients [ ] . an autopsy of a patient that died of covid- showed pericardial effusion. the macroscopic finding was described as "gray, red, fish-like," and microscopically showed diffuse inflammatory infiltrates that were composed of lymphocytes and macrophages with prominent eosinophils, which confirmed inflammation. the findings showed primary inflammation of the interstitium, which is associated with multiple foci of myocyte necrosis. it was present in both the right and left ventricles without vascular inflammation or fibrinoid necrosis, which was not angiocentric, granulomatous, or associated with vasculitis [ ] . the gross findings from the heart of a covid- patient showed cardiomegaly with right and left ventricular dilatation. the microscopy showed scattered individual cell myocyte necrosis and did not identify a significant lymphocytic inflammatory infiltrate, which is suggestive of viral myocarditis. this is a mechanism that is described by chen et al. and states that the pericytes might be infected with sars-cov- and cause capillary endothelial cell or microvascular dysfunction, which could cause individual cell necrosis [ , ] . a study that was performed in brazil showed fibrin thrombi in the alveolar arterioles of % of patients with covid- . this is evidence of the hypercoagulable state in severely ill patients, which leads to a ventilation-perfusion mismatch in the lungs and a peripheral ischemic event [ ] . the hypercoagulable state has been linked to a poor prognosis in patients with severe covid- , which leads to a microthrombi formation in the lungs, lower limbs, hands, brain, heart, liver, and kidneys, as a result of the activation of the coagulation pathway. this is mediated by the inflammatory cytokine, which can be explained by the hyperinflammation that is caused by covid- , as mentioned above [ ] [ ] . the hypercoagulable states can also explain the other findings, including those from the brain. a neuropathological finding from a patient who died of covid- complications revealed features of vascular and demyelinating etiologies. the neuropathological findings in this patient showed hemorrhagic white matter lesions throughout the cerebral hemisphere with a surrounding axonal injury, as well as macrophages. the subcortical white matter of the brain had clusters of macrophages, a range of associated axonal injuries, a perivascular acute disseminated encephalomyelitis (adem)-like appearance, and focal microscopic areas of necrosis with a central loss of white matter and marked axonal injury [ ] . autopsy reports of patients from hospital graz ii, austria, which is the second-largest public and academic teaching hospital in austria, showed thrombosis of the small-sized and midsized pulmonary artery at different stages in all patients, bronchopneumonia in six patients, and hepatic congestion in eight patients. the other findings in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, along with central vein thrombosis. other common findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of the spleen and lymph nodes [ ] . although it was not a common feature, there were also findings of direct renal infection with the presence of viral particles that were morphologically identical to sars-cov- . additionally, the identification of the tubular isometric vacuolization using light microscopy correlated with the double-membrane vesicles that contained vacuoles, which were observed using electronic microscopy [ ] . in another autopsy that was performed by the university medical center hamburg-eppendorf on patients, four deaths were identified as a direct cause of a pulmonary embolism, which arose from the deep veins of the lower extremities. the autopsy revealed deep vein thrombosis in seven out of patients, where thromboembolism had not been suspected at the time of death [ ] . the kidney can also be damaged with marked microthrombi of the glomerulus, which can be a sign of disseminated intravascular coagulation [ ] . the hematologic dysfunction can be explained by the virus-induced procoagulant and coagulopathy, virus invasion, and damage of the lymphocytes. this resulted in lymphopenia, which is the depletion of white pulp that leads to a predisposition to deep vein thrombosis and pulmonary thromboembolism [ ] . extrapulmonary findings from certain comorbidities, such as diabetes and hypertension, are related to septic shock, and other changes, including superficial perivascular dermatitis, orchitis, myositis, myocarditis, alteration in the renal glomeruli, and endothelium of small vessels and cerebral cortex, are related to the covid- virus [ ] . the most common postmortem findings were the pulmonary findings, which included diffuse alveolar damage in almost all cases. other pulmonary findings, including acute respiratory distress syndrome and tissue from the lungs, were usually positive for the -ncov antigen. the other significant extrapulmonary findings require further research, as understanding the pathological findings will be helpful for the treatment plans, including the use of anticoagulants in patients in hypercoagulable states. there is a strong association with the hyperinflammatory state, which can be explained by most of the signs and symptoms that are exhibited by covid- patients, including most of the pathological findings. who director-general's opening remarks at the media briefing on covid- pathological study of the novel coronavirus disease (covid- ) through postmortem core biopsies crystal structure of the -ncov spike receptor-binding domain bound with the ace receptor (preprint). biorxiv. coronavirus (covid- ): a review of clinical features, diagnosis, and treatment the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application clinical characteristics of deceased patients with coronavirus disease : retrospective study a pathological report of three covid- cases by minimally invasive autopsies (article in chinese) pathological inflammation in patients with covid- : a key role for monocytes and macrophages immunosuppression for hyperinflammation in covid- : a double-edged sword? macrophages in inflammation, repair and regeneration autopsy findings and venous thromboembolism in patients with covid- pulmonary and systemic involvement of covid- assessed by ultrasound-guided minimally invasive autopsy rose nr: viral myocarditis clinical predictors of mortality due to covid- based on an analysis of data of patients from wuhan, china fatal eosinophilic myocarditis in a healthy -year-old male with severe acute respiratory syndrome coronavirus (sars-cov- c) pulmonary and cardiac pathology in african american patients with covid- : an autopsy series from new orleans the ace expression in human heart indicates new potential mechanism of heart injury among patients infected with sars-cov- acute respiratory distress syndrome as an organ phenotype of vascular microthrombotic disease: based on hemostatic theory and endothelial molecular pathogenesis neuropathology of covid- : a spectrum of vascular and acute disseminated encephalomyelitis (adem)-like pathology pulmonary arterial thrombosis in covid- with fatal outcome: results from a prospective, single-center ultrastructural evidence for direct renal infection with sars-cov- clinicopathologic and immunohistochemical findings from autopsy of patient with covid- the emerging spectrum of cardiopulmonary pathology of the coronavirus disease (covid- ): report of autopsies from houston, texas, and review of autopsy findings from other united states cities in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -fo i jow authors: dalal, nimit; athwal, pal satyajit singh; tharu, biswaraj; shah, parth; shah, love title: legionnaires disease presenting as diarrhea: a case report date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: fo i jow legionnaires disease is primarily a pneumonic illness with possible multisystem involvement. major risk factors include immunodeficiency, smoking, alcoholism and chronic obstructive pulmonary disease among others. we report a peculiar case of legionnaires disease presenting with diarrhea as the chief complaint and no respiratory symptoms throughout the course of disease. the patient had no risk factors for the disease and had no recent travel history or sick contacts. acute diarrhea is not an uncommon manifestation of legionnaires disease, although isolated diarrhea symptoms with the absence of concurrent respiratory symptoms and no risk factors for legionella makes this case a diagnostic challenge, leading to possible delay in appropriate management. we are presenting this case to inform physicians of the possibility of legionnaires disease presenting as an isolated gastrointestinal involvement with no clinical symptoms of pneumonia at presentation. legionella pneumophila is gram negative bacteria known for legionnaires disease and pontiac fever. legionella is responsible for - % of community acquired pneumonia and can lead to multiorgan involvement with very high mortality without antibiotic therapy [ ] . in , members of american legion got infected from a point source in the hotel they were staying in and this incident framed the nomenclature of this bacterium [ ] . transmission is through breathing mist containing bacteria from a contaminated source. it presents mainly with respiratory symptoms like cough, shortness of breath, fever and myalgia following few days of exposure. isolated gastrointestinal symptoms are very rare and can lead to missed diagnosis. diagnosis is established based on sputum culture and urine antigen. treatment is based on antibiotics and supportive therapy. we report a case of legionnaires disease with isolated gastrointestinal symptoms which can lead to a missed diagnosis and development of complications without treatment. a -year-old female with past medical history of asthma, hypertension, hypothyroidism and chronic back pain presented to the ed with chief complaint of watery diarrhea and fever for four days. she denied any blood or mucus in stool. she was severely dehydrated. she also reported loss of appetite. she denied nausea, vomiting, chills, shortness of breath, cough and abdominal pain. the maximum recorded temperature at home was °f. on examination in the ed, her temperature was . °f, heart rate bpm, blood pressure / mmhg, respiratory rate of , o saturation was . respiratory examination and abdominal examination was normal. her labs on admission are shown in table . she was initially treated with iv fluids for suspected gastroenteritis. stool sample was negative for culture, gram staining, microscopy for ova/parasites, and occult blood. chest ct and chest x-ray done on the same day as per routine hospital protocol showed enlarged hilar lymph nodes with right lower lobe infiltrates and air bronchograms as shown in figure . she was started on iv ceftriaxone and iv azithromycin. ekg revealed tachycardia with premature atrial contractions and qtc prolonged to ms. legionella urine antigen came positive the next day and ceftriaxone was discontinued. infectious diseases team was consulted. after much discussion, a decision was made to continue azithromycin. covid- polymerase chain reaction (pcr) was ordered which turned out to be negative. the patient was kept under observation for a total of three days. repeat ekg was done on day of azithromycin as initial ekg showed prolonged qt interval. ekg showed sinus rhythm with qtc interval of ms. she was clinically stable during the entire stay with no temperature spikes or episodes of diarrhea. she was discharged on azithromycin mg for four more days making the total duration of azithromycin therapy seven days. the patient denied contact with any sick person and also denied recent travel. she worked in the kitchen to cook meals for homeless people. source of infection was not identified and no further cases were reported in our hospital during that period. legionella bacteria are gram-negative, intracellular bacteria that are important causes of communityacquired and nosocomial pneumonia. legionella infections can be acquired sporadically or during outbreaks. legionella bacteria are typically transmitted via inhalation aerosols from contaminated water or soil. no such exposure was found in our patient. the term legionellosis refers to any clinical syndrome associated with legionella infection. the two most common syndromes associated with legionella infection are: • legionnaires' disease, which refers to pneumonia caused by legionella spp • pontiac fever, which is an acute, self-limited febrile illness that is typically acquired during outbreaks [ ] . pneumonia caused by legionella is clinically and radiographically similar to other forms of pneumonia. predominant symptoms include fever, cough, and shortness of breath. symptoms typically arise two to days after exposure to contaminated water or soil. fever and fatigue often precede the onset of cough. rales and/or other signs of consolidation can be present on physical examination. radiographic findings are varied and nonspecific; however, the most common findings are patchy unilobar infiltrates, which can progress to consolidations [ ] . extra pulmonary symptoms are not uncommon and include nausea, vomiting, diarrhea, acute kidney injury and in rare cases myocarditis, acute disseminated encephalomyelitis and multiorgan failure [ ] . diagnosis can be established based on culture, direct fluorescent antibody test, urine antigen test, and serum antibodies [ ] . sensitivity and specificity of diagnostic modalities are listed in table though sensitivity and specificity for serum antibodies varies depending on method used [ , ] . this patient presented to the hospital with diarrhea as the chief complaint and no respiratory symptoms at all. it is very common to rule out pneumonia in a patient with no overt respiratory symptoms. chest x-ray done in the er as a part of admission protocol showed right middle lobe infiltrates and pneumonia was ruled in. treatment should be initiated as soon as diagnosis is established with macrolides. empiric therapy should be considered either as monotherapy with a macrolide or combined with a β-lactam agent. respiratory fluoroquinolones such as levofloxacin can also be used [ ] . we hypothesize that the mechanism of secretory diarrhea in our case maybe attributed directly to the host's cell mediated immune response when bacterium invades macrophages for multiplication. immune cascade is activated by lipopolysaccharide, lipid a, component of its outer membrane. lipid a directly stimulates tnf-alpha production, which causes massive cytokine release and is primarily responsible for chloride secretion and intestinal inflammation [ ] . it is important that clinicians be aware of this extra pulmonary manifestation of legionella infection, especially in patients with no risk factors or pulmonary symptoms of this disease. legionnaires' disease is caused by gram negative, intracellular bacteria known as legionella. it is a multisystem involvement infection predominantly present with respiratory symptoms. patients usually have history of travel or known exposure, both of these provide clue to legionella infection. we report a case of legionnaires' disease in -year-old female patient without any known history of travel, risk factors and pulmonary symptoms. such scenario poses a major challenge to diagnosis legionnaires' disease. the main goal of this case report is to familiarize physicians of the possibility of legionnaires disease presenting as an isolated gastrointestinal involvement with no clinical symptoms of pneumonia at presentation. human subjects: consent was obtained by all participants in this study. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. severe legionnaires disease complicated by multi-organ dysfunction in a previously healthy patient: a case report legionnaires' disease: description of an epidemic of pneumonia delay in appropriate therapy of legionella pneumonia associated with increased mortality legionella pneumonia complicated by rhabdomyolysis severe community-acquired pneumonia due to legionella pneumophila serogroup diagnostic testing for legionnaires' disease value of serological testing for diagnosis of legionellosis in outbreak patients clinical manifestations and diagnosis of legionella infection when diarrhea can become deadly: legionnaires' disease complicated by bowel obstruction key: cord- -z ifjsil authors: suwanwongse, kulachanya; shabarek, nehad title: lithium toxicity in two coronavirus disease (covid- ) patients date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: z ifjsil coronavirus disease (covid- ) is a highly contagious disease, which is currently causing a devastating pandemic resulting in more than millions of infected cases worldwide. emerging evidence reports the impact of several co-morbidities on the clinical features and outcomes of covid- . however, the evidence regarding the association of mental health illnesses and psychiatric treatment on the prognoses of covid- is still lacking. lithium is a commonly prescribed psychiatric medication that is also well known for its highly lethal toxicity. many factors can fluctuate the level of lithium, such as drug interaction, illness, and infection. prompt recognition and management of lithium intoxication is required to reduce patients’ morbidity and mortality. currently, there is no report regarding covid- and lithium toxicity. herein, we are presenting two patients with covid- who initially presented with signs and symptoms of lithium toxicity. our cases emphasize the need for special attention in taking care of patients who are taking lithium during the covid- pandemic. in general, we recommend obtaining lithium levels in all patients who have been taking lithium and have the diagnosis of covid- . severe acute respiratory syndrome coronavirus (sars-cov- ) infection resulting in coronavirus disease (covid- ) is currently a rapidly evolved public health issue, with almost five million people diagnosed and more than , deaths recorded [ ] . several comorbidities have been identified as negative prognostic outcomes in patients with covid- [ ] . however, there is a lack of evidence regarding the impact of mental health illnesses and psychiatric treatment on the severity and mortality related to covid- . lithium is a commonly prescribed psychiatric medication in both hospitalized and nonhospitalized patients. lithium has several clinical benefits and is considering a drug of choice for patients with bipolar disorder [ ] . despite its high effectiveness, lithium has a very narrow therapeutic window and its toxicity can be lethal especially if the toxicity is not recognized. also, the level of lithium can be affected by various causes, including the interaction with other medications, patients' illness, and infection. lithium intoxication leads to numerous fatal complications, such as cardiac arrhythmias, neurological disturbances, endocrine abnormalities, and kidney failure [ , ] . prompt recognition and management of lithium intoxication will help to limit patients' morbidity and mortality. to date, there is no report about lithium toxicity in patients with covid- . herein, we are reporting the clinical features and outcomes of two patients with covid- who initially presented with signs and symptoms of lithium toxicity. a -year-old woman with a past medical history of schizoaffective disorder, diabetes mellitus, hypertension, and hyperlipidemia was brought to the mental health clinic by her daughter due to behavior changes. her medications included lithium mg daily, quetiapine mg twice daily, insulin, empagliflozin, metformin, sitagliptin, atorvastatin, irbesartan, and aspirin. on examination, she was poorly groomed without any acute distress. her speech was unintelligible. she was disoriented to time, place, and person. her vital signs were as follows: respiratory rate (rr) breaths per minute (breaths/min) , temperature (t) . degrees fahrenheit (°f), heart rate (hr) beats per minute (bpm), blood pressure (bp) / mmhg, and oxygen saturation (spo ) % on room air. her lung exam revealed mild crepitation. laboratory tests showed white blood cell count (wbc) . x cells per cubic millimeter (/mm ) with lymphocytes . %, elevated creatinine (cr) . milligrams per deciliter (mg/dl) (baseline . mg/dl), and lithium level . mmol/l. electrocardiogram (ecg) was normal. computed tomography (ct) of the head was unremarkable. chest x-ray (cxr) showed bilateral patchy infiltrates as demonstrated in figure . a nasopharyngeal swab for the sars-cov- polymerase chain reaction test was done and returned positive. she was admitted to the medicine floor due to covid- pneumonia, acute kidney injury (aki), and lithium toxicity. on the first day of admission, she received a total of four liters of intravenous normal saline for the treatment of lithium intoxication and aki. she did not develop acute worsening of covid- symptoms from the administration of intravenous fluid and had good urine output. table demonstrates the changes in her wbc, cr, and lithium level during the hospital course. her mental status was improved, and lithium level was normalized. she received hydroxychloroquine for the treatment of covid- as per hospital protocol; however, her hospital course was complicated with acute hypoxic respiratory failure and eventually died on day of admission. an -year-old man with a past medical history of bipolar disorder, autistic spectrum disorder, attention deficit hyperactivity disorder, hypothyroidism, and mild persistent asthma was brought to the emergency department by her mother due to alteration of consciousness. his mother also reported that he had a fever, nasal congestion, and cough for seven days. his current medication included lithium mg twice daily, clozapine mg daily, and levothyroxine. on examination, he was somnolence but arousable. he was not in acute distress and could answer simple questions and oriented. his vital signs were as follows: rr breaths/min, t . °f, hr bpm, bp / mmhg, and spo % on room air. his lung exam was normal. laboratory tests showed wbc . x /mm with lymphocytes %, elevated cr . mg/dl (baseline mg/dl), and lithium level . mmol/l. ecg showed sinus tachycardia with an hr of bpm, as demonstrated in figure . cxr was normal. a nasopharyngeal swab for the sars-cov- polymerase chain reaction test returned positive. he was admitted to the pediatric intensive care unit due to covid- infection, aki, and lithium toxicity. aggressive intravenous normal saline was administered for the treatment of lithium intoxication and aki. he did not receive hemodialysis. his mental status was improved. lithium is a highly water-soluble ion, well absorbed by the gastrointestinal tract and excreted mostly by the kidneys [ ] . thus, the clearance of lithium largely depends on renal function and volume status. lithium is well recognized for its potency as well as its narrow therapeutic index. therapeutic ranges of lithium are between . and . meq/l, while the levels of . and above are associated with its toxicity [ ] . mental status changes and neurological symptoms are the most common presentations of lithium intoxication in the emergency department [ , ] . we report two patients initially presented with acute lithium intoxication in the setting of sars-cov- infection. to date, there is no evidence support or against the relationship between lithium toxicity and covid- . our patients had clinical features consistent with lithium toxicity including confusion, behavior change, and changes in mental status. both patients' mental status was improved after receiving aggressive intravenous fluid and did not require hemodialysis. however, the first patient had later developed severe covid- and passed away from acute hypoxemic respiratory failure. the second patient had mild covid- infection but complicated with aki and lithium intoxication. prompt diagnosis and treatment of lithium intoxication in the second patient has led to a favorable prognosis. our report may point out that the clinical characteristics and outcomes of covid- in patients with psychiatric illness and taking lithium are similar to those of the general population. patient was an older adult with several co-morbidities proven to increase risks of covid- mortality and had significant changes in her cxr. she later developed severe covid- and death. in contrast, patient is a teenager and had normal cxr. he had mild covid- and later resolved without complications. more research elucidates the relationship between lithium toxicity and covid- will be worthwhile. our cases also highlight the need for special attention in taking care of patients who are on lithium or any medications with a narrow therapeutic index during the covid- pandemic. patients with covid- are likely to have poor oral intake, dehydration, and declined renal function. some patients may be quarantined at home due to mild symptoms of covid- but at risk of lethal complications from medication toxicity. clinicians should be aware of the possibility of drug toxicity in suspected covid- patients, especially patients who are on medication with narrow therapeutic ranges. drug levels should be obtained in covid- patients who have a high risk for medication toxicity, such as patients with multiple comorbidities, elderly, and polypharmacy. prompt recognition and treatment of medication toxicity will prevent patients' morbidity and mortality. if possible, we would recommend obtaining lithium level in every suspected covid- cases regardless of severity. as these patients are at risk of developing fatal complications from lithium intoxication, early detection and prompt treatment is required to prevent death. patients with psychiatric illness and taking lithium may have similar clinical features and outcomes of covid- compared to those without. lithium intoxication is common in patients with acute illness. more research is needed to determine the association between lithium toxicity and covid- infection. lithium levels should be obtained in all covid- patients who currently taking lithium, particularly those of high risks. rapid recognition and management of lithium intoxication is required to limit patients' morbidity and mortality. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. who coronavirus disease (covid- ) situation report - clinical features of patients infected with novel coronavirus in wuhan, china. lancet. treatment of bipolar disorder lithium toxicity profile: a systematic review and meta-analysis lithium intoxication: incidence, clinical course and renal function a population-based retrospective cohort study key: cord- -vfcoyezy authors: kabashneh, sohaip; ali, hammad; alkassis, samer title: multi-organ failure in a patient with diabetes due to covid- with clear lungs date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: vfcoyezy the pandemic of coronavirus disease has emerged in late infecting millions of people worldwide. diabetes mellitus (dm) has been associated with severe illness and mortality mainly due to acute respiratory distress syndrome. we report a case of a middle-aged man with dm and covid- who developed seizure and altered mental status, found to have diabetic ketoacidosis (dka), acute kidney injury, hypovolemic shock, and hyperammonemia all contributing to metabolic encephalopathy. he was admitted to the icu and subsequently intubated for airway protection; with appropriate management his condition improved and was successfully extubated. the patient had no lung involvement throughout the illness. we report this case to highlight that covid- can lead to multi-organ failure in patients with dm even in the absence of lung involvement which all physicians should be mindful of. the pandemic of coronavirus disease (covid- ), a disease caused by severe acute respiratory syndrome-coronavirus- (sars-cov- ), has emerged as an easily transmissible disease affecting millions of people worldwide. the spectrum of covid- ranges from mild to critical illness; the majority ( %) of cases are mild and self-limiting; severe disease requiring hospitalization occurs in the remaining % mainly due to fulminant pneumonia and respiratory failure [ ] . diabetes mellitus (dm) has been associated with severe illness and mortality [ ] [ ] [ ] . the association between dm and covid- in the literature so far has always been in the setting of fulminant pneumonia and respiratory failure. however, covid- is an infection that can certainly trigger diabetic ketoacidosis (dka) and possibly multi-organ failure even in the absence of lung involvement. we report a case of a -year-old man with a past medical history of hypertension and dm, who presented to the ed after he had witnessed a new onset generalized tonic clonic seizure at home and then again en route to the hospital. few days prior, he had decreased oral intake and has not been acting like himself as per his wife; she did not notice vomiting, diarrhea, abdominal pain, fever, cough, or headache. on arrival to the ed he was unresponsive and unable to protect his airway; heart rate was beats/min, blood pressure / mmhg, and his oxygen saturation was % on nonrebreather mask. on exam he was unresponsive, not moving any of his extremities spontaneously; his pupils were equal, round, and reactive to light, he did not have a cough or gag reflex, and no facial droop was noted. his chest and abdomen exam were unremarkable. the patient was subsequently intubated for airway protection; basic labs showed multiple abnormalities including: dka with blood glucose (bg) , anion gap , hco , beta hydroxybutyrate . ; he also had acute kidney injury (aki) with creatinine (cr) of . (baseline was . ), blood urea nitrogen , potassium . , sodium , chloride , phosphorus . , lactic acid . ; there was also evidence of liver function abnormalities with elevated ammonia level at ; arterial blood gas was consistent with high anion gap metabolic acidosis with ph . , hco , paco , pao . complete blood count revealed elevated white blood cells at . , absolute lymphocyte count , hemoglobin . , and platelet ; urine drug screen was negative. ct head showed no evidence of acute intracranial process, and chest x-ray was unremarkable ( figure ) . infectious workup was done including covid- , urine analysis, urine culture, blood culture, cerebrospinal fluid (csf) analysis, and csf culture. the patient was started on an insulin drip and intravenous fluids for dka; he was started on levetiracetam to manage the seizures, and broad spectrum antibiotics with cefepime, vancomycin, ampicillin, and acyclovir empirically for meningitis. electroencephalography (eeg) which was done showed moderate to severe degree of cerebral dysfunction consistent with metabolic/hypoxic encephalopathy, the waveforms were not epileptiform in nature. on the second day of admission, the patient was still unresponsive. however, dka has resolved with bg , anion gap , hco , and therefore, the insulin drip was discontinued and was started on glargine and correction scale. his aki started to improve as cr trended down to . and potassium . . covid test came back positive and therefore he was started on hydroxychloroquine; the other infectious workup including urine analysis, urine culture, blood culture, csf analysis, and csf culture came back negative. the patient was breathing on minimal ventilator settings but was not extubated because of the mental status. on the third day, the patient's mental status improved; he became more awake, alert, and was able to follow simple command and was extubated successfully. antibiotics were discontinued, repeat labs showed normalization of kidney function, lactic acid trended down to . , ammonia level also improved to . given the overall clinical improvement the patient was transferred to medical floor and discharged after a total of seven days of admission without any evidence of lung involvement. covid- in severe cases can lead to death, mainly due to acute respiratory distress syndrome, and subsequent acute hypoxic respiratory failure [ ] [ ] [ ] . multiple studies have been conducted to explain the tendency of sars-cov- to affect the lungs concluding that angiotensin converting enzyme (ace ), an enzyme abundantly found in the lungs, serves as a portal of entry into cells for the sars-cov family [ ] [ ] . diabetes has been associated with worse outcome in covid- patients, as it has been postulated to enhance viral entry into cells and dampen the host immune response in fighting the infection [ ] . interestingly ace is present in the pancreas mainly the endocrine tissues, i.e. pancreatic islets that regulates blood glucose levels [ ] . this finding would explain the involvement of the pancreas and the resulting hyperglycemia seen in patients suffering from sars-cov- , like our patient above. an acute insult on the islet cells would result in hyperglycemia in patients with previously normal islet function and worsening hyperglycemia and potentially triggering dka in those with a history of dm [ ] . many viruses have been associated with the development of type i dm in humans. sars-cov in was associated with acute hyperglycemia and higher death rates in patients with dm. however, a three-year follow up did not show increased incidence of diabetes [ ] . follow up studies will be needed after the present pandemic to ascertain if same holds true for sars-cov- . in diabetic patients covid- can lead to dka and potentially multiorgan failure even without lung involvement like our patient above; thus diabetic patients with covid- require close monitoring of all organs not just the lungs, as those patients seem to be more susceptible to renal failure, encephalopathy, heart involvement, and shock compared to nondiabetics [ ] . diabetes mellitus has been associated with worse outcome in covid- mainly due to fulminant pneumonia. however, hyperglycemia and dka can result from covid- leading to altered mental status and admission to icus even in the absence of lung involvement. thus physicians should be mindful of glucose levels in patients admitted for covid- even if they do not have a previous history of diabetes. physicians should also closely monitor all organs in diabetic patients with covid- instead of just the lungs. human subjects: consent was obtained by all participants in this study. not needed issued approval not needed. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study severe outcomes among patients with coronavirus disease (covid- ) -united states binding of sars coronavirus to its receptor damages islets and causes acute diabetes comorbidities and multi-organ injuries in the treatment of covid- diabetes in covid- : prevalence, pathophysiology, prognosis and practical considerations key: cord- -amo jm authors: wood, james; datta, dibyadyuti; hudson, brenda l; co, katrina; tepner, sarah; hardwick, emily; john, chandy c title: prevalence of asymptomatic sars-cov- infection in children and adults in marion county, indiana date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: amo jm background and objectives: two community studies outside the us showed asymptomatic infection with severe acute respiratory syndrome coronavirus (sars-cov- ) in adults, but not in children < years of age. in this study, we assessed the prevalence of asymptomatic sars-cov- infection in children and adults in marion county, indiana. methods: individuals living in marion county with no symptoms of coronavirus disease (covid- ) within seven days of enrollment were eligible for this cross-sectional household study. study kits were delivered to the participant’s residence for self-swabbing, picked up by the study team, and tested by polymerase chain reaction (pcr) for sar-cov- infection. results: five hundred eleven nasal swabs were collected from children and adults ≥ years of age. one participant (seven years of age) tested positive, for an overall study prevalence of . % ( % ci , . %). the participant had no known contact with a person with sars-cov- infection, and five family members tested negative for infection. the child and family members all tested negative for infection and days after the first test, and none developed symptoms of covid- for days after testing. conclusions: asymptomatic sars-cov- infection can occur in children < years with no known covid- exposure. large cohort studies should be conducted to determine prevalence of asymptomatic infection and risk of transmission from asymptomatic infection in children and adults over time. a growing body of evidence suggests that asymptomatic and pre-symptomatic cases may significantly contribute to the spread of severe acute respiratory syndrome coronavirus (sars-cov- ), the virus responsible for coronavirus disease (covid- ) [ ] [ ] [ ] [ ] . it has been suggested that children are a reservoir for asymptomatic infection, but population-based studies in iceland and italy that assessed symptomatic and asymptomatic sars-cov- infection found no infections in children < years of age [ , ] . an understanding of the prevalence of asymptomatic sars-cov- infection in us communities is critical to designing effective infection prevention strategies. data on asymptomatic infection in us children and adults in the community are not currently available. for this reason, we conducted a community-based study of the prevalence of asymptomatic sars-cov- infection in adults and children in marion county, indiana. we conducted a cross-sectional household study of prevalence of asymptomatic the study recruitment and enrollment strategy is outlined in figure . participants were recruited using a state-wide research registry, all in for health, which has , households in marion county. a description of the study and directions on how to participate and enroll in the all in for health registry if interested were circulated through social media and local news outlets, including television and websites. households with primarily underrepresented minorities (urm) were first invited to participate, and one week later, a subset of households was chosen according to the household having children, having newly registered urm, or according to the need for proportionate representation from zip code clusters that comprised all of marion county. interested participants were sent an invitation to the screening survey using the secure, web-based software platform research electronic data capture (redcap) hosted at indiana university [ ] . eligible household members were then given a consent or assent (child aged - ) document to complete. after obtaining informed consent, participants were directed to the study website with instructions and a video of nasal swab collection procedures [ ] . study participants were confirmed to be asymptomatic via redcap prior to delivery of study kits with swabs and viral transport medium vials. based on previous studies finding a low overall community prevalence [ , ] , the study sample size had the power to detect a % prevalence ( % confidence interval [ci] . , . %) with % confidence interval for proportion based on normal approximation of asymptomatic infection. all other study data were descriptive. nasal swabs were collected on participants, including children < years of age, and individuals ≥ years of age. distribution of county and study population by age group is shown in table . racial and ethnic characteristics of the study and county populations, by zip code cluster and overall, are shown in figure . using american community survey data, zip codes with similar demographics were grouped into ten clusters. this figure shows a cluster's racial and ethnic breakdown, in terms of overall population percentage (the black horizontal bar) and the study participant percentage (the blue vertical bars). data and demographic analysis provided by the polis center at iupui. among the participants tested, one participant, a seven-year-old boy, tested positive for sars-cov- (prevalence . % [ % ci , . %]). the prevalence among children (n= ) was . % ( % ci , . %). the one child who tested positive was biracial (african-american/caucasian) and lived in a household with his mother and five siblings. one child declined study participation. the other four children and the mother were all negative for sars-cov infection. neither the infected child nor anyone else in the household reported having contact with a person known to have covid- . the cycle threshold (ct) values for the three target gene pcr reactions were - , low levels indicating a significant viral load. ten days after testing, the child, siblings, and mother all tested negative on repeat pcr testing and days after initial testing and all remained asymptomatic during this period. among the asymptomatic adults ≥ years of age, none tested positive for sars-cov- infection (prevalence %). multiple studies from china have reported asymptomatic sars-cov- infection in children, but these studies involved children in contact with infected individuals and were not community surveys of asymptomatic infection [ , ] . community surveys in iceland and italy that included symptomatic and asymptomatic individuals found a low prevalence of infection ( . % to . %), and both studies found no infection in children < years of age [ , ] . in the state of indiana, a community prevalence study of individuals > years of age found an active infection rate (by pcr) of . % and an overall prevalence of current (pcr) or previous infection (sars-cov- antibody) of . % [ ] . prevalence of asymptomatic infection in this study was . %, within the range of our finding of . % prevalence in the population [ ] . despite the concern about spread of sars-cov- infection from asymptomatic individuals in the community, there have been no published studies of sars-cov- infection in asymptomatic adults and children years and under in the united states to date. in the present study, we found no asymptomatic infection in adults ≥ years of age, but found that one of asymptomatic children ≤ years was infected (prevalence . %, % ci , . %). the sole infected individual was seven years of age, demonstrating, contrary to prior studies, that children under years of age in the community may carry asymptomatic infection. the source of the child's infection was unclear, as no other household members tested positive. it is possible other family members in the home were previously infected and no longer shedding. future serologic studies would be helpful and are planned. the positive result was reported to the indiana state department of health for further evaluation and contact tracing. the positive test rate in the state of indiana during the study period was . %, with an average of positive individuals per day [ ] . our study's finding of a very low prevalence of asymptomatic infection provides reassurance on the benefits of the state implementation of social distancing measures, which went in to effect march th with a stay at home order and a phased reopening starting may th in marion county. even with this low prevalence, infection in one child out of tested ( . %) yields an estimate of children asymptomatically infected in indianapolis/marion county ( % ci , ). the large confidence intervals demonstrate the preliminary nature of this data. larger studies of asymptomatic infection that include young children are needed to determine the relative prevalence of asymptomatic infection in children and adults with greater precision. additionally, longitudinal studies across multiple geographic areas are needed to determine how prevalence varies in different areas, especially as social distancing measures are relaxed. testing of antibodies to sars-cov- in these individuals could help to determine the rate of past infection, another important measure for which there is little data in children. antibody testing is planned in this cohort. the increasing reports of multisystem inflammatory syndrome in children (mis-c) temporally associated with prior sars-cov- infection, most of which appears to have been asymptomatic [ ] [ ] [ ] , underscore the importance and urgency of increasing our understanding of asymptomatic sars-cov- infection and its potential sequelae in children. strengths of this study include the specific investigation of asymptomatic individuals; use of community engagement to recruit a representative cohort of individuals; the innovative sample distribution and collection methods, which made the study possible in a period of active sars-cov- transmission; use of self/parent-administered nasal swabs, recently shown to be similar in sensitivity for sars-cov- detection to nasopharyngeal swabs [ , ] , which made home testing of children feasible; and the intentional inclusion of both children and adults in testing. the primary limitations were the relatively small sample size for a population study and the non-random selection of study participants. despite the small sample size, we were able to detect low frequency infection, but the % confidence intervals of the estimates included zero, so the study data are best viewed as important initial data on which to base future studies of asymptomatic infection in children and adults. we chose a non-random recruitment process because we had a research registry that mirrored overall population demographics and therefore was likely to provide a sample representative of the geographic and racial diversity of the county/city population. additionally, study enrollment required access to internet/email which may have biased our population to a higher socioeconomic class. random selection might have derived a population more fully representative of the county population, but participation rates would likely have been far lower, and the final sample may not have been substantially different from the sample we obtained. in the present study, we found asymptomatic sars-cov- infection in one seven-year-old child with no history of known sars-cov- exposure, out of children tested (prevalence . %, % ci, , . %) and in none of the adults ≥ years of age tested. the study demonstrates that children < years of age with no known sars-cov- exposure may harbor asymptomatic sars-cov- infection. in this instance the child did not transmit infection to close contacts. the study sets the stage for future larger studies of asymptomatic infection in children to determine risk and patterns of transmission in the community and devise strategies for infection prevention. asymptomatic carriers of covid- as a concern for disease prevention and control: more testing, more follow-up presumed asymptomatic carrier transmission of covid- spread of sars-cov- in the icelandic population presymptomatic transmission of sars-cov- amongst residents and staff at a skilled nursing facility: results of real-time pcr and serologic testing suppression of covid- outbreak in the municipality of the redcap consortium: building an international community of software platform partners interim guidelines for collecting, handling, and testing clinical specimens from persons for coronavirus disease (covid- ) population point prevalence of sars-cov- infection based on a statewide random sample -indiana indiana covid- dashboard. isdh -novel coronavirus: indiana covid- dashboard royal college of paediatrics and child health guidance: paediatric multisystem inflammatory syndrome temporally associated with covid- kawasaki-like disease: emerging complication during the covid- pandemic multisystem inflammatory syndrome in children (mis-c) associated with coronavirus disease assessment of sensitivity and specificity of patient-collected lower nasal specimens for sudden acute respiratory syndrome coronavirus testing patient-collected tongue, nasal, and mid-turbinate swabs for sars-cov- yield equivalent sensitivity to health care worker collected nasopharyngeal swabs acknowledgements: the authors thank the members of the indiana clinical and translational sciences institute (ctsi) and the john lab and medical student teams for their individual contributions to this work. we thank dustin lynch, michael goings and christian kautzman for their work in graphic design, database design and study participant contact and follow-up, respectively. lastly, we thank dr. aaron ermel for his donation of viral transport media to this study. human subjects: consent was obtained by all participants in this study. indiana university institutional review board issued approval a . this study, tracking asymptomatic covid- through indianapolis communities (tactic), was reviewed and approved by the indiana university institutional review board (irb). . animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -e ywn e authors: jose, merin; desai, krishna title: fatal superimposed bacterial sepsis in a healthy coronavirus (covid- ) patient date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: e ywn e coronavirus disease (covid- ) is a highly infectious disease caused by the newly discovered coronavirus, sars-cov- (severe acute respiratory syndrome coronavirus ). the novel coronavirus first emerged in wuhan, china, in december and has led to a global pandemic. the virus mainly spreads through respiratory droplets from an infected person, but environmental contamination can also act as a source of infection, making social distancing an important key in containing the spread of infection. those with underlying health conditions are more susceptible to complications such as acute respiratory distress syndrome, which can be fatal. however, healthy individuals experience a mild flu-like illness or may be asymptomatic, recuperating from the infection even without any particular intervention. we present a case of a healthy covid positive individual, with no underlying comorbidities, who rapidly deteriorated overnight on readmission to the hospital after initial discharge and succumbed to this disease due to a superimposed bacterial infection with covid pneumonia. this case report highlights the importance of educating covid- positive patients about the precautions, as well as signs and symptoms of a superimposed bacterial infection, when their plan of care is in a home setting. it also emphasizes the potential role of checking procalcitonin levels as a part of routine laboratory investigation at initial presentation in all suspected as well as confirmed covid- cases to rule out an on-going bacterial infection that can prove fatal in the course of the disease. coronaviruses can cause an array of respiratory conditions, ranging from common cold to severe acute respiratory syndrome (sars) to the middle east respiratory syndrome (mers). in december , a new betacoronavirus was identified, which is now known as severe acute respiratory syndrome coronavirus (sars-cov- ) [ ] . the initial clusters of pneumonia cases caused by this sars-cov- were traced in wuhan, china [ ] . in march , the world health organization declared the outbreak to be a pandemic, with more than four million infections worldwide and still counting [ ] . the spectrum of the presentation and clinical course of the infection may vary from mild to critical, with % of the infections being asymptomatic to mild, % patients developing severe disease such as dyspnea, hypoxia, or more than % lung involvement on imaging, and only % of the total infected cases progressing to a critical stage with respiratory failure and multiorgan dysfunction. overall case fatality rate was . %, with no deaths reported among non-critical cases [ ] . the most common presenting symptoms are fever, dry cough (few cases with reported concurrent sputum production), dyspnea, lethargy, myalgia, and, seldom, diarrhea, hemoptysis, dysgeusia, and anosmia. the lower respiratory tract involvement can offset pneumonia, which can rapidly progress into acute respiratory distress syndrome (ards) and is often associated with multiorgan failure, which appears to be the most dreaded complication, as it attributes to most fatalities from the infection [ , ] . patients with underlying comorbidities are more vulnerable to more severe complications and a poorer prognosis, as compared with healthy patients [ ] . we present a case of a healthy male with no underlying comorbidities who was clinically stable on presentation and was therefore discharged for home care. five days later, he presented again to the emergency department (ed) with worsening shortness of breath and diarrhea for three days and was found to have a superimposed bacterial infection. to our understanding, this caused a rapid deterioration in his clinical status and led to his early demise on the same day of his readmission. superimposed bacterial infection has not been a frequently reported feature of this infection so far. our emphasis from this case report is to highlight the risk of superimposed bacterial infection in covid- patients. our aim is to focus on the need to educate the patients on precautions to be taken during home care and using procalcitonin as a routine investigation for covid-positive patients even in the absence of clinical instability [ ] . a -year-old healthy male presented to the ed with complaints of cough, bodyache, and fever. the symptoms first appeared five days back. he had no chest pain, shortness of breath, or abdominal pain. the patient was in good health up until now, with no significant medical or surgical history. he worked as a packet distributor and was active at his baseline. he is a nonsmoker and has no known addictions. he had no history of recent travel, but had a history of contact with two covid-positive individuals (grandson and friend), and therefore covid was suspected, for which he tested positive. on examination, he was not in distress and his vitals were stable. chest x-ray showed clear lung and pleural spaces, a normal heart with minimally tortuous aorta, and no evidence of any active cardiopulmonary, disease, or mild hypertrophic changes in the spine, as shown in figure . given his stable clinical condition, normal x-ray findings, and no underlying comorbidities, he was discharged home with symptomatic treatment. following his discharge, in the next couple of days, he developed worsening shortness of breath, spiking fever with intermittent chills, diaphoresis, and diarrhea for three days. he presented to the ed again after five days of his initial presentation for these complaints. on examination, he was hypotensive with blood pressure of / mm hg and was hypoxic at room air saturating to %, which improved to % on l of non-rebreather. he was in distress with tachypnea. he was admitted and immediately intubated, and a nasogastric tube was placed. on initial investigations, his labs were as shown in table , and blood cultures were sent. wbc, white blood cell; rbc, red blood cell; bun, blood urea nitrogen; alp, alkaline phosphatase; ast, aspartate aminotransferase; alt, alanine aminotransferase figure shows chest x-rays from initial the ed visit on day and subsequent admission on day , comparing the drastic changes in a short span of five days. findings of the second chest x-ray were concerning for low lung volumes and development of infectious/inflammatory process with interval development of bilateral airspace opacities, including a focal consolidation in the left upper lung. ekg showed atrial fibrillation with rapid ventricular response and non-specific t wave abnormality. he was given . l of fluid bolus to address his hypotension. sodium bicarbonate and norepinephrine drip was also started for pressor support. digoxin . mg was given intravenously for atrial fibrillation and was started on amiodarone drip as options for rate control were limited, considering his hypotension. with the concern for possible superimposed bacterial infection, he was empirically started on cefepime and vancomycin intravenously (both renally dosed). he was also started on hydroxychloroquine and doxycycline. over the next six to seven hours, he continued to worsen clinically. blood cultures were followed up and it grew imipenem-resistant escherichia coli (it was sensitive to cefazolin and piperacillin/tazobactam). from being stable on day of presentation, our patient continued to deteriorate overnight on subsequent admission. he eventually became bradycardic and was asystolic within one minute. the patient had an advance directive of "do not resuscitate" and died on the same night of admission due to septic shock with multiorgan dysfunction secondary to superimposed bacterial infection. he developed multifocal pneumonia due to covid- , which was possibly accelerated by superimposed e. coli infection or vice-versa. the possible sources of his e. coli bacteremia were either translocation from the bowel, given he was having diarrhea for three days, or a genitourinary source, as no symptoms pertaining to it were reported. covid- is a systemic disease caused by the highly pathogenic sars-cov- , which led to a pandemic, globally infecting more than , , cases and causing , deaths worldwide as of now, with the united states of america having one-third of it [ ] . the incubation period for the infection is days after the exposure to the virus, but most cases show symptoms by the fifth day, with an average incubation period of four days [ ] . sars-cov- and previous betacoronavirus infections have overlapping clinical features. secondary bacterial and fungal infections are common coinfections in viral illness. other coronaviruses outbreaks such as sars and mers, as well as influenza, had concurrent superimposed infections [ ] . bacterial co-infection contributed to a significant amount of mortality during previous flu pandemics in and [ ] . these co-infections are associated with increased intensive care unit admissions and mortality. superimposed bacterial infection in influenza is reported to occur in approximately . % of healthy young patients and at least . % of older patients. a systematic review that was performed during the pandemic reported that one out of four h n -infected patients had a bacterial or fungi coinfection [ ] . secondary infection was found in % of non-surviving covid- patients [ ] . despite its commonality in prevalence and the extensive adversities it causes in sars-cov- infection, it seems to be a fairly inadequately researched topic. furthermore, the main focus of the published papers in the literature with respect to secondary infections with other pathogens is revolving around the prevention and cross-transmission [ ] . with this case report, we aim to accentuate the importance of meticulously identifying the presence of superimposed bacterial infections and attributing an adequate weightage along with other predictors for determining prognosis in a patient with sars-cov- infection. ards with multiorgan failure is the most dreaded and the most common complication attributable to mortality [ ] . cardiovascular complications such as an arrhythmia, heart failure, and myocardial ischemia can also be fatal complications in patients with pneumonia [ ] . patients suffering from chronic ailments such as longstanding hypertension, diabetes, cardiovascular diseases, immunosuppressive conditions (such as malignancies, chronic lung, and kidney diseases), chronic smoking history, and advanced age comparatively had relatively poorer outcomes [ , ] . they fall under the "high-risk population" and extra caution should be maintained to keep them from acquiring the infection. according to a study, the following four predictors of higher mortality in patients with covid- pneumonia were identified: ( ) age ≥ years, ( ) preexisting concurrent cardiovascular or cerebrovascular diseases, ( ) cd +cd + t cells ≤ cell·μl − , and ( ) cardiac troponin i ≥ . ng·ml − [ ] . another study suggests age, sequential organ failure assessment (sofa) score, and d-dimer as the determinants of prognosis. the same study also highlighted that sars-cov- directly causes sepsis, even in the absence of concurrent infection with a different pathogen, but the mechanism was not well understood [ ] . however, our patient with superimposed e. coli bacteremia succumbed to septic shock with multiorgan failure. he was otherwise a healthy individual in his sixties, indicating that bacterial superinfection is a risk factor even in healthy individuals without any prior hospitalization history. a meta-analysis recommended that serial procalcitonin measurement holds an important role in predicting the development of a more critical course of the disease. given the fact that the production of procalcitonin is ramped up in extra-thyroidal tissues in the presence of an underlying bacterial infection, its levels are also curtailed in viral infections by interferongamma, solidifying its correlation to complicated versus non-complicated disease processes [ ] . superimposed bacterial infections are important predictors of prognosis in sars-cov- infection. it can accelerate the deterioration and can prove to be fatal despite prior optimum health of a covid-positive patient. if the patient is clinically stable with low risk of mortality and if home care is planned, appropriate precautionary measures and warnings should be issued against bacterial and/or fungal infections and the need for immediate attention in case of any worsening of symptoms. also, through this case, we would like to report a case of bacterial coinfection in a patient with covid, which will help in tracking and recognizing the extent of co-or superinfection. serial procalcitonin measurements should be routinely performed at initial presentation and thereafter to monitor and predict the prognosis of the disease. clinical characteristics of coronavirus disease in china clinical features of patients infected with novel coronavirus in wuhan, china. lancet. coronavirus disease (covid- ): situation report - characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention clinical predictors of mortality due to covid- based on an analysis of data of patients from wuhan, china procalcitonin in patients with severe coronavirus disease (covid- ): a meta-analysis bacterial and fungal infections in covid- patients: a matter of concern co-infections: potentially lethal and unexplored in covid- clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study case-fatality rate and characteristics of patients dying in relation to covid- in italy predictors of mortality for patients with covid- pneumonia caused by sars-cov- : a prospective cohort study human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -apgdzgfz authors: lewis, thomas j; huang, jason h; trempe, clement title: reduction in chronic disease risk and burden in a -individual cohort through modification of health behaviors date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: apgdzgfz introduction health risk factors, including lifestyle risks and health literacy, are known to contribute to the chronic disease epidemic. according to the centers for disease control and prevention (cdc), chronic diseases account for % of healthcare costs, morbidity, and mortality. in the united states, healthcare providers attempt to modulate a limited set of risks. however, chronic diseases continue to proliferate despite expansion of wellness programs and drugs to manage and prevent chronic conditions. pandemics, exemplified by severe acute respiratory syndrome coronavirus (sars-cov- ), show that people in good health suffer mortality rates at % the rate compared to those with pre-existing chronic conditions. healthcare costs and morbidity rates often parallel mortality rates. new root-cause risk and health tools that accommodate low health literacy and are linked to personalized health improvement care plans are needed to reverse the chronic disease epidemic. reported here is a study on manufacturing employees in the midwest us using a personalized and group approach to chronic disease reversal and prevention which may also find utility in pandemic severity and policy decisions. methods health, lifestyle, behavior, and motivation data were collected on individuals at the beginning of a nine-month disease reversal and prevention program. the data were updated every two to six months over the period. inputs included information from a novel health risk assessment, serum biomarkers specific for chronic disease, and traditional medical information. using all these data we generated robust, personalized, and modifiable care plans that were implemented by the participant and guided by a care team including health coaches and medical providers. periodic renewal of profile data and biomarkers facilitated adjustment of care plans to optimize the path toward health goals set mutually by the participant and the care team. results ninety percent of participants experienced a favorable reduction in chronic disease biomarkers. the reduction in serum biomarkers coincided with a reduction in disease and risk attributes based on medical chart data and before and after interviews. hemoglobin a c, for example, lowered in all but one participant concomitant with reported improved energy and reduced need for medications in the majority of participants. markers of inflammation lowered across the population. most importantly each individual reported improvement in their overall health. conclusions this simple, inexpensive, root-cause based risk and health approach generates a “do no harm” action plan that guides a care team, including the participant, on a path to improved health. the data demonstrate that changes in a novel risk calculator score coincide with changes in sensitive biomarkers for chronic disease. when the risks of an individual are reduced, the biomarkers reflect that change with self-reported wellbeing also improved. this program and process may be of value to society plagued with escalating levels of chronic disease and merits further study and implementation. developed nations, and particularly the united states, continue to confront a chronic disease crisis. the world health organization (who) reported that in , non-communicable chronic diseases including: cardiovascular diseases, diabetes, cancers, and chronic respiratory diseases, accounted for / of deaths worldwide [ ] . the institute of medicine reported that america is less healthy compared to high income nations in obesity, diabetes mellitus, heart disease, chronic lung disease, and disability [ ] . the organization of economic cooperation and development (oecd) tracks the health of developed nations. the u.s. scores in the lower half among these nations on all major indicators of health, and longevity. when considering that the per person per year cost of healthcare in the united states is more than two and a half times that of the oecd nation average, yet our residents live . years less, a health paradox exists in the united states. this u.s. paradox is the worst cost-to-value benefit for chronic disease outcomes compared to the average of other developed nations. the chronic disease management system is failing people at both ends of the health spectrum. a root of the problem is that health and prevention recommendations currently supported by the major medical societies have proven ineffective at reversing or preventing chronic diseases. laboratory tests in common use remain of limited scope and provide little insight into chronic health status. pharmaceuticals prescribed based on test results have poor absolute statistical success at preventing or reversing disease. these assertions are borne out since % of the nation's nearly $ trillion in annual health care expenditures are for chronic conditions per the cdc. and the situation is not improving, for example, cardiovascular disease mortality, managed with statin drugs, blood pressure medications, and other usual care approaches across broad members of the u.s. population, increased nationally by . % between and [ ] . on average, residents of the united states with five or more chronic conditions spend times more on health services than people with no chronic conditions [ ] . as of , % of u.s. adults had at least one chronic condition, and % had more than one chronic condition. five percent of the population accounts for an estimated %- % of total health care expenses [ ] . the most expensive health conditions account for % of total health care expenses. the financial and productivity costs impact our corporations, who fund over half of the national healthcare at a price of roughly % of their gross revenues. and much of this cost is segmented in high-cost beneficiaries where, for example, the top % of claimants cost $ , /y compared to the population mean of $ /y. in a report compiled by the health care cost institute, there is a surprising large turnover from year to year among the highest cost healthcare spenders. three out of five top spenders in any given year were low or moderate spenders in the prior year. in , only % of the top % of spenders were in the top % of spenders in . moreover, this trend was consistent in each year from to . there is a need for better predictive analytics to determine who is and, more importantly, will be in this significantly high-cost segment of any population as a current tool, claims data, lacks predictive power. in pandemics, standard tests provide little information on projected outcomes, rather they simply indicate exposure and potential immunity. healthy people are much less likely to die compared to unhealthy or older people. physiological health, the main concern of practicing clinicians, is not well characterized through these tests. further, the main cause of death appears to be cytokine storm syndrome which is driven by innate, not adaptive immunity [ ] . thus, antibody testing does not adequately describe disease risk or severity. validated data on severe respiratory viral diseases and the correlation between mortality, immunocompromised status and existing chronic conditions in infected individuals indicate that a broad set of blood-based biomarkers may best serve to stratify risk and to set policy on containment strategies in populations [ ] . currently, the policy is being established with an incomplete set of evidence. in vivo blood biomarker analysis offers considerable opportunities for individual and population risk measurement. these tests afford fast analytical turn-around time, quantitative measurement, accessibility, serial monitoring and ready availability. in some instances, rapid and continuous monitoring is available. the measurement of and changes to a broad range of modifiable risk factors, and biomarkers connected to immune system activity through cytokine surrogates, offers the most important opportunity for the prediction of disease and improvement in global chronic and pandemic disease status. most industries recognize the value of early problem intervention. in the waste management industry, for example, there is a clear hierarchy of: . source reduction, . recycling, . treatment, and . land disposal. in healthcare, there is also a potential for a four-tiered approach to health maintenance: . prevention, . mitigation of asymptomatic disease in people with elevated predictive biomarkers, . mitigation upon the earliest detectable signs of early disease (dry macular degeneration is an example), and . advanced root-cause mitigation approaches within disease management approaches. most of the efforts in today's healthcare is on disease management with usual care which is only a small part of this suggested four-tiered approach. the who addressed major causes of chronic diseases with modifiable risk factors being: unhealthy diet; physical inactivity; and tobacco use. in addition, the who stated "these causes are expressed through the intermediate risk factors of raised blood pressure, raised glucose levels, abnormal blood lipids, overweight and obesity. the major modifiable risk factors, in conjunction with the non-modifiable risk factors of age and heredity, explain the majority of new events of heart disease, stroke, chronic respiratory diseases and some important cancers. the relationship between the major modifiable risk factors and the main chronic diseases is similar in all regions of the world." studies show that the u.s. experiences the same risks as exist globally. dietary factors, alone, are associated with nearly half of all cardiometabolic deaths. the highest proportions of cardiometabolic deaths were estimated to be related to excess sodium intake, insufficient intake of nuts/seeds, high intake of processed meats, and low intake of seafood omega- fats. dramatic changes in disease rates among migrating populations indicate that the primary determinants of these diseases are not genetic but environmental factors, including diet and lifestyle [ ] . studies on twins separated at a young age corroborate that chronic disease is much more related to environmental factors. expansion of the depth and breadth of risk assessment and concomitant prevention and disease amelioration programs represent an unmet healthcare need. a well-studied disease prevention arena is corporate wellness programs. most of these programs rely on "usual care" that includes: basic dietary recommendations, weight loss, smoking, alcohol consumption and metabolic and lipid index targets. a broad-based team of wellness professionals and academics evaluated workplace wellness programs. they unanimously concluded that few wellness programs meet expectations and most are abysmal failures. what separates bad, good, and great programs is "a combination of good design built on behavior change theory, effective implementation using evidence-based practices, and credible measurement and evaluation." to further support the need for more thorough risk assessment, in a global study of risks, the authors concluded "increasingly detailed understanding of the trends in risk exposure and the relative risks for each risk-outcome pair provide insights into both the magnitude of health loss attributable to risks and how modification of risk exposure has contributed to health trends [ ] . these types of data clearly illustrate a path to improved health outcomes through broader and deeper precision and personalized assessment. the risk evaluation tool used in this study, the chronic disease assessment™ (cda), is an on-line health risk assessment and mitigation tool and involves answering approximately questions that probe deeply into lifestyle and environmental sources of risks, behaviors, health attitudes, readiness to change, current and past complaints, problems and diagnoses. the output of the cda is an overall risk score and then sub-sets of scores by risk categories, and a score for each question/answer combination. the overall raw risk score is converted into a letter "grade" reflecting the extent of the individual's risk "portfolio." the letter grade is provided to participants as an easily understood value for their risks, to overcome a lack of health literacy that especially impacts high risk populations. in addition, the cda output generates a series of actions that provide personalized education and actionable solutions to each risk in a participant's risk portfolio. finally, a health revival care plan™ is generated from the risk portfolio, and adjusted by the health coach and the participant, to create a simplified, personalized roadmap to overcome risks and improve health. a major impediment to health improvement is low health literacy. the de facto intervention perpetuating this problem is a prescription for symptom management that requires little knowledge by the patient. deficits in health literacy are associated with poorer health outcomes and higher health-related costs for both individuals and systems. improved health literacy has been associated with reductions in risk behaviors for chronic disease, and decreased rates of hospitalization [ ] . health literacy is a critical and under-examined component of health disparities. according to the national assessment of adult literacy, over a third of u.s. adults have basic or below basic health literacy and have difficulty managing common health-related tasks. limited health literacy poses a significant economic burden to our society, with national estimates indicating that low health literacy costs the u.s. healthcare system from $ to $ billion each year in healthcare dollars [ ] . the nexus of this program, including the cda risk portfolio, actions, care plans, and health coaching, is designed to meet and exceed the united states department of health and human services national action plan to improve health literacy's three goals: ensuring equitable access to health information; creating 'person-centered health information and skills' and supporting the development of the skills needed to attain and maintain good health. a final important aspect of this process, not articulated by the action plan, is illumination of the connection of risks to problems and complaints. the cda collects and reports risks, problems, and complaints together. thus, participants are able to "connect the dots" between risks and problems, like oral health and joint pain or carbohydrate intake and fatigue, as examples. these upstreamdownstream connection realizations improve health literacy and stimulate more sustainable change which manifests in the adoption of actions and plans to eliminate the risks as a solution to their problems as opposed to the usual care option of a drug to control symptoms. this process empowers individuals to be a participant in their own health improvement through recognition of their control over causes and outcomes. within this study, health coaches interacted face-to-face and electronically with participants and groups of participants to implement care plans. coaching activates patients to change through collaborative learning and social support. patient engagement and p medicine, defined as predictive, preventive, personalized and participatory, is an increasingly important component of strategies to prevent and reverse chronic disease, at least within the functional and integrative medical communities. interventions that tailor support to the individual's level of activation, and that build skills and confidence, are effective in increasing patient activation. more highly activated people are more likely to engage in healthy behavior such as eating a healthy diet and getting regular exercise while avoiding health-damaging behavior such as smoking and illegal drug use. these behavioral changes have led to lower rates of hospitalizations and emergency department visits, compared to less activated patients [ ] . a bridge between risk factors and modification in certain intermediate factors like blood pressure and obesity are changes to blood-based biomarkers, which are more objective measures of health. the most routinely performed tests in usual care are for the assessment of kidney and liver health, blood chemistry, lipid markers and metabolic markers. heart disease continues to be the number one cause of morbidity and mortality in the u.s. and globally despite the broad use of cardiovascular disease medications for both prevention and intervention. a study of , patients hospitalized with a heart attack between and showed that almost % had ldl cholesterol levels within guidelines [ ] . these data imply there is room for testing to augment evaluation of cardiovascular risk and cause. in older populations, "concentrations of homocysteine alone can accurately identify those at high risk of cardiovascular mortality, whereas classic risk factors included in the framingham risk score do not" [ ] . in healthy men, adding creactive protein levels to traditional risk factors, the reynolds risk score, improved cardiovascular risk prediction. the intermountain risk score uses common blood measures and assesses risk from the group of markers to develop a risk score. although limited in application, this scoring system has been reported to be predictive of increased mortality risk and provides patients with a more definable goal, the improvement of the score. more comprehensive assessments for risk and disease are emerging including the "allostatic load" and "inflammaging" concepts. each of these approaches considers a broader molecular view, rather than an organ system view of disease. according to mcewen, "when these (our body's) adaptive systems are turned on and turned off again efficiently and not too frequently, the body is able to cope effectively with challenges that it might not otherwise survive. however, there are a number of circumstances in which allostatic systems may either be over-stimulated or not perform normally, and this condition has been termed "allostatic load" or the price of adaptation" [ ] . diabetes is a relevant example, where insulin production is frequently elevated in response to regular highly absorbable carbohydrate intake. claudio franceschi coined the term "inflammaging" in to describe the concept of low-grade chronic inflammation and its impact on health. inflammaging was described as an extension of the "network theory of aging" [ ] . similar to the allostatic load, a global reduction in the capacity to cope with a variety of stressors and a concomitant progressive increase in proinflammatory status are considered the major characteristics of the inflammation aging process and susceptibility to premature disease and mortality. biomarkers for inflammaging are readily available and inexpensive but seldom obtain in usual care, especially in the implementation disease prevention strategies. according to gay et al., the allostatic load leads to dysregulation of the neuroendocrine system and subsequent elevation in inflammatory markers, leading to metabolic syndrome and chronic diseases such as cardiovascular disease [ ] . thus, the allostatic load and inflammaging are both measured, at least in part, with inflammatory markers like c-reactive protein, cortisol levels, glycosylated hemoglobin, white blood cell counts, and fibrinogen as examples. independent of inflammatory markers, multiple biomarkers, in general, improve the predictive power of a panel. in a study of people assessed with biomarkers, persons with multi-marker scores in the highest quintile as compared with those with scores in the lowest two quintiles had elevated risks of death and major cardiovascular events of . and . (adjusted hazard ratios), respectively [ ] . this far exceeds the predictive hazard ratio for cholesterol which varies from . to . depending upon the study [ ] . a hazard ratio of < means cholesterol levels were determined to be protective and stave off early mortality. numerous studies and reviews consistently show the value of multiple markers in real-world prediction of disease events and premature mortality. the chronic disease temperature™ (cdt) risk scale used in this study combines emerging concepts for improving the evaluation of disease risk and measurement of active disease. the significant attributes of the cdt scale are: . consideration of multiple biomarkers, . selection of markers based on traditional and new predictive markers based on inflammaging and the allostatic load, . harmonizing each marker to a standard endpoint -increase in early mortality risk, . consideration of risk contribution based on log-linear deciles of marker levels and individual marker hazard ratios for mortality, and . combination of the risk values from each marker into a single number score to accommodate limited health literacy and to set an understandable objective target for health improvement. the aggregate cdt score is an indicator of early mortality and associated total morbidity, while the values for each marker reflect both mortality risk and disease risk based on the association of a given marker to disease. this single number may be an important bridge to better health literacy as most patients do not understand the meaning of their current lab values. the cdt does not constitute a medical diagnosis of disease any more than does any individual marker, like homocysteine, but does statistically afford better predictive capability and measurement of disease progression or regression. the cdt output promotes the concept that health and disease lie on a log-linear continuum rather than being an on/off switch. in this study, the implementation of risk assessment, health and disease measurement, care plans, and frequent measurement leading to continuous improvement represents a needed response to challenges society faces from chronic diseases. this "systems approach" is designed to better connect across fragmented divisions in healthcare without bias of discipline. that is, fundamentally, most chronic diseases are connected at root-cause physiological processes. the ultimate goal is to create new risk/plan/action/outcome connections that facilitate learning opportunities and iterative advancement in treatment and preventative methods for chronic disease. another consideration is the order applied to the interventions including "in series" or "in parallel". an example is diabetes that needs to be managed for the prevention of heart disease, yet these diseases lie in different medical silos. the final objective ensures that workup of any individual patient, regardless of the presumed scope of the illness, embraces all possible causal factors. the purpose of this study was to assess the effectiveness and safety of this novel care model for the prevention and reversal of a broad spectrum of chronic diseases and complaints over a nine-month period. primary endpoints to assess the effectiveness of the intervention were changes in health risk assessment scoring, changes in documented health complaints, changes in medication usage, changes in vital signs, changes to individual blood-based biomarkers designed to measure chronic health, and changes to the multiple marker risk score, the cdt. we conducted an open-label, randomized, controlled, before-and-after nine-month study of a high intensity remote and on-site care intervention named a health revival process (hrp). participants included a group of individuals who, at the time, were employed by a mid-west fortune , manufacturing company with approximately , employees at that site. no formal control group was established but non-participant health status over the period was tracked using claims data for diagnoses, complaints, medication use, and healthcare spending. participation was voluntary and recruitment started in november of , implemented by our company and the employer, focused on higher claims and more chronically sick individuals who were motivated to overcome unresolved chronic health issues. no rigid participation inclusion criteria were used other than each individual had at least one diagnosed chronic condition, was formerly or currently on a medication for a chronic disease, and was a high healthcare claimant (> $ /year currently or within the past three years) if that data was available. not all participants had claims data from previous years mainly due to their health plan and choice or employment history with the company. from those interested in the program and met the criteria, retrospective health data (medical claims) were reconciled to finalize the -person cohort without consideration for a specific type of condition. although not a formal clinical study, all procedures performed in the program involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the helsinki declaration and its later amendments or comparable ethical standards. ethical oversight was provided by the existing primary care clinic management organization, but not under any formal written agreement other than to monitor for patient safety. informed consent, medical releases, and participation contracts were obtained from all participants included in the program. these documents were completed after each participant was provided detailed information about the program. all data were acquired in strict conformance with health data privacy laws by medical personnel and all stored data were contained on a health insurance portability and accountability act (hipaa) compliant cloud. the health revival process: participants in the health revival process (hrp) underwent medical history review, completed a +/-question online health risk assessment (chronic disease assessment™ (cda)) and laboratory testing for serum-based biomarkers (chronic disease temperature™ (cdt)). participants without a medical exam within the past months had one perform by our doctor, to determine their baseline health and risk status. all data obtained on participants, including problems, diagnoses, health complaints, reconciled medications, vitals, food journal, and other measurements were entered into our proprietary health revival software. upon qualifying, hrp participants began one-on-one health coaching encounters. the initial coaching session included active listening by the coach and reconciliation between the output of the cda risk assessment and health concerns, problems, and information articulated by the participant at that first encounter. any discrepancy between the responses to the cda questions and information presented to the health coach were verified and the cda was appropriate updated and annotated. the health coach, using the recommendations promoted by the up-to-date hrp software record, developed a personalized health roadmap referred to as a person's health revival care plan™ (hrcp). our medical doctor reviewed and finalized that document and then conferred with the coach on next steps appropriate for the participant. our doctor and the non-hrp medical doctors ensured that the recommendations and suggestions made by the health coach did not violate the health coaches license to provide advice. there was reasonable fidelity to the hrp delivery as everyone saw the same coach and doctor over the same time period. however, participants experienced different levels of coaching and doctor intensity based on the extent of their risk portfolio and medical needs. participants had continuous access to their health information, suggestions, and progress within the hrp software which maintained much of their personal health information. specifically, a participant could follow, track, and monitor changes in health measures and interact with specific, personalized content (written, audio, and video) curated automatically by the hrp system based on their personalized health information inputs including, their cda risk assessment, cdt markers, and vital signs recorded in the system. in addition, the participant portal included their personalized hrcp that created the structure for their hrp. participants were able to work with their health coach on the plan, follow the plan through a selfguided process, or some hybrid between the two paths. the health coach was able to monitor the self-guided process through system feedback that included reports on system logins and completed "actions" and "goals." completed actions occurred after a participant accessed content relevant to a health risk determined by the hrcp and choose a selection after reviewing the information like "completed" or "deferred." most participants relied on the health coach for structure, direction, and motivation. figure shows features of the patient portal health revival dashboard. participants in the hrp retained their existing providers for acute disease management and routine medical checkups. care coordination between existing providers and hrp care team occurred as needed. in particular, the hrp doctor and pcp discussed any possible interactions between supplements, lifestyle changes, and current medications. of frequent concern was a need to change the dose or use of insulin, other diabetic medications, blood pressure, cholesterol, and corticosteroid medications as the participant's health improved through lifestyle modification. frequency and type of biomarker tracking, beyond the before-and-after cdt labs, were individualized by the hrp doctor on the basis of care needs and progress as recorded by participants in updated cdas and health coaches in updated hrcps and coaching notes. participants on insulin were contacted at least weekly to assess any potential for hypoglycemia. either the pcp or the hrp doctor made medication modifications. chronic disease assessment: the cda was available electronically through a web browser and included +/-questions through a series of shorter surveys, with the participant able to stop and restart the survey at any point where they left off. each question included fixed answer choices from a single option to as many as options depending upon the scope of the question. in some instances, a question allowed for multiple answer selections while in others, only a single response could be recorded. each question/answer combination was given a risk score and assigned one or more attributes of risk based on our study of the medical literature for potential outcomes associated with the specific behavior attribute. the cda included consideration of common risks and disease root causes determined from our own clinical experience and published clinical case studies, population and randomized clinical trials. for example, the cda gave considered to oral health, gut health, eye health status, macro-and micronutrient imbalances, and indications of chronic and occult infection. the output of the cda was a raw score that converted to a letter "grade" reflecting the extent of the risk "portfolio" determined by the assessment. each letter grade, a-f, spanned a range of raw scores. the purpose of the letter grade was to convert a numeric value into a more meaningful and recognizable risk level. in addition, the software interface outputted an action or a series of actions for many of the question/answer pairs, through if/then/else logic. the actions are those known or believed to lead to a reduction in that risk based on peer-reviewed published studies or our own experience. the actions are bundles of content that explain the risk or potential risks and offer suggestions to ameliorate the risk. all this content was made available to participants through their health revival dashboard (hrd). example questions from the cda are provided in figure . chronic disease temperature: routine labs and the cdt biomarker panel were drawn at the on-site clinic by non-hrp technicians working for the primary care provider company. the labs drawn on each individual and the thresholds for chronic health considerations are described elsewhere [ ] . in summary, reference intervals were not used to determine health status and risk. instead, our team of biostatisticians reviewed the medical literature to determine the threshold level or levels for each biomarker, they indicated a statistically significant increase in early mortality associated with that marker. each marker was assigned escalating risk based on log-linear curve fitting to published information on mortality risk and biomarker raw value. many of the cdt biomarkers are common biomarkers with some being less commonly obtained in usual care. the ordering doctor of record was held responsible for ensuring any participant with an abnormal lab value, based on usual care reference intervals, notified the participant and arranged for appropriate care to correct the abnormal value. the "tighter" thresholds used as part of the cdt labs were used only by the hrp doctor and not used for making a medical diagnosis. instead, this more sensitive scale of normal vs abnormal lab values was used to measure changes in participant's physiology concomitant with lifestyle changes. this more sensitive scale for each biomarker and the overall cdt value, helped assess participant's health trends by recognizing that disease is not an on/off switch, but rather a continuum. for example, and hba c level of . %, although not a diagnosis for type diabetes, is a strong indicator of future type diabetes. a goal value of < . % was established for all participants to optimize insulin sensitivity and avoid future diabetes risk, assuming that value was obtained through lifestyle improvement and not pharmaceutical intervention. this logic was applied to all cdt markers. the interventions affected by the hrp through the hrcp were individualized to each participant and included a consideration of the participant's readiness to change and the likely sustainability of any given change as determined by their responses to chronic disease assessment questions and discussions with their health coach. the intensity of coaching was predetermined, but not fixed, by the cda grade. the coaching time allotted to each participant based on the cda grade is provided in table . doctor time allocation was approximately / th coaching time. the main risk considerations were a reduction in inflammation through: more movement, increased nutrient density of foods, improvement in digestion/absorption by improving gut balance and activity, increasing probiotic and prebiotics foods, elimination of high glycemic foods, better oral health maintenance, increased intake of healthy fats and omega- fatty acids, increased micronutrients to support hormone production, stress reduction, brain health through reducing whole-body inflammation, and consumption of greater amounts of fat-soluble vitamins, as examples. no specific nutrition program was recommended to the participants as a whole. instead a simple process of substitution of one food, considered of low nutrient value for another of higher value, was made as recommended by the health coach. recommendations were made on an individualized basis based on participant preferences, to affect a gradual and sustainable change from the standard american diet (sad) that was prolific throughout the cohort, to a new food consumption pattern with increased micronutrient density, fiber, and fat with less carbohydrate and sugar consumption. short term (one to three months) nutritional ketosis was suggested for a few highly insulin resistant and diabetic patients but no participants fully achieved nutritional ketosis during the nine-month period. however, these participants achieved a significant reduction in total carbohydrate consumption with a shift to low glycemic index food and those containing higher concentrations of marine, monounsaturated, and saturated fats. supplements were provided as part of the program and compliance with supplementation was near % based on self-reporting and resupply orders. at the outset of the program, after evaluation of cdt labs, cda reported dietary information, and food journals, the participants were provided any or all of the following supplements based on individually assessed deficiencies: multivitamin/mineral ( qd); vitamin d ( - , iu, qd); cod liver oil ( - g, qd); magnesium glycinate ( - mg, qd); vitamin k ( mcg, qd); probiotic ( - billion organisms, qd). supplements were provided only when deemed appropriate by the hrp doctor and were phased in then phased out over the nine-month period as the doctor determine that nutritional deficiencies or insufficiencies were being mitigated by the program. the purpose of the supplements was to quickly overcome apparent nutritional deficiencies. as part of the hrcp, foods that contained nutrients provided by the supplements were recommended and, when adopted, enabled the gradual elimination of supplementation without compromising nutritional needs. the main behavioral change strategy, executed by the doctor and coach care team, was to slowly and gradually ease a participant into change. the frequency of coaching sessions, dictated by the need of the participant (cda letter grade), including their burden or disease and risk, and their motivation, was adjusted to improve compliance. most participants suffered from some health ailment that impacted their daily wellbeing. improvement in general wellbeing, which started to be noticed by participants by the end of month , provided the motivation to continue to adopt gradual modifications to lifestyle. to help participants understand that the hrp is not a quick fix, our coaches explained that we have determined a general "rule of thumb" for the time required to improve health significantly. if a disease, like diabetes, has been slowly developing over five years, it will take at least five months of effort to reverse the disease, assuming the interventions are appropriate. outcome measures: in-clinic vital signs, health risk assessment (cda) risk score and list, and biomarkers were obtained at baseline and at the end of the -month program. problems, complaints and medications were reconciled at each health coaching and doctor encounter. fasted and non-fasted blood draws were obtained by clinic pcp staff using routine procedures. samples were provided to and analyzed by quest diagnostics using standard operating procedures. primary outcomes were: changes in biomarker values; risk scores; reported diagnoses; vital signs; weight; and medication use. secondary outcomes included reported complaints, for example, lack of energy, chronic pain, sleeplessness, mood issues, and general lack of wellbeing. the baseline demographics of the final hrp participants are presented in table . all participants were caucasian of european heritage. at baseline, % of hrp participants were actively taking pharmaceuticals for a medical problem and % were diagnosed with at least chronic condition. this reflects a substantially higher percentage of chronically ill individuals compared to the u.s. national average of % of u.s. adults having at least one chronic condition. on average, the group was taking . prescriptions per person. the major class of medications included: diabetes medications, injectable insulin, statins, blood pressure lowering, pain, mood (ssris), bisphosphonates, steroids, thyroid hormone, and proton pump inhibitors. the final participant number of was established after left the program. two were dismissed from the program for compliance reasons, four left early to join a weight loss program, two left because of the time commitment, and two left due to potential interactions between current medications and supplements as encouraged by their pcp, for a total of . %. there was no clear demographic trend between those who remained in the program versus those who dropped out. chronic disease assessment™ (cda): on average, the -participant cohort lowered their cda score by points ( %) from a raw value of to a new value of over six months. each point lowered reflected a reduction in a disease risk or resolution of a health problem or complaint. risks were scored on a - scale, with representing a minor risk or problem and representing a major risk or problem. the initial population cda grade was d+, assigned based on a range of raw numeric scores calculated from the survey, and the final grade after months of the hrp was c+. ninety-four percent of the group experienced an improvement in their risks while % of the cohort experienced a worsening of their cda grade ( figure ) . participants did not have their initial cda answers to refer to when they retook the assessment six months into the program. chronic disease temperature™ (cdt): on average, the -participant cohort lowered their cdt score from . to . . the cdt is based on a "degree" scale calculated by adding the risk contribution from each biomarker to . to arrive at the participant's cdt. the average chronic disease risk reduction in cdt was % (figure ). all % of participants whose cda grade worsened also experienced an adverse change in their cdt score. three participants improved their reported cda grade but witnessed an adverse change in their cdt. the cdt included several markers that are classified as "acute phase" reactants. in "acute-phase proteins and other systemic responses to inflammation," the authors explain that markers of chronic systemic inflammation are also subject to change acutely [ ] . for example, c-reactive protein elevates during the acute phase of pneumococcal pneumonia. c-reactive protein has an acute phase relaxation half-life of approximately one day upon removal of the insult whereas the half-life of fibrinogen is about one week. two of the three participants with an improved cda but worsened cdt experienced adverse physiological changes due to documented acute circumstances. retest was not available during the nine-month program to confirm our suspicion about the cause of the elevation. one recently underwent surgery and was recovering slowly. another participant was receiving ongoing treatment for a complex acute condition managed by the patient's pcp. other participants whose cdt worsened were in the hrp and a calorie-restricting weight loss program administered by third parties. the weight loss program was calorie counting-based with no guidance provided on macro and micronutrients. these individuals, although in the hcp, were less flexible to our coach's dietary suggestions because of the calorie restriction. for example, a participant refused to take cod liver oil because each capsule contributed approximately calories to their daily calorie allotment. our results demonstrated, in this small subgroup, that people in poor health and with a highly elevated cdt, confirming their health status objectively, may be contraindicated for a sustained calorie restriction program without nutritional guidance. although the literature is rich in studies suggesting that calorie restriction improves lifespan and reduces inflammatory markers, emerging studies emphasize that calorie restriction must be implemented without malnutrition that comes from low nutrient-dense foods processed foods. macro-and micronutrient intake of all participants was monitored with a food journal. worsening in cdt markers in people on a calorie-restricted diet correlated to micronutrient malnutrition exacerbated by reduced total calorie intake. malnutrition status was established in these individuals by determining their daily nutrient recommendation from the dri calculator for healthcare professionals provided by the usda and comparing the results to nutrients consumed based on available nutritional labels for foods consumed. there are numerous studies on the association between lifestyle behaviors and chronic disease risk. in large prospective studies, like the nurses' health study, vague conclusions are made about the association of smoking, regular physical activity, maintaining normal body mass index, eating a healthy diet and chronic disease proliferation [ ] . the individualized cda risk values potentially increase the precision, personalization, and accuracy of risk-to-disease relationship measurement. figure provides a view of the change in the cda risk score and its relationship to the cdt value for the biomarker panel at the beginning and end of the -month hrp program for the entire population. the same data are presented in figure as bubble chart with the before and after data superimposed on the same scale. temperature score) before and after six months of the hrp program notable is the reasonably smooth relationship between the two risks scores, the subjective cda and the more objective cdt. we conclude, from these data, reducing the most basic health risks, over time, may lead to a reduction in cytokine burden with often concomitant change in diagnosed chronic diseases. increasing the "n" in our database and making appropriate adjustments to assigned subjective risk values within the algorithm offers the potential to improve the correlation between determinants of health risks and physiological health status. the individualized statistics for the cda, cdt, and biomarkers comprising the cdt to evaluate participants health and risk are provided in table . score mean before mean after mean difference standard deviation t test value cdt is the chronic disease temperature biomarker score as a relative value with . considered optimal and elevated values indicating chronic risk; hba c is expressed as a %; glucose is expressed as mg/dl; nlr is the neutrophil to lymphocyte ratio; hs-crp is high sensitivity c-reactive protein or c-reactive protein, cardiac expressed as mg/l; insulin is expressed as uiu/ml; hdl is expressed as mg/dl; triglycerides are expressed as mg/dl; vitamin d is expressed as ng/ml; uric acid is expressed as mg/dl; wbc is the white blood cell count expressed as cells/ul; rdw is the red blood cell distribution width expresses as a %; ab neutrophils are neutrophils (absolute) expressed as cells/ul; esr is the sedimentation rate-westergren expressed in mm/hr; fibrinogen is fibrinogen activity expressed as mg/dl; homocysteine is expressed as umol/l; and aip is the atherogenic index of plasma expressed as the log(triglycerides/hdl) glycosylated hemoglobin (a c): a c, a -day retrospective average of blood glucose, contributes to an assessment of metabolic risk along with fasting glucose and insulin. a current therapeutic goal in usual care is to lower the a c value of diabetics, those with a c values above . %, with pharmaceuticals. the accord study shows that tight pharmaceutical control of blood sugar in those with severe insulin resistance suffer a significant increase in adverse cardiovascular events and mortality compared to those with less tight control [ ] . lifestyle interventions offer another approach to glycemic control and does so without risk of hypoglycemia and other side effects of the pharmaceutical approach. in the cohort of , none had optimal a c levels, defined as . %- . %. even a . % increase in a c above % increases the year risk for diabetes (odds ratio > . ) and the risk of diabetes increases exponentially with a c. in the participant cohort, at the end of the hrp, % (all but ) lowered their a c value ( insulin is the most sensitive marker for early metabolic risk because it increases first as an individual becomes insulin resistant. even values slightly above normal, and well below a diagnosis of diabetes, contribute to serious chronic diseases in the future, including alzheimer's and cardiovascular disease. type diabetes is associated with increased risk of cancer. hyperinsulinemia (elevated insulin levels) and insulin resistance are apparently the link. in a -year mortality study, individuals in the highest quintile of serum insulin had a % higher risk of cancer mortality and a % higher risk of gastrointestinal cancer mortality [ ] . the authors of this study concluded that hyperinsulinemia/insulin resistance is associated with cancer mortality independently of diabetes, obesity/visceral obesity and metabolic syndrome. in the -person cohort, participants ( %) were at elevated metabolic and associated chronic risk. six of the ( %) experienced a double digit drop in fasting insulin, of ( %) dropped from the high-risk category to a lower risk level, ( %) lowered insulin levels sufficiently to reduce their cancer risk severity category, ( %) changed little and stayed in the same risk category and move up one risk category ( [ ] . in the -person cohort, % of participants who were at high risk for cardiovascular disease, based on hs-crp level > , lowered that risk ( table ) . [ ] . the aip average value before the hrp was . and lowered to . at the end of the hrp. conventionally the rdw test, which is a part of a complete blood count, is used to help determine anemia status. however, it is also a marker of inflammation and often tracks with crp. red blood cells elongate and deform when flowing through capillaries, which may explain the association between red blood cell widths, vascular inflammation, and increased cardiovascular morbidity and mortality. in the -person cohort, % of participants at elevated risk for cardiovascular disease based on rdw levels lowered their risk ( table ) . white blood cell counts (wbc) is a predictor of strokes, heart attacks, and fatal heart disease. in the women's health initiative involving , women from - years of age, those with approximately , white cells per ml had more than double the risk of fatal heart disease than women with cells per ml [ ] . white blood cell counts in the normal range for acute indications are now more widely recognized as a predictor of adverse chronic outcomes. in the -person cohort, three individuals had high cardiovascular disease risk based on wbc levels, and % lowered that risk through lifestyle modifications. in addition, % of those with moderate risk moved to either low or very low risk as assessed by risk quartiles for wbc. in general, % of participants moved from a high to a lower risk status ( table ) . multiple studies show a significant inverse relationship between -hydroxy vitamin d (d ) status and cancer mortality. in a fifteen-year study of nearly , participants, an increment increase of ng/ml was associated with a % reduction in total cancer incidence, % reduction in total cancer mortality and statistically significant reductions in colorectal, pancreatic, esophageal, oral, and pharyngeal cancer mortality [ ] . for cancer, optimal d levels are above ng/ml. at the start of the program, eight participants had optimal levels and that number increased to by the end of the program. insufficient vitamin d, as defined for bone health are values below ng/ml. initially there were participants insufficient for blood d and none were insufficient at the end of the program. the population d levels went from to ng/ml, on average, by the end of the hrp. these data indicate a high degree of compliance with the program recommendations as the increase in d status was largely attributable to consistent supplementation. in general, the increase observed required daily supplementation of iu d daily ( table ). the neutrophil-to-lymphocyte ratio (nlr) is reported to be a robust outcome prognosticator in existing solid tumor cancers. in a study on breast cancer, patients with an nlr > . had substantially higher oneyear and five-year mortality rates compared to those with an nlr < . . the nlr value has similar predictive ability for cardiovascular mortality [ ] . in the cohort of , had nlr above the threshold for adverse cancer outcomes. sixteen of ( %) saw their nlr ratios return to very low risk (normal values) by the end of the program ( and associated changes to cancer and cardiovascular mortality prognosis medication prescription reduction was achieved as part of the outcome measurement. the cohort experienced a % reduction in medication usage, reduction in dose in %, and an avoidance of two costly medications. the prices included in table , below, where the actual pharmacy costs realized by the health plan and did not include any co-pay. the cohort experienced a reduction in chronic disease burden. chronic disease reduction was determined by changes in any of the following: actual change to a medical diagnosis, elimination of a medication associated with an existing diagnosis, changes in a vital sign that indicated a migration out of a diagnosis that was affected without the use of a medication, or change in a biomarker value or values that were initially used to make the diagnosis into a "normal" range without the use of medications (table ) . this participant presented with major risk factors and complaints including lack or exercise, fast food diet, high carbohydrate diet, daily high fructose corn syrup containing beverage consumption, use of omega- containing oils in cooking, statin drug daily prescription for primary cardiac event prevention, severe arthritis, psoriasis, and cataract. the severity of the psoriasis and her job function put her at risk of imminently going on disability. she had seen multiple specialists, was placed on antihistamines and topical steroids but her psoriasis condition continued to worsen. the next treatment option for her was to be etanercept which she declined pending the outcome from the hrp. she indicated that she had not washed her hands without pain in over a year. the hrp included -minute semi-monthly health revival coaching following the participant and care team agreed upon care plan. cholesterol-lowering drug usage was eliminated in the first month as directed by our medical director. health coaching focused mainly on food substitutions, increasing activity, value and use of supplements, a limited set of supplements, and additional care to her oral hygiene. after six months of intensive health revival coaching, many risk factors and complaints, revealed on her cda report, were either removed or reduced including nagging chronic pain. her main complaint, debilitating psoriasis slowly, but completed resolved in five months ( figure ) . however, the first signs of improvement in her psoriasis condition did not appear until month of the program. normally, in the case of autoimmune diseases like psoriasis, food sensitivities or allergies must be addressed. this participant was unwilling to eliminate some of the common allergens like gluten and dairy. she was placed on a modest supplement regiment based on nutritional deficiencies determined from food journaling, including: cod liver oil ( g/day); vitamin d ( , iu/day) and a multivitamin/mineral supplement (taken per label instruction), and the other general supplements included in the "methods" section. positive changes in lab values included: -hydroxy vitamin d status ( to ng/ml); white blood cell counts ( , to , ) ; rdw ( . % to . %); and fibrinogen ( to mg/dl). case : rheumatoid arthritis and type diabetes - -year-old male factory worker with a high school education (table ) . over the first five months, the participant lost pounds through a reduction in carbohydrate consumption, but with no significant change in daily calorie intake. the participant embarked on a substitution diet where, over five months, gluten-containing foods were removed from his diet and replaced with vegetables and marine-and animal-based fats. he was also put on a modest supplementation program including cod liver oil ( g/day); vitamin d ( iu/day); magnesium glycinate ( mg/day); vitamin k ( mcg/day) and a multivitamin/mineral (per label instruction). his type diabetes was reversed as illustrated by his a c dropping from . % to . % and his fasting glucose dropping from to < mg/dl. his pain was substantially eliminated, based on a subjective pain score of / initially, to / . his ra improved to enable him to be able to bend his fingers into a full fist for the first time in over five years (figure ). this participant reported with a severe autoimmune disease, polychondritis, that produced monthly painful flares in cartilage above her shoulders including her ears and eyes. long-term use of steroidal antiinflammatories were implicated in the cataracts and a breast lump that was removed surgically. the cataracts had progressed sufficiently to cause her to be on disability and be unable to drive a car. cataract surgery was not an option due to the severity and unpredictability of eye flares that could cause extremely adverse outcomes if they coincided with surgery. she had seen several specialists including local rheumatologists, natural doctors, and doctors from cleveland clinic with no relief to her condition. she had researched polychondritis on her own, prior to joining this program and eliminated gluten and dairy from her diet but this change did not alter the disease severity or frequency. this participant had made significant changes in her lifestyle prior to this program as reflected in her cda grade, but these changes were insufficient to improve her blood biomarkers indicated by the high cdt value of . , indicative of serious health risk and poor prognosis. our health revival process guided her to continued better choices and involved semi-monthly -minute lifestyle coaching. the main changes made over a six-month period included: increasing healthy fats, reducing carbohydrate intake, increasing micronutrient density, stopping nicotine dependence, improving digestive health with optimizing food choices including increasing stomach acid status, and repopulating gut microflora. at month in the program, her eye and ear flares had subsided sufficiently to allow for a meaningful reduction in eye and oral steroids, ( mg/day to mg/day prednisone). in addition, she was able to have successful cataract surgery which enable her to start driving again, and return to work, both of which were curtailed over one year. the polychondritis may never be cured, however, with appropriate lifestyle management, it is no longer impacting her quality of life. prevention and reversal of chronic and non-communicable diseases continue to be a largely unmet need. a fresh approach is clearly warranted to curb this global scourge. one impediment is the lack of precision and personalization of risk with "poor diet" as an example. and there is a lack of measurement of a broad array of minor, yet important, risks that can easily be overcome. the same suite of risks is continually presented to individuals who historically have not been able to modify or overcome them, with smoking or alcohol consumption as examples. according to khullar in, "we're bad at evaluating risk, how doctors can help," a broader approach involves helping patients systematically identify what's important to them, and based on these goals and preferences, suggesting to them how to think about their options [ ] . this logic is best applied across the entire time-line that defines the slow and insidious development of chronic disease. it starts with lifestyle decisions and habit development early in life that perpetuate into mid-life and then into old age. measurement and a proper medical "workup" regardless of presumed health status is a key strategy and potential motivating factor that is currently lacking. changes in chronic disease biomarkers in asymptomatic people may afford an early warning sign of stealth changes to which many may respond. pathology changes, identified with advanced diagnostics, which generally develop after a long incubation period detectable with proper biomarker evaluation, may facilitate change in the more recalcitrant. each individual has their own motivations. thus, providing patients with an array of choices and recommendations along the health/disease continuum has a higher probability of inciting action and improving outcomes or preventative actions. this study evaluated a new population risk and health assessment and mitigation system where measurements of risk and disease were made across the disease continuum by using finely tuned biomarkers and risk assessment. the output was a broad-reaching care plan assembled through integration of current health survey results, biomarkers, problems, complaints, medications, vital signs, verbal input from the participant to the health coach, and contributions from the care team. the remediation path to improved health developed as a consensus between the participant and care team, of agreed upon steps and actions, that were malleable as the process moved forward. adjustments were made based on participant preferences, success and failures, a solid health data. according to khullar, "patients need to understand their values but also their possible futures. the idea is not to reduce uncertainty, but to help patients clearly envision what life would look like in one outcome versus another, and to better prepare them for the various futures that might unfold." this program was designed to give participants options beyond the management of disease once it has struck. and it included regular monitoring and concomitant course adjustments to help participants attain their goals. this study prospectively observed adults with chronic conditions and unresolved health complaints that remained unresolved under usual care management and treatment. following six months of hrp, participants achieved subjective and objective improvement in health status with % seeing a reduction in multiple blood-based biomarkers and % achieving a reduction is a broad measure of determinants of health risk factors. concurrently participants reported weight loss ( % of the total and % of those with a reported weight loss goal), reduction in reported pain, sleeplessness, memory issues, heartburn, skin rashes, migraines, and daily fatigue. the diabetics in the program had all progressively worsen over the previous two years, as measured by fasting glucose, hba c, and medication usage and all improved under the hrp program. hrp meaningfully improved hba c, fasting insulin, neutrophil-to-lymphocyte ratio, hs-crp, vitamin d, white blood cell counts, red blood cell distribution width, absolute neutrophils -all part of the cdt panel. in addition, hdl, fasting glucose, triglycerides, gfr, atherogenic index of plasma (aip) liver enzymes, and blood pressure improved is most participants with initial abnormal values. aip is emerging as a valuable representation of increased mortality risk. improvement in this lab value ratio was consistent with previous studies using carbohydrate-restricted interventions. however, although the hrp included some level of carbohydrate restriction, this was not a mandate and carbohydrate consumption goals were not set. instead, participants were afforded broader options that met each at their level of readiness to change and did not overwhelm anyone with unachievable objectives. in general, small swap-out suggestions were agreed upon at each encounter. the "pure" study reports are a set of studies that describe components of the nutritional approach used in the hrp. in "fruit, vegetable, and legume intake, and cardiovascular disease and deaths in countries (pure): a prospective cohort study," fruit, vegetable and legume consumption recommendations were - g/day to achieve maximum benefit at reducing non-cardiovascular and total mortality [ ] . the hrp coaches encouraged consumption of three to four servings of these foods per day, focusing on lowest glycemic index choices. in "associations of fats and carbohydrate intake with cardiovascular disease and mortality in countries from five continents (pure): a prospective cohort study," healthy fats were found to be indicated for a reduction of total mortality risk and saturated fats were shown to be inversely associated to stroke risk. the hrp coaches guided participants to swap out carbs, sugars, and some protein in favor of healthy fats in foods and cooking oils with emphasis on increasing saturated, mono-saturated, and marine fats. obtaining nutritional ketosis for a two to three months window was suggested for all the diagnosed type diabetics; however, none achieved sustained ketosis but their metabolic markers indicated improvement of their diabetic conditions during the -month hrp. this suggested that the broader, more personalized risk reduction approach of this hrp, compared to strict carbohydrate restriction, affords metabolic profile results without the potential risks associated with carbohydrate starvation in insulinresistant subjects. reducing whole body inflammation was the primary objective of each encounter, not just reducing the glycemic value of food. examples included switching out proinflammatory for anti-inflammatory cooking oils, lowering glycemic value and load of substituted foods, reducing frequency of fast food consumption, improving oral hygiene, managing stress, establishing better sleep and rest patterns, enhancing hydration, improving micronutrient density of foods consumed, establishing more frequent movement routines, and consuming more gut-supporting foods. the regular health coach encounters that included reviewing risk factors, vitals, and medication usage, with doctor supervision, may have provided behavior reinforcement. further, it is plausible that this multi-risk amelioration care model allowed from both broader and greater adoption and improvements compared to interventions focused on fewer factors. in this hrp we effectively leveraged credible measurement and evaluation, linked these findings to participant's unresolved and nagging health complaints, and facilitated behavioral change leading to health improvement in most participants. the program did not rely only on usual care measures of health. participants were not confronted with high hurdles to health improvement that often discourage engagement. instead, the program centered around meeting a person at their level of readiness and capitalizing on small triumphs that eventually led to measurable health improvements recognized by the individual that led to a cycle of improvement rather than deterioration. no episodes of adverse events were attributable to the hrp. one insulin-dependent type diabetic participant showed a sudden increase in fasting insulin, from . to μu/ml, which was reported to his pcp for medication adjustment. several participants reported dizziness and either the hrp or pcp lowered their blood pressure medication dose that, in all cases, resolved the complaint. prior studies have demonstrated favorable cost reductions in broad-based wellness and disease management programs. most of the cost-saving and health maintenance were attributed to the management of existing disease rather than prevention and required a strong evidence-based approach. a strength of this hrp was an emphasis on root-causes of and reversal of disease rather than just case management. additionally, this study reflected a real-world workplace environment with a distribution of both white-and blue-collar workers participating and with a range of diseases and aliments. weaknesses included a lack of a representative control group, single location and participants were mostly caucasian. the study was not of sufficient size and duration to measure hard endpoints including mortality and adverse health events. future studies of this nature could include multisite randomized controlled trials with greater racial and ethnic diversity, and longer duration. this highly personalized and scalable health revival study protocol demonstrated that a broad array of chronic health complaints and problems can be controlled and reversed by methodically eliminating seemingly small lifestyle-induced health risks. it also demonstrated that the lifestyle risk tool, the chronic disease assessment™, and the biomarker panel, the chronic disease temperature™, that were used to develop care plans, changed in correspondence with participant-and medical staff-reported health improvements. therefore, these tools may be valuable for the measurement and mitigation of chronic disease risk and chronic diseases generally. importantly, the implementation of this program is low cost, using inexpensive on-line survey tools, biomarkers, and health coaching. additionally, this program is well suited to be implemented in large populations through surveying, obtaining labs through national networks, and performing group coaching sessions based on common risks identified through the risk assessment tool. more studies using this overall hrp approach are required to validate the measurement methods, processes, and outcomes. this approach offers a potentially important health delivery modality in a world with escalating chronic disease morbidity and mortality. acquired in strict conformance with health data privacy laws by medical personnel and stored and managed in a hipaa compliant emr. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. global status report on 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neutrophil to lymphocyte ratio for long-term cardiovascular mortality in peripheral arterial occlusive disease we're bad at evaluating risk. how doctors can help . the new york times fruit, vegetable, and legume intake, and cardiovascular disease and deaths in countries (pure): a prospective cohort study the authors thank the invaluable assistance of dr. michael l. carter, dr. trent austin, and jasmin lewis human subjects: consent was obtained by all participants in this study. neco irb issued approval t.the neco irb has approved this study as it was conducted in conjunction with routine clinical practice. all procedures performed in the program involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the helsinki declaration and its later amendments or comparable ethical standards. ethical oversight was provided by the existing primary care doctors who were not part of the program. informed consent, medical releases, and participation contracts were obtained from all participants included in the program. these documents were completed after each participant was provided detailed information about the program. all data was key: cord- -jdvzpvdx authors: pata, rama kanth; ahmady, abolfazl; kiani, roudabeh title: human immunodeficiency virus: a dark cloud with silver lining during the covid- pandemic date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: jdvzpvdx in december , china reported a cluster of pneumonia patients infected by a new virus from the coronavirus family called severe acute respiratory syndrome coronavirus (sars-cov- ). the virus quickly spread around the world and infected millions of people, and the world health organization (who) declared coronavirus disease (covid- ) a pandemic on march , . although some patients show only mild or even asymptomatic response to this infection, severe disease with rapid progression to acute respiratory distress and multiorgan failure is also commonly seen. in this report, we discuss three cases of hiv patients who survived covid- . severe acute respiratory syndrome coronavirus (sars-cov- ) is a coronavirus with a positivesense single-stranded ribonucleic acid (rna). it is believed to have originated in bats because of the % genomic similarities it has with bat coronaviruses. the high incubation period ( - days) in conjunction with the high survivability of this virus and a high reproductive number (r ranging from . to . , with a mean of . in one study and to . in another) [ ] [ ] [ ] have caused it to spread quickly throughout the world. on march , , the world health organization (who) declared the coronavirus disease (covid- ) outbreak a global pandemic. the covid- pandemic has expanded rapidly worldwide. the number of cases has skyrocketed as days passed, and mortality has rapidly increased globally. in this report, we present three cases of hiv patients who survived covid- . on march , , a -year-old female with a past medical history of asthma, coronary artery disease (status post-coronary artery bypass graft two years ago), hypertension, hyperlipidemia, and hiv on antiretroviral medications [bictegrav/emtricit/tenofov ala (biktarvy® - - mg tablet, gilead sciences, foster city, ca) and darunavir/cobicistat (prezcobix® mg- mg tablet, janssen pharmaceutica, beerse, belgium)] was brought in by emergency medical services (ems) for progressively worsening shortening of breath associated with weakness and two episodes of watery non-bloody diarrhea for one day. she had sought medical attention two days ago at an emergency department where she had been tested for covid- [reverse transcription-polymerase chain reaction (rt-pcr)]. she had been discharged on levofloxacin. she returned to the hospital for worsening of symptoms but denied any new symptoms including fever or cough. the covid- rt-pcr came back positive later. her chest ct scan showed multifocal patchy consolidations of the bilateral upper and lower lobes, and the electrocardiogram showed normal sinus rhythm with corrected qt interval (qtc) of ms and t wave inversion in v . two sets of blood and urine cultures were negative. other laboratory findings are presented in table (column: case ) . she was admitted for covid- pneumonia and placed on cardiac monitoring due to elevated troponin levels ( . ng/ml) and d-dimer ( , ng/ml). additionally, she was started on iv antibiotics (ceftriaxone and azithromycin) and iv fluids. ct scan of the chest on admission incidentally showed cholelithiasis without cholecystitis likely due to acute pancreatitis; amylase and lipase were , u/l and > u/l respectively, and toxicology was negative for alcohol. she was kept npo; a hepatobiliary iminodiacetic acid (hida) scan was performed after she refused a ct scan of the abdomen, which showed no scintigraphic evidence of biliary obstruction. in addition, heparin [ , units every hours (q h)] was started as standard deep vein thrombosis (dvt) prophylaxis. she had an acute drop in hemoglobin during her stay, and a fecal occult blood test was performed, which came back positive (march , ). therefore, heparin was discontinued, and she remained npo in view of concomitant pancreatitis and was started on an iv proton pump inhibitor. hemoglobin levels were monitored, and no further drop in hemoglobin level, hematemesis, or melena was observed. her clinical condition improved, hence diet was modified based on what she could tolerate. during the first four days of admission, she had fluctuating fever spikes ( figure ) . additionally, throughout her stay, she had a few episodes of drops in her oxygen saturation ( figure ) . consequently, she was placed on high flow oxygen cannula ( . l/min), and her oxygen saturation subsequently improved ( table (column: case ). he developed desaturation with increasing respiratory distress and altered mental status during his medical floor stay. arterial blood gas (abg) at l nasal cannula showed hypoxia with pao of mmhg and o saturation of . % (figure ) . consequently, he was upgraded to the intensive care unit due to the impeding respiratory arrest for close monitoring and further management; however, he refused intubation. during his stay, he began saturating well on a non-rebreather ( table ) and was downgraded to the floor. he finished a course of ceftriaxone ( gm daily ivpb for eight days) and azithromycin ( mg ivpb daily for seven days) and received hydroxychloroquine ( mg po daily) for days while qtc interval and electrolytes level were monitored. additionally, he received hemodialysis as per his schedule. on april , , sputum culture grew klebsiella pneumonia for which he received antibiotics (meropenem mg daily for three days and ciprofloxacin mg po daily for two days). his medical condition improved ( figure ) , and he was downgraded to the floor after nine days of icu care. he was eventually discharged on april , , with a prescription of days of ciprofloxacin and instructions on social distancing and follow-up appointments. presented for feeling unwell for three days, specifically complaining of headaches, myalgia, dry cough, shortness of breath, and fever. his chest ct scan showed patchy infiltrates throughout both lungs with a ground-glass pattern, more prominent at the periphery and at the lung bases ( figure ) . additionally, a covid- rt-pcr test was positive, and two blood cultures showed no growth. moreover, the electrocardiogram showed sinus rhythm with a corrected qt interval (qtc) of ms. other blood test results are shown in table (column: case ). overall, he finished a course of ceftriaxone ( gm daily for six days), tamiflu® (roche pharma, basel, switzerland, mg daily for days), hydroxychloroquine ( mg for five days), and azithromycin ( mg daily for four days) while qtc interval and electrolytes level were monitored. during his admission, he had spikes of fever; consequently, he was put on vancomycin and meropenem until he was afebrile for hours. furthermore, he had a few episodes of the mild drop in his oxygen saturation for which he was put on l nasal cannula, and his saturation subsequently improved ( table ) . his symptoms improved gradually (figures , ) , and he was discharged on april , , and advised to practice social distancing. the leading cause of mortality in covid- patients is acute respiratory distress syndrome (ards). some covid- patients present with a cytokine profile resembling secondary haemophagocytic lymphohistiocytosis (shlh), a fulminant and fatal hypercytokinemia with multiorgan failure, which is most commonly triggered by a viral infection and most frequently presents with fever, cytopenias, and hyperferritinemia with the involvement of the lungs (ards) [ ] [ ] . systemic elevation in pyrogenic cytokines such as interleukin- (il- ), il- , and tumor necrosis factor-α (tnf-α) has been observed, suggesting that covid- triggers hyper inflammation that initiates ards via a complex inter-relationship of cytokines and proinflammatory mediators involving humoral and cellular responses [ , , ] . data suggest that the host immune status may influence the progression of covid- . some studies have shown higher levels of type i interferon (ifn-i) in hiv patients, which may help clear the covid- infection. additionally, delayed antibody response to covid- in hiv patients has been reported, suggesting a possible influence of immune deficiency in hiv patients on clearance of covid- [ ] . the impact of multiple anti-retroviral drugs such as lopinavir-boosted ritonavir, darunavir, and remdesivir on covid- has been studied. a case report by holshue et al. showed clinical improvement in the first case of covid- in the united states after the use of remdesivir [ ] . currently, gilead sciences has initiated two phase- studies investigating the efficacy of remdesivir for the treatment of covid- [ ] . clinical trials have shown varying levels of effectiveness of lopinavir-boosted ritonavir on reducing mortality rates in covid- patients. some reports suggest that the addition of lopinavir/ritonavir to the initial treatment reduces the overall death rate and intubation rate [ , ] . additionally, janssen has announced that even though anecdotal instances of darunavir being used for the treatment of covid- have been reported, it is ineffective in treating covid- patients due to its low affinity to coronavirus protease [ ] [ ] . we propose that hiv could have modulated the immune system in these three patients in a way that led to a less severe immune response to covid- . furthermore, the lower severity of covid- in these hiv patients could be explained by the effect of the anti-retroviral medications these patients were taking. in order to confirm the validity of these hypotheses and show that it was not just the heterogenicity playing a role in such less severe immune response to covid- , extensive retrospective studies or prospective randomized control studies should be conducted to further evaluate these hypotheses. additionally, we recommend further studies on anti-retroviral medications and their effect on covid- patients. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. the reproductive number of covid- is higher compared to sars coronavirus unique epidemiological and clinical features of the emerging novel coronavirus pneumonia (covid- ) implicate special control measures a comprehensive literature review on the clinical presentation, and management of the pandemic coronavirus disease (covid- ) covid- : consider cytokine storm syndromes and immunosuppression the role of cytokines including interleukin- in covid- induced pneumonia and macrophage activation syndrome-like disease acute lung injury/acute respiratory distress syndrome (ali/ards): the mechanism, present strategies and future perspectives of therapies early virus clearance and delayed antibody response in a case of covid- with a history of co-infection with hiv- and hcv (epub ahead of print) first case of novel coronavirus in the united states gilead sciences initiates two phase studies of investigational antiviral remdesivir for the treatment of covid- emerging pharmacotherapies for covid- covid- in patients with hiv: clinical case series lack of evidence to support use of darunavir-based treatments for sars-cov- we would like to acknowledge the hard work all the medical staff around the world, especially those in new york, did during the covid- pandemic. key: cord- - lj g tq authors: salah, omer; faisal, mohannad; alshahwani, israa; elhiday, abdelhaleem title: bilateral hemopneumothorax in covid- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: lj g tq a -year-old previously healthy male presented with fever and cough for seven days, positive for covid- , and was admitted to hazm meberik general hospital and treated as a case of severe covid- pneumonia. after improvement, he was transferred to a quarantine facility, and he later developed bilateral hemopneumothorax requiring bilateral chest tubes. high-resolution ct showed bilateral emphysematous bullous disease. tuberculosis workup was negative, and alpha anti-trypsin levels were normal. repeated chest x-ray showed improvement and chest tubes were removed. the patient was discharged with follow-up with the thoracic surgery clinic. covid , designated as severe acute respiratory syndrome coronavirus (sars-cov- ), was identified in late as a cause of pneumonia. secondary spontaneous pneumothorax (ssp) is defined as pneumothorax that presents as a complication of underlying lung disease [ ] . nearly every lung disease can be complicated by ssp, although the most commonly associated diseases are chronic obstructive pulmonary disease and, in endemic areas, tuberculosis (tb). other common causes include cystic fibrosis (cf), primary or metastatic lung malignancy, and necrotizing pneumonia [ ] . here, we present a case report of a patient who acquired covid- pneumonia. initially, he was having mild symptoms, but later he suddenly developed bilateral pneumohemothorax and bullous emphysematous disease, as revealed on high-resolution ct. these finding are not commonly known complications of covid- and are mostly only presented in case reports. we also reviewed some articles on the development of pneumothorax as a complication of covid- -associated pneumonia including tension pneumothorax, pneumomediastinum, and subcutaneous emphysema, in addition to case reports on cystic changes within the lungs as a sequel of covid- infection. a -year-old previously healthy male presented to al wakrah hospital with a seven-day history of fever and dry cough but did not experience any shortness of breath, chest pain, or palpitations. there was no history of smoking or alcohol use. he lives with three others in an apartment and works as a driver. review of the system was unremarkable. temperature was . °c, pulse rate was beats per minute, respiratory rate was breaths/minute, and blood pressure (bp) was / mmhg. chest examination showed equal breath sounds and no added sounds, and remaining of the examination was unremarkable. initial chest x-ray (cxr) only showed prominent bronchovascular marking ( figure ). covid- pcr (polymerase chain reaction) was positive. the patient was discharged with home isolation and was educated to come back if he developed worsening symptoms. after six days, the patient developed high-grade fever, body aches, and shortness of breath that was increasing for the past three days. he was brought to the hospital through ambulance. he was found to be febrile. temperature was . °c, respiratory rate was breaths/minute, bp was / mmhg, pulse was beats/minute, and spo was % on room air. he was kept on l face mask and maintained a saturation of %. examination showed equal breath sounds with bilateral crepitations. on re-evaluation, he became more breathless and tachypneic (rr = ) and saturation was % on a l non-rebreather mask. cxr showed multiple bilateral airspace infiltrates representing covid- pneumonia ( figure ) . he was transferred to the intensive care unit (icu) for continuity of care and was treated as a case of severe covid pneumonia; lab investigations are shown in table . the patient did not require intubation. he was started on hydroxychloroquine for days, cefuroxime and azithromycin for days, tocilizumab iv mg single dose, and methylprednisolone iv every hours for days. he also received convalescent plasma. the patient started to improve in terms of oxygen requirements and symptoms. after seven days of icu admission, his care was de-escalated to the ward, and on l nasal cannula he was saturating well. four days later, he was transferred to a quarantine facility. he was doing well until three days later where he started to deteriorate and developed shortness of breath and de-saturation. repeat cxr showed right-sided pneumothorax with mild shift of the mediastinum to the left side ( figure ). chest tube was inserted on the right side, and the right lung started to expand ( figure ). the patient was transferred back to the hospital icu. he was improving. daily cxr was performed for follow-up, and three days later, repeat cxr showed newly developed left-sided pneumothorax ( figure ). chest tube was inserted on the left side. high-resolution ct ( figure ) was performed, which showed bilateral emphysematous bullous complicated by pneumothorax due to rupture bullae with giant subpleural bullae in the left side measuring x cm and also a large one in the right side showing air-fluid level measuring . x . cm, indicating infected bullae versus lobulated hydropneumothorax. also, there are bronchiectasis changes with multiple patchy areas of ground glass attenuation mainly in the mid and lower lobe, and diffuse centrilobular, peribronchial septal thickening and patchy nodular opacities were noted. the right chest tube was removed as it stopped bubbling. he was saturating well on l nasal cannula. the patient was kept on salbutamol and tiotropium. two sets of acid-fast bacilli (afb) sputum for tb, tb pcr, and culture were negative. alpha anti-trypsin level was normal. follow-up cxr for the next five days showed no changes. on the sixth day, repeated cxr showed bilateral hydropneumothorax mostly on the left lung ( figure ). the chest tube was removed and the patient was monitored for four hours. he was feeling well and was discharged with follow-up with the thoracic surgeon. in the described case, the patient with covid- pneumonia had initially mild symptoms that later progressed requiring icu admission but not requiring endotracheal intubation. as he improved, his hospital course got complicated with the development of bilateral pneumohemothorax with underlying bullae formation noticed in ct scan of the chest. he managed by placing bilateral chest tubes and was discharged in good health. during his stay, he was worked up for other causes of the pneumothorax; two sets of tb afb smear sputum, culture, and pcr were sent, which turned out negative. alpha anti-trypsin level was normal. his ct of the chest showed bilateral emphysematous bullous complicated by pneumothorax due to rupture bullae with giant subpleural bullae along with lobulated hydropneumothorax. in view of the lack of previous history of underlying lung disease and the normal cxr on presentation along with the exclusion of some of the common causes of secondary pneumothorax, we think that covid- pneumonia and its complication induced cystic changes within the lung and lead to spontaneous pneumothorax. pneumothorax has been reported as a complication of covid- pneumonia and sometimes as a presenting feature reported by other case reports [ ] [ ] [ ] [ ] [ ] [ ] [ ] . in our case, in addition to cases reported by liu et al. [ ] , cystic changes within the lungs happened as a sequel of covid- pneumonia, as evidenced by ct scan, and this case did not require intubation during the course of the illness [ ] . we think that the covid- infection and its sequel may have had a destructive effect on the lung parenchyma causing cystic changes and may have lead to subsequent pneumothorax, which need further reports and studies to be proven. covid- could be a probable cause of spontaneous pneumothorax secondary to cystic changes and bullae formation within the lung parenchyma and should be kept in mind when evaluating patients with covid- and shortness of breath, but we need further studies on the association between and pathophysiology of the occurrence of infection and pneumothorax. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all spontaneous pneumothorax tension pneumothorax in a patient with covid- mediastinal emphysema, giant bulla, and pneumothorax developed during the course of covid- pneumonia covid- with spontaneous pneumothorax, pneumomediastinum and subcutaneous emphysema a case of spontaneous pneumothorax in covid- pneumonia een man met dyspneu na een covid- -pneumonie [chest pain and dyspnea during the recovery period of covid- pneumonia spontaneous pneumothorax and subcutaneous emphysema in covid- patient: case report. infect public health sars-cov- pneumonia with subcutaneous emphysema, mediastinal emphysema, and pneumothorax. medicine (baltimore) covid- with cystic features on computed tomography: a case report authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -deifddar authors: mcgregor, bradley a; vidal, gregory a; shah, sumit a; mitchell, james d; hendifar, andrew e title: remote oncology care: review of current technology and future directions date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: deifddar cancer patients frequently develop tumor and treatment-related complications, leading to diminished quality of life, shortened survival, and overutilization of emergency department and hospital services. outpatient oncology treatment has potential to leave cancer patients unmonitored for long periods while at risk of clinical deterioration which has been exaggerated during the covid pandemic. visits to cancer clinics and hospitals risk exposing immunocompromised patients to infectious complications. remote patient reported outcomes monitoring systems have been developed for use in cancer treatment, showing benefits in economic and survival outcomes. while advanced devices such as pulmonary artery pressure monitors and implantable loop recorders have proven benefits in cardiovascular care, similar options do not exist for oncology. here we review the current literature around remote patient monitoring in cancer care and propose the use of reliable devices for capturing and reporting patient symptoms and physiology. cancer is a leading cause of morbidity and mortality in the united states, with over . million new cancer diagnoses and more than , cancer deaths estimated for [ ] . furthermore, cancer care significantly impacts the overall healthcare system through high rates of emergency department utilization, hospital admission, and costly treatments whose toxicities have potential to diminish quality of life [ ] [ ] [ ] . cancer patients frequently experience local and systemic symptoms causally related to their malignancy. local symptoms are due to direct complications of the primary tumor or metastases and can include pain, neurological deficits, respiratory symptoms (cough, shortness of breath, hemoptysis) and obstruction (bowel, biliary, airway). systemic complications include cachexia, paraneoplastic syndromes, electrolyte abnormalities, metabolic alterations, and hematologic changes. these symptoms are a frequent cause of hospitalization. in a series reported by numico et al., % of hospitalizations of cancer patients were for conditions related to tumor involvement, with a minority for workup or treatment-related complications. the most common symptoms at the time of admission were dyspnea, pain, neurological (not specified by authors), fever, and gastrointestinal (vomiting, jaundice) [ ] . identifying and addressing cancer symptom burden prior to the need for admission is recognized as a critical need and has led to increased utilization of patient-reported outcome (pro) tools discussed in detail below. in addition to tumor-related morbidity, cancer patients suffer treatment-related complications. given the myelosuppressive nature of radiation and chemotherapy, anemia, neutropenia, and thrombocytopenia with associated malaise, infection, and bleeding can occur. one of the most serious complications, neutropenic sepsis, is associated with up to % mortality rate, average hospital cost of over $ , , and total expenditures of $ . billion per year in the us [ , ] . less severe though far more prevalent toxicities such as nausea, vomiting, and diarrhea can have a large negative impact leading to volume depletion, metabolic and electrolyte imbalances and renal failure. newer immunotherapies are associated with immunerelated adverse events with unpredictable timing and vagueness of symptoms, making identification and management especially challenging [ ] [ ] [ ] . modern technology can increase patients' connectivity to the healthcare system through mobile communications and remote physiologic monitoring [ ] . monitoring systems have been used most extensively for cardiovascular diseases such as congestive heart failure (chf) and arrhythmia detection. for patients that require long-term monitoring for either of these, implantable devices like cardiomems™ and implantable loop recorders (ilr) have been shown to decrease rates of hospitalization, improve arrhythmia detection, and lower costs compared with usual care [ , ] . in oncology, while implantable devices are not available, studies have shown that monitoring patient-reported outcomes reduces visits to the emergency department, decreases follow-up costs and improves overall survival [ ] [ ] [ ] [ ] . since the outbreak of a novel sars-cov- in (covid- ), the term "social distancing" has entered the common lexicon. however, social distancing has been a mainstay of oncologic care for decades as immunosuppressed cancer patients take precautions to minimize risk of infections. patients are instructed to eliminate interactions with sick contacts and avoid large gatherings. yet at the same time, patients attend frequent visits to outpatient cancer centers for clinical evaluations. for a neutropenic patient, each visit poses a risk for infectious exposure. the latter is further magnified since the onset of the covid- pandemic. as a result, the centers for medicare and medicaid services (cms) has broadened its coverage of telehealth services under the waiver authority and coronavirus preparedness and response supplementation appropriation act, which has significantly expanded the volume of patients receiving care via telemedicine [ ] . though this has reduced oncology patients' infectious exposure, it has created the dilemma for laboratory and vital sign monitoring for patients at risk for drug-induced toxicities. tools that facilitate social distancing while maintaining connectivity to the healthcare system and providing objective data for ongoing management are urgently needed [ , ] . representative prospective randomized studies of remote and/or electronic pro in cancer care are summarized in table . pro-ctcae™ (patient-reported outcomes version of the common toxicity criteria for adverse events) is a validated tool used to monitor and report toxicities related to cancer treatment in clinical trials. basch et al. reported results from a prospective randomized study from memorial sloan kettering cancer center evaluating the efficacy of an online symptom reporting tool [ , ] . a total of patients with advanced solid tumors undergoing systemic cytotoxic chemotherapy were randomized to either an online symptom reporting platform or usual care. in the experimental arm, patients received weekly email prompts to report on common treatment-related toxicities through a web-based portal called symptom tracking and reporting (star). a severe or marked change in symptom reporting prompted an email alert to an oncology nurse; summary reports were made available to the treating physician at the time of clinical visits. over the course of the study, the star platform was associated with an improvement in health-related quality of life scores ( % vs %, p < . ), with fewer visits to the emergency department ( % vs %, p = . ) compared to standard of care. median overall survival was also % longer in the pro arm ( . months vs . months, p = . ). the authors proposed that the mechanism of improved survival was related to early interventions including active remote symptom management, supportive medications, chemotherapy dose modifications, and referrals for specialty consultation that prevented downstream consequences. additionally, the pro group was able to tolerate continuation of chemotherapy for a longer duration ( . months vs . months, p = . ). [ ] . one of the earliest uses of patient-driven technology to monitor outcomes was the cancer care monitor used by the west clinic, memphis, tn, in [ ] . prior to each scheduled oncology visit, patients would report their symptoms on computers and later digital tablets (patient care monitoring) [ ] . this validated survey was used to support a web and mobile-based application prospectively applied to postmenopausal women starting new anti-hormonal therapy to assess whether this tool would improve symptom burden and medication adherence [ ] . of significance, this application was able to increase medication adherence at eight weeks, when complimented with weekly reminders ( % vs %, p < . ). additional ongoing prospective randomized trials evaluating remote patient monitoring and patient reported outcomes in oncology are summarized in table . in the united states, the symptom management implementation of patient reported outcomes in oncology (simpro) study aims to enroll , patients with thoracic, gastrointestinal, and gynecologic malignancies. patients randomized to the intervention arm will enter symptom data into the mobile electronic symptom management system (esym). the primary outcome is -day emergency department treat and release rate as measured through medical record abstraction [ ] . an additional ongoing us study, the thrive study, is a prospective, randomized trial evaluating a web-enabled application to improve adherence to hormonal therapy in women with breast cancer. the study will randomize patients into three separate arms: . a group that receives weekly reminders through the application, . a group that receives weekly reminders and tailored feedback, and a usual care group. the primary endpoint is medication adherence as determined using an electronic pillbox [ ] . [ ] . the primary outcome is measurement of symptom burden, with secondary outcomes including quality of life, supportive care needs, anxiety, self-care self-efficacy, work limitations, cost effectiveness, and changes in clinical practice in response to pro data. a similar study is being undertaken in australia for hematologic malignancies utilizing the patient remote intervention and symptom management system (prisms), a computer tablet-based software system that prompts patients to enter twice daily data regarding physical and emotional symptoms [ ] . the prisms study aims to enroll patients undergoing chemotherapy for chronic lymphocytic leukemia (cll), hodgkin's lymphoma, and non-hodgkin's lymphoma (nhl) in two australian hospitals. the primary outcome focuses on symptom burden due to nausea, mucositis, constipation, and fatigue. ubiquitous smartphones and miniaturization of sensor and communication technology has led to enormous data gathering enterprises in consumer and healthcare markets. smartphone accelerometers, gps tracking, and high-resolution cameras are critical to fitness and wellness applications but also as diagnostic tools such as remote skin cancer detection. these same devices when combined with subjective pro feedback can be used to guide patient care or provide prognostic data. performance status (ps), commonly measured using the karnofsky or eastern cooperative oncology group (ecog) ps scale, is one of the strongest predictors of cancer survival outcomes and risk of treatment toxicity. patients with a compromised ps have higher risks of morbidity and mortality, but current clinical ps assessments, despite their critical role in clinical trials, are limited by subjectivity and high rates of interobserver variability [ ] [ ] [ ] . many consumer and medical wearables contain three-axis accelerometers and three-axis gyroscopes, providing continuous readings of individual movement which holds significant promise as a means of overcoming the current limitations of physician identified performance status. gresham et al. evaluated the feasibility of using activity data from fitbit charge hr® wearable devices as a surrogate for ps in patients with cancer, % of whom had stage iv disease [ ] . they reported high correlations between average daily step counts and ecog-ps (r = . ); each increase in daily step count by was associated with a significant decrease in adverse events, hospitalization, and hazard for death. strong correlation was also reported between these activity metrics and pro data. subsequent systematic review of published studies evaluating the use of activity tracking in cancer care identified trials including active cancer patients and those undergoing follow-up and survivorship care [ ] . most trials included breast cancer patients ( %) and focused on exercise ( %) or behavioral ( %) interventions. twelve trials evaluated daily step counts, and the reported steps per day were slightly lower in patients on active cancer therapy ( to steps/day) compared to survivors ( to , steps per day). no studies included implantable monitoring devices. while pro platforms and wearable technology have potential to improve care, implementation in the clinic faces many challenges. web-based pro platforms rely on patient engagement, which can be increasingly problematic in an aging cancer population with less familiarity with technology. furthermore, waiting for patients to report symptoms lacks a proactive preventative solution. with regards to wearable technology, most studies demonstrate feasibility, however patient adherence remains a major limitation. seventeen of the studies included in the gresham systematic review reported adherence data, but adherence was defined differently in most studies [ ] . the most commonly reported adherence metric was three consecutive days of activity tracking (range: - consecutive days), with a valid wear time as to hours per day. these definitions of adherence leave large gaps in time where no data is gathered or reported, limiting the ability to produce high fidelity analytics and accurate diagnostic tools. additionally, for cancer patients facing several months of therapy, three to seven consecutive days of activity tracking does not represent reliable monitoring through the duration of treatment and follow-up. dreher et al. demonstrated similar adherence limitations in a study of fitbit® use in breast cancer patients, stating, "adherence to wearing the fitbit was low, with . % of patients never syncing their device." for patients who did sync their devices, the median number of valid activity tracking days (defined as > hours of use) during the -month duration of the study was only . % (median = . %, range % - %) [ ] . even the much-publicized apple watch® atrial fibrillation study, a population consisting of apple watch® owners, showed poor adherence with only % of those who received an irregular pulse notification initiating the first indicated visit [ ] . the studies utilizing wearable technology in oncology care demonstrate the importance of objective data gathering, but also highlight the limitations of systems that rely on patient adherence. alternatively, the studies involving cardiac referenced in the introduction show significant benefits associated with the reliable and continuous monitoring from implantable sensor technology, including disease control, survival, and economic endpoints. representative ongoing early phase or pilot studies evaluating emerging digital technology in cancer care are summarized in table . emerging research shows benefits in outcomes and costs of cancer care through use of remote monitoring technology especially electronic patient reported outcomes (epro). however, broad clinical adoption has been limited by a lack of commercially available oncology specific solutions, concerns about reimbursement, and limitations associated with low patient adherence. a preferred solution would securely and reliably gather digital physiologic data without requiring patient activation, much like pulmonary artery pressure monitors and implantable loop recorders in cardiology. additionally, such a system would contain mobile patient engagement and epro tools that could be tied to existing reimbursement framework facilitating rapid adoption. powerful analytic tools including machine learning and artificial intelligence could then be applied to identify early signs of common complications and provide individual patient health and risk profiles, allowing oncologists to make more informed and personalized treatment recommendations. the use of an implantable device in oncology has already been explored, as oncologic cardiologists at md anderson cancer center have utilized implantable loop recorders and cardiomems® to monitor patients at high risk of complications from cardiotoxic systemic therapy, but data regarding safety and efficacy is lacking [ ] . to our knowledge, oncodisc, a san francisco-based medical technology start-up, is the only company developing implantable monitoring technology and mobile epro solutions for oncology. the oncodisc device, an intelligent implantable vascular access port, takes advantage of existing oncology workflow and a common minimally invasive procedure with established reimbursement. the current covid- pandemic has highlighted the need for reliable connected systems to facilitate home care while reducing hospitalizations and clinic visits, especially in immunocompromised cancer patients. early studies show significant benefits to pro-based systems, including lower costs and prolongation of survival. further advances in sensor technology and mobile communications hold great promise for improving cancer outcomes while at the same time reducing costs. however, widespread adoption has been hampered by a lack of commercially available solutions. to that end, implantable physiologic sensor systems and associated data analytic tools, 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use of an emerging technology fitbit usage in patients with breast cancer undergoing chemotherapy large-scale assessment of a smartwatch to identify atrial fibrillation implantable devices track cardiac events in cancer patients in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. key: cord- -opjjowcq authors: kenanidis, eustathios; anagnostis, panagiotis; arvaniti, kostoula; potoupnis, michael e; tsiridis, eleftherios title: organizing an orthopaedic department during covid- pandemic to mitigate in-hospital transmission: experience from greece date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: opjjowcq the new severe acute respiratory syndrome coronavirus (sars-cov- ) emerging in wuhan city of china, was the cause of a rare type of pneumonia evolving rapidly in pandemic early at the beginning of . the rapid human-to-human transmission of sars-cov- increases the risk of in-hospital transmission, requiring re-definement of musculoskeletal trauma management and postoperative care. following the review of the existing literature on covid- and similar infectious diseases, national and hospital board instructions for infectious diseases, as well as the consensus for surgical care by the consortium of the orthopaedic department directors, we present the outline of the implemented principles in the orthopaedic departments of a tertiary academic hospital in greece to operate during covid- pandemic. our overall objectives were to decrease the admission load and mitigate the risk of in-hospital transmission of sars-cov- . the principles involve the management of the orthopaedic medical and nursing personnel, alterations of the workflow in the wards, operating rooms and outpatient clinics from the admission to the discharge of an orthopaedic patient. in addition, we present the recommended principles of management of traumatic orthopaedic injuries highlighting those deserving admission and in-hospital care and those that can be treated in the outpatient setting or day surgery clinics. the new severe acute respiratory syndrome coronavirus (sars-cov- ) has arisen as the reason for an uncommon group of viral pneumonia cases in china, evolving rapidly into a worldwide health emergency [ ] . on march , the world health organization (who) announced coronavirus disease (covid- ) outbreak a pandemic causing international concern and global anxiety [ ] . at the time of writing this article, the number of confirmed cases worldwide has exceeded , , [ ] . as the rapid human-to-human transmission of sars-cov- has been established, the risk of in-hospital transmission is high [ ] . the spread of the virus is expected following the care of the confirmed covid- patients but may be equal for symptomatic and asymptomatic patients that are infected [ ] . the government of greece has taken strict hospital and social distancing measures early at the very beginning of the covid- outbreak reducing transmission and limiting the need for inhospital or intensive unit care. at the time of writing, we had confirmed positive patients, of which died [ ] . the exposure and immunity of the population are largely unknown as only . % of the population of greece has been tested [ ] . the spread of sars-cov- in the community remains unknown; thus, the mitigation of in-hospital transmission remains a considerable task. overall, greece's performance has been satisfactory in mitigating sars-cov- transmission and infection, thereby limiting morbidity and mortality. thus far, the greek national health service has successfully been able to accommodate the demand for inpatient care during the pandemic [ ] . the aim of this paper is to review the existing orthopaedic literature and to present the principles of management and care implemented in the orthopaedic departments of a tertiary academic hospital in greece to operate during covid- pandemic in order to mitigate the risk of in-hospital transmission of sars-cov- to the medical, nursing and administrative orthopaedic personnel. the principles included the management of the staff and the modification of workflow and practices in the wards, the operating rooms and the outpatient clinics beginning from the event of admission and up to the discharge of an orthopaedic patient. in addition, we presented the clinical indications to delineate orthopaedic patients who deserve emergency or urgent in-hospital care from those that can be treated in the outpatient setting, as well as from the day surgery clinics or could not be admitted in the hospital, in order to decrease the sars-cov- transmission load. these principles are based on the existing orthopaedic literature on covid- prevention and care as well as similar infectious diseases from the past, the greek national society of public health and infectious diseases, the hospital board of infectious diseases, the hospital medical management board and the consensus for surgical care by the consortium of the orthopaedic department directors of our tertiary academic hospital [ ] [ ] [ ] . the proposed principles of management and care are deployed below as ( ) general management of the orthopaedic departments, ( ) recommendations for the management of traumatic orthopaedic injuries, ( ) hospital pathways for the admitted orthopaedic patients ( ) workflow of the isolated and negative pressure covid- operating theatre (cot) and ( ) postoperative care of the covid- infected patients. Νon-covid- patients must be admitted in the standard non-covid orthopaedic (nco) wards and the covid- patients in the special negative pressure isolated covid orthopaedic (co) wards [ ] . the suspected but unconfirmed covid- patients who need orthopaedic care should temporarily be admitted in a dedicated ward for suspected patients (sco) away, and separated from co wards until the molecular testing for covid- becomes available ( figure ). the results of the tests were available within hours. infectious disease specialists performed the screening in the cubicles just in front of the entrance of the hospital ( figure ). the screening was based mainly on the following criteria: the previous testing for covid- , living with a person that was affected of covid- or was a health worker, travelling abroad, contact with a suspected person, smoking, symptoms mainly fever> , chest pain, trouble breathing, fatigue, chronic conditions as asthma and other pulmonary chronic conditions, chronic kidney disease, cancer and diabetes. all elective orthopaedic surgery cases were postponed [ ] . only oncological cases following the oncology mdt (multidisciplinary oncology team) evaluation and life or limb-threatening injuries, were admitted for surgery [ ] [ ] . due to the reduction of elective admissions, nco orthopaedic wards were amalgamated in order to free staff and beds for co wards. non-covid patients suffering from non-life-or limb-threatening injuries were admitted in the nco wards if surgery was to be performed urgently; patients who could clinically afford to be operated on at a later stage were discharged home, with a specific plan to be admitted for daycase surgery when indications and operating room availability allowed [ ] . non-covid patients admitted for surgery were discharged postoperatively as soon as possible without compromising their health. patients who could be treated conservatively were discharged from the emergency department (ed) and followed up in the outpatient clinic with a specific appointment in a dedicated outpatients area [ ] . covid patients should be admitted in the co wards and preferably treated conservatively or at a later stage if possible. if they needed urgent surgery, management was discussed by a multidisciplinary team comprising of the anesthesiologist, the orthopaedic surgeon, the infectious disease internist. the elected procedure was performed in the specially dedicated negative pressure covid operating theatres (cot) under the management of a special cot nurse coordinator. the staff was advised to avoid needless travelling. the temperature and respiratory symptoms of all staff were monitored by the head of the nursing staff, twice a day in the beginning and the end of the shift to identify staff at risk [ , ] . pregnant, immunocompromised or over years of age staff were protected; thus, we preferred to involve healthy younger personnel for the care of covid- patients [ ] . in addition, personnel working at the co wards were not mixed with personnel at nco wards at any time [ ] . standard staff groups comprising of designated consultants-residents-nurses were put on duty together; thus, if one of the group members was infected, only the group was quarantined and not the whole department. as the greek government imposed strict social distancing measures, and the incidence of musculoskeletal injuries and subsequent admissions was lessened by %, the number of medical and nursing staff required during the on-call duty was also reduced. during the trauma on-call, we involved two hours shifts, each one of which comprised of two residents in the ed, two residents in the nco wards and two consultants. all medical staff received special training on how to properly dress, enter and exit the co wards and cot; the nursing staff was is standard shifts in co wards and cot wearing personal protective equipment (ppe) at all times. the catchment area of our hospital is . million people populated urban area. all staff required provision of ppe (n respirators, personal goggles, gown and gloves) and were trained systematically to use ppe, especially cleaning, disinfecting, storing, and inspecting ppe for any damage [ ] . the use of a simple surgical mask was advised for the routine care of low-risk patients (no fever or respiratory symptoms, no history of recent travel or close contact with a covid- patient) [ , ] . once the community spread of the virus was confirmed, routine prevention measures included the wearing of n masks, eye protection, gown, and gloves [ , , ] . the initial patient clinical screening in the ed (medical history, clinical examination, temperature) could not thoroughly exclude the possibility of infection, due to the day long incubation time of sars-cov- [ , ] . following admission, fever, respiratory and gastrointestinal symptoms, as well as the loss of smell and taste or myocardial dysfunction, were monitored every day to identify late covid- patients [ , , ] . suspected inpatients were immediately put to the deep pharyngeal swab polymerase chain reaction (pcr) testing for sars-cov- , and the same time moved to the designated sco wards until the result was made available. transferring the suspected patient was challenging; with the patient always wearing a full face mask and via a specific pathway when possible within the hospital. contamination of the nco wards from a late covid- positive case would require nco ward closure, disinfection and -day quarantine of the involved personnel. the management of orthopaedic trauma during the pandemic was modified to mitigate the risk of sars-cov- in-hospital transmission. admission was offered to patients suffering from life or limb-threatening injuries needing emergent or urgent surgery [ ] . all other patients needing surgery were admitted only if the urgent procedure could be planned; otherwise, patients were discharged and scheduled for day surgery at a different timepoint [ ] . all other injuries were not admitted but managed in the ed and followed up in the outpatient clinics. all patients admitted for surgery should undergo a deep pharyngeal swab pcr testing for sars-cov- ( table ) . relative indication for admission contraindication to admission non-absolute indication for admission (non-life-and limb-threatening injuries); admit if urgent surgery is planned otherwise discharge and plan for day surgery no indication for admission: to be managed in the ed and followed in the outpatient clinic to facilitate prompt treatment, especially in the absence of qualified surgeons, hemiarthroplasty may be the best treatment option for the majority of patients with sub-capital hip fractures two special cubicles were located in the area in front of the ed and outside the hospital for covid- triage. no patient could enter the ed or the outpatient clinics without entering the covid triage first. covid- non-suspected, suspected or confirmed patients were managed in dedicated areas and wards via specific pathways, as indicated in figure . the suspected covid- patients were managed in the sco area, where a chest radiograph and a deep pharyngeal swab pcr testing for sars-cov- were taken. when admission was deemed necessary, patients remained in the sco ward until the test result was made available; in all other cases, the patient was advised to return home for isolation, waiting for the result. emergency trauma or polytrauma patients were treated as covid- suspected cases regardless of their symptoms and until proven otherwise and followed the above screening process in the sco area ( figure ). two operating theatre complexes with negative pressure and ventilation systems and an integrated high-efficiency particulate air (hepa) filter to decrease viral dissemination were chosen for surgery of covid- patients [ , , , ] . the cot was autonomous, immediately next to the co wards and non-connected with ncot to diminish the risk of contamination of non-covid patients [ ] . the covid triage, co ward and cot were all distinct, isolated and marked with yellow floor tape and named covid pathway [ ] (figure ). experienced and limited numbers of nursing and medical personnel were dedicated to the surgical care of covid- patients in every shift [ , ] . the majority of them who were senior enough in order to execute quick and efficient surgery were all provided with the necessary ppe [ ] . preoperatively surgeons, anaesthesiologists and scrub nurses should meet to ensure proper coordination and surgical planning [ ] . in addition, a senior staff nurse was coordinating the staff, making sure that communication and limited cot traffic was occurring during surgery [ ] . all equipment and drugs needed for the surgery should be preselected and brought into the cot. in addition, all anaesthetic monitors, computers, and ultrasound device surfaces should be covered with plastic wrap to decrease the risk of contamination and to facilitate cleaning [ ] . whenever possible, single-use equipment could be used [ ] [ ] . new workflows of staff, senior coordination, movement of medical equipment, infection prevention practices, and decontamination were established following the procedure [ ] . the most experienced anaesthesiologist using a powered air-purifying respirator (papr) ought to perform the anaesthesia for speed and accuracy [ ] . all anaesthesia has to be induced in the cot directly, and no preoperative anaesthetic room allowed to be used. regional is favoured over general anaesthesia with the patient wearing a surgical face mask during the operation [ , ] . when needed, oxygen is administered via nasal prongs under the surgical mask [ , ] . aerosol-generating procedures (airway manipulation, face mask ventilation) should be avoided to reduce the risk of viral aerosolization [ , , ] . when general anaesthesia is decided, preoxygenation could be performed via a well-fitting face mask. bag-mask ventilation is not recommended, but if unavoidable, one should proceed with small tidal volumes at low pressure [ ] . before intubation, deep anaesthesia is advised [ ] . video-laryngoscopy for intubation is highly recommended as the anaesthetist stays away from the patient's airway and ppes usually impede vision during direct laryngoscopy [ ] . during intubation, a closed airway suctioning with a rigid suction catheter to decrease the chance of infecting the surroundings could be an alternative procedure [ ] . it is recommended to use anti-emetics to diminish the risk of postoperative vomiting [ ] . after extubating, the patient must wear a surgical face mask, and nasal prongs underneath the face mask to receive supplemental oxygen [ , ] . the patient should fully recover in the cot and be transferred directly to the co ward as recovery areas are not available for safety reasons. only oncological and emergency life or limb-threatening orthopaedic trauma surgeries were allowed for covid- confirmed patients [ ] [ ] . blood donations are limited during covid- pandemic; thus, adequate blood inventory preoperatively is necessary to support the procedure [ ] [ ] . preoperative templating is required to choose the appropriate type of implant and to decrease intraoperative exposure and time. covid- patients should wear a surgical face mask at all time [ , ] . the most experienced surgeon with limited scrubbed personnel using well-fitted n respirator, eye protection, cap, gown, and double gloves, should perform the operation in a fast and efficacious manner [ ] . damage control surgery principles should apply for emergency and urgent orthopaedic surgery. when possible closed reduction and k-wires or external fixators should be elected to limit exposure and surgical time [ ] . smoke suction diathermy must be used to eliminate spread and contamination, and absorbable sutures were advised for closure [ ] . full documentation of all involved staff is in place to facilitate contact tracing. all staff should also take a shower and change into a clean set of scrubs following surgery [ ] . routine postoperative ward rounds should be minimized to reduce movement of staff, exposure and spread of covid- into the hospital [ ] . the transportation of infected patients is also limited; when possible, portable x-ray equipment should be used for postoperative diagnostic imaging [ ] [ ] . if this is not possible, a satellite radiography centre using dedicated radiography equipment is developed next to the co ward to decrease the risk of transmission [ ] . if the transfer of a patient to the regular radiology department is unavoidable, the patient should wear a surgical mask during the transfer [ ] . all radiological equipment, including probes and image viewing station mouse and keyboards, need to be disinfected after every contact with suspected or infected patients [ ] [ ] . postoperative rehabilitation may not be feasible. as a result, early postoperative full weightbearing of patients operated on for hip fractures should allow early rehabilitation and discharge [ ] . easily changeable postoperative dressings and splints would be selected to facilitate remote follow-up [ ] . follow-up appointments are minimised to those necessary; a postoperative x-ray is asked when it is possible to make an important adjustment in management. remote follow-up using telephone or video calls are also considered [ ] . postoperative imaging is also decreased to those necessary; however, a postoperative xray is asked when it is possible in order to make an important adjustment of management [ ] . in the era of covid- pandemic, the knowledge and the information applied to the clinical practice in orthopaedics change daily. the basic principles that govern the musculoskeletal hospital care are re-designed to build a universal model for the national health services. the orthopaedic setting of a hospital is split into two pathways, the covid and non-covid. these pathways are distinct, far away from each other, separately equipped, and separately staffed with properly trained nursing personnel. in our paper, we provide a process of care for the admitted, emergency and urgent musculoskeletal injuries; the majority of the orthopaedic cases are either postponed or treated conservatively. in the future, we will have the opportunity to evaluate the outcome and the morbidity caused by this management. early transmission dynamics in wuhan, china, of novel coronavirus infected pneumonia world health organisation. coronavirus disease (covid- ) outbreak world health organisation. coronavirus disease (covid- ) overview clinical features of patients infected with novel coronavirus in wuhan, china. lancet. epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study greek government. covid -greece infection control and anesthesia: lessons learned from the toronto sars outbreak possible sars coronavirus transmission during cardiopulmonary resuscitation practical recommendations for critical care and anaesthesiology teams caring for novel coronavirus ( -ncov) patients infection prevention and control of epidemic-and pandemicprone acute respiratory diseases in health care. who guidelines covid - pandemic: perspectives on an unfolding crisis (in press) preparing for a covid- pandemic: a review of operating room outbreak response measures in a large tertiary hospital in singapore (in press) boast -management of patients with urgent orthopaedic conditions and trauma during the coronavirus pandemic hospital emergency management plan during the covid- epidemic what we do when a covid- patient needs an operation: operating room preparation and guidance role of air distribution in sars transmission during the largest nosocomial outbreak in hong kong. indoor air covid- ) situation summary special article: personal protective equipment for care of pandemic influenza patients: a training workshop for the powered air purifying respirator how severe acute respiratory syndrome (sars) affected the department of anaesthesia at singapore general hospital anaesthesia and sars infection control measures for operative procedures in severe acute respiratory syndrome-related patients coronavirus disease : coronaviruses and blood safety (in press) coronavirus (covid- ) outbreak: what the department of radiology should know microbiology for radiologists: how to minimize infection transmission in the radiology department in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -b pfm i authors: winn, soe p; oo, zin thawdar; htun, nyein nyein; soe, may hnin pwint; aung, may m title: diabetic ketoacidosis in coronavirus disease patients with type diabetes mellitus date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: b pfm i the occurrence of diabetes is increasing globally and carries a variety of complications, such as thromboembolism, acute cerebrovascular accidents, and diabetic ketoacidosis (dka). although dka is not commonly associated with type diabetes (t d), it can manifest in patients who have underlying comorbidities predisposed to dka. since the emergence of the coronavirus disease (covid- ) pandemic, we have seen many cases and studies on the underlying pathophysiology of the severe acute respiratory syndrome coronavirus (sars-cov- ) pneumonia with or without respiratory failure. we have also learned that the angiotensin-converting enzyme receptor is one of the major entry sites of sars-cov- infection, and it might be one of the causes that predispose patients to dka. however, few studies exist that explore the development of dka in t d with sars-cov- infection. we present two cases of patients with dka and covid- treated with an insulin regimen with no further complications. severe acute respiratory syndrome coronavirus (sars-cov- ) infection has transformed into pandemic after the first case of coronavirus disease (covid- ) was identified in december in wuhan, china [ ] . information was limited regarding sars-cov- infection before the outbreak, and there were no treatment guidelines or vaccines for prevention. according to the us centers for disease control and prevention, covid- poses a high risk of mortality and morbidity in specific groups of people, including those older than years or people with underlying medical conditions like heart disease, lung disease, diabetes, and chronic kidney disease [ ] . diabetic ketoacidosis (dka) is characterized by elevated blood glucose levels > mg/dl, arterial ph < . , and increased serum ketone level > mmol/l or significant ketonuria, which has been classically associated with uncontrolled type diabetes [ ] . it is also associated with type diabetes (t d) in african american patients, in a condition called ketosis-prone t d or flatbush diabetes [ ] . during the covid- global pandemic, we have seen increasing cases of covid- patients with underlying diabetes presenting with dka in non-african american patients. we report two cases of t d with unusual presentation of dka in patients infected with sars-cov- . a -year-old hispanic man with a body mass index of . kg/m and medical history of hypertension, t d with neuropathy, and hyperlipidemia without previous exposure to glucocorticoid presented to the emergency department (ed) with mild fever, headache, and shortness lasting three days. his blood glucose levels had been well controlled with glipizide, metformin, and liraglutide, and his recent glycated hemoglobin was . % (two months before presentation). on his arrival to the ed, his body temperature was . °f, blood pressure was / mmhg, heart rate was /beats per minute, his respiratory rate was /breaths per minute, and peripheral capillary oxygen saturation (spo ) was % on l of high-flow nasal cannula (spo was % on room air). his initial blood glucose level was mg/dl with positive serum ketone of . he was admitted to the intensive care unit and treated with intravenous (iv) fluid and rapidacting insulin infusion with closed monitoring of arterial blood gas for ag and serum sodium, chloride, bicarbonate, potassium magnesium, and phosphate every four hours. every hour, we assessed his blood glucose levels and respiratory status for dka, and we checked for respiratory distress. he was given broad-spectrum antibiotics (iv ceftriaxone mg, twice daily, oral hydroxychloroquine mg once daily, oral azithromycin mg once daily), and supportive care for covid- infection. his dka resolved after hours of insulin infusion with closed ag. we tested his serum c peptide level on the second day of his admission to assess endogenous insulin secretion, and it was low ( . ng/ml; reference range: . - . ng/ml) with a blood glucose of mg/dl. his lipase level was within the reference range, indicating the patient was in an insulinogenic state. on the st day of hospital admission, he was discharged to home with the continuation of the same dose and regimen of oral antihyperglycemic medication (metformin extended-release, , mg orally, twice per day and glipizide, mg, once per day) with advice to follow up with his primary care physician in two weeks. a -year-old hispanic man with a medical history of t d presented to the ed with fever, lethargy, cough, and diaphoresis lasting days. he had stopped his diabetes medications and insulin for three days because of feelings of malaise and fatigue. his home oral antihyperglycemic agents are glipizide mg, once per day and metformin extended-release , mg once per day. he has no previous history of hospitalization for diabetic complications, including dka or surgery. on presentation, his body temperature was °f, respiratory rate was breaths per minute, heart rate was beats per minute, blood pressure was / mmhg, and his spo was % on room air. his initial blood glucose was mg/dl with arterial blood gas showing ag of , with ph of . , pco of mmol/l, po of mmol/l, and hco of mmol/l. urine ketone was positive, and serum ketone was . mmol/l (reference range: . - . mmol/l). d-dimer assay revealed , ng/ml (reference < ng/ml). his complete blood count was significant for nlr of with white blood cell counts of , /µl. both blood and urine cultures showed no growth. chest x-ray and ct revealed diffuse bilateral ground-glass opacities/pneumonia compatible with covid- (figures , ) . this was later confirmed by a positive sars-cov- pcr test. he was admitted to the hospital due to severe hypoxia with dka and covid- diagnosis. he was treated with high-flow nasal cannula l/minute for hypoxia, subcutaneous insulin u followed by iv rapid-acting insulin infusion ( . u/kg/hour) in normal saline briefly with hourly blood glucose monitoring until ag closure, fluid and electrolytes replacement for dka, oral acetaminophen mg every four hours as needed for fever, and subcutaneous enoxaparin mg daily for deep vein thrombosis prophylaxis. the patient was discharged nine days after hospital admission with clinical improvement. dka is the major cause of morbidity and mortality in patients with diabetes. it usually results from a reduction of insulin levels in the body due to reduced secretion from beta cell units of the pancreas or increased insulin requirement due to stressors like sepsis. in one prospective observational study, the strongest risk factor for dka development was precipitating infection compared with other risk factors, such as mismanaged insulin dosage, initial presentation, and other unknown causes [ ] . covid- , like many other diseases, can predispose a patient to dka due to the increased production of the stress hormone by stimulating cytokines. interestingly, sars-cov- enters the body through inhalation of respiratory droplets by utilizing its envelope spike glycoprotein via binding to angiotensin-converting enzyme (ace ) receptor on human cell membranes [ ] . therefore, another possible mechanism for dka development may be due to the deployment of ace receptors by sars-cov- during their host-viral interaction, causing direct destruction and reduced function of pancreatic beta cells [ ] . an animal-model study reported increased expression of ace receptors in the pancreas of diabetic mice compared with non-diabetic, euglycemic mice [ ] . therefore, for patients with diabetes, it is reasonable to assume that the enhanced use of ace receptors upon viral entry may cause receptor downregulation and increase the unopposed angiotensin- -induced acute damage to pancreatic beta cells. yang et al. also stated that the human pancreas also expresses ace , and therefore, patients with diabetes are more vulnerable to sars-cov- infection than the general population [ ] . in our cases, the transient damage of pancreatic beta-cell function leading to reduced levels of serum c peptide may be the reason for our patients experiencing acute insulin-dependent dka for a brief period during the course of covid- . in the respiratory system, ace is necessary to break down angiotensin ii to angiotensin - , which are involved in the mas receptor pathway to counteract inflammation and fibrosis. therefore, a sars-cov- infection with the deployment of ace yields a decline in the body's defense mechanism alongside imbalanced metabolic function, leading to dka and multiorgan dysfunction [ ] . in the patients' follow-up visits, they resumed their oral diabetic medications without insulin requirements. we did not perform follow-up c peptide level measurements because of the patients' healthy fasting glucose levels managed with oral antihyperglycemic medications only. as illustrated by the these two patient cases, covid- patients with t d may present with unusual presentations of dka. covid- may cause dka by increasing insulin requirement induced by ace -mediated destruction of pancreatic beta cells, as evidenced by reversible decreased serum c peptide levels or other unexplored mechanisms. physicians should be aware of covid- with a concomitant increase in the risk of dka patients with t d. however, more studies are needed for a better understanding of the pathogenesis of dka in patients with coexisting t d and covid- , and the prevention of poor outcomes in patients with diabetes. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. pneumonia of unknown cause -china: disease outbreak news people who are at increased risk for severe illness diabetic ketoacidosis and hyperosmolar hyperglycemic state diabetic ketoacidosis: a common debut of diabetes among african americans with type diabetes precipitating risk factors, clinical presentation, and outcome of diabetic ketoacidosis in patients with type diabetes endocrine and metabolic link to coronavirus infection sars-cov- cell entry depends on ace and tmprss and is blocked by a clinically proven protease inhibitor characterization of ace and ace expression within different organs of the nod mouse binding of sars coronavirus to its receptor damages islets and causes acute diabetes key: cord- - uki b d authors: mian, muhammad s; razaq, laiba; khan, safeera; hussain, nadia; razaq, mahrukh title: pathological findings and management of covid- patients: a brief overview of modern-day pandemic date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: uki b d today the world is facing one of the deadliest pandemics caused by covid- . this highly transmissible virus has an incubation period of to days. it acts by attaching to the angiotensin-converting enzyme (ace ) with the help of glycoprotein spikes, which it uses as a receptor. real-time polymerase chain reaction (pcr; rt-pcr) is the gold standard diagnostic test, and chest x-ray and computed tomography (ct) scan are the other main investigations. several medications and passive immunization are in use to treat the condition. we searched using pubmed and google scholar using keywords such as covid- , coronavirus, and their combination with pathological findings, clinical features, management, and treatment to search for relevant published literature. after the removal of duplications and the selection of only published english literature from the past five years, we had a total of papers to review. most of the covid- affected patients have mild pneumonia symptoms, and those with severe disease have comorbidities. patients with covid- had pathological findings, like ground-glass opacities, consolidations, pleural effusion, lymphadenopathy, and interstitial infiltration of inflammatory cells. radiological changes show lung changes such as consolidations and opacities, and the pathological findings were infiltration of inflammatory cells and hyalinization. patients with mild symptoms should self-quarantine, whereas those with severe acute respiratory distress syndrome (ards) are treated in the hospital. medications under trial include antivirals, antibacterials, antimalarials, and passive immunization. supportive treatment such as oxygen therapy, extracorporeal membrane oxygenation, and ventilator support can also be used. the symptoms shown by patients are very mild and self-limiting. there is no definitive treatment, although a combination of hydroxychloroquine and azithromycin have shown good results, and passive immunization also shows promising results, their safety profile is yet to be studied in detail. as of april , there are a total of , , confirmed cases and , reported deaths due to this deadly virus, which is given the name of covid- [ ] . the fatality rate of the virus is . % [ ] . the death rate is higher in people of age above and those having comorbid conditions like hypertension, diabetes, and chronic respiratory disorders [ ] . approximately % of the people who have had fatal outcomes had a comorbid condition, % were hypertensive, % were diabetics, and % had coronary heart disease [ ] . this virus belongs to the family of viruses called coronaviridae. there are four genera of coronaviruses (ɑ, ,ɣ, ), covid- belongs to the beta-coronaviruses as its genome matches % and % to the other coronaviruses which are sars and mers, respectively [ ] . it is believed that initially, the virus transmitted from animals to humans, and among humans, the virus transmitted via respiratory droplets [ , ] . the virus has very high transmissibility as it has affected the whole world in a brief period. when infected, there is an incubation period of - days after which the patient develops the symptoms of high fever, cough, shortness of breath, myalgias, and fatigue, and the virus is contagious during the incubation period [ ] . the covid- in susceptible patients causes pneumonia, which rapidly progresses to acute respiratory distress syndrome (ards). the exact pathogenesis is currently unknown; however, it is suggested that it is most likely to be similar to that of sars cov and mers cov, which attach to ace enzyme on the cell surface with the help of their glycoprotein spikes. after the entry of the virus, its antigens are presented to major histocompatibility complex (mhc) via the antigen-presenting cells (apc). then these antigens are recognized by specific cytotoxic lymphocytes that destroy the infected cells [ ] . on chest x-ray and chest computed tomography (ct), ground-glass opacities, patchy consolidation, and interstitial changes at the periphery of the lungs are typical findings [ ] . real-time polymerase chain reaction (rt-pcr) is used to make the diagnosis of the suspected cases [ ] . there is currently no recommended treatment for covid- , only supportive care like oxygen, and mechanical ventilation is provided to patients in severe respiratory distress [ ] . two drugs, remdesevir and chloroquine, have shown some good results, but it is too soon to state their efficacy as there is limited data on the effectiveness of these drugs in covid- patients. researchers are also considering the passive immunization of critical patients with the convalescent sera, and it has shown some good results [ ] . as we know, currently, there is limited knowledge available on the pathophysiology and treatment options for the covid- . and what little information is known is not well organized yet. in this review article, we aim to identify and highlight clinical features, pathological and radiological findings, and possible treatment options for covid- patients and to organize the little information we have on this pathogen. we conducted this research to analyze and review the clinical and pathological findings in covid- affected patients. we used pubmed and google scholar as our primary database research engines to find the relevant data. keywords used were novel coronavirus, covid- , pathological findings, antivirals, treatment, management, and passive immunity. mesh keyword coronavirus was also used. we included papers from the past years, they were mostly peer-reviewed, and full-text was available. all selected articles were in the english language, and no geographical boundaries were considered. we extracted (pubmed), and (google scholar) researches using the keyword covid- . a combination of keywords coronavirus and pathological findings gave pubmed, and google scholar articles, and covid- and treatment gave pubmed articles. covid- and management gave published research papers. covid and antivirals gave thirtyfive pubmed articles. lastly, covid- and passive immunization yielded results. out of these results, a total of forty articles relevant to our topic were selected. after applying the inclusion-exclusion criteria and removing the duplications, we finally got twenty-nine papers that were reviewed. among the selected papers, there were no clinical trials, most of the relevant papers were case reports which showed the clinical features and the effects of tried medical interventions. some of them were simple recommendations and guidelines about how the patient should be managed. three of these studies showed that a combination of lopinavir/ritonavir combination was effective in decreasing viral load. five studies argued that convalescent plasma showed promising results but most of these studies were not of highquality evidence. three other papers discussed the role of remdesivir, and five studies discussed the role of chloroquine in these patients which showed some positive effects however its safety profile is not clear. table shows the studies included. three out of four patients improved clinically, especially their pneumonia-related symptoms, whereas others also showed significant improvement. more studies, however, are needed to establish their efficacy. covid- may have produced intense effects worldwide due to rapid transmission and the fact that almost everyone is susceptible. still, mostly the disease is mild, especially in children and immunocompetent adults [ ] . a research paper written by jin yh et al. divided different groups of exposed individuals under various categories of cases. these included the suspected cases (with two early clinical manifestations and an epidemiological risk), confirmed cases (with a positive rt-pcr result), close contacts (with contact history to a confirmed case of novel coronavirus without protection), clustered cases (one confirmed case + many cases showing symptoms in a small area within days) and suspicious exposure [exposure to the contaminated environment without adequate protection [ ] . this classification made it easy for a health professional to know what type of patient one is and how he should be managed. a patient may present with clinical features of the disease depending upon the severity of the disease. the different degrees are mild, severe, and critical [ ] . patients with mild disease presented with dry cough, fever, sore throat, with or without nasal congestion, generalized body ache, headache, and fatigue. in severe form, the symptoms were tachypnea and dyspnea. in critical cases, patients complained of respiratory failure (severe dyspnea, respiratory distress > /min, tachypnea and hypoxia), fever, decreased blood oxygen saturation of less than or equal to %, lung filtrates, shock, and multiple organ dysfunctions or even failure [ , ] . research also showed that in severe conditions, patients showed signs of weakened breath sound, moist rales, dull percussion, and a decrease in tactile speech tremor [ ] . the disease causes not only respiratory symptoms but also gastrointestinal symptoms such as diarrhea [ ] . laboratory complete blood count tests may show normal or reduced white blood cell count or reduced lymphocyte count in the early stages of the disease onset [ , ] . patients also show elevated c-reactive protein levels [ ] . researchers from china studied the effect of infection on pregnant women suffering from covid- on the neonates. the study showed that the women that were confirmed cases during the prenatal stage had problems like premature rupture of membranes, intrauterine distress, abnormal amniotic fluid, umbilical cord, and position of the placenta. the neonates born also presented with shortness of breath, fever, tachycardia, vomiting, inability to take proper feed, diarrhea, and bloating [ ] . the complications are mostly seen in patients with an underlying chronic illness or are old. complications included acute respiratory distress syndrome (ards), rnaemia, acute cardiac injury, and secondary infection. the patients with complications were admitted to the intensive care unit (icu) [ ] [ ] . these clinical features indicate that the absence of these symptoms in an individual does not rule out the diagnosis of covid- . if a person has a history of exposure to the virus regardless of the symptoms that he shows, he should be kept under medical observation, isolated from others, and examined thoroughly [ ] . the diagnosis should be made on history, examination, symptoms, and certain investigations that are necessary and gold standard in virus detection (rt-pcr, ct scan, poct of igg and igm, elisa, and blood culture) [ ] . according to the reviewed data, patients had similar presenting features and progression of the disease with some minor differences according to the individual immune status of the subject and how they were treated in their health settings. the majority recovers without complications;deaths involve the high-risk group like the geriatric age group or persons with co-morbidities. the consistent findings were fever, dry cough, sore throat, myalgia, fatigue, and shortness of breath. the distinct findings in different cases were tactile speech tremor, gi symptoms, hemoptysis, ards, and septic shock [ , , , [ ] [ ] . radiological findings: a case review series by lin x et al. showed that both patients had groundglass opacities on ct scans, which later progressed to patchy consolidation of lungs. the lesions were mostly distributed along the subpleural regions in both lungs. no pleural effusion or lymphadenopathy was observed in subjects included in this study [ ] . another case report by shi f et al. showed that in this subject initially, ground-glass opacities were seen on ct scan, which later on progressed to consolidation. on the th day, the patient had increased consolidation, and the patient showed diffuse haziness in both lungs. other findings were bat wing appearance, crazy paving pattern, and air-bronchogram sign. the lesions involved the peripheral regions of both the lungs [ ] . another study conducted by xu x et al., which included patients out of which were males and females. the median age of the patients was years. more than % of the patients had bilateral multifocal lesions in their lungs distributed along the periphery. pneumonia in these patients presented with groundglass opacities in %, consolidations in %, crazy paving pattern in %, interlobular thickening in % and adjacent pleural thickening in % of patients. twenty-three percent of the patients did not show any of these findings [ ] . figure summarizes the findings of this research. uncommon findings were pleural effusion, thoracic lymphadenopathy, pulmonary emphysema, and pericardial effusion. ct scan of patients was redone after six days, % of them showed no changes in ct scan while % had resolution of the disease, and % showed progression. % of the patients who didn't have any characteristic findings on a previous ct scan developed bilateral ground-glass opacities [ ] . another study carried out by albarello f, et al. based on two cases showed somewhat uncommon findings. the chest x-ray of the two patients showed interstitial involvement, lung opacities, pleural effusion and calcification, hilar enlargement, and cardiac silhouette. their ct findings were typical ones like ground-glass opacities with consolidation. some uncommon findings like pleural effusion, calcifications, mediastinal lymphadenopathy, and pericardial effusions were also seen [ ] . a study carried out by pan f et al. showed the different phases of recovery in patients, excluding the patients who developed ards and severe pneumonia. the study included a total of patients with confirmed covid- diagnosis. the study showed there are four stages in the disease progression based on ct findings. early-stage ( - days after the onset of initial symptoms) of the disease showed unilateral or bilateral ground-glass opacities, mostly in the lower lobes of lungs. progressive stage ( - days after the onset of initial symptoms) in this stage ground-glass opacities progressed to crazy paving patterns and consolidation. peak stage ( - days after the onset of initial symptoms) consolidations became denser and more prevalent, and there were residual parenchymal bands. absorption stage ( or more days after the onset of initial symptoms) consolidation gradually absorbed, there was no crazy paving pattern observed, but extensive ground-glass opacities were still observed [ ] . figure shows the ct findings in covid- patients. based on the studies reviewed, the findings on the ct scan of covid- patients are groundglass opacities, consolidation, crazy paving pattern, and air bronchogram sign. these findings are consistent with the majority of the patients, and these are the characteristic findings of covid- . in some patients, mediastinal lymphadenopathy, pleural effusion, pulmonary emphysema, and pericardial effusion are seen and are mostly in older patients and the high-risk groups. ct scan findings of covid- patients are also helpful in determining the severity of disease and the stage of the disease. also, in the areas where they have limited testing services, ct scan findings can be used as a diagnostic tool for covid- . there is a specific pattern in which these findings present at the initial stages of the infection, ground-glass opacities are frequently bilateral and present in the lower lobes and the periphery. they may then progress to develop consolidation and crazy paving patterns. consolidation will start becoming denser, and parenchymal bands will appear, followed by a peak. in most cases, consolidation starts resolving, and the ct scan becomes normal again within two weeks. therefore, a ct scan can be used to monitor the progression of the disease. pathological findings: a study conducted by luo w, et al. based on the autopsy findings of the patient who died of covid- . on gross examination of the lungs, the surface appears diffusely congested, hemorrhagic necrosis was evident and was more marked in the outer regions of the lungs. mucinous and hemorrhagic exudates were present in the bronchi. on histopathology, extensive pulmonary interstitial fibrosis with hyaline degeneration was evident. there were signs of a hemorrhagic infarct. small vessels showed severe congestion, thickening of walls and occlusion or stenosis of the blood vessel; lumen and microthrombi were present in the vessels. focal infiltration of lymphocytes, plasma cells, macrophages was marked. there was marked necrosis of bronchial walls. mainly type pneumocytes were affected, and various metaplastic changes of epithelium were observed. multinucleated giant cells and intracytoplasmic viral inclusions were also observed [ ] . another study conducted by xu z et al. based on the biopsy samples taken from the deceased covid- patient showed diffuse alveolar damage bilaterally with cellular fibromyxoid exudates. there was the formation of the hyaline membrane and interstitial infiltration of inflammatory cells. pneumocytes were atypically enlarged, having large nuclei, granular cytoplasm, and prominent nucleoli showing the viral cytopathic change [ ] . another study conducted by zhang h et al. based on the biopsy findings of deceased covid- patients showed diffuse alveolar damage and type pneumocyte hyperplasia. fibrinous exudates were seen in the alveoli, and interstitial fibrosis was evident. interstitial infiltration of inflammatory cells was also observed [ ] . based on the studies reviewed, on gross examination, lungs were markedly congested, and hemorrhagic necrosis was seen, and several exudates were present in bronchi. on the other hand, characteristic histopathological findings were severe pulmonary interstitial fibrosis, hemorrhagic infarction. small vessels were mainly affected, and they showed signs of congestion and were occluded by microthrombi. type pneumocytes were the primary cells that affected their nuclei were atypically enlarged, and nucleoli were prominent. metaplastic change in the epithelium was seen. infiltration of inflammatory cells i-e lymphocytes, plasma cells, macrophages were marked, showing a severe inflammatory reaction. multinucleated giant cells were also seen, and some studies also suggested the presence of intracytoplasmic viral inclusions. several options are in use and proposed to prevent covid- infection. some are simple preventive measures suggested to the general public, like frequent hand washing, social distancing, self-isolating if feeling sick. these measures proved to be effective in flattening the curve of covid- infection and keeping the total cases within the healthcare system's capabilities. it is proposed that any person who is exposed to the confirmed case of covid- or is suspected of having these symptoms should practice self-isolation. this will prevent passing the virus to other healthy and vulnerable individuals; however, once they develop symptoms like fever or cough, it is advisable to consult a physician to get tested. for mild symptoms the advice is different in different geographical regions, some advise the covid- -positive individuals with mild symptoms to quarantine at home, practice selfisolation, keep a check on their symptoms along with symptomatic measures like antipyretic. whereas in some regions where the healthcare system is not overwhelmed, they are being held in quarantine under supervision until they test negative to avoid it's spread [ ] . for moderate to severe symptoms, however, the patients are shifted to the hospital and are managed there. some of the patients do progress to severe form of the disease or ards and multi-organ failure and then need icu care and other supportive measures. several factors cause the progression of the disease from mild symptoms to severe and poor prognosis of the disease. one of these factors is old age, where comorbidities and polypharmacy make them vulnerable and worsen their symptoms. other factors include comorbidities and status of the existing disease like increased d-dimer levels and high sepsisrelated organ assessment score (sofa score) for sepsis. although there is no definitive treatment available when the patient does develop symptoms, he is managed using one of the proposed treatment options along with other supportive options. these proposed treatment options are based on the previous epidemics because of other coronaviruses like sars and mers cov. figure shows some of those options. antivirals: one of the mainstays of treatment remains antivirals in any viral infection. among antivirals are the neuraminidase inhibitors which worked in sars and mers, oseltamivir is one of those and is a widely used anti-viral. arabi et al. found zanamivir and panamivir to be as effective as oseltamivir in patients with influenza and h n infections [ ] . however, these anti-virals are not that effective in covid- patients. although there is not enough evidence to support their effectiveness in this latest outbreak, the combination of lopinavir/ritonavir is found to be effective in some patients. a case report by lim et al. showed that the combination of lopinavir and ritonavir significantly reduced the viral load in a -year-old patient [ ] . another case series by wang z et al. showed the results of this combination in four patients where severe pneumonia and respiratory symptoms significantly improved, and one patient tested negative and was discharged later [ ] . remdesivir, another broad-spectrum antiviral, is being used in these patients to find potential treatment and is among the ones that are relatively effective in covid- [ ] . elfiky showed in a study that sofosbuvir, remdesivir, and ribavirin showed that they could help manage and treat this virus [ ] . antibacterials: superimposed bacterial infections are common in patients with viral pneumonia, and use of antibacterial medications alongside as prophylaxis in moderate to severe infections or wherever there is suspected superimposed infection. it is, however, recommended to avoid a combination of broad-spectrum antibiotics or their blind administration [ , ] . the antibiotic treatment recommended for community-acquired pneumonia, like azithromycin, fluoroquinolones can be administered to cover common bacterial pathogens. immune modulator drugs: chloroquine and hydroxychloroquine, the immune modulator drugs used as antimalarials, and as a dmard in rheumatoid arthritis and also in autoimmune diseases like lupus were found effective in sars infection and so were tried in covid- patients as well. they also act as a broad-spectrum antiviral drug. several clinical trials are in progress throughout the world to assess its efficacy and safety in these patients. an in-vitro study testing the efficacy of broad-spectrum anti-virals like remdesivir, favipiravir, ribavirin penciclovir, and chloroquine showed that chloroquine and remdesivir were effective against covid- virus in-vitro [ ] . another study involving patients by gao et al. also showed similar results; it showed an increased efficacy of chloroquine in preventing symptom exacerbation, preventing progression to severe pneumonia, and improving radiological findings without any serious side effects [ ] . chloroquine has both anti-viral and immunemodulating properties, which increase its effectiveness in stopping the viral replication in vivo [ , ] . chloroquine, however, is associated with some uncommon but serious side-effects like qt interval prolongation, which may be severely harmful in cardiac patients. therefore, more clinical trials are needed to assess its safety profile in this group of patients. convalescent plasma and passive immunization: convalescent plasma has already been in use for some diseases; it was also effective in mers-cov infection. its safety and efficacy were tested by arabi et al. and showed that it could be used as a potential treatment option in covid- [ ] . the who recently recommended its use as passive immunization in all serious patients because of the unavailability of active immunization in the form of vaccines [ ] .the plasma of recovered patients was used in different patients and had shown positive effects. a case review series by shen et al. discussed five critically ill patients having covid- with ards who were given antibody-rich convalescent plasma. they showed significant improvement in clinical status, their sofa score improved, temperature improved, and they also were weaned off from a ventilator [ ] . the results, however, cannot be considered as significantly reliable because of the small sample size. another case study showed significant improvement in symptoms and a decrease in viremia and viral load in seven out of patients without any serious side effects [ ] . despite the positive results and considering that most of the studies had weak evidence, it can help manage patients. still, more studies are needed to assess its potential serious side-effects like transfusion-related acute lung injury (trali). supportive treatment: supportive treatment like oxygen therapy via mask is used if patients develop shortness of breath and hypoxemia. in the case of resistant hypoxemia, extracorporeal membrane oxygenation (ecmo) is used. patients with severe respiratory distress may need ventilator support. corticosteroids may be used as a supportive therapy, but its use and efficacy are controversial as they may make patients more prone to infections [ ] . most of the clinical trials are currently ongoing. most of them involved fewer patients, which makes it difficult to make valid conclusions. only the papers that were published in the english language were selected for our review. most of the interventions are under trial; therefore, not much data was available about their safety in this population, and thus conclusions were hard to draw and are not valid. a detailed quality appraisal of the papers was not done. the research was oriented to identify clinical features, pathological and radiological findings, and possible treatment options of covid- . the majority of the patients experience fever, cough, shortness of breath, and myalgia whereas some may develop pneumonia and ards. frequently seen radiological and pathological findings are bilateral ground-glass opacities in peripheries of lungs, consolidations, crazy paving pattern, air bronchogram sign, diffuse alveolar damage, fibrinous exudates in bronchi, formation of hyaline membrane, inflammatory cells infiltration, and metaplastic change in the alveolar epithelium. there is no definitive treatment, but the role of antivirals like remdesivir and lopinavir, azithromycin, hydroxychloroquine, and passive immunization like convalascent plasma is being researched. currently, the focus is on the prevention of disease by practicing social distancing until a vaccine is developed. there is a great need for more work on vaccine development and educating the medical community and the public. strict protocols are needed in the future to prevent such crises. disclosures world health organization di napoli r: features, evaluation and treatment coronavirus (covid- ) clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study. the lancet molecular immune pathogenesis and diagnosis of covid- clinical analysis of neonates born to mothers with -ncov pneumonia a rapid advice guideline for the diagnosis and 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treatment of covid- associated pneumonia in clinical studies feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with middle east respiratory syndrome coronavirus infection: a study protocol treatment of critically ill patients with covid- with convalescent plasma effectiveness of convalescent plasma therapy in severe covid- patients in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -riftp g authors: bhatta, sabita; sayed, abida; ranabhat, bandana; bhatta, raj kumar; acharya, yogesh title: new-onset seizure as the only presentation in a child with covid- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: riftp g we present a child with a new-onset isolated afebrile seizure in coronavirus disease (covid- ). this patient, an -year-old hispanic male, was brought to our ed in new york city on may , , during the ongoing covid- crisis with seizure. there was no fever and/or respiratory and gastrointestinal complaints. his general and systemic examination did not reveal any abnormality. similarly, his biochemical profiles were within normal limits, and the radiological study, including a chest x-ray and ct scan, showed normal findings. his polymerase chain reaction (pcr) was positive for sars-cov . the patient was admitted for observation after consultation with pediatric neurology, and his condition progressively improved with anti-seizure medications. this case highlights the need for recognizing an uncommon and atypical presentation in covid- as the new cases are unfolding rapidly across the globe. the novel coronavirus disease (covid- ) has impacted thousands of children worldwide [ ] . despite being generally mild in children, we have witnessed vague clinical pictures in covid- , ranging from asymptomatic in the mildest form to severe respiratory distress [ ] . recently, there have been multiple reports of atypical symptoms in children, necessitating recognition of uncommon disease presentations to protect the vulnerable populations, and minimize complications [ ] [ ] . neurological manifestations in children have not been widely reported. here, we aim to report an uncommon neurological manifestation, isolated afebrile seizure, in a child with covid- . an -year-old hispanic male child was brought to our ed with abnormal shakiness of the body that lasted one to two minutes. his mother described the event as sudden shakiness of the whole body, associated with stretching and tightening of all four limbs, uprolling of eyes, frothing from the mouth, and tongue bite without urinary or bowel incontinence. he recovered slowly and started recognizing and talking to his mother after - minutes following the event. the patient was generally well, and there were no other complaints, including fever or shortness of breath. there was no significant past medical or surgical history, and his birth was uneventful. his immunization status was up-to-date, and he achieved all his age-appropriate during his er visit in our hospital, he had another generalized tonic-clonic seizure that lasted for two to three minutes. there was generalized jerking movement of the whole body associated with abnormal tightening of both upper and lower limb, uprolling of the eye, and clenching of teeth. the seizure was terminated using lorazepam mg intravenous stat. on examination, the patient was well-appearing and interactive. he was alert and oriented to time, place, and person. his temperature was ℉, respiratory rate breaths/min, blood pressure / mmhg, heart rate beats/min, and oxygen saturation %. there was a bite mark in the tongue with minimal bleeding. the head ear nose throat (heent) examination revealed normo-cephalic and atraumatic head with b/l equal and reactive pupils, and normal conjunctiva. the neck was supple with a complete range of motion. his nervous system examination showed intact cranial nerves (cn i-xii), normal motor examination with normal bulk and power, normal deep tendon reflexes, intact sensation, and no cerebellar signs. cardiovascular examination showed a normal rate, regular rhythm, normal heart sounds, and no gallop or murmur signs. pulmonary/chest examination revealed no signs of respiratory distress, wheezing, or rales. abdominal examination revealed normal bowel sounds with no signs of distention and tenderness. his skin was warm and dry without diaphoresis and erythema. examination of the musculoskeletal system displayed a normal range of joint motion with absent edema and tenderness. as the patient belonged to the current covid- endemic area, his new-onset seizure was suspected to be triggered by covid infection. laboratory and radiological investigations were planned to support the diagnosis and rule out other serious causes of seizures in children, including meningitis, encephalitis, hypoglycemia, dyselectrolytemia, and substance abuse. laboratory findings showed white blood cells (wbc) . cells/mm , and comprehensive metabolic panel (cmp) with na meq/l and k . meq/l. his coagulation profile, c-reactive protein (crp), procalcitonin, ferritin, and d-dimer were within normal limits. blood toxicology, including the drug panel, was negative. there were no abnormalities in the chest x-ray and brain ct (figures - ) . his viral polymerase chain reaction (pcr) test for the severe acute respiratory syndrome coronavirus (sars-cov- ) ribonucleic acid (rna) was positive; however, the test for influenza was negative. we consulted with the pediatric neurology department and decided to admit the patient for observation. the electroencephalogram (eeg) was planned only if a patient had clinical deterioration. he was managed with levetiracetam mg twice daily. during the in-ward hospital stay, the patient was stable and did not have seizures or other complaints. he was discharged the next day and scheduled for a follow-up in a week. during his follow-up, the patient looked fine and reported neither seizure nor any complaints in the preceding week. the majority of the children with covid- are either asymptomatic or present with mild symptoms when compared to adults [ ] . fever, cough, and gastrointestinal symptoms are common; however, many atypical presentations have been reported recently [ ] . description of isolated afebrile seizure in covid- is scarce among children, and neurological manifestations have not been extensively studied [ ] [ ] . our case highlights seizure as one of the uncommon, but potential presentations of covid- in children. following nasal infection, the sars cov- can enter the brain via olfactory bulbs, resulting in inflammation and myelin damage. mao et al. evaluated covid-confirmed patients for neurological manifestations [ ] . their findings revealed central nervous system manifestations in one-fourth of the patients: dizziness and headache being the most common presentation. the central nervous system's involvement in covid- can cause headaches, dizziness, altered consciousness, ataxia, seizures, and even encephalitis and meningitis in severe form. in pediatric age groups, the neurological complications have not been widely reported [ ] . but as the new cases are unfolding every day, we cannot ignore the possibilities of atypical symptoms and/or variable presentations. musolino et al. investigated preliminary covid- findings and found one out of infected children with seizures, while others presented predominantly with fever, cough, and diarrhea [ ] . subsequently, dugue et al. reported seizures in covid-positive infants. however, this patient also had a fever and mild hypertension, along with a history of siblings with streptococcal pharyngitis [ ] . the fit was associated with a sustained upward gaze, bilateral leg stiffening, and reduced responsiveness. the sars-cov- rna and rhinovirus c sequences in swab samples (nasopharyngeal/anal) were positive in this particular patient, confirming a co-infection. seizures are generally common in viral infections, particularly with adenovirus, influenza, rhinovirus, and respiratory syncytial virus (rsv) in children years and younger [ ] . coronavirus in infants can be associated with a % chance of a co-infection with rhinovirus, and there is a possibility of other coinfection [ ] [ ] . in our case, the patient did not have any respiratory or gastrointestinal symptoms. however, viral pcr tested positive for covid- . we admitted the patient for observation/isolation and subsequently ruled out more severe seizure etiologies, like hypoglycemia, dyselectrolytemia, and infections. although we could not trace the potential source of covid- infection in the patient's family, we can assume that the patient contracted the disease owing to a recent surge in covid- cases in his residential area across new york city, usa. this case underlines the uncommon neurological manifestation, seizure, triggered by covid- . seizure in children can have serious consequences, including physical damages; therefore, it is crucial to recognize the potential causes and manage them without delay. there is a necessity for general guidelines that incorporate detailed clinical investigations with a neurological examination in pediatric patients, especially from endemic areas, to rule out any severe neurological sequelae of covid- in this pandemic. our case describes a new-onset isolated afebrile seizure in a child with covid- . as new cases are unfolding each day, it is essential to recognize seizure as a potential covid- presentation in the pediatric age groups. neurological involvement can lead to severe complications and long-term sequelae. therefore, we recommend physicians to rule out neurological involvement in all children with covid- . human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to covid- : a puzzle with many missing pieces exclusive: national alert as 'coronavirus-related condition may be emerging in children coronavirus disease (covid- ) and neonate: what neonatologist need to know features, evaluation and treatment coronavirus (covid- ) coronavirus infections in children including covid- : an overview of the epidemiology, clinical features, diagnosis, treatment and prevention options in children why is covid- so mild in children central nervous system manifestations of covid- : a systematic review neurologic manifestations of hospitalized patients with coronavirus disease seizures associated with coronavirus infections . seizure. lung ultrasound in children with covid- : preliminary findings neurologic manifestations in an infant with covid- burden and risk factors for coronavirus infections in infants in rural nepal clinical and ct features in pediatric patients with covid- infection: different points from adults key: cord- - l hqsr authors: escher, allan r title: an ounce of prevention: coronavirus (covid- ) and mass gatherings date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: l hqsr widespread, non-stop, and often sensational coverage of the coronavirus (covid- ) has caught many governments flat-footed in efforts to protect the health and safety of their citizens. in response to the current global health event, the world health organization (who) declared covid- a pandemic. mass gatherings present a historic challenge in protecting the health and safety of attendees. the majority of the prominent mass gatherings are religious in nature. global sporting events, such as the olympics and the world cup, pose unique health risks to attendees and host nations. deferment or cancellation of such mass gatherings may exert an extraordinary economic loss to the host nation. universal adoption of best practices for infection control is the surest way for governments to prepare for mass gatherings. in these uncertain times, it is up to intergovernmental organizations to be the voice of reason. the novel coronavirus ( -ncov) came to world attention in december in wuhan, china; the world health organization (who) designated it a pandemic on march , [ ] . at first, many individuals and nations assumed that it would be contained within china due to rapid implementation of quarantine for the city of wuhan and the remarkable construction of two hospitals in only days. the zoonotic transmission of covid- from wildlife to humans led to a chinese ban on wildlife trade; however, the rapid spread of covid- shows a systematic and expeditious transmission between humans [ ] . as of this writing, the current number of infected is , , along with , deaths and cases in countries, areas, or territories [ ] . governments have been hesitant in their response with border and school closures, bans on public gatherings, and screening of passengers at transportation hubs. the question remains whether this is truly effective. some authorities have advocated the usage of thermal scanners to identify those who are febrile. these scanners could be used today to identify febrile individuals who will be in close contact with heads of state, government, or business. although well-intentioned, this is imprecise for mass gatherings. as seen below, many infected, yet non-febrile individuals will be missed with such screening tools ( figure ). in the current climate, it is essential to take a common-sense approach to mass gatherings. the who defines a mass gathering as a "concentration of people at a specific location for a specific purpose over a set period of time which has the potential to strain the planning and response resources of the country or community" [ ] . examples of sporting events include the olympics in tokyo or the world cup in qatar. religious pilgrimages such as the hajj in islam and lourdes in catholicism draw millions of pilgrims every year. the triennial kumbh mela, the hindu religious pilgrimage festival, can draw up to million people over two months [ ] . the health and safety of vulnerable populations in such events are quite challenging. in response, the who recently published, "key planning recommendations for mass gatherings in the context of the current covid- outbreak (interim guidance)" [ ] . this technical guidance is a revision of the prior documents: "mass gatherings in the context of pandemic (h n ) influenza" and "international meetings attended by individuals from ebola virus disease-affected countries." [ } the who guidelines are a comprehensive resource for governments on how to plan for the myriad logistics of mass gatherings. risk assessment, response, and surveillance are cornerstones of preparation; the international organization for standardization (iso) is a well-accepted approach to risk management [ ] . recent consequences of this standard have resulted in the cancellation of mass gatherings in lourdes and the closure by saudi arabia of pilgrims to umrah. it remains to be seen if the olympics will proceed as scheduled or deferred until a later date. the ebola experience merits special consideration. after covid- patients have successfully recovered, there needs to be surveillance of patients who are cured. caution must be exercised in deeming a patient "virus-free." during the ebola outbreak, some patients were declared "virus-free"; subsequently, the non-transmissible, but present, ebola virus was detected in the immune-privileged eye [ ] . this is but one example of the difficulties faced by public health officials in treating covid- patients. governments are tasked with three critical duties in the response to covid- : the coordination of services with access to covid- testing kits, medical supplies and equipment, accurate and timely communication, and maintaining public trust in their government [ ] . intergovernmental organizations serve as valuable resources in a pandemic. the who has a variety of tools to assist governments in their response to covid- . these include technical guidance such as "critical preparedness, readiness and response actions" and "responding to community spread of covid- " [ ] . it is up to the host nation, however, to educate its population on best practices for infection control: consistent hand hygiene, social distancing, respiratory hygiene, testing, and the use of quarantine. with adherence to the existing who mass gathering guidelines, governments have a narrow window to mitigate the spread of the novel coronavirus ( -ncov), optimize their healthcare system, and maintain the people's trust in their government. disclosures covid- ) outbreak insights into the recent novel coronavirus (sars-cov- ) in light of past human coronavirus outbreaks world health organization: public health for mass gatherings: key considerations mass gatherings medicine: public health issues arising from mass gathering religious and sporting events are high-performing health systems resilient against the covid- epidemic? in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. key: cord- -l vkzja authors: iltaf, samar; fatima, meraj; salman, salma; salam, jawwad-us; abbas, saira title: frequency of neurological presentations of coronavirus disease in patients presenting to a tertiary care hospital during the coronavirus disease pandemic date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: l vkzja background coronavirus disease (covid- ), caused by infection with the severe acute respiratory syndrome coronavirus (sars-cov- ), usually presents clinically with cough, fever, shortness of breath, and loss of taste and/or smell. covid- can also present with neurologic signs and symptoms, including headache, hyposmia/anosmia, encephalopathy, meningoencephalitis, guillain-barré syndrome, stroke, and seizure. viral transmission occurs through aerosols generated when an infected person coughs, sneezes, or exhales and by direct touching of contaminated surfaces. the present study evaluated the frequency of neurologic presentations of coronavirus disease in patients presenting at a tertiary care hospital during the covid- pandemic. methodology this cross-sectional study included inpatients and outpatients (self-isolated) with polymerase chain reaction-confirmed sars-cov- infection who presented at dow international medical college of karachi between march and june . of these patients, ( . %) presented with neurological signs and symptoms and were further evaluated. the data were analyzed statistically using ibm statistical product and service solutions (spss) for windows, version . (ibm corp., armonk, ny). results the patients with sars-cov- infection included ( %) men and ( %) women; of these, ( . %) were married, and ( . %) were unmarried. patients ranged in age from to years (mean ± standard deviation, . ± . years), with ( . %) having neurological manifestations. headache was the most frequent neurological symptom, reported in ( %) patients, followed by vertigo in patients ( . %), numbness/paresthesia in ( . %), altered level of consciousness in seven ( %), hyposmia/anosmia in five ( . %), and encephalitis in three ( . %). other symptoms included sudden hemiparesis (stroke) in two patients ( . %), flaccid paralysis due to guillain-barre syndrome in one ( . %), and seizure in one ( . %). conclusion neurological involvement is not infrequent in patients with covid- . neurologic manifestations should be carefully monitored in infected patients. covid- should be suspected in patients presenting with neurological abnormalities and should be included in the differential diagnosis to prevent further virus transmission. the patients with sars-cov- infection included ( %) men and ( %) women; of these, ( . %) were married, and ( . %) were unmarried. patients ranged in age from to years (mean ± standard deviation, . ± . years), with ( . %) having neurological manifestations. headache was the most frequent neurological symptom, reported in ( %) patients, followed by vertigo in patients ( . %), numbness/paresthesia in ( . %), altered level of consciousness in seven ( %), hyposmia/anosmia in five ( . %), and encephalitis in three ( . %). other symptoms included sudden hemiparesis (stroke) in two patients ( . %), flaccid paralysis due to guillain-barre syndrome in one ( . %), and seizure in one ( . %). the severe acute respiratory syndrome coronavirus (sars-cov- ) is a ribonucleic acid (rna) virus belonging to the family coronaviridae that is transmitted via respiratory aerosols, fomites, and directly from person to person. coronavirus disease (covid- ) was declared a worldwide pandemic by the world health organization on march , [ ] . covid- was first diagnosed in the city of wuhan, china [ ] . the pulmonary system is the most commonly affected, with symptoms including shortness of breath, fever, and cough the most commonly reported features. observational studies have suggested that covid- may have neurologic manifestations, including headache, nausea, vomiting, myalgia, dizziness, hyposmia/anosmia, encephalitis, and impaired consciousness (encephalopathy) [ , ] . although the exact mechanism by which sars-cov- enters the central nervous system has not been determined, it may spread directly from the cribriform plate through the blood circulation, via mechanisms that include free radical or immune-mediated injury [ ] . this study aimed to evaluate the frequency of neurologic presentations of coronavirus disease in patients presenting at a tertiary care hospital during the covid- pandemic. this cross-sectional study assessed the frequency of various neurological presentations of covid- in patients treated for this disease at dow university of health sciences (duhs), a public sector tertiary care teaching hospital at karachi, pakistan, from march to june . all patients, both inpatients and outpatients, who had oropharyngeal or nasopharyngeal swabs polymerase chain reaction (pcr)-positive for sars-cov- , were recruited. patients positive for immunoglobulin g antibodies to sars-cov- were excluded, as were patients with prior neurological or psychiatric diseases, systemic malignancy, hypercoagulability state, intracranial tumors, uncontrolled hypertension or diabetes mellitus, extremes of ages or anemia. the study protocol was approved by the ethics committee of the university, and all patients provided written informed consent. a survey on neurological manifestations was specially designed for covid- patients by researchers in the clinical faculty of the neurology department. this subjective survey addressed neurological manifestations of covid- : headache, altered sensation, nausea and vomiting, sudden hemiparesis (stroke), numbness and paresthesia, vertigo, ataxia, seizure, encephalitis/meningitis, guillain-barré syndrome (gbs), and myelitis. neurological manifestations were later confirmed by a thorough review of all available patient records. the sample size was calculated using the raosoft® sample size calculator (raosoft, inc., seattle, wa), based on a . % response distribution, a confidence interval of %, and a margin of error of %, resulting in a sample size of patients. statistical analyses were performed using ibm statistical product and service solutions (spss) statistics for windows, version . . (ibm corp., armonk, ny). quantitative variables were summarized as mean and standard deviation (sd) and qualitative variables as frequency and percentage. qualitative variables were cross-tabulated with age group and gender and compared by chi-square tests. a p-value < . was considered statistically significant. the patients included ( %) men and ( %) women; of these, ( . %) were married, and ( . %) were unmarried. patients ranged in age from to years, with a mean ± sd age of . ± . years. overall, patients ( . %) developed neurological manifestations ( figure ) . headache was the most common neurological symptom, observed in ( %) patients, followed by vertigo in ( . %), numbness/paresthesia in ( . %), altered level of consciousness in seven ( %), hyposmia/anosmia in five ( . %), and encephalitis in three ( . %) ( figure ). other symptoms included sudden hemiparesis (stroke) in two ( . %) patients, flaccid paralysis due to gbs in one ( . %), and seizure in one ( . %). no significant association was found in neurological manifestation between covid- patients aged < years and > years ( [ ] [ ] [ ] [ ] . our study confirmed that headache ( %), altered level of consciousness and encephalopathy ( %), hemiparesis (stroke; . %), gbs ( . %) and seizure ( . %) were the most frequently reported neurological presentations [ , , , ] . covid- patients may present with neurological symptoms, including encephalitis and altered level of consciousness (encephalopathy). genome sequencing showed that sars-cov- was present in the cerebrospinal fluid (csf) of a japanese patient who presented clinically with symptoms of meningoencephalitis [ ] . in another case study, a woman presented with a threeday history of fever, cough, and altered mental status and was diagnosed with covid- by detection of sars-cov- rna in a nasopharyngeal swab [ ] . in contrast, her csf was negative for bacteria and viruses, and a computed tomography scan of the brain without contrast revealed symmetric bilateral hypointense signals in thalamus bilaterally, suggesting that this virus can cause encephalitis [ ] . this may be due to increased expression of cytokines, including interleukin (il)- , il- , il- , tumor necrosis factor, granulocyte colony-stimulating factor, interferon-gamma, and free radicals associated with the severity of covid- . anosmia/hyposmia is one of the more common neurological manifestations of covid- and may be the only presenting symptom in some patients [ ] . a case study reported that a patient positive for sars-cov- presented with isolated sudden onset anosmia but no other symptoms of covid- [ ] . anosmia/hyposmia presents mostly in patients in their early s and asymptomatic, healthy patients [ ] . the pathophysiology of hemiparesis (stroke) during for sars-cov- infection is multifactorial. increased levels of acute-phase reactants, including leukocyte count and serum concentrations of c-reactive protein, d-dimer, ferritin, and lactate dehydrogenase, are the most common predictors of stroke. viral infection of vascular endothelial cells accompanied by damage to the vasculature can predispose to infarct. septicemia can predispose to coagulopathy, one of the manifestations of sars-cov- infection associated with hypercoagulability, and reduce the level of angiotensin-converting enzyme , resulting in tissue destruction leading to stroke [ , ] . the increased level of cytokines associated with sars-cov- infection is also the most potent cause of neuronal damage and stroke [ , ] . sars-cov- induced hypercoagulability may be the most important mechanism by which patients without any vascular risk factors develop cerebrovascular disease [ , ] . timely diagnosis and management are vital in preventing morbidity and mortality in patients with acute stroke. gbs is an immune-mediated demyelinating disorder to the peripheral nerves usually occurring after gastrointestinal or respiratory tract infection. campylobacter jejuni, zika virus, and influenza virus are the most frequent causes of gbs. various neuromuscular disorders have been associated with covid- , as have other neurological disorders overlapping with gbs, such as bickerstaff's encephalitis [ ] . seizures (generalized tonic-clonic seizures) and altered levels of consciousness have been reported in covid- patients. one study of patients diagnosed with covid- found that only two ( . %) had developed seizures [ ] . risk factors for mortality in covid- patients who require admission to hospital have been described [ ] . the mechanism underlying the development of coronavirus-associated neurological complications remains unclear. these neurological manifestations may be due to the release of pro-inflammatory cytokines that predispose to vascular endothelial injury and increase the permeability of the blood-brain barrier [ ] . a recent analysis of eight studies from china that included , infected patients found that hypertension ( %), diabetes mellitus ( %), and cardiovascular diseases ( %) were the most prevalent comorbidities [ ] . moreover, coronavirus-induced hypercoagulability may be the most potent mechanism for inducing cerebrovascular disease (stroke) in patients without any vascular risk factors [ , ] . the present study had several limitations, including its retrospective design and collection of data from a single center. laboratory and radiological investigations were not performed in all patients, as many were self-isolated. moreover, this study did not include long-term evaluations. neurological manifestations of sars-cov- -infected patients have not been documented during this pandemic. the present study evaluated the neurological manifestations of covid- in patients in karachi, pakistan. the incidence of covid- has grown dramatically around the world in recentmonths, and most cases are asymptomatic or mild and self-managed. therefore, the actual numbers of cases are under-reported. the association of neurological manifestations with covid- is still uncertain because many cases are also misdiagnosed as other febrile illnesses. therefore, neurological manifestations of covid- should be included in the differential diagnosis of patients with these neurological signs and symptoms. diagnostic tests for sars-cov- should be performed in all patients with symptoms of respiratory illness and neurological symptoms. basic definitions and standard guidelines for research identifying the neurological manifestations of covid- are warranted. territorial, national, and global joint efforts by clinicians and researchers concentrated on high-caliber, straightforward, moral, and evidencebased exploratory practices would help push the worldwide health care network toward progress against this pandemic. human subjects: consent was obtained by all participants in this study. institutional review board was informed. issued approval not applicable. the institutional review board was informed about collection of data,however as no intervention was required in this study so proper documented irb wasn't taken. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. who declares covid- a pandemic the covid- epidemic clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china. jama. neurologic manifestations of hospitalized patients with coronavirus disease a first case of meningitis/encephalitis associated with sars-coronavirus- covid- -related stroke neuromuscular disorders in severe acute respiratory syndrome new onset acute symptomatic seizure and risk factors in coronavirus disease : a retrospective multicenter study covid- -associated acute hemorrhagic necrotizing encephalopathy: ct and mri features anosmia and ageusia: common findings in covid- patients isolated sudden onset anosmia in covid- infection. a novel syndrome anosmia, hyposmia, and dysgeusia as indicators for positive sars-cov- infection neurological complications of coronavirus and covid- . complicacionesneurológicas por coronavirus y covid- analysis of clinical characteristics and laboratory findings of cases of novel coronavirus pneumonia in wuhan the interface between stroke and infectious disease: infectious diseases leading to stroke and infections complicating stroke covid- presenting as stroke hypercoagulability of covid- patients in intensive care unit. a report of thromboelastography findings and other parameters of hemostasis clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study i would like to acknowledge the faculty of neurology and medicine department of dow university of health sciences ojha campus for their support in this study. key: cord- - cvth j authors: anyfantakis, dimitrios title: holy communion and infection transmission: a literature review date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: cvth j the holy communion originated in the last supper of jesus christ, nearly , years ago. according to the bible, the night before his crucifixion, jesus christ shared with his apostles a meal of bread and wine. during the meal, christ instructed his disciplines to eat and drink in his memory, saying that bread is his body and wine is his blood. today, faithful people worldwide share the consecrated bread and wine retracted from a chalice with a holy communion spoon. the novel coronavirus that emerged in december recorded a rapid exponential spread across space and time. the ongoing pandemic of coronavirus disease has affected people from all cultures and religions. in greece, the pandemic concurred with the easter celebration. measures of social distancing have been implemented. among others, churches have closed their doors to the public in order to avoid religious mass gatherings. the issue of the novel coronavirus transmission by partaking holy communion has received much criticism. in this review, we aimed to retrieve articles that summarize the current knowledge on the selected topic. in order to offer a balanced analysis of the subject, we have also assessed the theological framework of the holy mystery. eucharist or holy communion is a christian ritual through which a member of the church (bishop or presbyter) offers to the worshipers the holy gifts, the consecrated bread and wine [ ] . the word "eucharist" derives from the greek word "eucharistia" which means "thanksgiving". the eucharistic practice in the orthodox faith consists of dipping the consecrated bread into the chalice together with the consecrated wine [ ] . this practice is named intinction [ ] . the elements of the holy communion are retrieved from the chalice with a small spoon and are placed directly into the recipient's mouth. participants share holy communion from the same cup. furthermore, the common spoon is not wiped between recipients [ ] . a recent pandemic has recorded a rapid spread worldwide and has resulted in high rates of hospitalization and intensive care unit admission [ ] . social distancing policies have been implemented in order to avoid public gathering. in front of the easter celebration in greece, religious services have been performed behind closed doors for the public [ ] . the issue of coronavirus transmission by sharing the holy communion has been a subject of debate between science and the greek orthodox church. currently, the german government, although permitted attendance on religious services, prohibited the participation of the faithful population in the mystery of holy communion. in this paper, we aimed through a literature search of published studies to provide a comprehensive overview of this topic. in order to offer a balanced analysis, we also assessed theological and historical views. the mystery of eucharist, also called holy communion has been instituted by jesus christ before his death [ ] . during the passover meal, which is named last supper, jesus gave his disciples bread and wine and told them: "take it; this is my body. then he took the cup, gave thanks, and gave it to them, saying, "drink from it all of you; this is my blood" [ , ] . previously he had stated that "whoever eats my flesh and drinks my blood has eternal life, and i will raise them up at the last day" [ ] [ ] [ ] . by saying this word, he wanted to confirm that the elements of the holy communion were his "body" and his "blood" and not simply bread and wine [ ] [ ] [ ] . for over years, the celebration of the holy communion makes people actual members of the orthodox church [ ] [ ] [ ] . in the same direction, saint john of damascus clarifies that the consecrated bread and wine are not symbols of the body and blood of christ, but christ's body itself [ ] . he also underlines that the communion is realistic and not metaphoric, and by partaking holy communion human bodies become bodies of jesus christ [ ] . according to saint ignatius, the holy eucharist, "is the medicine of immortality and the antidote against death, so that we might live forever in jesus christ" [ ] . therefore, christian theology cannot accept that contact with the chalice or the holy communion spoon, may act as a vehicle of transmission of pathogens to the worshiper [ , ] . in support of this, priests consume the remainder content of the chalice at the end of divine liturgy. consequently, they should be the first infected persons [ ] . the case of the priest of the lepers on spinalonga, monk chrysanthos koutsoulogiannakis may sustain this argument [ ] . spinalonga is an islet located in north-eastern crete that was historically used to isolate patients with hansen's disease from the healthy population [ ] . for a period of years, monk chrysanthos served holy communion to the patients with hansen's disease. he partook of the holy communion from the same spoon, without getting infected. similarly, elder evmenios saridakis served and blessed patients in a leprosy hospital on saint barbara, athens, without manifesting the disease. the issue of the potential transmission of infectious diseases through the holy communion has given rise to a growing number of research efforts since the late th century [ ] . a hypothesis that pathogens of the mouth may contaminate wine on the communion cup has been formulated by hobbs et al. [ ] . researchers have performed experiments, through which volunteers were asked to drink sacramental wine that contained . % of alcohol from a common silver communion cup or chalice [ ] . remarkably, the number of pathogens located in the rim of the chalice was found considerably low [ ] . the authors concluded that the risk of the transmission of the infection through a common communion cup is negligible [ ] . furthermore, rotation of the chalice was ineffective in reducing bacterial colonization [ ] . wiping the rim of the chalice with a cloth reduced bacterial counts by % [ ] . in the same direction, burrows and hemmens investigated the potential transmission of pathogens, from one person to another by the common use of the chalice [ ] . interestingly, the authors have reported that under the most favorable conditions only . % of organisms were transmitted from the saliva of one person to the mouth of another [ ] . remarkably, streptococcus pyogenes swabbed from the polished surface of the chalice died of rapidly [ ] . manangan et al. disclosed that the issue of potential transmission of bacteria through the common communion cup is controversial [ ] . they stated that even if transmission occurs, it does not imply inoculation neither infection [ ] . disease requires a minimum number of pathogens to be transmitted from person to person [ ] . furthermore, the common communion cup has never been associated with a pandemic outbreak [ ] . despite the considerable debate on this issue, in , the centre of disease and control prevention attempted to achieve a balance between scientific principles and respect for religious beliefs [ ] . in this route, a study performed among worshippers partaking holy communion disclosed that they did not exert a higher risk of infection compared to those with less or no religious service attendance [ ] . another study investigated the risk of contamination by partaking holy communion following the practice of intinction of the holy gifts [ ] . the authors reported that although intinction did not eliminate the risk, significantly reduced the hazard of infection compared to the practice of sipping from a common communion cup. they suggested intinction to be a safer alternative method for receiving the holy communion [ ] . fiedler et al. remarked the high risk that poses immunodeficient patients during holy communion and suggested the use of individual chalices for all the participants. they reported that intinction would be a more favorable method to avoid infections [ ] . expert medical opinions in regards to the transmission of coronavirus through participation in the mystery of eucharist divided the scientific community in greece [ ] . dr eleni giamarelou, a prominent professor of internal medicine in the university of athens, an expert in the area of infectious diseases, stated that "holy communion is the greatest mystery of the orthodox faith that cannot be interpreted through logical reasoning" [ ] . she also added that those who believe that through the holy communion receive the "body and the blood of jesus christ" and not simply wine and bread can partake without fearing the coronavirus [ ] . she also argued against the use of personal plastic teaspoons [ ] . her opinion has received much criticism from the greek politics and expert scientists. metropolitan mesogaias nikolaos has disclosed an interesting statement [ ] . the primary goal of science is the discovery of the truth of the created world [ ]. religion's aim is the disclosure of the truths of god [ ]. these will not be achieved if science is dominated by arrogance and religious thoughts by narrowness [ ] . he emphasized that interpretation of the holy eucharist as a vehicle through which a contagious disease may be transmitted, derives from the lack of faith and the human rationality [ ] . it is remarkable that in front of this human disaster, the requirement of a spiritual way of living has emerged. medical doctors occupied in countries seriously affected by the coronavirus pandemic such as italy, witnessed religious conversions among infected healthcare workers [ ] . they have recognized the importance of spirituality and faith to alleviate stress and psychical sufferance [ ] . infections associated with religious rituals covid- : towards controlling of a pandemic the basic book of the eucharist the largest last supper: depictions of food portions and plate size increased over the millennium spiritual care of the sick what happens in holy communion? writings: the fount of knowledge . fathers of the church letter to the ephesians. the faith of the early fathers: pre-nicene and nicene eras blessed is the kingdom, now and forever: reflections on the divine liturgy devastating epidemics in recent ages greek populations experiments on the communion cup survival of bacteria on the silver communion cup risk of infectious disease transmission from a common communion cup lagrange loving a: a controlled study on intinction: a safer alternative method for receiving holy communion infektionsgefährdung durch abendmahlskelche--eine unterschätzte gefahr? [danger of infection from communion cups--an underestimated risk? metropolitan of mesogaia and lavreotiki nikolaos: if there is life i want to live an italian experience of spirituality from the coronavirus pandemic maintaining health and well-being by putting faith into action during the covid- pandemic religion, spirituality, and health: the research and clinical implications . isrn psychiatry effect of religiosity/spirituality and sense of coherence on depression within a rural population in greece: the spili iii project key: cord- -elrzlbsg authors: gurala, dhineshreddy; al moussawi, hassan; philipose, jobin; abergel, jeffrey r title: acute liver failure in a covid- patient without any preexisting liver disease date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: elrzlbsg in december , an outbreak of novel coronavirus started in wuhan, china, which gradually spread to the entire world. the world health organization (who) on february , , officially announced the name for the disease as coronavirus disease , abbreviated as covid- . it is caused by severe respiratory distress syndrome coronavirus (sars-cov- ). the who declared sars-cov- as a pandemic on march , . sars-cov- mainly causes fever as well as respiratory symptoms such as cough and shortness of breath. gastrointestinal/hepatic sequelae such as diarrhea, nausea, vomiting, and elevated liver enzymes have been reported as well. studies and data so far on coronavirus infections from china, singapore, and other countries showed that liver enzymes elevation could be seen in - % of cases. more severe disease can correlate with the worsening of liver enzymes. however, acute liver failure in patients with covid- has not been described. herein we report a case of acute liver failure in an elderly patient with covid- infection who did not have a history of preexisting liver disease. until recently, seven types of coronaviruses had been reported to cause infections in humans [ ] . coronaviruses can use animal hosts and then can evolve to infect humans. this process is thought to explain the emergence of sars-cov (severe respiratory distress syndrome coronavirus) in , mers-cov (middle eastern respiratory syndrome) in , and sars-cov- in . sars-cov- has % genome sequence similarity to sars-cov and % genome sequence homology to mers-cov. covid- symptoms range from mild (fever, cough, or dyspnea) to moderate (respiratory failure requiring oxygen support) and can progress to ards (acute respiratory distress syndrome) and multiorgan failure. in one of the earlier studies, % of cases were mild, but the mortality rate ranged from . % to . % [ ] . higher mortality rates were reported in countries like italy, possibly secondary to resource depletion in an overwhelmed health care system. gastrointestinal symptoms such as diarrhea have been reported in approximately - % of patients [ ] , with a lower rate in china ( . %) as compared to singapore ( %) [ ] . liver injury has been reported in % of patients with sars-cov [ ] and has also been reported in patients infected with mers-cov [ ] . studies also suggest that sars-cov- can affect the liver [ ] [ ] [ ] . in a recent study published in shanghai, ( . %) out of patients were found to have elevated liver enzymes with sars-cov- [ ] . in another study published in the lancet in february by huang et al., an increase in aspartate aminotransferase (ast) was observed in % in intensive care unit (icu) patients compared to % in non-icu patients, indicating that more severe disease correlates with worsening of liver enzymes [ ] . several other studies showed that liver injury in the form of an increase in ast/alanine aminotransferase (alt) levels with a mild increase in bilirubin ranging from . % to % [ ] . in patients who died of sars-cov- , liver injury was reported as high as . % [ ] . the highest levels recorded included an alt of , u/l and an ast of , u/l [ ] . generally speaking, transaminase elevations are mild in patients with covid- . here, we report a case of acute liver failure in an elderly patient with covid- infection who did not have a history of preexisting liver disease. an -year-old male with a medical history of diabetes, hypertension, dyslipidemia, asthma, coronary artery disease with bypass graft, atrial fibrillation on warfarin, and heart failure with preserved ejection fraction with an automatic implantable cardiac defibrillator and pacemaker presented to the emergency department (ed) in march with intermittent fever, productive cough, and shortness of breath (sob) for four to five days. he initially started noticing fever that was partially relieved by acetaminophen five days prior to presentation (maximum temperature of °f at home). this was associated with sob on exertion, which progressed to sob at rest and a productive cough. he denied any recent travel, contact with sick person, herbal medications use, or a recent change in home medications. his home medications included oral warfarin daily, oral metoprolol tartrate two times daily, oral metformin er daily, oral aspirin daily, oral atorvastatin, and budesonide-formoterol inhaler twice daily. the review of systems was otherwise negative. the patient did not have a history of smoking, alcohol consumption, illicit drugs, or high-risk sexual behavior. vitals at the time of admission showed a temperature of . °f, heart rate of beats/minute, blood pressure / of mm hg, respiratory rate of breaths/minute, and oxygen saturation of % on room air. physical examination was positive for bilateral wheeze and rhonchi in all lung fields, + pedal edema bilateral. his chest was without spider angiomas and abdomen with no hepatosplenomegaly, and he had no shifting dullness, with normoactive bowel sounds and no palmar erythema. on neurological examination, he was alert, oriented to time, place/person, followed commands, and had no focal deficits. laboratory examination results are shown in table the patient had normal liver enzymes at presentation but had elevated transaminases on day . the examination at that time was negative for asterixis or encephalopathy. atorvastatin was stopped, and the recommendation was made to start n acetylcysteine (nac), and workup for acute and chronic liver disease was ordered. his respiratory status continued to deteriorate, requiring increased oxygen support. his radiologic findings worsened with enlarging infiltrates on a chest x-ray on day , as shown in figures - . the patient then developed cytokine release syndrome (crs) (elevated interleukin [il]- and il- as mentioned in table ), and he expired on day . covid- is a pandemic illness that primarily affects the respiratory system with a wide spectrum of disease presentation that ranges from mild disease (fever, cough) to severe (ards, multiorgan failure). the gastrointestinal/hepatic systems are the next most commonly affected, with symptoms such as nausea, vomiting, diarrhea, and an increase in liver enzymes. currently, studies on the exact pathophysiology of liver injury in these patients are limited, but it is believed either to be a direct effect of the virus or immune-mediated inflammatory response, such as crs, hypoxemia, and failure of innate immune regulation, or to be drug-induced. ) it is postulated that both sars-cov- and sars-cov bind to angiotensin-converting enzyme (ace ) receptors to enter the target cell [ ] where the virus replication begins and starts to infect cells of the upper respiratory tract. based on the scrna-seq data, chai et al. [ ] found that ace receptors also found in the hepatobiliary system (high in bile duct cells, cholangiocytes, when compared to liver cells). cholangiocytes play a critical role in liver regeneration and immune responses [ ] . thus, the authors concluded that potential damage of cholangiocytes by -ncov might lead to profound consequences in the liver rather than the direct effect of the virus on hepatocytes. ) crs is a group of disorders caused by a wide variety of inflammatory etiologies, resulting in a profound increase in inflammatory markers such as il- , il- , il- granulocyte colonystimulating factor, interferon-γ inducible protein , monocyte chemo-attractant protein , macrophage, inflammatory protein -α, and tumor necrosis factor-α. this can ultimately lead to hemodynamic instability, multiorgan dysfunction, and death [ ] . elevations in il- , il- , procalcitonin, and ferritin, as well as thrombocytopenia have been associated with severe covid and potentially severe liver injury as seen in our patient [ ] . ) ischemic hepatitis, also known as shock liver, is characterized by a significant increase in serum aminotransferases due to reduced oxygen delivery to the liver, usually seen in shock and thromboembolic disease [ ] . ) clinicians should also consider drug-induced liver injury due to hepatotoxicity associated with drugs used in treating covid such as lopinavir, ritonavir, and hydroxychloroquine that are recently approved by the fda for the treatment of covid. our patient, who had no previous history of liver disease and normal liver enzymes at presentation, developed elevated liver enzyme levels on day . initial differential diagnosis was broad, including ischemic hepatitis, drug-induced liver injury, viral hepatitis, cholestasis of sepsis, and autoimmune diseases. on laboratory workup, viral infections such as hepatitis (a, b, c), epstein-barr virus, cytomegalovirus, herpes simplex virus, hiv, autoimmune, and metabolic causes were ruled out. since his blood pressure was stable until day of his hospitalization without any pressor support, ischemic hepatitis was unlikely [ ] . tylenol toxicity was excluded (levels were less than ug/ml). the remainder of the patient's medications were reviewed, and none of the patient's medications was likely to be the culprit. for example, the patient's home medication coumadin is a rare cause of acute liver injury and usually results in a cholestatic pattern rather than a hepatocellular one, which is what our patient demonstrated. aspirin has been associated with an increase in liver enzymes but usually only with dosages of more than , to , mg daily. metoprolol and metformin have been associated with only mild elevations in liver enzymes. hydroxychloroquine used to treat sars-cov- has been rarely associated with clinically apparent liver injury. a single case series (two cases) of acute liver failure attributed to hydroxychloroquine was published, but these patients took the medication for more than two weeks. in summary, we describe the first case of acute liver failure caused by the covid- infection. acute liver failure was diagnosed clinically by rising liver function tests and inr, as well as progressive encephalopathy. we could not conclusively prove that the covid- was the etiologic agent as the patient declined a liver biopsy. however, alternative causes of acute liver failure were effectively ruled out. bloodwork did not identify another etiology, and the patient's hypotension was too late in his course and too mild to cause ischemic hepatopathy. additionally, none of his medications was among the usual suspect for acute liver failure. as we learn more about this new infection, we expect to better understand the spectrum, pathophysiology, and treatment of the resultant liver injury. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. sars-cov- : an emerging coronavirus that causes a global threat clinical characteristics of novel coronavirus infection in china enteric involvement of coronaviruses: is faecal-oral transmission of epidemiologic features and clinical course of patients infected with sars-cov- in singapore sars-associated viral hepatitis caused by a novel coronavirus: report of three cases histopathology of middle east respiratory syndrome coronovirus (mers-cov) infection -clinicopathological and ultrastructural study clinical features of covid- -related liver damage epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study liver injury in covid- : management and challenges clinical features of patients infected with novel coronavirus in wuhan, china. lancet. liver injury during highly pathogenic human coronavirus infections clinical characteristics of non-survivors with covid- in wuhan epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study the novel coronavirus ( -ncov) uses the sars- coronavirus receptor ace and the cellular protease tmprss for entry into target cells specific ace expression in cholangiocytes may cause liver damage after -ncov infection cholangiocyte pathobiology the use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease (covid- ): the perspectives of clinical immunologists from china thrombocytopenia is associated with severe coronavirus disease (covid- ) infections: a meta-analysis hypoxic hepatitis: a review and clinical update athlete's hepatitis in a young healthy marathon runner key: cord- -gl ip authors: hussain, azhar; kaler, jasndeep; dubey, arun kumar title: emerging pharmaceutical treatments of novel covid- : a review date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: gl ip as a new decade began, covid- quickly gained importance as it became the cause of the current global pandemic. research has been focusing on studying the structure of sars-cov- and investigates possible pharmaceutical approaches. with the number of cases increasing every day, globally, multiple drugs are being researched as possible candidates. although multiple drugs show promise in the treatment of covid- via either inhibiting viral replication or preventing fusion of the virus to the ace receptors, further investigation is still warranted and necessary before the admission of any type of pharmaceutical agent. furthermore, several supplements have also been documented in being utilized as treatment of covid- . the exact mechanism and efficacy of current candidate drugs are still being explored through clinical trials. despite the advancements in current research with emerging treatments, social distancing and engaging in preventative measures remains crucial to attempt to prevent the occurrence of more cases and deaths, worldwide. this review explores various drugs and their mechanism of action which are either currently being used in clinical trials or may be used in the future for the treatment of covid- . since the emergence of the virus in china in december of , severe acute respiratory syndrome coronavirus (sars-cov- ) has spread across the globe resulting in the current global pandemic. as of march , , covid- has been confirmed in , people worldwide, carrying a mortality rate of approximately . %, compared to the mortality rate of less than % from influenza [ ] . as the number of those affected by novel covid- increases, globally, so does the urge to find an appropriate pharmaceutical intervention. antimicrobials and antivirals are at the center of the current exploration for the appropriate treatment. many of the agents currently being tested through clinical trials are pre-existing medications that have been a part of the current market. these medications are being tested in hopes that they can be repurposed and with an adequate dose, inhibit either viral replication or inhibit host cell entry. the global pandemic related to sars-cov- originated in wuhan, china in december and was thought to have a zoonotic transmission with bats being the reservoir host. sars-cov- is an enveloped virus with a large positive-stranded rna genome. on the surface of the virus is a spike protein; a type i membrane glycoprotein that constitutes peplomers and plays an integral role in the initiation of viral infectivity [ ] . the spike protein is responsible for binding to the angiotensin-converting enzyme (ace ) receptor through which the virus gains entry into the type ii pneumocyte present in the alveolar wall of the respiratory system. upon binding to the ace receptor, sars-cov- is endocytosed into the cytoplasm of the pneumocyte where the lysosomal enzymes of the host cell will break down the lipid bilayer of the virus, a process that is known as uncoating. the virus will utilize the host cell rna dependent rna polymerase to replicate its viral genome, increasing the viral load within the host cell [ ] . once the viral genome and the structural proteins have been replicated within the type ii pneumocyte, the sar-cov- will bud off of the cell and in the process of budding off, destroying the pneumocyte. the destruction of the type ii pneumocytes causes monocytes and macrophages to release cytokines such as interleukin- (il- ), interleukin- (il- ), and tissue necrosis factoralpha (tnf-α). the increased release of cytokines causes systemic manifestations such as the presentation of fever, acute inflammation, smooth muscle dilation as the cytokines reach the systemic circulation. the cytokine storm leads to systemic inflammatory response syndrome (sirs) in which systemic manifestations can lead to multi-system organ failure (msof) [ , ] . many pharmaceutical options target the various steps in the lifecycle of sars-cov- , including viral entry. many drugs show promise in the management of covid- , however, no pharmaceutical approach has been solidified. this manuscript aims to summarize the emerging pharmacological interventions for covid- , the mechanisms of action, and the adverse effects that are currently being researched. there is an increased amount of pressure prevalent within the scientific and medical communities in attempting to find a proper medical strategy in managing and treating covid- . several drugs are currently being researched that seem to be promising in the treatment of covid- , however, it should be noted with caution that these medical interventions are still being researched as no one approach has been solidified. several antimicrobials and antivirals are currently being researched and investigated as they inhibit various steps within the lifecycle of sars-cov- , as will be discussed. supplements such as vitamin c and zinc are also under trial. while some of these pharmaceutical agents are administered as an independent dose, multiple drugs are co-administered. although the mechanism of action amongst several agents may be similar, the adverse effects and the recommended dosing differ substantially. for each pharmaceutical agent reviewed, there will be an extensive focus on the mechanism of action and adverse effects along with any dosing recommendations that may have been explored. camostat mesylate is a potent serine protease inhibitor that is approved for the treatment of pancreatic inflammation in japan [ ] . sars-cov- entry into the cell depends on the viral spikes protein to cellular receptors, angiotensin-converting enzyme (ace ), and s protein priming by host proteases (tmprss ) [ ] . camostat mesylate has recently been shown to block sars-cov- entry into the cell by inhibiting the cellular host tmprss [ ] . with direct inhibition of entry into the cells, sars-cov- is unable to replicate as the virus requires the host's rna-dependent rna polymerase. without access to adequate machinery, an infected individual may present as more of an asymptomatic carrier. camostat mesylate is currently undergoing further clinical trials to fully understand the mechanism of action and if this protease inhibitor would prove to be a viable option in the treatment of covid- . arbidol (also known as umifenovir) is a promising repurposed antiviral agent with a unique mechanism of action targeting the s protein/ace interaction and inhibiting membrane fusion of the viral envelope to the host cell [ ] . arbidol is an antiviral drug that particularly focuses on inhibiting the fusion of the virion and the type ii pneumocyte. arbidol is a russian-made potent broad-spectrum antiviral that has an established mechanism of action against influenza a and v viruses [ ] . arbidol is better known in china and russia and to a lesser extent in western countries. the predominant mode of action of arbidol is based on its intercalation into membrane lipids leading to the inhibition of membrane fusion between virus particles and plasma membranes, and between virus particles and the membranes of endosomes [ ] . the efficacy and safety of arbidol monotherapy were analyzed and on day after admission, no viral load was detected [ ] . arbidol has been noted as a well-tolerated molecule with a high therapeutic index, when administered on periods ranging from a few days to a month, however, no studies have addressed the long-term administration of arbidol, such as in the context of chronic infections [ ] . the maximum blood concentration of arbidol occurs . to . hours after the administration of a dose and the half-life of the drug in the body is to hours [ ] . arbidol is metabolized in the body and is excreted mostly through bile and an insignificant amount through kidneys [ , ] . arbidol is typically well-tolerated and has low toxicity, however, the main adverse effects include nausea, diarrhea, dizziness, and elevated serum transaminase [ ] . currently, chloroquine/hydroxychloroquine is one of the most promising compounds that has gained international attention for its potential activity against covid- [ ] . chloroquine is active against malaria as well as amongst many autoimmune diseases, such as systemic lupus erythematosus or rheumatoid arthritis. several clinical trials in china have shown chloroquine phosphate to be effective against covid- at a dose of mg/day [ ] . hydroxychloroquine is reported to be as active as chloroquine, however less toxic [ ] . due to the increased toxicity concerns that limit the use of chloroquine, a compound that differs from chloroquine by a single hydroxyl group, hydroxychloroquine, is used [ ] . chloroquine was shown to increase endosomal ph, which presents virus/cell fusion and it also interferes with the glycosylation of cellular receptors of sars-cov [ ] . increasing the ph of the lysosome prevents protease activity such that the fusion process is disrupted [ ] . chloroquine has been shown to exert an antiviral effect during pre-and post-infection conditions by interfering with the glycosylation of the ace receptor thus, reducing the binding efficiency between ace on host cells and the sars-cov- spike protein [ ] . while the drug was shown to inhibit the virus in vitro, the required dose in humans is thought to be quite high and lead to severe toxicity [ ] . both chloroquine and hydroxychloroquine are also said to have immunomodulatory effects through attenuation of cytokine production and inhibition of autophagy and lysosomal activity in host cells [ ] . the cytokine production in covid- occurs when the replicated virion is budding off of the type ii pneumocyte and is responsible for many systemic processes such as fever, and various other processes that ultimately can lead to the fatal complication of acute respiratory distress syndrome. inhibiting the cytokine production would be beneficial to prevent the progression of the viral disease, however, the adverse reactions become a significant obstacle that needs to be overcome. while the use of chloroquine and hydroxychloroquine is considered safe in pregnancy, the adverse effects are plenty as they range from qt prolongation, hypoglycemia, neuropsychiatric effects and retinopathy [ , ] . lopinavir is a human immunodeficiency virus (hiv)- protease inhibitor administered in fixeddose combination with ritonavir, a potent cyp a inhibitor that 'boosts' lopinavir concentrations [ ] . the use of this combination was shown to have potent antiviral activity against the severe acute respiratory syndrome (sars) virus [ ] . lopinavir is a highly potent and selective inhibitor of the hiv type (hiv- ) protease, an essential enzyme for the maturation of the virus [ ] . inhibiting the enzyme arrests the maturation of the virus and thus, blocking its infectivity. without the protease function, only immature, non-infectious viral particles are formed, thus attenuating the viral load of sars-cov- amongst infected patients. enzyme chymotrypsin-like protease ( clpro) plays a crucial role in processing the viral rna and with lopinavir administration, it has been postulated that lopinavir may inhibit the action of clpro, disrupting the process of viral replication and release from host cells [ ] . although lopinavir does not affect the already infected cells, the main antiviral action of the protease inhibitor is to prevent subsequent infection of cells. ritonavir is administered in a lower dose than lopinavir and in doing so, the co-administration inhibits metabolic inactivation of lopinavir and acts as its pharmacokinetic enhancer [ , ] . lopinavir is a cytochrome p inhibitor and thus, drug interactions with lopinavir/ritonavir are fairly common. the treatment of lopinavir-ritonavir was shown to be effective as post-exposure prophylaxis against other viral diseases including middle east respiratory syndrome (mers) [ ] . a study compared patients with the severe acute respiratory syndrome (sars) treated with ribavirin monotherapy and patients with sars treated with lopinavir/ritonavir and ribavirin; patients treated with the combined therapy had a lower risk of acute respiratory distress syndrome (ards) and death [ , ] . in , chu et al. evaluated that lopinavir at µg/ml and ribavirin at µg/ml inhibited sars-cov- after hours of incubation and that the agents were synergistic when used together [ ] . the most frequent side effects observed are gastrointestinal, such as diarrhea, nausea, and vomiting [ ] . lopinavir is primarily metabolized by the liver and thus, drug concentrations may increase in individuals with hepatic impairment or slow acetylators. the timing of administration during the early peak viral replication phase (initial - days) appears to be important because delayed therapy initiation with lopinavir/ritonavir did not affect clinical outcomes [ , ] . ivermectin has been identified very largely in the search for appropriate pharmaceutical intervention in covid- . ivermectin is an fda-approved broad-spectrum antiparasitic agent that in recent years, has shown to have antiviral activity against a broad range of viruses in vitro [ ] . ivermectin possesses the ability to disassociate the preformed imp α/β heterodimer which is responsible for the nuclear transport of viral protein cargos [ ] . the inhibition of imp α/β disrupts the immune evasion mechanism of the virus [ ] . studies on sars-cov proteins have revealed a potential role for imp α/β during infection in the signal-dependent nucleocytoplasmic shutting of the sars-cov nucleocapsid protein that may impact host cell division [ ] . the exact mechanism behind ivermectin is still under investigation but studies have found that a single treatment of ivermectin in a covid- patient can cause the effect of a ~ -fold reduction in viral rna at hours [ , ] . due to an immensely significant decrease in viral load with just one dose, ivermectin holds a significant amount of promise and thus, warrants further investigation in humans. ribavirin, a guanine analog, inhibits viral rna-dependent rna polymerase [ ] . ribavirin was first approved in the s and has been used clinically for the respiratory syncytial virus, viral hemorrhage fever, and in combination with interferon for hepatitis c [ ] . by inhibiting rnadependent rna polymerase, ribavirin inhibits the initiation and elongation of rna fragments, resulting in the inhibition of viral protein synthesis [ ] . to further promote the destabilization of viral rna, ribavirin inhibits natural guanosine generation by directly inhibiting inosine monophosphate dehydrogenase in a pathway that is vital for the production of guanine precursor to guanosine [ ] . guanosine is necessary for the capping of rna to prevent degradation. without proper guanosine available, rna degradation will more readily occur and thus, decreasing the viral load. in the case of sars-cov- , the virion genome will be destabilized due to the missing guanosine cap. it should be noted that these various mechanisms of action of ribavirin are dose-dependent, however, currently, there is no knowledge regarding which dose will cause which effect [ , ] . ribavirin should be administered via intravenous infusion at a dose of mg for adults, to times/day in combination with interferon-α or lopinavir/ritonavir for no more than days [ ] . the in vitro activity against sars-cov was limited and required high concentrations to inhibit viral replication, necessitating high dose, and combination therapy [ ] . the high doses of ribavirin used in the sars trials resulted in hemolytic anemia in more than % of patients, resulting in a severe dose-dependent hematologic toxicity [ , ] . the adverse effect of anemia is seen particularly at the dosages for which it has been tested for mers (~ - mg/day) [ ] . with the increased risk of anemia at the doses necessary, ribavirin should not be implicated as the first drug of choice in covid- patients. ribavirin is also a known teratogen and contraindicated in pregnancy [ ] . this contraindication should be tested further to understand the exact effects of teratogenicity. remdesivir, a broad-spectrum antiviral, is another potential drug that is under investigation for the treatment of covid- . animal experiments indicate that remdesivir can effectively reduce the viral load in lung tissue of mice infected with mers-cov, improve lung function, and alleviate pathological damage to lung tissue [ ] . remdesivir is an investigational monophosphoramidate prodrug of an adenosine analog that, in its active triphosphate nucleoside form, binds to rna-dependent rna polymerase and acts as an rna-chain terminator against the ebola virus [ ] . the first clinical use of remdesivir was for the treatment of ebola, however, successful case reports describing the use of remdesivir for covid- have been reported [ , ] . remdesivir is also highly selective for viral polymerases and is therefore expected to have a low propensity to cause human toxicity [ ] . remdesivir is metabolized into its active form, gs- , that obscures viral rna polymerase and evades proofreading by viral exonuclease, causing a decrease in viral rna production [ ] . in vitro studies with mice, hepatitis virus showed that remdesivir inhibits coronavirus replication through interference with the viral polymerase, despite the presence of a viral proofreading exoribonuclease [ ] . the first case of covid- in the united states was noted to be in washington. this patient was compassionately treated with intravenous remdesivir for the progression of pneumonia on day of hospitalization [ ] . the patient's condition had notably improved and no obvious adverse effects were observed [ ] . despite the nasopharyngeal and oropharyngeal swabs remaining positive four days following the administration of remdesivir, authors had noted a trend in the decline of viral load [ , ] . the -day regime of remdesivir treatment consists of an initial dose of mg on day , followed by subsequent doses of mg for nine consecutive days via intravenous infusion [ , ] . a trial sponsored by the national institute of allergy and infectious diseases (niaid) presented with promising preliminary results. the trial consisted of patients and had initially begun on february , . preliminary results indicate that patients who received remdesivir had a % faster time to recovery than those who received a placebo and furthermore, the median time to recovery was days for patients treated with remdesivir compared with days for those who received the placebo [ ] . with such promising results, remdesivir is currently being referred to as the standard of care for covid- . favipiravir is a prodrug of a purine nucleotide, favipiravir ribofuranosyl- '-triphosphate that inhibits the rna polymerase, halting viral replication [ ] . in addition to its anti-influenza virus activity, favipiravir is capable of blocking the replication of flavi-, alpha-, filo-, bunya-, arena-, novo-, and other rna viruses [ ] . a loading dose is recommended ( to mg every hours x doses) followed by a maintenance dose ( mg to mg every hours) [ ] . favipiravir has mild adverse effect profile and is overall well-tolerated, although the adverse event profile for higher dose regimens is limited [ , ] . the exact antiviral effect of favipiravir in patients with covid- needs demanding data to support as several clinical trials are evaluating this agent in different combination regimens [ ] . tocilizumab, as immunotherapy, is a humanized anti-interleukin monoclonal antibody for the treatment of rheumatoid arthritis [ , ] . it inhibits both membrane-bound and soluble interleukin- (il- ) receptors [ ] . covid- patients present with hyperinflammatory states and cytokine storms that include elevated levels of il- . il- is one of the several cytokines that are released by both monocytes and macrophages in response to destruction to the type ii pneumocytes. type ii pneumocytes are destroyed as the replicated virion genome buds off of the pneumocyte. il- is a cytokine that is a key player in causing fever and acute inflammation. currently tocilizumab is being tested in patients with the potential risk of cytokine stormdriven hyper inflammation (also known as cytokine release syndrome) that can be triggered by infections, including covid- [ ] . given the experience, tocilizumab has been used in a small series of severe covid- cases with early reports of success [ ] . a report of patients with covid- showed receipt of tocilizumab, mg, was associated with clinical improvement in % of patients as measured by improved respiratory function, rapid defervescence, and successful discharge, with most patients only receiving one dose [ ] . a preprint (nonpeer reviewed) case series of patients treated with tocilizumab between february and , in china reported marked success, including rapid resolution of fever and c-reactive protein, decreased oxygen requirements, and resolution of lung opacities on computerized tomography imaging [ ] . tocilizumab presents with promising effects as depicted in various trials surrounding covid- . the recommended dose is - mg/kg or mg standard dose iv once, with the option to repeat a dose in hours [ , ] . the optimal timing of tocilizumab administration during the disease course is not yet defined, nor is there a known il- threshold for progression to severe disease [ ] . there were no reported adverse events in the tocilizumab-treated patients submitted to the fda [ ] . sarilumab, another il- receptor antagonist that has been approved for use in rheumatoid arthritis, is being studied for hospitalized patients with severe covid- [ ] . given their antiviral activity against influenza, considerable attention has been paid to oseltamivir, and a lesser degree baloxavir, as potential treatment options for covid- [ ] . oseltamivir is a neuraminidase inhibitor that is approved for the treatment of influenza, however, it has no documented in vitro activity against sars-cov- [ ] . the correlation of oseltamivir and baloxavir with covid- is purely coincidental. the covid- outbreak in china initially occurred during peak influenza leading to a large proportion of patients received empirical oseltamivir therapy until the discovery of sars-cov- as the cause of covid- [ ] . neither oseltamivir nor baloxavir plays any role in the management of covid- in cases where influenza has been excluded or is not comorbid. as the outbreak of covid- continues to create fear within the medical community, investigating all possible pharmaceutical options is necessary. several different pharmacological options are constantly emerging and looking into each of the interventions is crucial in attempts to contain the current pandemic. currently, there are no fully verified antiviral drugs or vaccines that are specific to fighting sars-cov- . many pharmaceutical approaches being currently explored are those that have been used for various different conditions. the repurposing of these drugs provides hope that a cocktail of drugs currently on the market may appropriately target various steps in the lifecycle of sars-cov- , allowing for the ultimate degradation of the virus. decreasing the viral load by destabilizing the rnadependent rna polymerase will hinder the replication of the virion, and ultimately, decreasing the infectivity of sars-cov- . other approaches focus on impairing the fusion of sars-cov- with the type ii pneumocytes ace receptor. inhibiting fusion prevents any type of destruction of the type ii pneumocytes, eliminating any type of infectivity of the virus. it should be noted that almost all the pharmaceutical approaches are currently being further researched through clinical trials. these clinical trials will ultimately provide insight into the efficacy and safety of these candidate drugs, thus providing the medical field with appropriate alternatives to treating those infected by this pandemic. covid- : consider cytokine storm syndromes and immunosuppression structural polypeptides of coronavirus ibv coronavirus transcription: a perspective jpn guidelines for the management of acute pancreatitis: medical management of acute pancreatitis angiotensin-converting enzyme is a functional receptor for the sars coronavirus covid- treatment: the race against time pharmacologic treatments for coronavirus disease (covid- ): a review arbidol: a broad-spectrum antiviral compound that blocks viral fusion membranotropic effects of arbidol, a broad anti-viral molecule, on phospholipid model membranes 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review of lopinavir therapy for sars coronavirus and mers coronavirus-a possible reference for coronavirus disease- treatment option antiviral treatment of covid- a review of sars-cov- and the ongoing clinical trials the fda-approved drug ivermectin inhibits the replication of sars-cov- in vitro potential interventions for novel coronavirus in china: a systematic review novel coronavirus treatment with ribavirin: groundwork for an evaluation concerning covid- comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against mers-cov first case of novel coronavirus in the united states remdesivir as a possible therapeutic option for the covid- prophylactic and therapeutic remdesivir (gs- ) treatment in the rhesus macaque model of mers-cov infection arguments in favour of remdesivir for treating sars-cov- infections remdesivir in adults with severe covid- : a randomised, double-blind, placebo-controlled, multicentre trial experimental treatment with favipiravir for ebola virus disease (the jiki trial): a historically controlled, single-arm proof-of-concept trial in guinea potential therapeutic agents against covid- : what we know so far fda approval summary: tocilizumab for treatment of chimeric antigen receptor t cell-induced severe or life-threatening cytokine release syndrome clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china. jama. key: cord- - incf e authors: parikh, priyanka a; shah, binoy v; phatak, ajay g; vadnerkar, amruta c; uttekar, shraddha; thacker, naveen; nimbalkar, somashekhar m title: covid- pandemic: knowledge and perceptions of the public and healthcare professionals date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: incf e background and objective the recent pandemic due to the novel severe acute respiratory syndrome coronavirus (sars-cov- ) has become a major concern for the people and governments across the world due to its impact on individuals as well as on public health. the infectiousness and the quick spread across the world make it an important event in everyone’s life, often evoking fear. our study aims at assessing the overall knowledge and perceptions, and identifying the trusted sources of information for both the general public and healthcare personnel. materials and methods this is a questionnaire-based survey taken by a total of , respondents, out of which belonged to the healthcare personnel and were laypersons/general public. there were two different questionnaires for both groups. the questions were framed using information from the world health organization (who), uptodate, indian council of medical research (icmr), center for disease control (cdc), national institute of health (nih), and new england journal of medicine (nejm) website resources. the questions assessed awareness, attitude, and possible practices towards ensuring safety for themselves as well as breaking the chain of transmission. a convenient sampling method was used for data collection. descriptive statistics [mean(sd), frequency(%)] were used to portray the characteristics of the participants as well as their awareness, sources of information, attitudes, and practices related to sars-cov- . results the majority ( . %) of the respondents were indians. about % of the healthcare professionals and % of the general public were worried about being infected. various websites such as icmr, who, cdc, etc., were a major source of information for the healthcare professional while the general public relied on television. almost % of healthcare professionals and % of the general public, respectively, identified ‘difficulty in breathing” as the main symptom. more than % of the respondents in both groups knew and practiced different precautionary measures. a minority of the respondents ( . % of healthcare professionals and . % of the general public) knew that there was no known cure yet. almost all respondents from both the groups agreed on seeking medical help if breathing difficulty is involved and self-quarantine if required. conclusion most healthcare professionals and the general public that we surveyed were well informed about sars-cov- and have been taking adequate measures in preventing the spread of the same. there is a high trust of the public in the government. there are common trusted sources of information and these need to be optimally utilized to spread accurate information. in december , the novel coronavirus disease caused by novel severe acute respiratory syndrome coronavirus (sars-cov- ) emerged in china, followed by a rapid spread all over the world. on march , , the world health organization (who) raised its pandemic alert. as of april , , covid- had caused over , deaths in countries and overseas territories or communities [ ]. in a connected world, fake news and rumor-mongering are common due to a surge in the use of the internet and social media. a confused comprehension in an emerging communicable disease of which even the experts have inadequate knowledge can lead to fear and chaos, even excessive panic, which has the probability to aggravate the disease epidemic [ ] . during the sars epidemic from to , there were misconceptions and hence excessive panic in the general public concerning sars. this led them to be resistant to comply with suggested preventive measures such as avoiding public transportation, going to a hospital when sick, etc. this contributed to the rapid spread of sars and resulted in a more serious epidemic situation [ ] . a similar experience occurred during the ebola outbreak in in africa. these experiences underscore the vital role of engaging with the general public and healthcare professionals and the importance of monitoring their perception of disease epidemic control, which may affect the compliance of community to the precautionary strategies. understanding related factors affecting and influencing people to undertake precautionary behavior may also help decision-makers take appropriate measures to promote individual or community health. hence, it is crucial to understand people's risk perception and identify their trusted sources of information to effectively communicate and frame key messages in response to the emerging disease [ ] . since it is the novel coronavirus, its epidemiological features are not well known and new studies and publications will take anywhere from a month to a year making it important to know and understand the level of knowledge and preparedness of the healthcare personnel in terms of the managing the virus affected patients. today healthcare professionals managing covid- across the world are in an unprecedented situation, having to make tough decisions and working under extreme pressures. decisions include equitable distribution of scant resources among the needy patients, balancing their own physical and mental healthcare needs along with those of the patients, aligning their desire and duty to patients with those to family and friends, and providing care for all unwell patients with constrained or inadequate resources. this may cause some to experience moral distress or mental health problems [ ] . effective communication is a priority in who's covid- roadmap; accurate and salient messages will enhance trust and enable the public to make informed choices based on recommendations [ ] . as the outbreak intensified, social media has taken on new and increased importance with the large-scale implementation of social distancing, quarantine measures, and lockdown of complete cities. social media platforms have become a way to enable homebound people to survive isolation and seek help, co-ordinate donations, entertain, and socialize with each other. social media platforms arguably support the conditions necessary for attitude change by exposing individuals to correct, accurate, health-promoting messages from healthcare professionals in order to investigate community responses to sars-cov- , we conducted this online survey among the general public and healthcare professionals to identify awareness of sars-cov- (perceived burden and risk), trusted sources of information, awareness of preventative measures and support for governmental policies and trust in authority to handle sars-cov- outbreak and put forward policy recommendations in case of similar future conditions. we performed a cross-sectional survey of a convenient sample of respondents. the ethical approval for the study was taken from the institutional ethics committee - , hm patel centre for medical care and education, karamsad via letter iec/ hmpcmce/ / ex. / dated march , . all participants were above years of age conveniently selected from the public at large by reaching out to the general public and healthcare professionals by the authors. the participants were largely from india. the consent of the participants was taken at the beginning of the survey. two different self-administered questionnaires were used. the one for non-medical personnel (general public) is shown in table , while the one for medical and paramedical personnel is shown in table . descriptive statistics [mean (sd), frequency (%)] were used to portray the characteristics of the participants as well as their awareness, sources of information, attitudes, and practices related to sars-cov- . due to large sample sizes in the healthcare professional group as well as the general public group, exploratory visual comparisons were presented without typical statistical tests of significance. a total of health and allied professionals and persons from people at large consented and completed the survey. a majority ( . %) of the participants were indian residents with insignificant responses from outside india. it is presumed that the majority of the respondents are of indian residents but the possibility of a handful of them being non-indians cannot be ruled out because we did not collect demographic data. a comparison of awareness about sars-cov- between the general public and healthcare professionals is shown in table . half of the general public respondents showed eagerness for the sars-cov- test without difficulty in breathing. a similar trend was observed among health professionals. almost all respondents from the general public ( %) and the healthcare professionals ( %) endorsed seeking medical help if the breathing difficulty was involved. slightly more healthcare professionals reported regular influenza vaccination as compared to the general public [ ( . %) vs ( . %)]. almost all the respondents agreed for selfisolation if needed. the majority of the respondents reported that they were washing the hands more frequently and knew the correct way of handwashing. we present here a study of the awareness of sars-cov- among healthcare professionals and the general public with a comparison of many features among them. it is heartening to note that the knowledge with respect to sars-cov- is relatively high among the respondents. there are, however, various limitations of the study and these are inherent due to the circumstances in which this survey was done. the study was begun on march , , one day after janata curfew in india as requested by the prime minister and one day before the lockdown on march , [ ] . the survey was filled during the days of the lockdown when the respondents had a lot of time on their hands and were probably active on social media as well as watching the television news. hence, it is quite relevant that many individuals have their information from these two sources, making it important to ensure that accurate information through verified channels and healthcare professionals are presented and broadcasted to the people. this also points towards the importance of the right people being active on social media so that they can communicate the scientifically validated information to the masses. the curfew and the lockdown ensured that the seriousness of the disease was impressed upon by the highest offices in the country, which is reflected in people taking good precautionary measures to protect themselves from the disease as well as break the chain of transmission. the cases in india have hence not risen to a very high number as rapidly as expected/projected, which also probably indicates that the message was well conveyed and well perceived. as this is a survey that was filled remotely, we need to be cautious in drawing strong conclusions. another limitation of the study is that the questionnaire was in the form of google forms and the language of conduct was english. this implies that the people who did not have access to the internet and were not literate were unable to be a part of this survey. but as the source of information for all the general public remains similar (television is ubiquitous in india), we can infer that they would have a similar response. we base this inference as the main sources of information of the public at large were newspapers, television, and whatsapp despite having access to websites and other online sources. in villages, often the literate readout regional newspapers and news received on mobiles to the rest of the family/friends to ensure dissemination of information. it is now known that the basic reproductive number (r ) of coronavirus is more in healthcare professionals as compared to the lay public and hence the relative indifference or "no worries" approach of healthcare professionals towards getting infected by sars-cov- is a concern. in the scenario where adequate personal protective equipment (ppe) may not be available to the healthcare facilities in india due to increased global demand, it is important that healthcare workers know their risk for being infected. in a recent study in mumbai, % of the healthcare professionals were aware of the various ppe required with only . % of them being aware of isolation procedures needed for sars-cov- infected patients [ ] . the numbers for paramedical staff were also lower. india imports raw materials for ppe production from china and south korea. due to the shortage of materials and low rate of supply, the availability has taken a massive hit resulting in an acute shortage in the market. it is highly likely that many healthcare professionals will not use appropriate ppe, will get infected, and further spread infections to patients [ ] [ ] [ ] . the bhilwara cohort in rajasthan is an example of how a healthcare professional needs to protect against infection since he/she is likely to transmit it to others [ ] . another example in mumbai is saifee hospital, which was shut down due to an infected healthcare professional who continued to work and passed on the infection to many during the asymptomatic phase. the sars-cov- disease presents a unique organism that can be spread for at least five days before developing symptoms and up to days after presentation [ , ] . given its high infectivity, it is a recipe for disaster if healthcare personnel gets it. we have not collected demographic information from the participants and hence it is possible that many of them work in situations where they may not anticipate getting infected. the previous few months have shown how surgeons, orthopedicians, dentists, etc., who typically do not deal with infectious diseases are getting infected by coronavirus [ , ] . in this scenario, it is worrying that only % of healthcare professionals were worried while the public was slightly more worried ( %). the difference in the source of information for healthcare professionals and the general public is stark when we compare information garnered through social media. social media at . % is the second-highest source for the general public, while the healthcare professionals give it a measly %. since social media is prone to fake news, it is heartening that healthcare professionals are not learning from it. however, the reliance of the general public on social media indicates that healthcare professionals, professional organizations, and government officers need to invest a significant proportion of their time and resources to be active on social media to disseminate correct news. the shots heard round the world rapid-response network is an example that needs to be followed [ ] . in another example, we have dr. roberto burioni who has successfully given accurate data on social media. if more healthcare professionals were to enrich social media, it would be a useful platform for the public [ , ] . while many government officials are active on twitter in india, the platform that is commonly used in india is whatsapp, telegram, instagram, and tiktok and these are dynamic and keep changing. whatsapp in the middle of this pandemic reduced the forwarding to just one person for a message that had been forwarded five times from the previous number of forwarding to five people (which was unlimited initially) [ ] . it indicates the importance of this platform across the world for the spreading of messages. the healthcare professionals rated scientific journals at just about . %. it may be due to the low availability of high-quality evidence or poor access that many healthcare professionals in india have to scientific journals, which are mostly published out of developed countries [ ] . in a pandemic situation, this disparity in access can be catastrophic and hence most journals have provided open access to all coronavirus-related publications. healthcare professionals accessed websites such as who, medscape, mohfw, cdc, worldometers, covid .com, icmr, uptodate, and pubmed, for reliable information, which is an indicator of their faith in health organizations across the world. interestingly though at a low . %, much of the general public accessed similar websites such as who, mohfw, cdc, and icmr. at the time that the survey was administered, online webinars via zoom or other applications were just beginning in india to educate clinicians searching for answers. this is not reflected in our current study due to many of the responses being filled before the same or the respondents not being part of these audiences. the study authors have attended many of these meetings conducted by the indian academy of pediatrics, etc., and this information is made available via email or whatsapp messages. in a changing world, both healthcare professionals and the general public need to have reliable and accurate sources of information. the severity of illness was well identified by all who were surveyed as being difficulty in breathing. another heartening aspect was that precautionary measures were well known to both the groups of participants with appropriate hand washing techniques, avoidance of public gatherings, and covering of the mouth while coughing and sneezing as the top three precautionary measures. during the first week of march in india, all the telephone and cellular caller tunes were changed to advisories of how to prevent coronavirus disease and when to seek medical help, which included the above messages apart from appeals on television, etc [ ] . there was less knowledge related to treatment and vaccine among both healthcare professionals and the general public, which was a disappointing finding for healthcare professionals as they were expected to be aware of this. the same could be said of the knowledge of the infectivity period and duration of being asymptomatic after infection. there was a good knowledge of the usage of masks among the general public and healthcare professionals except for the usage of medical masks for healthy people to protect themselves. the icmr and other bodies have issued guidelines on the usage of masks and this seems to have been disseminated widely [ ] . there was also a low insistence on the need for testing those without respiratory difficulty. in a scenario where testing resources are limited, this is an appropriate response but since it is possible to have the infection without respiratory difficulty, especially early on, this disinterest in getting tested, especially in healthcare personnel is worrisome when there is enough evidence of spread from asymptomatic and mildly symptomatic persons. it is also likely that this response may be due to the fact during the time that this questionnaire was administered, the total cases rose from + to about + and the testing strategy of icmr was limited to those with contact or travel to sars-cov- -affected areas [ ] . since writing this manuscript, except for a single source event of a religious gathering in delhi, which caused the doubling of cases to increase from about seven days to . days, it is reasonable to conclude that adequate knowledge exists among the general public. we can only hope that this would be enough to ensure that lockdown to reduce transmission and flatten the curve will be successful [ ] [ ] [ ] [ ] . the covid- pandemic has affected the world in various ways. the deficiency of information, the need for accurate information, and the rapidity of its dissemination are important, as this pandemic requires the cooperation of entire populations. the rapid survey that we conducted had a good response and we show that healthcare professionals and the general public were quite well informed about the coronavirus. they are aware of the measures needed to be taken to reduce the spread of the disease. the knowledge present allows the authors to speculate that the lockdown in india would be effective. the public receives a large amount of information from social media such as whatsapp and the medical fraternity and government need to develop strategies to ensure that accurate information needs to spread in these fora. the public awareness is quite high and it is important that the knowledge of communication channels be known and be kept at the topmost priority throughout the pandemic. the following is part of the text of the approval letter indicating approval for the study. "your research proposal 'response of the public and health care providers to a pandemic of a new virus' was submitted for review and approval by committee members under exempt review. as it involves collection of data using anonymous online questionnaire with maintenance of privacy and confidentiality, it qualified for an exempt from full committee review. the matter was reviewed by committee members and decided to review it under 'exempt from full committee' review. after review and subsequent clarification by you, the project is approved by iec in its present form. as the online form has information and consent section, which needs to be read and accepted by the respondents before answering the study questions, committee waivers the need for any other consent for data collection.". animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. the public's response to severe acute respiratory syndrome in toronto and the united states monitoring community responses to the sars epidemic in hong kong from day to day epidemiology of severe acute respiratory syndrome (sars): adults and children managing mental health challenges faced by healthcare workers during covid- pandemic who -communicating risk in public health emergencies india will be under complete lockdown for days: narendra modi -economic times covid- awareness 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during - on every call you make, you will hear a person coughing and that is annoying -indiatoday ministry of health and family welfare -guidelines on use of mask by public strategy of covid testing in india it would've been in . days -economic times how tablighi jamaat event became india's worst coronavirus vector flattening the much-talked covid- curve-how close are we in india? -research matters lockdown may help flatten coronavirus curve in india, says study -business today we are thankful to dr. mili shah for language check of our manuscript. key: cord- - el o qq authors: mahmood, syed uzair; crimbly, faine; khan, sheharyar; choudry, erum; mehwish, syeda title: strategies for rational use of personal protective equipment (ppe) among healthcare providers during the covid- crisis date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: el o qq as the coronavirus (covid- ) began spreading globally with no clear treatment in sight, prevention became a major part of controlling the disease and its effects. covid- spreads from the aerosols of an infected individual whether they are showing any symptoms or not. therefore, it becomes nearly impossible to point exactly where the patient is. this is where personal protective equipment (ppe) comes in. these are masks, respirators, gloves, and in hospitals where the contact with the infected and confirmed patient is direct, also gowns or body covers. the ppes play a major role in the prevention and control of the covid- . the ppe is able to prevent any invasion of the virus particles into the system of an individual which is why it is an essential item to have for healthcare workers. due to the high demand for ppes all around the world, it is important to optimize the use of protective gear and ration the supplies so that the demand are met. however, there are guidelines recommended by the world health organization (who) and the centers for disease control and prevention (cdc) to maintain the supply in the wake of this increased demand of ppe, how the manufacturers should track their supplies, and how the recipients should manage them. various strategies can be used to increase the re-use of ppes during the covid- pandemic that has modified the donning and doffing procedure. personal protective equipment (ppe) is an article used to prevent the wearer from coming in contact with hazardous, infectious, chemical, radiological, electrical, and physical agents. it contains components illustrated in figure [ ] . the surge in demand and misuse of ppe has led to an acute shortage of protective gear, endangering the lives of healthcare workers [ ] . more than , healthcare workers (hcw) in the united states (us) and more than , in italy have been infected with covid- [ ] [ ] . a total of hcw in pakistan have been exposed to covid- as of april , [ ] . many doctors are performing their duty without any ppe and are at high risk of becoming infected [ ] . there have been peaceful protests all over the world by doctors, nurses, and other healthcare professionals demanding ppe. in the wake of the covid- pandemic, ppe plays a significant role, with face masks and gloves being the most essential. doctors, nurses, and other frontline healthcare responders are using them to minimize the risk of contaminated contact or droplet exposure. some studies suggest that the psychological impact of ppe is such that individuals using them might feel more protected than they actually are in reality [ ] . it should be ensured that the wearer practices hand hygiene before wearing and after removing the protective gear. also, an appropriate method for its disposal should be considered. the primary mode of transmission of coronavirus is known to be droplet or contact-based. infected individuals are prone to spread the virus while coughing, sneezing, or speaking. this micro virus, when ejected, can travel up to a distance of six feet. wearing a face mask, along with other precautionary measures like hand hygiene and self-isolation, limits the transmission of infectious agents [ ] [ ] . initially, the usage of masks among the general public was highly controversial. experts discouraged healthy people from wearing masks due to the scarce supply. this equipment was reserved for those in direct contact with infected patients [ ] . however, the rapid rise in the degree of local transmission has caused many countries to allow their citizens to wear nonmedical/cloth masks, along with practicing social distancing [ , ] . evidence-based studies reveal that the concomitant use of household (non-medical) face masks, as well as using a proper handwashing regimen, reduces the probability of local transmission, thereby decreasing the death toll [ ] . it should be noted that according to the world health organization (who) guidelines, medical masks and respirators should only be reserved for healthcare workers [ ] . factors that determine the efficiency of face masks are listed in table [ ]. the shape of the mask the main types of masks being used are respirators, medical masks, and non-medical/cloth masks. these are protective equipment which provides an almost accurate facial fit and effective filtration of airborne particles. they provide a proper seal around the mouth and nose, providing optimal protection. according to the recent who, cdc, and fda guidelines, such masks are only reserved for healthcare providers [ , [ ] [ ] . the fda has labeled these masks as single-use, disposable devices; however, in cases of shortage in supplies, these can be sterilized and reused [ ] . while the respirator masks are highly efficient, they still do not provide complete protection. improper and misuse of these masks can lead to the spread of infection in the user [ ] . these are thin, pleated, and disposable masks that protect the user from inhaling dust particles, contaminated liquid droplets, and bacteria. they are usually two layers thick and made from unwoven fabric. these masks only act as a physical barrier between the user's nose and mouth and the infected environment. they do not possess a proper seal and are less effective than respirators. these are loose masks, which allow comfortable breathing and reduce transmission probability [ ] . according to recent studies, asymptomatic and pre-symptomatic carriers of the novel coronavirus have been detected and can transmit the virus. in the face of this discovery, cdc experts recommend that the general public uses non-medical/cloth coverings to shield their mouth and nose. these textile masks are made up of layers of cloth. some of them also possess a paper towel layer, which increases the filtration capability. they do not offer full protection but, along with other precautionary measures, are useful to slow down the spread of coronavirus [ ] . as a general safety precaution, every frontline healthcare worker (hcw) should know which ppe needs to be used in different clinical settings [ ] [ ] . ) under any clinical setting where there is a risk of getting infected, the individual should don (put on) a medical face mask, gloves, gown, and eye protection, ) if the hcw is more than meters away from the patient, he/she should use a fluid-resistant medical face mask with or without eye and face protection, depending on whether there is exposure to flashes or droplets. ) in case of an ongoing aerosol-generating procedure (agp), all individuals present should wear a respirator, face and eye protection, gloves, and long-sleeved fluid-repellent gown. it is essential that every hcw should know the proper way to put on (donning) and remove (doffing) ppe. any mistake in doing so can render the individual exposed to infections agents. according to standard infection prevention and control (ipc) guidelines, ppe is a single-use, disposable item. however, due to the current shortage of ppe, health care providers are challenged to rationally use the limited supplies by decontaminating and reprocessing them. it should be noted that there is no proven effectiveness of these practices and priority is given to the rapid manufacture of protective items [ ] . improper or inadequate decontamination of equipment before reuse is unsafe and can pose serious threats [ ] . when disinfecting ppe, it is important to keep in mind the efficacy of the method used, check for any residual toxicity, and make sure that the functional integrity of the material is maintained. general strategies include following the manufacturer's guidelines to disinfect and reprocess the ppe. routine inspection of protective material should be carried out, along with the replacement of the equipment if the integrity is not maintained or it is damaged. ) usually cleaning prior to disinfection is required. respirators and medical masks lose their protective property when they undergo cleaning. ) considering the current conditions, these items can be worn by a single hcw for multiple shifts. factors, such as humidity and shelf-life, limit their use. ) medical masks can be reprocessed using the environment protection agency (epa)registered disinfectants. filtering facepiece respirators can be decontaminated using vaporous hydrogen peroxide, moist heat, and bleach solution. gowns ) submerge in hot water and detergent, then thoroughly scrub the gown. ) afterward, soak in . % chlorine solution for about minutes. ) rinse in clean water and ideally allow drying in the sun. ) gowns having small holes and tears could be mended whereas worn out gowns should be discarded. ) clean first the inside and then the outside surface of the visor using a detergent-soaked clean cloth. ) clean the outside of the visor with a clean cloth saturated with disinfectant. ) wipe the outside of the visor with clean water. ) use towels or dry air to completely dry the visor. ) immerse in warm water and neutral detergent solution. ) rinse with clean water. ) wipe with disinfectant and then again rinse with clean water. ) dry completely using towels or dry air. potentially infectious medical waste (pimw), such as covid testing kits and ppe, have a serious risk of coming in contact with infectious bodily fluids. these materials should be kept safely on site (hospitals, testing centers) in secure containers. they should then transferred to storage facilities, where they are disinfected and disposed of off to landfill sites [ ] . individuals responsible for waste management should take caution and should wear appropriate gear. it is extremely critical to properly decontaminate and dispose of any waste material that could infect people who come in contact with it. the escalating demand for ppe has given rise to new state and local strategies to ensure the careful optimization of available resources. this policy helps reserve the reduced amount of ppe for the most critical conditions. as the situation improves and the ppe supply is sufficient again, the state can return to its conventional ppe guidelines. the following strategies should be observed to overcome the shortage of ppe [ ] . there is a difference in the demand and supply of ppe, with severe shortages in supply on all fronts. it is crucial that all the equipment is used with care to prevent wastage, to ensure a continuous supply of protective equipment despite limited production [ , ] . ) the healthcare professionals who are working with patients of covid- and are in direct contact should have ppe consisting of gloves, gowns, masks, face shields, and goggles. ) the same respirator can be used while examining multiple patients at a time. since the shortage of supply is a fact in most places, it is recommended to keep wearing a single one for multiple patients than to not have any respirator on. ) hcw performing or assisting with invasive procedures should be wearing respirators, eye protection (like goggles), and a face shield aligned with the gown and gloves. if the gowns allow fluid to pass through, an additional layer of protective coverage like an apron should be worn. ) people who are taking care of the sick at home should be provided with medical masks at home for their own protection and to limit the spread of the disease. ) individuals who remain asymptomatic or do not show any signs of illness can use nonmedical masks and should not opt for medical masks. inappropriate use of medical masks may increase the demand and can also impede the supply to professionals who need them the most. the need for ppe can be minimized by the following interventions [ ] : ) limit patient contact and use alternate tools, such as telemedicine, for non-emergency cases. ) make sure that no personnel who is not immediately needed for the patients' care should enter the premise of the covid- ward that should be a separated and isolated area. the visitors should either not be allowed at all or should have minimal contact with the patients. ) all non-urgent procedures/appointments should be postponed. ) ppe should be used beyond their shelf life making sure they are not worn out or damaged. ) in the case of the absolute absence of ppe, alternate methods for barrier control (e.g., glass shields) should be employed. these practices do not guarantee the absolute safety of healthcare professionals, and their effectiveness is questionable. however, under the present circumstances, these crisis strategies given by the cdc should be duly addressed. the supply should be monitored and demand adjusted [ , ] . this can be done using the following methods: ) use of rational quantification-based forecasts regarding ppe. this helps in rationing available supplies to meet the demand. ) the request for ppe from countries, as well as major responders, should be monitored and controlled. the distribution of ppe to healthcare institutions should be controlled and monitored. ) to avoid stock duplication, a centralized request management system should be applied that takes notice of whether the stock management rules are being followed or not. this helps in controlling the wastage and overstock. ) keep a check on the end-to-end distribution of ppe. due to the recent ease in lockdown measures and the commencement of the holy month of ramadan in the muslim world, an abrupt rise in public gatherings is feared. therefore, it is highly critical that ppe's should be used in all clinical and non-clinical settings. citizens should use a cloth barrier while stepping out of the house and public gatherings should be strictly avoided. the proper protocol should be followed when healthcare professionals consider reusing ppe. as pakistan is one of the major distributors of ppe throughout the world, it has set an exemplary approach during this pandemic. the pakistani government and national disaster management authority (ndma) have made tireless efforts to increase the manufacturing and distribution of ppe. moreover, many non-governmental organizations (ngos) and medical students have come forward to combat this deadly disaster and distribute ppe to those fighting on the frontline. disclosures risk at work -personal protective equipment (ppe) shortage of personal protective equipment endangering health workers worldwide health-care workers have been infected with the coronavirus italian health workers infected with virus: study infections amongst healthcare workers increase by pc in a week uk doctors finding it harder to get ppe kit to treat covid- patients use of ppe in response of coronavirus (covid- ): a smart solution to global economic challenges rational use of face masks in the covid- pandemic keep your distance to slow the spread advice on the use of masks in the context of covid- recommends people wear cloth masks to block the spread of covid- . surgical masks and n respirators should be reserved for health care workers face masks against covid- : an evidence review . n respirators and surgical masks n respirators and surgical masks (face masks improper use of medical masks can cause infections use of cloth face coverings to help slow the spread of covid- accessed updated guidance on personal protective equipment (ppe) for clinicians personal protective equipment use in health care use personal protective equipment (ppe) when caring for patients with confirmed or suspected covid- operational considerations for personal protective equipment in the context of global supply shortages for coronavirus disease (covid- ) pandemic: non-us healthcare settings rational use of personal protective equipment ( ppe) for coronavirus disease ( covid- ) : interim guidance water, sanitation, hygiene and waste management for covid- strategies to optimize the supply of ppe and equipment sourcing personal protective equipment during the covid- pandemic critical preparedness, readiness and response actions for covid- : interim guidance in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -ssk jkx authors: suwanwongse, kulachanya; shabarek, nehad title: successful conservative management of acute appendicitis in a coronavirus disease (covid- ) patient date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ssk jkx appendectomy is the gold standard of treatment for acute appendicitis; however, recent evidence suggests conservative management with intravenous antibiotics may provide similar outcomes and can be used as an alternative in selected patients. performing appendectomy in acute appendicitis patients with novel coronavirus disease (covid- ) is challenging, as it involves considerable operative risks for the patients and risks for health care professionals (hcps) exposed to covid- . medical management eliminates the morbidity and mortality associated with surgery but involves significant risks of treatment failures that, in turn, may lead to perforation, peritonitis, and death. we are reporting a case of a middle-aged man with multiple co-morbidities, who was diagnosed with covid- and acute appendicitis. our patient received intravenous antibiotics for seven days with a significant improvement in symptoms. our case report illustrates the implementation of successful conservative treatment for acute appendicitis in covid- patients. acute appendicitis is the most common cause of surgical abdomen, with a lifetime prevalence of % [ ] . appendectomy is the gold standard of care for patients with acute appendicitis, but recent evidence showed that conservative treatment with intravenous antibiotics may provide similar outcomes [ ] . non-operative treatment for acute appendicitis has additional benefits, including the elimination of the mortality and morbidity risks associated with surgery, as well as the complications of anesthesia, infection, and bleeding, the obliteration of the long-term complications of abdominal surgery, such as bowel obstruction and chronic wound pain, a decrease in the treatment cost and the length of hospital stay [ ] [ ] [ ] . patients with the novel coronavirus disease (covid- ) have substantially higher operative risks due to the compromise of lung function and the cytokine storms that result in systemic inflammatory response syndrome (sirs) and multiple organ dysfunction. to date, there is no report regarding the outcomes of non-operative treatment for acute appendicitis in covid- patients. we are presenting a case of successful conservative management of acute appendicitis in a covid- patient to support the role of non-operative management for acute appendicitis in selected cases. a -year-old male presented to the emergency department with worsening generalized open access case abdominal pain, which was aggravated by movement and associated with nausea and vomiting. he also reported fever, dry cough, and mild dyspnea. his past medical history included diabetes mellitus, hypertension, and morbid obesity with a body mass index (bmi) of . . on initial evaluation, his vital signs were unremarkable. oxygen saturation was % on room air. his lung exam was normal. the abdominal exam revealed generalized tenderness without guarding. his chest x-ray (cxr) showed bilateral multiple patchy infiltrates as demonstrated in figure . he was admitted to the medicine floor due to covid- pneumonia and acute appendicitis. hydroxychloroquine and azithromycin were given for five days for the treatment of covid- . due to the substantially high operative risks, the shared decision was made to provide medical management for his acute appendicitis. he received intravenous piperacillin/tazobactam . milligrams every six hours for seven days and his abdominal pain was resolved. he was discharged on hospital day without complications. the diagnosis of acute appendicitis may be challenging in covid- patients. fever, nausea, vomiting, and abdominal pain may be mistaken as symptoms of covid- . in our patient, there was no sign of peritonitis on the abdominal exam, which was likely due to his morbid obesity. acute appendicitis was diagnosed based on clinical signs but other investigations including ultrasound and ct scan of the abdomen are helpful in difficult cases. misdiagnosis of acute appendicitis can lead to appendiceal perforation, appendiceal abscess, peritonitis, sepsis, and death. clinicians should include acute appendicitis in the differential diagnosis of covid- patients who report abdominal pain. although there is increasing evidence that intravenous antibiotics can be used as alternative management, especially in patients with a high operative risk, appendectomy remains the gold standard of care for patients with acute appendicitis. surgical appendectomy provides curative treatment without a recurrence of appendicitis but associated with significant operative risks, post-surgical complications, higher costs, and longer recovery times. conservative management is less invasive but associated with treatment failure and the chances of recurrences appendicitis [ ] [ ] [ ] . covid- patients have considerable operative risks as a result of direct lung injury and multiple organ dysfunctions. our patient has multiple co-morbidities and had hypoxemia and acute kidney injury from covid- , which posed significantly high morbidity and mortality risks from an operation. thus, the shared decision was made to initiate medical management with intravenous antibiotics, which successfully treated his conditions. to date, there is a lack of good evidence, i.e., high-quality randomized controlled trials (rcts) supporting the use of antibiotics in the treatment of covid- . thus, the selection of antibiotics for the medical management of acute appendicitis in covid- patients may not differ from the general population. the non-operative management of acute appendicitis provides an additional advantage in terms of limiting the health care professionals' (hcps') exposure to covid- , particularly in the setting of limiting personal protective equipment. our case report suggests the role of conservative treatment of acute appendicitis in covid- patients. however, more research is needed to evaluate the short-and long-term outcomes of the conservative treatment of acute appendicitis in patients with covid- . intravenous antibiotics may be used as an alternative treatment of acute appendicitis in covid- patients to eliminate operative risks and the risks of hcps' exposure to covid- . to date, there is no high-quality evidence demonstrating the benefit of any antibiotics on covid- treatment outcomes. therefore, the optimal selection of antibiotics for the medical management of acute appendicitis in covid- patients should be similar to that in patients not suffering from covid- . the epidemiology of appendicitis and appendectomy in the united states randomized clinical trial of antibiotic therapy versus appendicectomy as primary treatment of acute appendicitis in unselected patients conservative treatment of acute appendicitis antibiotics as first-line therapy for acute appendicitis: evidence for a change in clinical practice human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -itdorszt authors: farha, loulwa; abi jaoude, joseph title: lebanese healthcare system: how will the aftermath look? date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: itdorszt the recent lebanese port explosion came as a continuation of a series of socioeconomic disasters the country has been facing during the past year. in addition, the massive impact of the coronavirus disease- (covid- ) pandemic further hastened the collapse of the lebanese healthcare system. in light of all those events, the lebanese healthcare sector has faced major blows that will be difficult to recuperate from. in the aftermath of the beirut port explosion, lebanon received immense financial and medical support from the international community in a timely fashion, which secured first level care to victims of the explosion. nevertheless, this forced lebanon, which was considered a prominent tertiary medical hub in the middle east, to slowly regress into an exclusive primary care provider. as such, it is crucial for local and regional stakeholders to build strong collaborations, and shape a unified vision of lebanon’s future healthcare system. on august , beirut, the capital of lebanon, witnessed one of the biggest explosions in the history of mankind [ ] . although not really a nuclear explosion, the blast was strong enough for people from around the world to question a potential nuclear nature to the event, with some going to the extent of dubbing the explosion "beirutshima", owing to its similarity with the tragic events of the hiroshima bombing [ ] . the explosion led to the deaths of hundreds, wounded thousands, and resulted in a colossal physical and financial burden on the country [ ] . while this particular day was truly incomparable, it merely comes as a continuation of a wave of disasters the country has faced during the past year. as a matter of fact, the recent political and economic situation has driven lebanon into one of the most serious financial breakdowns in its modern history, and has pushed a large proportion of its population below the poverty line. in addition, the massive impact of the coronavirus disease- (covid- ) pandemic further compounded the effects of the lebanese financial collapse [ ] . in light of all those events, it becomes quite evident that the major blows sustained by the lebanese healthcare system have elicited a negative chain reaction that will be difficult to recuperate from. from the beginning of the lebanese economic crisis which began around a year ago, many of the small-scale hospitals and medical centers faced threats of potential bankruptcy. however, with the continuous financial strain, even the bigger tertiary medical centers had to succumb to those dire circumstances and adopt harsh measures to stay afloat [ ] . the most noteworthy measures included laying-off a considerable number of hospital staff, and closing some of the hospital wards that were operating at suboptimal capacity [ ] . moreover, many highly qualified physicians and nurses opted to leave lebanon for better opportunities abroad as a result of pay cuts that were later accompanied by a depreciation of the national currency. as the lebanese pound lost approximately % of its value, the importation of medications and medical equipment became exceptionally difficult and restricted. as such, the pressure on the healthcare system began to build up early on, sending shock waves into the foundations of what was once considered one of the top healthcare systems in the region. as the number of covid- cases drastically increased around the world, lebanon was no exception. the covid- pandemic began to pick up pace in the country just weeks prior to the explosion with infections reaching the range of a couple hundred new cases registered daily [ ] . although the absolute number may seem small, the number of covid- infections is considered to be relatively high after accounting for the country's small population size (with rates reaching as high as cases per million persons as of july ) [ ] . hospitals and medical centers have been suffering for months to keep up with the increase in demand for intensive care unit beds, medical equipment, and medications necessary to cater to patients with severe covid- infections. it would thus come as no surprise that the events of august were the final nail in the coffin of an already toppling healthcare system. the consequences of the explosion were directly evident as the number of injured people was estimated at approximately , patients [ ] . healthcare workers who have already been suffering from psychological burnout due to the covid- pandemic were also among those who lost their lives or were severely injured. to make things worse, the capital was faced with yet another repercussion that served as both a direct obstacle, and will serve as a future impediment, and that is the destruction of several hospital facilities. three of the major tertiary medical centers serving the beirut area were severely damaged rendering them completely non-operational, and forcing them to evacuate their patients immediately. furthermore, most of the hospitals and medical centers in beirut and the neighboring areas were also affected, albeit to a lesser extent. those facilities sustained damages to their infrastructure and medical equipment which forced them to operate under harsh conditions. as such, in a matter of hours, lebanon was faced with an acute increase in demand for healthcare, only to be met by a massive and abrupt decrease in supply. within hours, lebanon transformed from a major tertiary medical hub, to the equivalent of a huge emergency room, providing nothing but the most basic medical services to its patients. in the aftermath of all this chaos, lebanon received and is still receiving immense financial and medical support from the international community. a significant fraction of this aid came in the form of financial funding to trusted non-governmental organizations (ngos). other notable support was offered in the form of basic nutrition and medical supplies, such as field hospitals, medical equipment, and medications. this remarkable aid was offered in a timely fashion, and allowed the situation in lebanon to slightly stabilize. although far from optimal, this secured first level care to victims of the explosion, which was of prime significance in such an exceptional situation. nevertheless, this rapid and chaotic surge in hospital admissions further increased the rate of covid- infections, which posed yet another problematic issue to an already struggling sector. lebanon's healthcare system has been on the receiving end of repeated blows that have already started to change the nature and quality of its healthcare delivery. a once prominent tertiary medical hub in the middle east is slowly turning into an exclusive primary care provider. for that reason, it is now crucial for local and regional stakeholders to start planning out the aftermath of these unfortunate events. despite vital support from the international community, funding is currently being distributed among several entities that lack common management that is capable of assessing the gaps in the entire sector, and allocating resources so as to reestablish a coherent system. the prevailing circumstances also necessitate the immediate resumption of functions at tertiary medical care centers that offer specialized treatments, disease screening, and disease prevention. similarly, tackling the psychological and financial stress of healthcare personnel is essential to prevent further losses of valuable human resources. finally, given the unstable political and socioeconomic condition in the country, it becomes of utmost importance to build a solid collaboration among the key contributors who will help shape a unified vision of lebanon's future healthcare system. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. why beirut's ammonium nitrate blast was so devastating coronavirus infections-more than just the common cold major beirut medical centre lays off hundreds as crisis bites covid- response in lebanon: current experience and challenges in a lowresource setting key: cord- -nrhe aek authors: shah, kaushal; mann, shivraj; singh, romil; bangar, rahul; kulkarni, ritu title: impact of covid- on the mental health of children and adolescents date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: nrhe aek the coronavirus disease (covid- ) outbreak was first reported in wuhan, china, and was later reported to have spread throughout the world to create a global pandemic. as of august th, , the coronavirus had spread to more than countries with at least , , confirmed cases, resulting in , deaths globally. several countries declared this pandemic as a national emergency, forcing millions of people to go into lockdown. this unexpected imposed social isolation has caused enormous disruption of daily routines for the global community, especially children. among the measures intended to reduce the spread of the virus, most schools closed, canceled classes, and moved it to home-based or online learning to encourage and adhere to social distancing guidelines. education and learnings of . % of students are impacted globally due to coronavirus in countries. the transition away from physical classes has significantly disrupted the lives of students and their families, posing a potential risk to the mental well-being of children. an abrupt change in the learning environment and limited social interactions and activities posed an unusual situation for children's developing brains. it is essential and obligatory for the scientific community and healthcare workers to assess and analyze the psychological impact caused by the coronavirus pandemic on children and adolescents, as several mental health disorders begin during childhood. countries across the globe, including the united states, are in the dilemma of determining appropriate strategies for children to minimize the psychological impact of coronavirus. the design of this review is to investigate and identify the risk factors to mental health and propose possible solutions to avoid the detrimental consequence of this crisis on the psychology of our future adult generations. since the first reported coronavirus case in wuhan, china, in , the outbreak, now known as covid- , has spread globally [ ] . the world health organization (who) acknowledged this coronavirus epidemic as a pandemic and declared the outbreak as a public health emergency of international concern [ - ]. most regions around the world are affected severely, including the united states, brazil, india, russia, and europe, which have seen an increasing number of cases and deaths than the rest of the world [ - ] . as of august th, , the coronavirus had spread to more than countries and has at least , , confirmed cases, resulting in , confirmed deaths globally. in the united states, between january th and august th, , there have been , , confirmed cases of covid- with , deaths [ ] . the spread of the virus has caused global economic and social disruptions and has brutally overwhelmed the healthcare and educational systems [ ] . the unexpected disruption of the social fabric and norms has affected the behavioral and mental health of the public, including children. the mental health of children has been influenced by several ways, as this unprecedented situation changed a way they typically grow, learn, play, behave, interact, and manage emotions. children with pre-existing psychiatric disorders such as attention-deficit/hyperactivity disorder (adhd), anxiety, depression, mood disorders, and behavior disorders could be adversely impacted during this stressful situation [ ] . mental disorders are the leading cause of disability worldwide in adolescents and children. about % of children and adolescents in the world have mental health disorders or conditions. nearly % of mental disorders start to affect the children by the age of . if left untreated, a child's mental development has been found to be drastically and detrimentally impacted. it is well established that mental health is one of the essential parts of human development and determines the outcome of a child's educational attainments and the potential to live fulfilling and productive lives [ ] . mental illness can affect children at any point during their childhood, but it most significantly affects them during adolescence. among the several mental illnesses that can be prevalent in childhood, depression is one of the major leading causes of mental illness amongst children. in , an estimated , deaths were due to adolescent suicide, which is the third leading cause of morbidity in this group. this emphasizes that adolescence is a period of vulnerability for the onset of mental health conditions [ ] . as of august th, , countries have closed schools and educational facilities worldwide due to the covid- pandemic, impacting , , , learners, consisting of about . % of students globally. it has forced several countries to implement home-based learning or online training [ ] [ ] [ ] . approximately . billion students and their families have been affected by school closures due to the pandemic. these students are experiencing further distress due to the unavailability of adequate help and attention from the trained instructors, making education more expensive for them and their families as they need to utilize additional time, support, and resources. due to the closing of schools, students' interaction and communication with school mates, play, exercises, and peer-activities are hindered, which have proven vital for the growth, development, and learning of the young human minds [ ] . the children who are at most significant risk are the youngest ones as their brains are still developing and are being exposed to high levels of stress and isolation, which can lead to permanent abnormal development. children exposed to stressors such as separation through isolation from their families and friends, seeing or being aware of critically ill members affected with coronavirus, or the passing of loved ones or even thinking of their own death from the virus can cause them to develop anxiety, panic attacks, depression, and other mental illnesses [ ] [ ] . the conducted literature search was through medline, pubmed, pubmed central, and embase using the keywords, 'coronavirus,' 'covid- ,' 'mental health,' 'child and adolescent,' 'behavioral impact,' 'psychological conditions,' 'quarantine,' and 'online education.' the indexed search aimed to identify literature and articles relevant to our focused topic. the objectives of this review article are . to understand the overall psychological impact of covid- on children and adolescents; . identifying factors contributing adversely to their mental health; and . proposing interventions based on the guidelines and evidence-based practices. the outbreak of covid- has disrupted the lives of many people across the world. the pandemic has imposed a sense of uncertainty and anxiety, as the world was unable to predict or prepare for this crisis. it has caused a tremendous stress level among children, adolescents, and all students in general, primarily due to the closure of their schools. this stress may lead to undesirable adverse effects on the learning and psychological health of students [ ] . children exposed to these incidents can precipitate the development of anxiety, panic attacks, depression, mood disorders, and other mental illnesses [ ] . distressing events such as separation from family and friends, seeing or being aware of critically ill members affected with coronavirus, or the passing of loved ones or even thinking of themselves perhaps dying from the virus would have a detrimental effect on the mental health. additionally, the healthy daily routines of children have been disrupted due to the covid- , which contributes to the additional stress and sleeping difficulties that many children face. uncertainty of their future ambitions, academics, personal relationships, and inactivity due to the pandemic poses a significant threat to their mental well-being and putting them at risk of drug abuse [ ] . covid- can seriously leave a negative impact on children's mental health, just like other traumatic experiences humans may face. it can lead to higher rates of depression, anxiety, and post-traumatic stress disorder. this causes fear in children because the virus threatens not just them but also their families and surroundings, especially as they see their parents working from home, leading to fear and shock [ ] . previous studies on severe acute respiratory syndrome (sars), middle east respiratory syndrome (mers), and ebola have revealed that the disease causes severe emotional distress during the outbreaks. unfortunately, studies were not adequately conducted on the children and adolescents during the past outbreaks to measure its impact on their mental health, but several parallels can be drawn. the situation of covid- is comparable with the mers and sars, as similar claims made about the severity of mers caused fear, worry, and anxiety among the public. a study on the sars survivors with psychiatric disorders revealed that about % of the patients showed signs of post-traumatic stress disorder (ptsd), and . % of them had worsening depression [ ] . this finding corresponds to the increased suicide deaths among sars survivors, consisting of older adults from hong kong in and [ ] . among those mers survivors, lower quality of life was also noticed. neuropsychiatric linkage has been established based on the previous outbreaks [ ] . during this pandemic, children and their families have been exposed to direct or indirect factors that could pose stress and emotional disturbance. several weeks of homestay has forced parents and/or caregivers to work from home. also, many families lost their financial independence due to job losses [ ] . this disease is installing fear in children because children are worried about not only getting infected but also having their parents staying at home and not leaving for work [ ] . some families are struggling to feed their children, as many were dependent on school programs or food stamps, and not all families with resources can provide adequate supplies [ ] . however, the reach of the pandemic is unequal as numerous families have lost loved ones while others live in regions untouched by the virus. some children have parents who work on the front lines in covid- settings, and others have parents who now work from home or have recently been terminated [ ] . additionally, international students are impacted by uncontrollable factors such as school closure, campus closure, and travel restrictions. nations across the globe have restricted their borders to internationals to help mitigate the pandemic as many students might not have any other place to reside. this sudden closure of many nations to outsiders has placed a great burden on school administrators to ensure housing, sustenance, and safety of their international students [ ] [ ] . while transitioning to online classes has helped both international and national students to continue their education, several children and faculty members are experiencing distress because they may not have the technological capability or expertise required to navigate this new mode of interaction. the online teaching method has raised questions for the faculty about their capability to deal with the existing technology [ ]. the covid- pandemic has caused unprecedented health and humanitarian crisis. it has created an economic downturn due to the necessary measures to contain the spread of the virus. as per the latest global financial stability report, there is likely to be financial instability, which would lead to a devastating recession. the combined economic uncertainty and emotional distress placed on a family will challenge the overall well-being of families as well as their mental health [ ] . it is paramount to encourage and adopt healthy behavior to maintain the overall well-being of families. the well being of caregivers or parents can directly impact the mental health of the children. parents are advised to follow and practice the guideline provided by the world health organization (who). the who has urged people to follow social distancing guidelines and avoid close contact with anyone, especially from the person showcasing any respiratory symptoms [ ] . the health organization has also emphasized maintaining better hygiene by consistently washing hands and using appropriate protective gear such as facial masks [ ] . it has also advised to take breaks from watching, reading, or listening to news stories, including social media, because continually being bombarded by news of the pandemic can be distressing. exercising regularly, practicing yoga or meditation, eating healthy, taking adequate and proper sleeping properly, and avoiding alcohol or drugs is key to maintaining mental health. it is also crucial that parents provide enough support to their children and help them to process the information about the pandemic because these interventions could help minimize their anxiety or fear [ ] . schools, parents, and healthcare institutions can also implement psychological first aid (pfa) guidelines to assist children with their mental distress. pfa can provide psychosocial support to any survivors of epidemic or disaster [ ] . it is developed to mitigate acute distress and assess the need for more advanced psychiatric care. it is beneficial to implement it during the early stages of crisis to assist survivors in coping with grief and avoiding the long-term impact of stress on mental health. the 'rapid' model of the john hopkins pfa tool includes five steps, (i) r -rapport and reflective listening, implemented throughout the interaction; (ii) a -assessing and evaluating the psychological needs; (iii) p -prioritizing the needs based on severity; (iv) i -intervening to mitigate distressing factors; (v) d -disposition and distribution of intervention to stabilize the survivor [ ] [ ] . schools should emphasize the mental health of students by supporting and providing updated health organization guidelines through online lectures. also, a licensed counselor should help students manage the covid- related stress by providing coping mechanisms and strategies in both group and individual sessions. counseling services should be available to support the mental health and well being of students on time. universities can establish a task force to make a plan to reduce the spread of the virus and for the following centers for disease control and preventions (cdc) guidelines. the committee should include members from diverse professional backgrounds and experiences, such as public health department, physicians, psychiatrists, psychologists, social workers, administrators, health and human services, international services center, human resources, admission offices, enrolment, and billing department, athletic department, and teachers. to reduce the distress experienced by students and faculty related to information technology (it) issues, a technical team should be available continuously, and learning tutorial videos should be shared with the end-users. similarly, teachers and faculty should support students and their parents through clear communication and assigning clear expectations [ ] . a licensed counsel should take a comprehensive assessment of students deemed susceptible through risk factors such as psychological issues, including poor mental health before the crisis, bereavement, injury to self or family members, life-threatening circumstances, panic, separation from family, and low household income. minimizing the interruption of psychiatric care for patients with pre-existing conditions via telepsychiatry will be helpful to continue monitoring patients as the pandemic may worsen some patients' conditions and would adversely impact them if they were unable to contact their doctor. psychological assessment will help them to cope with their mental issues and stabilize their condition as they gain more education and discuss the impact of a pandemic. it will provide them support and reassurance to build resilience and encourage them to stay positive and motivated [ ] . mental health involves the regulation of our emotions, psychological, and social well-being. per the cdc, mental health affects how we think, feel, and act. it also helps determine how we react to stress, correlate with others, and our decision-making. mental health is significant throughout our lives, from early childhood to adolescence and through adulthood. mental illnesses occur when mental health is affected and leads to conditions that affect the way a person thinks, feels, or behaves, such as depression, anxiety, bipolar disorder, or schizophrenia. mental health can cause conditions that may be acute or chronic and alter the way we live our lives daily by our rationalizations. psychological and physical health are interdependent, both working together to form who we are. mental illness, especially depression, limits rational thinking, and increases the risk for other health problems such as diabetes. the presence of chronic conditions can increase the risk of mental illness. it is vital to strike a healthy balance between students' physical and psychological well-being [ ] . protecting and maintaining the mental health of the future adult generation is only possible with the robust schooling and healthcare system. it is necessary to have adequate resources to overcome this crisis. recruiting additional school personnel, clinicians, and mental health counselors are needed to address the strain on the system for supporting students during this pandemic [ ] [ ] . comprehensive school mental health systems (csmhss) is required to deliver adequate assistance for the students effectively [ ] . csmhss is a school-community association developed for all students to provide a variety of services for every type of students, such as mental health services, health promotion and prevention, early identification and interventions of diseases, and treatments for students evidence-based medicine [ ] . the csmhss should be enabled to collaborate with counselors, community mental health, and physical healthcare providers to help prevent mental health issues and make necessary referrals through an online interface for the treatment. the recruitment of additional school personnel and mental health counselors will help the students manage their anxiety, depression, and/or stress due to covid- ; and to stabilize any previously diagnosed mental illness or prevent new mental illness from developing [ , ] . moreover, children with inadequate information about why quarantine measures have been taken are found to have more anxiety. therefore, it is essential to expose children to more information about covid- through several sources, such as the evening news [ ] [ ] . this will make children more aware of the reason behind not only why quarantine measures were put in place, but they will also learn more about what covid- is. parents and guardians are encouraged to speak with their children about the information they learned, which may help lessen the negativity associated with covid- and quarantine. additionally, communicating with children about how they are processing the information will provide children with the emotional tools they require to do well in quarantine [ ] . not only can parents inform children about quarantine, but they can also employ "positive parenting" [ ] . children are prone to observe parents' and family members' moods during quarantine, which the children react to. through positive parenting, parents, guardians, and family members can create consistent daily routines to avoid the distress of unstructured days [ ] [ ] . while parents can provide a deeper understanding of the covid- and quarantine, school systems can provide further reassurances and educate children about emotions [ ] . school systems have the unique opportunity to provide consistent information to a large student body, who is unable to access other mental health programs in the areas [ ] . furthermore, school systems must adapt to the new online learning method and help students adjust and thrive in online classes [ ] [ ] . additionally, children can be taught coping mechanisms to self-regulate their own emotions without dependence on others. one method that achieves this goal is behavioral activation, which focuses on participating in activities they enjoy and not employing avoidance behaviors [ ] [ ] . alongside the other interventions mentioned above, behavioral activation can help children improve their problem-solving skills by engaging in healthy behaviors rather than unhealthy ones [ ] . due to the isolation indirectly imposed by the pandemic, children would be expected to prosper better in these times when they are taught ways to help themselves [ , ] . the epidemiology and clinical information about covid- covid- strategy update children's mental health child and adolescent mental health adolescent mental health empowering students with disabilities during the covid- crisis covid- is hurting children's mental health coping with stress as coronavirus prompts colleges to close, students grapple with uncertainty long-term psychiatric morbidities among sars survivors a revisit on older adults suicides and severe acute respiratory syndrome (sars) epidemic in hong kong coronavirus: universities are shifting classes online -but it's not as easy as it sounds covid- crisis poses threat to financial stability focus on mental health during the coronavirus (covid- ) pandemic: applying learnings from the past outbreaks sustainability of psychological first aid training for the disaster response workforce the johns hopkins model of psychological first aid (rapidpfa): curriculum development and content validation the role of psychological first aid to support public mental health in the covid- pandemic guidance to states and school systems on addressing mental health and substance use issues in schools how essential is to focus on physician's health and burnout in coronavirus (covid- ) pandemic? lifetime prevalence of mental disorders in u.s. adolescents: results from the national comorbidity survey replication-adolescent supplement (ncs-a) lifetime prevalence and age-of-onset distributions of mental disorders in the world health organization's world mental health survey initiative. world psychiatry psychological burden of quarantine in children and adolescents: a rapid systematic review and proposed solutions mental health effects of school closures during covid- psychological interventions during covid- : challenges for low and middle income countries mental health interventions in schools in low-income and middle-income countries school closure and management practices during coronavirus outbreaks including covid- : a rapid systematic review key: cord- - ecik xw authors: lagziel, tomer; quiroga, luis; ramos, margarita; hultman, charles s; asif, mohammed title: two false negative test results in a symptomatic patient with a confirmed case of severe acute respiratory syndrome coronavirus- (sars-cov- ) and suspected stevens-johnson syndrome/toxic epidermal necrolysis (sjs/ten) date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ecik xw the recent outbreak of covid- has put significant strain on the current health system and has exposed dangers previously overlooked. the pathogen known as severe acute respiratory syndrome coronavirus (sars-cov- ), is notable for attacking the pulmonary system causing acute respiratory distress, but it can also severely affect other systems in at-risk individuals including cardiovascular compromise, gastrointestinal distress, acute kidney injury, coagulopathies, cutaneous manifestations, and ultimately death from multi-organ failure. unfortunately, the reliability of negative test results is questionable and the high infectious burden of the virus calls for extended safety precautions, especially in symptomatic patients. we present a confirmed covid- case that was transferred to our burn center for concern of steven johnson syndrome/toxic epidermal necrolysis (sjs/ten) overlap syndrome after having two negative confirmatory covid- tests at an outside hospital. a -year-old female with a history of morbid obesity, htn, gout, cml managed with imatinib, and chronic kidney disease presented as a transfer from a community hospital to our burn center. the patient was admitted to her community hospital with febrile, acute respiratory distress. imaging and clinical presentation was consistent with covid- and lab tests for the pathogen were ordered. during observation, while waiting for results, she was placed under patient under investigation (pui) protocol. once negative results were obtained, the pui protocol was abandoned despite ongoing symptoms. subsequently, dermatological symptoms developed and transfer to our burn center was initiated. after a second negative test result, the symptomatic patient was transferred to our burn center for expert wound management. given the lack of resolve of respiratory symptoms and concern for the burn patient population, the patient was placed in pui protocol and an internal covid- was ordered. the patient’s initial exam under standard covid- airborne precautions revealed % total body surface area of loss of epidermis affecting bilateral thighs, bilateral arms, and face. a dermatopathological biopsy suggested a bullous drug reaction with an erythema multiform-like reaction pattern versus sjs/ten. moreover, the internal covid- test returned positive. the delayed positive test results and complicated hospital course with our patient required us to scale back and notify every patient and staff member whom they came in contact with, across multiple institutions. we suggest that whenever a suspected covid- patient is transferred to a specialized center, they should be isolated and re-checked before joining the new patient population for treatment of the unique condition. a -year-old female with a history of morbid obesity, htn, gout, cml managed with imatinib, and chronic kidney disease presented as a transfer from a community hospital to our burn center. the patient was admitted to her community hospital with febrile, acute respiratory distress. imaging and clinical presentation was consistent with covid- and lab tests for the pathogen were ordered. during observation, while waiting for results, she was placed under patient under investigation (pui) protocol. once negative results were obtained, the pui protocol was abandoned despite ongoing symptoms. subsequently, dermatological symptoms developed and transfer to our burn center was initiated. after a second negative test result, the symptomatic patient was transferred to our burn center for expert wound management. given the lack of resolve of respiratory symptoms and concern for the burn patient population, the patient was placed in pui protocol and an internal covid- was ordered. the patient's initial exam under standard covid- airborne precautions revealed % total body surface area of loss of epidermis affecting bilateral thighs, bilateral arms, and face. a dermatopathological biopsy suggested a bullous drug reaction with an erythema multiform-like reaction pattern versus sjs/ten. moreover, the internal covid- test returned positive. the delayed positive test results and complicated hospital course with our patient required us to scale back and notify every patient and staff member whom they came in contact with, across multiple institutions. we suggest that whenever a suspected covid- patient is the world is in the midst of a pandemic led by the recent outbreak of a novel coronavirus. the new pathogen is known as the severe acute respiratory syndrome coronavirus (sars-cov- ) and by its official world health organization (who) disease name, covid- [ ] . although, this virus is notable for attacking the pulmonary system, causing acute respiratory distress syndrome (ards), it can also severely affect other systems in at-risk individuals including cardiovascular compromise, gastrointestinal distress, acute kidney injury, coagulopathies, cutaneous manifestations and ultimately death from multi-organ failure [ ] [ ] . at present, april , the united states has surpassed every country in the number of active cases, with over , cases and approximately , confirmed deaths since it was announced as a pandemic in late january [ ] . currently, the gold-standard for quick confirmation of covid- is a real-time reverse-transcriptase polymerase chain reaction (rrt-pcr) [ ] . unfortunately, this test is not % accurate and early reports from china suggest a false-negative result rate of up to % [ ] [ ] [ ] . the high infectious burden of covid- brings into question the reliability of negative test results when managing high-risk patient populations. we present a covid- case that was transferred to our burn center for concern of steven johnson syndrome/toxic epidermal necrolysis (sjs/ten) overlap syndrome after having two negative confirmatory covid- tests at an outside hospital. a -year-old female with a history of morbid obesity, hypertension (htn), gout, chronic myeloid leukemia (cml) managed with imatinib for four years, and chronic kidney disease (ckd), presented as a transfer from a community hospital with suspected sjs/ten overlap syndrome. the patient was prescribed levofloxacin and oseltamivir by her primary care physician for complaints of one week of coughing, fevers, and fatigue, despite having negative influenza testing. after one week, she presented to her local emergency room with worsening respiratory symptoms, a fever of . o f, and % o saturation on room air. a chest radiograph (cxr) and chest computed tomography (ct) scan demonstrated multifocal pneumonia. the patient was immediately placed under patient under investigation (pui) protocol, broad-spectrum antibiotics including vancomycin, and piperacillin and tazobactam were started after obtaining blood cultures and a covid- test. the hospital course was complicated by acute kidney injury (aki) with creatinine levels of . mg/dl that peaked . mg/dl prior to dialysis intervention. six days later, the covid- test results were negative and the pui protocol was abandoned despite ongoing respiratory distress. her pulmonary symptoms continued to be managed with antibiotic and supportive therapy. the following day, during routine physical examination in the general ward, the patient was noted to have a disseminated erythematous and papular skin rash. prophylactic hydrocortisone therapy was initiated for a suspected allergic reaction, especially concerning given her pulmonary symptoms, and antibiotics were held due to possible drug reaction. during the next hours, the rash developed into vesicles and bullae with desquamation, forming widespread, large, open wounds. sjs/ten was suspected and her treatment team requested to transfer her to our tertiary care burn center for expert wound care and management. given her persistent respiratory distress, a second covid- test was rushed and administered prior to transfer which also returned negative and the patient transfer was processed after hours. the patient arrived at our hospital in severe respiratory distress concomitant with blistering dermatological lesions. given that treating the patient in the burn unit requires exposure to an immunocompromised patient population, a decision was made to place the patient in the surgical intensive care unit (sicu) for pui protocol in a negative pressure room. the patient's initial exam under standard covid- airborne precautions revealed % total body surface area of epidermal loss affecting bilateral thighs, bilateral arms, and face ( figure ). the combined risk of the uncertain validity of external covid- tests, the severe symptomatic nature of the patient, and the vulnerable burn unit patient population prompted the decision to order a third, internal, covid- test, and to obtain an additional cxr (figure ). a dermatopathological biopsy suggested a bullous drug reaction with an erythema multiformlike reaction pattern versus sjs/ten. the biopsied sections demonstrated detached epidermis with a "basket-weave" stratum corneum that is separated at the dermal-epidermal junction. there were spongiosis and subtle basilar vacuolar changes with rare dyskeratotic cells. the dermis demonstrated superficial edema and a mildly dense, superficial, perivascular, and interstitial infiltrate composed of lymphocytes and histiocytes with occasional eosinophils and melanophages. the final dermatological clinical picture with no oral mucosal involvement was most consistent with resolving bullous interface dermatitis, not sjs/ten. the skin lesions were treated with local wound care using silver antimicrobial foam dressing, changed twice a week with the patient placed on a taper of oral prednisone. the covid- test results, however, returned positive after hours. subsequently, the patient's hemodynamic status improved and she was transferred to a designated regular covid- unit floor and days later discharged to a skilled nursing facility for further wound care and management. the patient was able to finish the prednisone treatment as an outpatient successfully and recover from covid- . the novel coronavirus is still in the early stages of medical investigation and as pulmonary management advances, we begin to examine the multi-system manifestations of this deadly contagion. the previous global spreads of severe acute respiratory syndrome (sars) and the middle east respiratory syndrome (mers) have demonstrated the respiratory and epidemiologic manifestations of covid- , but also has demonstrated that this new viral disease has unique characteristics [ ] . little peer-reviewed literature is available on the dermatologic symptoms of sars-cov- . however, a review of covid- positive patients in lombardo, italy, reported patients with cutaneous manifestations, none of whom were suspected for sjs/tens [ ] . the broad range of dermatologic symptoms suggests an unclear pathologic mechanism. a hematologic review of immunosuppressive medications was performed in italy to examine their therapeutic role in the setting of covid- and their findings suggest a possible advantage of imatinib, for cml, in fighting covid- [ ] . skin adverse effects are common in imatinib users (especially women), but generally appear within one month of beginning therapy [ ] [ ] . given these findings, the relationship between skin findings in our patient and imatinib is unclear but the drug's presence could have even played a role in the patient's resolution. it has been recently reported that genetic predisposition, given specific polymorphisms, could play a significant role in autoimmune/inflammatory manifestations of covid- [ ] . while no petechiae or purpuric manifestations were noted in our patient, recent correspondence from the new england journal of medicine reported a patient with immune thrombocytopenic purpura (itp) as a result of covid- [ ] . the mechanism for this manifestation is unclear but we suggest the cutaneous symptoms in our patients could have resulted from paradoxical cutaneous micro-emboli and hypercoagulation. treatment of skin drug reactions has the additional challenge of the unknown effects of systemic steroids, which has been a mainstay of treatment for these conditions in covid- positive patients [ ] . in the case presented, the patient received oral steroids which were tapered over a week and had concurrent resolution of covid- disease. covid- has rapidly become a significant burden on the global health system due to its unknown characteristics and disease severity in at-risk individuals. because of the extreme dangers associated with this virus along with many unknown variables, we advise that every suspected hospitalized case should be treated as a potential covid- case, and that the interpretation of any test should follow, as always, the clinical judgment. our report exemplifies this, because most of the patients in the burn unit are in an immunocompromised state whether due to medications or the severe burn wounds. in addition, the burn unit lacks negative pressure rooms suited for covid- patients. if the patient had not been transferred to the sicu, but directly to the burn center, they would have placed the entire floor and staff at risk of infection. due to the extreme infective burden of covid- , protecting healthcare staff and at-risk patients should be a priority. the delayed positive test results and complicated hospital course with our patient required us to scale back and notify every patient and staff member that they came in contact with across multiple institutions. we suggest that whenever a suspected covid- patient is transferred to a specialized center, they should be isolated and re-checked before joining the new patient population for treatment of the unique condition. in addition, as long as symptoms remain, the suspected patient should be maintained in a pui protocol because the high false-negative rate of rrt-pcr testing can put patients and staff at risk. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all naming the coronavirus disease (covid- ) and the virus that causes it covid- : what has been learned and to be learned about the novel coronavirus disease covid- , sars and mers: are they closely related? world health organization diagnosis of the coronavirus disease (covid- ): rrt-pcr or ct? real-time rt-pcr in covid- detection: issues affecting the results false-negative results of real-time reverse-transcriptase polymerase chain reaction for severe acute respiratory syndrome coronavirus : role of deeplearning-based ct diagnosis and insights from two cases covid- : a meta-analysis of diagnostic test accuracy of commercial assays registered in brazil the epidemiology and pathogenesis of coronavirus disease (covid- ) outbreak cutaneous manifestations in covid- : a first perspective the cov- outbreak: how hematologists could help to fight covid- european leukemianet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia serious skin reaction associated with imatinib in a patient with chronic myeloid leukemia could sarscoronavirus- trigger autoimmune and/or autoinflammatory mechanisms in genetically predisposed subjects? immune thrombocytopenic purpura in a patient with covid- challenges of covid- pandemic for dermatology authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -v t oos authors: wilenius, lukas; partinen, markku title: attention-deficit/hyperactivity disorder patients may have undiagnosed narcolepsy date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: v t oos background attention-deficit/hyperactivity disorder (adhd) patients have many comorbidities. narcoleptic patients have a big prevalence of adhd ( %- %). both groups suffer from similar symptoms and benefit from the same class of medications. as such, narcolepsy could be masked in adhd patients. low serum ferritin has been found both in adhd patients as well as in patients with narcolepsy. materials & methods we enrolled participants ( adhd patients and controls). they answered several questionnaires, and blood samples were obtained from participants. we had clear exclusion criteria. results using the ullanlinna narcolepsy scale (uns), we identified three possible narcolepsy patients within the adhd group and no suspects in the control group. there was a statistically significant negative correlation between serum iron levels and adhd symptom severity. no correlation was found measuring serum ferritin levels. conclusions narcolepsy may be more common within adhd patients than in the general population. some of these patients could benefit from a change in medication. low serum iron and ferritin levels could be relevant in adhd pathophysiology. this requires further exploratory research. adhd is a psychiatric disorder characterized by inattention, hyperactivity, and impulsiveness, with an estimated worldwide prevalence of . %, according to a meta-analysis [ ] . the diagnostic criteria divide the patients into either inattentive, hyperactive-impulsive, or a combined presentation. interestingly, adhd in children and adolescents is much more common in the young male population (the ratio is : ) [ ] . adhd persists into adulthood in about % of all cases and is therefore a very common disease even among adults [ ] . the pathophysiology of adhd is not yet fully understood, but it has been proposed that problems could occur because of hypoactive monoaminergic neurons, which project to the prefrontal cortex. this hypothesis has been founded on the phenomenon where the prefrontal cortical functions of adhd patients are briefly hypoactive [ ] . astrocytes, energy deficiency, and the hypothesized lactate shuttle may be involved too. glucose is taken up from the blood by astrocytes. as this undergoes glycolysis, pyruvate and adenosine triphosphate (atp) are produced. further, pyruvate can either be converted to glycogen for storage or be metabolized to lactate. the lactate shuttle is now able to transfer lactate from astrocytes to neurons, where it is used as energy. catecholamines (dopamine and noradrenaline) bind to their respective receptors on astrocytes inducing glycogenolysis [ ] . this results in elevated glucose concentrations and lactate production. therefore, reduced catecholamine levels could cause lower lactate concentrations and less energy in the neurons. this lack of energy could be the reason behind the reduced prefrontal cortical function [ ] . adhd patients are at greater risk for several psychiatric disorders such as depression, bipolar disorder, and anxiety disorders [ ] . overlapping and distinctive features between these disorders are, however, notable [ ] . according to katzman et al., substance use disorder and personality disorders are more common among adhd patients than in the general population. up to % of all adhd children suffer from restless legs syndrome (rls), and % of rls patients are reported suffering from adhd or at least severe adhd symptoms [ ] . iron deficiency in children with adhd and lower ferritin levels have been associated with the severity of rls symptoms [ ] [ ] . in a meta-analysis, it was found that peripheral serum ferritin levels were lower for children with adhd than for controls but serum iron and transferrin levels did not differ [ ] . percinel et al. found no difference in iron parameters between adhd patients and controls in children [ ] . hyperactivity scores, on the other hand, negatively correlated with serum ferritin levels. the prevalence of adhd in women with iron deficiency anemia could be higher than in the general population [ ] . stimulants (methylphenidate and amphetamines) are first-line pharmacological agents and the most commonly used in adhd. methylphenidate appears to be the most efficient treatment [ ] . atomoxetine is also commonly used and is superior to a placebo [ ] . another promising non-stimulant is modafinil. according to a double-blind study, it appears to improve adhd significantly as compared to placebo [ ] . modafinil is the most commonly used medication in narcolepsy, and it is also used as an off-label medication in adhd. narcolepsy is a chronic neurological condition. it is characterized by two main symptoms, excessive daytime sleepiness (eds) and cataplexy. the reported global mean prevalence is approximately per , [ ] . other symptoms are, for example, sleep paralysis and hypnagogic hallucinations. narcolepsy was first divided into two subtypes: narcolepsy type (with cataplexy) and narcolepsy type (without cataplexy) by the international classification of sleep disorders (icsd). this subdivision has now been replaced by the icsd- , according to which type narcolepsy (nt ) is with hypocretin (also called orexin) deficiency and type narcolepsy (nt ) is without hypocretin deficiency, e.g. the absence of cataplexy. the hla-dqb * : allele has been associated with narcolepsy. according to a population-stratified analysis, hla-dqb * : increased the risk for both nt and nt , but the odds ratio was significantly higher for nt than nt ( . vs. . ) [ ] . methylphenidate has been used in the treatment of narcolepsy but, nowadays, modafinil is more commonly used [ ] . modafinil is used particularly for treating eds, atomoxetine and venlafaxine are first-line medications for cataplexy, but pitolisant could be both safe and efficient [ ] [ ] . three out of adhd children showed narcolepsy-like symptoms during their sleep [ ] . although researchers at this time do not know if the children suffered from narcolepsy, this high percentage ( %) serves as an indicator for possible comorbidity. causality is unclear because sleep disorders can induce adhd-like symptoms, which could be due to excessive daytime sleepiness [ ] . narcoleptic patients are more prone to adhd than the general population. as much as % of all patients suffering from narcolepsy without cataplexy and % of narcoleptics with cataplexy had symptoms of adhd [ ] . in a swedish study, % of all narcolepsy patients had adhd [ ] . the same study revealed no correlation between hypocretin levels and adhd symptoms. narcoleptics have a higher prevalence of major depression than the general population [ ] . also, temper tantrums are very common in narcolepsy [ ] . adhd patients often suffer from daytime sleepiness; in addition, some of them are also using medications as in narcolepsy (e.g., methylphenidate), and it is possible that at least mild forms of narcolepsy remain masked. our aim was to clarify the prevalence of narcolepsy symptoms among adult adhd patients as compared to controls of the same age and gender. this included defining the appearance of daytime sleepiness and cataplectic symptoms. we also wanted to evaluate the association of low serum ferritin and iron levels to adhd and symptoms of narcolepsy. fourteen adult adhd patients ( women and men; age range - years) and agematched (± years) healthy controls ( women and men) were included. the information was gathered during the timeframe of march to october . exclusion criteria for controls included a prior diagnosis of adhd or narcolepsy. the adhd patients had either been previously diagnosed by an experienced psychiatrist or were recruited from the finnish union for adhd patients. the dsm- diagnostic criteria of the american psychiatric association for adhd were used [ ] . the controls were workers from different healthcare organizations and other healthy volunteers. we excluded all patients and controls who had been diagnosed with a psychotic disease or had been prescribed an antipsychotic drug. neither did we include patients who had received treatment in the form of tricyclic antidepressants, selective serotonin reuptake inhibitors (ssris), clonidine, or atomoxetine since these could have reduced cataplectic symptoms. we also excluded patients and controls that scored > on the alcohol use disorder identification test (audit), as well as subjects that had misused intoxicating substances such as methylphenidate or modafinil. patients and healthy controls matched in terms of years of education (± five years). all patients had a caucasian origin. all participants had been informed on what they were to undergo, and written informed consent was obtained in all cases. we used a structured questionnaire based on the basic nordic sleep questionnaire (bnsq) to chart the participants for narcoleptic symptoms, other sleep disorders, adhd severity, and general well-being. for the mapping of the narcoleptic symptoms, the ullanlinna narcolepsy scale (uns) was also used [ ] . the questionnaire also included the epworth sleepiness scale (ess), world health organisation-five well-being index (who- ), and questions on the sleepwake rhythm and other sleep disorders. the questionnaire can be obtained by request from the authors free of charge. all participants responded to self-administered questionnaires. we mapped adhd symptoms using the wender utah rating scale (wurs) and the adult adhd self-report scale (asrs) version . . adhd patients and controls answered all questionnaires. the clinical assessments included taking of the medical history and computing the body mass index (bmi; kg/m ) was computed from weight and height. serum samples were analyzed in an accredited laboratory of the university of helsinki. statistical computations were done using stata . (statacorp, texas). the normality of the distributions was tested by the shapiro-wilk test. parametric or non-parametric tests were used according to the distribution. means and % confidence intervals (ci) were computed. for normally distributed variables student's t-test and linear regression were used. fisher's exact test was used in cross-tabulations. we used two-sided p-values with a limit of significance of p < . . the ethical approval was given by the helsinki and uusimaa district ethical committee. the age among the participants was normally distributed (shapiro-wilk normality test, p-value = . ). the gender ( women and men among patients vs. women and men among controls) of the participants did not statistically differ (fisher's exact = . ) and the age did not differ among groups (means: . vs. . , p = . ) ( table ) . with uns, we managed to compare both groups for eds and cataplexy. in the clinic, a cut-off point of ≥ is used for screening for narcolepsy. using this, three out of patients, whereas no controls were screened positive for narcolepsy. however, this was not statistically significant (fisher's exact = . ). a two-sample t-test revealed no difference between the groups (means: vs. . , p = . ). when only counting the points for cataplexy in uns, we used a cut-off point of ≥ for addressing cataplexy. this point was chosen due to it being the best point for separating between if the symptoms are felt on a weekly-monthly basis or not. using this, five out of adhd patients screened positive for cataplectic symptoms, whereas no controls did. this difference was statistically significant (fisher's exact p = . ). for eds, five out of screened positive and one out of controls also did. this was not statistically significant (fisher's exact = . ). using ess, a two-sample t-test revealed no difference between the groups (means: . vs. . , p = . ). the prevalence of wurs scores greater than (likely adhd) was nine out of nine in the adhd group and three out of in the control group. the lowest wurs score in the adhd group was higher than the highest score from the controls, indicating a strong difference between groups. using the asrs questionnaire as a diagnostic tool, where on getting a score of ≥ in part a, none of the controls had adulthood adhd, whereas seven out of of the adhd group qualified. a two-sample t-test, comparing who- scores among groups, revealed a statistically significant difference in favor of controls (means: . vs. . , p = . ). comparing patients with uns ≥ with the others for who- scores revealed no difference between groups (means: vs. . , p = . ). we used the whole asrs questionnaire to get a score for the severity. this was done by adding up all questions. the serum iron and asrs score negatively correlated (cor = - . , calculated with spearman's rank correlation coefficient formula), and a linear regression revealed the statistical significance of this negative correlation (p-value = . ). this correlation is illustrated in figure . the serum iron score was not normally distributed (pvalue = . in a shapiro-wilk normality test), and, therefore, we used spearman's test for calculating correlations. serum iron levels were higher for controls than for adhd patients (means: . vs . , p = . ) but regarding serum ferritin levels, we identified no difference (means: . vs , p = . ). blood hemoglobin levels did not differ (means: . vs . , p-value = . ) among groups. asrs: adult attention-deficit/hyperactivity disorder (adhd) self-report scale as far as we know, no studies comparing adult adhd patients with healthy controls, regarding narcoleptic symptoms, has been made before. uns revealed three possible narcolepsy patients in the adhd group. and this is, although not statistically relevant, at least clinically relevant. the pharmacological treatment of eds experienced in narcolepsy resembles the pharmacological treatment in adhd, but there are differences. one could hypothesize whether these three patients are receiving the wrong treatment. could the patients possibly be doing better if receiving modafinil instead of methylphenidate, as is the case now? in our study, only two of the possible narcoleptics answered the who- , making a statistical analysis comparing these persons to others unreliable. we strongly believe that a bigger cohort could reveal a statistical difference between the groups. if the prevalence of narcolepsy would be as big as in this study (≈ %), it would mean that the global prevalence of narcoleptic symptoms would be higher than what is assumed at the present. a study revealed a mean uns score of . within nt patients and . in nt [ ] . the uns scores for the nt patients were higher in that study than for any patients in the present study. we cannot make final inferences regarding this issue. it is also possible that our three patients with uns ≥ could have narcolepsy type . adhd patients have more cataplectic symptoms than controls. what we do not know is if the patients affected experience these symptoms as handicapping. one could also speculate whether these patients could benefit from a cataplexy-reducing agent. considering atomoxetine, which is a second-line agent for adhd but first-line treatment for cataplexy, the question is: whether these patients would benefit from an atomoxetine medication, possibly allowing them to stop their stimulant medication. we did not find any differences between the groups regarding excessive daytime sleepiness either from the questions regarding eds in uns nor from ess. it has to be kept in mind that all adhd patients use stimulants on a daily basis, which reduces eds symptoms. it would be very interesting to see a study comparing adult adhd patients not receiving stimulants with healthy controls regarding this subject. we found a statistically significant negative correlation between serum iron levels and adhd symptom severity, as well as a statistically significant difference between the groups regarding serum iron levels. serum ferritin levels have been believed to estimate the bodies' iron reservoir in a better manner than serum iron, but we found no statistical correlation between serum ferritin levels and adhd symptom severity. with a bigger sample, we would get more clear estimates on the possible correlations and, therefore, the relevance of these markers. unfortunately, our study has several weaknesses. the sample size is small. finding participants was even more difficult than we expected. we are aiming to find more subjects, which is, however, even more difficult during the present time . due to the present situation, obtaining blood samples and actigraphic measures from all participants was not timely. the samples taken were obtained in - . this led to the fact that a part of the participants didn't have results on some variables. we didn't measure hypocretin levels in the cerebrospinal fluid (csf), which is a more specific diagnostic tool for narcolepsy type than uns. with hypocretin levels, we could estimate the prevalence more precisely. however, nt patients have normal csf-hypocretin levels. therefore we cannot exclude the possibility that some of our patients may have had low csf-hypocretin levels. our study shows that narcolepsy may be more common in subjects with adhd than in subjects without adhd. if this is the case, one could hypothesize that these patients could benefit from a change in medication. serum ferritin levels are widely used clinically for various purposes. serum-free iron levels, however, are not as commonly measured or used. serum iron levels correlated negatively with the asrs score. more studies are needed in this regard. at the present time, we do not know whether adhd patients or a sub-group of adhd patients could benefit from iron supplementation. we also need randomized controlled studies on the use of iron supplementation in patients with narcolepsy. disclosures prevalence of attentiondeficit/hyperactivity disorder: a systematic review and meta-analysis attention deficit disorder: a review of the past years attention deficit hyperactivity disorder in adults: a guide for the primary care physician is attention-deficit/hyperactivity disorder an energy deficiency syndrome characterization of the glycogenolysis elicited by vasoactive intestinal peptide, noradrenaline and adenosine in primary cultures of mouse cerebral cortical astrocytes adult adhd and comorbid disorders: clinical implications of a dimensional approach restless legs syndrome and attention-deficit/hyperactivity disorder: a review of the literature iron deficiency in children with attentiondeficit/hyperactivity disorder iron and the restless legs syndrome peripheral iron levels in children with attention-deficit hyperactivity disorder: a systematic review and meta-analysis iron deficiency parameters in children and adolescents with attention-deficit/hyperactivity disorder. child psychiatry hum dev the investigation of symptoms and diagnoses of adult-attention deficit/hyperactivity disorder in women with iron deficiency anemia. noro psikiyatr ars pharmacotherapy of adult attention deficit hyperactivity disorder (adhd): a meta-analysis attention-deficit hyperactivity disorder narcolepsy as an autoimmune disease: the role of h n infection and vaccination correlation between hla-dqb * : and narcolepsy with and without cataplexy: approving a safe and sensitive genetic test in four major ethnic groups. a systematic meta-analysis pharmacological management of narcolepsy with and without cataplexy safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial sleep-related disorders in children with attention-deficit hyperactivity disorder: preliminary results of a full sleep assessment study excessive daytime sleepiness in patients with adhd-diagnostic and management strategies attention-deficit/hyperactivity disorder (adhd) symptoms in pediatric narcolepsy: a cross-sectional study psychiatric comorbidity and cognitive profile in children with narcolepsy with or without association to the h n influenza vaccination american psychiatric association: diagnostic and statistical manual of mental disorders, fifth edition (dsm- ) ullanlinna narcolepsy scale in diagnosis of narcolepsy we would like to thank anne huutoniemi for helping with several logistical and practical arrangements, as well as her expertise in sleep medicine. we would like to thank sami leppämäki and the finnish adhd-union for enrolling patients as participants. we also thank stiftelsen dorothea olivia, karl walter och jarl walter perkléns minne, and finska läkaresällskapet for funding the study. key: cord- -o nscint authors: roy, sayak; khalse, maneesha title: epidemiological determinants of covid- -related patient outcomes in different countries and plan of action: a retrospective analysis date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: o nscint current development around the pandemic of novel coronavirus disease (covid- ) presents a significant healthcare resource burden threatening to overwhelm the available nationwide healthcare infrastructure. it is essential to consider, especially for resource-limited nations, strategizing the coordinated response to handle this crisis effectively and preparing for the upcoming emergence of calamity caused by this yet-to-know disease entity. relevant epidemiological data were retrieved from currently available online reports related to covid- patients. the correlation coefficient was calculated by plotting dependant variables - the number of covid- cases and the number of deaths due to covid on the y-axis and independent variables - critical-care beds per capita, the median age of the population of the country, the number of covid- tests per million population, population density (persons per square km), urban population percentage, and gross domestic product (gdp) expense on health care - on the x-axis. after analyzing the data, both the fatality rate and the total number of covid- cases were found to have an inverse association with the population density with the variable - the number of cases of covid- - achieving a statistical significance (p-value . ). the negative correlation between critical care beds and the fatality rate is well-justified, as intensive care unit (icu) beds and ventilators are the critical elements in the management of complicated cases. there was also a significant positive correlation between gdp expenses on healthcare by a country and the number of covid- cases being registered (p-value . ), although that did not affect mortality (p-value . ). this analysis discusses the overview of various epidemiological determinants possibly contributing to the variation in patient outcomes across regions and helps improve our understanding to develop a plan of action and effective control measures in the future. a significant epidemic focus of new coronavirus disease was identified in december in wuhan, china, which rapidly progressed across countries in europe, north america, asia, and the middle east, affecting more than half a million people [ ] . later, this disease outbreak, caused by a novel coronavirus sars-cov- with an unknown origin, was declared as a significant pandemic by the world health organisation (who) on march , . europe has become the new major epicenter with the total number of cases and deaths being reported as , and , , respectively [ ] . this is the third coronavirus outbreak with a novel strain in the last two decades and presents an ensuing healthcare resource burden that threatens to overwhelm available healthcare resources [ ] . as a result, the challenges presented seem to be unique in the disease prospect, considering disparate resource settings across countries, especially when applying strategies from high-technology intensive care settings to less developed areas. the global burden of covid- , which is an infectious agent with high transmissibility and a moderate fatality rate, is likely to fall hardest on the vulnerable groups in low middle-income countries (lmics). therefore, a systematic strengthening in its ability from the technical and financial fronts is warranted to respond to this challenging situation successfully. public health measures, such as surveillance, exhaustive contact tracing, social distancing, travel restrictions, public education on hand hygiene, ensuring flu vaccinations for the frail and immunocompromised, and temporarily suspending non-essential surgical procedures and services will play their part in delaying the spread of infection and dispersing pressure on hospitals [ ]. sars-cov- is likely to play havoc on the world economy, heading to an apprehended shrinkage of the global economy in by % [ ] . in this brief analysis, we tried to overview various socioeconomic determinants possibly contributing to variation in covid- -related outcomes across regions and then make a plan of action based on the evidence. given the unpredictable course of this global crisis, infection and mortality rates vary widely from one country to another. apart from the baseline demographic features of patients, socioeconomic factors, such as income groups, population density, access to health care, and quality of health system resources, may account for the observed variations in mortality rates. different testing strategies, reporting systems, and data availability play an essential part in these highly variable statistics, even with the number of unreported cases believed to be quite considerable in some countries. the total number of cases worldwide is , , and the disease has caused , ( . %) deaths from december , , to march , [ ] . however, the highest mortality was found in italy, spain, united kingdom, france, and iran. the overall case fatality rate of march in italy ( . %) is substantially higher than in china ( . %). now, the fatality rate of italy has increased to . % as of april (number of cases recorded , and number of deaths , ), which is closely followed by the united kingdom with a fatality rate of . % (number of covid- cases being , and number of deaths being , ) [ ] [ ] . this feature demonstrates the daily change in the fatality rate in a pandemic. moreover, the infections occurred predominantly ( %) in people to years old. the most likely populations requiring mechanical ventilation are the elderly and people with pre-existing comorbidities (in particular, cardiovascular disease and hypertension, followed by diabetes mellitus) with a predicted mortality of around % to % [ ] . despite the known impact of per capita expenditure on health care and reduced mortality in previous influenza pandemics ( ), the findings in the recent outbreak entail no significant correlation between health care spending and the covid- -related mortality observed in the population [ ] . in particular, the mortality rates are highly variable in different high-income countries, as noticed in europe and the usa based on their health spending. as per the world bank statistics, the us spent . % of its gross domestic product (gdp) on health care while other countries, including india, are lagging behind primarily due to the income category of these countries [ ] . surprisingly, this did not affect the total number of cases infected with covid- [ ] . this consistent observation was reported in a descriptive analysis study (in preprint). in that study, there was no significant correlation between the gdp growth of the country and the number of treating physicians/ patient population with any covid- -related outcome but a negative correlation between covid- -related deaths and the number of beds available per population. additionally, there was an inverse correlation between the number of tests conducted per million population with the rates of active infections, new cases, and new deaths due to covid- [ ] . herein, we try to analyze the impact of various socioeconomic and demographic features of a few selected countries, namely, united states of america (usa), germany, italy, france, south korea, spain, japan, united kingdom (uk), china, and india, concerning covid- -related cases and fatality rates. we retrieved data between january and april , , related to population and population density, the median age of the population of a country, urban population, number of covid- testing employed per million population, gdp expense of each country on health, critical care beds available per capita, from various sources as mentioned in the reference section, stated next to each of these variables in table , along with the total number of covid- cases and the case fatality rate (as per who situation report, [ ] ). we then applied pearson's correlation coefficient to see the correlation of various demographic features and covid- cases and deaths due to covid- using the online calculator available, https://www.socscistatistics.com/tests/pearson/default .aspx [ ] . the correlations between population characteristics and socioeconomic variables in various countries as discussed earlier with respect to outcome in terms of total positive cases and fatality rate due to covid- are summarized in table . r-value p-value there is a strong positive correlation between gdp expense on the health of a country with the number of cases getting detected. the reason for this is the affordability of easily testing a higher number of patients in high-income countries; however, this expense, on the other hand, did not show any significance with deaths due to covid- (p-value . ). the result showed that both the case fatality rate and the number of covid- cases are negatively correlated to population density, which seems quite strange. however, on further analysis, by taking the usa and the european countries only on the x-axis and case fatality from these countries on the y-axis, the same pearson's correlation coefficient r-value becomes . (p-value . ), which is now positively related and not statistically significant after adjustment. the same calculation using the population density of these countries on the x-axis and the number of cases on the y-axis gives us a pearson's r-value of . (p-value . ), which again changes from a negative correlation to a positive correlation after adjustment. the negative correlation between critical care beds and the fatality rate is justified, as intensive care unit (icu) beds and ventilators are critical elements in the management of complicated cases. this importance of ventilators had previously been recognized in the study, which states that the provision of mechanical ventilators to developing countries has the unique potential to help make a dramatic improvement in the care of the world's most vulnerable patients [ ] . mass testing in all suspected cases in germany and south korea, as laid down by who, could also be one of the reasons why they manage to reduce the number of new infections since it allows them to quickly identify possible outbreaks as early as possible for covid- , and we can also observe the pandemic curve for death rate to have bent quite effectively from the early days of the pandemic [ ] [ ] . this approach proved to be a successful strategy to achieve a low fatality rate in both countries, as they used to test-admit/isolate-treat protocol. the national health service (nhs) of the uk used the contain-delay-mitigate-research strategy at the beginning and that turned out to be futile, with a possible association with a high case fatality rate [ ] . the number of tests done per day differed significantly among various countries from the beginning, as shown in figure , and the day-by-day basis of covid- tests per , people in table , which clearly shows aggressive testing done to pick up cases early in south korea while italy, france, and the uk lagged way behind and, now, these three countries have a huge case fatality burden. adapted from: our world in data [ ] the covid- epidemic has placed a significant burden on the health care system. this crisis has dramatically affected the delivery of critical care due to a lack of resources. this pandemic has exposed the skeleton of healthcare systems around the world, as well as the lack of preparedness of most of the countries to tackle a major crisis like this. the present search for estimating the contributing factors to covid- -related outcomes may not be likely to have been exhaustive. however, these findings have important implications for public health actions, as much of the world will witness a massive community epidemic of covid- over the coming weeks and months. we try to make out a plan of action based on a few study reports that tried to address the gaps in nhs and the healthcare system as such in post-peak period the public will understandably wish to return to some semblance of normal life. deep economic damage will be a powerful motivation to lift restrictions on personal freedoms. but to do so too early will lead inevitably to a second peak. the government must make the public aware of this phase. to conclude, the present analysis acts as just the beginning of the development of a thorough understanding of the impact of various epidemiological factors in coronavirus disease-infected patient outcomes. this will help the resource-limited regions to strategize a coordinated response for effectively managing and preparing for the emergence of this yet-to-be-known disease entity. given the fact that this covid- pandemic, for now, will have a long-term implication for all members of society, a collaborative effort among society, government, public health experts, and healthcare professionals will be needed to ensure efficient recovery from this pandemic disaster as early as possible. human subjects: all authors have confirmed that this study did not involve human participants or tissue. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. covid- : towards controlling of a pandemic who. coronavirus disease ( covid- ) : situation report a review of sars-cov- and the ongoing clinical trials global economy could shrink by almost % in due to covid- pandemic: united nations world health organization case-fatality rate and characteristics of patients dying in relation to covid- in italy characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention an ecological study of the determinants of differences in pandemic influenza mortality rates between countries in europe health spending frequency of testing for covid infection and the presence of higher number of available beds per country predict outcomes with the infection countries in the world by population the countries with the most critical care beds per capita coronavirus update (live) coronavirus testing criteria and numbers by country pearson correlation coefficient calculator the need for ventilators in the developing world: an opportunity to improve care and save lives who director-general's opening remarks at the media briefing on covid daily confirmed covid- deaths: are we bending the curve our world in data. total covid- tests per , people offline: covid- and the nhs-"a national scandal clinical ethics recommendations for the allocation of intensive care treatments, in exceptional, resource-limited circumstances:the italian perspective during the covid- epidemic the extraordinary decisions facing italian doctors how a south korean city is changing tactics to tamp down its covid- surge critical preparedness, readiness and response actions for covid- key: cord- -fycwhyfv authors: goel, ashish; raizada, alpana; bansal, kamakshi; gaur, nikhil; abraham, jyotika; yadav, anil title: profile of patients suspected to be covid- : a retrospective analysis of early pandemic data date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: fycwhyfv background and objectives coronavirus disease (covid- ), a global public health emergency of profound magnitude, has brought life to an unprecedented near-standstill. the clinical profile of the disease is still emerging and is marked by considerable geographical variability in terms of transmissibility, clinical profile, virulence, and mortality of the disease. as clinical data is being reported from around the globe, it becomes important to focus on local subjects in a global milieu, lest one misses the trees for the forest. our study is a short retrospective analysis of the demographic and clinical profiles of subjects presenting with a mild flu-like illness to our hospital who were tested for covid- . it compares the differences in age and sex of those who tested positive with those negative. in addition, it reviews the length of time it might take for a case testing positive on reverse transcriptase-polymerase chain reaction (rt-pcr) test to become negative. methodology a retrospective analysis of data from adults who presented to our hospital with a mild flu-like illness between the months of march and may was conducted to understand the disease profile. the nasal/oropharyngeal swabs were collected from each patient and were transported to state-approved laboratories chain for rt-pcr analysis. information was collected from reports received, clinical information forms, and sample collection forms that were being maintained as a part of the clinical management protocol. data were analysed using stata software, version (statacorp llc, college station, tx, usa). observations and results three thousand twenty-six subjects presented to our hospital with either mild flu-like symptoms or with suspected exposure to a confirmed case of covid- . the subjects had a mean age of . (± . ) years and , ( . %) were males. a regression analysis revealed an adjusted odds of . ( % confidence interval (ci): . , . ) for testing positive for males as compared to females. for every one year increase in age, the odds for testing positive increased by . ( % ci: . , . ). of the , individuals for whom data was available, ( . %) were found positive on rt-pcr analysis. those testing positive were significantly older ( . years vs . years; p = . ) and more likely to be male (number: ; . % vs . %; p = . ). cough, followed by fever, was a common presenting feature. a survival time analysis using data from participants documented days of the total observation period. a median time of eight days was required for the test to convert from positive to negative if the patient remained mildly symptomatic and did not develop a severe complicated illness. the time to conversion did not differ with age or sex. conclusions our analysis shows that patients with covid- have presented with milder symptoms and have recovered well. the low test positivity rate is indicative of the early phase of the pandemic in the country and is a reflection of active infection control measures. coronaviruses, a family of viruses that range from the common cold to the coronavirus disease (covid- ) and include the middle east respiratory syndrome (mers) coronavirus and the severe acute respiratory syndrome (sars) coronavirus, has rapidly become a common household name in the space of a few months [ ] . covid- was declared a global public health emergency and has brought life to an unprecedented near-standstill owing to an unexpected, practically global lockdown. while comparisons have been drawn to the spanish flu pandemic of , the public health interventions in the present pandemic have been both brisk and far more severe. being an entirely new virus, a clinical profile of the disease is now emerging and has been characterized largely from chinese studies [ ] [ ] [ ] [ ] . as covid- paves its way into india (there are over , active cases at the time of writing this paper), the disease dynamics in a naïve indian population are only now being elaborated [ ] [ ] . considerable geographical variability has been noticed in the transmissibility, clinical profile, virulence, and mortality of covid- . consequently, the covid- dashboard, maintained by the johns hopkins bloomberg school, indicates that while the case fatality rate in the united kingdom is . %, australia has managed to escape with . % [ ] . india has had just over , deaths with the case fatality rate consistently under . %. when the differences are so wide and cannot be explained by the preparedness of healthcare systems alone, it becomes important to explore hostcharacteristics. as clinical data emerge from areas outside of china, it becomes important to focus on local subjects in a global milieu, lest one misses the trees for the forest [ ] [ ] [ ] . a recent case series of patients from delhi answers some questions but also raises several more unanswered questions [ ] . we present a short retrospective analysis of the demographic and clinical profiles of subjects presenting with a mild flu-like illness to our hospital who were tested for covid- . it compares the differences in age and sex of those who tested positive with those negative. in addition, it reviews the length of time it might take for a case testing positive on reverse transcriptase-polymerase chain reaction (rt-pcr) test to become negative. the proposal was reviewed by the institutional ethics committee-human research (iec-hr), university college of medical sciences, university of delhi, delhi (#iec-hr/ / / r), and a waiver of consent was approved for the present work. a retrospective analysis of data from subjects who presented to our hospital with mild flu-like illness between the months of march and may was conducted to understand the disease profile. data from adults who presented to our hospital (a non-covid-designated facility during march through may ) in delhi were included. nasal/oropharyngeal swabs were collected from each patient and were transported to state-approved laboratories, maintaining the appropriate cold chain for rt-pcr analysis. information was collected from the reports received, clinical information forms, and sample collection forms that were being maintained as a part of the clinical management protocol. data were analyzed using stata software, version (statacorp llc, college station, texas, usa). differences in proportions by groups (sex, clinical symptoms) were tested by using chisquare tests and the differences in means for age were examined using the t-test. the data was set-up as a survival time analysis to determine the median duration required for conversion from a positive to a negative test. data were available for , subjects who presented to our hospital with either mild flu-like symptoms or with suspected exposure to a confirmed case of covid- during the early phases of the pandemic. the subjects had a mean age of . (± . ) years and , ( . %) were males. the mean age was similar in males and females. a regression analysis revealed an adjusted odds of . ( % confidence interval (ci): . , . ) for testing positive for males as compared to females. every one year increase in age increased the odds for testing positive by . ( % ci: . , . ) of the , individuals on whom data was available, ( . %) were found to be positive on rt-pcr analysis and reports were inconclusive for ( . %). those testing positive were significantly older ( . years vs . years; p = . ) and more likely to be male (n: , . % vs . %; p = . ). the age distribution of patients based on the test report is presented in figure . limited data were available on the clinical profile of patients who had tested positive. the mean age of this group was . years (± . ) and there were ( . %) males. only one patient had symptoms for more than a week. most individuals who were found to be positive presented in the first week of illness. among these patients who tested positive, the commonest presenting features were cough (seen in patients, %), fever (seen in eight patients, %), myalgia (seen in three patients, %), and breathlessness (seen in three patients, %) with some overlap between symptoms. ten patients who were found to be positive did not have a clear history of exposure at presentation. in this retrospective analysis, we report that among subjects presenting to the hospital with a mild flu-like illness, those who tested positive for covid- were significantly older and more likely to be men. patients who tested positive took a median of eight days to become negative for covid- by rt-pcr. in a retrospective study by xiao et al. of confirmed covid- patients hospitalized at tongji hospital in wuhan, china, the median age was years and . % were male [ ] . the median period between onset of symptoms and positive severe acute respiratory syndrome coronavirus- (sars-cov- ) rt-pcr results was days (iqr: - , n = ). the median period of rt-pcr results to turn negative was days (iqr: - ; n = ). infected patients ≥ years old stayed contagious longer ( days vs days, p = . ). in another study conducted by liu et al. at wuhan in the early days of the pandemic, , cases were tested for sars-cov- [ ] . the median age was years (iqr: ) with . % of the subjects being male. out of the , patients, , ( . %) were positive by rt-pcr. males had a significantly higher positivity rate than females ( . % vs . %, respectively; p < . ) [ ] . escalera-antezana et al. evaluated subjects in a retrospective cross-sectional analysis and found that ( . %) of them returned positive results by real-time reverse-transcriptase polymerase chain reaction (rrt-pcr) [ ] . the median age of the infected subjects was years (iqr: - ) and half of them were male. most subjects remained mildly symptomatic and all recovered. the earliest data to emerge from across the world have consistently described patients who have presented with a milder illness and have rapidly recovered [ , [ ] [ ] . kim et al. observed covid- patients in south korea and found that % remained asymptomatic [ ] . others had a cough ( %) and hypoxia ( %). joshi et al. described nine relatively younger men in a small case series from nepal who had a mean age of - years [ ] . in a retrospective analysis of patients hospitalized during three weeks in march in the united kingdom, tomlins et al. reported that less than half of them could be discharged and one in five patients died [ ] . they reported that diabetes, cerebrovascular, and cardiovascular illness were associated with a poorer outcome. most of their patients presented with fever and cough, while anosmia was under-represented. those presenting with breathlessness had a greater chance of dying. while mortality appears to be considerably higher in their study as compared to other international reports, it is noteworthy that their patients were older (mean: years). goyal et al. retrospectively analysed data from patients, with a mean age of years, hospitalized in new york with common symptoms of cough, fever, and breathlessness [ ] . forty patients ( . %) died, and obese men had more severe disease. colaneri et al. from italy retrospectively studied covid- -positive patients and nearly % of the patients in their study developed a serious illness, while two ( . %) died [ ] . closer home, in a series of case studies, gupta et al. documented a mean age of . years with male preponderance ( . %) [ ] . the most common clinical presentation was cough and fever. however, . % of individuals were asymptomatic. hypertension, followed by diabetes, was the most common comorbidity seen. the covid- patients in india are younger as compared to their western counterparts. male preponderance has been seen worldwide. the proportion of asymptomatic individuals seems to be substantial and may be attributable to active contact tracing and surveillance in the country. time taken to document covid- negativity by rt-pcr in our study is lesser and may be explained by the relatively younger age composition in our study. however, we did not find any difference in time to negativity based on age. the test positivity rate of . % represents the early phase of the pandemic in india and is also a marker of the prompt availability of free testing facilities and active surveillance by the government. the present study is the first analysis of structured patient data inclusive of those who tested negative for covid- from india. the study can be used as a baseline to assess changes in test positivity rates overtime that may show the transition of the pandemic from one phase to another. the study provides important inputs for informed decision-making in patient management and helps in understanding the local trend of the disease. there is limited data available since, during the early part of the pandemic, data collection and electronic registries were not as robust, leading to gaps in information. our analysis shows that patients with covid- have presented with milder symptoms and have recovered well. of the individuals who were tested for covid- , . % were found to be covid- positive and most patients recovered after a mild illness. if global trends are to be believed, the pandemic could still be in its early stages in delhi and the numbers have remained low due to the early, brisk, and effective public health measures taken by the state. however, there is little room for complacence and the disease may take a more severe form in the not so distant future, as has been sadly realized by other countries. human subjects: consent was obtained by all participants in this study. institutional ethics committee-human research (iec-hr), university college of medical sciences, university of delhi, delhi issued approval iec-hr/ / / r. decision: accept in present form. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. accessed clinical characteristics of deceased patients with coronavirus disease : retrospective study clinical features of fatal cases of covid- from wuhan. a retrospective observational study clinical features of patients infected with novel coronavirus in wuhan, china. lancet. clinical characteristics of patients infected with sars-cov- in wuhan covid- statewise status clinical and epidemiologic profile of the initial covid- patients at a tertiary care centre in india. monaldi arch chest dis covid- ) in the united states clinical characteristics of coronavirus disease (covid- ) early findings from a teaching hospital in pavia, north italy, to february clinical characteristics of covid- in dynamic profile of rt-pcr findings from covid- patients in wuhan, china: a descriptive study positive rate of rt-pcr detection of sars-cov- infection in cases from one hospital in clinical features of the first cases and a cluster of coronavirus disease (covid- ) in bolivia imported from italy and spain clinical profile of cases of covid- in far western province of nepal clinical characteristics of asymptomatic and symptomatic patients with mild covid- clinical features of sequential hospitalised patients with novel coronavirus disease (covid- ), the first uk cohort the authors wish to thank professor karen bandeen-roche, chair, department of biostatistics at johns hopkins bloomberg school of public health, baltimore, md for her guidance in statistical analysis. we also wish to thank mr. sandeep, nursing officer at the guru teg bahadur hospital for his help to assemble the data. the samples of the patients were tested at lady hardinge medical college, delhi; max pathology labs, delhi, and at the institute of liver and biliary sciences, delhi during the early part of the pandemic before the facility was initiated at our hospital. we would like to thank dr. manoj jais, professor at lady hardinge medical college, new delhi for his support in the early phase of the pandemic. key: cord- -lb jcl m authors: patel, jay; patel, radhika; rodriguez, lyd-marie; blanco, anamarys; hamza, alan title: cardiovascular considerations of experimental hydroxychloroquine therapy on patients diagnosed with covid- : a case series review date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: lb jcl m the severe acute respiratory syndrome coronavirus (sars-cov- ) pandemic and its high virulence along with its variable presentation have generated a significant amount of interest within the medical community. the heterogeneous nature of the symptoms of the disease caused by sars-cov- , coronavirus disease (covid- ), ranging from being asymptomatic to severe acute respiratory distress syndrome (ards), has created significant interest in potential therapeutics. given the lack of randomized controlled trials, most medications are experimental, and only anecdotal evidence is available so far regarding their efficacy. one medication that emerged as an early frontrunner as a promising therapeutic was hydroxychloroquine (hcq), a common antimalarial and lupus drug. the adverse side effects that could result from its use did not gain much attention initially. we present the cases of two covid- -positive patients treated with hcq at our institution, which showed adverse effects of the medication. while hcq may have some therapeutic effect, it should be borne in mind that patients may experience more harm than benefit from its use. the ongoing coronavirus disease (covid- ) pandemic has led to global panic regarding its highly infectious process. in the race to find novel treatment strategies for covid- , numerous pharmacological agents are being touted as the silver bullet. the unfortunate reality of the covid- pandemic is that, as providers, we are dealing with a highly virulent, variable, and potentially aggressive pathogen as evidenced by a reported r-naught (r ) of . [ ] . hydroxychloroquine (hcq), a common antimalarial and lupus drug, has been shown to potentially reduce viral carriage and the number of symptomatic days in covid- patients according to an open-label non-randomized french case study of patients [ ] . however, the findings of a subsequent randomized controlled trial have led to the fda revoking hcq's emergency use authorization [ ] . the purpose of this case series was to highlight some of the cardiovascular complications related to hcq and to engage in a risk-benefit analysis of its use in mild/moderate presentations of covid- . a -year-old female with a past medical history of coronary artery disease (cad), chronic obstructive pulmonary disease, and autoimmune hepatitis on tacrolimus presented with a sixday history of fatigue, dry cough, shortness of breath, chest tightness, nausea, vomiting, and diarrhea. her vitals were stable and the exam demonstrated bilateral decreased breath sounds and wheezing on admission. she was admitted initially for possible community-acquired pneumonia and started on empiric coverage of ceftriaxone and azithromycin (azm). ondansetron was also started due to her nausea. on day two of hospitalization, the patient's condition improved symptomatically, but she was subsequently found to be covid- -and influenza-b positive. hcq and tamiflu® (roche pharmaceuticals, basel, switzerland) were started while azm was continued. labs demonstrated troponin of . ng/ml (three sets), potassium (k) level of . meq/l, magnesium (mg) level of . meq/l, and white blood cell (wbc) count of . thousand/mm at the time of initiation. on the morning of admission, the patient was found to have a qtc of ms ( figure a) . a chest x-ray demonstrated a left perihilar infiltrate ( figure b) . echocardiogram demonstrated left ventricular ejection fraction of % and no diastolic dysfunction. clostridium difficile testing was negative. a repeat ekg on day five of hospitalization demonstrated prolongation of qtc to ms, and several premature ventricular contractions with r-on-t waves were noted ( figure c ). she was asymptomatic at this time. hcq, ondansetron, and azm were subsequently discontinued. furthermore, her electrolytes were optimized, specifically with mg of > . meq/l and k of > . meq/l. by hospital day nine, the patient stated that her symptoms had improved. her qtc was noted to be ms on ekg on the same day ( figure d ). she made an uneventful recovery and was discharged on hospital day . this patient had a moderate presentation of covid- infection. her case was complicated by co-infection with influenza b, radiographic evidence of perihilar infiltrate, and leukopenia. given these combined findings, the initial benefit of hcq seemed superior to the risk given the fear of rapid progression to severe acute respiratory distress syndrome (ards). however, after a day of supportive therapy, the patient's condition dramatically improved. it is important to note that her tisdale score was after hcq, ondansetron, and azm administration (high risk for qt prolongation) [ ] . she was also having premature ventricular contractions (pvcs) throughout her hospitalization. especially worrisome were r-on-t waves noted on her telemetry, which could be a forewarning for impending ventricular fibrillation, especially in the setting of acquired long qt and her history of cad [ ] . in this case, the patient's hospital course was clearly complicated by hcq in addition to the many qtc-prolonging agents she was prescribed; hence, the overall benefit seemed marginal. a -year-old female with no significant medical history presented with a one-day history of nausea, vomiting, and diarrhea. she stated that she had recently returned from scotland and had begun experiencing symptoms of rhinorrhea starting in late january . she was not tested immediately for covid- due to a lack of fever. she was given a steroid dose-pack and a five-day course of azm at that time. she improved initially but later relapsed one week prior to admission when she developed symptoms of shortness of breath and mild wheezing. figure ) noted marked sinus bradycardia with a ventricular rate of bpm. the patient had no prior history of arrhythmias. it was believed that her symptoms of sudden diarrhea, nausea, and vomiting were secondary to hcq as was the bradycardia. the medication was discontinued, and her symptoms resolved; her heart rate improved to bpm, and she was uneventfully discharged on no antimicrobial medication. this case showed a mild incidence of covid- in a patient who was at low risk for qt prolongation given a tisdale score of . given the low risk of adverse effects, it initially appeared reasonable that the patient's primary care provider had started her on hcq treatment. the marked sinus bradycardia was a worrisome finding that thankfully resolved with discontinuation of the medication. it should be noted that the patient's baseline ekg was unknown. providers should consider obtaining a baseline ekg, renal panel, and hepatic panel prior to the administration of hcq in these patients. this case illustrates the fact that hcq provided little benefit for such a mild presentation of covid- as in this patient. while hcq was demonstrated to be effective in the french study by gautret et al., it is not a proven treatment modality and it should be used with caution. the above two cases add to the ongoing discussion as to whether hcq therapy in covid- patients is beneficial for all, especially given how it was paired with another arrhythmogenic agent azm. we believe these are among the first few cases illustrating adverse cardiovascular effects of the experimental five-day hcq therapy in mild/moderate presentations of covid- . while the safety profile on hcq is relatively favorable, the drug is a well-known arrhythmogenic medication that can lead to life-threatening ventricular arrhythmias, most commonly recognized as torsades de pointes (tdp) [ ] . admittedly, the relationship between qtc prolongation and tdp is not linear; nevertheless, clinicians are well aware of the risks of prolonged qtc. the tisdale risk stratification scoring system was invented for predicting the risk of qt prolongation [ ] . as shown in table with respect to our patients, the tisdale score characterizes patients as low risk (score< ), moderate risk (score - ), and high risk (score > ). case , which was considered as high risk, involved a patient with potentially lethal asymptomatic prolongation of the qtc segment. additionally, the r-on-t phenomenon noted on telemetry was worrisome as this could have potentiated a polymorphic ventricular tachycardia (pvt) or even ventricular fibrillation [ ] . these were clear complications of the hcq and, subsequently, prolonged the patient's hospital stay. case , considered as low risk, demonstrated how hcq therapy initiated in an outpatient resulted in an adverse outcome that led to hospital admission. the bradycardia was thankfully recognized early as this could have progressed to potential atrioventricular block had the patient continued the medication [ ] . both of these cases throw light on hcq-related complications resulting in prolonged hospital stay/hospitalization that exposed these patients to potential hospital-acquired infections or even re-infection with covid- , which has only been sporadically reported [ ] . age ≥ years the american college of cardiology (acc) has issued guidance on how to proceed in patients who could potentially receive hcq for covid- therapy. in the outpatient setting, a baseline assessment with ekg, renal function panel, and hepatic function panel should be completed and, if possible, the ekg should be assessed by an electrophysiologist [ ] . furthermore, other qtc-prolonging agents should be discontinued if possible [ ] . relative contraindications in these patients would include: ) history of long qt syndrome, ) qtc of > ms, and ) tisdale score of ≥ [ ] . for inpatients, the recommendations include the same as above plus: ) placing patients on telemetry ) obtaining serum potassium on a daily basis, and ) obtaining ekg two to three hours after the second dose of hcq. guidance on qtc increases of > ms or overall qtc of > ms seems to point towards the discontinuation of azm and subsequent dose decrease of hcq. if qtc does not improve, the acc recommends complete discontinuation of hcq [ ] . the emergence of new data regarding hcq's application in the early disease course of covid- has called its use into question. in the outcomes related to covid- treated with hydroxychloroquine among in-patients with symptomatic disease (orchid) trial conducted by the petal network, patients were enrolled in a double-blinded, placebo-controlled randomized trial to determine if five-day therapy with hcq led to more favorable outcomes [ ] . the dosing regimen included hcq sulfate mg po twice daily on day one followed by mg twice daily doses on days two to five [ ] . the initial results from the trial suggested that there was no benefit or harm from hcq use, and the trial was subsequently halted in mid-june [ ] . the data is still awaiting full analysis for submission to peer review [ ] . in june , the fda officially revoked emergency use authorization for hcq as there was no benefit demonstrated from the aforementioned trial [ ] . moreover, the agency has cautioned against its use in the outpatient setting given its potential cardiovascular complications and inability to closely monitor patients [ ] . the trial data and fda recommendations in their totality demonstrate that hcq use likely is not beneficial in the early disease course of these patients. regarding the lack of harm shown by the orchid trial, more subgroup analysis is warranted in these patients to fully determine if patients with cardiovascular disease burden suffered harm, despite the absence of mortality among patients. the potential for arrhythmogenic effects of these medications, especially in patients with cardiovascular disease, should be seriously weighed against their benefit before administration. based on the recent preliminary analysis of data from the orchid trial, there is no benefit from hcq use. if hcq is commenced by providers for the treatment of covid- in patients with a cardiac history, it should be done at the guidance of an infectious disease physician in conjunction with a cardiologist. while the prospect of potential lifesaving therapeutics seems tempting, the long-standing principle of "do no harm" is of importance now more than ever. experimental therapy with hcq in mild/moderate presentations of covid- should be balanced with considerations of the risk of potential cardiac complications in both inpatient and outpatient settings. this is especially the case as there have been no double-blinded randomized control trials with results demonstrating that the benefits of the therapy outweigh the risks. disclosures high contagiousness and rapid spread of severe acute respiratory syndrome coronavirus . emerg infect dis hydroxychloroquine and azithromycin as a treatment of covid- : results of an open-label non-randomized clinical trial (epub ahead of print) fda cautions against use of hydroxychloroquine or chloroquine for covid- outside of the hospital setting or a clinical trial due to risk of heart rhythm problems development and validation of a risk score to predict qt interval prolongation in hospitalized patients r-from-t as a common mechanism of arrhythmia who malaria policy advisory committee meeting: the cardiotoxicity of antimalarials heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in patients treated with hydroxychloroquine for connective tissue diseases recurrence of positive sars-cov- rna in covid- : a case report ventricular arrhythmia risk due to hydroxychloroquineazithromycin treatment for covid- outcomes related to covid- treated with hydroxychloroquine among in-patients with symptomatic disease (orchid) orchid: outcomes related to covid- treated with hydroxychloroquine among in-patients with symptomatic disease human subjects: consent was obtained by all participants in this study. hca institutional review board issued approval - . this research activity was determined to be exempt or excluded from the institutional review board (irb) oversight in accordance with current regulations and institutional policy. the internal reference number for this determination is - . conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -jjd fyh authors: singhavi, ravi; sharma, kamal; desai, hardik d; patel, rahul; jadeja, dhigishaba title: a case of hemolytic anemia with acute myocarditis and cardiogenic shock: a rare presentation of covid- date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: jjd fyh coronavirus disease (covid- ) cases are on the rise globally, and mortality- and survival-related data are emerging every day. in addition, upcoming reports are suggestive of increased risk of cardiac ailments in high-risk patients. in the context of cardiac involvement, acute myocarditis has become one of the unexplored areas in covid- patients, which could influence the long-term outcomes. in this report, we present a rare case that warrants further study on the subject due to the paucity of data in the literature. to date, no case of severe hemolytic anemias with stress cardiomyopathy/acute myocarditis in a patient of covid- has been formally reported in the literature. the bedside echocardiogram had shown a possibility of acute myocarditis. the patient’s marked left ventricular (lv) functional recovery without coronary intervention further corroborates the same. clinicians should be aware of the diversity of cardiovascular/hematological complications, as well as focused cardiac ultrasound study and the importance of echocardiography as a good screening modality for cardiovascular and hematological complications of covid- infection. as of july , , the novel causative virus -the severe acute respiratory syndrome coronavirus (sars-cov- ) -has affected , , people and caused , deaths, with a case fatality rate (cfr) of . globally [ ] . recent studies have shown that mortality in the takotsubo syndrome (tts) variant of myocardial involvement in coronavirus disease (covid- ) has been higher than mortality in tts without covid- and it affects both genders almost equally [ ] . in this report, we present a case of acute hemolytic anemia with acute myocarditis and cardiogenic shock in a male patient with covid- infection. a -year-old male presented to the emergency department with a one-day history of low-grade fever that had peaked to °f just the night prior to the hospitalization with minimal flu-like symptoms. physical examination on presentation showed blood pressure of / mmhg, heart rate of /minute, respiratory rate of breaths/minute, and % oxygen saturation on room air. the patient had no significant past or family medical history. laboratory tests on day one showed an elevated c-reactive protein (crp) of mg/l, erythrocyte sedimentation rate (esr) of mm for one hour, and elevated serum glutamic-pyruvic transaminase (sgpt) of iu. on day two of admission in the covid- intensive care unit (icu), laboratory findings returned with a hemoglobin of . gm%, total white cell count of , /cmm with a reduced platelet count of , /cu mm. peripheral smear showed normocytic hypochromic anemia with few fragmented rbcs and schistocytes with reticulocytosis with the possibility of hemolytic anemia due to smear features of fragmented rbcs. lactate dehydrogenase (ldh), which is often a surrogate marker of both hemolytic anemia and inflammation, was elevated at mg%. elevated cardiac biomarkers, viz. troponin i of , . ng/l and brain natriuretic peptide of , pg/ml, were also recorded. lactate was . mmol/l and serum creatinine was . mg/dl. electrocardiogram was mimicking of acute coronary syndrome, showing mild st depression and t wave inversion ( figure ). echocardiography revealed global hypokinesia, with a preserved wall thickness ( figure ) , and left ventricular ejection fraction (lvef) of %. high-resolution ct thorax (video ) and ct of abdomen-pelvis were unremarkable. the patient was managed in the icu on inotropes. covid- was strongly suspected despite normal high-resolution ct. differential diagnoses included acute coronary syndrome, sepsis, acute fulminant myocarditis, and vasospasm in the setting of covid- infection. a nasopharyngeal swab was positive for high viral load (by cycle time) for sars-cov- by reverse transcription-polymerase chain reaction (rt-pcr). given his positive covid- test and hemoglobin of a mere . gm%, the decision was made to defer coronary angiography. the patient was transfused pack cell volume to correct anemia along with iv noradrenaline infusion, low molecular weight heparin, iv vitamin k, and a low dose of diuretics and steroids in the form of injection methylprednisolone pulse therapy. clinically, the patient developed cardiogenic shock during the course of hospitalization and required uptitration of norepinephrine. he stabilized over the next two to three days and was finally discharged on day with a hemoglobin level of . gm%. discussion covid- has been primarily a respiratory disease, but many studies have reported that it affects multiple systems. cardiogenic shock due to myocarditis has been extensively reported as among the most common cardiovascular complications of covid- [ ] . previous studies have reported that angiotensin-converting enzyme (ace ) receptors mediated effects on lungs, kidneys, heart, vascular endothelium by downregulating their expression and enhanced vasoconstriction with deleterious effects of the unopposed reticuloendothelial system [ ] . it is also likely that virus-mediated immune response can cause consumption coagulopathies, acute hemolytic anemias, and other blood cell dyscrasias [ , [ ] [ ] . cardiac findings of previously published autopsy series of patients with covid- have reported cell necrosis without lymphocytic-myocarditis with no evidence of direct viral cytotoxicity [ ] . both acute myocarditis and acute hemolytic anemias and consequent severe anemia can together or alone produce acute heart failure and dilated lv/poor lv function. in this report, we presented a case of a covid- patient who developed acute myocarditis and severe acute hemolytic anemia, as evident from peripheral blood smear showing schistocytes (fragmented rbcs) in peripheral smear with acute severe anemia along with elevated ldh, which is also a surrogate marker for hemolysis. acute heart failure with cardiogenic shock with possible stress cardiomyopathy is often characterized by transient severe global lv dysfunction in the absence of significant coronary artery disease. the cardiogenic shock was diagnosed based on the intraaortic balloon pump in cardiogenic shock ii (iabp-shock ii) definition: systolic blood pressure of mmhg that requires more than minutes of inotropic support. exclusion of sepsis was supported by the normal value of serum procalcitonin apart from the corroborative echo finding of severe lv dysfunction [ ] . in this patient, despite low oxygen saturation, the ct scan was clear, and the low saturation could be explained by central oxygenation impairment apart from peripheral vasoconstriction due to low cardiac output and inotropes that were being administered to the patient. pao and sao correlation varies more widely below % saturation and hence may be misleading. severe acute myocarditis may sometimes manifest with low forward output and minimal pulmonary congestive manifestations [ ] . it is hypothesized that high catecholamines, exaggerated inflammatory/immune-mediated response, and direct viral cytotoxicity and consequent effects of acute anemia (high co state) may be the mechanism behind the development of such reversible transient stress cardiomyopathy secondary to acute heart failure due to acute myocardial damage and/or rapid rbc breakdown [ ] . to date, no case of severe hemolytic anemias with stress cardiomyopathy/acute myocarditis in a patient of covid- have been formally reported in the literature. in our patient, the bedside echocardiogram had shown a possibility of acute myocarditis. the patient's marked lv functional recovery without coronary intervention further corroborates the same. it is anticipated that as the number of covid- cases rises worldwide, there will be an increase in the number of associated cardiovascular manifestations and myriad complications. clinicians should be aware of the diversity of cardiovascular/hematological complications and focused cardiac ultrasound study and critical care echocardiography as good screening modalities for cardiovascular complications of covid- infection. human subjects: consent was obtained by all participants in this study. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. takotsubo syndrome a rare entity in patients with covid- : an updated review of case-reports and case-series cardiovascular complication in covid- sars-cov- receptor and regulator of the renin-angiotensin system: celebrating the th anniversary of the discovery of ace covid- update: covid- -associated coagulopathy autoimmune haemolytic anaemia associated with covid- infection rs: pulmonary and cardiac pathology in african american patients with covid- : an autopsy series from new orleans cardiogenic shock correlation between the levels of spo and pao . lung india international expert consensus document on takotsubo syndrome (part i): clinical characteristics, diagnostic criteria, and pathophysiology key: cord- -t ahmh h authors: elkattawy, sherif; alyacoub, ramez; noori, muhammad atif masood; talpur, afrah; khimani, karim title: a rare complication of myocardial infarction: ventricular septal defect date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: t ahmh h ventricular septal defect (vsd) is a rare but lethal complication of myocardial infarction. we present a case of a -year-old male who presented with a history of progressive shortness of breath associated with productive cough. physical examination was significant for crepitation in both lower lung fields and bilateral lower extremity edema. chest x-ray revealed bilateral reticular opacities with small bilateral pleural effusions. polymerase chain reaction (pcr) for covid was positive. echo showed a left ventricular ejection fraction (lvef) of - %, ischemic cardiomyopathy, and muscular ventricular septal defects with left to right shunting and severely elevated pulmonary artery systolic pressure. overtime during the hospital course, he developed respiratory and fulminant hepatic failure. our patient had vsd due to an undiagnosed old myocardial infarction (mi). initially heart failure was compensated and treated with medical management. later on, he developed respiratory complications related to covid- infection as well as hepatic failure in addition to a cardiomyopathy which made him a poor surgical candidate leading to death. a ventricular septal defect (vsd) is an abnormal communication between the left and right ventricle through a defect in the septal wall of the heart. vsd is a rare but lethal complication of myocardial infarction (mi), it is also referred to as a ventricular septal rupture (vsr). a vsr after mi is uncommon and occurs only - % of the time [ ] . the event occurs - days after an infarction and often leads to cardiogenic shock. conservative treatment is associated with % mortality, while surgical treatment is associated with % mortality during the first days [ ] . making a decision to perform surgery is complicated by the critical preoperative condition of the patients and the myocardial tissues necrosis. patients with a right ventricular infarction or cardiogenic shock and a ventricular septal rupture have high in-hospital mortality rate [ ] . here we are presenting a case of vsd post myocardial infarction, which subsequently lead to multisystem organ failure. a -year-old caucasian male with past medical history significant for hepatitis and hiv complicated by multiple pneumocystis pneumonia (pcp) infections [not on highly active antiretroviral therapy (haart)] initially presented to the emergency room for evaluation for severe depression after his cat passed away. the patient stated that he had a sense of depression for three weeks prior to his admission. he conveyed that during that three-week stretch, he experienced decreased appetite, unintentional weight loss of roughly pounds, and suicidal ideation. furthermore, during that time frame, he also complained of progressively worsening shortness of breath associated with a cough productive of yellow-whitish sputum, diffuse body aches, weakness, and bilateral lower extremity edema. the patient denied coming into contact with individuals who were ill and denied exposure to the covid- virus. however, he did admit to living in a boarding home where he shared public areas, such as bathrooms, with other tenants. the patient revealed that he had a significant history of substance abuse spanning the last years. he admitted to the use of marijuana and cocaine, with his last use being days prior to his admission. the patient's urine drug screen (uds) was positive for cannabinoids. moreover, he denied the use of iv drug use. upon evaluation in the emergency room, the patient was found to be afebrile with an oral temperature of . c, normotensive with a blood pressure of / , saturating at % on room air, and with a heart rate of bpm. electrocardiogram (ekg) shows normal sinus rhythm. his complete blood count (cbc) revealed no leukocytosis with a white blood cell (wbc) count of . k/ul ( . - . k/ul). troponin was negative. the patient's chest x-ray revealed bilateral reticular opacities (left significantly greater than right) with small bilateral pleural effusions. after review of his comprehensive metabolic panel (cmp), the patient was noted to have an elevated creatinine of . mg/dl ( . - . mg/dl). arterial blood gas (abg) studies revealed a partial pressure of oxygen (po ) of mmhg (> mmhg) and a partial pressure of carbon dioxide (pco ) of . mmhg ( - mmhg). upon admission to the hospital, the patient was noted to have acute kidney injury (aki) with a creatinine . mg/dl ( . - . mg/dl). further evaluation via ultrasound revealed a left renal cyst. ultimately, the patient's creatinine mildly improved during the course of his treatment to . mg/dl. after undergoing a more thorough work-up, the patient was found to be positive for covid- . he also had a transthoracic echocardiogram, which showed a left ventricular ejection fraction (lvef) of - %, ischemic cardiomyopathy, and muscular ventricular septal defects with left to right shunting and severely elevated pulmonary artery systolic pressure as seen in video . view video here: https://vimeo.com/ over time, the patient's bilirubin and aspartate transaminase/alanine transaminase (ast/alt) continued to rise, peaking at an ast of , u/l ( - u/l) and an alt of u/l ( - u/l). the patient's international normalised ratio (inr) also became elevated reaching a maximum of . with a prothrombin time (pt) of . seconds ( . - . sec). evidently, the patient was in fulminant hepatic failure. furthermore, he was also in renal failure with a blood urea nitrogen (bun) > mg/dl ( - mg/dl). also, the patient was found to have an elevated d-dimer of > , ng/ml ( - ng/ml). however, the patient was unable to receive anticoagulation due to his elevated inr. on physical examination, he had multiple petechiae and ecchymoses throughout his body, was severely jaundiced, but was awake, alert and oriented to date, place and person (aaox ). no cardiac murmur was appreciated on examination. an extensive conversation was held with the patient with regards to goals of care in which patient made himself do-not-resuscitate/do-not-intubate (dnr/dni). unfortunately, his health continued to deteriorate. both cardiology and nephrology were on board as he was treated symptomatically. during hospital course, the patient became dyspneic and was subsequently started on mg of iv morphine for comfort as per family discussion. the next morning, the patient was found unresponsive with dilated pupils and no brain stem reflexes and was pronounced dead. ventricular septal defect (vsd) is a rare mechanical complication of myocardial infarction, especially in the era of reperfusion therapy [ ] . it usually occurs days two to seven following a transmural infarction secondary to complete occlusion of any of the coronary vessels with septal branches supplying the interventricular septum in the absence of collaterals. occlusion of the left anterior descending artery is the most common cause [ ] . ventricular septal rupture (vsr) can occur following both anterior and inferior mi. typically, the defect due to anterior mi is apical and simple. vsr secondary to inferior mi tends to be a more complex lesion with more significant tissue destruction. it has been reported as a complication of right ventricular infarction [ ] . cardiac rupture occurring hours after mi is the result of dissecting intramural hematoma. the subacute course which occurs within a week after myocardial infarction is the result of a cascade of pathological events that starts with ischemia of the myocardium then coagulative necrosis then neutrophilic infiltration with subsequent macrophages infiltration and removal of necrotic tissue leading to the weakening of the tissue culminating in complications such as a ventricular free wall rupture, interventricular septum rupture, or a papillary muscle rupture. a much rarer type can occur > weeks following perforation of thinned aneurysmal myocardium [ ] . ventricular septal rupture complicates . % of acute mis, compared with - % before thrombolysis was introduced [ ] . multiple observational studies identified severe risk factors that increase the risk of cardiac rupture, including rupture of the interventricular septum, first incidence of mi, st-segment elevation, female sex, previous stroke, positive initial cardiac biomarkers, older age (> ), and higher heart rate. on the other hand, a history of mi with primary percutaneous coronary intervention (pci) and the use of low-molecular-weight heparin and beta-blockers during the first hours were identified as protective factors for cardiac rupture [ ] [ ] [ ] [ ] . patients with a ruptured septum may present with a wide range of symptoms and signs, ranging from mild dyspnea at exertion to severe cardiogenic shock. when the onset of hemodynamic compromise is immediate, hypotension and tachycardia are present. biventricular heart failure with predominant right-sided failure may be present. rupture of the septum leads to left to right shunt with subsequent right ventricular failure that can progress to pulmonary edema and biventricular failure. on physical exam, a new cardiac murmur is nearly always present. the new murmur is typically harsh, loud, and holosystolic, and is heard best at the lower left and usually right sternal borders. in some cases, the murmur is heard best at the apex and may be mistaken for acute mitral regurgitation. a thrill can be detected in up to % of patients; right ventricular lift and a hyperdynamic precordium may also be noted. diagnosis is confirmed by transthoracic echocardiography, which will show disrupted ventricular septum with evidence of left-to-right shunt by color doppler, left cardiac catheterization (evidence of left-to-right shunt by ventriculography). if done, pulmonary artery catheterization can reveal step up in the oxygen saturation in the right ventricle and pulmonary artery compared to the right atrium. post mi vsd has a high in-hospital mortality rate. cardiogenic shock is an independent predictor of in-hospital mortality. these patients often require mechanical circulatory support [ ] . in-hospital mortality is about % in patients who were surgically treated compared to % who were medically treated [ ] . patients usually require initial afterload reduction prior to definitive intervention, with the timing of intervention being an important factor in survival [ ] . treatment of post-mi vsd is challenging. the timing of intervention and the treatment approach continues to be an area of debate, depending on the type and size of the defect, clinical condition of the patient, and technical expertise [ ] [ ] [ ] . surgical management has been the standard treatment. however, the trans-catheter approach has increasingly become an alternative modality to surgical repair, especially in patients that are at high risk for surgery. immediate surgical closure is associated with high mortality due to hemodynamic instability and friable tissue surrounding the septal defect in the acute phase of an mi. a systemic review looking at the differences between management options found no significant difference in the mortality among patient who had early trans-catheter approach compared with initial surgical closure group but the overall mortality among all trans-catheter approach and late transcatheter approach groups were significantly lower when compared with the late surgical closure group [ ] . our patient had a vsd due to an old undiagnosed mi. he was in compensated heart failure at first and was treated with medical management. later on, he developed respiratory complications related to covid- infection as well as hepatic failure in addition to cardiomyopathy that made him a poor surgical candidate. ventricular septal defect is a known however rare complication of myocardial infarction. symptoms range from mild dyspnea to overt cardiogenic shock. our study highlights a fortunate patient in which a vsd secondary to myocardial infarction (mi) did not result in catastrophic outcome during the initial admission for mi. bringing awareness to this fatal complication may result in health care providers recognizing it quicker and acting accordingly. more research studies should be geared towards optimal ways to detect and manage vsds secondary to myocardial infarctions. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. postinfarction ventricular septal rupture risk factors, angiographic patterns, and outcomes in patients with ventricular septal defect complicating acute myocardial infarction hemodynamic complications of ventricular septal rupture after acute myocardial infarction ventricular septal defect: early against late surgical repair trends in the clinical and pathological characteristics of cardiac rupture in patients with acute myocardial infarction over years in-hospital outcome of patients with post-mi vsd: a single-center study surgical management of post-infarction ventricular septal defect, mitral regurgitation and ventricular aneurysm factors related to heart rupture in acute coronary syndromes in the global registry of acute coronary events management of post-myocardial infarction ventricular septal defects: a critical assessment acute mechanical complications in patients suffering from acute myocardial infarction. vessel plus key: cord- - oyvia d authors: farooque, umar; shabih, sohaib; karimi, sundas; lohano, ashok kumar; kataria, saurabh title: coronavirus disease -related acute ischemic stroke: a case report date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: oyvia d coronavirus disease (covid- ) is an active worldwide pandemic with diverse presentations and complications. most patients present with constitutional and respiratory symptoms. acute ischemic stroke remains a medical emergency even during the covid- pandemic. here we present a case of a patient with covid- who presented with acute ischemic stroke in the absence of common risk factors for cerebrovascular accidents. a -year-old male patient, with no prior comorbidities, presented to the emergency department (ed) with fever, cough, and shortness of breath for four days, and altered level of consciousness and right-sided weakness with the sensory loss for one day. on examination, the patient had a score of / on the glasgow coma scale (gcs). there was a right-sided sensory loss and weakness in both upper and lower limbs with a positive babinski's sign. the pulmonary examination was remarkable for bilateral crepitation. on blood workup, there was leukocytosis and raised c-reactive protein (crp). d-dimer, ferritin, thyroid-stimulating hormone (tsh), vitamin b , and hypercoagulability workup were normal. transthoracic echocardiography was also normal. covid- polymerase chain reaction (pcr) detected the virus. chest x-ray showed infiltrations in the left middle and both lower zones of the lungs in the peripheral distribution. computed tomography (ct) scan of the chest showed peripheral and mid to basal predominant multilobar ground-glass opacities. ct scan of the head showed a large hypodense area, with a loss of gray and white matter differentiation, in the left middle cerebral artery territory. magnetic resonance imaging (mri) of the head showed abnormal signal intensity area in the left parietal region. it appeared isointense on t image and hyperintense on t image. it also showed diffusion restriction on the diffusion-weighted (dw ) image with corresponding low signals on the apparent diffusion coefficient (adc) map. these findings were consistent with left middle cerebral artery territory infarct due to covid- . the patient was intubated in the ed. he was deemed unfit for thrombolysis and started on aspirin, anti-coagulation, and other supportive measures. patients with covid- should be evaluated early for neurological signs. timely workup and interventions should be performed in any patient suspected of having a stroke to reduce morbidity and mortality. the severe acute respiratory distress syndrome coronavirus- (sars-cov- ) appeared from wuhan, china, at the end of and became a pandemic involving the whole world [ ] . it can , be asymptomatic or present with fever, fatigue, body aches, dry cough, dyspnea, and complications like acute respiratory distress syndrome (ards), severe pneumonia, acute kidney injury, myocarditis, multiorgan failure, and death [ , ] . patients can also present with atypical gastrointestinal and neurological manifestations. here we report a case of a patient with covid- who presented with acute ischemic stroke without any predisposing conventional risk factors for cerebrovascular accident. a -year-old male presented to the emergency department (ed) with complaints of fever, cough, and shortness of breath for four days and altered level of consciousness, and right-sided weakness with sensory loss for one day. the patient was in his usual state of health when he developed fever and cough which was initially dry and later became productive with whitish sputum. the sputum was two teaspoons in quantity and difficult to expectorate. the patient also developed dyspnea during this time. the shortness of breath was sudden in onset, not associated with exertion, chest pain, sweating, palpitations, leg swelling, or any history of immobilization. the patient also denied any associated orthopnea or paroxysmal nocturnal dyspnea. three days later, he developed an altered level of consciousness which was sudden in onset and associated with right-sided paralysis and loss of sensations. there was no associated neck stiffness, headache, or seizure. the patient did not have any comorbidities, including hypertension or diabetes. there was no family history of hypertension, or diabetes as well. he did not smoke or drink alcohol. there was no recent travel history or any prior history of similar complaints. on physical examination, the patient was not oriented to time and place. his blood pressure was / mmhg, pulse was beats/minute, respiratory rate was breaths/minute, spo was % on % non-rebreather mask, and temperature was o f. on neurological examination, the patient had a score of / on the glasgow coma scale (gcs). power was / in both upper and lower extremities on the right side and / on the left side in both lower and upper extremities. babinski's sign was also positive on the right side. sensations were also absent in the right upper and lower limbs. there were no signs of neck rigidity. lung examination was notable for harsh vesicular breathing with bilateral crepitation. other systemic examinations were unremarkable. on laboratory investigations, complete blood count revealed a total leukocyte count of , cells/mcl (normal range: , to , cells/mcl), hemoglobin of . g/dl (normal range - . to . g/dl) with a mean corpuscular volume (mcv) of fl/cell (normal range - to fl/cell), and platelet count of , /mcl (normal range: , to , /mcl). serum electrolytes including serum sodium, potassium, chloride, urea, and creatinine were within the normal range. hemoglobin a c was . % (normal range: % to . %). d-dimer, ferritin, thyroid-stimulating hormone (tsh), vitamin b , and hypercoagulability workup were within normal limits. transthoracic echocardiography was unremarkable. real-time polymerase chain reaction (rt-pcr) testing for sars-cov- was performed using a nasopharyngeal swab which was positive. c-reactive protein (crp) was elevated to mg/l (normal value: less than mg/l). blood and urine culture did not yield any growth. a chest x-ray showed bilateral airspace opacifications in both lungs, more pronounced in the left middle and both lower zones, with relative sparing of the left upper zone and peripheral distribution ( figure ). this is a chest x-ray in the posteroanterior (pa) view showing bilateral infiltrates in both lower and left middle zones of lungs in the peripheral distribution ct scan of the chest showed multilobar ground-glass opacities with peripheral and mid to basal predominance. there was air space consolidation in the left lower lobe. there was no significant mediastinal lymphadenopathy. these findings were consistent with covid- ( figure ). the patient was intubated in the ed for hypoxemic respiratory failure. he was not deemed a suitable candidate for thrombolysis or neuro-intervention. so consequently, the patient was shifted to the intensive care unit (icu) and started on aspirin mg twice daily, subcutaneous low molecular weight heparin (lmwh) . ml twice daily, and intravenous dexamethasone cc twice daily. the family eventually decided to pursue comfort measures. covid- is a current worldwide pandemic with diverse complications. recent literature has shown multiple neurological manifestations including cerebrovascular accidents in patients with severe infection [ , ] . a single-center study of patients showed that cerebrovascular events were more common in patients with stroke risk factors such as hypertension, diabetes, and previous history of cerebrovascular accidents. the mean age of patients who developed stroke was also higher and the stroke group had a higher frequency of hepatic and renal dysfunction [ ] . sars-cov- infection has also been shown as an independent risk factor for ischemic stroke [ ] . here in our case also, the patient developed acute ischemic stroke in the absence of conventional vascular risk factors. the exact pathophysiology behind these cerebrovascular accidents is yet to be established. infectious/inflammatory syndromes are associated with an increased risk of stroke, probably due to different mechanisms involving prothrombotic state, alterations in lipid metabolism, platelet aggregation, and modifications in endothelial function [ ] . sars-cov- binds to the angiotensin-converting enzyme receptor. this binding results in a cytokine storm which leads to a hypercoagulable state in patients with covid- [ ] . critically ill patients with sars-cov- also show elevated d-dimer levels and platelet counts, which increases the propensity towards acute cerebrovascular episodes [ ] . the current covid- pandemic necessitates that extra measures be taken to provide care to stroke patients, along with measures aimed at minimizing the spread of infection. paramedics should develop an infectious screening policy in all patients before bringing them to the hospital [ ] . all suspected stroke patients should receive brain imaging within minutes of arrival in the ed. negative pressure carrier isolators can be used to isolate covid- patients during neurovascular imaging. the possibility as to whether anticoagulant or antiplatelet agents may be superior in stroke patients with covid- requires further consideration. similarly, no data exists to suggest a clear-cut benefit or risk with using intravenous recombinant thromboplastin plasminogen activator (rt-pa) therapy. a low threshold for initiating intubation, mechanical ventilation, and general anesthesia may be required in patients with covid- infection who are selected for mechanical thrombectomy to reduce exposure risk during the procedure [ ] . the mortality rate in covid- patients with stroke is very high [ ] . older age, high sequential organ failure assessment (sofa) score, cardiovascular diseases, secondary infections, ards, acute renal injury, lymphopenia, and elevated liver enzymes, crp, ferritin, fibrin, and d-dimers are some of the factors in covid- cases which can identify patients at risk of in-hospital mortality [ ] . patients of covid- can present with cerebrovascular accidents. stroke teams should be aware of this fact and screen the suspected patients for acute neurologic changes as soon as possible, so that management can be initiated in time, and morbidity and mortality can be reduced. in future, further analysis is needed on a larger scale to find out the true relationship between covid- and ischemic stroke and its pathogenesis. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all covid- presenting as stroke evolutionary history, potential intermediate animal host, and cross-species analyses of sars-cov- neurological complications of covid- : a systematic review of literature. preprint (version ) available at research square neurologic manifestations of hospitalized patients with coronavirus disease acute cerebrovascular disease following covid- : a single center, retrospective, observational study covid- is an independent risk factor for acute ischemic stroke immunohematologic characteristics of infection-associated cerebral infarction covid- : consider cytokine storm syndromes and immunosuppression nervous system involvement after infection with covid- and other coronaviruses protected code stroke: hyperacute stroke management during the coronavirus disease (covid- ) management of acute ischemic stroke in patients with covid- infection: insights from an international panel trends in in-hospital mortality among patients with stroke in china clinical predictors of mortality due to covid- based on an analysis of data of patients from wuhan, china authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. key: cord- -afq authors: ghanchi, hammad; patchana, tye; wiginton, james; browne, jonathan d; ohno, ai; farahmandian, ronit; duong, jason; cortez, vladimir; miulli, dan e title: racial disparity amongst stroke patients during the coronavirus disease pandemic date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: afq introduction the global coronavirus disease (covid- ) pandemic has had deleterious effects on our healthcare system. lockdown measures have decreased the number of patients presenting to the hospital for non-respiratory illnesses, such as strokes. moreover, there appears to be a racial disparity among those afflicted with the virus. we sought to assess whether this disparity also existed for patients presenting with strokes. methods the get with the guidelines national stroke database was reviewed to assess patients presenting with a final diagnosis of ischemic stroke, transient ischemic attack (tia), subarachnoid hemorrhage (sah), or spontaneous/nontraumatic intraparenchymal hemorrhage (iph). the period of february - may was chosen given the surge of patients affected with the virus and national shutdowns. data from this same time during was used as the control population. our hospital numbers and four additional regions were assessed (california hospitals, pacific state hospitals, western region hospitals, and all hospitals in the united states). patients were categorized by race (white, black/african american, asian, native american, hispanic) in each cohort. the primary endpoint of this study is to compare whether there was a significant difference in the proportion of patients in each reported racial category presenting with stroke during the covid- pandemic caused by severe acute respiratory syndrome coronavirus (sars-cov- ). results a downward trend in total number of patients was noted in all five regional cohorts assessed. a statistically significant increase in the number of black and hispanic patients presenting with strokes was noted in california, pacific hospitals, western hospitals, and all hospitals in the united states during various months studied comparing to . a statistically significant increase in the hispanic population was noted in february and march in all california hospitals (p= . and . , respectively) and pacific coast hospitals (p= . and . , respectively). the western region and all national hospitals noted a significant increase in strokes in the hispanic population in april (p= . and . , respectively). a statistically significant increase of strokes in the black population was noted in april in pacific hospitals, western region hospitals, and all national hospitals (p= . , . , and . , respectively). conclusion the covid- pandemic has adversely affected certain racial groups more than others. a similar increase is noted in patients presenting with strokes in these specific racial populations. moreover, lack of testing for the sars-cov- virus may be missing a possible link between racial disparity for patients infected with the virus and patients presenting with stroke. the authors advocate for widespread testing for all patients to further assess this correlation. the coronavirus disease pandemic, caused by the severe acute respiratory syndrome coronavirus (sars-cov- ), has affected many aspects of healthcare, including stroke care. significant racial disparities among populations affected by covid- have recently made headlines. some sources have also cited sars-cov- as a possible cause of stroke [ ] . nationally, hispanics and blacks are disproportionately represented among laboratory-confirmed covid- cases [ ] . as of june , age-adjusted covid- -associated hospitalization rates were highest among people who are non-hispanic american indian/alaska native, non-hispanic black, and hispanic/latino according to the covid- -associated hospitalization surveillance network (covid-net) [ ] . higher rates of covid- deaths were reported in counties with a high black population, especially in rural and small metro counties [ ] . this is not the first time in history that racial disparity has existed in medicine; surgeries on black women without anesthesia by dr. sims [ ] and the tuskegee syphilis study are two examples of racism and prejudice that have caused distrust towards the medical sciences among this population [ ] . there are no known unethical practices during the recent pandemic, however, this lingering mistrust can lead to delayed presentation in the setting of stroke and render black patients to be ineligible for receiving intravenous tissue plasminogen activator (iv-tpa) treatment [ ] . despite the national decline in the mortality rate from stroke, it remains the second leading cause of death in blacks [ ] . moreover, black individuals have been shown to have a higher mortality rate [ ] and a higher chance of experiencing disability [ ] following a stroke compared to whites. furthermore, the american heart association (aha) stroke council scientific oversight committee has reported a history of racial discrepancies in stroke risk factors, incidence, prevalence, and symptom recognition [ ] . given the recent pandemic and racial disparity among patients afflicted with sars-cov- and the possible link of this virus and cerebrovascular accidents (cva), we sought to analyze whether there was a disparity for stroke patients presenting to hospitals during this time using the get with the guidelines (gwtg) national stroke database. the primary endpoint of this study is to assess whether disparity exists at our own hospital. we also wanted to expand this scope to the regional and national levels to assess for any possible racial disparities. the gwtg stroke registry at our institution, a level primary stroke center certified by the healthcare facilities accreditation program, was retrospectively reviewed to assess the impact of the sars-cov- outbreak on the number of patients presenting with stroke to our hospital. demographics with regards to patients' race were collected. data were stratified by date and comparison was made between the covid- period (february -may ) and similar timeframe pre-covid- (february -may ). the months preceding the covid- period (october -janurary ) were avoided as a control as it is hard to know whether sars-cov- was propagating in the population during this time. the gwtg database was used to review records at our hospital, all california hospitals, west and pacific regions, and all hospitals nationally. patients presenting to these hospitals with a final diagnosis of ischemic stroke, transient ischemic attack (tia), subarachnoid hemorrhage (sah), or spontaneous/nontraumatic intraparenchymal hemorrhage (iph) were reviewed. after data was extracted from the database, the cohorts were stratified into five groups: (a) our hospital, (b) all california hospitals, (c) all pacific coast hospitals (alaska, washington, oregon, california, and hawaii), (d) all western hospitals (pacific plus montana, idaho, wyoming, nevada, utah, colorado, arizona, and new mexico), and (e) all hospitals in the united states that submit data to the registry. among these groups, the number and relative proportion of each reported race (white, black/african american, asian, native american, or hispanic) were reviewed each month during covid- and a similar time frame pre-covid- . proportions were chosen instead of volume of patients to limit any confounding decreases/changes in the number of patients in each time frame as recent data has suggested a decrease in total number of stroke patients presenting to the hospital during this time [ ] . the primary endpoint of this study is to compare whether there was a significant difference in the proportion of patients in each reported racial category presenting to our institution with stroke during the covid- pandemic caused by sars-cov- . the same analysis was conducted for the pacific hospitals, western hospitals, and all national hospitals. statistical analysis was performed using z-test to compare the proportions for all races for any significant difference month by month (i.e. february compared to february , march compared to march , etc.). there was an average of . patients per month in and patients per month in during the time frame studied at our hospital. this downward trend in compared to in total patients per month was echoed in all the groups studied (california, pacific, western region, and national). the total number of patients in each subgroup can be viewed in the appendix. to remove the confounding effect of decreased patient numbers, as this decrease became more evident on the regional and national levels (i.e. mean of , . patients nationally february through may versus , . patients during the same months in ) during the covid- months, the percentage of each race presenting to each hospital category was calculated (see appendix). looking at our hospital's local population, a significant difference in native hawaiian/pacific islander population was noted in february compared to (p= . ) but other racial cohorts remained similar ( table ) . data for asian and american indian or american native populations were insufficiently powered to perform statistical analysis. expanding the scope to include all california hospitals, a significant difference was noted again in the native hawaiian/pacific islander population in february compared to the prior year (p< . ). the hispanic population also showed a significant difference for the months of february and march (p= . and p= . , respectively). the remainder of racial cohorts in california remained stable during the studied time studied. racial disparities are well documented in all aspects of stroke as it relates to differences in stroke risk factors, incidence, prevalence, and symptom recognition in comparison to the white population [ ] . while disparity in stroke may partially be explained by geography [ ] , neighborhood socioeconomic status [ ] , or age [ ] , there is substantial evidence emphasizing racial predisposition to stroke. the first-stroke risk at age is . times higher in black individuals compared to white individuals, with black patients having higher rates of ischemic and hemorrhagic stroke [ ] . in one cohort study, black patients also had a % greater risk of recurrent stroke within two years compared to white patients, as well as higher prevalence of key vascular risk factors, including hypertension, diabetes mellitus, smoking, and high bmi [ ] . prevalence of underlying comorbidities and differences in leisure-time physical activity and diet may be contributing to the racial disparity among patients presenting with stroke prior to and during the covid- period. among patients hospitalized for covid- with data on underlying conditions, . % had at least one underlying condition according to the u.s. centers for disease control and prevention [ ] . these included preventable vascular risk factors related to poor diet and physical inactivity, such as hypertension, cardiovascular disease, obesity, and diabetes [ ] . relative to non-hispanic whites, blacks have historically been found to be less physically active [ ] and have poorer diets [ ] . this trend is consistent with the disproportionate increase in blacks presenting with stroke on a national level in march from the prior year. in contrast, hispanics have been found to have healthier diets than whites [ ] [ ] [ ] although poorer diets have been reported among those with high acculturation status [ ] . this interaction between acculturation status and dietary behavior may be contributing to the difference in trend seen among hispanic patients presenting with stroke at a regional versus national level. as of late june , age-adjusted covid- -associated hospitalization rates were highest among people who are non-hispanic american indian/alaska native, non-hispanic black, and hispanic/latino according to the covid- -associated hospitalization surveillance network (covid-net) [ it has previously been reported that covid- patients may present with ischemic stroke [ ] . influenza-like illnesses have also been linked to stroke [ ] . while yet to be proven, there are several proposals on how covid- may increase the risk of stroke. angiotensin converting enzyme (ace) ii receptor is a functional receptor and entry point for sars-cov and sars-cov- . involved in cardiovascular homeostasis, the receptor is expressed on several vital tissues, including vascular endothelium, arterial smooth muscle, and the brain [ ] . sars-cov infection appears to downregulate ace ii [ ] , which may contribute to increased stroke risk. cardiac embolism from virus-related cardiac injury [ ] , hypercoagulability exhibited by elevated d-dimer levels [ ] , and inflammatory reactions due to cytokine storm [ ] are other mechanisms in which covid- may lead to increased risk of stroke. stress from lockdowninduced isolation increases sympathetic release cytokines which affects the comorbidities of this end-organ disease. these factors amplify the effects of stroke in this population. furthermore, during the month of february , the data demonstrate an increase in the total number of patients presenting with strokes in all subgroups (appendix table ). given the possibility of sars-cov- causing vascular injury, this rise may be attributed to early stages of the covid- pandemic, i.e. sars-cov- was propagating in february in the united states possibly causing increase in stroke numbers. this rise in total numbers was then mitigated during the following months by the nationwide lockdowns and patient fears of contracting the infection. testing for sars-cov- was not being performed at this time, so this postulation is difficult to prove. moreover, given the possibility of carriers of this virus being asymptomatic from a respiratory standpoint, patients presenting with stroke may fall into this category. one major limitation of this study is the lack of widespread testing for sars-cov- . the cause for the increase in the number of strokes in february before lockdown measures is uncertain but given the virus was circulating during this time along with the vascular injury it causes make it a possible suspect. moreover, lack of widespread testing the months following also limits our ability to assess whether the increase in certain races being more adversely affected from the virus and increase in the number of strokes in the same ethic groups is related. thus, we hope to advocate for universal testing for sars-cov- for all patients presenting to the hospital to further isolate possible carriers who are asymptomatic from a respiratory standpoint. moreover, given the retrospective nature of this study, we are unable to retroactively implement these goals. the global covid- pandemic has had many devastating effects on not only our economy and lifestyles, but also our healthcare system. certain races are being more adversely affected than others from this virus due to the effects on the human physiology and the ability of the virus amplify the negative health effects of the comorbid conditions of stroke. the potential for this virus to cause strokes may be causing our observed increase in minority cerebrovascular accidents. increase in stroke numbers prior to lockdowns may be related to early propagation of the virus. further work is needed to assess this relationship as well as more widespread testing for sars-cov- to determine the true pathophysiology of this illness. human subjects: consent was obtained by all participants in this study. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. characteristics and outcomes of covid- patients in new york city's public hospital system coronavirus disease case surveillance -united states accessed assessing differential impacts of covid- on black communities the medical ethics of the "father of gynaecology disparities and distrust: the implications of 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incident ischemic stroke with risk factors trends and racial differences in first hospitalization for stroke and -day mortality in the us medicare population from to association of black race with recurrent stroke risk hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease nutrition and health are closely related - - dietary guidelines racial/ethnic disparities in exercise and dietary behaviors of middleaged and older adults racial/ethnic disparities in dietary intake of u.s. children participating in wic racial/ethnic disparities in us adolescents' dietary quality and its modification by weight-related factors and physical activity higher fat intake and lower fruit and vegetables intakes are associated with greater acculturation among mexicans living in washington state covid- presenting as stroke influenza-like illness as a trigger for ischemic stroke severe acute respiratory syndrome coronavirus infection and ischemic stroke sars-coronavirus modulation of myocardial ace expression and inflammation in patients with sars covid- and the heart neurologic manifestations of hospitalized patients with coronavirus disease in wuhan, china influence of covid- on cerebrovascular disease and its possible mechanism key: cord- -u gm kyh authors: baksh, mizba; ravat, virendrasinh; zaidi, annam; patel, rikinkumar s title: a systematic review of cases of acute respiratory distress syndrome in the coronavirus disease pandemic date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: u gm kyh the outbreak of coronavirus disease (covid- ) was declared a global pandemic after it spread to countries and has the highest total number of cases worldwide. about % of covid- infections are mild or asymptomatic and never require hospitalization but about % of patients become critically ill and develop acute respiratory distress syndrome (ards). the widely used management for ards in covid- has been in line with the standard approach, but the need to adjust the treatment protocols has been questioned based on the reports of higher mortality risk among those requiring mechanical ventilation. treatment options for this widespread disease are limited and there are no definitive therapies or vaccines until now. although some antimalarial and antiviral drugs may prove effective against severe acute respiratory syndrome coronavirus (sars-cov- ), their safety and efficacy are still under clinical trials. we conducted a systematic review of case reports on ards in sars-cov- infection to summarize the clinical presentation, laboratory and chest imaging findings, management protocols, and outcome of ards in covid- -positive patients. we need more data and established studies for the effective management of the novel sars-cov- and to reduce mortality in high-risk patients. an outbreak of a cluster of cases of pneumonia with an unknown cause was first reported in late december in wuhan in the hubei province of china. this respiratory illness during the coronavirus disease (covid- ) is caused by a novel severe acute respiratory syndrome coronavirus (sars-cov- ) [ ] . covid- was declared a global pandemic on january , , after it spread to countries, areas, or territories including the us, where the first case was reported on january , [ , ] . community transmission of covid- in the us was first reported in february that spread widely later on through close person-to-person contact via respiratory droplets, and through the infected surface to a person's eyes, nose, or mouth [ ] . as a result, active surveillance, contact tracing, quarantine, and strict social distancing were implemented worldwide to contain the transmission of the virus [ ] . the overall cumulative covid- incidence in the us was . cases per , population on april [ ] . sars-cov- is a positive single-strand enveloped ribonucleic acid (rna) virus that contains viral membrane e type glycoprotein that binds and enters sensitive cellular receptors by endophagocytosis in organ systems including epithelial cells in the respiratory tract [ ] . the novel beta coronavirus strain that causes covid- is in the same subgenus as the sars virus of the outbreak [ ] . there is only sporadic information on the pathophysiology of the disease at an early and evolving stage of the pandemic outbreak. in previous animal models and human studies on sars pathology, it is mentioned that the sars-cov protein binding to angiotensin-converting enzyme (ace ) could lead to acute lung injury through ace downregulation and angiotensin (at) a receptor stimulation [ , ] . animal studies found that elastase, a major protease induced in lung inflammation, might also be involved in sars pathogenesis [ , ] . clinical pathology of autopsy cases of sars helped in the significant understanding of the nature of the disease. the overall pathological changes in the lungs were of diffuse alveolar damage-causing ards [ ] . microscopic examination of pulmonary lesions revealed extensive bilateral consolidation, hemorrhagic infarction, desquamative pulmonary alveolitis and bronchitis, hyaline membrane formation, and viral inclusion bodies in alveolar epithelial cells [ ] . imaging findings range from no abnormalities to bilateral lung consolidation on chest radiographs or peripheral ground-glass opacities on ct scan [ ] . the included four case reports were published between february and april ; two of them were from china, one was from singapore, and one was from the us [ ] [ ] [ ] [ ] . a total of six patients with covid- were studied for the development of critical illness and/or ards. patients were adults with an age range of to years. the most common initial presentation of covid infection was a history of two to seven days of cough with or without fever, chills, dyspnea, and fatigue [ ] [ ] [ ] [ ] . one of the patients from iran was detected incidentally on a chest ct scan when he presented to the emergency room for follow-up of a two-weekold rib fracture from a fall with pain unresponsive to over-the-counter painkillers [ ] . the course and development of critical illness or ards were similar in most cases with the patient's condition deteriorating within - hours of initial presentation. most of them developed dyspnea and severe hypoxemia with declining oxygen saturation (sao ) during the second week of illness requiring oxygen supplementation or assisted ventilation. the patient who was diagnosed accidentally at early stages of infection was immediately treated with oseltamivir mg twice daily (bid) and hydroxychloroquine mg stat, based on the iranian interim guideline for "clinical management of covid- ", though the patient developed fever and dyspnea three days later [ ] . management was switched to a focused antiviral treatment regimen with oseltamivir mg and lopinavir/ritonavir / mg bid and the patient gradually improved attaining normal oxygen saturation without the need of intubation or supplemental oxygen [ ] . all six patients were tested positive for sars-cov- using the reverse rt-pcr assay of a respiratory specimen. in two of the six cases, a detailed laboratory investigation revealed lymphopenia and elevated c-reactive protein [ , ] . in one of the cases, flow cytometric analysis showed decreased peripheral cluster of differentiation (cd) cells and cd cells [ ] . liver and renal function tests showed an elevated aspartate transaminase/alanine transaminase ratio and lactate dehydrogenase levels, and lung biopsy showed bilateral ards [ , ] . three cases of critically ill, mechanically ventilated patients with ards required continuous monitoring of d-dimer and fibrinogen levels since it involved treatment with a fibrinolytic agent: tissue plasminogen activator (tpa) [ ] . chest x-ray and chest ct scan on admission showed predominant bi-basilar ground-glass opacities in all six patients [ ] [ ] [ ] [ ] . treatment modalities and clinical management options for covid- -induced ards were variable among these patients but mainly supportive and similar to standard ards management. infection control measures that included patient placement in isolation wards and standard contact and airborne precautions were pre-requisite. oxygen supplementation was a standard protocol for most patients who developed dyspnea and hypoxemia. antiviral therapy was tried in three of the six cases mentioned either as lopinavir/ritonavir mg bid or in combination with oseltamivir as / mg bid [ ] [ ] [ ] . one patient died of hypoxemia and sudden cardiac arrest (patient was on the do-not-resuscitate code status), but the other two showed marked improvement after receiving treatment [ ] [ ] [ ] . the other medication commonly used (in four of six cases) was hydroxychloroquine stat mg, in combination with either azithromycin or oseltamivir ( mg) [ , ] . empiric broad-spectrum antibiotics such as moxifloxacin were used in two mechanically ventilated patients to prevent secondary infection; however, one patient developed ventilator-associated pneumonia that necessitated the use of culture-guided antibiotics [ , ] . corticosteroids, such as intravenous methylprednisone, were administered in one patient to decrease lung inflammation [ ] . the study on tpa treatment for covid- -associated ards, which involved measuring the partial pressure of oxygen (pao )/fraction of inspired oxygen (fio ) ratio for oxygenation status, reported one out of three cases had % improvement post-tpa but the effect was transient [ ] . this case series also mentions the use of anticoagulants like heparin with tpa infusion to decrease the risk of bleeding [ ] . there are few in vivo studies on the use of plasminogen activators for the prevention of acute lung injury in animal studies, and so more trials are required to determine the optimal dosing and therapeutic effects of tpa [ , ] . vasopressors such as norepinephrine, phenylephrine, and vasopressin have been proved effective for hemodynamic support, sedation, and chemical paralysis [ ] [ ] [ ] . few studies have summarized the use of non-ventilatory interventions as rescue therapy in non-compliant patients with refractory hypoxemia [ , ] . a descriptive summary of all case reports that met our inclusion criteria is shown in table . demographics initial about % of patients with covid- have mild disease and never require hospitalization, and about % of patients become critically ill, with the risk of ards being highest in icu patients [ , ] . there could be a high risk of mortality (about two-thirds) in ventilated patients according to new data from the united kingdom's intensive care national audit and research center (icnarc), but this was unclear [ ] . other less frequent complications include acute cardiac injury, acute kidney injury, and septic shock, followed by multi-organ failure [ ] . of the six patients in our review, two died from complications within one to two weeks of clinical presentation [ , ] . the reported causes of death included cardiac arrest even after receiving invasive ventilation and chest compression and the other patient in wang et al.'s study died due to multi-organ failure with secondary bacterial infection [ , ] . the other four patients showed a good prognosis with no inpatient death. antiretroviral protease inhibitors, such as lopinavir/ritonavir, and antimalarials like hydroxychloroquine, for which us food and drug administration (fda) has issued an emergency use authorization (eua), were used in all studies but randomized clinical trials (rcts) to assess their efficacy and safety are still ongoing [ ] . sanders et al. suggested that remdesivir can be a promising therapy for covid- as it has already shown broad antiviral activity in both in vitro and in vivo studies against related viruses: middle east respiratory syndrome (mers)-cov and sars-cov [ ] . oseltamivir has no role in covid- treatment and corticosteroids that have been widely used in many patients in china may potentially prolong the course of illness by causing delayed viral clearance [ ] . antimalarial drugs like chloroquine or hydroxychloroquine monotherapy or combination therapy with azithromycin may prove effective, especially in severe disease, but these benefits need to be determined with rcts that are already underway [ , ] . so treatment options are limited and there are no definitive therapies or vaccines until now and additional studies are needed to evaluate their effectiveness [ ] . according to previous reports from china and new icnarc findings from england, mortality was higher among those requiring mechanical ventilation than those who did not and appears higher than that for patients treated in icu for other types of viral pneumonia [ , ] . the widely used management for ards in covid- has been in lines with the standard approach, but treatment protocols need to be adjusted according to the characteristics of disease pathophysiology, making more gradual positive endexpiratory pressure changes for the atypical type of ards seen with covid- [ ] . our systematic review of published cases of ards in covid- -positive patients will help healthcare professionals to clearly understand and implement updated treatment strategies and confront the covid- pandemic and its medical consequences. nonetheless, we need more rcts and treatment guidelines for developing effective management of the novel sars-cov- and thus improve survival and reduce mortality in high-risk and critical patients. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have 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