key: cord-1031598-0acqouj5
authors: Long, Brit; Carius, Brandon M.; Liang, Stephen Y.; Chavez, Summer; Brady, William J.; Koyfman, Alex; Gottlieb, Michael
title: Clinical update on COVID-19 for the emergency clinician: Presentation and evaluation
date: 2022-01-21
journal: Am J Emerg Med
DOI: 10.1016/j.ajem.2022.01.028
sha: b59a6b15a495aa4798d3064ef5ad38f287699a16
doc_id: 1031598
cord_uid: 0acqouj5

INTRODUCTION: Coronavirus disease of 2019 (COVID-19) has resulted in millions of cases worldwide. As the pandemic has progressed, the understanding of this disease has evolved. OBJECTIVE: This first in a two-part series on COVID-19 updates provides a focused overview of the presentation and evaluation of COVID-19 for emergency clinicians. DISCUSSION: COVID-19, caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), has resulted in significant morbidity and mortality worldwide. Several variants exist, including a variant of concern known as Delta (B.1.617.2 lineage) and the Omicron variant (B.1.1.529 lineage). The Delta variant is associated with higher infectivity and poor patient outcomes, and the Omicron variant has resulted in a significant increase in infections. While over 80% of patients experience mild symptoms, a significant proportion can be critically ill, including those who are older and those with comorbidities. Upper respiratory symptoms, fever, and changes in taste/smell remain the most common presenting symptoms. Extrapulmonary complications are numerous and may be severe, including the cardiovascular, neurologic, gastrointestinal, and dermatologic systems. Emergency department evaluation includes focused testing for COVID-19 and assessment of end-organ injury. Imaging may include chest radiography, computed tomography, or ultrasound. Several risk scores may assist in prognostication, including the 4C (Coronavirus Clinical Characterisation Consortium) score, quick COVID Severity Index (qCSI), NEWS2, and the PRIEST score, but these should only supplement and not replace clinical judgment. CONCLUSION: This review provides a focused update of the presentation and evaluation of COVID-19 for emergency clinicians.

. Data are controversial whether the Omicron variant is associated with reduced disease severity (43) (44) (45) . Several reports announced a decrease in disease severity, with one finding a 29% reduction in hospitalization rate in those infected with the Omicron variant (43) (44) (45) . A report released on December 22, 2021, found a 20-25% reduced risk of any hospitalization and 40-45% reduced risk of multiday hospitalization (45) . Further studies are underway evaluating vaccine efficacy and the risk of severe disease associated with the Omicron variant.

COVID-19 infection is generally divided into symptomatic and asymptomatic, with symptomatic cases further categorized as critical, severe, and non-severe (2,46) ( Table 2 ). The majority of patients have mild disease (over 80%) (2,3,46-48-33) . Clinically asymptomatic infection rates may approximate 33% of those testing positive for COVID-19 based on one meta-analysis, but this number varies (20, 47, 48) . However, literature suggests severe disease (defined as hypoxia or > 50% lung involvement) can occur in over 15% of patients and critical disease (consisting of respiratory failure, multiorgan injury, or shock) in up to 5%, though this depends on the patient population (1) (2) (3) 26, 48, 49) . More recently a third category of pre-symptomatic proposes that as many as half of these persons who do not declare symptoms at the time of positive testing develop symptoms later (47, 50, 51) . Table 2 . COVID Severity Classifications (2, 46) .

Reported rates of hospitalization, mechanical ventilation, and mortality vary significantly due to several variables including patient age, healthcare and testing availability, and containment J o u r n a l P r e -p r o o f measures, among others. Initial studies suggested high rates of hospitalization and mortality, but with current therapies and vaccination, risks of hospitalization, mechanical ventilation, and mortality have declined (1, 2, 20, (52) (53) (54) (55) (56) (57) (58) (59) (60) (61) (62) (63) (64) (65) (66) (67) . Early in the pandemic, overall mortality rates for admitted patients reached 20%, but in those admitted to the ICU, mortality approximated 40% (1, 2, 20, (52) (53) (54) (55) (56) (57) (58) (59) (60) (61) (62) (63) (64) (65) (66) (67) . As the pandemic has progressed, ICU survival rates have improved from 58% to 80% (62) . Of those hospitalized with COVID-19, up to 35% require admission to an ICU (20, 48, 52) . More recent literature suggests the case fatality rate is under 2% in all patients with COVID-19, though this depends on age (20, 48, 57) . In those over age 60 years this rises to 6.4%, in those over age 80 years it is over 13%, and in those over age 90 years mortality is over 25% (57) .

Several factors are associated with worse prognosis in patients with COVID-19. Risk factors for severe disease include age > 75 years, diabetes, cancer, history of transplant, hypertension, and prior cardiac or pulmonary disease (23, 26, 52, (63) (64) (65) (66) (67) . Obesity is associated with increased mortality and need for intubation, independent of other factors including race, sex, and other comorbidities, especially in patients less than 65 years of age (68, 69) . One study suggested mortality was four-fold higher in patients with a body mass index (BMI) > 45 (69) . Heart failure is associated with longer hospital length of stay, increased need for intubation and ventilation, and mortality (70) . Unfortunately, the Delta variant is also associated with worse outcomes, including need for hospitalization, ICU admission, and mortality (33, 71) . Other poor prognostic factors include an initial oxygen saturation < 88%, lymphopenia, thrombocytopenia, acute kidney injury, elevated lactate dehydrogenase, C-reactive protein (CRP) > 200 mg/L, D-dimer > 2500 ng/mL, elevated troponin, and ferritin > 2500 ng/mL (23, 26, 52, 63) . J o u r n a l P r e -p r o o f

Approximately 98% of patients who develop symptoms will do so within 12 days of viral exposure (3, 20) . Although symptomatic COVID-19 patients exhibit a variety of signs and symptoms, most present with fever, changes in taste and/or smell, myalgias, and respiratory tract symptoms such as cough (1) (2) (3) 20, 52, (72) (73) (74) (75) (76) . However, there are no clinical features with high enough specificity to reliably differentiate COVID-19 from other infections for diagnosis (75) .

Literature suggests that the most common symptoms include cough (60-86%), shortness of breath (53-80%), and change in taste or smell disturbance (64-80%) (72) (73) (74) (75) (76) . Fever can be present in approximately half of patients at the time of initial presentation depending on the study, but overall, literature suggests 20-99% of patients experience fever during the course of the disease (1, 2, 18, 23, 49, 53, 72) . Literature varies on the definition of fever, with temperature thresholds as low as 37.1C (75, 77, 78) . Viral pneumonia, hypoxemic respiratory failure, and acute respiratory distress syndrome (ARDS) may result from COVID-19, with hypoxemic respiratory failure the most common reason for ICU admission (1) (2) (3) 20, 23, 60, 74, 75) . Bacterial or fungal co-infections affect up to 8% of patients (79) . These are a major source of morbidity and mortality; in one study, half of those who died experienced a secondary infection (23, 80, 81) . Bacterial respiratory infections most commonly include Streptococcus pneumoniae, Klebsiella pneumoniae, and Haemophilus influenzae, though other infections such as pulmonary aspergillosis and mucormycosis may also occur (80) (81) (82) (83) (84) (85) (86) (87) . Mucormycosis has primarily been documented in India, with diabetes and steroid treatment the most common risk factors (84) (85) (86) (87) . Concurrent viral infections are also common, J o u r n a l P r e -p r o o f with one study finding 20.7% of patients with COVID-19 infected with at least one other virus (82) .

As the pandemic has progressed, a variety of extrapulmonary effects have been uncovered.

Myocardial disease, manifested by dysrhythmias, acute coronary syndrome (ACS), heart failure, and myocarditis (22,88-90-76) , occur in over 20% of patients admitted to the ICU with COVID-19 (22) . Dysrhythmias include AV blocks, bradycardia, and supraventricular and ventricular tachycardias (22, (88) (89) (90) . Torsades de pointes may occur due to QT prolongation. The QT interval can be prolonged due to electrolyte changes (diarrhea, dehydration), systemic inflammation, and comorbidities (preexisting cardiac disease) (88, 91, 92) . ACS is likely associated with severe inflammation (88) (89) (90) (91) (92) (93) (94) (95) (96) . This may result in plaque rupture and ST elevation myocardial infarction (93) (94) (95) . Cardiomyopathy, heart failure, and myocarditis can also occur, with acute left heart failure occurring in 23% of patients (23, 88, 90, 92) . Left heart failure is associated with increased mortality and was present in 52% of those who died in one study (23) . Right heart failure is more likely associated with lung injury and ARDS, as well as the hyperinflammatory state, thrombotic events, and viral damage (96, 97) . Literature suggests right ventricular dilation occurs in 20-31% of cases (96, 97) . Myocarditis is more likely in those with heart failure or shock who have no prior history of cardiac disease (88, 90) . Myocarditis was the cause of death in 7% of patients and contributed to one third of deaths in one study (23) . However, cardiac involvement is likely more common than originally thought. One study of patients with mild to moderate COVID-19 who underwent cardiac magnetic resonance imaging found abnormal findings in 78%, most J o u r n a l P r e -p r o o f commonly cardiac inflammation (98) , and a second study found 56% of patients had cardiac inflammation and edema (99) . Other studies suggest cardiac involvement is present even in patients with minimal or no symptoms (100) .

Neurologic effects associated with the disease vary, ranging from mild illness to severe manifestations such as stroke. Up to 80% of patients experience neurologic symptoms during the course of the disease (101) . Mild symptoms such as headache and dizziness affect up to 40% of patients during acute illness, which may increase as the illness progresses (101) (102) (103) . Changes in smell and taste are common. This may be the first symptom in approximately one-third of patients (102, 103) . Up to 80% of patients will experience a change in taste or smell during the course of illness, and almost half will have complete loss of taste or smell (72, 75, 103, 104) .

Literature suggests severe neurologic complications occur in a significant number of patients with COVID-19, including seizure, encephalopathy, and cerebral ischemia (105) . Mental status changes due to encephalopathy are more common in older patients with COVID-19 and associated with worse outcomes (101, 105) , with delirium occurring in up to 55% of critically ill patients with COVID-19 (106) . Meningoencephalitis may occur due to direct central nervous system (CNS) invasion or systemic inflammation due to COVID-19. Immune-mediated complications such as Guillain-Barre Syndrome and myasthenia gravis have been reported (107) .

Cerebral ischemia due to stroke may occur in up to 6% of critically ill patients with COVID-19 and can present as small or large vessel occlusion; however, the risk of cerebrovascular accident (CVA) is less than 1% in other populations with COVID-19 (108) (109) (110) . CVA most commonly occurs in the first several weeks after symptom development (108) (109) (110) . While rare, cerebral J o u r n a l P r e -p r o o f venous thrombosis has also been documented and is associated with high mortality rate in COVID-19 (111, 112) . These patients can present with headache, seizure, focal neurologic deficit, or altered mental status. Acute disseminated encephalomyelitis and posterior reversible encephalopathy syndrome have also been reported. Finally, patients are at risk of psychiatric complications such as mood disorders, anxiety, insomnia, and psychotic disorders (103) .

Gastrointestinal (GI) symptoms are common, with up to one-third of patients with COVID-19

presenting first with GI symptoms (24, 114, 115) . Nausea and vomiting may be present in up to two-thirds of patients with COVID-19 (115) . Approximately 40% of patients with COVID-19

will have loss of appetite, and up to 50% will have diarrhea (24, 115) . Abdominal pain is less common, occurring in less than 10% (24, 115) . In critically ill patients, acute liver injury, cholecystitis, pancreatitis, ileus, pseudo-obstruction, and mesenteric ischemia may occur (116) .

Dermatologic manifestations of COVID-19 occur in 0.4-20% of cases but are often non-specific consisting of erythema or urticaria-like lesions on the trunk or, less frequently, the extremities (74, (117) (118) (119) (120) (121) . Similarly, small case series and reports describe livedo reticularis, vesicular eruptions, maculopapular lesions, and areas of thickened erythema resembling chilblains (117) (118) (119) (120) (121) . New pernio-like lesions are also suggestive of COVID-19 (74, 118) .

J o u r n a l P r e -p r o o f Hematologic issues including thrombotic complications are common in critically ill patients with COVID-19. This risk is thought to be associated with systemic inflammation (122) (123) (124) (125) (126) (127) (128) (129) (130) (131) (132) . Initial studies suggested patients with COVID-19 were at a high risk of venous thromboembolic event (VTE), with rates of VTE reaching 31% in critically ill patients (122, (124) (125) (126) . More recent studies have found that the overall risk of VTE, including pulmonary embolism (PE), in patients with COVID-19, no matter the severity of illness, is lower than initially suspected (< 1%), though the risk remains higher than the general non-COVID-19 population (132) . A second international study found COVID-19 was not an independent risk factor for PE, with 15% in the pandemic era and 15% of patients in the prepandemic era experiencing PE (132) . Routine evaluation for PE in all COVID-19 patients is not recommended (132) . Evaluation for PE should be considered in patients with other risk factors for PE; those with hypoxia, tachycardia, or hypotension out of proportion to clinical evaluation; sudden decompensation; or those whose symptoms are not explained by chest radiograph. significantly improved with nasal vestibular and middle turbinate swabs or the use of saliva (133) (134) (135) (136) (137) (138) (139) (140) . Sensitivity may approach 100% when there is 500-5000 viral RNA/mL (135) .

However, timing of testing can have significant impact on RT-PCR test characteristics, with the highest sensitivity at 2-3 days after symptom onset and the lowest sensitivity immediately after exposure (20, 138) .

Although RT-PCR can be performed in a condensed timeline, the sheer volume of tests performed in major centers has prompted examination of shorter-turnaround point-of-care testing, such as rapid SARS-CoV-2 antigen (Ag) testing to detect viral proteins. This process utilizes a nasal turbinate swab with a simple qualitative indicator when reagent is applied, with results available in approximately 15 minutes compared to the 60-120 minutes required for NAAT (140) (141) (142) (143) (144) (145) . Despite generally high specificity, SARS-CoV-2 Ag testing demonstrates highly variable sensitivity (31-93%), likely due to varying viral loads, and it has less sensitivity at lower viral loads (20, 133, 137, (140) (141) (142) (143) (144) (145) . Most SARS-Cov-2 Ag tests demonstrate higher sensitivities with a lower cycle threshold (Ct), which describes the number of PCR cycles required to detect the virus (141) (142) (143) (144) . SARS-CoV-2 Ag tests demonstrate higher sensitivities for those with a PCR Ct of <25, compared to those with higher Ct values (133, 137, (140) (141) (142) (143) (144) (145) . Due to this variability, SARS-CoV-2 Ag testing can be considered for rapidly screening patients who appear highly symptomatic with suspected or confirmed exposure. Current society guidelines recommend that SARS-CoV-2 Ag testing be employed in isolation only when NAAT is not available, or as screening for patients in conjunction with NAAT for definitive diagnosis ( Figure   1 ) (20, 140, 143) . Limited evaluation of SARS-CoV-2 Ag tests against Omicron variant infections J o u r n a l P r e -p r o o f do not demonstrate a significant decrease in overall sensitivity for symptomatic individuals (146, 147) . 

Patients with normal vital signs who appear well do not require laboratory assessment other than SARS-CoV-2 testing. However, additional laboratory testing can assist with risk stratification in determining the need for admission (1) (2) (3) 20) . A complete blood count (CBC) can provide several markers of interest. For example, the CBC may reveal lymphopenia (absolute lymphocyte count <1.0 x 10 9 /L), which can be found in up to half of patients overall and 83% of hospitalized patients, portending an increased risk for the combined outcome of severe disease course and mortality compared to those with normal levels (76% vs. 26%, p < 0.001) (20, 38, (148) (149) (150) (151) (152) (153) (154) (155) .

Lymphopenia tends to worsen with the severity of COVID-19 symptoms and is associated with an increased risk for respiratory failure (odds ratio [OR] 2.69, p < 0.001) (152) (153) (154) (155) . Total leukocyte counts are variable but generally remain within a normal range of 4-10 x 10 9 /L, though median values for more severe patients are more commonly below this lower limit at 3.7-3.9 x 10 9 /L (18, 20, 151, 155) . Mild thrombocytopenia (platelet count < 150 x 10 9 /L) is seen in 12-33% of patients overall, with a higher proportion found in those with more severe illness (57.7% vs. 31.6%) (18, 20, 149, 151, 153, 155) .

Chemistry and liver function testing can be obtained to evaluate for organ injury and other complications in COVID-19 patients. Serum creatinine has been found to be elevated in less than 10% of patients, although one study found elevated creatinine in 28.8% of patients (18, (154) (155) (156) (157) (158) (159) .

Common electrolyte derangements found in COVID-19 include hyponatremia (20.4-50%) and hypokalemia (15.1-62%), with most exhibiting mild depletion (Na 130-135 mmol/L, K 3.0-3.5 mmol/L) (53, (156) (157) (158) (159) . Lower sodium levels have been associated with more severe illness (139 mmol/L vs. 136 mmol/L, p < 0.0001) (53, 157, 160) . Those with severe hypokalemia (< 3 mmol/L) are also more likely to have severe COVID-19 (p < 0.001) (157, 158) . Hyperglycemia is found in approximately half of patients, and in patients with diabetes, a venous blood gas panel should be considered to evaluate for COVID-19-triggered diabetic ketoacidosis (153, 161, 162) .

Lactate dehydrogenase (LDH) is elevated (>250 U/L) in 27-92% of COVID-19 patients (18, 20, 149, (151) (152) (153) (154) (155) .

Liver function tests demonstrate statistically significant elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in 10-28% and 9-36% of patients overall, respectively; however, at this time the clinical significance of this is not well established (20, 148, 153, 155) . Scattered case reports suggest COVID-19 can present as acute hepatitis, while small studies show elevated AST and ALT in COVID-19 with preexisting hepatitis B infection (163, 164) . However, there is no clear correlation at this time.

As in most inflammatory processes, inflammatory markers including CRP and erythrocyte sedimentation rate (ESR) tend to be elevated in COVID-19. This includes significant CRP elevation (≥10 mg/L) in 46-99% COVID-19 patients (18, 20, 53, 149, 155) . ESR is elevated (> 15 J o u r n a l P r e -p r o o f mm/h) in 24-96% of patients, albeit with less supporting studies relative to CRP (53, 149, 153, 155) . CRP ≥10 mg/L demonstrates increased risk of respiratory failure (OR 5.91) and thrombotic events (OR 2.7) in COVID-19 patients, while ESR > 40 mm/h shows similar association with thrombosis (OR 2.64) in isolated studies (127, 151, 152) .

Potential thrombotic complications may prompt evaluation for fibrinogen and coagulation studies, with serum D-dimer often elevated. While studies vary on D-dimer levels to define elevation, 46% of COVID-19 patients demonstrate levels > 0.5 mg/L and 36% have levels > 1.5 mg/L (20, 127, 149, 153, 165) . The predictive ability of elevated D-dimer for thrombotic events in these patients increases proportionally to the elevation, with increasing risk from 1-2.5 mg/L (OR 1.75) to >2.5 mg/L (OR 4.40), 5-10 mg/L (OR 5.55) and ≥10 mg/L (OR 7.09) (127) (128) (129) (130) .

The degree of D-dimer elevation is also associated with severity of illness, with higher levels associated with more severe disease (155) . Less often, prolonged prothrombin (PT) and activated partial thromboplastin (aPTT) times are found in approximately 5-11% and 6-26% of patients, respectively, without significant correlation between abnormal levels and illness severity or bleeding complications (20, 53, 119, 120, 153, 155) .

Chest radiography is generally employed for initial evaluation of COVID-19 patients with respiratory symptoms, although studies reveal significant variation in the frequency of their findings (1) (2) (3) 18, (166) (167) (168) (169) (170) (171) (172) . A normal chest X-ray (CXR) may be found in a significant proportion of patients with COVID-19 (5.6-53.6%), with 10.9% later progressing to abnormal findings on subsequent plain films (18, (166) (167) (168) (169) (170) (171) (172) . The most common abnormal CXR findings include J o u r n a l P r e -p r o o f peripheral consolidations (5.3-88.9%) or ground glass opacities (14.1-63.1%), with the latter described as hazy increased attenuation with reticular consolidation (166) (167) (168) (169) (170) (171) (172) (Figure 2 ).

Patients most commonly have bilateral lung involvement (up to 76%) (166) (167) (168) (169) (170) (171) (172) . Computed tomography (CT) of the chest without contrast demonstrates improved sensitivity for detecting lung abnormalities (pooled sensitivity 87.9% to 90.6%) and should be considered in COVID-19 patients with severe respiratory symptoms despite unremarkable CXR (166, 169, (171) (172) (173) (174) (Figure   3 ). Up to 10% of patients can have a normal CT. A classification system has been proposed with 4 stages (173, 174) . Stage 1 includes ground glass appearance (days 0-4), stage 2 is an increased crazy-paving pattern (days 5-8), stage 3 consists of consolidation (days 9-13), and stage 4 is gradual resolution (days ≥14) (174) . (175) (176) (177) (178) (179) (180) (181) (182) (183) . B-line progression with enhanced consolidation suggests increasing disease severity and should raise concern for a potential need for enhanced respiratory support (176, 177, 179) . 

Over 20 prognostic scoring systems have been created for COVID-19. This review will not discuss all of these scores. Many of these scoring tools are a combination of clinical, laboratory, and imaging findings (184) (185) (186) (187) (188) (189) (190) (191) (192) (193) (194) , and unfortunately, many of these have proven unreliable in the clinical setting. These scores are primarily derived from homogenous, small populations of patients, and many lack extensive validation or are too complex for clinical use (184, 185) .

However, several demonstrate utility when used appropriately. When utilized, these scores should supplement clinical decision making, but they cannot replace clinical judgment (194) .

One of the most robust and validated scores to predict mortality in patients with COVID-19 is the 4C (Coronavirus Clinical Characterisation Consortium) score. The 4C score has been validated in several settings in over 57,000 patients and considers age, sex, comorbidities, respiratory rate, oxygen saturation on room air, Glasgow Coma Scale, blood urea nitrogen, and CRP (Table 3 ) (186, 187) . The derivation receiver-operator characteristic (ROC) curve was 0.79, J o u r n a l P r e -p r o o f with 0.77 in the validation cohort (ROC 0.5 suggests no discrimination, 0.7-0.8 suggests an acceptable level of discrimination, and greater than 0.8 is considered excellent) (186, 187) . Table 3 . 4C Score.

The quick COVID Severity Index (qCSI) is an effective physiological risk score that can be used at the bedside. It was initially created to determine risk of progressing to respiratory failure and critical illness within 24 hours of hospital admission and is comprised of respiratory rate, pulse oximetry, and supplemental oxygen flow rate (Table 4 ) (188) . The initial ROC curve was 0.81, with other studies suggesting the score may be similar to the NEWS score and outperform other risk scores such as 4C and CURB-65 (188, 189) . NEWS2 is another physiologic score comprised of respiratory rate, saturation, systolic blood pressure, pulse, consciousness, and temperature (190) (191) (192) (Table 5 ). This score demonstrates area under receiver operating characteristic (AUROC) curves of 0.78 for determining who will deteriorate over 24 hours and for in-hospital mortality (192) . The PRIEST score, comprised of respiratory rate, oxygen saturation, heart rate, systolic blood pressure, temperature, alertness, inspired oxygen, sex, age, and performance status, reported a c-J o u r n a l P r e -p r o o f statistic of 0.80, with a score > 4 demonstrating a 98% sensitivity and 34% specificity to predict adverse events (193) (Table 6 ). Table 6 . PRIEST score. Several risk scores may assist in prognostication. Attributes of variant of concern None as of December 311, 2021

Evidence of more severe infection, increased hospitalization, decreased vaccine and treatment efficacy, failure of diagnostics Table 2 . COVID Severity Classifications (2, 46) .

Critical Acute respiratory distress syndrome, sepsis, septic shock, or other conditions requiring life-sustaining therapies (mechanical ventilation or vasopressor therapy)

Oxygen saturation < 90%, signs of severe respiratory distress (accessory muscle use, unable to speak in full sentences)

Non-severe Any patient not meeting criteria for critical or severe Table 3 . 4C Score.

Age in years J o u r n a l P r e -p r o o f

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Diagnosing COVID-19 in the Emergency Department: A Scoping Review of Clinical Examinations, Laboratory Tests, Imaging Accuracy, and Biases

Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease. Cochrane Database Syst Rev

Acute Olfactory Loss Is Specific for COVID-19 at the Emergency Department

Body temperature screening to identify SARS-CoV-2 infected young adult travellers is ineffective

A novel artificial intelligence-assisted triage tool to aid in the diagnosis of suspected COVID-19 pneumonia cases in fever clinics

Bacterial and Fungal Coinfection in Individuals With Coronavirus: A Rapid Review To Support COVID-19 Antimicrobial Prescribing

Bacterial and fungal infections in COVID-19 patients: A matter of concern

Co-infection with respiratory pathogens among COVID-2019 cases

Rates of Co-infection Between SARS-CoV-2 and Other Respiratory Pathogens

COVID-19 associated with pulmonary aspergillosis: A literature review

The impact of COVID-19 outbreak on the incidence of acute invasive fungal rhinosinusitis

Guidelines for the Diagnosis, Staging and Management of Rhino-Orbito-Cerebral Mucormycosis in the Setting of COVID-19

Invasive Fungal Sinusitis in Post COVID-19 Patients: A New Clinical Entity

Mucor in a Viral Land: A Tale of Two Pathogens

Cardiovascular complications in COVID-19

Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19) [published correction appears in JAMA Cardiol

Potential Effects of Coronaviruses on the Cardiovascular System: A Review

COVID-19, Arrhythmic Risk, and Inflammation: Mind the Gap!

Approach to Acute Cardiovascular Complications in COVID-19 Infection

Management of Acute Myocardial Infarction During the COVID-19 Pandemic: A Position Statement From the Society for Cardiovascular Angiography and Interventions (SCAI), the American College of Cardiology (ACC), and the American College of Emergency Physicians (ACEP)

Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic

ST-Elevation Myocardial Infarction in Patients With COVID-19: Clinical and Angiographic Outcomes

Spectrum of Cardiac Manifestations in COVID-19: A Systematic Echocardiographic Study

Right Ventricular Dilation in Hospitalized Patients With COVID-19 Infection

Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19) [published correction appears in JAMA Cardiol

Cardiac Involvement in Patients Recovered From COVID-2019 Identified Using Magnetic Resonance Imaging

Cardiovascular Magnetic Resonance Findings in Competitive Athletes Recovering From COVID-19 Infection

Frequent neurologic manifestations and encephalopathy-associated morbidity in Covid-19 patients

Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study

Acute-onset smell and taste disorders in the context of COVID-19: a pilot multicentre polymerase chain reaction based case-control study

The Prevalence of Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis. Otolaryngol Head Neck Surg

A Prospective Study of Neurologic Disorders in Hospitalized Patients With COVID-19 in New York City

COVID-19 Intensive Care International Study Group. Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study

Guillain-Barré Syndrome Associated with SARS-CoV-2

Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: a retrospective case series study. medRxiv. Preprint posted online

Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young

Temporary Emergency Guidance to US Stroke Centers During the Coronavirus Disease 2019 (COVID-19) Pandemic: On Behalf of the American Heart Association/American Stroke Association Stroke Council Leadership

Cerebral Venous Thrombosis in COVID-19: A New York Metropolitan Cohort Study

Cerebral Venous Thrombosis in Patients with COVID-19 Infection: a Case Series and Systematic Review

6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records

COVID-19 gastrointestinal manifestations: a systematic review

Review article: gastrointestinal features in COVID-19 and the possibility of faecal transmission

Gastrointestinal Complications in Critically Ill Patients With COVID-19

Cutaneous manifestations in COVID-19: a first perspective

Dermatologic manifestations and complications of COVID-19

Cutaneous manifestations in COVID-19: the experiences of Barcelona and Rome

Cutaneous, skin histopathological manifestations and relationship to COVID-19 infection patients

Characterization of acute acral skin lesions in nonhospitalized patients: A case series of 132 patients during the COVID-19 outbreak

COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review

Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia

Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia

Incidence of thrombotic complications in critically ill ICU patients with COVID-19

Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study

COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection

Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System

Thrombotic complications in 2928 patients with COVID-19 treated in intensive care: a systematic review

Thrombotic and haemorrhagic complications in critically ill patients with COVID-19: a multicentre observational study

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The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Molecular Diagnostic Testing

How good are COVID-19 diagnostic PCR tests? College of American Pathologists

Stability issues of RT-PCR testing of SARS-CoV-2 for hospitalized patients clinically diagnosed with COVID-19

Comparison of Rapid Antigen Tests for COVID-19

Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure

Diagnostic Accuracy of Rapid Antigen Test Kits for Detecting SARS-CoV-2: A Systematic Review and Meta-Analysis of 17,171 Suspected COVID-19 Patients

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Performance of a Point-of-Care Test for the Rapid Detection of SARS-CoV-2

Real-world clinical performance of commercial SARS-CoV-2 rapid antigen tests in suspected COVID-19: A systematic meta-analysis of available data as of

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Assessment of the analytical sensitivity of ten lateral flow devices against the SARS-CoV-2 omicron variant

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Laboratory findings of COVID-19: a systematic review and meta-analysis

Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study [published correction appears in Signal Transduct Target Ther

Usefulness of Easy-to-Use Risk Scoring Systems Rated in the Emergency Department to Predict Major Adverse Outcomes in Hospitalized COVID-19 Patients

Development and validation of a prediction model for severe respiratory failure in hospitalized patients with SARS-CoV-2 infection: a multicentre cohort study (PREDI-CO study)

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical Characteristics and Outcome of Patients with Suspected COVID-19 in Emergency Department (RESILIENCY Study II)

Laboratory findings in COVID-19 diagnosis and prognosis

Electrolyte imbalance in COVID-19 patients admitted to the Emergency Department: a case-control study

Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19)

Assessment of Hypokalemia and Clinical Characteristics in Patients With Coronavirus Disease

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COVID-19 and Diabetic Ketoacidosis: A Single Center Experience

Diabetic ketoacidosis precipitated by COVID-19: A report of two cases and review of literature

COVID-19 Presenting as Acute Hepatitis

Clinical characteristics of COVID-19 patients with hepatitis B virus infection -a retrospective study

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

Frequency and Distribution of Chest Radiographic Findings in Patients Positive for COVID-19

Chest X-ray in new Coronavirus Disease 2019 (COVID-19) infection: findings and correlation with clinical outcome

Radiographic findings in 240 patients with COVID-19 pneumonia: time-dependence after the onset of symptoms

Systematic review and meta-analysis of chest radiograph (CXR) findings in COVID-19

Portable chest X-ray in coronavirus disease-19 (COVID-19): A pictorial review

Diagnostic accuracy of X-ray versus CT in COVID-19: a propensity-matched database study

Thoracic imaging tests for the diagnosis of COVID-19

Time Course of Lung Changes at Chest CT during Recovery from Coronavirus Disease 2019 (COVID-19)

Lung Ultrasonography for the Diagnosis of SARS-CoV-2 Pneumonia in the Emergency Department

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Point-of-care lung ultrasound in intensive care during the COVID-19 pandemic

A preliminary study on the ultrasonic manifestations of peripulmonary lesions of non-critical Novel Coronavirus Pneumonia (COVID-19). SSRN. Preprint posted online

Point-of-Care Lung Ultrasound findings in novel coronavirus disease-19 pneumoniae: a case report and potential applications during COVID-19 outbreak

Chinese Critical Care Ultrasound Study Group (CCUSG). Findings of lung ultrasonography of novel coronavirus pneumonia during the 2019-2020 epidemic

Can Lung US Help Critical Care Clinicians in the Early Diagnosis of Novel Coronavirus (COVID-19) Pneumonia?

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Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19

Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score

GEMELLI AGAINST

Predicting In-Hospital Mortality in COVID-19 Older Patients with Specifically Developed Scores

Development and Validation of the Quick COVID-19 Severity Index: A Prognostic Tool for Early Clinical Decompensation

Performance of the quick COVID-19 severity index and the Brescia-COVID respiratory severity scale in hospitalized patients with COVID-19 in a community hospital setting

Predictive value of National Early Warning Score 2 (NEWS2) for intensive care unit admission in patients with SARS-CoV-2 infection

National Early Warning Score 2 (NEWS2) on admission predicts severe disease and in-hospital mortality from Covid-19 -a prospective cohort study

Systematic evaluation and external validation of 22 prognostic models among hospitalised adults with COVID-19: an observational cohort study

Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19: The PRIEST observational cohort study

Evaluation of the Risk Prediction Tools for Patients With Coronavirus Disease 2019 in Wuhan, China: A Single-Centered, Retrospective, Observational Study

All authors conceived the idea for this manuscript and contributed substantially to the writing and editing of the review. This manuscript did not utilize any grants, and it has not been presented in abstract form. This clinical review has not been published, it is not under consideration for publication elsewhere, its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder.