cord-253312-bf35afpj	2020	
cord-253468-pf0xubii	2020	title: Ketonuria with or without ketoacidosis as the presenting manifestation of SARS-CoV-2 (COVID-19) among uncontrolled Type 2 Diabetic patients We hereby present the data of 3 patients presented to our OPD and were admitted as diabetic ketoacidosis (DKA) and 2-3 days later they developed manifestations suggestive of and proved by swabbing as positive cases. Chest auscultation and chest X ray were unremarkable and hence chest CT scan was requested ( Figure 1 ) and showed picture suggestive of mild-moderate COVID-19, swabbing was done and came positive Case 2: A 51-year-old male, presented by dizziness over last 2-3 days and when examined found to have high RBS and ketonuria, and hence admitted as KDA, and was acidotic (PH 7). A 62-year-old male patient who was not compliant with his medicines over the last 2 months, presented for renewal of medicine without any clinical manifestations, found to have panic RBS measurement, and was positive for urine ketones.
cord-254094-ed1epul1	2020	In particular, we refer to the TMPRSS2 expression profile, balance of androgen and estrogen, blood group-A and/or B, nonsynonymous mutations in ORF3, and proteins NS7b and NS8 in SARS-CoV-2. In the first months of the COVID-19 pandemic, most authors focused their attention on features such as the high expression of ACE2 in the salivary glands in asymptomatic infection [4] , and the maturity and binding capacity of ACE2 [5, 6] . A higher 2D:4D ratio is associated with COVID-19 severity in men [14] , this means that sex hormones play a role in protection, thus, causing women to develop less serious complications or an asymptomatic COVID-19 Infection [12] . An in-depth study of the factors associated with asymptomatic subjects can provide information to limit severe COVID-19 as much as possible. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated
cord-254162-tu81j66h	2020	Sixth, AAT inhibition of elastase can antagonize the formation of neutrophil extracellular traps (NETs), a complex extracellular structure comprised of neutrophil-derived DNA, histones, and proteases, and implicated in the immunothrombosis of COVID-19; indeed, AAT has been shown to change the shape and adherence of non-COVID-19-related NETs. Seventh, AAT inhibition of endothelial cell apoptosis may limit the endothelial injury linked to severe COVID-19-associated acute lung injury, multi-organ dysfunction, and pre-eclampsia-like syndrome seen in gravid women. First, AAT is a serine protease inhibitor (SERPIN) shown to inhibit TMPRSS-2, the host serine protease that cleaves the spike protein of SARS-CoV-2, a necessary preparatory step for the virus to bind its cell surface receptor ACE2 to gain intracellular entry. First, AAT is a serine protease inhibitor (SERPIN) shown to inhibit TMPRSS-2, the host serine protease that cleaves the spike protein of SARS-CoV-2, a necessary preparatory step for the virus to bind its cell surface receptor ACE2 to gain intracellular entry.
cord-254411-e9vvjv8w	2020	In this article, we provide a novel hypothesis to describe how an increase in cellular adenosine triphosphate (c-ATP) can potentially improve the efficiency of innate and adaptive immune systems to either prevent and fight off COVID-19. In this article, we aim to provide a new hypothesis to describe how the repletion of cellular adenosine triphosphate (c-ATP) can promote immunity against COVID-19. Secondly, ATP-depletion can potentially prone the recruited immune cells to earlier exhaustion against COVID-19. Therefore, one may conclude that ATP-repletion can prevent the so-called "cytokine storm" and improve the cellular energy to better counteract with COVID-19. From the perspective of cellular energy, this process potentially occurs through IFN-mediated T-cell activation that results in c-ATP depletion. have shown that following IFN-γ stimulation, mitochondrial hyperpolarization and ATP depletion occurs in T-cells that results in apoptosis (10) . It demonstrates how an increase in c-ATP can decrease the effect of COVID-19 on immune dysregulation.
cord-256092-bph9ys72	2020	Current data suggest a direct correlation between the lower level of serum testosterone, inflammatory cytokines, disease severity, and poor clinical outcomes among male patients with COVID-19. Current data suggest a direct correlation between the lower level of serum testosterone, inflammatory cytokines, disease severity, and poor clinical outcomes among male patients with COVID-19. Lower levels of testosterone result in the upregulation of ACE2 and TMPRSS2 receptors, facilitating SARS-CoV-1 entry into the alveolar cells, and deregulating a lung-protective pathway (4) . Thereby we hypothesize that low testosterone levels in males have a direct correlation with the severity of disease and a worse outcome in COVID-19. Patients with low testosterone have reportedly developed severe manifestations requiring assisted ventilation because of the upregulation of ACE-2 receptors in lower respiratory cells, increased risk of lung damage, and respiratory muscle catabolism. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China
cord-258272-uu6t6tnh	2020	key: cord-258272-uu6t6tnh title: Bioactive compounds with possible inhibitory activity of Angiotensin-Converting Enzyme-II; a gate to manage and prevent COVID-19 cord_uid: uu6t6tnh Angiotensin-Converting Enzyme-II (ACE-II) receptor, most likely the COVID-19 target, plays essential roles in virus transmission to the alveolar cells (2) . Accordingly, agents with potential inhibition or regulation of ACE-II receptors might be effective in COVID-19 management (3) . Glycyrrhizin can inhibit COVID-19 S-protein binding to ACE-II receptors (7) . Emodin, a bioactive antiviral agent may prevent S-protein binding to ACE-II receptors. Thus, Emodin and probably Aloe-emodin can stave off the COVID-19 infection via competing with S-protein in binding to ACE-II (7) . Angiotensin converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system Potential natural compounds for preventing 2019-nCoV infection Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction Anti-SARS coronavirus 3C-like protease effects of Rheum palmatum L. The authors of this manuscript have no conflict of interest.
cord-258670-dphg8ukj	2020	title: Endothelial progenitor cells and mesenchymal stem cells to overcome vascular deterioration and cytokine storm in critical patients with COVID-19 In light of this information, the sufficient repair of the endothelial lining of blood vessels with Endothelial progenitor cells (EPCs) treatment may have a crucial role to overcome the vascular collapse driving forces in COVID-19 patients, as well as to modulate human immune system. Accumulating evidence leads to suggest that bone marrow-derived EPCs for repairing endothelial damage is now considered as an important novel potential therapeutic option for vascular repair (7, 8) . In critical patients in the course of COVID-19, EPCs may have an important contribution to stem cell treatments to maintain vascular endothelin functions. In critical patients who do not respond to current treatment, the restoration of vascular endothelial function and modulation of immune system by synergistic use of EPCs and MSCs may have a crucial role to overcome the vascular collapse driving forces in COVID-19 patients.
cord-261370-jp5sqqwc	2020	It is thought that surfactant, which is already approved by the Food and Drug Administration for intratracheal administration to treat neonatal respiratory distress syndrome in infants, could benefit COVID-19-infected individuals by: (1) restoring surfactant damaged by lung infection and/or decreased due to the virus-induced death of the type II pneumocytes that produce it and (2) reducing surface tension to decrease the work of breathing and limit pulmonary edema. In addition, a constituent of surfactant, phosphatidylglycerol, could mitigate COVID-19-induced lung pathology by: (3) decreasing excessive innate immune system activation via its inhibition of toll-like receptor-2 and -4 activation by microbial components and cellular proteins released by damaged cells, thereby limiting inflammation and the resultant pulmonary edema, and (4) possibly blocking spread of the viral infection to non-infected cells in the lung.
cord-261574-zcazhkad	2020	
cord-264916-c4n0kyog	2020	A pandemic outbreak of a viral respiratory infection (COVID-19) caused by a coronavirus (SARS-CoV-2) prompted a multitude of research focused on various aspects of this disease. In this work, we discuss the significance of natural protective factors related to anatomical and physiological properties of the eyes and preventing the deposition of large number of virus-loaded particles on the ocular surface. Specifically, we advance the hypothesis that the standing potential of the eye plays an important role in repelling aerosol particles (microdroplets) from the surface of the eye and discuss factors associated with this hypothesis, possible ways to test it and its implications in terms of prevention of ocular infections. This hypothesis could be tested by measuring the electrical charge of bioaerosol generated by normal breathing in healthy subjects and in patients with viral infections caused by different viruses, causing respiratory infections or with suspected aerosol transmission pathway.
cord-265322-3854ddb9	2020	Based on both structural and syndromic similarities with SARS-CoV, a hypothesis is formed on SARS-CoV-2 potential to affect the host''s metabolism as part of its lifecycle. In the literature, SARS-CoV has been known to cause de novo diabetes by ACE2-dependent uptake on pancreatic isle cells, and furthermore dysregulate lipid autophagy in favor of the viral lifecycle. Their study provided the foundation for a hypothesis put forth by Fang and colleagues indicating that diabetic and hypertensive patients exposed to ACE2 inhibitors may be at an increased risk of more severe COVID-19 (7) . In another study, SARS-CoV was shown to cause diabetes by ACE2-dependent infection of pancreatic isle cells (10) . Future studies should determine SARS-CoV-2 interaction and effect on the human transcriptome, further identifying drug targets using pharmacogenomic enrichment analyses. Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity?
cord-265724-fdt00qw1	2020	Apart from ACE-2, recently EMMPRIN, has been regarded as a target for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attachment and entry into the host cell. Since one of the routes of entry for the virus is the oral cavity, it becomes imperative to percept oral comorbidities such oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs) in terms of EMMPRIN as a target for SARS-CoV-2. 1 Angiotensin-Converting Enzyme 2 (ACE-2) on the host cells is the attachment protein for the spike receptor present on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). [4] [5] [6] Apart from ACE-2, recently extracellular matrix metalloproteinase inducer (EMMPRIN), which is also called BASIGIN/CD147, has been regarded as a target for SARS-CoV-2 attachment and its entry into the host cell. OSCC, by the virtue of upregulation of EMMPRIN expression (potential and alternative site for ''S'' receptor), increases the susceptibility to SARS-CoV-2 infection.
cord-267612-1h7xpkbe	2020	
cord-268425-xg8xnjf9	2020	5 Importantly, neutrophils, whose activation and transit into lung interstitial tissue and alveolar space is a key mediator of the respiratory distress syndrome associated with COVID-19, are highly responsive to the functionally suppressive effects of A2AR, as are the endothelial cells whose activation attracts and enables transendothelial passage of activated neutrophils. Most studies with DIP have focused on its platelet-stabilizing effects -which presumably could provide some protection from SARS-CoV-2''s pro-thrombotic effects -but experimental studies also show that DIP can act on neutrophils to suppress superoxide production, adhesion to endothelial cells, and, in a mouse model of anti-phospholipid syndrome (a sometime feature of COVID-19), NETosis formation. 79 Supplemental glucosamine may likewise up-regulate the type 1 interferon responses to viruses, while exerting anti-inflammatory effects that render it protective in rodent models of sepsis and lung inflammation induced by LPS or cigarette smoke.
cord-269563-2979u47a	2020	
cord-270740-3su8pc3f	2020	
cord-270805-o6rbfmie	2020	In this letter, the author describes an immunological explanation for the double-peaked epidemic curve of new viral diseases including Covid-19. This theory claims that a double-peaked pattern of new cases in a new viral epidemic is intrinsically determined by the pattern of pathogen interaction with the host. According to this hypothesis, relaxation of the community control measures is not responsible; at least in part, for resurgence of cases. Assuming the above hypothesis is true; a viral epidemic curve will show an early upstroke corresponding to persons who pass into viremia upon initial exposure to the virus followed by a second slower rise due to cases who develop the disease after repeated process of inoculation and clearance at the point of entry. In conclusion, the author describes an immunological explanation for a double-peaked epidemic curve of Covid-19 and other new viral diseases.
cord-271785-vmnc8yg6	2020	As competitive inhibitors of HMG-CoA-reductase, the key enzyme of the "mevalonate pathway" through which essential compounds, not only cholesterol, are synthesized, statins decrease the levels of cholesterol, and thus LDLs, as an innate defense mechanism, with controversial results in decreasing mortality from cardiovascular disease. In the attempt to decipher the enigma of SARS-CoV-2 infectivology, the hypothesis should be tested whether the population of subjects who succumbed to Covid-19 may have developed a compromised immunity at sub-clinical levels and have become more susceptible to fatal consequences from SARS-Cov-2 infection due to statin therapy. Statins are cholesterol-lowering drugs that act as competitive inhibitors of the enzyme -Hydroxy--Methyl-Glutaryl-Coenzyme-A (HMG-CoA)-reductase, the key enzyme of the "mevalonate pathway". 27 Thus, subjects with already low LDL levels and possibly weakened leukocyte function because of statin treatment would be even more susceptible to infection and its fatal consequences.
cord-274510-fo7p98np	2020	Based on the aforementioned findings and on documented analogies between SARS-CoV-2 and HIV [13] , we hypothesized that the reduced conversion activity of the Gc protein (human groupspecific component (Gc)) into the macrophage activating factor (MAF) could have a key role in the dysregulate immune response induced by SARS-CoV-2, just like for HIV infected patients [14] [15] . In particular, based on their antiviral activity [68] , chloroquine and hydroxychloroquine, initially conceived as antimalarial therapeutics, were proposed to treat patients hospitalized with COVID-19, better if associated to azithromycin, showing promising efficacy in "inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virus negative conversion and shortening the disease course" [69] [70] . So, in sight of this, given its multifunctional properties, we believe that GcMAF could have a very important role in the pathophysiology of organ damage induced by SARS-CoV-2, providing explanations which are consistent with the clinical, radiological and histopathological findings observed in patients with COVID-19. Effects of vitamin D(3)-binding protein-derived macrophage activating factor (GcMAF) on angiogenesis
cord-274698-i3mzzxwq	2003	Chloramines at blood concentrations between 1 and 2 mmol/L inactivate lipid enveloped virus and chloramines at blood concentrations below 0.5 mmol/L, i.e. at oxidant concentrations that do not affect thrombocytes or hemostasis factors, act antithrombotically by activation of the physiologic PMN mediated fibrinolysis; this thrombolysis is of selective nature, i.e. it does not impair the hemostasis system of the patient allowing the antithrombotic treatment in patients where the current risky thrombolytic treatment is contraindicated. The 60 mM NH 2 Cl (about 10 times the concentration generated by activated PMN!) is ulcerogenic in rat stomachs, taurine application (1 ml 200 mM) attenuates the deleterious action of NH 2 Cl (102), NH 2 Cl induces apoptosis in gastric mucosa (103) . Singlet oxygen ð 1 O 2 Þ-generating chloramines at concentrations that are tolerable for normal hemostasis function inactivate the lipid enveloped vesicular stomatitis virus in human blood Taurine chloramine inhibits prostaglandin E2 production in activated RAW 264.7 cells by post-transcriptional effects on inducible cyclooxygenase expression
cord-274715-dcs1rgd0	2020	Novel coronavirus (NCoV-19), also known as SARS CoV-2, is a pathogen causing an emerging infection that rapidly increases in incidence and geographic range, is associated with the ever-increasing morbidity and mortality rates, and shows sever economic impact worldwide. We are suggesting here a strategy for the COVID-19 treatment that could be effective in curing the patients in the current scenario when no efficient medicine or Vaccine is currently available, and Clinicians solely depend upon the performing trials with drugs with known antiviral activities. If the albumin is used to stabilize and deliver the EGCG and Curcumin for targeting the intracellular virus components in combination with the drug that could block the virus fusion and/or entry to a cell, this strategy might represent an effective way of treating the SARS CoV-2 infection.
cord-275353-ezrmuw48	2020	Compounds derived from Allium sativum (garlic) have the potential to decrease the expression of proinflammatory cytokines and to reverse the immunological abnormalities to more acceptable levels. Leptin''s role in boosting proinflammatory cytokines and in appetite decreasing suggest the possible beneficial effect of decreasing the concentration of this proinflammatory adipose tissue hormone in relieving some symptoms detected during COVID-19 infection. In conclusion, Allium sativum may be an acceptable preventive measure against COVID-19 infection to boost immune system cells and to repress the production and secretion of proinflammatory cytokines as well as an adipose tissue derived hormone leptin having the proinflammatory nature. It is a well-known fact that immune dysfunction plays an important role in the development and progress of several diseases and this functional food may contribute to the prevention and treatment of pathologies such as obesity, metabolic syndrome, cardiovascular disorders, gastric ulcer, and even cancer [17, 18] . Decreased leptin concentrations caused by garlic may be helpful to alleviate appetite loss observed in patients with COVID-19 infection.
cord-275569-i5y23mmz	2020	Though it is intuitively tempting, on the basis of physiopathological common knowledge, to predict a greater risk of contracting the SARS-CoV-2 infection in tobacco smokers, an analysis of studies from various countries shows that hospitalized COVID-19 patients have a lower, and apparently inversely proportional, rate of current tobacco smoking, in comparison with the respective general population, although once the disease has developed meta-analyses suggest that smoking is associated with a worse prognosis [1] . Incidentally, this behavior reminds the proposed effects of tobacco smoking, protective against initial SARS-CoV-2 infection and deleterious in the florid phase of the COVID-19 disease. Taken together, all these elements suggest that the oral use of tobacco, continuously exposing to non-pathogenic but immunogenic TMV particles, and chronically stimulating a natural antiviral response, may induce a state of resistance to the initial SARS-CoV-2 infection.
cord-276564-o21ncldx	2020	This hypothesis suggests that a deficiency of nicotinamide adenine dinucleotide (NAD + ) may be the primary factor related to the SARS-Cov-2 disease spectrum and the risk for mortality, as subclinical nutritional deficiencies may be unmasked by any significant increase in oxidative stress. This hypothesis suggests that a deficiency of nicotinamide adenine dinucleotide (NAD + ) may be the primary factor related to the SARS-Cov-2 disease spectrum and the risk for mortality, as subclinical nutritional deficiencies may be unmasked by any significant increase in oxidative stress. Vulnerable patient groups would potentially be less likely or unable to ensure sufficient activation of SIRT1 due to low NAD + levels or associated nutritional deficiencies including Zn ++ , and as such contribute to an inability to control viral replication and reduce the uncontrolled expression of pro-inflammatory cytokines.
cord-276715-d1nh2dvb	2020	Besides, Cu can kill several infectious viruses such as bronchitis virus, poliovirus, human immunodeficiency virus type 1(HIV-1), other enveloped or nonenveloped, singleor double-stranded DNA and RNA viruses. Based on available data, we hypothesize that enrichment of plasma copper levels will boost both the innate and adaptive immunity in people. Copper exposure to human coronavirus 229E destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes [16] . Copper deficiency could lead a decreased number of circulatory blood cells with a greater susceptibility towards infection in older people In a study of 11 men on a low-Cu diet (0.66 mg Cu/day for 24 days and 0.38 mg/day for another 40 days) showed a decreased proliferation response of their white blood cells when presented with an immune challenge in cell culture [33] . Thujaplicin-copper chelates inhibit replication of human influenza viruses Effects of low-copper diets on human immune response
cord-277931-3hxhsmw8	2020	We propose to examine the potential utility of oral activated charcoal with the hypothesis that such treatment would lower absorption of microbiome derived toxins and ameliorate systemic oxidant stress and inflammation. We propose to examine the potential utility of oral activated charcoal with the hypothesis that such treatment would lower absorption of microbiome derived toxins and ameliorate systemic oxidant stress and inflammation. It appears that age, renal dysfunction and obesity are amongst the most important risk factors for serious or fatal COVID-19 infection 3, 4 . To test this hypothesis, we would suggest first a proof of concept study where a relatively small group of patients at high risk for COVID-19 complications are given activated charcoal at doses similar to that used in previous renal failure studies 18, 19 when the diagnosis is first made. Uremic Toxins Activates Na/K-ATPase Oxidant Amplification Loop Causing Phenotypic Changes in Adipocytes in In Vitro Models Protein-bound uremic toxins, inflammation and oxidative stress: a cross-sectional study in stage 3-4 chronic kidney disease
cord-278271-rpq62xhl	2020	
cord-279084-bbae1qyx	2020	I hypothesized that the damage induced by free DNA is a reason for severe COVID-19, which can explain many symptoms of this disease, such as cytokine storm, acute respiratory distress syndrome (ARDS) and muscus plug, acute injuries of heart, liver and kidney, and some special symptoms of COVID-19. I hypothesized that the damage induced by free DNA is a reason for severe 23 COVID-19, which can explain many symptoms of this disease, such as cytokine 24 storm, ARDS and muscus plug, acute injuries of heart, liver and kidney, and some 25 special symptoms of COVID-19. Level 60 of lymphocytes is thought as the early identification of risk factors for severe 61 COVID-19, [1] [2] [3] 8 while I hypothesized that it was related to free DNA-related cytokine 62 storm and blood vessel damage, which can explain many symptoms of this disease, 63 including some "special" symptoms in COVID-19, as shown in Figure 1 .
cord-279138-dmhphgp5	2020	Populations in areas with higher levels of air pollution both indoors and outdoors show increased mortality rates when infected with coronavirus disease 2019 (COVID-19). In this paper, fine particulate matter (PM) is identified as a source of disrupted activation of the hypothalamic–pituitary–adrenal (HPA) axis; therefore, a contributable variable to COVID-19 mortality. Populations in areas with higher levels of air pollution both indoors and outdoors show increased mortality rates when infected with coronavirus disease 2019 . In this paper, fine particulate matter (PM) is identified as a source of disrupted activation of the hypothalamicpituitary-adrenal (HPA) axis; therefore, a contributable variable to COVID-19 mortality. Therefore, chronic exposure to fine PM may be contributable variable that disrupts HPA system activation typically associated with the altered regulation of circulating glucocorticoids resulting in inefficient or delayed immune response to COVID-19 infection.
cord-281354-sa27k8o3	2020	title: Role of Latent Tuberculosis Infections in Reduced COVID-19 Mortality: Evidence from an Instrumental Variable Method Analysis However, these studies ignore an important fact: according to World Health Organization estimates, about a quarter of the world''s population may have latent tuberculosis infection (LTBI), a condition in which there is no evidence of clinically active tuberculosis but persistent immune responses are stimulated by Mycobacterium tuberculosis antigens. However, such studies ignore the important fact that about one-quarter of the world''s population may have latent TB infection (LTBI), a condition in which there is no evidence of clinically active TB but persistent immune responses are stimulated by Mycobacterium tuberculosis antigens. As explained above, the logarithm of the number of TB infections per 100,000 individuals (lntb10) can be used as a proxy variable for LTBIs. For this regression analysis to be statistically accurate, the explanatory variable X must first be correlated with the error term u (i.e., the covariance of X and u must be zero).
cord-282853-l0c69uul	2005	In this work we propose a simple mathematical model for the analysis of the impact of control measures against an emerging infection, namely, the severe acute respiratory syndrome (SARS). The model provides a testable hypothesis by considering a dynamical equation for the contact parameter, which drops exponentially with time, simulating control measures. In contrast, with control measures, which reduce the contact rate to about 25% of its initial value, the expected final number of cases is reduced to 1778 in Hong Kong and 226 in Toronto (Canada). The aim of this work is to provide a projection of what would have happened with the course of severe acute respiratory syndrome (SARS) epidemic if the universal procedures to reduce contact were not implemented in the affected areas. The model projects that, in the absence of control, the final number of cases would be 320,000 in Hong Kong and 36,900 in Toronto (Canada).
cord-282899-kp114q7n	2020	
cord-286038-a62k3lma	2020	The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. We hypothesize that HCQ especially as an aerosol application will prevent or at least markedly reduce the replication rate of the SARS-CoV-2 virus in the early phase of the infection and subsequently substantially lower the number of severe pneumonias and casualties. This hypothesis is new since the major assumption in ongoing clinical studies and actual recommendations is that HCQ and CQ should be used in oral application form in patients with severe covid-19 pneumonia and only when other treatment strategies have failed. If our hypothesis is true, HCQ as an aerosol might not only reduce the side effect potential of the oral application form but can also be clinically used as an efficient antiviral agent in the early phase of COVID-19 and eventually lower the rate of severely ill patients and fatalities.
cord-287824-zg5akivn	2020	title: Advanced drug delivery systems can assist in managing influenza virus infection: A hypothesis This article provides an insight into a novel hypothesis that describes how the integration of nanomedicine, with the development of drugs and vaccines can potentially enhance body immune response and the efficacies of anti-viral therapeutics to combat influenza infections. In the recent years, an 66 increasing trend of influenza outbreaks have been observed, prompting medical researchers to 67 design and develop suitable vaccines and novel therapeutic modalities [10] . Targeting 411 neutrophils using novel drug delivery systems in chronic respiratory diseases Increasing 440 complexity and interactions of oxidative stress in chronic respiratory diseases: An 441 emerging need for novel drug delivery systems Interactions 501 with the macrophages: An emerging targeted approach using novel drug delivery 502 systems in respiratory diseases Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: 537 Another emerging application of nanomedicine
cord-288009-8i3gsq9p	2020	
cord-288733-c51lfwd6	2020	An analysis of clinical trials registered on ClinicalTrials.gov revealed that this may continue as many studies combine HCQ with agents that prolong the QT interval. Here we describe an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma and discuss how this approach may reduce side-effects and improve efficacy. Chloroquine and hydroxychloroquine (HCQ) were two of the earliest drugs to 33 receive attention as possible repurposable treatment options for COVID-19 3 . Concerns associated with severe side effects 41 are such that the FDA and EMA now formally recommend against taking HCQ for COVIDEffects of chloroquine on 178 viral infections: An old drug against today''s diseases? FDA Drug Safety Communication: FDA cautions 199 against use of hydroxychloroquine or chloroquine for COVID-19 outside of the 200 hospital setting or a clinical trial due to risk of heart rhythm problems Optimizing hydroxychloroquine 210 dosing for patients with COVID-19: An integrative modeling approach for effective 211 drug repurposing
cord-289049-4ozwhcyi	2020	title: Renin-angiotensin system: The unexpected flaw inside the human immune system revealed by SARS-CoV-2 Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy Renin-angiotensin system: The unexpected flaw inside the human immune system revealed by SARS-CoV-2 In humans the renin-angiotensin system is the hormone system which regulates blood pressure and vascular resistances, as well as electrolytic balance; within this important system, the angiotensinconverting enzyme (ACE), present on the surface of vascular endothelial cells, in particular those of the lungs, is deputed to the conversion of angiotensin I to angiotensin II (AII), a potent vasoconstrictive peptide [1] . In addition, homologous ACE2 receptors have been identified on the oral mucosa, in type-II pneumocytes, along the intestine and on the kidney and heart endothelia [1, 2] ; these receptors have been found overexpressed in course of ACE inhibitors and AII receptor antagonists administration in murine models [3, 4] . Angiotensin-converting enzyme 2-a new cardiac regulator Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target Upregulation of angiotensin-converting enzyme (ACE) 2 in hepatic fibrosis by ACE inhibitors
cord-289332-hvakv08t	2004	High mobility group box 1 protein (HMGB1) is released by necrotic cells or activated macrophages/monocytes, and functions as a late mediator of lethal systemic and local pulmonary inflammation. In light of observations that three Chinese herbal formulations recommended for treatment of severe acute respiratory syndrome (SARS) specifically inhibited the release of HMGB1 from innate immune cells, we hypothesize that HMGB1 might occupy a pathogenic role in SARS by mediating an injurious pulmonary inflammatory response. High mobility group box 1 protein (HMGB1, formerly known as HMG-1 or amphoterin) has recently been identified as a new proinflammatory cytokine and a late mediator of inflammation, sepsis, and acute lung injury. In light of observations that several Chinese herbal remedies recommended for treatment of SARS specifically inhibited the release of HMGB1 from activated innate immune cells, we hypothesize that HMGB1 might occupy a pathogenic role in SARS by mediating an injurious pulmonary inflammatory response.
cord-289905-dvl2pud2	2020	
cord-290803-v5ndlk9c	2020	Therefore in the light of these known facts we hypothesized that viral S protein molecule may bind to the other overexpressed receptor molecules in glioma cells and may play some role in glioma tumorogenesis. Thus we leverage docking analysis (HEX and Z-DOCK) between viral S protein and epidermal growth factor receptors (EGFR), vascular endothelial growth factor receptors (VEGFR) and hepatocyte growth factor receptors (HGFR/c-MET) to investigate the oncogenic potential of COVID-19. Thus we leverage docking analysis (HEX and Z-DOCK) between viral S protein and epidermal growth factor receptors (EGFR), vascular endothelial growth factor receptors (VEGFR) and hepatocyte growth factor receptors (HGFR/c-MET) to investigate the oncogenic potential of COVID-19. Considering the importance of these surface receptors on glioma cells, we studied the interaction between EGFR, VEGFR and c-MET receptor proteins with S protein of COVID-19. Our preliminary findings suggested that COVID-19 S protein might have a binding affinity to EGFR, c-MET and VEGFR on glioma cells.
cord-291037-19csqq89	2020	title: Vitamin K epoxide reductase complex subunit 1 (VKORC1) gene polymorphism as determinant of differences in Covid-19-related disease severity A genetic polymorphism in the vitamin K epoxide reductase complex 1, VKORC1 -1639A, is particularly prevalent in East Asia and associates with low vitamin K recycling rates. A genetic polymorphism in the vitamin K epoxide reductase complex 1, VKORC1 -1639A, is particularly prevalent in East Asia and associates with low vitamin K recycling rates. We speculate that the disparity in morbidity and mortality from Covid-19 between East and West may be at least partially explained by differences in the allele distribution of a VKORC1 polymorphism determining the rate of vitamin K recycling. If the VKORC1 -1639A allele is shown to be associated with decreased thrombotic complications and/or death, it would further support the hypothesis that vitamin K metabolism is an important determinant of Covid-19-related disease severity.
cord-291722-xnfdjriz	2020	
cord-291781-gs81g1db	2020	We reviewed the literature concerning the innate response from nasal and oral epithelial cells and their reaction to hydrogen peroxide (H(2)O(2)). Therefore, nose/mouth/throat washing with hydrogen peroxide may enhance those local innate responses to viral infections and help protect against the current coronavirus pandemic. [2] We reviewed the literature concerning the innate response from nasal and oral epithelial cells to evaluate the role of hydrogen peroxide (H 2 O 2 ). [5] Virus-induced oxidative stress plays an important role in the regulation of the host immune system and the specific oxidant-sensitive pathway is one of the effective strategies against viral infections. [5] Virus-induced oxidative stress plays an important role in the regulation of the host immune system and the specific oxidant-sensitive pathway is one of the effective strategies against viral infections. There are no randomized controlled trials or clinical observational studies concerning the curative or preventive effect of hydrogen peroxide against viral infections.
cord-293059-2iwzieqm	2020	It has been approved that inflammation-induced pathogenesis in COVID-19 infection has a strong correlation with incidence of cardiovascular metabolic diseases and gastrointestinal injury (1) . However, studies on the correlation between pro-inflammatory cytokine responses and bone metabolism in COVID-19 patients are still lacking. In this special background, will inflammatory disorder and immune imbalance affect bone metabolism after COVID-19 infection? Simultaneously, hypoxia inducible factor (HIF-1) was proven to facilitate osteoclast differentiation by overexpressing RANKL and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) (14) . As osteoblasts and osteoclasts exist in approach with immune cells in medullary cavity, it''s no wonder that immune system shares massive regulatory cytokines, signaling molecules and transcription factors with bone biology. Apart from that, NF-κB and AP-1 stimulate the expression of many elements which required for inflammatory cytokines, driving up osteoclast activity and usually implicated inhibition on proliferation and differentiation of osteoblasts (22) .
cord-293860-6kz0iws6	2020	
cord-296253-bxyzhsfs	2020	To determine whether the perinasal lymphatic system or lymphatic vessels are involved in cerebral immune defence and play a role in causing CNS infections (especially respiratory tract-related infections), we performed an anatomic study to investigate the drainage differences between the perinasal and intracerebral lymphatic systems by using injection of Evans blue and anatomic surgery, together with immunohistochemistry and immunofluorescence assays. To determine whether the perinasal lymphatic system or lymphatic vessels are involved in cerebral immune defence and play a role in causing CNS infections (especially respiratory tract-related infections), we performed an anatomic study to investigate the drainage differences between the perinasal and intracerebral lymphatic systems by using injection of Evans blue and anatomic surgery, together with immunohistochemistry and immunofluorescence assays. Under an anatomic (20× magnification) microscope, we dissected the mouse intracranial nervous system after injection of Evans blue (perinasal lymphatic reflux assay) and found that lymphatic vessels that exist in the pituitary and loop the cerebral lymphatic circulation are responsible for the perinasal-pituitary lymphatic drainage.
cord-297178-moxhk2e0	2020	Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus disease 2019 (COVID-19) is provoking devastating consequences on economic and social fields throughout all continents. Amongst the components of rennin-angiotensin system (RAS), the angiotensin-converting enzyme 2 (ACE2) has gained great prominence for being directly associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the coronavirus related to COVID-19 [4, 5] . ACE2 is a fundamental piece in the pathophysiology of COVID-19, since the high replication capacity of SAR-CoV-2 is directly related to the coupling to ACE2 and cell infection. The ACE2 level reduction caused by SARS-CoV-2 infection may be directly related to the pathogenesis of COVID-19 [26] . The reduction in ACE2 expression may be related to pulmonary inflammation and subsequent cytokine storm seen in patients with severe COVID-19. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severeacute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensinconverting enzyme-2 (ACE2)
cord-299911-v95pf3eg	2020	Based on the conclusions drawn from the currently rapidly evolving knowledge about COVID-19, our hypothesis is built on the potential modulation of CYPs activity by the inflammatory environment provoked by SARS-CoV-2 infection, as well as the pathologic involvement of the liver which harbors the majority of the drug metabolizing enzymes (DMEs). Systemic inflammation and immune response represent a substantial element in many acute and chronic diseases which is strongly implicated in altering drug pharmacokinetics through, mainly, modulating the expression and activity of DMEs. As a main contributor to the metabolic biotransformation of most drugs, CYPs are widely involved in such disease-drug interactions [19] . For decades, IL-6 has been recognized as the major inflammatory element that provokes a significant repressive effect on the expression and activity of different CYPs. Human recombinant interleukin 6 (rhIL-6) has shown concentration-dependent blocking of phenobarbital-mediated induction of CYP2B1/2 mRNA and activity in rat hepatocytes [48] .
cord-301619-0ojayw16	2020	Based on this observation, our proposed hypothesis is that 5-alpha-reductase inhibitors, that are commonly used for BPH treatment, may be one of the factors contributing to poorer prognosis in males. Based on this observation, our proposed hypothesis is that 5-alpha-reductase inhibitors, that are commonly used for BPH treatment, may be one of the factors contributing to poorer prognosis in males. Consequently, we introduce hypothesis that 5-alpha-reductase inhibitors may disrupt androgens metabolism in lungs, which in turn may have a negative impact on course of COVID-19 infection. Under this assumption, 5-alpha-reductase inhibitors might increase androgen concentration in lungs hampering their regeneration. Due to high prevalence of 5-alpha-reductase inhibitor in BPH treatment, its potential negative influence on recovery after COVID-19 infection, should be established. According to presented hypothesis, patients receiving 5-alpha-reductase inhibitors, might be vulnerable to COVID-19 infection with poorer prognosis. May patients receiving 5 alpha-reductase inhibitors be in higher risk of COVID-19 complications
cord-302212-zt4lv5g4	2020	Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 20% of children and up to 10% of adults (1) . Its pathogenesis involves environmental factors that interact with genetic skin barrier defects and immune Th2 Adverse psychological effects induced by the COVID-19 quarantine have been associated with increase of itch in some chronic skin disease, also due to neuroendocrine modulation of skin inflammation (4). Obviously, quarantine is associated with less exposure to sunlight that, together with high temperature and low humidity, may exert an immunosuppressive effect on skin inflammation of AD (2) . All these considerations suggest the hypothesis that COVID-19 pandemic may be associated with changes in lifestyle of AD patients that can significantly influence their clinical disease activity. Effects of climate change on skin diseases Mass quarantine measures of COVID-19 pandemic: psychosocial implications for chronic skin conditions and a call for qualitative studies
cord-303022-9hqoq7tf	2020	In addition to furin, another protease cathepsin L is also elevated in chronic periodontitis and oral cancer, which in turn could be a result of the interleukin 6 mediated activation of the caveolin -1 mediated JNK-AP-1 signaling pathway [8] [9] [10] . 3) Following binding of the S1 subunit to the ACE-2 receptors, the virus fuses with the host cell in two mechanisms: (a) endosomal fusion which is mediated by cysteine proteases cathepsin B/L and (b) plasma membrane fusion mediated by the serine protease TMPRSS2. Based on the above-mentioned data, it can be hypothesized that the increased protease levels in chronic periodontitis and oral cancer could potentially increase the risk of an oral mucosa mediated SARS-corona virus-2 infection (figure 1). In addition to increasing proteases, chronic periodontitis, and oral cancer patients have also reported having a low melatonin level [14, 15] .
cord-304658-vxu33v7i	2020	
cord-306146-i4a74j3r	2020	In addition to its role in various psychiatric, neurologic, and cardiovascular functions, there is increasing evidence that NE plays a role in the symptomatology associated with serious systemic infections such as influenza, including activation of cytokine signaling such as IL-6 as well as the manifestation of psychological effects associated with infection 3 . I suggest here that this cytokine storm may be counteracted by a range of clinically used drugs that reduce NE transmission (but that may not act through direct effects on viral replication or viral entry into cells) 5 : alpha2 agonists such as clonidine, guanfacine, dexmedetomidine; various beta blockers such as propranolol, nebivolol, carvedilol, atenolol; and various alpha1 antagonists such as prazosin 4 . If COVID-19 is accompanied by systemically elevated NE signaling, the various drugs listed above may also counteract deleterious psychological effects associated with this infection 3 . Conflicts of interest The author reports no conflicts of interest, and no funding source directly supported this work
cord-308279-gsk4qel5	2020	I herein propose the viral protein fragment theory of COVID-19 pathogenesis based on my observations in cultured human vascular cells that SARS-CoV-2 spike protein can activate cell signaling events without the rest of the viral components. I hypothesize that, as humans are infected with SARS-CoV-2, the virus releases a fragment of the spike protein that can target host cells for eliciting cell signaling without the rest of the viral components. This hypothesis is based on my experimental observations in cultured human vascular cells that the recombinant full length S1 subunit of SARS-CoV-2 spike protein can activate cell signaling events without the rest of the viral components. I propose a scenario that, as humans are infected with SARS-CoV-2, the virus releases a fragment of the spike protein that can target host cells for eliciting cell signaling.
cord-310217-p9nqcz5d	2020	Currently available expert opinions suggest reduction of immunosuppression therapy for renal transplant recipients with symptomatic COVID-19 infection with either antiviral drugs, hydroxychloroquine and/or azithromycin. Currently available expert opinions suggest reduction of immunosuppression therapy for renal transplant recipients with symptomatic COVID-19 Inspired by our experience in treatment of CMV pneumonia and literature data on the potential benefit of convalescent plasma for treatment of different viral diseases we suggest use of the hyperimmune anti-CMV gamma globulins in addition to other available therapies. Inspired by our experience in treatment of CMV pneumonia and literature data on the potential benefit of convalescent plasma for treatment of different viral diseases we suggest use of the hyperimmune anti-CMV gamma globulins in addition to other available therapies. In conclusion, we suggest the use of hyperimmune anti-CMV immunoglobulins for treatment of COVID-19 especially when occur as coinfection with CMV instead of the convalescent plasma which may be unavailable for majority of patient.
cord-310928-g553afo9	2020	
cord-311673-z4hkw17g	2020	As the visceral fat possesses an intense immune activity, is involved in metabolic syndrome and is at the crossroad between the intestines, the systemic circulation and the lung, we hypothesized that it plays a major role in severe forms of SARS-CoV-2 infection. Several factors may increase intestinal permeability including, direct enterocyte damage by SARS-CoV2, systemic inflammatory response syndrome (SIRS) and epithelial ischemia secondary to SARS-CoV2associated endothelial dysfunction. This increase permeability further leads to translocation of microbial components such as MAMPS (microbial-associated molecular pattern), triggering an inflammatory immune response by TLR-expressing cells of the mesentery fat (mostly macrophages and adipocytes). As the increased volume of mesentery fat in overweight men play a key role in the occurrence of metabolic syndrome [8] , we hypothesized that the visceral adipose tissue plays a central role in severe forms of COVID-19.
cord-312912-i1yyz5lg	2020	
cord-313382-prxc0lue	2020	
cord-314679-lmfalzni	2020	
cord-315576-bgcqkz0p	2020	
cord-317238-uszhwugw	2020	
cord-318114-q29zax2j	2020	
cord-319822-h1zm94p4	2020	My thesis is supported and described on the basis of a physicist''s model which studies the droplets behavior when emitted by the respiratory apparatus of an infected person, symptomatic or not. The intermediate dimensioned droplets are proved to be changed into aerosol, losing their water content and becoming seriously contagious, but in their initial phase they could be easily caught by a simple surgical mask. This habit, There are non doubts about the fact that expiratory particles transmit the pandemic, but we must make a coarse distinction among droplets and their dynamic evolutions when emitted by infected people. These droplets have a substantial viral load, they are quite numerous, some thousands of them can contain just one single virion each and they are probably the most contagious and dangerous elements[14]; if not stopped on time, they constitute the real element of airborne infection [15] .
cord-320508-egw7bvzf	2019	The phosphatidylserine (PS) molecule is present in cell membranes where it is actively kept on their inner leaflets but when cells are damaged it moves to the surface and become a signal for their removal, the platform upon which the coagulation cascade takes place and a ligand that activates a feedback cycle of inflammatory cytokine secretion and initiates the wakeup call for the innate immune response. The phosphatidylserine (PS) molecule is present in cell membranes where it is actively kept on their inner leaflets but when cells are damaged it moves to the surface and become a signal for their removal, the platform upon which the coagulation cascade takes place and a ligand that activates a feedback cycle of inflammatory cytokine secretion and initiates the wakeup call for the innate immune response. The hypothesis presented here is that annexin V''s therapeutic administration in Ebola can prevent its Th1 cell generated inflammatory cytokine storm, stop the cascade generated hemorrhagic consumptive coagulopathy and prevent macrophage and dendritic cell infection.
cord-320959-sgdqhtns	2020	In membrane biophysics, Vitamin E is a linactant and a potent modulator of lateral phase separation that effectively reduces the line tension at the two-dimensional phase boundaries and thereby exponentially increases the surface viscosity of the pulmonary surfactant. Supplementation of pulmonary surfactants which retain moderate level of cholesterol and 10 controlled hypothermia for patients are recommended when the hypothesis that the line-active property of the vitamin derivative drives the pathogenesis of EVALI holds. Currently, there are 5 five established non-antioxidative properties of Vitamin E in the biological system: i) its ability to induce gel-liquid crystalline phase transition, ii) its active deposition in the lipid droplet of macrophages, iii) its modulation of the antidiabetic cascade involving diacylglycerol kinase (DGK) and protein kinase C (PKC), iv) its activation of the xenobiotic-sensing pregnane X receptor (PXR) signaling, and v) its ability to modulate lateral phase separation.
cord-322880-zfc9w5y6	2020	title: Respiratory droplets get suspended longer and spread wider in temperate environments compared to tropics and implications for SARS-CoV-2 transmission The combined effect of change in size of the droplet as well as the density amplifies the influence that environmental relative humidity would have on the particle settling velocity. It is possible that droplets discharged from infected individuals in places like New York City could shrink in size quickly and remain airborne for considerable period of time. A simple understanding of the mechanics of droplet size, dispersion and displacement could help infection control and public health measures to minimize spread and mitigate the risk of people getting infected especially in hotspots like hospital environments or other closed spaces. A simple understanding of the mechanics of droplet size, dispersion and displacement could help infection control and public health measures to minimize spread and mitigate the risk of people getting infected especially in hotspots like hospital environments or other closed spaces.
cord-323310-tq9muytr	2020	
cord-323749-lvtfv7ny	2020	Although macrolides like azithromycin and clarithromycin etc., have been reported to act against respiratory infections but they lack the ability of immunity enhancement through defensins. The aminoglycosides were proved to have defensin mediated antiviral activity, that could enhance the immunity. So, Consideration of aminoglycosides can be a double edge sword viz., against respiratory infection as well as Immunity enhancer (along with anti-virals) for COVID-19 regimen. Although various nations throughout the globe making several strategies viz, different drug combinations, proposing lock downs and herd immunity etc., to control the wide spread of COVID-19 and to tolerate its severity, the radical behaviour of virus is evident. In the instances like current pandemic of COVID-19, where infection control becomes a great challenge, immune mediators could be a vital link. However, aminoglycosides (AGs) were proved to produce functional peptides from theta defensins (called as retrocyclins) that are active against HIV 10 .
cord-324949-sqy03dks	2020	
cord-326849-vqpwdlj7	2020	
cord-327809-9uhhqasl	2020	A study in China, comparing burnout of front line workers with that of normal ward staff, in COVID context, used Maslach questionnaire for medical workers and the results were interesting and quite unexpected [3] . The aim of our study was to compare the frequency of burnout syndrome between medical residents considered to work on the front line (emergency unit, radiology and intensive care unit) and those working in normal hospital wards (surgery, obstetrics and gynecology, obstetrics). The burnout was significantly more frequent in normal wards workers (lot B) (prevalence 86%) compared to medical residents working in places that we considered front-line departments: emergency unit, radiology, including CT/MRI department and intensive care unit -lot A in our study, that showed a prevalence of burnout of only 66% (p<0.05, from chi-square statistic test) (table 2).
cord-328587-vctvcyim	2020	According to the existing clinical data, some patients not only suffer from respiratory diseases, but also have complications such as acute renal injury and even renal necrosis [2] [3] [4] , in addition, SARS-CoV-2 was also found in recent semen analysis of male patients [5] . Previous clinical data have shown that in addition to respiratory diseases, some male patients with COVID-19 are accompanied by kidney damage and even renal failure [2] [4], which suggest that SARS-CoV-2 may affect male fertility. Furthermore, clinical data also show that the receptor protein ACE2 that mediates the entry of SARS-CoV-2 into host cells is not only expressed in alveolar cells, but also highly expressed in male renal tubular cells [4] [21] [30] .All these suggest that SARS-CoV-2 not only causes damage to the respiratory system of patients, but also has a certain impact on the reproductive system of male patients.
cord-331140-5b0y1xzb	2020	key: cord-331140-5b0y1xzb title: SARS-CoV-2 and Prostatitis: dangerous relationship for male sexual and reproductive health cord_uid: 5b0y1xzb . Recently, SARS-CoV-2 was detected in semen samples (5) . Therefore, it is not unreasonable to believe that the latest coronavirus could potentially be transmitted via semen (6) . It was also reported that angiotensin converting enzyme 2 (ACE2) is a functional receptor that mediates the entry of SARS-CoV-1 (7) and 2 (8) , and this receptor is expressed in the prostate. Perhaps in the coming years, the real effect of SARS-CoV-2 on prostatitis cases will be evaluated and scope for researching factors that cause the clinical syndrome will be expanded. Male infertility: a public health issue caused by sexually transmitted pathogens Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease SARS-CoV-2 and the Testis: similarity to other viruses and routes of infection Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus
cord-331428-6pvr2vew	2020	
cord-332365-20u06444	2020	We suppose that ash and gases emitted from the Mount Etna contributed to air pollution, potentially favouring the major contagion of COVID-19 in the eastern flank of the mountain, as in Catania city. Heavy metals have been dosed in the groundwater of the Etna (used for water plants or to drink), especially in the eastern and southern sectors of the volcano, and they are believed to contribute to intoxication of public health and to pulmonary or neurodegenerative diseases [12, 14, 15] . This is the first paper that elaborates the hypothesis of a potential role of volcanic gases and heavy metals-related air pollution, combined to specific climatic conditions and regional topography, in favouring severe COVID-19 diffusion in Sicily. This is the first paper that elaborates the hypothesis of a potential role of volcanic gases and heavy metals-related air pollution, combined to specific climatic conditions and regional topography, in favouring severe COVID-19 diffusion in Sicily.
cord-334543-gavnscor	2020	This potential relationship between SARS-CoV-2 infection and clock genes, coupled with previously reported effects of night shift work on health leads us to hypothesize that night shift workers may be at an increased physiological risk of coronavirus disease-19 (COVID19) . This potential relationship between SARS-CoV-2 infection and clock genes, coupled with previously reported effects of night shift work on health leads us to hypothesize that night shift workers may be at an increased physiological risk of coronavirus disease-19 (COVID19) . The mechanisms that drive these associations are not well understood; however, current literature suggests that the disruption of circadian rhythms may cause downstream hormonal and immune effects that render night shift workers more susceptible to disease. The mechanisms that drive these associations are not well understood; however, current literature suggests that the disruption of circadian rhythms may cause downstream hormonal and immune effects that render night shift workers more susceptible to disease.
cord-334709-z70oevy2	2020	Similarly, to other corona viruses and influenza A, the receptor for adherence of SARS-CoV-2 is ACE2 which is abundant on respiratory and gastrointestinal mucosal cells, especially on alveolar type 2 pneumocytes [2] . Theoretically using of recombinant S1 protein, which will attach to the ACE2 receptors, may actively compete with the SARS-CoV-19 and prevent infection. They found affinity of HDEF5 binding to ACE2 of 76.2 nM, efficient blocking of SARS-CoV-2 receptor binding domain (RBD), and significant inhibition of invasion into Caco-2 cells. The next step, after preparing recombinant HDEF5, active and functioning, with high affinity to both receptor and ligand, is to make the protein available in powder, with small enough particles to be aerosolized and sprayed. Blocking the receptor for SARS-CoV-2 virus, ACE2, on the respiratory tract epithelium, especially the alveolar type 2 pneumocytes, will probably prevent invasion of the virus, at least for a short while.
cord-337493-8yhd697t	2020	key: cord-337493-8yhd697t authors: Choquenaira-Quispe, Celia; Saldaña-Bobadilla, Vanessa; Kenedy Ramirez, J. title: Factors involved in low susceptibility to covid-19: an adaptation of high altitude inhabitants cord_uid: 8yhd697t Consequently, populations from high altitude areas would be less susceptible to hypoxia during the infection. Consequently, SARS-CoV-2 infected populations from high altitude areas have greater lung adaptive capacity than those that live at low altitude. The three factors above would perform an important role in high altitude inhabitants, because they decrease the susceptibility to develop severe symptoms in SARS-CoV-2 infection. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Hepcidin and anemia: A tight relationship Does the pathogenesis of SARS-CoV-2 virus decrease at high-altitude? HIF stabilizers in the management of renal anemia: from bench to bedside to pediatrics The authors declare that there is no conflict of interest. The authors declare that there is no conflict of interest.
cord-337627-1a2gpqdl	2020	
cord-338585-ep9r1n8t	2020	title: A hypothesis for examining dihydroxyacetone, the active component in self-tanning products, as a topical prophylactic against SARS-COV-2 transmission This hypothesis raises the interesting prospect that dihydroxyacetone (DHA), the key ingredient in self-tanning creams, when applied daily to the face and hands may have prophylactic action against SARS-COV-2 transmission and infection. The Maillard Reaction, comprises a manifold of reactions including Schiff-base formation, aldol-type condensations, Amadori rearrangements, and dehydrative and/or oxidative aromatization events that modify lysine amines and give rise to crosslinks, (12) which are consistent with other advanced glycation events seen in diabetic patients. Together, such studies would systematically advance this hypothesis from well-established in vitro results to an easily monitored clinical trial, that would lead to a medically justified recommendation for daily topical prophylactic application of DHA to the face and hands for reducing SARS-COV-2 infection.
cord-344170-qrupbtem	2020	
cord-346281-sma6e891	2020	Pentoxifylline (PTX) is a phosphodiesterase inhibitor that increases cyclic adenosine monophosphate levels, which in turn activate protein kinase, leading to a reduction in the synthesis of proinflammatory cytokines to ultimately influence the renin-angiotensin system (RAS) in vitro by inhibiting angiotensin 1 receptor (AT1R) expression. The rheological, anti-inflammatory, and renin-angiotensin axis properties of PTX highlight this drug as a therapeutic treatment alternative for patients with COVID-19 by helping reduce the production of the inflammatory cytokines without deleterious effects on the immune system to delay viral clearance. 5 Overall, the rheological, anti-inflammatory, and renin-angiotensin axis properties of PTX highlight this drug as a therapeutic treatment alternative for patients with COVID-19, which can help reduce the production of the inflammatory cytokines TNF-α, IL-6, IFN-γ, and IL-17 and increase the anti-inflammatory cytokine IL-10.
cord-349718-x5i460bc	2020	Dr. Chandrasekaran''s reply to "Exercising and face masks: an important hypothesis buried in a selective review" This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. Dr. Chandrasekaran''s reply to "Exercising and face masks: an important hypothesis buried in a selective review" Thank you very much for your interest and critical feedback on our recent hypothesis article published in "Medical Hypotheses" journal. Firstly, we would like to clarify to the authors and readers that our article focuses only on the possible physiological mechanisms that could be associated with wearing the tight custom made cloth masks during moderate to heavy exercise (60 -80% VO2 max or above anaerobic threshold). Our hypothesis pertains to the use of tight custom made masks during moderate to vigorous exercise, not general household work nor in healthcare professionals.
cord-352911-9wbq9qo2	2020	The mortality related to severe acute respiratory distress syndrome (ARDS) and multi-organ failure in COVID-19 patients has been suggested to be connected with cytokine storm syndrome (CSS), an excessive immune response that severely damages healthy lung tissue. Total extracts from monolayer cell cultures infected with SARS-CoV-2 and treated with rhein under the conditions described above will be analysed using commercially available protein arrays to determine the levels and activation state of proteins involved in the TLR-, Akt-, MAPK-, and NF-B-regulated signalling pathways. The mechanisms of action involved include the control of hyperinflammatory conditions by multi-faceted cytokine inhibition of IL-1, IL-2, IL-6, IL-8, IL-12, IL-18 and TNF-α; anti-platelet aggregation activity; and potential effects on viral infection and replication. Rhein suppresses lung inflammatory injury induced by human respiratory syncytial virus through inhibiting NLRP3 inflammasome activation via NF-κB pathway in mice
cord-353716-gxgvhhv1	2020	title: SARS-CoV-2 cell entry receptor ACE2 mediated endothelial dysfunction leads to vascular thrombosis in COVID-19 patients Based on the circumstantial evidence present in the literature, we propose a SARS-CoV-2 cell entry receptor ACE2 based mechanism for vascular thrombosis in COVID-19 patients. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative pathogen for COVID-19 has been shown to bind to angiotensin converting enzyme 2 (ACE2) protein in human epithelial cells, which facilitates its entry in the organ and mediate tissue specific pathogenesis (4,5). Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative pathogen for COVID-19 has been shown to bind to angiotensin converting enzyme 2 (ACE2) protein in human epithelial cells, which facilitates its entry in the organ and mediate tissue specific pathogenesis (4,5). SARS-CoV-2 binding to the cell entry receptor ACE2 downregulates receptor expression that in turn induces vascular endothelial dysfunction, which activates prothrombotic cascade and eventually leads to vascular thrombosis observed in COVID-19 patients.