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Preprint REVIEW | doi:10.20944/preprints202004.0203.v1

Face Masks Against COVID-19: An Evidence Review

Jeremy Howard, Austin Huang, Zhiyuan Li, Zeynep Tufekci, Vladimir Zdimal, Helene-Mari van der Westhuizen, Arne von Delft, Amy Price, Lex Fridman, Lei-Han Tang, Viola Tang, Gregory L. Watson, Christina E. Bax, Reshama Shaikh, Frederik Questier, Danny Hernandez, Larry F. Chu, Christina M. Ramirez, Anne W. Rimoin

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; SARS-CoV-2; masks; pandemic

Online: 12 April 2020 (17:41:10 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202007.0025.v1

COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective Case Series Study

Martin Scholz, Roland Derwand, Vladimir Zelenko

Subject: Medicine And Pharmacology, Pharmacy Keywords: SARS-CoV-2; COVID-19; outpatients; treatment; zinc; hydroxychloroquine; azithromycin

Online: 3 July 2020 (08:52:22 CEST)

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Objective: To describe outcomes of patients with coronavirus disease 2019 (COVID-19) in the outpatient setting after early treatment with zinc, low dose hydroxychloroquine, and azithromycin (the triple therapy) dependent on risk stratification. Design: Retrospective case series study. Setting: General practice. Participants: 141 COVID-19 patients with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the year 2020. Main Outcome Measures: Risk-stratified treatment decision, rate of hospitalization and all-cause death. Results: Of 335 positively PCR-tested COVID-19 patients, 127 were treated with the triple therapy. 104 of 127 met the defined risk stratification criteria and were included in the analysis. In addition, 37 treated and eligible patients who were confirmed by IgG tests were included in the treatment group (total N=141). 208 of the 335 patients did not meet the risk stratification criteria and were not treated. After 4 days (median, IQR 3-6, available for N=66/141) of onset of symptoms, 141 patients (median age 58 years, IQR 40-67; 73% male) got a prescription for the triple therapy for 5 days. Independent public reference data from 377 confirmed COVID-19 patients of the same community were used as untreated control. 4 of 141 treated patients (2.8%) were hospitalized, which was significantly less (p<0.001) compared with 58 of 377 untreated patients (15.4%) (odds ratio 0.16, 95% CI 0.06-0.5). Therefore, the odds of hospitalization of treated patients were 84% less than in the untreated group. One patient (0.7%) died in the treatment group versus 13 patients (3.5%) in the untreated group (odds ratio 0.2, 95% CI 0.03-1.5; p=0.16). There were no cardiac side effects. Conclusions: Risk stratification-based treatment of COVID-19 outpatients as early as possible after symptom onset with the used triple therapy, including the combination of zinc with low dose hydroxychloroquine, was associated with significantly less hospitalizations and 5 times less all-cause deaths.

Preprint ARTICLE | doi:10.20944/preprints202004.0315.v1

In Search of Preventative Strategies: Novel Anti-Inflammatory High-CBD Cannabis Sativa Extracts Modulate ACE2 Expression in COVID-19 Gateway Tissues

Bo Wang, Anna Kovalchuk, Dongping Li, Yaroslav Ilnytskyy, Igor Kovalchuk, Olga Kovalchuk

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: COVID-19; SARS-CoV2; ACE2 receptor; medical cannabis; CBD

Online: 19 April 2020 (02:45:50 CEST)

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With the rapidly growing pandemic of COVID-19 caused by the new and challenging to treat zoonotic SARS-CoV2 coronavirus, there is an urgent need for new therapies and prevention strategies that can help curtail disease spread and reduce mortality. Inhibition of viral entry and thereby spread constitute plausible therapeutic avenues. Similar to other respiratory pathogens, SARS-CoV2 is transmitted through respiratory droplets, with potential for aerosol and contact spread. It uses receptor-mediated entry into the human host via angiotensin-converting enzyme II (ACE2) that is expressed in lung tissue, as well as oral and nasal mucosa, kidney, testes, and the gastrointestinal tract. Modulation of ACE2 levels in these gateway tissues may prove a plausible strategy for decreasing disease susceptibility. Cannabis sativa, especially one high in the anti-inflammatory cannabinoid cannabidiol (CBD), has been proposed to modulate gene expression and inflammation and harbour anti-cancer and anti-inflammatory properties. Working under the Health Canada research license, we have developed over 800 new Cannabis sativa lines and extracts and hypothesized that high-CBD C. sativa extracts may be used to modulate ACE2 expression in COVID-19 target tissues. Screening C. sativa extracts using artificial human 3D models of oral, airway, and intestinal tissues, we identified 13 high CBD C. sativa extracts that modulate ACE2 gene expression and ACE2 protein levels. Our initial data suggest that some C. sativa extract down-regulate serine protease TMPRSS2, another critical protein required for SARS-CoV2 entry into host cells. While our most effective extracts require further large-scale validation, our study is crucial for the future analysis of the effects of medical cannabis on COVID-19. The extracts of our most successful and novel high CBD C. sativa lines, pending further investigation, may become a useful and safe addition to the treatment of COVID-19 as an adjunct therapy. They can be used to develop easy-to-use preventative treatments in the form of mouthwash and throat gargle products for both clinical and at-home use. Such products ought to be tested for their potential to decrease viral entry via the oral mucosa. Given the current dire and rapidly evolving epidemiological situation, every possible therapeutic opportunity and avenue must be considered.

Preprint ARTICLE | doi:10.20944/preprints202208.0151.v1

Cardiovascular Effects of the BNT162b2 mRNA COVID-19 Vaccine in Adolescents

Suyanee Mansanguan, Prakaykaew Charunwatthana, Watcharapong Piyaphanee, Wilanee Dechkhajorn, Akkapon Poolcharoen, Chayasin Mansanguan

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: BNT162b2 mRNA COVID-19 vaccine; COVID-19 vaccine; cardiovascular effects; myocarditis; adolescents; Thailand

Online: 8 August 2022 (10:40:23 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202101.0412.v1

Raspberry PI for Kill Mosquitoes by Laser

Ildar Rakhmatulin

Subject: Biology And Life Sciences, Insect Science Keywords: laser for mosquito control; deep learning for mosquito control; insect detection; mosquito neutralization; pest detection; insect recognition; Raspberry Pi3; Raspberry Pi4; OpenCV for small object detect

Online: 21 January 2021 (09:27:07 CET)

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Preprint REVIEW | doi:10.20944/preprints202003.0235.v1

Vitamin D Supplementation Could Prevent and Treat Influenza, Coronavirus, and Pneumonia Infections

William B. Grant, Henry Lahore, Sharon L. McDonnell, Carole A. Baggerly, Christine B. French, Jennifer L. Aliano, Harjit Pal Bhattoa

Subject: Medicine And Pharmacology, Dietetics And Nutrition Keywords: ascorbic acid; cahtelicidin; coronavirus; COVID-19; cytokine storm; influenza, pneumonia; prevention; respiratory tract infection; UVB; vitamin C; Vitamn D; solar radiation; treatment; observational; trial

Online: 15 March 2020 (01:47:19 CET)

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Preprint REVIEW | doi:10.20944/preprints202004.0203.v2

Face Masks Against COVID-19: An Evidence Review

Jeremy Howard, Austin Huang, Zhiyuan Li, Zeynep Tufekci, Vladimir Zdimal, Helene-Mari van der Westhuizen, Arne von Delft, Amy Price, Lex Fridman, Lei-Han Tang, Viola Tang, Gregory L. Watson, Christina E. Bax, Reshama Shaikh, Frederik Questier, Danny Hernandez, Larry F. Chu, Christina M. Ramirez, Anne W. Rimoin

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; SARS-CoV-2; masks; pandemic

Online: 13 May 2020 (13:16:04 CEST)

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The science around the use of masks by the general public to impede COVID-19 transmission is advancing rapidly. Policymakers need guidance on how masks should be used by the general population to combat the COVID-19 pandemic. Here,we develop an analytical framework to examine an overlooked aspect of mask usage: masks as source-control targeting egress from the wearer with benefits at the population-level, rather than as PPE used for ingress control for health-care workers with focus on individual outcomes. We consider and synthesize the relevant literature to inform multiple areas: 1) transmission characteristics of COVID-19, 2) filtering characteristics and efficacy of masks, 3) estimated population impacts of widespread community mask use, and 4) sociological considerations for policies concerning mask-wearing. A primary route of transmission of COVID-19 is likely via respiratory droplets, and is known to be transmissible from presymptomatic and asymptomatic individuals. Reducing disease spread requires two things: first, limit contacts of infected individuals via physical distancing and other measures, and second, reduce the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces the transmissibility per contact by reducing transmission of infected droplets in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. The decreased transmissibility could substantially reduce the death toll and economic impact while the cost of the intervention is low. Given the current shortages of medical masks we recommend the adoption of public cloth mask wearing, as an effective form of source control for now, in conjunction with existing hygiene, distancing, and contact tracing strategies. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.

Preprint ARTICLE | doi:10.20944/preprints202002.0051.v1

Tobacco-Use Disparity in Gene Expression of ACE2, the Receptor of 2019-nCov

Guoshuai Cai

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Wuhan 2019-nCov; ACE2; expression; susceptibility; race; age; gender; smoking

Online: 5 February 2020 (02:56:53 CET)

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Preprint HYPOTHESIS | doi:10.20944/preprints202004.0023.v1

Kinins and Cytokines in COVID-19: A Comprehensive Pathophysiological Approach

Frank van de Veerdonk, Mihai G. Netea, Marcel van Deuren, Jos W.M. van der Meer, Quirijn de Mast, Roger J. Bruggemann, Hans van der Hoeven

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; bradykinin; ACE2; pulmonary angioedema; ARDS; icatibant

Online: 3 April 2020 (04:13:43 CEST)

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Most striking observations in COVID-19 patients are the hints on pulmonary edema (also seen on CT scans as ground glass opacities), dry cough, fluid restrictions to prevent more severe hypoxia, the huge PEEP that is needed while lungs are compliant, and the fact that anti-inflammatory therapies are not powerful enough to counter the severity of the disease. We propose that the severity of the disease and many deaths are due to a local vascular problem due to activation of B1 receptors on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2, a cell membrane bound molecule with enzymatic activity that next to its role in RAS is needed to inactivate des-Arg⁹ bradykinin, the potent ligand of the bradykinin receptor type 1 (B1). In contrast to bradykinin receptor 2 (B2), the B1 receptor on endothelial cells is upregulated by proinflammatory cytokines. Without ACE2 acting as a guardian to inactivate the ligands of B1, the lung environment is prone for local vascular leakage leading to angioedema. Angioedema is likely a feature already early in disease, and might explain the typical CT scans and the feeling of people that they drown. In some patients, this is followed by a clinical worsening of disease around day 9 due to the formation antibodies directed against the spike (S)-antigen of the corona-virus that binds to ACE2 that could contribute to disease by enhancement of local immune cell influx and proinflammatory cytokines leading to damage. In parallel, inflammation induces more B1 expression, and possibly via antibody-dependent enhancement of viral infection leading to continued ACE2 dysfunction in the lung because of persistence of the virus. In this viewpoint we propose that a bradykinin-dependent local lung angioedema via B1 and B2 receptors is an important feature of COVID-19, resulting in a very high number of ICU admissions. We propose that blocking the B1 and B2 receptors might have an ameliorating effect on disease caused by COVID-19. This kinin-dependent pulmonary edema is resistant to corticosteroids or adrenaline and should be targeted as long as the virus is present. In addition, this pathway might indirectly be responsive to anti-inflammatory agents or neutralizing strategies for the anti-S-antibody induced effects, but by itself is likely to be insufficient to reverse all the pulmonary edema. Moreover, we provide a suggestion of how to ventilate in the ICU in the context of this hypothesis.

Preprint ARTICLE | doi:10.20944/preprints202005.0057.v1

Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study

Francisco Javier Membrillo de Novales, Germán Ramírez-Olivencia, Miriam Estébanez, Begoña de Dios, María Dolores Herrero, Tatiana Mata, Alberto M. Borobia, Carlos Gutiérrez, María Simón, Ana Ochoa, Yolanda Martínez, Alejandro Aguirre, Francisco de Asís Alcántara, Pablo Fernández-González, Elena López, Sergio Campos, María Navarro, Lucía Elena Ballester

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; treatment; drug; survival; antiviral; hydroxychloroquine

Online: 5 May 2020 (03:32:22 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202302.0350.v1

Is there a Link between the 2021 COVID-19 Vaccination Uptake in Europe and 2022 Excess All-Cause Mortality?

Jarle Aarstad, Olav Andreas Kvitastein

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; vaccination; all-cause mortality; excess mortality; causal inferences; ecological fallacy; individualistic fallacy

Online: 21 February 2023 (03:49:52 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0226.v1

Potential Inhibitor of COVID-19 Main Protease (M^pro) From Several Medicinal Plant Compounds by Molecular Docking Study

Siti Khaerunnisa, Hendra Kurniawan, Rizki Awaluddin, Suhartati Suhartati, Soetjipto Soetjipto

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-2019; Mpro; 6LU7; medicinal plant compounds; docking

Online: 13 March 2020 (03:19:02 CET)

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Preprint REVIEW | doi:10.20944/preprints202004.0203.v3

Face Masks Against COVID-19: An Evidence Review

Jeremy Howard, Austin Huang, Zhiyuan Li, Zeynep Tufekci, Vladimir Zdimal, Helene-Mari van der Westhuizen, Arne von Delft, Amy Price, Lex Fridman, Lei-Han Tang, Viola Tang, Gregory L. Watson, Christina E. Bax, Reshama Shaikh, Frederik Questier, Danny Hernandez, Larry F. Chu, Christina M. Ramirez, Anne W. Rimoin

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; SARS-CoV-2; masks; pandemic

Online: 12 July 2020 (16:11:50 CEST)

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The science around the use of masks by the general public to impede COVID-19 transmission is advancing rapidly. Policymakers need guidance on how masks should be used by the general population to combat the COVID-19 pandemic. In this narrative review, we develop an analytical framework to examine mask usage, considering and synthesizing the relevant literature to inform multiple areas: population impact; transmission characteristics; source control; PPE; sociological considerations; and implementation considerations. A primary route of transmission of COVID-19 is via respiratory droplets, and is known to be transmissible from presymptomatic and asymptomatic individuals. Reducing disease spread requires two things: first, limit contacts of infected individuals via physical distancing and other measures, and second, reduce the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces the transmissibility per contact by reducing transmission of infected droplets in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. The decreased transmissibility could substantially reduce the death toll and economic impact while the cost of the intervention is low. Given the current shortages of medical masks we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory droplets become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask-wearing by infectious people ("source control") with benefits at the population-level, rather than mask-wearing by susceptible people, such as health-care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.

Preprint ARTICLE | doi:10.20944/preprints202003.0422.v1

SARS-CoV-2 Prion-Like Domains in Spike Proteins Enable Higher Affinity to ACE2

George Tetz, Victor Tetz

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: COVID-19; SARS; SARS-CoV-2 Prion-like domain

Online: 29 March 2020 (06:16:20 CEST)

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Preprint REVIEW | doi:10.20944/preprints202010.0330.v2

COVID-19: Rethinking the Lockdown Groupthink

Ari Joffe

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; Public Health; Lockdowns; Cost-benefit analysis; Groupthink

Online: 4 November 2020 (10:14:33 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0455.v1

Eucalyptol (1,8 cineole) from Eucalyptus Essential Oil a Potential Inhibitor of COVID 19 Corona Virus Infection by Molecular Docking Studies

Arun Dev Sharma, inderjeet kaur

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; Essential oil; Eucalyptol; Molecular docking

Online: 31 March 2020 (10:16:13 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202209.0430.v1

COVID-19 Vaccines: The Impact on Pregnancy Outcomes and Menstrual Function

James A. Thorp, Claire Rogers, Michael P. Deskevich, Stewart Tankersley, Albert Benavides, Megan D. Redshaw, Peter A. McCullough

Subject: Medicine And Pharmacology, Obstetrics And Gynaecology Keywords: COVID-19 vaccines; menstruation; pregnancy outcomes; Influenza vaccines; VAERS

Online: 28 September 2022 (03:50:35 CEST)

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Preprint REVIEW | doi:10.20944/preprints202006.0159.v1

SeXX and COVID-19: Tussle between the Two

Ashlesh Patil, Jaya Prasad Tripathy, Vishwajit Deshmukh, Bharat Sontakke, Satyendra C. Tripathi

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Sex; COVID-19; SARS Cov-2; ACE2; innate immunity; adaptive immunity

Online: 14 June 2020 (03:18:35 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202309.0131.v1

Forensic Analysis of the 38 Subject Deaths in the 6-Month Interim Report of the Pfizer/BioNTech BNT162b2 mRNA Vaccine Clinical Trial

Corinne Michels, Daniel Perrier, Jeyanthi Kunadhasan, Ed Clark, Joseph Gehrett, Barbara Gehrett, Kim Kwiatek, Sarah Adams, Robert Chandler, Leah Stagno, Tony Damian, Erika Delph, Chris Flowers

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: BNT162b2 vaccine; Pfizer/BioNTech; cardiovascular events; COVID-19

Online: 4 September 2023 (08:19:54 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201803.0122.v1

Accelerated Reported Battery Capacity Loss in 30 kWh Variants of the Nissan Leaf

Daniel Myall, Dima Ivanov, Walter Larason, Mark Nixon, Henrik Moller

Subject: Engineering, Energy And Fuel Technology Keywords: electric vehicle; Nissan Leaf; lithium-ion battery; capacity loss; battery degradation

Online: 15 March 2018 (07:19:52 CET)

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Preprint REVIEW | doi:10.20944/preprints202307.1198.v1

Autopsy Proven Fatal COVID-19 Vaccine-Induced Myocarditis

Nicolas Hulscher, Roger Hodkinson, William Makis, Peter McCullough

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: myocarditis; sudden death; chest pain; autopsy; necropsy; COVID-19; COVID-19 vaccines; mRNA; SARS-CoV-2 vaccination; death; excess mortality; spike protein; organ system

Online: 18 July 2023 (09:34:51 CEST)

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Background: COVID-19 vaccines have been linked to myocarditis which in some circumstances can be fatal. This systematic review aims to investigate potential causal links between COVID-19 vaccines and death from myocarditis using post-mortem analysis. Methods: We performed a systematic review of all published autopsy reports involving COVID-19 vaccination-related myocarditis through July 3^rd, 2023. All autopsy studies that include COVID-19 vaccine-induced myocarditis as a possible cause of death were included, without imposing any additional restrictions. Causality in each case was determined by three independent reviewers with cardiac pathology experience and expertise. Results: We initially identified 1,691 studies and, after screening for our inclusion criteria, included 14 papers that contained 28 autopsy cases. The cardiovascular system was the only organ system affected in 26 cases. In 2 cases, myocarditis was characterized as a consequence from multisystem inflammatory syndrome (MIS). The mean and median number of days from last COVID-19 vaccination until death was 6.2 and 3 days, respectively. Most of the deaths occurred within a week from the last injection. We established that all 28 deaths were causally linked to COVID-19 vaccination by independent adjudication. Conclusions: The temporal relationship, internal and external consistency seen among cases in this review with known COVID-19 vaccine-induced myocarditis, its pathobiological mechanisms and related excess death, complemented with autopsy confirmation, independent adjudication, and application of the Bradford Hill criteria to the overall epidemiology of vaccine myocarditis, suggests there is a high likelihood of a causal link between COVID-19 vaccines and death from suspected myocarditis in cases where sudden, unexpected death has occurred in a vaccinated person. Urgent investigation is required for the purpose of risk stratification and mitigation in order to reduce the population occurrence of fatal COVID-19 vaccine-induced myocarditis.

Preprint ARTICLE | doi:10.20944/preprints202002.0179.v1

A Simulation on Potential Secondary Spread of Novel Coronavirus in an Exported Country Using a Stochastic Epidemic SEIR Model

Kentaro Iwata, Chisato Miyakoshi

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: novel coronavirus; SEIR model; outside China

Online: 14 February 2020 (02:34:55 CET)

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Preprint REVIEW | doi:10.20944/preprints202003.0235.v2

Evidence That Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

William B. Grant, Henry Lahore, Sharon L. McDonnell, Carole A. Baggerly, Christine B. French, Jennifer L. Aliano, Harjit Pal Bhattoa

Subject: Medicine And Pharmacology, Dietetics And Nutrition Keywords: acute respiratory distress syndrome (ARDS); ascorbic acid; cathelicidin; coronavirus; COVID-19; cytokine storm; influenza; observational; pneumonia, prevention; respiratory tract infection; solar radiation; treatment; UVB; vitamin C; vitamin D

Online: 30 March 2020 (05:48:43 CEST)

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The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

Preprint ARTICLE | doi:10.20944/preprints202308.0148.v1

GPT-4 Can't Reason

Konstantine Arkoudas

Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: GPT-4; LLM; AI; reasoning; inference

Online: 2 August 2023 (04:10:57 CEST)

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Preprint REVIEW | doi:10.20944/preprints202005.0226.v1

Transgender Women in The Female Category of Sport: Is the Male Performance Advantage Removed by Testosterone Suppression?

Emma N. Hilton, Tommy R. Lundberg

Subject: Social Sciences, Tourism, Leisure, Sport And Hospitality Keywords: androgens; athletic performance; cross-hormone therapy; gender dysphoria; muscle; sex hormones; sporting policies; strength; transgender men; transgender women

Online: 13 May 2020 (11:25:23 CEST)

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Sex dimorphism starts during early embryogenesis and is further manifested in response to hormones during puberty. As this leads to physical divergence that is measurably different between sexes, males enjoy physical performance advantages over females within competitive sport. While this advantage is the underlying basis of the segregation into male and female sporting categories, these sex-based categories do not account for transgender persons who experience incongruence between their biological sex and their experienced gender identity. Accordingly, the International Olympic Committee determined criteria by which a transgender woman may be eligible to compete in the female category, requiring total serum testosterone levels to be suppressed below 10 nmol/L for at least 12 months prior to and during competition. Whether this regulation removes the male performance advantage has not been collectively scrutinized. Here, we aim to review how differences in biological characteristics between biological males and females affect sporting performance and assess whether evidence exists to support the assumption that testosterone suppression in transgender women removes the male performance advantage. In this review, we report that the performance gap between males and females amounts to 10-50% depending on sport. The performance gap is more pronounced in sporting activities relying on muscle mass and strength, particularly in the upper body. Longitudinal studies examining the effects of testosterone suppression on muscle mass and strength in transgender women consistently show very modest changes, where the loss of lean body mass, muscle area and strength typically amounts to approximately 5% after 1 year of treatment. Thus, current evidence shows that the biological advantage enjoyed by transgender women is only minimally reduced when testosterone is suppressed. Sports organizations may therefore be compelled to reassess current policies regarding participation of transgender women in the female category of sport.

Working Paper HYPOTHESIS

The First, Comprehensive Immunological Model of COVID-19: Implications for Prevention, Diagnosis, and Public Health Measures

Paolo Matricardi, Roberto Dal Negro, Roberto Nisini

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: antibodies; COVID-19; glycans; immunoglobulin M; SARS-CoV-2; pneumonia; prediction; protection

Online: 24 April 2020 (10:25:27 CEST)

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Working Paper ARTICLE

Individual Variation of the SARS-CoV2 Receptor ACE2 Gene Expression and Regulation

Jiawei Chen, Quanlong Jiang, Xian Xia, Kangping Liu, Zhengqing Yu, Wanyu Tao, Wenxuan Gong, Jing-Dong J. Han

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: COVID19; ACE2; SARS-CoV2

Online: 12 March 2020 (03:15:15 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202101.0132.v1

Genomic Evidence of a Sars-Cov-2 Reinfection Case With E484K Spike Mutation in Brazil

Carolina Kymie Vasques Nonaka, Marília Miranda Franco, Tiago Gräf, Ana Verena Almeida Mendes, Renato Santana de Aguiar, Marta Giovanetti, Bruno Solano de Freitas Souza

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2; reinfection; E484K

Online: 6 January 2021 (20:38:36 CET)

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Preprint ARTICLE | doi:10.20944/preprints202005.0486.v1

Azithromycin and Hydroxychloroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19

Violaine Guérin, Pierre Lévy, Jean-Louis Thomas, Thierry Lardenois, Philippe Lacrosse, Emmanuel Sarrazin, Natacha Regensberg de Andreis, Martine Wonner

Subject: Medicine And Pharmacology, Pharmacy Keywords: COVID-19; SARS-CoV-2; azithromycin; hydroxychloroquine; primary care

Online: 31 May 2020 (17:51:52 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0457.v1

Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19

Anton S.M. Dofferhoff, Ianthe Piscaer, Leon J. Schurgers, Jona Walk, Jody M.W. van den Ouweland, Tilman M. Hackeng, Petra Lux, Cecile Maassen, Esther G.A. Karssemeijer, Emiel F.M. Wouters, Rob Janssen

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; vitamin K; vitamin K antagonists; SARS-CoV-2; matrix Gla protein; desmosine; protein C; protein S

Online: 25 April 2020 (03:13:45 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202209.0430.v2

COVID-19 Vaccines: The Impact on Pregnancy Outcomes and Menstrual Function

James A. Thorp, Claire Rogers, Michael P. Deskevich, Stewart Tankersley, Albert Benavides, Megan D. Redshaw, Peter A. McCullough

Subject: Medicine And Pharmacology, Obstetrics And Gynaecology Keywords: COVID-19 vaccines; menstruation; pregnancy outcomes; Influenza vaccines; VAERS; stillbirth; miscarriage

Online: 30 December 2022 (09:39:28 CET)

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Preprint REVIEW | doi:10.20944/preprints202010.0330.v1

COVID-19: Rethinking the Lockdown Groupthink

Ari Joffe

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; Public Health; Lockdowns; Cost-benefit analysis

Online: 15 October 2020 (16:02:58 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202004.0124.v1

Does Zinc Supplementation Enhance the Clinical Efficacy of Chloroquine/Hydroxychloroquine to Win Todays Battle Against COVID-19?

Martin Scholz, Roland Derwand

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; SARS-CoV-2; Therapy; Chloroquine; Hydroxychloroquine; Zinc

Online: 8 April 2020 (10:54:33 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202301.0204.v3

Forgotten “Primum Non Nocere” and Increased Mortality after Covid-19 Vaccination

Srecko Šorli, Tomaz Makovec, Zivan Krevel, Rado Gorjup

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Covid-19 vaccination; death rate; sick status days

Online: 13 February 2023 (04:27:07 CET)

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Preprint HYPOTHESIS | doi:10.20944/preprints202303.0441.v1

IgG4 Antibodies Induced by mRNA Vaccines Generate Immune Tolerance to SARS-CoV-2’spike Protein by Suppressing the Immune System

Vladimir N. Uversky, Elrashdy M. Redwan, William Makis, Alberto Rubio-Casillas

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: IgG4 antibodies; mRNA vaccines; immuno-tolerance; auto-immunity; SARS-CoV-2; COVID-19.

Online: 27 March 2023 (03:56:26 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202003.0180.v1

First Case of COVID-19 Infection with Fulminant Myocarditis Complication: Case Report and Insights

Jia Hui Zeng, Ying-Xia Liu, Jing Yuan, Fu-Xiang Wang, Wei-Bo Wu, Jin-Xiu Li, Li-Fei Wang, Hong Gao, Yao Wang, Chang-Feng Dong, Yi-Jun Li, Xiao-Juan Xie, Cheng Feng, Lei Liu

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; coronavirus; fulminant myocarditis; infection; echocardiography

Online: 11 March 2020 (04:57:10 CET)

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Preprint ARTICLE | doi:10.20944/preprints202103.0271.v1

Clinical Characteristics, Activity Levels and Mental Health Problems in Children with Long COVID: A Survey of 510 Children

Danilo Buonsenso, Ferran Espuny Pujol, Daniel Munblit, Sammie Mcfarland, Frances Simpson

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: long covid; children; SARS-CoV-2

Online: 9 March 2021 (12:37:24 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0333.v1

Identification of Potent COVID-19 Main Protease (Mpro) Inhibitors from Natural Polyphenols: An in Silico Strategy Unveils a Hope against CORONA

Sevki Adem, Volkan Eyupoglu, Iqra Sarfraz, Azhar Rasul, Muhammad Ali

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; SARS-CoV-2; molecular docking; flavonoids

Online: 23 March 2020 (04:30:47 CET)

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Working Paper BRIEF REPORT

Design of an Epitope-Based Synthetic Long Peptide Vaccine to Counteract the Novel China Coronavirus (2019-nCoV)

Florina Bojin, Oana Gavriliuc, Michael-Bogdan Margineanu, Virgil Paunescu

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: 2019-nCoV; coronavirus; peptide vaccine; CD4+ epitope; CD8+ epitope

Online: 8 February 2020 (05:56:31 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0214.v1

Revealing the Potency of Citrus and Galangal Constituents to Halt SARS-CoV-2 Infection

Rohmad Yudi Utomo, Muthi' Ikawati, Edy Meiyanto

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS-Cov-2; Citrus sp.; Galangal; Curcuma sp.; Sappan wood

Online: 12 March 2020 (13:59:40 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0078.v1

Susceptibility Analysis of COVID-19 in Smokers Based on ACE2

Jin Wang, Qiulin Luo, Rui Chen, Tao Chen, Jianxiang Li

Subject: Biology And Life Sciences, Behavioral Sciences Keywords: cigarette smoke; ACE2; HCoV-19; susceptibility

Online: 5 March 2020 (03:15:43 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0058.v1

Was School Closure Effective in Mitigating Coronavirus Disease 2019 (COVID-19)? Time Series Analysis Using Bayesian Inference

Kentaro Iwata, Asako Doi, Chisato Miyakoshi

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: coronavirus disease 2019 (COVID-19); school closure; time series analysis; Japan

Online: 6 April 2020 (13:11:12 CEST)

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Preprint ESSAY | doi:10.20944/preprints202106.0491.v1

Strengths and Weaknesses of Semi-Structured Interviews in Qualitative Research: A Critical Essay

Charles Kakilla

Subject: Business, Economics And Management, Accounting And Taxation Keywords: Semi-structured Interview; SSI; In-depth interview; Strength and Weakness

Online: 21 June 2021 (08:52:20 CEST)

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Working Paper ARTICLE

Coronavirus Disease 2019 (COVID-19) During Pregnancy: A Case Series

Weiyong Liu, Qianli Wang, Qi Zhang, Ling Chen, Junbo Chen, Bo Zhang, Yanjun Lu, Shaoshuai Wang, Liming Xia, Lu Huang, Kai Wang, Lu Liang, Yongli Zhang, Lance Turtle, David Lissauer, Ke Lan, Ling Feng, Hongjie Yu, Yingle Liu, Ziyong Sun

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: pregnancy; neonate; COVID-19; SARS-CoV-2; vertical transmission

Online: 25 February 2020 (11:38:47 CET)

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Preprint ARTICLE | doi:10.20944/preprints202002.0408.v1

A Hint on the COVID-19 Risk: Population Disparities in Gene Expression of Three Receptors of SARS-CoV

Guoshuai Cai, Xiang Cui, Xia Zhu, Jun Zhou

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Wuhan SARS-CoV-2; ACE2; DC-SIGN; L-SIGN; expression; susceptibility; race; age; gender; smoking; single cell

Online: 27 February 2020 (12:45:26 CET)

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Preprint ARTICLE | doi:10.20944/preprints202002.0315.v1

Two Things about COVID-19 Might Need Attention

Xiaodong Jia, Chengliang Yin, Shanshan Lu, Yan Chen, Qingyan Liu, Junfan Bai, Yinying Lu

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; adipose tissue; cancer; ACE2

Online: 23 February 2020 (10:30:06 CET)

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Preprint HYPOTHESIS | doi:10.20944/preprints202003.0279.v1

Repositioning Chloroquine as Ideal Antiviral Prophylactic against COVID-19 - Time is Now

Raymond Chang, Wei-Zen Sun

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: chloroquine; COVID-19; SARS-CoV2; antiviral; viral prophylaxis

Online: 17 March 2020 (15:57:38 CET)

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Preprint COMMUNICATION | doi:10.20944/preprints202005.0126.v1

Re-thinking the Potential for Airborne Transmission of SARS-CoV-2

Joseph Allen, Linsey Marr

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: SARS-CoV-2; COVID-19; airborne; aerosol; transmission

Online: 7 May 2020 (13:20:42 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0548.v1

Why Does COVID-19 Disproportionately Affect the Elderly?

Amber L. Mueller, Maeve S. McNamara, David A. Sinclair

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: COVID-19; coronavirus; SARS-CoV-2; aging; immunosenescence; inflammaging; inflammation; cytokine storm; epigenetics; biological clock; sirtuin; glycome

Online: 30 April 2020 (22:38:53 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201908.0233.v1

Estimating Flight Characteristics of Anomalous Unidentified Aerial Vehicles

Kevin H. Knuth, Robert M. Powell, Peter A. Reali

Subject: Physical Sciences, Applied Physics Keywords: UAP; UAV; UFO; Nimitz; TicTac; JAL1628

Online: 22 August 2019 (11:50:30 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202002.0299.v1

scRNA-seq Profiling of Human Testes Reveals the Presence of ACE2 Receptor, a Target for SARS-CoV-2 Infection, in Spermatogonia, Leydig and Sertoli Cells

Zhengpin Wang, Xiaojiang Xu

Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: SARS-CoV-2; infection; scRNA-Seq; ACE2; spermatogonia

Online: 21 February 2020 (02:42:15 CET)

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Preprint HYPOTHESIS | doi:10.20944/preprints202004.0349.v1

COVID-19: Beta-Thalassemia Subjects Immunised?

Edouard Lansiaux, Philippe Pierre Pebay, Jean Laurent Picard, Joachim Son-Forget

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Novel Coronavirus; respiratory distress; Favipiravir; statistics; correlation; beta thalassemia; immunisation; Italy; Sardinia; regression; heme

Online: 19 April 2020 (13:48:56 CEST)

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Preprint REVIEW | doi:10.20944/preprints202003.0346.v1

The Molecular Story of COVID-19; NAD⁺Depletion Addresses All Questions in this Infection

Shirin Kouhpayeh, Laleh Shariati, Maryam Boshtam, Ilnaz Rahimmanesh, Mina Mirian, Mehrdad Zeinalian, Azhar Salari-jazi, Negar Khanahmad, Mohammad Sadegh Damavandi, Parisa Sadeghi, Hossein Khanahmad

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; nCoV 19; oxidative stress; PARP; PARG; TRPM2

Online: 23 March 2020 (07:40:50 CET)

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Working Paper REVIEW

Review of Infective Dose, Routes of Transmission, and Outcome of COVID-19 Caused by the SARS-CoV-2 Virus: Comparison with Other Respiratory Viruses

Sedighe Karimzadeh, Raj Bhopal, Huy Nguyen Tien

Subject: Biology And Life Sciences, Virology Keywords: infective dose; SARS-CoV-2; COVID-19; respiratory viruses; viral load; viral dynamics

Online: 25 July 2020 (16:21:53 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202006.0013.v1

Challenges and Possibilities of Online Education during Covid-19

Alaul Alam

Subject: Social Sciences, Education Keywords: online education; corona crisis; challenges; possibilities

Online: 3 June 2020 (08:25:46 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202002.0242.v2

Potential Therapeutic Agents for COVID-19 Based on the Analysis of Protease and RNA Polymerase Docking

Yu-Chuan Chang, Yi-An Tung, Ko-Han Lee, Ting-Fu Chen, Yu-Chun Hsiao, Hung-Ching Chang, Tsung-Ting Hsieh, Chan-Hung Su, Su-Shia Wang, Jheng-Ying Yu, Shang-shung Shih, Yu-Hsiang Lin, Yin-Hung Lin, Yi-Chin Ethan Tu, Chun-Hua Hsu, Hsueh-Fen Juan, Chun-Wei Tung, Chien-Yu Chen

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; molecular docking; HIV protease inhibitor; nucleotide analogues

Online: 29 February 2020 (12:43:40 CET)

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Preprint ARTICLE | doi:10.20944/preprints202012.0072.v1

Constructivism Theory: The Factors Affecting Students’ Academic Performance in Higher Education

ALI Mugahed Al-Rahmi

Subject: Computer Science And Mathematics, Algebra And Number Theory Keywords: constructivism theory; social media; educational quality; students’ academic performance; engagement

Online: 2 December 2020 (15:39:28 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202007.0178.v1

Brief Report: Rapid Clinical Recovery from Critical COVID-19 with Respiratory Failure in a Lung Transplant Patient Treated with Intravenous Vasoactive Intestinal Peptide

Jihad Georges Youssef, Faisal Zahiruddin, Mukhtar Al-Saadi, Simon Yau, Ahmad Goodarzi, Howard J. Huang, Jonathan C. Javitt

Subject: Medicine And Pharmacology, Internal Medicine Keywords: Aviptadil; Vasoactive Intestinal Peptide; VIP; SARS-CoV-2; COVID-19; Corona Virus; Acute Respiratory Distress Syndrome; ARDS; Acute Lung Injury; ALI; surfactant; Alveolar Type II; ATII

Online: 9 July 2020 (07:54:22 CEST)

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Preprint REVIEW | doi:10.20944/preprints202303.0140.v1

Autoimmune Inflammatory Reactions Triggered by the COVID-19 Genetic Vaccines in Terminally Differentiated Tissues

Panagis Polykretis, Alberto Donzelli, Janci C. Lindsay, David Wiseman, Anthony M. Kyriakopoulos, Michael Mörz, Paolo Bellavite, Masanori Fukushima, Stephanie Seneff, Peter A. McCullough

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: COVID-19; genetic vaccines; adverse reactions; autoimmunity; immunohistochemistry; spike protein

Online: 8 March 2023 (02:57:33 CET)

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Preprint REVIEW | doi:10.20944/preprints202004.0204.v1

Is COVID-19 an Endothelial Disease? Clinical and Basic Evidence

Celestino Sardu, Jessica Gambardella, Marco Bruno Morelli, Xujun Wang, Raffaele Marfella, Gaetano Santulli

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Covid-19; coronavirus; cardiovascular disease; thrombosis; hypertension; endothelial dysfunction

Online: 13 April 2020 (02:23:33 CEST)

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Preprint REVIEW | doi:10.20944/preprints202002.0283.v1

Emerging Understanding of Etiology and Epidemiology of the Novel Coronavirus (COVID-19) infection in Wuhan, China

Daibing Zhou, Peng Zhang, Chen Bao, Youzhi Zhang, Ning Zhu

Subject: Biology And Life Sciences, Virology Keywords: Etiology; Epidemiology; COVID-19; Wuhan

Online: 19 February 2020 (11:58:13 CET)

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Preprint ARTICLE | doi:10.20944/preprints202005.0057.v2

Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study

Francisco Javier Membrillo, Germán Ramírez-Olivencia, Miriam Estébanez, Begoña de Dios, María Dolores Herrero, Tatiana Mata, Alberto M. Borobia, Carlos Gutiérrez, María Simón, Ana Ochoa, Yolanda Martínez, Alejandro Aguirre, Francisco de Asís Alcántara, Pablo Fernández-González, Elena López, Paula Valle, Sergio Campos, María Navarro, Lucía Elena Ballester

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; treatment; drug; survival; antiviral; hydroxychloroquine

Online: 9 May 2020 (04:45:37 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202006.0044.v1

Major Concerns on the Identification of Bat Coronavirus Strain RaTG13 and Quality of Related Nature Paper

xiaoxu lin, Shizhong Chen

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Epidemiology; COVID-19; coronavirus; bat; RaTG13; BtCoV/4991; SARS-CoV-2; Pangolin Coronavirus; next generation sequencing

Online: 5 June 2020 (06:17:26 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202101.0127.v1

Wave-Like Properties of Time

Goutam Kumar Chandra

Subject: Physical Sciences, Acoustics Keywords: Tools and Metrology; Time and Frequency; Philosophy of Science; Special Relativity; Semiconductors

Online: 6 January 2021 (15:09:15 CET)

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Preprint ARTICLE | doi:10.20944/preprints202002.0258.v1

Asians and Other Races Express Similar Levels of and Share the Same Genetic Polymorphisms of the SARS-CoV-2 Cell-Entry Receptor

Ying Chen, Kejia Shan, Wenfeng Qian

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2; cell-entry receptor; ACE2 expression; The Cancer Genome Atlas; susceptibility; demographic factors; race

Online: 18 February 2020 (06:40:01 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0356.v1

Initial Review and Analysis of COVID-19 Host Genetics and Associated Phenotypes

Yosuke Tanigawa, Manuel Rivas

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: COVID-19; SARS-CoV-2; host genetics; genetics; polygenic risk score

Online: 24 March 2020 (08:36:20 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0457.v2

Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19

Anton S.M. Dofferhoff, Ianthe Piscaer, Leon J. Schurgers, Jona Walk, Jody M.W. van den Ouweland, Tilman M. Hackeng, Pim A. de Jong, Reinoud Gosens, Petra Lux, Henny van Daal, Cecile Maassen, Esther G.A. Maassen, Loes E.M. Kistemaker, Cees Vermeer, Emiel F.M. Wouters, Rob Janssen

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Covid-19; desmosine; dp-ucMGP; elastic fibers; factor II; matrix Gla protein; PIVKA-II; protein S; vitamin K; vitamin K antagonist

Online: 29 May 2020 (04:16:20 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202002.0258.v2

Asians Do Not Exhibit Elevated Expression or Unique Genetic Polymorphisms for ACE2, the Cell-Entry Receptor of SARS-CoV-2

Ying Chen, Kejia Shan, Wenfeng Qian

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2; cell-entry receptor; ACE2; The Cancer Genome Atlas; susceptibility; demographic factors; polymorphism

Online: 25 February 2020 (06:30:17 CET)

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Preprint HYPOTHESIS | doi:10.20944/preprints202004.0090.v1

Hydroxychloroquine as an Aerosol Might Markedly Reduce and Even Prevent Severe Clinical Symptoms after SARS-CoV-2 Infection

Ansgar Klimke, Gudrun Hefner, Bianca Will, Ursula Voss

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19: hydroxychloroquine aerosol; pharmacotherapy; prevention; SARS-CoV-2

Online: 7 April 2020 (11:11:09 CEST)

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Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10 %. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. 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. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 hours after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects.

Preprint ARTICLE | doi:10.20944/preprints202104.0702.v1

Acceptability of Vaccination Against COVID-19 Among Selected Residents of the Cities of Caloocan, Malabon, and Navotas, Philippines

Angelito Palma Bautista Jr., Doris Gelvoligaya Bleza, Dianne Morta Balibrea, Cynthia Equiza

Subject: Business, Economics And Management, Accounting And Taxation Keywords: COVID-19; vaccine acceptance; vaccine willingness; vaccine hesitancy; quantitative; online survey; Philippines

Online: 27 April 2021 (10:12:47 CEST)

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Working Paper HYPOTHESIS

Potential Natural Compounds for Preventing 2019-nCoV Infection

Hansen Chen, Qiaohui Du

Subject: Medicine And Pharmacology, Pharmacy Keywords: 2019-nCov; Baicalin; Scutellarin; Hesperetin; Nicotianamine; Glycyrrhizin

Online: 30 January 2020 (03:06:07 CET)

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Preprint DATA DESCRIPTOR | doi:10.20944/preprints201608.0191.v1

688,112 Statistical Results: Content Mining Psychology Articles for Statistical Test Results

Chris H. J. Hartgerink

Subject: Social Sciences, Behavior Sciences Keywords: nhst; p-values; apa; content mining; tdm; errors

Online: 23 August 2016 (10:33:53 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202002.0242.v1

Potential Therapeutic Agents for COVID-19 Based on the Analysis of Protease and RNA Polymerase Docking

Yu-Chuan Chang, Yi-An Tung, Ko-Han Lee, Ting-Fu Chen, Yu-Chun Hsiao, Hung-Ching Chang, Tsung-Ting Hsieh, Chan-Hung Su, Su-Shia Wang, Jheng-Ying Yu, Shang-shung Shih, Yu-Hsiang Lin, Yin-Hung Lin, Yi-Chin Ethan Tu, Chun-Wei Tung, Chien-Yu Chen

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; molecular docking; HIV protease inhibitor; nucleotide analogues

Online: 17 February 2020 (07:28:31 CET)

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Working Paper SHORT NOTE

Understanding the Origin of ‘BatCoVRaTG13’, a Virus Closest to SARS-CoV-2

Monali C. Rahalkar, Rahul A. Bahulikar

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; RATG13; BtCoV/4991; SARS-like (SL-) corona virus; pneumonia

Online: 24 May 2020 (20:02:22 CEST)

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Genomic analysis indicates that SARS-CoV-2 is most related to RaTG13, a beta corona virus derived from bats by 96% ¹. At present, RaTG13 is only available on the public database in the form of a genome sequence. The genome of RaTG13 (MN996532.1) was sequenced from the RNA of a bat faecal swab collected in 2013 from Yunnan, China, however the exact location is not mentioned. Since RaTG13 is one of the main supports for SARS-CoV-2 to have a natural origin, it is of utmost importance to understand the sample location. RNA dependent RNA polymerase (RdRp) sequence of RaTG13 shows that it is 100% similar to that of bat corona virus BtCoV/4991 and 98.7-98.9% similar to SARS-CoV-2 RdRp ². BtCoV/4991 was described to be a SARS-like (SL-) corona virus from bat faeces sampled in an abandoned mine from Mojiang ². Both the publications ^1,2 are authored by Dr. Zheng-li Shi (Z-L Shi), who is described as the bat woman of China ³. However, BtCoV/4991 has not been mentioned by Zhou et al 2020 ¹ where novel corona virus was first described. Based on the RdRp sequence similarities, similarities in sample collection dates, sample locations, and the fact that RaTG13 is mentioned synonymous to BtCoV/4991 on the Chinese bat database, it is predicted that RaTG13 and BtCoV/4991 originate from the same sample. The sample, bat faecal swab was collected in 2013 from an abandoned mineshaft in Mojiang by Dr. Shi and her work group. In 2012, in a Mojiang mineshaft, six mine workers suffered from atypical pneumonia and three of them died. These workers were engaged in the work of clearing debris from a mineshaft which had a lot of bats and bat faeces ³^,4. A detailed health investigation indicated that the miners suffered from atypical pneumonia mostly of the viral origin ⁴. Therefore, in the light of the present Covid-19 caused by SARS-CoV-2, the fact that its phylogenetic neighbour RaTG13 originated from bat faeces collected from a mineshaft, which was also the origin of pneumonia-like disease in miners in 2012, should be noted.

Preprint ARTICLE | doi:10.20944/preprints202003.0081.v1

Structurally Observed Electrostatic Features of the COVID-19 Coronavirus-Related Experimental Structures inside Protein Data Bank: A Brief Update

Wei Li

Subject: Biology And Life Sciences, Biophysics Keywords: COVID-19; electrostatic feature; salt bridging network; structural update

Online: 5 March 2020 (03:37:44 CET)

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Preprint REVIEW | doi:10.20944/preprints202004.0203.v4

Face Masks Against COVID-19: An Evidence Review

Jeremy Howard, Austin Huang, Zhiyuan Li, Zeynep Tufekci, Vladimir Zdimal, Helene-Mari van der Westhuizen, Arne von Delft, Amy Price, Lex Fridman, Lei-Han Tang, Viola Tang, Gregory L. Watson, Christina E. Bax, Reshama Shaikh, Frederik Questier, Danny Hernandez, Larry F. Chu, Christina M. Ramirez, Anne W. Rimoin

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; SARS-CoV-2; masks; pandemic

Online: 2 November 2020 (10:18:00 CET)

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The science around the use of masks by the general public to impede COVID-19 transmission is advancing rapidly. Policymakers need guidance on how masks should be used by the general population to combat the COVID-19 pandemic. In this narrative review, we develop an analytical framework to examine mask usage, considering and synthesizing the relevant literature to inform multiple areas: population impact; transmission characteristics; source control; PPE; sociological considerations; and implementation considerations. A primary route of transmission of COVID-19 is via respiratory droplets, and is known to be transmissible from presymptomatic and asymptomatic individuals. Reducing disease spread requires two things: first, limit contacts of infected individuals via physical distancing and other measures, and second, reduce the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces the transmissibility per contact by reducing transmission of infected droplets in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. The decreased transmissibility could substantially reduce the death toll and economic impact while the cost of the intervention is low. Given the current shortages of medical masks we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory droplets become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask-wearing by infectious people ("source control") with benefits at the population-level, rather than mask-wearing by susceptible people, such as health-care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.

Preprint CASE REPORT | doi:10.20944/preprints202206.0308.v1

A Case Report: Multifocal Necrotizing Encephalitis and Myocarditis after BNT162b2 mRNA Vaccination against Covid-19

Michael Mörz

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: mRNA Vaccine; autopsy

Online: 22 June 2022 (07:53:57 CEST)

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Preprint REVIEW | doi:10.20944/preprints202003.0197.v1

2019 Novel Coronavirus (COVID-19) Outbreak: A Review of the Current Literature and Built Environment (BE) Considerations to Reduce Transmission

Leslie Dietz, Patrick F. Horve, David Coil, Mark Fretz, Kevin Van Den Wymelenberg

Subject: Biology And Life Sciences, Virology Keywords: Built Environment (BE); building operations; novel coronavirus; COVID-19; SARS-CoV-2

Online: 12 March 2020 (04:18:26 CET)

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Preprint ARTICLE | doi:10.20944/preprints202007.0486.v2

Intuitive Representation of Computable Knowledge

Steven Vercruysse, Martin Kuiper

Subject: Computer Science And Mathematics, Information Systems Keywords: knowledge representation; curation; biocuration; semantics; systems biology; ontology; user interface; VSM

Online: 29 July 2020 (17:29:20 CEST)

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Working Paper CASE REPORT

Clinical Pathology of Critical Patient with Novel Coronavirus Pneumonia (COVID-19)

Weiren Luo, Hong Yu, Jizhou Gou, Xiaoxing Li, Yan Sun, Jinxiu Li, Lei Liu

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Novel coronavirus pneumonia; COVID-19; SARS-CoV-2; Pathology; Critical patient

Online: 27 February 2020 (12:30:45 CET)

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Preprint COMMUNICATION | doi:10.20944/preprints202008.0021.v1

Safe Fieldwork Strategies for At-Risk Individuals

Amelia-Juliette Demery, Monique Pipkin

Subject: Social Sciences, Safety Research Keywords: diversity; inclusion; equity; fieldwork; research

Online: 2 August 2020 (11:55:47 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0148.v1

Effect of COVID-19 on the Indian Economy and Supply Chain

Shruti Agrawal, Anbesh Jamwal, Sumit Gupta

Subject: Business, Economics And Management, Economics Keywords: Covid-19; Indian economy; supply chain; manufacturing industries; barriers

Online: 9 May 2020 (10:01:56 CEST)

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Preprint REVIEW | doi:10.20944/preprints202003.0275.v1

Chloroquine as a Potential Treatment and Prevention Measure for the 2019 Novel Coronavirus: A Review

John Kearney

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Antimalarial; Chemoprophylaxis; Chloroquine; Coronavirus; COVID-19; Global Health; Hydroxychloroquine; Public Health; SARS-CoV-2; Virus

Online: 17 March 2020 (09:17:53 CET)

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Working Paper COMMUNICATION

Developing a Low-Cost and Accessible COVID-19 Vaccine for Global Health

Peter J. Hotez, Maria Elena Bottazzi

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: COVID-19; SARS 2; coronavirus

Online: 31 March 2020 (22:41:36 CEST)

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Preprint CONCEPT PAPER | doi:10.20944/preprints202004.0432.v1

Nitazoxanide/Azithromycin Combination for COVID-19: A Suggested New Protocol for COVID-19 Early Management

Mina Kelleni

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS CoV-2; COVID-19; Nitazoxanide; Azithromycin; Interferons

Online: 24 April 2020 (09:24:23 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0302.v1

Focusing on the Unfolded Protein Response and Autophagy Related Pathways to Reposition Common Approved Drugs against COVID-19

Serguei Nabirotchkin, Alex E. Peluffo, Jan Bouaziz, Daniel Cohen

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-2019; SARS-CoV-2; 2019-nCoV; repositioning; UPR/Autophagy; real-world evidence; pathways

Online: 20 March 2020 (03:55:55 CET)

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More than 179,000 individuals have fallen ill of the Coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus, which first emerged in China less than four months ago in December 2019. As of today, there exist no approved treatments against COVID-19. Vaccines are being developed, but they will take time, at least one year, to reach the population. Drug repositioning represents a fast track because already approved medicines have been broadly tested through multiple trials. We developed a repositioning strategy that mostly leads to candidates that are commonly used. The advantages are that they will facilitate proof of concept in humans through a “real-world evidence” approach and should be rapidly available to the population. We focus on the established research results that the unfolded protein response (UPR) and autophagy pathways of the host cells are essential to the life cycle of previously known coronaviruses. We performed the relevant bioinformatics analysis to understand and confirm if SARS-CoV-2 may interact with these druggable pathways. Based on these considerations, we prioritized two additional druggable pathways, which are important to the viral life cycle and tightly connected to UPR/autophagy signaling: the mitochondrial permeability transition pores (MPTP) and NLRP-3 inflammasome pathways. These four important pathways are perturbed in most major common diseases and have therefore been targeted by numerous broadly prescribed drugs. We have identified 97 approved drugs that are known to modulate these four identified pathways, and which represent, therefore, interesting repositioning candidates. Although it is indisputable that these drugs should never be used for immediate self-medication against COVID-19, we notice that some of them could also be prescribed to individuals who have COVID-19 comorbidities (e.g., hypertension). It is debated if these comorbidities are linked to the pathology itself (e.g., hypertension) or the drugs used to treat the pathology (e.g., sartans). Therefore, relevant preclinical tests and massive electronic health records (i.e., real-world evidence) must be used to pre-screen them and check the COVID-19 prognosis of individuals taking these drugs.

Working Paper CASE REPORT

Thalidomide Combined with Low-dose Glucocorticoid in the Treatment of COVID-19 Pneumonia

Chengshui Chen, Feng Qi, Keqing Shi, Yuping Li, Ji Li, Yongping Chen, Jingye Pan, Tieli Zhou, Xiangyang Lin, Jinsan Zhang, Yongde Luo, Xiaokun Li, Jinglin Xia

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Coronavirus; SARS-CoV-2; COVID-19; Thalidomide; pneumonia

Online: 26 February 2020 (12:31:47 CET)

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Preprint CASE REPORT | doi:10.20944/preprints201912.0264.v1

38-Month Long Progression-Free and Symptom-Free Survival of a Patient With Recurrent Glioblastoma Multiforme: A Case Report of the Paleolithic Ketogenic Diet (PKD) Used As a Stand-Alone Treatment after Failed Standard Oncotherapy

Csaba Tóth, Andrea Dabóczi, Madhvi Chanrai, Mária Schimmer, Zsófia Clemens

Subject: Medicine And Pharmacology, Dietetics And Nutrition Keywords: glioblastoma; brain tumor; paleolithic diet; ketogenic diet; paleolithic ketogenic diet; metabolic therapy; intestinal permeability; cancer treatment

Online: 20 December 2019 (06:36:16 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0311.v1

Pathological Study of the 2019 Novel Coronavirus Disease (COVID-19) through Post-Mortem Core Biopsies

Sufang Tian, Yong Xiong, Huan Liu, Li Niu, Jianchun Guo, Meiyan Liao, Shu-Yuan Xiao

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; COVID-19; pathology; post-mortem biopsy

Online: 20 March 2020 (09:24:10 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0219.v1

Socio-economic Implications of the COVID-19 Pandemic on Smallholder Livelihoods in Zimbabwe

David Mhlanga, Emmanuel Ndhlovu

Subject: Business, Economics And Management, Economics Keywords: COVID-19; livelihoods; smallholders; Zimbabwe

Online: 14 April 2020 (08:50:30 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0161.v1

The Small Intestine, an Underestimated Site of SARS-CoV-2 Infection: From Red Queen Effect to Probiotics

Zhijie Feng, Yan Wang, Wei Qi

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: coronaviruses receptors; angiotensin-converting enzyme 2 (ACE2); COVID-19; SARS-Cov-2; the Red Queen hypothesis; segmented filamentous bacteria

Online: 10 March 2020 (08:45:34 CET)

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Working Paper CASE REPORT

A COVID-19 Case Report from Asymptomatic Contact: Implication for Contact Isolation and Incubation Management

Chang-Qiang Zhu, Shi-Ding Gao, Xiao-Hong Yang, Fu-Qiang Ye, Le-Le Ai, Rui-Chen Lv, Bin Zhang, Yin Li, Heng Lv, Yun-Sheng Liu, Chun-Meng Shi, Chun-Hui Wang, Wei-Long Tan

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: patient; COVID-19; asymptomatic contact

Online: 9 March 2020 (10:34:58 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0347.v1

Vitamin B12 May Inhibit RNA-Dependent-RNA Polymerase Activity of nsp12 from the SARS-CoV-2 Virus

Naveen Narayanan, Deepak T. Nair

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: nsp12; RNA-dependent-RNA polymerase; SARS-CoV-2; inhibitor; vitamin B12

Online: 23 March 2020 (07:46:54 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0345.v1

Incidence of Venous Thromboembolism in Hospitalized Patients with COVID-19

Saskia Middeldorp, Michiel Coppens, Thijs F. van Haaps, Merijn Foppen, Alexander P. Vlaar, Marcella C.A. Muller, Catherine C.S. Bouman, Ludo F.M. Beenen, Ruud S. Kootte, Jarom Heijmans, Loek P. Smits, Peter I. Bonta, Nick van Es

Subject: Medicine And Pharmacology, Clinical Medicine Keywords: COVID-19; venous thrombosis; pulmonary embolism; venous thromboembolism; anticoagulants; mortality

Online: 19 April 2020 (13:08:16 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0374.v1

Global Comparison of Changes in the Number of Test-Positive Cases and Deaths by Coronavirus Infection (COVID-19) in the World

Akihiro Hisaka, Hideki Yoshioka, Hiroto Hatakeyama, Hiromi Sato, Yoshihiro Onouchi, Naohiko Anzai

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; coronavirus; infectious disease; infection management; PCR test; mortality; kinetic analysis

Online: 21 April 2020 (05:42:47 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201803.0062.v1

Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease

Marianne J. Middelveen, Eva Sapi, Jennie Burke, Katherine R. Filush, Agustin Franco, Melissa C. Fesler, Raphael B. Stricker

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Lyme disease; Borrelia burgdorferi; Tickborne disease; Chronic infection; Spirochete culture

Online: 8 March 2018 (07:08:02 CET)

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Working Paper ARTICLE

Citrus Fruits Are Rich in Flavonoids for Immunoregulation and Potential Targeting ACE2

Liping Cheng, Weikang Zheng, Ming Li, Jie Huang, Shuzheng Bao, Qiang Xu, Zhaocheng Ma

Subject: Biology And Life Sciences, Food Science And Technology Keywords: citrus flavnoids; naringin; immunoregulation; ACE2; 2019-nCoV

Online: 23 February 2020 (09:49:10 CET)

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Preprint BRIEF REPORT | doi:10.20944/preprints202002.0424.v1

Insufficient Sensitivity of RNA Dependent RNA Polymerase Gene of SARS-CoV-2 Viral Genome as Confirmatory Test using Korean COVID-19 Cases

Soyoun Kim, Dong-Min Kim, Baeckseung Lee

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; Korean COVID-19; Wuhan Corona virus; real time PCR Ct Value; Sensitivity; False Negative

Online: 28 February 2020 (12:03:13 CET)

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Preprint ARTICLE | doi:10.20944/preprints202007.0599.v1

Crisis Self-Efficacy and Work Commitment of Education Workers among Public Schools during COVID-19 Pandemic

Erick Baloran, Jenny Hernan

Subject: Social Sciences, Education Keywords: crisis self-efficacy; work commitment; education workers; public schools; COVID-19 pandemic

Online: 24 July 2020 (14:47:56 CEST)

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Preprint REVIEW | doi:10.20944/preprints202005.0265.v1

The Essential Role of Vitamin D in the Biosynthesis of Endogenous Antimicrobial Peptides May Explain Why Deficiency Increases Mortality Risk in COVID-19 Infections

Patrick J. McCullough, Jeffrey Amend, William P. McCullough, Steven J. Repas, Jeffrey B. Travers, Douglas S. Lehrer

Subject: Medicine And Pharmacology, Dietetics And Nutrition Keywords: vitamin D; cathelicidin; antimicrobial peptides; bacteria; mycobacteria; virus; coronavirus; sunshine; UVB phototherapy; tuberculosis; COVID-19; photosynthesis

Online: 16 May 2020 (16:02:26 CEST)

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Abstract: A primary action of vitamin D is regulation of gene transcription. Many cell types possess genes that make antimicrobial peptides (AMPS) (endogenous antibiotics), recently discovered to be regulated by vitamin D. Two examples are cathelicidin and beta defensins, both bioactive against many different bacteria, fungi, mycobacteria, parasites and viruses. The signal transduction pathway is triggered by sensing microorganisms via cell surface receptors, causing intracellular production of calcitriol (1,25(OH)2D) and vitamin D receptors, leading to upregulation of AMP production. Serum 25(OH)D concentrations required to sustain adequate AMP production to eradicate infections are unknown. Vitamin D3 is photosynthesized in skin in amounts ranging from 10,000 (250 mcg) to 25,000 (625 mcg) International Units (IU) from 7-dehydrocholesterol after whole-body exposure to one minimal erythemal dose (MED) of ultraviolet B (UVB) radiation, and is impacted by many factors including geographic localities, seasonal changes and skin pigmentation. We and others have reported extended daily oral dosing with these amounts of vitamin D3 safe. We routinely observe serum 25(OH)D concentrations below 20ng/ml on new admissions, which have been reported insufficient to sustain AMP production. In contrast serum 25(OH)D concentrations above 100ng/ml have been reported after serial UVB treatments for psoriasis. Little vitamin D naturally occurs in food, and insufficient sun exposure may be causing worldwide deficiency. We review evidence suggesting that higher daily intakes of vitamin D3 than the currently recommended 600 (15 mcg) IU/day may be necessary to sustain AMP production in the face of an overwhelming infection, particularly in non-Hispanic blacks, a high risk population suffering the worst outcomes from COVID-19. We propose that increased vitamin D supplementation could provide a safe and cost-effective way to protect all populations from infections, in particular those from pandemic COVID-19.