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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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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 ARTICLE | doi:10.20944/preprints202003.0444.v1

Rapid Prototyping of Reusable 3D-Printed N95 Equivalent Respirators at the George Washington University

Destie Provenzano, Yuan James Rao, Konstantin Mitic, Sofian N. Obaid, Dominique Pierce, James Huckenpahler, Jeffrey Berger, Sharad Goyal, Murray H. Loew

Subject: Engineering, Industrial And Manufacturing Engineering Keywords: COVID-19; SARS-CoV-2; coronavirus; novel coronavirus; 3D printing; N95; respirator; mask

Online: 31 March 2020 (04:44:06 CEST)

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Preprint REVIEW | doi:10.20944/preprints202403.0881.v1

Concerns regarding Transfusions of Blood Products Derived from Genetic Vaccine Recipients and Proposals for Specific Measures

Jun Ueda, Hideyuki Motohashi, Yuriko Hirai, Kenji Yamamoto, Yasufumi Murakami, Masanori Fukushima, Akinori Fujisawa

Subject: Medicine And Pharmacology, Transplantation Keywords: COVID-19 vaccine; genetic vaccine; blood product; blood transfusion; spike protein; post-vaccination syndrome; harm–benefit assessment; prion; spikeopathy; inspection standard; diagnostic criteria

Online: 15 March 2024 (08:54:06 CET)

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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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Working Paper COMMUNICATION

Evidence That Quinine Exhibits Antiviral Activity against SARS-CoV-2 Infection In Vitro

Maximilian Große, Natalia Ruetalo, Ramona Businger, Sascha Rheber, Christian Setz, Pia Rauch, Janina Auth, Ekkehard Brysch, Michael Schindler, Ulrich Schubert

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; Quinine; Hydroxy-Chloroquine; Chloroquine; COVID-19; antiviral

Online: 6 July 2020 (09:19:06 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/preprints202003.0267.v1

Binding Mechanism of Remdesivir to SARS-CoV-2 RNA Dependent RNA Polymerase

Leili Zhang, Ruhong Zhou

Subject: Chemistry And Materials Science, Physical Chemistry Keywords: COVID-19; SARS-CoV-2; RNA-dependent RNA polymerase (RdRp); remdesivir; homology model; molecular dynamics; free energy perturbation

Online: 17 March 2020 (04:07:15 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 ARTICLE | doi:10.20944/preprints202107.0472.v3

Decoding State Vaccination Rates Using educational aptitude, Income, and Political Affiliation

Azad Kabir, Raeed Kabir, Jebun Nahar, Ritesh Sengar

Subject: Social Sciences, Psychology Keywords: Online misinformation; COVID-19 vaccination; fully vaccinated; Intelligence Quotient; per capita income

Online: 20 September 2021 (12:12:19 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0286.v1

Network Bioinformatics Analysis Provides Insight into Drug Repurposing for COVID-2019

Xu Li, Jinchao Yu, Zhiming Zhang, Jing Ren, Alex E. Peluffo, Wen Zhang, Yujie Zhao, Kaijing Yan, Daniel Cohen, Wenjia Wang

Subject: Medicine And Pharmacology, Pharmacy Keywords: COVID-2019; SARS-CoV-2; repurposing; network bioinformatics

Online: 18 March 2020 (08:50:10 CET)

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Preprint HYPOTHESIS | doi:10.20944/preprints202003.0138.v1

Medical Countermeasures Analysis of 2019-nCoV and Vaccine Risks for Antibody-Dependent Enhancement (ADE)

Darrell O. Ricke, Robert W. Malone

Subject: Biology And Life Sciences, Virology Keywords: 2019-nCoV; SARS-CoV-2; COVID-19; ADE; antibody depedendent enhancement

Online: 8 March 2020 (15:35:27 CET)

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Background: In 80% of patients, COVID-19 presents as mild disease^1,2. 20% of cases develop severe (13%) or critical (6%) illness. More severe forms of COVID-19 present as clinical severe acute respiratory syndrome, but include a T-predominant lymphopenia³, high circulating levels of proinflammatory cytokines and chemokines, accumulation of neutrophils and macrophages in lungs, and immune dysregulation including immunosuppression⁴. Methods: All major SARS-CoV-2 proteins were characterized using an amino acid residue variation analysis method. Results predict that most SARS-CoV-2 proteins are evolutionary constrained, with the exception of the spike (S) protein extended outer surface. Results were interpreted based on known SARS-like coronavirus virology and pathophysiology, with a focus on medical countermeasure development implications. Findings: Non-neutralizing antibodies to variable S domains may enable an alternative infection pathway via Fc receptor-mediated uptake. This may be a gating event for the immune response dysregulation observed in more severe COVID-19 disease. Prior studies involving vaccine candidates for FCoV^5,6 SARS-CoV-1^7-10 and Middle East Respiratory Syndrome coronavirus (MERS-CoV) ¹¹ demonstrate vaccination-induced antibody-dependent enhancement of disease (ADE), including infection of phagocytic antigen presenting cells (APC). T effector cells are believed to play an important role in controlling coronavirus infection; pan-T depletion is present in severe COVID-19 disease³ and may be accelerated by APC infection. Sequence and structural conservation of S motifs suggests that SARS and MERS vaccine ADE risks may foreshadow SARS-CoV-2 S-based vaccine risks. Autophagy inhibitors may reduce APC infection and T-cell depletion¹² ¹³. Amino acid residue variation analysis identifies multiple constrained domains suitable as T cell vaccine targets. Evolutionary constraints on proven antiviral drug targets present in SARS-CoV-1 and SARS-CoV-2 may reduce risk of developing antiviral drug escape mutants. Interpretation: Safety testing of COVID-19 S protein-based B cell vaccines in animal models is strongly encouraged prior to clinical trials to reduce risk of ADE upon virus exposure.

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 ARTICLE | doi:10.20944/preprints202009.0631.v1

Engineering Novel Epitope-Based Subunit Vaccine against SARS-CoV-2 by Exploring the Immunoinformatics Approach

Bishajit Sarkar, Md. Asad Ullah, Yusha Araf, Mohammad Shahedur Rahman

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: COVID-19; SARS-CoV-2; In silico; Immunoinformatics; Vaccine designing

Online: 26 September 2020 (13:01:26 CEST)

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Preprint REVIEW | doi:10.20944/preprints202303.0344.v2

Strategies for the Management of Spike Protein-Related Pathology

Matthew T.J. Halma, Cristof Plothe, Paul Marik, Theresa A. Lawrie

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: Long Covid; Covid-19 vaccine; thrombosis; clots; inflammation; therapeutics

Online: 12 April 2023 (10:04:23 CEST)

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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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Working Paper REVIEW

Immunogenicity of Clinically Relevant SARS-CoV-2 Vaccines in Non-human Primates and Humans

P.J. Klasse, D. F. Nixon, J. P. Moore

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; S-protein; RBD; COVID-19; neutralizing antibodies; serology; T-cells; vaccines; animal models; Operation Warp Speed

Online: 27 October 2020 (11:25:32 CET)

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Preprint ARTICLE | doi:10.20944/preprints202002.0220.v1

Pulmonary Pathology of Early Phase SARS-COV-2 Pneumonia

Sufang Tian, Weidong Hu, Li Niu, Huan Liu, Haibo Xu, Shu-Yuan Xiao

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

Online: 16 February 2020 (14:41:28 CET)

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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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Preprint ARTICLE | doi:10.20944/preprints202005.0264.v1

Rapid Quantification and Neutralization Assays for Novel Coronavirus SARS-CoV-2 Using Avicel RC-591 Semi-Solid Overlay

Anna N. Honko, Nadia Storm, David J. Bean, Jhonatan Henao Vasquez, Sierra N. Downs, Anthony Griffiths

Subject: Biology And Life Sciences, Virology Keywords: plaque assay; neutralization; SARS; SARS-CoV-2; coronavirus; Avicel; methylcellulose; COVID

Online: 16 May 2020 (15:51:52 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0085.v1

Structural Elucidation of SARS-CoV-2 Vital Proteins: Computational Methods Reveal Potential Drug Candidates Against Main Protease, Nsp12 RNA-dependent RNA Polymerase and Nsp13 Helicase

Muhammad Usman Mirza, Matheus Froeyen

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; CoV-Mpro; CoV-Nsp12 polymerase; CoV-Nsp13 helicase

Online: 5 March 2020 (11:50:45 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0360.v1

Transcriptional Inhibition of Host Viral Entry Proteins as a Therapeutic Strategy for SARS-CoV-2

Xinchen Wang, Ryan Dhindsa, Gundula Povysil, Anthony Zoghbi, Joshua Motelow, Joseph Hostyk, David Goldstein

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2; transcriptional inhibition; COVID-19; drug repurposing; TMPRSS2

Online: 24 March 2020 (14:26:57 CET)

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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 REVIEW | doi:10.20944/preprints202004.0377.v1

The Dynamics of Humoral Immune Responses Following SARS-CoV-2 Infection and the Potential for Reinfection

Paul Kellam, Wendy Barclay

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; immune response; antibodies

Online: 21 April 2020 (06:56:12 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0090.v1

The SIR and SEIR Epidemiological Models Revisited

John P. Maassen

Subject: Computer Science And Mathematics, Mathematical And Computational Biology Keywords: epidemiological model; basic reproduction number; SIR; SEIR; COVID-19; stochas-tic model; Monte-Carlo simulation

Online: 6 May 2020 (03:15:02 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202012.0710.v1

Evaluation of the Effect of D614G, N501Y and S477N Mutation in SARS-CoV-2 through Computational Approach

Sarmilah Mathavan, Suresh Kumar

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; D614G; N501Y; S477N; mink; VOC 202012/01; B.1.1.7

Online: 28 December 2020 (17:00:23 CET)

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an outbreak of COVID-19 disease in humans with the aid of spike protein. It consists of a receptor-binding domain (RBD) that recognizes and binds to the host receptor angiotensin-converting enzyme 2 (ACE2). The aim of this study was to examine the mutational effect of spike protein on the sequence through an interaction study of the mutant spike protein and the human ACE2 protein at the structural level. A total of 17,227 spike proteins from Asia, Africa, Europe, Oceania, South America, and North America were compared to the Wuhan spike protein reference sequence (Wuhan-Hu-1). The structural and stability implications of D614G, N501Y, and S477N mutations were evaluated. The binding affinity between mutated RBD and human ACE2 protein was also studied. The D614G mutation may have originated in Germany, Europe based on the date of the first sample collection report. It is now widely circulated all over the world with most occurrences in North America. The mutations N501Y and S477N may have originated from Oceania based on the date of the first sample collection report and also have the highest occurrences in Oceania. Based on the computational analysis of mutational effects, the D614G, N501Y, and S477N mutations decreased stability and were tolerated. For disease propensity prediction, N501Y was more prone to disease compared to D614G, while S477N was not prone to disease. The mutation of D to G at position 614 and S to N at position 477 for secondary structure prediction shows no changes in secondary structure while remaining in the coil region, whereas the mutation of N to Y at position 501 changes from coil structure to extended strand. N501Y mutation has a higher affinity to human ACE2 protein compared to D614G and S477N based on a docking study. D614G spike mutation was identified to exist between the two hosts based on a comparison of SARS-CoV-2 derived between the mink and human. Further research is needed on the link between the mink mutation N501T and the mutation N501Y in humans, which has evolved as a separate variant.

Preprint ARTICLE | doi:10.20944/preprints202002.0438.v1

Simeprevir, Potential Candidate to Repurpose for Coronavirus Infection: Virtual Screening and Molecular Docking Study

Faezeh Sadat Hosseini, Massoud Amanlou

Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: COVID-19; Simeprevir; Protease inhibitor; Virtual screening; Docking

Online: 28 February 2020 (13:14:38 CET)

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Preprint REVIEW | doi:10.20944/preprints202012.0129.v1

Oil Palm in the 2020s and Beyond: Challenges and Solutions

Denis Murphy, Kirstie Goggin, Russell Paterson

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: oil palm; breeding; sustainability; certification; diseases; basal stem rot; phytophthora; climate change; modelling; supply chains; biodiesel; covid-19

Online: 7 December 2020 (08:50:30 CET)

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Background Oil palm (OP), Elaeis guineensis , is by far the most important global oil crop, supplying about 40% of total traded vegetable oil. Palm oils are key dietary components consumed daily by over three billion people, mostly in Asia, and also have a wide range of important non-food uses including in cleansing and sanitising products. Main body Oil palm is a perennial crop with a >25-year life cycle and an exceptionally small land footprint compared to annual oilseed crops. Oil palm crops globally produce an annual 81 million tonnes (Mt) of oil from about 19 million hectares (Mha). In contrast, the second and third largest vegetable oil crops, soybean and rapeseed, yield a combined 84 Mt oil but occupy over 163 Mha of increasingly scarce arable land. Despite this advantage, oil palm has acquired a poor environmental reputation, especially in Europe and North America, although soybean planting is now responsible for more deforestation. Oil palm crops face other challenges in the 2020s. On the demand side, these include changing consumer purchasing habits, threats to global trade systems, and diminishing demand for liquid fuels as transport systems become increasingly electrified. On the supply side, major issues include stagnant yields in ageing plantations, sluggish replanting of improved varieties, labour shortages, diseases and climatic/ environmental threats. The latter include the increasing incidence of new and existing pests/diseases and a general lack of climatic resilience, especially relating to elevated temperatures and increasingly erratic rainfall patterns. This review surveys the oil palm sector in the 2020s and beyond, its major challenges and options for future progress. Conclusions Oil palm crops face many future challenges, including emerging threats from climate change and new pests and diseases, that require more effective international collaboration. Nevertheless, new breeding technologies are providing the promise of improvements, such as much higher yielding varieties, improved oil profiles, enhanced disease resistance and modified crop architecture to enable harvesting mechanisation. The industry also needs to redouble its efforts to engage with global consumers in a constructive dialogue aimed at addressing its image problem and explaining the many benefits of its products.

Working Paper ARTICLE

Geographic and Genomic Distribution of SARS-CoV-2 Mutations

Daniele Mercatelli, Federico Manuel Giorgi

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; genomics coronavirus; COVID-19 evolution

Online: 3 July 2020 (09:45:43 CEST)

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Working Paper REVIEW

Optimal Nutritional Status for a Well-Functioning Immune System is an Important Factor to Protect Against Viral Infections

Philip C. Calder, Anitra C. Carr, Adrian F. Gombart, Manfred Eggersdorfer

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: immune system; viral infection; influenza; COVID-19; micronutrients; vitamins; omega-3 fatty acids; minerals; vitamin C; vitamin D

Online: 12 March 2020 (04:30:45 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0334.v1

Molecular Docking and Molecular Dynamic Study of Two Viral Proteins Associated with SARS-CoV-2 with Ivermectin

Lenin Andres Gonzalez Paz, Carla A. Lossada, Luis S. Moncayo, Freddy Romero, J. L. Paz, Joan Vera-Villalobos, Aleivi E. Perez, Ernesto San-Blas, Ysaias J. Alvarado

Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: SARS-COV-2; folding/unfolding; antiparasitic; molecular docking; molecular dynamics; COVID-19; Ivermectin

Online: 19 April 2020 (06:56:09 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0073.v2

SEIR Modeling of the Italian Epidemic of SARS-CoV-2 Using Computational Swarm Intelligence

Alberto Godio, Francesca Pace, Andrea Vergnano

Subject: Computer Science And Mathematics, Mathematics Keywords: SARS-CoV-2; COVID-19; SEIR modeling; Italy; stochastic modeling; swarm intelligence; Google COVID 19 Community Mobility Reports

Online: 5 May 2020 (16:10:48 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202002.0308.v1

Pharmacoinformatics and Molecular Dynamic Simulation Studies Reveal Potential Inhibitors of SARS-CoV-2 Main Protease 3CL^pro

Mubarak A. Alamri, Muhammad Tahir ul Qamar, Safar M. Alqahtani

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS-CoV-2; COVID-19; 3CL protease; molecular docking; molecular dynamics and simulations

Online: 23 February 2020 (02:17:46 CET)

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Working Paper CONCEPT PAPER

Public Use of Masks to Control the Coronavirus Pandemic

Nicholas R. Longrich, Samuel K. Sheppard

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; face masks; epidemiology; coronavirus; pandemics

Online: 12 April 2020 (08:41:58 CEST)

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The current Coronavirus Disease 19 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, is unprecedented in recent history and threatens the lives and livelihoods of billions worldwide. The rapid spread and lack of modern parallels have left governments, health agencies, and the public racing to understand how to best mitigate and ultimately suppress the pandemic, but we are still working to understand the strengths and weaknesses of various interventions at our disposal. Few issues have been as contentious as the public use of face masks to control the pandemic’s spread. There is ongoing debate about their effectiveness, but an increasing body of evidence suggests that masks could be a useful in preventing the spread of coronavirus, leading several governments and health agencies to review and revise their policies. Here, we review the theory and evidence behind use of masks. The theory behind masks is that they prevent the spread of viral particles by infected persons, and inhalation of viral particles by uninfected persons. Even assuming masks are not 100% effective in preventing infection, they may reduce severity of infection by reducing viral dosing. Laboratory studies suggest masks may be effective in stopping both exhalation and inhalation of viral particles. However, real-world studies provided limited evidence for the use of masks in controlling influenza transmission and highlight potential problems associated with their misuse, such as poor compliance or improper use. Evidence for efficacy of face masks against the first SARS virus, SARS-CoV-1, implies that they may be effective against the current outbreak of SARS-Cov-2 virus. This is important as mathematical modeling suggests that even small reductions of in transmission rates can make a large difference over time, potentially slowing the pace of viral pandemics and limiting their spread. Perhaps the strongest argument for the use of masks is that countries with early adoption of masks have tended to see flatter pandemic curves, even without strict nationwide lockdowns. There is little evidence that respirators are more effective than surgical masks, but this may be due to misuse or poor compliance. Studies suggest some non-medical masks perform on par with medical masks. Improvised masks are less effective than medical masks, but may provide better protection than nothing at all. While many governments now encourage the use of improvised face coverings, more will need to be known about material, design, and who needs to wear masks, and when, to ensure effectiveness. Proper use of masks will also be important; if masks are used improperly or infrequently they may provide limited protection. It is important that public health policy makers consider the debate and the potential of masks as part of multi-faceted coronavirus control strategies.

Preprint HYPOTHESIS | doi:10.20944/preprints202003.0428.v1

A Furin Cleavage Site Inserted into the Spike Protein of SARS-CoV-2: A Structural Implication?

Wei Li

Subject: Biology And Life Sciences, Biophysics Keywords: COVID-19; SARS-CoV-2; furin cleavage site (FCS); salt bridging analysis

Online: 29 March 2020 (08:54:42 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202004.0009.v2

A Flexible Genome-Scale Resource of SARS-CoV-2 Coding Sequence Clones

Dae-Kyum Kim, Jennifer J. Knapp, Da Kuang, Patricia Cassonnet, Payman Samavarchi-Tehrani, Hala Abdouni, Ashyad Rayhan, Dayag Sheykhkarimli, Etienne Coyaud, Sylvie van der Werf, Caroline Demeret, Anne-Claude Gingras, Brian Raught, Yves Jacob, Frederick P. Roth

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; COVID-19; coronavirus; coding sequences; collections

Online: 4 May 2020 (18:28:01 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0102.v3

Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (M^pro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study

Trina Ekawati Tallei, Sefren Geiner Tumilaar, Nurdjannah Jane Niode, Fatimawali Fatimawali, Billy Johnson Kepel, Rinaldi Idroes, Yunus Effendi

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Medicinal plants; Mpro; 3CLpro; spike (S) glycoprotein; COVID-19; SARS-CoV-2

Online: 1 July 2020 (08:37:49 CEST)

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Since the outbreak of the COVID-19 (Coronavirus Disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit the Main Protease (M^pro) and Spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. A rule of five (RO5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as M^pro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development lead compounds to treat infections caused by SARS-CoV-2.

Preprint HYPOTHESIS | doi:10.20944/preprints202003.0042.v1

Virtual Screening of Inhibitors Against Spike Glycoprotein of 2019 Novel Corona Virus: A Drug Repurposing Approach

Kanishka Senathilake, Sameera Samarakoon, Kamani Tennekoon

Subject: Biology And Life Sciences, Virology Keywords: COVID -19; 2019-nCoV; spike (S) protein; zorubicin; aclarubicin

Online: 3 March 2020 (11:41:51 CET)

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Preprint REVIEW | doi:10.20944/preprints202306.1903.v1

Exploring Autophagy in Treating Spike Protein-related Pathology

Matthew T.J. Halma, Paul E. Marik, Yusuf M. Saleeby

Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Fasting; autophagy; long-COVID; post-vaccination syndrome; spike protein; mitochondria; mitophagy

Online: 27 June 2023 (12:33:46 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0272.v1

Anosmia and Ageusia as Initial or Unique Symptoms after SARS-COV-2 Virus Infection

Calixto Machado, Joel Victor Gutierrez

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2 (CoV-2); COVID-19; coronavirus; pandemic; smell; anosmia; taste; ageusia

Online: 16 April 2020 (12:42:44 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0337.v1

Reporting Two SARS-CoV-2 Strains Based on A Unique Trinucleotide-Bloc Mutation and Their Potential Pathogenic Difference

Mustak Ibn Ayub

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; strains of SARS-CoV-2

Online: 19 April 2020 (07:14:52 CEST)

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SARS-CoV-2, the novel coronavirus behind COVID-19 pandemic is acquiring new mutations in its genome. Although some mutations provide benefits to the virus against human immune response, a number of them may result in their reduced pathogenicity and virulence. By analyzing more than 3000 high-coverage, complete genome sequences deposited in the GISAID database, here I report a unique 28881-28883:GGG>AAC trinucleotide-bloc mutation in the SARS-CoV-2 genome that results in two sub-strains, described here as SARS-CoV-2g (28881-28883:GGG genotype) and SARS-CoV-2a (28881-28883:AAC genotype). Computational analysis and literature review suggest that this bloc mutation would bring 203-204:RG(arginine-glycine)>KR(lysine-arginine) amino acid changes in the nucleocapsid (N) protein affecting the SR (serine-arginine)-rich motif of the protein, a critical region for the transcription of viral RNA and replication of the virus. Thus, 28881-28883:GGG>AAC bloc-mutation is expected to modulate the pathogenicity of the SARS-CoV-2. Remarkably, SARS-CoV-2g and SARS-CoV-2a strains can be linked with the heterogeneity of COVID-19 cases across different regions within and between countries by analyzing existing data. Sequence analysis suggests that severely affected cities, such as Milan, Lombardy, New York, Paris have the predominant presence of SARS-CoV-2g strains, whereas less affected places like Abruzzo, Lyon, Valencia have a relatively higher presence of SARS-CoV-2a, an indication that the latter strain may contribute to the reduced cases of COVID-19. A similar relationship is observed when Netherlands, Portugal are compared with Spain, France and Germany. These analyses suggest that the SARS-CoV-2 has already evolved into a less infective SARS-CoV-2a affecting COVID-19 cases in different regions. The time a country or region needs to acquire SARS-CoV-2a strains may be indicative to the time it would need to overcome the peak of the COVID-19 cases. To confirm these assumptions, prompt retrospective and prospective epidemiological studies should be conducted in different countries to understand the course of pathogenicity of the SARS-CoV-2a and SARS-CoV-2g. Potential drugs can be designed targeting 28881-28883 region of the N protein to modulate virus pathogenicity.

Preprint REVIEW | doi:10.20944/preprints202004.0234.v1

Compounding Health Risks and Increased Vulnerability to SARS-CoV-2 for Racial and Ethnic Minorities and Low Socioeconomic Status Individuals in the United States

Elise M. Myers

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: coronavirus; COVID-19; comorbidity; race and ethnicity; health disparities; income; inequality; influenza

Online: 15 April 2020 (09:25:47 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0479.v1

Open Source High-Temperature RepRap for 3-D Printing Heat-Sterilizable PPE and Other Applications

Noah G. Skrzypczak, Nagendra G. Tanikella, Joshua M. Pearce

Subject: Engineering, Mechanical Engineering Keywords: open source; open hardware; COVID-19; medical hardware; RepRap; 3-D printing; open source medical hardware; high temperature 3-D printing; additive manufacturing; ULTEM; polycarbonate

Online: 31 May 2020 (16:18:20 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0011.v1

SARS-CoV-2: Jumping the Species Barrier, Lessons from SARS and MERS, Its Zoonotic Spillover, Transmission to Humans, Preventive and Control Measures and Recent Developments to Counter This Pandemic Virus

Kuldeep Dhama, Shailesh Kumar Patel, Khan Sharun, Mamta Pathak, Ruchi Tiwari, Mohd. Iqbal Yatoo, Yashpal Singh Malik, Ranjit Sah, Ali A. Rabaan, Parmod Kumar Panwar, Karam Pal Singh, Izabela Michalak, Wanpen Chaicumpa, D. Katterine Bonilla-Aldana, Alfonso J. Rodriguez-Morales

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; SARS-Cov-2; bat coronavirus; zoonosis; spillover; expanding host range

Online: 2 April 2020 (04:43:45 CEST)

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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/preprints202012.0817.v2

Hunting for Previous Coronavirus Pandemics Using Corpus Linguistic Analysis of 19th Century British Newspapers

Rosita Solovejute, Derek Gatherer

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: COVID-19; OC43; coronavirus; pandemic; influenza; historical revisionism; corpus linguistics

Online: 21 December 2022 (09:56:55 CET)

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Preprint BRIEF REPORT | doi:10.20944/preprints202008.0595.v1

De-novo Assembly of RaTG13 Genome Reveals Inconsistencies Further Obscuring SARS-CoV-2 Origins

Mohit Singla, Saad Ahmad, Chandan Gupta, Tavpritesh Sethi

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: COVID-19; de novo assembly; metagenomics; data quality

Online: 27 August 2020 (07:56:01 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202103.0503.v1

The Clubhouse Phenomenon: Do We Need Another Social Network?

Wadim Strielkowski

Subject: Business, Economics And Management, Accounting And Taxation Keywords: social networks; digital surge; COVID-19 pandemic; technology industry; Clubhouse

Online: 19 March 2021 (14:52:38 CET)

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Preprint REVIEW | doi:10.20944/preprints202009.0337.v1

Alcohol-Based Hand Sanitizers – A Multidimensional Perspective

Nasser N. Nyamwweya, Kennedy O. Abuga

Subject: Public Health And Healthcare, Primary Health Care Keywords: hand sanitizers; hand rubs; alcohol based; disinfection; hand hygiene; coronavirus; COVID-19

Online: 15 September 2020 (09:07:09 CEST)

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Preprint REVIEW | doi:10.20944/preprints202306.1306.v1

Exploring Therapeutic Applications of Autophagy in Spike Protein-Related Pathology

Matthew Halma, Paul Marik, Yusuf Saleeby

Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Fasting; autophagy; long-COVID; post-vaccination syndrome; spike protein; mitochondria; mitophagy

Online: 19 June 2023 (07:39:57 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0291.v1

Co-infection of Coronavirus Disease 2019 and Influenza: A Report from Iran

Zohre Khodamoradi, Mohsen Moghadami, Mehrzad Lotfi

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: co-infection; coronavirus disease 2019; COVID-19; influenza

Online: 19 March 2020 (02:00:47 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0372.v1

Inhibitors of SARS-CoV-2 Main Protease from a Library of Marine Natural Products: A Virtual Screening and Molecular Modeling Study

Davide Gentile, Vincenzo Patamia, Angela Scala, Maria Teresa Sciortino, Anna Piperno, Antonio Rescifina

Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: COVID-19; SARS-CoV-2; Marine natural product; Virtual screening; Docking

Online: 25 March 2020 (08:23:57 CET)

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Preprint HYPOTHESIS | doi:10.20944/preprints202004.0143.v1

Inflamm-Aging: Why Older Men Are the Most Susceptible to SARS-Cov-2 Complicated Outcomes

Massimiliano Bonafè, Francesco Prattichizzo, Angelica Giuliani, Gianluca Storci, Jacopo Sabbatinelli, Fabiola Olivieri

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; COVID-19; IL-6; inflamm-aging; immune senescence; host-directed therapies

Online: 9 April 2020 (08:38:22 CEST)

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Preprint REVIEW | doi:10.20944/preprints202011.0558.v1

Recombinant Protein Vaccines, a Proven Approach Against Coronavirus Pandemics

Jeroen Pollet, Wen-Hsiang Chen, Ulrich Strych

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; Adjuvants; Vaccine Production; Vaccine Delivery; Clinical Trials; Neutralizing Antibodies; Th1

Online: 22 November 2020 (11:57:51 CET)

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Preprint REVIEW | doi:10.20944/preprints202003.0353.v1

In Search of Feasible Interventions for the Prevention and Cure of Novel Coronavirus Disease 2019

Sunil Kumar Verma

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; SARS-CoV-2; Severe Acute Respiratory Syndrome Coronavirus-2; Curcumin

Online: 24 March 2020 (03:16:22 CET)

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Preprint ARTICLE | doi:10.20944/preprints202005.0134.v1

A Crispr-Cas9 System Designed to Introduce Point Mutations into the Human ACE2 Gene to Weaken the Interaction of the ACE2 Receptor with the SARS-CoV-2 S Protein

Pedro Tanaka, Jadson Santos, Ernna Oliveira, Natane Miglioli, Amanda Assis, Ana Monteleone-Cassiano, Vitor Ribeiro, Max Duarte, Mayara Machado, Romario Mascarenhas, Alex Souza, Leticia Brito, Leticia Oliveira, Eduardo Donadi, Geraldo Passos

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Crispr-Cas9; ACE2 gene; SARS-CoV-2; new coronavirus; COVID-19

Online: 7 May 2020 (15:26:06 CEST)

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Preprint REVIEW | doi:10.20944/preprints202105.0423.v1

Anti-Fibrotic Agents Could Be the Game Changer for Post‑COVID Pulmonary Fibrosis Treatment – A Mini Review

Pallab Chakraborty, Kaustav Chakraborty

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; post-COVID pulmonary fibrosis; lung injury; anti-fibrotic agents

Online: 18 May 2021 (11:32:07 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0149.v1

Potential Inhibitors of SARS-CoV-2 Main Protease (M^pro) Identified from the Library of FDA Approved Drugs Using Molecular Docking Studies

Dipesh Verma, Srajan Kapoor, Satyajeet Das, Krishan Thakur

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: COVID-19; SARS-CoV-2; Mpro; Molecular docking; MM-GBSA

Online: 9 April 2020 (11:05:55 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0188.v1

Multiple Indirect ELISAs for Serological Detection of SARS-CoV-2 Antibodies

Abdullah Algaissi, Mohamed A. Alfaleh, Sherif Hala, Turki S. Abujamel, Sawsan S. Alamari, Khalid A. Alluhaybi, Haya I. Hobani, Reem M. Alsulaiman, Rahaf H. Alharbi, Mohammad Z. El-Assouli, Wesam H. Abdulaal, Afrah A. AL-Somali, Fadwa S. Alofi, Asim A. Khogeer, Ahmad Bakur Mahmoud, Almohanad A Alkayyal, Naif A.M. Almontashiri, Arnab Pain, Anwar M. Hashem

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2 serology; ELISA; N protein; COVID-19; serosurvey

Online: 11 May 2020 (04:53:31 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202102.0192.v1

Challenges Faced by UK University Students Due to the Coronavirus Crisis in the Higher Education

Siddharth Suhas Kulkarni, Parmjit Chima

Subject: Social Sciences, Education Keywords: UK higher education; student; COVID-19; pandemic; academic performance; student evaluations; online learning; loss of income; educational disruptions

Online: 8 February 2021 (11:36:40 CET)

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Preprint HYPOTHESIS | doi:10.20944/preprints202004.0247.v1

Epigallocatechin-Gallate and Theaflavin-Gallate Interaction in SARS CoV-2 Spike-Protein Central-Channel with Reference to the Hydroxychloroquine Interaction: Bioinformatics and Molecular Docking Study

Smarajit Maiti, Amrita Banerjee

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: SARS CoV-2; COVID 19; pandemic global-outbreak; Spike glycoprotein; ACE2; PatchDock; hydroxychloroquine

Online: 15 April 2020 (10:50:13 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0281.v2

Mutation Hot Spots in Spike Protein of SARS-CoV-2 Virus

Feroza Begum, Arup Kumar Banerjee, Upasana Ray

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; S protein; RBD; S1; S2

Online: 7 September 2020 (04:15:59 CEST)

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Preprint REVIEW | doi:10.20944/preprints202002.0399.v1

Preliminary Case Report on the SARS-CoV-2 Cluster in the UK, France, and Spain

Emma B. Hodcroft

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19 SARS-CoV-2 hCOV-19 coronavirus epidemiology contact-tracing cluster outbreak epidemic

Online: 27 February 2020 (11:08:56 CET)

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Preprint BRIEF REPORT | doi:10.20944/preprints202002.0167.v1

Profiling the Immune Vulnerability Landscape of the 2019 Novel Coronavirus

James Zhu, Jiwoong Kim, Xue Xiao, Yunguan Wang, Danni Luo, Ran Chen, Lin Xu, He Zhang, Guanghua Xiao, Xiaowei Zhan, Tao Wang, Yang Xie

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: 2019-nCoV; Immune; B cell; T cell; COVID-19

Online: 13 February 2020 (10:53:40 CET)

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Preprint ARTICLE | doi:10.20944/preprints202005.0333.v1

An In Silico Analysis of Potential SARS-CoV-2 Interactions with Proteins Involved in Placental Functions

Ashikh A. Seethy, Sunil Singh, Indrani Mukherjee, Karthikeyan Pethusamy, Kakali Purkayastha, Jai Bhagwan Sharma, Ruby Dhar, Subhradip Karmakar

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2; COVID-19; pregnancy; trophoblasts; interactome; placenta

Online: 21 May 2020 (03:38:05 CEST)

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COVID-19 is a rapidly evolving medical emergency that has drawn global attention, unprecedented in any disease of its kind in recent times. The magnitude of the health crisis emerging from this pandemic has overwhelmed health care workers worldwide and called in for extraordinary measures to contain this virus. A simple Pubmed query on “COVID-19” returned with 12214 articles (as on May 17^th, 2020), published just within a few months. A detailed survey revealed around 250 clinical reports, 8 clinical trials, 9 meta-analyses, and 906 reviews that were published during this time span. Combining the strings “COVID-19 and Pregnancy” yielded a total of 132 reports while querying “COVID-19 and Placenta” returned with just 11 articles Even taking into considerations that few materials are in the PrePrint Server, we still have a gross under-representation of studies addressing the effect of this disease on pregnancy outcome and maternal & child health. An essential aspect of a successful pregnancy is proper placentation, where transiently invasive placental trophoblast cells invade the maternal endometrium to establish a functional feto-maternal communication. Based on the elegant study by David. E. Gordon, et al. published in Nature (April 30, 2020), which identified 332 human host proteins interacting with SARS-nCoV2 using an affinity-based purification, we interrogated several gene expression data sets available at NCBI-GEO related to trophoblast invasion and differentiation. Both of these processes are indispensable for placentation and fetal survival. Our analysis showed several overlaps with the interactome proteins implying that SARS-CoV-2 infection can affect several proteins, which are crucial for trophoblasts function. GeneMANIA and STRING based functional analysis further revealed that several of that SARS-CoV-2 interacting trophoblast proteins as a hub for the protein-protein interaction network. Our study thus elucidates the possible effect of SARS-CoV-2 infection on placenta formation and pregnancy outcome.

Preprint REVIEW | doi:10.20944/preprints202002.0380.v1

Nomenclature: Coronavirus and the 2019 Novel Coronavirus

Zhiwen Hu, Zhongliang Yang, Qi Li, Yongfeng Huang

Subject: Social Sciences, Sociology Keywords: human coronaviruses (HCoVs); infodemic; PHEIC; 2019-nCoV; COVID-19; SARS-CoV-2

Online: 25 February 2020 (12:33:45 CET)

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Preprint ARTICLE | doi:10.20944/preprints202005.0020.v1

Coronavirus (2019-nCoV) Deactivation via Spike Glycoprotein Shielding by Old Drugs, Bioinformatic Study

Mohammad Reza Dayer

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; , 2019-nCoV; Heparin; Ivermectin; Spike Shielding

Online: 2 May 2020 (16:21:32 CEST)

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Preprint REVIEW | doi:10.20944/preprints202002.0358.v3

Coronavirus Disease 2019 Assosiated Pneumonia in China: Current Status and Future Prospects

Temoor Ahmed, Muhammad Noman, Ahmad Almatroudi, Muhammad Shahid, Mohsin Khurshid, Farheen Tariq, Muhammad Tahir ul Qamar, Rongrong Yu, Bin Li

Subject: Biology And Life Sciences, Virology Keywords: Infectious diseases; Coronavirus; SARS-CoV-2; COVID-19; Pneumonia; China

Online: 28 February 2020 (13:21:43 CET)

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Preprint ARTICLE | doi:10.20944/preprints202104.0725.v1

Effect of the Pandemic on Students’ Learning Habits in India

Pratiksha Bongale, Chahat Tandon, Arpita T M, Sanjana R R, Dr. Hemant Palivela, Dr. Nirmala C R

Subject: Social Sciences, Education Keywords: COVID-19, Students' learning habits, Pandemic

Online: 27 April 2021 (14:18:23 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202004.0151.v2

ACE Inhibitors and AT1R Blockers for COVID-2019: Friends or Foes ?

Daniele Focosi, Marco Tuccori, Fabrizio Maggi

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; ACEI; ARB; SARS; ALI; ARDS

Online: 22 April 2020 (09:46:54 CEST)

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Preprint REVIEW | doi:10.20944/preprints202006.0216.v2

Detection and Survival of SARS-coronavirus in Human Stool, Urine, Wastewater and Sludge

Andrew Singer, Rachel Wray

Subject: Biology And Life Sciences, Virology Keywords: SARS-coronavirus; Severe Acute Respiratory Syndrome; COVID-19; Stool; Urine; Wastewater; Wastewater-based epidemiology

Online: 18 June 2020 (09:29:00 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0326.v1

Antibodies to SARS-CoV-2 and Their Potential for Therapeutic Passive Immunization

P.J. Klasse, John P. Moore

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; neutralizing antibodies; immunotherapy; vaccine

Online: 19 April 2020 (04:52:17 CEST)

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Working Paper REVIEW

SARS-CoV-2 Vaccines: ‘Warp Speed’ Needs Mind Melds not Warped Minds

John P. Moore, P. J. Klasse

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: SARS-CoV-2; S-protein; RBD; COVID-19; neutralizing antibodies; serology; vaccines; animal models; Warp Speed

Online: 21 June 2020 (15:44:06 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0325.v1

A Retrospective Analysis of Influence of Environmental/Air Temperature and Relative Humidity on SARS-CoV-2 Outbreak

Md. Arifur Rahman, Md. Golzar Hossain, Atul Chandra Singha, Md Sayeedul Islam, Md Ariful Islam

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; infectivity; temperature; humidity

Online: 23 March 2020 (01:30:06 CET)

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Preprint HYPOTHESIS | doi:10.20944/preprints202003.0247.v1

Prediction of Potential 3CLpro-Targeting Anti-SARS-CoV-2 Compounds from Chinese Medicine

Ning Sun, Wing-Leung Wong, Jiao Guo

Subject: Medicine And Pharmacology, Pharmacy Keywords: SARS-CoV-2; COVID-19; molecular docking; Chinese medicine; lithospermic acid B; specnuezhenide; neonuezhenide; rutin; neodiosmin

Online: 15 March 2020 (15:11:22 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202002.0354.v1

SARS-CoV-2 May Persist in Digestive Tract Longer than Respiratory Tract

Yilin Hu, Lisha SHEN, Zheming XU, Jianying Zhou, Hua Zhou

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: SARS-CoV-2; Covid-19; case

Online: 24 February 2020 (14:03:12 CET)

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Preprint REVIEW | doi:10.20944/preprints202005.0178.v1

SARS-CoV-2 and the Possible Connection to ERs, ACE2 and RAGE: Focus on Susceptibility Factors

Roberta Sessa Stilhano, Angelica Jardim Costa, Michelle Sayuri Nishino, Shahin Shams, Cynthia Silva Bartolomeo, Ana Cristina Breithaupt-Faloppa, Eduardo Alexandre Silva, Ana Lopez Ramirez, Carla Maximo Prado, Rodrigo Portes Ureshino

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; estrogen; RAGE; ACE2

Online: 10 May 2020 (17:46:13 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202101.0404.v1

A Low-Cost Air Flow Sensor/Transducer for Medical Applications: Design and Experimental Characterization

Jesús Calderón, Carlos Rincón, Bray Agreda, Sebastián Calero, Manuel Bornas, Juan José Jiménez de Cisneros

Subject: Engineering, Automotive Engineering Keywords: air flow medical sensor; emergency air flow sensor; low-cost air flow sensor; COVID-19

Online: 20 January 2021 (16:14:23 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202005.0209.v1

Heart Rate Variability in a Patient with Coronavirus Disease 2019

Christoph Baumann, Reiner Buchhorn, Christian Willaschek

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: COVID-19 virus disease; Autonomic nervous system; Electrocardiography; Heart rate

Online: 12 May 2020 (12:22:06 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0161.v2

High Throughput Virtual Screening to Discover Inhibitors of the Main Protease of the Coronavirus SARS-CoV-2

Olujide O. Olubiyi, Maryam Olagunju, Monika Keutmann, Jennifer Loschwitz, Birgit Strodel

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; docking; drug repurposing; natural products; in silico drug design; viral replication inhibition

Online: 1 June 2020 (02:42:54 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202202.0043.v1

Core Elements Affecting Sharing Evidence From The European Union

Olga Lingaitienė, Virginija Grybaitė, Aurelija Burinskienė

Subject: Social Sciences, Decision Sciences Keywords: sharing activity; Covid-19 impact; core elements; sustainable development

Online: 3 February 2022 (09:58:24 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0433.v1

Design of a Peptide-Based Subunit Vaccine against Novel Coronavirus SARS-CoV-2

Parismita Kalita, Aditya K. Padhi, Kam Y.J. Zhang, Timir Tripathi

Subject: Biology And Life Sciences, Virology Keywords: adjuvant; COVID-19; immunogenic epitopes; peptide vaccine; subunit vaccine; molecular dynamics simulation

Online: 29 March 2020 (11:14:42 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202003.0400.v1

Susceptibility of the Elderly to SARS-CoV-2 Infection: ACE-2 Overexpression, Shedding and Antibody-dependent Enhancement (ADE)

Jean Pierre Schatzmann Peron, Helder Nakaya

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: SARS-CoV-2; COVID-19; ACE-2

Online: 27 March 2020 (02:48:01 CET)

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Preprint REVIEW | doi:10.20944/preprints202202.0224.v1

Omicron Variant: Secrets Behind the Great Escape Artist

Henry Sutanto, Djoko Santoso

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; pandemic; SARS-CoV-2; Omicron variant; emerging disease; global health; virus; genome; mutation

Online: 18 February 2022 (05:23:18 CET)

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Preprint REVIEW | doi:10.20944/preprints202004.0207.v1

Chinese Guidelines Related to Novel Coronavirus Pneumonia

Tingting Qiu, Shuyao Liang, Monique Dabbous, Yitong Wang, Ru Han, Mondher Toumi

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Chinese Guidelines; COVID-19; pharmaceutical treatment

Online: 13 April 2020 (03:43:37 CEST)

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Background and Objective: China has managed to control the coronavirus disease (COVID-19) with confinement measurements and treatment strategies, while other countries are struggling to contain the spread. This study discusses the guidelines related to COVID-19 in China in order to provide important references for other countries in the fight against COVID-19. Methods: Chinese guidelines relevant to COVID-19 were systematically searched via the China National Knowledge Infrastructure database, YiMaiTong database, and World Health Organization (WHO) COVID-19 database on March 20^th, 2020. Guideline information was extracted, including date of publication, source, objectives and the target population. Guidelines specific to the pharmacological treatment of COVID-19 were further investigated to identify the types of antivirus drugs recommended and to report on how treatment recommendations for COVID-19 have evolved overtime. Results: A total of 114 guidelines were identified, of which 87 were national guidelines and 27 were regional guidelines. The scope of included guidelines consisted of: the diagnosis and treatment of COVID-19, the management of hospital departments and specific diseases during the outbreak of COVID-19. Sixty-four of the included guidelines targeted all COVID-19 patients, while the remaining guidelines concentrated on special patient populations (i.e., geriatric population, pediatric population, and pregnant population) or patients with coexisting diseases. Twenty-three guidelines focused on the pharmacological treatments for all COVID-19 patients. Interferon, Lopinavir/Ritonavir, Ribavirin, Chloroquine, and Umifenovir represented the most recommended antivirus drugs. With the emergence of encouraging results from preclinical and preliminary clinical studies, Chloroquine Phosphate was recommended in the national Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (6^th version) on February 19^th, 2020. Thereafter, more detailed guidelines regarding the adjustment of dosage regimens and the monitoring of adverse events of Chloroquine Phosphate were published. To date, 8 Chinese guidelines have recommended Chloroquine Phosphate or Hydroxychloroquine as mainstream antivirus drug for the treatment of COVID-19. Conclusions: China has generated a plethora of guidelines covering almost all aspects of COVID-19. Chloroquine, as one widely affordable treatment, holds great potential to become the gold standard choice as more clinical evidence is shared by researchers from China as well as other countries.

Preprint REVIEW | doi:10.20944/preprints202106.0218.v1

Mucormycosis: Botanical Insights Into The Major Causative Agents

Naser A. Anjum

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Mucormycosis; Causative agents; Rhizopus sp.; Mucor sp.; Botanical insights; COVID-19

Online: 8 June 2021 (13:36:36 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202207.0181.v2

The mint versus Covid hypothesis

Chris Buck

Subject: Medicine And Pharmacology, Other Keywords: COVID-19; Covid19; SARS-CoV-2; pandemic; coronavirus; Lamiaceae, perilla; sage; tea; caffeic acid

Online: 5 October 2022 (09:48:05 CEST)

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Working Paper CASE REPORT

SARS-CoV-2 Infection in the Central Nervous System of a 1-Year-Old Infant

Ismael Carlos Gomes, Karina Karmirian, Julia Oliveira, Carolina Pedrosa, Mayara Abud Mendes, Fernando Colonna Rosman, Leila Chimelli, Stevens Rehen

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2 neuroinvasion; COVID-19; infant; Choroid plexus

Online: 15 March 2021 (13:03:33 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0280.v1

Effects of 2019 Novel Coronavirus on Male Reproductive System: A Retrospective Study

Jinzhuo Ning, Wei Li, Yuan Ruan, Yuqi Xia, Xiongfei Wu, Ke Hu, Xuhong Ding, Xiaojun Wu, Lilei Yu, Jianlin Zhou, Zhangfan Mao, Wanzhou Xu, Weimin Yu, Fan Cheng

Subject: Medicine And Pharmacology, Urology And Nephrology Keywords: COVID-19; 2019-nCoV; male reproductive system; a retrospective study

Online: 16 April 2020 (13:50:47 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202104.0710.v2

Estimation of Oxygen Cylinder Availability and Classification of Its Types, Suitability Using Machine Learning and Data Analysis

Anurag Sinha

Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: covid-19, machine learning, oxygen cylinder.

Online: 6 May 2021 (14:58:50 CEST)

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This is break direction on oxygen sources and conveyance methodologies for COVID-19 treatment. It has been adjusted from WHO and UNICEF's specialized details and direction for oxygen treatment gadgets, which is important for the WHO clinical gadget specialized arrangement, 1 and depends on current information on the circumstance in China and different nations where cases have been distinguished. This direction is proposed for wellbeing office chairmen, clinical leaders, acquisition officials, arranging officials, biomedical architects, foundation engineers and strategy producers. It portrays how to: measure oxygen interest, to distinguish oxygen sources that are accessible, and select suitable flood sources to best react to COVID-19 patients' requirements, particularly in low-and-center pay nations. WHO will refresh these suggestions as new data opens up. Coronavirus pandemic spurred fake interest for oxygen gas chambers for clinical use - both at emergency clinics and inquisitively, for home use by patients. A few patients and surprisingly sound people investigate the conceivable outcomes and likely benefits of utilizing oxygen from chambers for private utilization. Be that as it may, this isn't continuously protected, and sufficient safety measures are to be taken, bombing which there can be fatalities. This paper investigates the significance of keeping up satisfactory degrees of oxygen levels appropriate for human utilization. It advises the clinical use and the advantages and disadvantages of putting away oxygen chambers at home. The investigation likewise addresses lawful and administrative perspectives. The investigation's discoveries can help people settle on an educated choice on the protected use regarding oxygen gas. Further, it cautions on the expanded significance of guidelines and limiting access and use. This paper aims at designing an oxygen level monitoring technique in an oxygen cylinder. The amount of oxygen present inside the oxygen cylinder is very vital information when such cylinder is in use for supply of oxygen to a critical patient. The amount of oxygen present inside the cylinder is measured by the pressure at the outlet nozzle. The pressure is measured using a high precision MEMS Pressure Sensor. The output of the MEMS pressure sensor is voltage of the order milli. An amplifier is used to amplify this milli volt signal. A microcontroller is used in cascade to process the signal and display the pressure of oxygen cylinder.

Preprint REVIEW | doi:10.20944/preprints202006.0025.v1

CRISPR-Based Assays for Rapid Detection of SARS-CoV-2

Vivek S. Javalkote, Nagesh Kancharla, Bhaskar Bhadra, Manish Shukla, Badrish Soni, Ajit Sapre, Michael Goodin, Anindya Bandyopadhyay, Santanu Dasgupta

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: CRISPR; Covid detection

Online: 4 June 2020 (06:03:16 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0199.v1

Revealing SARS-CoV-2 Functional Druggability Through Multi-Target Cadd Screening of Repurposable Drugs

Yash Gupta, Dawid Maciorowski, Raman Mathur, Catherine M. Pearce, David J. Ilc, Hamza Husein, Ajay Bharti, Daniel Becker, Rathi Brijesh, Steven B Bradfute, Ravi Durvasula, Prakasha Kempaiah

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS-CoV-2; COVID-19; CADD; virtual screening; approved drugs; drug repurposing; essential targets; molecular docking; molecular dynamics simulations

Online: 11 May 2020 (13:14:18 CEST)

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The emergence of SARS/MERS drug resistant COVID-19 with high transmission and mortality has recently been declared a deadly pandemic causing economic chaos and significant health problems. Like all coronaviruses, SARS-CoV-2 is a large virus that has many druggable components within its proteome. In this study, we focused on repurposing approved and investigational drugs by identifying potential drugs that are predicted to effectively inhibit critical enzymes within SARS-CoV-2. We shortlisted seven target proteins with enzymatic activities known to be essential at different stages of the virus life cycle. For virtual screening, the energy minimization of a crystal structure or modeled protein was carried out using Protein Preparation Wizard (Schrödinger LLC, 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs (n=5903) that are already approved by worldwide regulatory bodies including the FDA, using the ZINC database. Screening was performed against viral targets using three sequential docking modes (i.e. HTVS, SP and XP). Our in-silico virtual screening identified ~290 potential drugs based on the criteria of energy, docking parameters, ligand and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. A top lead from each target group was further subjected to molecular dynamics simulation (MDS) using the Desmond module to validate the efficacy of the screening pipeline. All of the simulated hit-target complexes were predicted to strongly interact and with highly stable binding. Thus, we have identified a number of approved and investigational drugs with high likelihood of inhibiting a variety of key SARS-CoV-2 proteins. Follow-up studies will continue to identify inhibitors suitable for combination therapy based on drug-drug synergy to thwart resistance. In addition, the screening hits that we have identified provide excellent probes for understanding the binding properties of the active sites of all seven targets, further enabling us to derive consensus molecules through computer-aided drug design (CADD). While infections are expanding at a rampant pace, it must be recognized that resistance will grow commensurately through either genetic shift and/or genetic drift to all small molecule drugs identified. Vaccines should provide a more permanent solution through prevention, but resistivity is still a possible scenario. Nevertheless, a persistent multi-target drug development program is essential to curb this ongoing pandemic and to keep reemergence in check.

Preprint REVIEW | doi:10.20944/preprints202004.0054.v1

Distributed Manufacturing of Open-Source Medical Hardware for Pandemics

Joshua Pearce

Subject: Engineering, Industrial And Manufacturing Engineering Keywords: pandemic; influenza pandemic; open source; open hardware; COVID-19; COVID-19 pandemic; medical hardware; open source medicine

Online: 6 April 2020 (12:38:59 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202203.0076.v1

The Advantage of Inactivated Vaccine for Preventing the Omicron Outbreak

Xinbo Lian, Jianping Huang, Li Zhang, Yingjie Zhao, Danfeng Wang, Shuoyuan Gao, Rui Wang, Xiaodong Song

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: COVID-19; Omicron; inactivated vaccines

Online: 4 March 2022 (09:10:15 CET)

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Preprint REVIEW | doi:10.20944/preprints202004.0330.v1

Brainstem Dysfunction in SARS-COV2 Infection Can Be a Potential Cause of Respiratory Distress

Calixto Machado, Joel Victor Gutierrez

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: SARS-CoV-2 (CoV-2); COVID-19; coronavirus; pandemic; respiratory distress; brainstem; respiratory center

Online: 19 April 2020 (05:37:30 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0285.v1

Understanding the Molecular Mechanism(s) of SARS-CoV2 Infection and Propagation in Human to Discover Potential Preventive and Therapeutic Approach

Sibi Raj, Vaishali Chandel, Brijesh Rathi, Dhruv Kumar

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: coronavirus; COVID-19; SARS-CoV2; vaccines; infection; prevention; therapeutics

Online: 16 April 2020 (16:05:27 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0466.v1

The Disruption of SARS-CoV-2 RBD/ACE-2 Complex by Ubrogepant Is Mediated by Interface Hydration

Olaposi Omotuyi, Oyekanmi Nash, Bashiru Ajiboye, Damilohun Metibemu, Babatunji Oyinloye, Ayodeji Ojo, kunle Okaiyeto

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; SARS-CoV-2 RBD; Ubrogepant; ACE-2; MD simulation

Online: 31 March 2020 (22:50:27 CEST)

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Preprint REVIEW | doi:10.20944/preprints202103.0490.v1

Long COVID, A Comprehensive Systematic Scoping Review

Hossein Akbarialiabad, Mohammad Hossein Taghrir, Ashkan Abdollahi, Nasrollah Ghahramani, Manasi Kumar, Shahram paydar, Babak Razani, John Mwangi, Ali A. Asadi-Pooya, Leila Malekmakan, Bahar Bastani

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Covid-19; Long Covid-19; Long Haulers Covid; Post Covid-19 Syndrome; Post-Acute Covid-19; Corona Virus; SARS-Cov-2; Novel Corona Virus 2019; Post-Acute SARS-CoV-2; PASC, Post-Acute Sequelae of COVID-19; Late Sequelae COVID-19

Online: 18 March 2021 (17:16:52 CET)

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Introduction: Despite more than one year passed since the first cases of SARS-CoV-2 were reported, there is still no consensus on the definition and clinical management of post-acute-COVID-19. The condition has heterogeneously been named as Chronic COVID syndrome, Post COVID-19 Syndrome, post-acute sequela of SARS-CoV-2 (PASC), and the more familiar long COVID. Method: In order to capture all relevant published studies, we undertook a multi-step search with no language restriction. The following four-step search strategy was utilized: First, a preliminary (limited) search was conducted on January 20, 2021, in Google Scholar and PubMed to identify the appropriate keywords. Then, on January 30, 2021, we adopted a search strategy of electronic databases from Cochrane Library, PsycINFO, PubMed, Embase, Scopus, and Web of sciences, using those keywords. Then, after duplicate removal, we screened all titles, abstracts, and full texts. This resulted in 66 eligible studies. Subsequently, after a forward and backward search of their references and citations an additional 54 publications were found, resulting in a total of 120 publications that formed the basis of the present analysis. The titles, abstracts, and full-texts of non-English articles were translated using Google Translate for further evaluation. We conducted our scoping review based on the PRISMA-ScR Checklist.Results: We found only one randomized clinical trial in our search. Of the 67 original studies, 22 were cohort and 28 were cross-sectional studies totaling 74.6% of the original studies. Of the total of 120 publications, 59 (49.1%) focused on signs and symptoms, 28 (23.3%) were focused on management, and 13 (10.8%) focused on pathophysiology. Ten (9%) publications focused on imaging studies. Ninety-one percent of the original investigations came from high and upper-middle-income countries, highlighting the scarcity of reports originating from low-income and lower-middle-income countries.Conclusion: The predominant symptoms among those with the so-called “Long COVID” were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness. The ambiguity and controversies in its definition have impaired proper recognition and management of those requiring additional support following the resolution of the acute phase of this infection. This has resulted in long-standing distress for the patients and their families. Our findings highlight the need for a multidisciplinary approach, support, and rehabilitation for these patients in terms of long-term mental and physical health.

Preprint REVIEW | doi:10.20944/preprints202402.1267.v1

Inadvertent Exposure to Pharmacologically Designed Lipid Nanoparticles Via Bodily Fluids: Biologic Plausibility and Potential Consequences

Matthew Halma, Jessica Rose, Peter McCullough

Subject: Medicine And Pharmacology, Transplantation Keywords: Covid-19 vaccination; mRNA vaccine; lipid nanoparticles; blood transfusion; breastfeeding exposure; pharmacovigilance

Online: 22 February 2024 (04:00:44 CET)

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Exposure to vaccine lipid nanoparticles, mRNA, adenoviral DNA, and or Spike protein from one of the approved Covid-19 vaccines, or through secondary exposure, as through blood transfusion, is a potential source of harm. Blood reactions are an acknowledged side-effect of Covid-19 vaccination, not limited to hemolysis, paroxysmal nocturnal hemoglobinuria, chronic cold agglutinin disease, immune thrombocytopenia, haemophagocytosis, hemophagocytic lymphohistiocytosis, and many other blood related conditions. The observation of adverse events has motivated investigation into the cardiovascular mechanisms of harm by Covid-19 vaccines, and the biodistribution of vaccine contents. Biodistribution may not be limited to the body of the vaccine recipient, as a growing body of evidence demonstrates the possibility of secondary exposure to vaccine particles. These can be via bodily fluids and include the following routes of exposure: blood transfusion, organ transplantation, breastfeeding, and possibly other means. As covid-19 vaccines are associated with an increased risk of stroke, the persistence of vaccine artifacts in the blood presents a possible threat to a recipient of a blood donation from a vaccinated donor who suffered from vaccine induced thrombosis or thrombocytopenia. (VITT) We assess the feasibility and significance of these risks through an overview of the case report literature of blood disorders in vaccinated individuals, pharmacovigilance reports from the US Vaccine Adverse Events Reporting System (VAERS) and a meta-analysis of the available literature on organ transplants from vaccinated organ donors. Our analysis establishes biological mechanistic plausibility, a coherent safety signal in pharmacovigilance databases for secondary vaccine contents exposure (for the cases of blood transfusion and breastfeeding) and also an elevated level of adverse events in organ transplants from VITT-deceased donors, echoing increases in organ transplantation related complications seen in national statistics for some countries. Secondary exposure to vaccine artifacts is a potential explanation for some of the cases put forth, and requires a deeper investigation.

Preprint REVIEW | doi:10.20944/preprints202104.0481.v1

Minimizing Errors in RT-PCR Detection and Quantification of SARS-CoV-2 RNA for Wastewater Surveillance

Warish Ahmed, Stuart Simpson, Paul Bertsch, Kyle Bibby, Aaron Bivins, Linda Blackall, Silvia Bofill-Mas, Albert Bosch, Joao Brandao, Phil Choi, Mark Ciesielski, Erica Donner, Nishita D'Souza, Andreas Farnleitner, Daniel Gerrity, Raul Gonzalez, John Griffith, Pradip Gyawali, Charles Haas, Kerry Hamilton, Chanditha Hapuarachchi, Valerie Harwood, Rehnuma Haque, Greg Jackson, Stuart Khan, Wesaal Khan, Masaaki Kitajima, Asja Korajkic, Giuseppina La Rosa, Blythe Layton, Erin Lipp, Sandra McLellan, Brian McMinn, Gertjan Medema, Suzanne Metcalfe, Wim Meijer, Jochen Mueller, Heather Murphy, Colleen Naughton, Rachel Noble, Sudhi Payyappat, Susan Petterson, Tarja Pitkanen, Veronica Rajal, Brandon Reyneke, Fernando Roman, Joan Rose, Marta Rusinol, Michael Sadowsky, Laura Sala-Comorera, Yin Xiang Setoh, Samendra Sherchan, Kwanrawee Sirikanchana, Wendy Smith, Joshua Steele, Rosalie Sabburg, Erin Symonds, Phong Thai, Kevin Thomas, Josh Tynan, Simon Toze, Janelle Thompson, Andy Whiteley, Judith Wong, Daisuke Sano, Stefan Wuertz, Irene Xagoraraki, Qian Zhang, Amity Zimmer-Faust, Orin Shanks

Subject: Environmental And Earth Sciences, Waste Management And Disposal Keywords: COVID-19; SARS-CoV-2; Wastewater; Surveillance; False-positive; False-negative; RT-PCR

Online: 19 April 2021 (13:08:13 CEST)

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Wastewater surveillance for pathogens using the reverse transcription-polymerase chain reaction (RT-PCR) is an effective, resource-efficient tool for gathering additional community-level public health information, including the incidence and/or prevalence and trends of coronavirus disease-19 (COVID-19). Surveillance of SARS-CoV-2 in wastewater may provide an early-warning signal of COVID-19 infections in a community. The capacity of the world’s environmental microbiology and virology laboratories for SARS-CoV-2 RNA characterization in wastewater is rapidly increasing. However, there are no standardized protocols nor harmonized quality assurance and quality control (QA/QC) procedures for SARS-CoV-2 wastewater surveillance. This paper is a technical review of factors that can lead to false-positive and -negative errors in the surveillance of SARS-CoV-2, culminating in recommendations and strategies that can be implemented to identify and mitigate these errors. Recommendations include, stringent QA/QC measures, representative sampling approaches, effective virus concentration and efficient RNA extraction, amplification inhibition assessment, inclusion of sample processing controls, and considerations for RT-PCR assay selection and data interpretation. Clear data interpretation guidelines (e.g., determination of positive and negative samples) are critical, particularly during a low incidence of SARS-CoV-2 in wastewater. Corrective and confirmatory actions must be in place for inconclusive and/or potentially significant results (e.g., initial onset or reemergence of COVID-19 in a community). It will also be prudent to perform inter-laboratory comparisons to ensure results are reliable and interpretable for ongoing and retrospective analyses. The strategies that are recommended in this review aim to improve SARS-CoV-2 characterization for wastewater surveillance applications. A silver lining of the COVID-19 pandemic is that the efficacy of wastewater surveillance was demonstrated during this global crisis. In the future, wastewater will play an important role in the surveillance of a range of other communicable diseases.

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