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Preprint REVIEW | doi:10.20944/preprints202004.0540.v1

What is Happening with Smokers and COVID-19? A Systematic Review and a Meta-Analysis

Jesus Gonzalez-Rubio, Carmen Navarro-Lopez, Elena Lopez-Najera, Ana Lopez-Najera, Lydia Jiménez-Díaz, Juan D. Navarro-López, Alberto Nájera

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: cholinergic anti-inflammatory pathway; novel coronavirus; SARS-CoV-2; COVID-19; meta-analysis; Cytokine Release Syndrome; nicotine; smokers

Online: 30 April 2020 (17:01:38 CEST)

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Preprint REVIEW | doi:10.20944/preprints202107.0129.v3

A Potential Benefit of Hypochlorous Acid - Facial Sanitisation

Avis Aman Nowbuth, Josh Barrie Armstrong, Thomas Eugene Cloete, Pieter Rousseau Fourie

Subject: Medicine And Pharmacology, Other Keywords: HOCl; hypochlorous; antimicrobial; antiinflammatory; SARS-CoV-2; infections; sanitisation

Online: 3 December 2021 (10:13:20 CET)

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Preprint REVIEW | doi:10.20944/preprints202004.0040.v3

COVID-19 Virus Infection and Transmission are Observably Less in Highly Dengue-endemic Countries: Can Dengue Vaccines be “Repurposed” to Prevent COVID-19?

Subhajit Biswas, Soumi Sukla

Subject: Biology And Life Sciences, Virology Keywords: Dengue; COVID-19; SARS-CoV-2; epidemiology; infection; mortality; cross-protection; Dengue vaccine; ELISA; Dengvaxia

Online: 5 May 2020 (03:00:34 CEST)

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Preprint REVIEW | doi:10.20944/preprints202005.0041.v1

Vimentin as a Multifaceted Player and Potential Therapeutic Target in Viral Infections

Irene Ramos, Konstantinos Stamatakis, Clara L. Oeste, Dolores Pérez-Sala

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Vimentin; Cell surface vimentin; SARS-CoV; Vimentin-pathogen interactions; Anti-vimentin autoantibodies; Inflammation

Online: 3 May 2020 (09:00:43 CEST)

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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/preprints202004.0359.v1

Genomic Diversity and Evolution, Diagnosis, Prevention, and Therapeutics of the Pandemic COVID-19 Disease

M. Nazmul Hoque, Abed Chaudhury, Md. Abdul Mannan Akanda, M. Anwar Hossain, Md Tofazzal Islam

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: SARS-CoV-2; genetic diversity; genome evolution; diagnostics; therapeutics; vaccines

Online: 20 April 2020 (02:33:15 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 REVIEW | doi:10.20944/preprints202004.0351.v1

BCG Vaccination Strategy for Preventaion against COVID-19: Hype or Hope?

Keshav Rajarshi, Aroni Chatterjee, Shashikant Ray

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: COVID-19; BCG immunization; SARS-CoV-2; immunity and tuberculosis

Online: 19 April 2020 (13:55:50 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0510.v1

A Structural View at SARS-CoV-2 RNA Replication Machinery: RNA Synthesis, Proofreading and Final Capping

Maria Romano, Alessia Ruggiero, Flavia Squeglia, Giovanni Maga, Rita Berisio

Subject: Biology And Life Sciences, Biophysics Keywords: SARS-CoV-2; COVID19; RNA replication; protein structure; infectious disease

Online: 29 April 2020 (12:52:18 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0372.v1

Pathogenesis, Diagnosis and Possible Therapeutic Options for COVID-19

Yusha Araf

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; Diagnosis; Pathogenesis; Treatment; SARS-CoV-2

Online: 21 April 2020 (04:44:40 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202202.0197.v1

Mat-O-Covid: Validation of a SARS-CoV-2 Job Exposure Matrix (JEM) Using Data from a National Compensation System for Occupational Covid-19

Alexis Descatha, Grace Sembajwe, Fabien Gilbert, Marc Fadel

Subject: Public Health And Healthcare, Health Policy And Services Keywords: public health; occupational; Covid; SARS-CoV-2; work; job exposure matrix; JEM; compensation; predictivity; validity; accuracy

Online: 16 February 2022 (09:47:18 CET)

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Preprint COMMUNICATION | doi:10.20944/preprints202012.0543.v1

In-vitro Virucidal Activity of Commercial Enzyme Preparations against SARS-CoV-2 Virus

Anuradha V. Chitnis, Abhijit Rathi

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2; enzymes; virucidal; biocide

Online: 21 December 2020 (19:10:09 CET)

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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/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.

Preprint ARTICLE | doi:10.20944/preprints202103.0609.v1

Evaluation of a Bioaerosol Sampler for Indoor Environmental Surveillance of Severe Acute Respiratory Syndrome Coronavirus 2

Patrick F. Horve, Leslie Dietz, Dale Northcutt, Jason Stenson, Kevin G. Van Den Wymelenberg

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; COVID-19; Aerosols; Environmental Surveillance; Air Sampling

Online: 24 March 2021 (17:29:23 CET)

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Preprint ARTICLE | doi:10.20944/preprints202005.0338.v1

Community Pharmacy Response to Infection Control during COVID-19. A Cross-Sectional Survey.

Zachary Sum, Charmane Ow

Subject: Public Health And Healthcare, Public, Environmental And Occupational Health Keywords: pharmacy practice; infection control; sanitation; COVID-19; SARS-CoV-2; pharmacists; public health; workplace safety

Online: 21 May 2020 (08:37:52 CEST)

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Background: Australia received its first case of coronavirus on 25 January 2020. Since then the demands of COVID-19 has presented unparalleled levels of strain on the public healthcare systems in the country. In this time of crisis, pharmacists and community pharmacy staff have modified work strategies according to the rapidly changing environment. With a delayed dissemination of resources and guidelines, pharmacist and pharmacies are practicing innovative infection control methods across Australia to protect their staff, patients and the community. This article seeks to explore the current activities undertaken by pharmacists in various community pharmacy settings across Australia in relation to the safety of the workplace environments for staff and patients. Information collected can help inform future decisions in pandemic preparation for pharmacies in response to similar health crisis now and in the future. Methods: An online cross-sectional survey study was conducted in Australia during the COVID-19 outbreak from 1^st to 30^th April 2020. The questionnaire addressed community pharmacist’s awareness and response to infection and sanitation control. Results: A total of 137 pharmacists took part in the survey, with almost half (45.26%) belonging to the age group of 25 to 34 years. Community pharmacy formed the bulk (89.05%) of the respondent’s primary place of practice. There was a good uptake of safety measures by pharmacists and their pharmacies to protect staff and patients. However the task of reassigning high health risk staff was not heavily practiced (34.31%). Regular cleaning took place in the pharmacy, but the use of gloves while cleaning was not practiced in 48.18% of respondents. In addition, only 46.72% of respondents reported observing script baskets being cleaned and disinfected. About one-third (37.96%) of pharmacists were aware of the two-step cleaning and disinfecting process, but only 18.98% of pharmacists reported observing or performing this sanitation procedure. More than half of surveyed pharmacists reported having difficulty keeping up with infection control changes and pharmacy practice guidelines during the pandemic. Conclusion: This study demonstrates that the majority of pharmacists are not fully aware of the infection control measures needed in a community pharmacy setting. The influx of coronavirus updates has made it difficult for pharmacists to implement accurate procedures on some aspects of workplace hygiene, which may have led to some gaps in infection control measures. Pharmacists must aim to uphold their public health ambassador role and aim to keep up-to-date with professional guidance to provide the necessary infection control measures to ensure staff, patient and public health safety.

Preprint HYPOTHESIS | doi:10.20944/preprints202005.0144.v1

Pyridoxal 5'-phosphate to mitigate immune dysregulation and coagulopathy in COVID-19

Julie Desbarats

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: COVID-19, SARS-CoV-2, pyridoxal 5'-phosphate, pyridoxine, vitamin B6, immune response, IL-6, TNF, type I interferon, lymphopenia, blood clotting, coagulopathy, cytokine storm, sphingosine-1-phosphate, kynurenine, inflammasome, serine hydroxymethyltransferase 2 (SHMT2), hypertension, angiotensin

Online: 8 May 2020 (12:36:03 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0071.v1

Covid-19: Immunological Lessons from Bats, Pangolins and Old Coronaviruses; And How We Can Apply Them in a Timely Way for a Better Outcome

Devika Dua, Madhur Yadav, Pranav Jetley, Radhika Dua

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; SARS CoV; macrophage activation syndrome; cytokine storm; immunology

Online: 6 April 2020 (16:22:42 CEST)

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Preprint REVIEW | doi:10.20944/preprints202003.0103.v2

MERS-CoV and SARS-CoV Infections in Animals: A Systematic Review and Meta-Analysis of Prevalence Studies

D. Katterine Bonilla-Aldana, María C. Cardona-Trujillo, Alejandra García-Barco, Yeimer Holguin-Rivera, Isabella Cortes-Bonilla, Hugo A. Bedoya-Arias, Leidy Jhoana Patiño-Cadavid, Juan David Tamayo-Orozco, Alberto Paniz-Mondolfi, Lysien I. Zambrano, Kuldeep Dhama, Ranjit Sah, Ali A. Rabaan, Graciela J. Balbin-Ramon, Alfonso J. Rodriguez-Morales

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Coronavirus; SARS-CoV; MERS-CoV; serology; molecular diagnosis; reservoir; public health

Online: 19 May 2020 (04:13:19 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0439.v1

Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site

Umesh Kalathiya, Monikaben Padariya, Marcos Mayordomo, Małgorzata Lisowska, Judith Nicholson, Ashita Singh, Maciej Baginski, Robin Fåhraeus, Neil Carragher, Kathryn Ball, Juergen Haas, Alison Daniels, Ted R. Hupp, Javier Antonio Alfaro

Subject: Biology And Life Sciences, Biophysics Keywords: SARS-CoV-2; COVID-19; spike glycoprotein; variability; molecular docking; molecular dynamics; inhibitors

Online: 24 April 2020 (11:42:01 CEST)

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Preprint REVIEW | doi:10.20944/preprints202006.0086.v2

An Overview of Basic Molecular Biology of SARS-CoV-2 and Current COVID-19 Prevention Strategies

Ankur Das, Raja Ahmed, Suraiya Akhtar, Khaleda Begum, Sofia Banu

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; Genome organisation and expression; Polyproteins; Prevention strategies

Online: 14 June 2020 (16:49:10 CEST)

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Preprint CONCEPT PAPER | doi:10.20944/preprints202005.0097.v5

Why Blood Group A Individuals Are at Risk Whereas Blood Group O Individuals Might Be Protected from SARS-CoV-2 (COVID-19) Infection: A Hypothesis Regarding How the Virus Invades the Human Body via Abo(H) Blood Group-Determining Carbohydrates

Peter Arend

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2–human carbohydrate interaction; trans-species glycosylation; A-like/Tn structure; trans-species glycan bridge

Online: 13 November 2020 (09:42:18 CET)

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Preprint ARTICLE | doi:10.20944/preprints202009.0375.v1

Unexpected Co-infection with Different Strains of SARS-CoV-2 in Patients with COVID-19

Hayder O. Hashim, Mudher K. Mohammed, Mazin J. Mousa, Hadeer H. Abdulameer, Alaa T.S. Alhassnawi, Safa A. Hassan, Mohammed Baqur S. Al-Shuhaib

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: co-infection; SARS-CoV-2; pike glycoprotein; stop mutations

Online: 17 September 2020 (05:33:59 CEST)

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There is a rising global concern for the ongoing outbreak of SARS-CoV-2 due to its high transmission rate and unavailability of treatment. Through the binding of its spike glycoprotein with angiotensin type 2 (ACE2), SARS-CoV-2 can efficiently get in the cells of patients and start its pandemic cycle. Herein, the biological diversity of SARS-CoV-2 infection was assessed in Babylon province of Iraq by investigating the possible genetic variations of the spike glycoprotein. A specific coding region of 795 bp within the viral spike (S) gene was amplified from 19 patients who suffered from obvious symptoms of SARS-CoV-2 infection. Sequencing results identified fifteen novel nucleic acid variations with a variety of distributions within the investigated samples. The electropherograms of all the identified variations showed obvious co-infections with at least two different viral strains per sample. Within these co-infections, the majority of samples exhibited three nonsense single nucleotide polymorphism (SNP)s, p.301Cdel, p.380Ydel, and p.436del, which yielded three truncated SARS-CoV-2 spike glycoproteins of 301, 380, and 436 amino acids length, respectively. The network and phylogenetic analyses indicated that for all viral infections were derived from multi-ancestral origins. Results inferred from the specific clade-based tree entailed that some viral strains were derived from European G-clade sequences. In conclusion, our data demonstrated the absence of any single strain infection among all investigated viral samples in the studied area, which may entail a higher risk of SARS-CoV-2 in this country. Through the identified high frequency of truncated spike proteins, we suggest that defective SARS-CoV-2 may depend on helper strains having intact spikes in its infection. Alternatively, another putative ACE2-independent route of viral infection way also suggested. To the best of our knowledge, this is the first report to describe the co-infection of multiple strains of SARS-CoV-2 in patients with COVID-19.

Preprint ARTICLE | doi:10.20944/preprints202006.0032.v1

Emergence of RBD and D614G Mutations in Spike Protein: An Insight from Indian SARS-CoV-2 Genome Analysis

VINAYAGAM SAMYUKTHA, VENKATESAN NAVEEN KUMAR

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; Spike protein; COVID-19; Mutation; hACE2 Receptor; Real-time PCR; Vaccine

Online: 4 June 2020 (08:48:03 CEST)

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Currently, entire world is crumbled due to COVID-19 caused by novel SARS-CoV-2. Globally, over 5 million people are infected by SARS-CoV-2 with 6% fatality rate. The surface spike (S) protein plays a key role in the pathogenesis of SARS-CoV-2 by mediating viral entry through human angiotensin converting enzyme 2 (hACE2) receptors on the host cell and there is a big global race to find viral neutralizing antibodies and vaccine against S protein of SARS-CoV-2. Since SARS-CoV-2 evolved into 10 different clades in a very short span, a study on sipke protein mutation is essential to have effective vaccine coverage globally. Based on the mutation analysis of S protein from 166 Indian SARS-CoV-2 genome, a total of 40 different SNPs comprising of 14 synonymous and 26 non-synonymous mutations were observed, and notably, Indian S protein diverged into two major clusters, D614 and G614, with 11 different types. Majority of Indian strains fall in A2a and O clusters. Alarmingly, we have observed six SNPs at RBD and notably two of them at RBM (S438F and S494P). S494P SNP, similar to Bat–SARS like-CoV, may indicate a low ACE2 binding affinity. Interestingly 38% of Indian strains harbor a characteristic D614G SNP which was found predominantly in A2a cluster, mostly comprising USA and European strains with high disease severity. The association of disease severity with D614G SNP is well-correlated in states with high death rate except Maharashtra. Notably, more than 50% of D614G mutation were observed in Northern part of India and 14% in Southern part but not in Kerala and Tamil Nadu strains. Highly conserved motif, D614 (608-VAVLYQDVNCT-618) in upstream and also few downstream, of S1/S2 furin cleavage site may indicate specific key role in efficient interaction with host proteases in pathogenesis. Further studies are warranted to clarify the impact of SD614G SNP association to disease severity . Interestingly, C2367T (Y789Y) synonymous SNP is observed in 37% of Indian strains and notably similar SNPs with degeneracy bases were observed which is a key indication for the possibility of misdiagnosis by Real-Time PCR and revised strategies are needed for the precise diagnosis. Circulation of high number of signature SNPs [D614G and C2367T (Y789Y)] in certain states may be an early indication of emergence of community transmission in India. Further large genome sequence data from India will aid in deep understanding on the diversity of circulating SASR-Cov-2 and its impact on disease severity, origin of imported cases to India, community spread, effect on diagnosis and vaccine coverage.

Preprint ARTICLE | doi:10.20944/preprints202004.0425.v1

Non-Coding RNAs and Innovative Therapeutic Strategies to Target the 5’UTR of SARS-CoV-2

Antonella Baldassarre, Alessandro Paolini, Stefania Paola Bruno, Cristina Felli, Alberto Eugenio Tozzi, Andrea Masotti

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2; COVID-19; 5’UTR; miRNAs; RNAi; GapmeRs

Online: 24 April 2020 (04:16:20 CEST)

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Working Paper REVIEW

A Critical Review of Disinfection Processes to Control SARS-CoV-2 Transmission in the Food Industry

Adrián Pedreira, Yeşim Taşkın, Míriam R. García

Subject: Biology And Life Sciences, Food Science And Technology Keywords: SARS-CoV-2; COVID-19 pandemic; food industry; disinfection trade-offs; one-health

Online: 15 December 2020 (12:58:18 CET)

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Working Paper BRIEF REPORT

Potential for Developing a SARS-CoV Receptor Binding Domain (RBD) Recombinant Protein as a Heterologous Human Vaccine against Coronavirus Infectious Disease (COVID)-19

Wen-Hsiang Chen, Peter J. Hotez, Maria Elena Bottazzi

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: heterologous vaccine; receptor-binding domain; subunit vaccine; coronavirus; COVID-19; SARS; SARS-CoV-2

Online: 4 March 2020 (05:19:16 CET)

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Working Paper ARTICLE

COVID-19 Perfect Storm (Part II): Role of Vitamins as Therapy or Preventive Strategy in Aged People

Sirio Fiorino, Claudio Gallo, Maddalena Zippi, Sergio Sabbatani, Roberto Manfredi, Renzo Moretti, Elisa Fogacci, Caterina Maggioli, Francesca Travasoni Loffredo, Enrico Giampieri, Ivan Corazza, Christoph Dickmans, Claudio Denitto, Michele Cammarosano, Michele Battilana, Paolo Emilio Orlandi, Francesco Del Forno, Francesco Miceli, Michela Visani, Giorgia Acquaviva, Paolo Leandri, Elio Jovine, Roberto Iovine, Dario de Biase

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS; CoV-2; COVID-19; vitamins; therapeutic strategy

Online: 18 May 2020 (12:51:05 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0357.v1

Overview of Trans-National Recommendations for COVID-19 Transmission Control in Dental Care Settings

Mohamed Jamal, Maanas Shah, Sameeha Husain Almarzooqi, Hend Aber, Summayah Khawaja, Rashid El Abed, Zuhair Alkhatib, Lakshman Perera Samaranayake

Subject: Medicine And Pharmacology, Dentistry And Oral Surgery Keywords: coronavirus; COVID-19; SARS-CoV2; dentistry; oral health; transmission

Online: 20 April 2020 (02:14:36 CEST)

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Preprint REVIEW | doi:10.20944/preprints202007.0262.v1

Epidemiological Models of SARS-CoV-2 (COVID-19) to Control the Transmission Based on Current Evidence: A Systematic Review

Swati Arora, Rishabh Jain, Harendra Pal Singh

Subject: Public Health And Healthcare, Health Policy And Services Keywords: SARS-COV-2; COVID-19; Lockdown; Epidemiological Models; Machine Learning; Transmission

Online: 12 July 2020 (15:18:48 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0369.v2

Repurposing of Approved Drugs with Potential to Interact with SARS-CoV-2 Receptor

Abu Sajib

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; spike protein; ACE1; ACE2; host-virus interaction; drug repurposing

Online: 2 August 2020 (09:23:18 CEST)

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Preprint REVIEW | doi:10.20944/preprints202005.0204.v1

A Review on SARS-CoV-2 Virology, Pathophysiology, Animal Models and Anti-Viral Interventions

Sabarinath Neerukonda, Upendra Katneni

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; COVID-19; animal models; anti-virals

Online: 12 May 2020 (05:45:58 CEST)

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Preprint REVIEW | doi:10.20944/preprints202001.0364.v2

A Review on the Factors Contributing to 2019-nCoV Virus Outbreaks in Wuhan

Zhong Sun, Thilakavathy Karuppiah, S. Suresh Kumar, Guozhong He

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: 2019-nCoV; SARS-CoV; drought; bat; green light

Online: 4 February 2020 (10:31:47 CET)

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Preprint REVIEW | doi:10.20944/preprints202006.0321.v1

Hesperidin and SARS-CoV-2: New Light on the Healthy Functions of Citrus Fruit

Paolo Bellavite, Alberto Donzelli

Subject: Biology And Life Sciences, Food Science And Technology Keywords: Citrus fruits; Citrus sinensis; hesperidin; COVID-19; vitamin C; SARS-CoV-2; sweet orange

Online: 28 June 2020 (08:45:24 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202004.0286.v1

Comparative Domain-Fold Analysis of the SARS-CoV-2 ORF1ab Polyprotein: Insight into Co-Evolution, Conservation of Folding Patterns, Potential Therapeutic Strategies, and the Possibility of Reemergence

Srijeeb Karmakar, Sachin Kumar, Vimal Katiyar

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; domain-fold; evolutionary fingerprint; conserved domain; point mutation; recombination

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

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Preprint BRIEF REPORT | doi:10.20944/preprints202004.0407.v2

New Coronavirus (COVID-19) Pandemic: Complexities Resulting in a Tragedy

Gabriele Grunig, Nedim Durmus, Leigh Marsh

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: covid; covid-19; SARS-CoV-2; zoonosis; ethnic disparities; health care disparities; virus strains; virus subtypes; virus variants

Online: 26 April 2020 (05:13:37 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202008.0447.v1

Spike Protein of SARS-CoV-2: Impact of Single Amino Acid Mutation and Effect of Drug Binding to the Variant-in Silico Analysis

Pratibha Manickavasagam

Subject: Biology And Life Sciences, Virology Keywords: spike protein; SARS-CoV-2; mutation; drug repurposing; digitoxin

Online: 20 August 2020 (08:24:41 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0068.v2

Discovery of Multi-Target-Directed Ligands by Targeting Host-specific SARS-CoV-2’s Structurally Conserved Main Protease

Rakesh Joshi, Shounak Jagdale, Sneha Bansode, S. Shiva Shankar, Meenakshi Tellis, Vaibhav Kumar Pandya, Ashok Giri, Mahesh Kulkarni

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: coronavirus; COVID-19; hACE-2; MPro; multi-target-directed ligand; protease inhibito; RdRp; SARS-CoV-2 virus

Online: 9 April 2020 (05:13:05 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202005.0359.v1

Entry of SARS-CoV2 through the Basal Surface of Alveolar Endothelial Cells – A Proposed Mechanism Mediated by CD147 in COVID-19

Francia Acosta Saltos, Alejandro David Acosta Saltos

Subject: Biology And Life Sciences, Virology Keywords: Covid-19; Endothelial; CD147; SARS-CoV2

Online: 23 May 2020 (05:26:13 CEST)

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Working Paper ARTICLE

Complementary Application of the Ozonized Saline Solution in Mild and Severe Patients with Pneumonia Covid-19: A Non-randomized Pilot Study

Adriana Schwartz, Gregorio Martínez-Sánchez, Alejandra Menassa de Lucía, Sergio Mejía Viana, Constanta Alina Mita

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: ozone therapy; ozonized saline solution; SARS-CoV-2; COVID-19; pneumonia

Online: 12 July 2020 (16:30:51 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202010.0574.v1

Bacteria Filtration Efficiency of Different Face Masks Worn during COVID-19 Pandemic in North-Eastern Tanzania: An In Vitro Study

Marianne Gnanamuttupulle, Shilanaiman Hilary Ntundu, Oliver Henke, Abias Anthon Moshi, David Msuya, Kondo Chilonga, Samuel G. Chugulu

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; COVID-19; face masks; filtration efficiency; Tanzania

Online: 28 October 2020 (09:43:55 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0344.v1

A Quantitative Genomic View of the Coronaviruses: SARS-COV2

Sk Sarif Hassan, Ranjeet Kumar Rout, Vipul Sharma

Subject: Computer Science And Mathematics, Mathematical And Computational Biology Keywords: fractal dimension; Shannon entropy; Hurst Exponent; GC Content & SARS-CoV2

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

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Preprint HYPOTHESIS | doi:10.20944/preprints202004.0269.v1

Antibiotics Against COVID-19 and Mitochondria? Urgent Thinking Out of the Box

Jaroslaw Tyszka, Karolina Kobos, Aleksandra Tyszka

Subject: Chemistry And Materials Science, Theoretical Chemistry Keywords: COVID-19; SARS-CoV-2; pandemic; antibiotics; immune response; mitochondria; epidemiology; health policy

Online: 16 April 2020 (12:14:30 CEST)

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Italian, Spanish, French vs German, Austrian or Norwegian COVID-19 tracks? Antibiotics might have a partial impact on COVID-19 death rates in various countries. Our working hypotheses based on recent publications is that that antibiotics may be a major factor that negatively affects patients’ immune system during viral infections. We are all aware that there is no specific and effective medical treatment for COVID-19 so far. However, we know that our immune system is the only efficient weapon that fights against this syndrome right now. In fact, antibiotics are very often prescribed to prevent secondary infections following an antiviral immune response. Various antibiotic therapies have also been commonly applied to support COVID-19 treatments in China and Italy. Unfortunately, the frequent antibiotic off-site targets include mitochondria that are genetically and evolutionary closely linked to bacteria. Mitochondria are multifunctional organelles responsible for bioenergetics in nearly all our cells, acting as signaling hubs in antiviral and antibacterial immune responses. Several studies have demonstrated that mitochondria are vulnerable to antibacterial treatments, interrupting their physiology. Inhibition of these processes by antibiotics might render the immune system less capable of fighting acute COVID-19 viral infections. Some antibiotics, including those prescribed for COVID-19 in Wuhan, have been shown to inhibit the synthesis of mitochondrial DNA. The question is whether antibiotics support such a treatment or weaken patient immune responses in this case. This hypothesis should be evaluated based on comparative clinical data that seem to be unavailable at the moment. Possibly the COVID-19 risk group should be extended to all patients being treated with antibiotics, including those who finished antibiotic therapies days up to several months before SARS-CoV-2 infection. We therefore urge health service response groups to evaluate the impact of antibiotics on COVID-19 recovery vs death retrospective data. We would like to motivate international, national and local health authorities to share available clinical treatment data, discuss and optimize treatment strategies.

Preprint REVIEW | doi:10.20944/preprints202008.0353.v1

Rethinking Aptamers as Nanotheranostic Tools for SARS-COV-2 and COVID-19 Infection

christian Dzuvor

Subject: Biology And Life Sciences, Virology Keywords: aptamers; theranostics; SARS-COV-2; COVID-19; bioaffinity

Online: 17 August 2020 (08:01:15 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202003.0350.v1

A Radiation Oncology Departmental Policy for the 2019 Novel Coronavirus (COVID-19) Pandemic

Yuan James Rao, Destie Provenzano, Hiram A. Gay, Paul W. Read, Martin Ojong, Sharad Goyal

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: COVID-19; SARS-CoV-2; coronavirus; novel coronavirus; department policy; radiation oncology

Online: 23 March 2020 (09:55:24 CET)

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Preprint REVIEW | doi:10.20944/preprints202001.0230.v1

Structure-Activity Relationship and Mechanistic Insights for Anti-HIV Natural Products

Ramanpreet Kaur, Pooja Sharma, Girish K. Gupta, Fidele Ntie-Kang, Dinesh Kumar

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: AIDS; anti-HIV; natural products; SARs

Online: 21 January 2020 (03:15:50 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0063.v1

A Proposal for Isotherm World Maps to Forecast the Seasonal Evolution of the SARS-CoV-2 Pandemic

Nicola Scafetta

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; Pandemic geographical distribution; Epidemic forecasting; Weather conditions; Climatic zones.

Online: 6 April 2020 (14:11:52 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0195.v1

Single-Cell RNA-seq Identifies Cell Subsets in Human Placenta That Highly Expresses Factors to Drive Pathogenesis of SARS-CoV-2

Nancy Ashray, Anshul Bhide, Priyanka Chakarborty, Stacy Colaco, Anuradha Mishra, Karisma Chhabria, Mohit Kumar Jolly, Deepak Modi

Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: Placenta; trophoblast; SARS-CoV-2; Coronaviruses; COVID-19; Single cell RNAseq; scRNA-seq; ACE2; TMPRSS2; CD147; CTSL; inflammation

Online: 11 May 2020 (12:50:48 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0365.v1

Molecular Modelling and Docking Experiments Examining the Interaction between SARS-CoV-2 Spike Glycoprotein and Neuronal Nicotinic Acetylcholine Receptors

Konstantinos Farsalinos, Elias Eliopoulos, Demetres Leonidas, Georgios Papadopoulos, Socrates Tzartos, Konstantinos Poulas

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: COVID-19; SARS-CoV-2; smoking; nicotine; nicotinic cholinergic system; inflammation; acetylcholine receptors

Online: 23 May 2020 (10:06:14 CEST)

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Preprint CONCEPT PAPER | doi:10.20944/preprints202004.0158.v1

How studies on inflamm-aging may help to understand and combat COVID-19 pandemic.

Gianluca Storci

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Covid-19; SARS-CoV-2; Inflamm-aging; mtDNA; Telomere; Inflammation

Online: 9 April 2020 (14:43:41 CEST)

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More than 1,000,000 confirmed cases of COVID-19 have been registered worldwide since the beginning of the pandemic in Wuhan on December 2019. The high mortality rate of COVID-19 is associated with age, gender and the presence of comorbidities. Biochemical data have shown that COVID-19 patients develop a local and systemic hyper-inflammatory response associated with poor outcome. Therefore, the understanding of the biological mechanisms underlying SARS-CoV-2-induced inflammation is a compelling need. Following this reasoning, here we will focus on the importance of the progressive age-related development of a pro-inflammatory state (aka inflamm-aging) in the understanding of the unbalanced inflammatory response against SARS-CoV-2 in aged people. In particular, we underpin the role of mitochondrial DNA and genomic DNA telomeric sequences in local and systemic mechanisms of inflammation. Indeed, the leakage of mtDNA out of its natural compartment (i.e. the mitochondrion), into the cytoplasm and in the extracellular environment is a powerful trigger of innate immunity and inflammation, as part of an evolutionary-conserved signaling mechanism of cellular damage (e.g. viral infection). High levels of circulating mtDNA are increased in aged people and set up as inflammatory markers of poor prognosis in intensive care unit patients. In turn, telomeric DNA, which can be released into the cytoplasm and in the extracellular environment upon cell damage, has been proven to exert potent anti-inflammatory activity. Since that aged people (particularly those affected by co-morbidity) are equipped with shortened telomeres, we posit that, in aged people affected by COVID-19 the release of mtDNA, coupled with insufficient telomeric DNA favors the onset of a detrimental inflammatory response. In this regard, we highlight that the mechanism of action of some currently used drugs, as well as potential new ones may be better understood under the light of the above-depicted theoretical framework thus explaining how studies on inflamm-aging may help to understand and combat COVID-19 pandemic.

Preprint REVIEW | doi:10.20944/preprints202005.0141.v1

Risk of Human-to-Wildlife Transmission of SARS-CoV-2

Sophie Gryseels, Luc De Bruyn, Ralf Gyselings, Sébastien Calvignac-Spencer, Fabian Leendertz, Herwig Leirs

Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: mammals; wildlife; SARS-CoV-2; human-to-wildlife transmission; COVID-19

Online: 8 May 2020 (09:56:01 CEST)

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It has been a long time since the world has experienced a pandemic with such a rapid devastating impact as the current COVID-19 pandemic. The causative agent, the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is further unusual in that it appears capable of infecting many different mammal species. As a significant proportion of people worldwide are infected with SARS-CoV-2 and may spread the infection unknowingly before symptoms occur or without any symptoms ever occurring, there is a non-negligible risk of humans spreading SARS-CoV-2 to wildlife, in particular mammals. Because of SARS-CoV-2’s evolutionary origins in bats and reports of humans transmitting the virus to pets and zoo animals, regulations for prevention of human-to-animal transmission have so far focused mostly on these animal groups. Here, we summarize recent studies and reports that show that a wide range of distantly related mammals are likely susceptible to SARS-CoV-2 and that susceptibility or resistance to the virus is in general not predictable, or only to some extent, by phylogenetic proximity to known susceptible or resistant hosts. In the absence of solid evidence on the SARS-CoV-2 susceptibility/resistance for each of the >5,500 mammal species, we argue that sanitary precautions should be taken when interacting with any mammal species in the wild. Preventing human-to-wildlife SARS-CoV-2 transmission is important for protecting these (sometimes endangered) animals from disease, but also to avoid establishment of novel SARS-CoV-2 reservoirs in wild animals. The risk of repeated re-infection of humans from such a wildlife reservoir could severely hamper SARS-CoV-2 control efforts. For wildlife fieldworkers interacting directly or indirectly with mammals, we recommend sanitary precautions such as physical distancing, wearing face masks and gloves, and frequent decontamination, which are very similar to regulations currently imposed to prevent transmission among humans.

Working Paper ARTICLE

Clinical Characteristics, Laboratory Findings, Radiographic Signs and Outcomes of 52,251 Patients with Confirmed COVID-19 Infection: A Systematic Review and Meta-Analysis

Ali Pormohammad, Saeed Ghorbani, Behzad Baradaran, Alireza Khatam, Raymond Turner, Mohammad Ali Mansournia, Demetrios N. Kyriacou, Juan-Pablo Idrovo, Nathan C. Bahr

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: COVID-19; SARS-CoV-2; coronavirus; severe acute respiratory syndrome coronavirus; meta-analysis

Online: 16 March 2020 (01:06:04 CET)

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Introduction: The 2019 novel coronavirus (COVID-19) is very contagious, and can be transmitted to other people by droplet, aerosol, sneezing, infected surface, and cough. There is no vaccine or effective treatment at this time. Therefore, the prevention of COVID-19 and the rapid diagnosis of infected patients is crucial. Method: We searched all relevant literature published up to February 28, 2020, from Embase, Scopus, PubMed, Web of Science, and the Cochrane library to collect the studies that reported clinical and laboratory characteristics of COVID-19 infected patients. The study quality was assessed with the Critical Appraisal Checklist. Depending on the heterogeneity test, we used either random or fixed-effect models to analyze the appropriateness of the pooled results. Result: Twenty studies were included in the meta-analysis, including a total of 52,251 patients with confirmed COVID-19 infection. 69.5% (95% CI 54.5-81, p < 0.001) of patients had a history of recent travel to Wuhan, contact with people from Wuhan, or lived in Wuhan. The most common symptoms among COVID-19 infected patients were fever 85.6 % (95% CI 73 -93, p < 0.001), and cough 63 % (95% CI 55.5-70, p < 0.001), respectively. The laboratory analysis showed that thrombocytosis was present in 91% (95% CI 81-98, p < 0.001) CRP was elevated in 81% (95% CI 65-91, p < 0.001), and lymphopenia in 62.5% of cases (95% CI 42-79, p < 0.001). The most common radiographic signs were bilateral involvement in 76.8% (95% CI 62.5-87, p < 0.001) and consolidation in 75.5% (95% CI 50.5-91, p < 0.001) of patients. Most patients (85.4%) were hospitalized, 20.6% of patients were admitted to the ICU in critical condition, and the mortality rate was 5.6%. Conclusions: Fever and cough are the most common symptoms of COVID-19 infection in the literature published to date. Thombocytosis, lymphopenia, and increased CRP were common lab findings although most patients included in the overall analysis did not have laboratory values reported. The most common radiographic sign was bilateral involvement in and consolidation. Among Chinese patients with COVID-19, rates of hospitalization, critical condition, and hospitalization were high in this study, but these findings may be biased by reporting only confirmed cases.

Preprint SHORT NOTE | doi:10.20944/preprints202008.0205.v3

The Anomalous Nature of the Fecal Swab Data, Receptor Binding Domain and Other Questions in RaTG13 Genome

Monali Rahalkar, Rahul Bahulikar

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: RaTG13; SARS-COV-2; Illumina sequencing, amplicon sequencing, NGS; fecal swab

Online: 5 October 2020 (12:20:17 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0309.v1

FONDENOXAVID: A Retrospective Analysis on Utility of Thromboprophylaxis with Fondaparinux and Enoxaparin in Patients with COVID19 Infection in Italy

Giuseppe Vito Viggiano, Giuseppe Cardillo, Vincenzo Russo, Sara Mangiacapra, Antonella Cavalli, Chiara Pesci, Andrea Fontanella, Federica Agrusta, Annamaria Bellizzi, Maria Amitrano, Mariateresa Iannuzzo, Clara Sacco, Corrado Lodigiani, Pierpaolo Di Micco

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: covid19; sars cov2; fondaparinux; enoxaparin; venous thrpmbpembolism; inflammatory diseases

Online: 19 May 2020 (04:07:50 CEST)

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Background: After the outbreak of a novel coronavirus (i.e. SARS COV2) in China and its diffusion around the world, great attentions was reserved to the increased incidence of venous thromboembolism in these patients. A specific antiviral action of heparins toward SARS COV2 has been reported in vitro such as a well know action of heparins to prevent VTE in inpatients with infective disease has already been reported since several years. Yet, because fondaparinux represent the pharmacological antithrombotic active sequence of all heparins and because its clinical indication o prevent VTE in inpatients is similar to heprains, we realized a retrospective analysis in inpatients with SARS COV2 on the incidence of VTE during pharmacological prophylaxis with enoxaparin or fondaparinux. This retrospective analysis was named FONDENOXAVID. Methods: We conducted a retrospective cohort study that used patients with SARS COV2 during the Italian outbreak from February 18, 2020 to April 30, 2020. Our aim was to compare the clinical characteristics, prophylactic treatment and outcomes in inpatients positive to SARS COV2 at risk to develop venous thromboembolism, in particular venous thrombosis with or without pulmonary embolism, during in-hospital primary thromboprophylaxis with enoxaparin (40 mg or 60 mg once daily) or fondaparinux (2.5 mg once daily). Statistical analysis was conducted with using MatLab R2016B and eventually ad hoc functions. Results: There were not significative differences in clinical characteristics between patients that used enoxaparin or fondaparinux as thromboprpophylaxis for SARS COV2. The cumulative incidence of thrombotic events was not different in patients that used enoxaparin or fondaparinux as thromboprpophylaxis. No differences were found also in d-dimer and fibrinogen levels test at the admission and after 3 weeks as markers of prolonged inflammation due to SARS COV2. Discussion: The increased incidence of VTE in vivo has been reported in several studies although prophylaxis with low molecular weight heparin was conducted in some of them. The clinical indication to prevent VTE was similar for heparins and fondaparinux. In our results a non-inferiority to prevent VTE was recorded when inpatients with SARS COV2 were treated with prophylactic doses of enoxaparin or fondaparinux according to international guidelines. The incidence of VTE in this retrospective analysis showed that Fondaparinux at fixed doses of 2.5 mg daily was not inferior to enoxaparin (4000 UI daily). Our results testify that fondaparinux and enoxaparin showed the same efficacy to reduce the incidence of VTE in inpatients with SARS COV2.

Preprint HYPOTHESIS | doi:10.20944/preprints202004.0317.v2

Minimum Size of Respiratory Droplets Containing SARS-CoV-2 and Aerosol Transmission Possibility

Byung Uk Lee

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); COVID19; Middle East Respiratory Syndrome Coronavirus; bioaerosol; aerosol

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

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Preprint ARTICLE | doi:10.20944/preprints202105.0381.v1

Building-Level Wastewater Monitoring for COVID-19 Using Tampon Swabs and RT-LAMP for Rapid SARS-Cov-2 RNA Detection

Aaron Bivins, Megan Lott, Marlee Shaffer, Zhenyu Wu, Devin North, Erin Lipp, Kyle Bibby

Subject: Environmental And Earth Sciences, Water Science And Technology Keywords: SARS-CoV-2; wastewater monitoring; environmental surveillance; RT-LAMP; building-level; near-source; passive sampling

Online: 17 May 2021 (10:07:04 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202006.0249.v1

TMPRSS2 Protease Inhibitors May Prolong But Heparins Accelerate SARS-CoV-2 Clearance

Shu Yuan, Si-Cong Jiang, Zhong-Wei Zhang, Zi-Lin Li, Chang-Quan Wang, Ming Yuan, Yang-Er Chen, Qi Tao, Ting Lan, Xiao-Yan Tang, Guang-Deng Chen, Jian Zeng

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: SARS-CoV-2; TMPRSS2; antibody epitopes; glycosylation sequons; heparin

Online: 21 June 2020 (10:12:34 CEST)

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Preprint SHORT NOTE | doi:10.20944/preprints202004.0501.v1

COVID-19 and Amazonia: Sustainable alternatives for an economic collapse

Luisa Diele-Viegas, Eder Pereira

Subject: Environmental And Earth Sciences, Environmental Science Keywords: Economic recession; SARS-CoV-2; Deforestation; Climate Change; Amazonia Integrity; Green Bonds

Online: 29 April 2020 (05:05:33 CEST)

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The severity of the ongoing COVID-19 outbreak demand from countries to adopt extreme measurements of social isolation to stop the spread and flatten the curve of contamination. Although social isolation measures may have negative impacts on economy, historically it has been showed to be more effective in saving lives and less damaging to economy than not adopting these measurements during a viral pandemic. In Brazil, despite the positioning of the president against social isolation due to the consequent economic recession, the rapid spread of the virus has worried the governors of the Brazilian states, which are thus managing stringent social isolation measurements to avoid the advance of the virus. Since one of the main strategies to guarantee progress and economic growth in Brazil has been the exploitation of natural resources from the Amazonia biome, here we discuss the importance of this biome to Brazilian economy during the post-pandemic recession and highlights potential strategies to burst the economy without promoting Amazonia destruction. We show that, together with the REDD+ and the Amazon Fund, the Forest bonds represents good strategies to burst Brazilian economy in a sustainable way, showing that it is possible to improve the commodities without increasing Amazonia deforestation or the greenhouse gases emissions. Amazonia is a biome of global importance for the avoidance of another global crisis, which will occur if we reach the climatic tipping point of 1.5°C. Thus, governmental actions should go towards its preservation, not exploitation and depletion. The commitment of the government with environmental conservation is paramount so that these economic strategies have positive results, especially in a post-pandemic scenario, where the economy will be extremely weakened. The COVID-19 brings us a lesson regarding how our attitudes can impact the world, and what we can expect from a global crisis. Perhaps we can apply these lessons and focus on change our economy towards a sustainable direction to avoid another global crisis in the years to come.

Preprint ARTICLE | doi:10.20944/preprints202005.0113.v1

Prevalence of Current Smoking and Association with Adverse Outcome in Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis

Konstantinos Farsalinos, Konstantinos Poulas, Riccardo Polosa, Anastasia Barbouni, Pasquale Caponnetto, Raymond Niaura

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: SARS-CoV-2; COVID-19; inflammation; smoking; nicotine; hospitalization; adverse outcome

Online: 7 May 2020 (08:52:04 CEST)

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Background: The purpose of this study was to examine the prevalence and effects of current smoking on adverse outcomes among hospitalized COVID-19 patients. Methods: We performed a systematic review of the literature (PubMed) for studies published until April 25. Studies were included into the analysis if they satisfied all of the following criteria: 1. To present hospitalized patients with COVID-19. 2. To classify patients into less and more severe disease, irrespective of the severity definition (defined as “adverse ourtcome”). 3. To present data on the smoking status, separately for each severity classification. We identified 18 (from a total of 1398) relevant studies. Pooled current smoking prevalence was compared with the gender-adjusted, population-based expected prevalence by calculating Prevalence Odds Ratio (POR). The association between current, compared to non-current and former, smoking and adverse outcome was examined by calculating Odds Ratio (OR). All analyses were performed using random-effects meta-analysis. Results: Among 6515 patients, 440 of whom were current smokers, the pooled prevalence of current smoking was 6.8% (95%CI: 4.8-9.1%) and the POR was 0.21 (95%CI: 0.16-0.26, P < 0.001). In Chinese studies only, the POR was 0.22 (95%CI: 0.17-0.27, P < 0.001). Current smokers were more likely to have an adverse outcome compared to non-current smokers (OR: 1.53, 95%CI: 1.06-2.20, P = 0.022). However, they were less likely to have an adverse outcome compared to former smokers (OR: 0.42, 95%CI: 0.27-0.74, P = 0.003). Conclusion: An unexpectedly low prevalence of current smoking was observed among hospitalized patients with COVID-19. Hospitalized current smokers had higher odds compared to non-current smokers but lower odds compared to former smokers for an adverse outcome. The possibility that nicotine may have a protective effect in COVID-19 which may be masked by smoking-related toxicity and by the abrupt cessation of nicotine intake when smokers are hospitalized should be explored.

Preprint CONCEPT PAPER | doi:10.20944/preprints202004.0133.v2

The Airborne and Gastrointestinal Coronavirus SARS-COV-2 Pathways

Tomás Santa-Coloma

Subject: Biology And Life Sciences, Virology Keywords: ACE2, airborne; coronavirus; COV-2; COVID-19; food chain; intestinal infection; Kepler conjecture; rebound epidemic; packaging; particle size; SARS; surgical masks.

Online: 13 April 2020 (10:12:52 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0367.v1

Potential Drug Candidates Underway Several Registered Clinical Trials for Battling COVID-19

Fahmida Mina, Md. Rahman, Sabuj Das, Sumon Karmakar, Mutasim Billah

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; drugs; 2019-nCoV; clinical trials; SARS-CoV-2

Online: 20 April 2020 (15:53:56 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0022.v1

Structural and Genetic Analysis of Coronaviruses Spike Proteins Suggest Pangolin as a Proximate Intermediate Host of SARS-CoV-2 (COVID-19)

Sohail Raza, Muhammad Asif Rasheed, Wajeeha Zahir, Muhammad Tariq Navid, Rana Aamir Diwan, Muhammad Awais, Tahir Yaqub, Masood Rabbani, Muhammad Rashid

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; origin; bat; pangolin

Online: 2 May 2020 (16:29:38 CEST)

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Preprint TECHNICAL NOTE | doi:10.20944/preprints202008.0659.v1

Noisy Genome Data and Faulty Clade Statistics Undermine Conclusions on SARS-CoV-2 Evolution and Strain Typing in the Brazilian Epidemy: A Technical Note

Marcelo R. S. Briones, Fernando Antoneli, Renata C. Ferreira, Isabel M. V. G. Carvalho, Luiz M. R. Janini

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

Online: 30 August 2020 (11:22:12 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202002.0147.v4

The clinically validated viral superinfection therapy (SIT) platform technology could cure early cases of COVID-19 disease

Imre Kovesdi, Volker Sandig, Shimon Slavin, Wolfgang Renz, Marc Van Ranst, Peter M. Chumakov, Tibor Bakács

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Coronavirus; SARS-CoV-2; COVID-19; interferon; IFN; superinfection therapy; SIT; infectious bursal disease virus; IBDV; R903/78; safety; treatment

Online: 1 February 2021 (16:07:55 CET)

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Preprint REVIEW | doi:10.20944/preprints202005.0518.v1

From Extracellular Vesicles to Global Environment: A Cosmopolite SARS-Cov-2 Virus

Veronika Kralj-Iglič, Raja Dahmane, Tjaša Griessler Bulc, Polonca Trebše, Saba Battelino, Mojca Bavcon Kralj, Metka Benčina, Klemen Bohinc, Darja Božič, Mojca Debeljak, Drago Dolinar, Aleš Iglič, Darja Istenič, Zala Jan, Monika Jenko, Marko Jeran, Gregor Jereb, Mojca Jevšnik, Aleksandra Krivograd Klemenčič, Tomaž Lampe, Irina Milisav, Andreea Oarga-Mulec, Andrej Ovca, Borut Poljšak, Franja Prosenc, Anna Romolo, Nina Resnik, Robert Sotler, Anja Šoštarič, Vid Šuštar, Urška Šunta, Urška Štibler, Bojana Uršič, Domen Vozel

Subject: Biology And Life Sciences, Biophysics Keywords: virus; extracellular vesicles; COVID-19; SARS-CoV-2; membrane vesicluation

Online: 31 May 2020 (21:35:23 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0262.v1

ACE-1 I/D Polymorphism Associated with COVID-19 Incidence and Mortality: An Ecological Study

Chris Kenyon

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: angiotensin-converting enzyme; I/D polymorphism; ACE; SARS-CoV-2; COVID-19 mortality rate; testing intensity

Online: 16 April 2020 (08:04:35 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202008.0530.v1

Antiviral phytochemicals identified in Rhododendron arboreum petals exhibited strong binding to SARS-CoV-2 M^Pro and Human ACE2 receptor

Maneesh Lingwan, Shagun Shagun, Yogesh Pant, Bandna Kumari, Ranjan Nanda, Shyam K Masakapalli

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: R. arboreum, Antiviral phytochemicals, SARS-CoV-2, MPro, ACE2, COVID-19

Online: 24 August 2020 (11:14:07 CEST)

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Background: Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) affects human respiratory function causing COVID-19 disease. Safe natural products with potential antiviral phytochemicals with benefits to control high-altitude sickness could be adopted as adjunct therapy for COVID-19. The red petals of Rhododendron arboreum, commonly available and consumed in the Himalayan region may have phytochemicals with potential antiviral properties against COVID-19 targets.Purpose: This study was aimed to profile the secondary metabolites of R. arboreum petals, to assess their absorption, distribution, metabolism and elimination (ADME) properties and evaluate their antiviral potential by docking against COVID-19 targets such as SARS-CoV-2 main protease (M^pro PDB ID: 6LU7) and Human Angiotensin Converting Enzyme 2 (ACE2) receptor (PDB ID: 1R4L) that mediates the viral replication and entry into the host respectively.Methods: The phytochemicals of R. arboreum petals were mainly profiled using Gas Chromatography-Mass Spectroscopy (GC-MS) and ¹H-NMR. In addition, the phytochemicals reported from the literature were tabulated. The ADME properties of the phytochemicals were predicted using SwissADME tool. Molecular docking simulation of the phytochemicals against SARS-CoV-2 main protease (M^pro PDB ID: 6LU7) and Human Angiotensin converting enzyme 2 (ACE2) receptor (PDB ID: 1R4L) were carried out using PyRx.Results: R. arboreum petals were found to be rich in appreciable proportions of secondary metabolites such as Quinic acid, 3-Caffeoyl-quinic acid, 5-O-Coumaroyl-D-quinic acid, 5-O-Feruloylquinic acid, 2,4-Quinolinediamine, Coumaric acid, Caffeic acid, Epicatechin, Catechin, 3-Hydroxybenzoic acid, Shikimic acid, Protocatechuic acid, Epicatechin gallate, Quercetin, Quercetin-O-pentoside, Quercetin-O-rhamnoside, Kaempferol-O-pentoside and Kaempferol. Several of these phytochemicals were reported to exhibit inhibitory activities against a range of viruses. From the molecular docking studies, 5-O-Feruloylquinic acid, 3-Caffeoyl-quinic acid, 5-O-Coumaroyl-D-quinic acid, Epicatechin and Catechin showed strong binding affinity with SARS-CoV-2 M^pro and human ACE2 receptor.Conclusion: This report showed that R. arboreum petals are rich in several antiviral phytochemicals that also docked against SARS-CoV-2 M^Pro and Human ACE2 receptor. This is the first report highlighting R. arboreum petals as a reservoir of antiviral phytochemicals with potential for synergetic activities. The outcomes merit further in vitro, in vivo and clinical studies on R. arboreum phytochemicals to develop natural formulations against COVID-19 disease for therapeutic benefits.

Working Paper COMMUNICATION

Open Questions for Harnessing Autophagy-Modulating Drugs in the SARS-CoV-2 War: Hope or Hype?

Patrick Brest, Jonathan Benzaquen, Daniel J. Klionsky, Paul Hofman, Baharia Mograbi

Subject: Biology And Life Sciences, Virology Keywords: anti-viral; COVID-19; SARS-CoV-2; autophagy; chloroquine; hydroxychloroquine; immunology; infection; inflammation; lysophagy; microbiology; Plaquenil; SARS; virophagy

Online: 23 May 2020 (10:45:40 CEST)

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Preprint REVIEW | doi:10.20944/preprints202008.0372.v1

A Review of Evidence: Using Respirators to prevent Sars-Cov-2 Transmission

Adam Nulty

Subject: Medicine And Pharmacology, Dentistry And Oral Surgery Keywords: sars-cov-2, covid, covid-19, masks, dentistry, respirator, n99, n95, ffp2, ffp3,

Online: 18 August 2020 (04:30:45 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202105.0108.v1

Physical Effectiveness of Safety Interventions in Fire Engines to Reduce Potential Airborne Transmission of SARS-CoV-2 (COFIRE)

Elmar Bourdon, Thomas Schaefer, Maximilian Kittel, Matthias Raedle, Alexandra Heininger

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: SARS-CoV-2; COVID-19; Safety Interventions; Fire Engine; Vehicle, Aerosol; Fine Dust Measurement

Online: 6 May 2021 (15:24:53 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0403.v1

Environmental Impact of Corona Virus (COVID-19) and Nationwide Lockdown in India: An Alarm to Future Lockdown Strategies

Suresh Kumar, Shishir Bhardwaj, Akash Singh, Hemant K. Singh, Puneet Singh, Uzzwal K. Sharma

Subject: Environmental And Earth Sciences, Environmental Science Keywords: zoonotic; corona virus; COVID-19; SARS; MERS; global health emergency; India; lockdown strategies

Online: 24 May 2020 (19:34:03 CEST)

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Global emerge of zoonotic novel corona virus (COVID-19) became a pandemic and its effect to mankind is talk of the town now a days. This tiny, invisible enemy has affected every country in the world and almost every living directly or indirectly and nationwide complete lockdown has triggered a short-term environmental impact. Since 2003, corona virus came into existence in the form of Severe Acute Respiratory Syndrome (SARS) and more evolved Middle East Respiratory Syndrome (MERS) in 2012. This time, at the end of December 2019, outbreak of novel corona virus COVID-19 (also known as SARS-CoV₂, nCoV-2019) draw attention as global health emergency. World Health Organization (WHO) report says that the outbreak of this virus is so immense, it has already affected 35,57,235 people and caused death to 2,45,150 people worldwide and 46,433 Indians got affected with 1568 death as on 5^th May 2020 (2:00 am) and these numbers are increasing exponentially day by day. Virologist, micro-biologist and science community are hammering their head very hard to find out cure and vaccine against this powerful virus and to prevent mass demise of mankind. In order to curb the spread of COVID-19, Janta curfew on 22.03.2020 and nationwide complete lockdown was implemented in India for 21 days (phase-I, from 25.03.2020 to 14.04.2020) to stop community transmission of third stage, for 19 days (phase-II, 15.04.2020 to 03.05.2020) and 14 days (phase-III, 04.05.2020 to 17.05.2020) complete lockdown to minimize the community transmission effect. During complete lockdown and quarantine period a drastic change in Earth’s atmosphere, including reduction in emission of greenhouse gases, air pollution (~50% fall in air quality index), noise pollution, water pollution and solid waste pollution, have been recorded by government agencies as well as private agencies. In this paper we considered data of Janta curfew, phase-I and phase-II lockdown to link between geological and environmental aspect related to environmental impact due to emerge of COVID-19 and massive reduction in pollution level during complete lockdown in India. We propose future lockdown strategies to minimize the emission of greenhouse gas by ~100 Mt to ~200Mt (3.33% to 6.66%) of GHG_total per year by 2-4 days per month nationwide lockdown or ~70 Mt to ~140 Mt (2.33% to 4.66%) of GHG_total per year by 2-4 days per month complete lockdown of energy sectors only.

Preprint ARTICLE | doi:10.20944/preprints202009.0327.v1

Transmission of SARS-CoV-2 in Northern Ghana; Insights from Whole Genome Sequencing

Augustina Angelina Sylverken, Philip El-Duah, Michael Owusu, Julia Schneider, Richmond Yeboah, Ayisi-Boateng Ayisi-Boateng, Richmond Gorman, Eric Adu, Alexander Kwarteng, Michael Frimpong, Sherihane Aryeetey, Jesse Addo Asamoah, Yaw Ampem Amoako, John Humphrey Amuasi, Jörn Beheim-Schwarzbach, Ellis Owusu-Dabo, Yaw Adu-Sarkodie, Kwasi Obiri-Danso, Victor Max Corman, Christian Drosten, Richard Phillips

Subject: Biology And Life Sciences, Virology Keywords: Ghana; SARS-CoV-2; transmission; Phylogenetics

Online: 15 September 2020 (04:24:17 CEST)

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In regions lacking genomic data, analysis of sequences from the early stages of an outbreak can provide important insights into the diversity of pathogens present. Following the detection of the first imported case of COVID-19 in the Northern sector of Ghana on 13^th March 2020, we have now molecularly characterized and phylogenetically analysed sequences including three (3) complete genomes of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) isolated from nine (9) patients observed in Ghana. Eight (8) of these patients reported with a recent history of foreign travel and one (1) with no history of foreign travel. We performed high throughput sequencing for 9 samples following the determination of high concentration of viral RNA. In addition, we estimated the potential impact that long distance transportation of samples to testing centres may have on sequencing outcomes. Here, two samples that were closest in terms of viral RNA concentration but transported from sites which are over 400km apart were assessed. All sequences were compared to previous sequences from Ghana and representative sequences from regions where our patients had previously travelled. Complete genomes were obtained for three (3) sequences and with another near complete genome with a coverage of 95.6%. Sequences with coverage in excess of 80% were found to belong to three lineages namely A, B.1 and B.2. Our sequences clustered in two different clades with the majority falling within a clade composed of sequences from sub-Saharan Africa. Less RNA fragmentation was seen in sample KATH23 which was collected 9km compared with sample TTH6 which was collected and transported over a distance of 400km to the testing site. The clustering of several sequences from sub-Saharan Africa suggests regional circulation of the viruses in the subregion. Importantly, there may be the need to decentralize testing sites and build more capacity across Africa to boost the sequencing output of the subregion.

Preprint ARTICLE | doi:10.20944/preprints202004.0512.v6

The Structure of the Membrane Protein of SARS-CoV-2 Resembles the Sugar Transporter semiSWEET

Sunil Thomas

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; Coronavirus; Virus; sugar transporter; SemiSWEET; Membrane glycoprotein, Pandemic

Online: 19 October 2020 (10:48:05 CEST)

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the disease COVID-19 that has decimated the health and economy of our planet. The virus causes the disease not only in people but also in companion and wild animals. People with diabetes are at risk of the disease. As yet we do not know why the virus is highly successful in causing the pandemic within 3 months of its first report. The structural proteins of SARS include, membrane glycoprotein (M), envelope protein (E), nucleocapsid protein (N) and the spike protein (S). The structure and function of the most abundant structural protein of SARS-CoV-2, the membrane (M) glycoprotein is not fully understood. Using in silico analyses we determined the structure and potential function of the M protein. The M protein of SARS-CoV-2 is 98.6% similar to the M protein of bat SARS-CoV, maintains 98.2% homology with pangolin SARS-CoV, and has 90% homology with M protein of SARS-CoV; whereas, the similarity was only 38% with the M protein of MERS-CoV. In silico analyses showed that the M protein of SARS-CoV-2 has a triple helix bundle, form a single 3-transmembrane domain (TM), and are homologous to the prokaryotic sugar transport protein semiSWEET. SemiSWEETs are related to the PQ-loop family that function as cargo receptors in vesicle transport, mediates movement of basic amino acids across lysosomal membranes, and is also involved in phospholipase flippase function. The advantage and role of the M protein having a sugar transport-like structure is not clearly understood. The M protein of SARS-CoV-2 interacts with S, E and N protein. The S protein of the virus is glycosylated. It could be hypothesized that the sugar transporter-like structure of the M protein influences glycosylation of the S protein. Endocytosis is critical for the internalization and maturation of RNA viruses, including SARS-CoV-2. Sucrose is involved in endosome and lysosome maturation and may also induce autophagy, pathways that help in the entry of the virus. Overall, it could be hypothesized that the semiSWEET sugar transporter-like structure of the M protein may be involved in multiple functions that may aid in the rapid proliferation, replication and immune evasion of the SARS-CoV-2 virus. Biological experiments would validate the presence and function of the semiSWEET sugar transporter.

Preprint REVIEW | doi:10.20944/preprints202003.0271.v2

Role of the Eye in Transmitting Human Coronavirus: What We Know and What We Do Not Know

Chuan-bin Sun, Yue-ye Wang, Geng-hao Liu, Zhe Liu

Subject: Medicine And Pharmacology, Ophthalmology Keywords: Coronavirus; 2019-nCOV; SARS-CoV-2; transmission; infection; conjunctiva; eye

Online: 24 March 2020 (06:42:35 CET)

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The outbreak of recently identified 2019 novel coronavirus (2019-nCOV) infection has become a world-wide health threat. Currently, more information is needed for further understanding the transmission, clinical characteristics, and infection control procedures of 2019-nCOV. Recently, the role of the eye in transmitting 2019-nCOV has been intensively discussed. Previous investigations about other high infectious human COVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide helpful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, mechanisms of human CoVs infection, and infection control procedures. The role of the eye in the transmission of SARS-CoV and 2019-nCOV is discussed. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of ocular surface and upper respiratory tract is connected by nasolacrimal duct and share same entry receptors for some respiratory viruses. The eye is rarely involved in human CoVs infection, conjunctivitis is quite rare in patients with SARS-CoV and 2019-nCoV infection, and COV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with SARS-CoV and 2019-nCoV infection is also very low, which imply that the eye is neither a preferred organ of human COVs infection, nor is a preferred gateway of entry for human COVs to infect respiratory tract. However, pathogens exposed to the ocular surface might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through lacrimal duct, and then cause respiratory tract infection. Considering close doctor-patient contact is quite common in ophthalmic practice which are apt to transmit human COVs by droplets and fomites, hand hygiene and personal protection are still highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.

Preprint COMMUNICATION | doi:10.20944/preprints202005.0367.v1

Children Have Lower SARS-CoV-2 Viral Loads Than Adults

David Curtis

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: SARS-CoV-2; COVID-19; viral load; children

Online: 23 May 2020 (10:15:07 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202008.0114.v1

Two SARS-CoV-2 IgG Immunoassays Comparison and Time-Course Profile of Antibodies Response

Ruggero Dittadi, Haleh Afshar, Paolo Carraro

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Immune response; SARS-CoV-2 antibodies response; Covid-19 management; Maglumi; Architect; method comparison.

Online: 5 August 2020 (08:09:11 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0409.v2

YoungJoon Park, Ju Won Ahn, Sojung Hwang, Kyoung Su Sung, Jaejoon Lim, KyuBum Kwack

Subject: Biology And Life Sciences, Virology Keywords: angiotensin-converting enzyme 2; SARS-CoV-2; spike protein; COVID-19

Online: 9 April 2020 (09:59:37 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202104.0552.v1

Role of Information Technology in COVID19 Vaccination Drive: An Analysis of the COVID-19 Global Beliefs, Behaviors, and Norms Survey

Debjyoti Talukdar, Kire Stojkovski, Daniel Suarez

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID19; vaccine; SARS nCoV-2; information technology; COVID19 vaccine survey; MIT vaccine survey

Online: 20 April 2021 (14:35:05 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0535.v1

Novel Polybasic Cleavage Site in SARS-CoV-2 Genome Is Likely to Induce a Major Change in the RNA Secondary Structure

Amirhossein Manzourolajdad, Zhenming Xu, Diako Ebrahimi

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2 RNA Secondary Structure; Spike Protein; Furin; TMPRSS2

Online: 30 April 2020 (14:13:36 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0137.v1

Genome Wide Analysis of Severe Acute Respiratory Syndrome Coronavirus-2 Implicates World-Wide Circulatory Virus Strains Heterogeneity

M. Rafiul Islam, M. Nazmul Hoque, M. Shaminur Rahman, J. Akter Puspo, Masuda Akhter, Salma Akter, A. S. M. Rubayet-Ul-Alam, Munawar Sultana, Keith A. Crandall, M. Anwar Hossain

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; genomes; nucleotide; amino-acid; mutations; replacements

Online: 9 April 2020 (05:56:35 CEST)

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Preprint REVIEW | doi:10.20944/preprints202007.0079.v1

Animal Models of SARS-CoV-2: A Systematic Review

Prabudh Goel, Vishesh Jain, Anjan Kumar Dhua, Devendra Kumar Yadav, Ajay Verma, Aparajita Mitra, Tripti Khanna, Sandeep Agarwala, Minu Bajpai

Subject: Medicine And Pharmacology, Veterinary Medicine Keywords: animal models; experimental models; SARS-CoV-2; COVID-19; rhesus macaque; monkey; hamster; ferrets; transgenic mice

Online: 5 July 2020 (15:07:53 CEST)

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Background: The use of animal models for biomedical research provides us with a convenient and feasible route to establish causal relationships by recapitulating the temporal sequence of events in a controlled environment with a potential to manipulate the variables at multiple levels including genetic, protein, physiological or environmental. Objectives: The current review was conducted to gain insights into various animal models for the SARS-CoV-2 virus. Material and Methods: A literature review (PUBMED, PUBMED Central, PMC, Google Scholar, Google search engine) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines performed in early April 2020 revealed 9 articles of interest. Search terms included covid 19, covid-19, novel corona virus, SARS-CoV-2, animal models, experimental models, laboratory models & covid 19 animal models. Two independent reviewers extracted the data; the third reviewer was involved in case of discrepancy. Results: SARS-CoV-2 shares an identical receptor binding domain with the SARS-CoV virus and has a superior binding affinity to the host ACE2. Based on this, the role of rhesus macaques, golden Syrian hamsters, transgenic hACE2 mice and ferrets as animal models have been studied. All four animals are susceptible to infection with SARS-CoV-2 with variable clinical presentation but universal recovery. The respiratory tract is primarily involved in all four models. Involvement of intestines was also seen in at least one study in each animal. Transfer to naïve animals in close contact has been documented in case of hamsters and ferrets. Seroconversion was documented in all although the role of convalescent sera was tested in hamsters only, with positive results though. Air-borne transmission was documented in ferrets and the possibility of feco-oral transmission was suggested for hamsters. The possibilities of recurrence and re-infection were ruled out by experiments upon the rhesus macaques. The fulfilment of Koch’s postulates has been highlighted. Discussion: The various studies available on animal models have been able to establish models of infection and transmission that recapitulate different aspects of disease in humans. However, the response between different animals and the same animal in different experiments is not completely coherent. Some of them do not manifest the disease clinically while others behave differently at molecular and immunological levels. Moreover, the physiology of these animals is not identical to human beings and the findings may not be extrapolated to human beings in an ‘as-is’ manner. Conclusions: The review acknowledges the achievements made by these experiments in a short span of time and highlighted the urgent need for a deeper dive in search of a quintessential animal model which can be studied for efficacy and safety of newer drugs and vaccines before a make-shift from the petri-dish to the human body can be contemplated.

Preprint ARTICLE | doi:10.20944/preprints202004.0347.v1

Potential Chimeric Peptides to Block the SARS-CoV-2 Spike RBD

Debmalya Barh, Sandeep Tiwari, Bruno Silva Andrade, Marta Giovanetti, Ranjith Kumavath, Preetam Ghosh, Aristóteles Góes-Neto, Luiz Carlos Junior Alcantara, Vasco Azevedo

Subject: Biology And Life Sciences, Virology Keywords: antiviral peptides; COVID-19; SARS-CoV-2; nCoV-19; peptide design; ACE2; Spike protein

Online: 19 April 2020 (13:21:44 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0045.v1

The Conceptual Framework for SARS-CoV-2 Related Lymphopenia

Ilnaz Rahimmanesh, Shirin Kouhpayeh, Hossein Khanahmad

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: SARS-CoV-2; lymphopenia; NAD+ depletion; CD38

Online: 6 April 2020 (09:28:00 CEST)

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Preprint REVIEW | doi:10.20944/preprints202005.0223.v1

COVID-19 Vaccines:A Race Against Time in the Middle of Death and Devastation!

Mohammad Khuroo, Mohammad Khuroo, Mehnaaz Khuroo, Ahmad Sofi, Naira Khuroo

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: COVID-19; SARS-CoV-2; coronavirus; vaccine; platform technology; clinical trials

Online: 13 May 2020 (05:10:48 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0279.v1

Chinese Stock Market Sector Indices Performance in the Time of Novel Coronavirus Pandemic

Venus Khim-Sen Liew, Chin-Hong Puah

Subject: Business, Economics And Management, Finance Keywords: novel coronavirus; COVID-19; SARS-CoV-2; pandemic; Chinese stock market; Exponential Generalized Autoregressive Conditional Heteroscedasticity

Online: 17 May 2020 (03:11:38 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202006.0370.v2

Defining and Computing Reproduction Numbers to Monitor the Outbreak of Covid-19 or Other Epidemics

Paulo Zingano, Janaina Zingano, Alessandra Silva, Carolina Zingano

Subject: Computer Science And Mathematics, Computational Mathematics Keywords: Covid-19 outbreak; SARS-Cov-2 coronavirus; reproduction numbers; SEIR models; parameter determination; herd immunity against Covid-19

Online: 16 February 2021 (13:18:54 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0542.v1

Histamine Antagonists to Temper the Cytokine Overproduction in Gastrointestinal Cells Infected by SARS-CoV-2

Han Geurdes, Ivo Koutsaroff

Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: Cytokine storm; IL-1 and IL-6 production via SARS-CoV-2; gastrointestinal H4R receptor antagonists

Online: 30 April 2020 (17:14:34 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202005.0192.v1

Saliva Glycoproteins Bind to Spike Protein of SARS-CoV-2

Dapeng Zhou, Chenghao Wu

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: SARS-CoV2; corona virus; affinity proteomics; glycoproteins; glycoprotein-binding domains

Online: 11 May 2020 (10:24:43 CEST)

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Working Paper BRIEF REPORT

The Potential Role of Th17 Immune Responses in Coronavirus Immunopathology and Vaccine-induced Immune Enhancement

Peter Hotez

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: COVID-19; SARS 2; coronavirus; Th17; eosinophils; heart disease

Online: 9 April 2020 (14:45:33 CEST)

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Preprint REVIEW | doi:10.20944/preprints202008.0321.v1

COVID-19 Pandemic and its Implications on Food Systems

Hilal A Makroo, Darakshan Majid, Mushtaq A Siddiqi, Ralf Greiner, B.N. Dar

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; coronavirus; pandemic; food; hygiene

Online: 14 August 2020 (11:16:44 CEST)

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Preprint REVIEW | doi:10.20944/preprints202009.0439.v1

Dental Professionals Knowledge, Attitude, and Practice Towards to COVID-19: Systematic Review and Meta-Analysis

Amare Teshome Tefera, Kirubel Asefaw, Biruk Bekele, Aynishet G/Mariam, Anteneh Ayelign, Hailu Aragie, Sileshi Ayhualem, Yonas Akalu, Meseret Derbew Molla, Abebe Muche

Subject: Medicine And Pharmacology, Dentistry And Oral Surgery Keywords: KAP; Dental professionals; COVID-19; Pandemic; risk of infection, SARS-CoV-2

Online: 18 September 2020 (12:15:24 CEST)

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Background: Dental professions are at high risk of contracting novel corona virus (COVID-19) infections during the dental procedure due to the droplets and aerosols generated during various dental procedures on infected patients. To prevent and avoid the cross-infection of the infection to dental professionals or the patients attending the dental clinic, good knowledge of the infection and its prevention mechanisms is mandatory among the professionals. Until to date, there is no pooled estimate on the knowledge,attitude and practice (KAP) of dental professionals to COVID-19 in the globe. Hence, this study aimed to determine the pooled estimate of KAP of dental professionals in this pandemic disease. Methods: Article search was done electronically using Medline, Scopus, Web of Science, EMBASE, SciELO and Google Scholar from June 1, 2020 to August 20, 2020. All studies that assessed the KAP of dental professionals to COVID-19 were searched and included in this review after passing the inclusion criteria. The pooled analysis of their knowledge (sign and symptom, mode of transmission and prevention mechanisms), attitude (their concern, intention to treat suspected patients) and practice (face mask usage, hand washing and alcohol based hand rub usage, handshaking practice, deferred procedures and checkup of patients temperature) was computed using RevMan 5.3 and random effect model was used. The presence of publication bias was assessed using the funnel plot. Results: Twelve articles with a total of 5,362 study participants were included in this study. The pooled estimate revealed that 59.91% of the dental professionals had good knowledge of the signs and symptoms of COVID-19. Two-third of dental professionals know the prevention mechanisms of the infection, and 70.13% had enough knowledge of the transmission modalities of the infection. The professional attitude revealed that only 36.43% of the participants had intention to treat a patient with cough or suspected COVID-19 (36.43%, 95%CI: 8.57, 64.29). Moreover, 47.85% of the dentists were concerned about their life, and the fate of their profession due to this pandemic disease (47.85%, 95%CI: 26.74, 68.97). The pooled analysis showed only 50.86% (95%CI: 18.64, 83.09) of the study participants worn face mask and 52.63% (95%CI: 10.54, 94.71) had avoided handshaking practice during this pandemic period. Non-emergency dental procedures were canceled by 83.98%. Conclusion: The dental professional KAP is not optimal. Thus, dental professionals should be aware of the recently updated knowledge about COVID-19 and practice according to the standards of treatment guidelines, and the recommended infection control measures in dental settings. Moreover, as saliva and droplets are the major sources of infection, dentists should follow essential protocols to regulate droplet and aerosol contamination in the dental practice

Preprint ARTICLE | doi:10.20944/preprints202002.0265.v1

Structural Identification of the Electrostatic Hot Spots for Severe Acute Respiratory Syndrome Coronavirus Spike Protein to Be Complexed with Its Receptor ACE2 and Its Neutralizing Antibodies

Wei Li

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: SARS-CoV; Spike protein; Electrostatic hot spots; Angiotensin-converting enzyme 2 (ACE2); Neutralizing antibody

Online: 18 February 2020 (11:03:10 CET)

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Preprint ARTICLE | doi:10.20944/preprints202005.0031.v1

COVID-19 Pandemic Prediction for Hungary: A Hybrid Machine Learning Approach

Gergo Pinter, Imre Felde, Amir Mosavi, Pedram Ghamisi, Richard Gloaguen

Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: COVID-19; Coronavirus disease; Coronavirus; SARS-CoV-2; model; prediction; machine learning

Online: 3 May 2020 (07:44:03 CEST)

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Preprint REVIEW | doi:10.20944/preprints202012.0663.v1

Ciliary Dysfunction Secondary to COVID-19. Explanation of the Pathogenesis From Analysis of Human Interactome With Sars-Cov-2 Proteome

Alejandro Jesús Bermejo-Valdés, Alexander Ariel Padrón-González, Jessica Archer-Jiménez

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: COVID-19; SARS-CoV-2; interactome; ciliary-flagellar dysfunction; infertility; pathogenicity

Online: 25 December 2020 (13:18:03 CET)

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Preprint REVIEW | doi:10.20944/preprints202008.0696.v1

SARS-CoV-2 Infection Reaches the Human Nervous System: How?

Vladimir N. Uversky, Fatma Elrashdy, Abdullah Aljadawi, Syed Moasfar Ali, Rizwan Hasan Khan, Elrashdy M. Redwan

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; neurotropic virus; Blood-nervous system barrier; bloodcerebrospinal-fluid-barrier; blood-brain-barrier; blood-nerve barrier; olfactory route; Lymphatic brain drainage route; Peripheral nerve or neuronal retrograde route; Macrophage/monocytes cargo route; Double membrane vesicles cargo route; nicotinic acetylcholine receptor

Online: 31 August 2020 (04:43:34 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0087.v1

While We Wait for a Vaccine Against SARS-CoV-2, Why Not Think About Available Drugs?

Francisco J. Barrantes

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Coronavirus; COVID-19; SARS-CoV-2; design drugs; ACE2; prophylaxis

Online: 7 April 2020 (11:02:13 CEST)

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At the time of reception of this article (April 2, 2020), efforts to develop a specific vaccine against SARS-Cov-2, the causative agent of the coronavirus disease 2019 (COVID-19), had just begun trial phase 1, but full validation of this and other current developments is likely to take many more months to reach completion. The ongoing pandemic constitutes a major health burden of world proportions that is also having a devastating impact on whole economies worldwide, the knock-on effects of which could be catastrophic especially in poorer countries. Alternative measures to ameliorate the impact and hamper or minimally slow down disease progression are urgently called for. This review discusses past and currently evolving data on the etiological agent of the current pandemic, SARS-CoV-2, and its host cell receptors with a view to disclosing alternative drugs for palliative or therapeutic approaches. Firstly, SARS-CoV-2 exhibits marked tropism for cells that harbor the membrane-bound metalloprotease angiotensin-converting enzyme 2 (ACE2) at their plasmalemma, predominantly in cells lining the oral cavity, upper respiratory tract, and bronchoalveolar cells, making these epithelial mucosae the most likely viral receptor cell targets and entry routes. Secondly, the crystal structures of several coronavirus spike proteins in complex with their cell host target receptors, and of SARS-Cov-2 in complex with an inhibitor, are now available at atomic resolution through X-ray diffraction and cryo-electron microscopy studies. Thirdly, viral entry of other viruses has been successfully blocked by inhibiting viral endogenous proteases or clathrin/dynamin-dependent endocytosis, the same internalization pathway followed by ACE2 and some viruses. Fourthly, the target cell-surface receptor molecules and SARS-CoV-2 possess other putative sites for drugs potentially modulating receptor activity or virus processing. A multi-pronged pharmacological approach attacking more than one flank of the viral-receptor interactions is worth considering as a front-line strategy.

Preprint REVIEW | doi:10.20944/preprints202103.0416.v1

Science’s Response to COVID-19

Yimon Aye, Marcus Long

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; CoVID-19 Dignosis; CoVID-19 Chemistry & Biology

Online: 16 March 2021 (11:54:28 CET)

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Preprint REVIEW | doi:10.20944/preprints202009.0425.v1

COVID-19 Pandemic and the South African Podiatrist

Bernhard Zipfel, Nadia Dembskey

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: SARS-CoV-2; Coronavirus; podiatry; foot

Online: 18 September 2020 (09:58:49 CEST)

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Preprint REVIEW | doi:10.20944/preprints202104.0354.v1

Does COVID-19 Take a Breath? The Chinese Current Situation

Abdul Qadeer, Muhammad Sohail, Ayesha Younas, Haroon Iqbal, Asif Ullah, Hanif Ullah, Anam Razzaq, Bouzid Menaa, Ijaz ul Haq, Zulfiqar Ahmed, Fazle Rabbi, Nangial Khan, Faisal Raza, Saqib Nawaz, Imran Khan, Muhammad Izhar ul Haque, Farid Menaa

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: SARS-CoV-2; COVID-19; Genetics; Epidemiology; Theranostics; Vaccines and Preventive Infectiology

Online: 13 April 2021 (13:00:35 CEST)

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