REVIEW | doi:10.20944/preprints202009.0153.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Virus; Vaccine; SARS-CoV-2; Coronavirus; Covid-19; Covid-19 vaccine
Online: 7 September 2020 (03:46:59 CEST)
This tutorial is organized into three major sections—viruses, vaccines and the race for a Covid-19 vaccine. The goal is to provide enough background on viruses, history of vaccines, and the science of vaccinology founded on the principles of immunity. The hope is that this will enable us to understand the challenges, methods and prospects for developing a safe and effective vaccine against SARS-CoV-2. Many important viruses such as smallpox, HIV, HCV and SARS-CoV-2 which is responsible for causing the Coronavirus disease 2019 (Covid-19) are presented in detail, which is then followed by a description of different vaccine development methods and strategies. The tutorial then discusses different candidate SARS-CoV-2 vaccines and provides specific details of many of the prospective vaccines on the leader-board which are undergoing clinical trials. The tutorial concludes with a realistic projection for a safe and effective vaccine against SARS-CoV-2 based on the historical scientific record.
ARTICLE | doi:10.20944/preprints202209.0033.v1
Subject: Life Sciences, Other Keywords: vaccine side effects; inactivated COVID-19 vaccine; sinopharm vaccine; sinovac vaccine; whole attenuated vaccine; COVID-19 vaccination; vaccine hesitancy
Online: 2 September 2022 (05:12:45 CEST)
Vaccination is one of the most effective methods for preventing morbidity and mortality from COVID-19. Vaccine hesitancy has led to a decrease in vaccine uptake; driven by misinformation, fear, and perceptions of vaccine safety. Whole inactivated vaccines have been used in one-fifth of the vaccine recipients in Africa, however there is limited real-world data on their safety. We evaluated the reported side effects and factors associated with reported side effects following vaccination with whole inactivated COVID-19 vaccines - BBiBP-CorV (Sinopharm) and CoronaVac (Sinovac). A quantitative survey evaluating attitudes and side effects from vaccination was administered to 1016 adults presenting at vaccination centers. Two follow-up telephone interviews were conducted to determine side effects after the first and second vaccination dose. Overall, the vaccine was well tolerated; 26.0% and 14.4% reported side effects after the first and second dose respectively. The most frequent local and systemic side effects were pain at the injection site and headaches respectively. Most symptoms were mild, and no participants re-quired hospitalization. Participants who perceived COVID-19 vaccines as safe or had a personal COVID-19 experience were significantly less likely to report side effects. Our findings provide data on the safety and tolerability of whole inactivated COVID-19 vaccines in an African population, providing the necessary data to create effective strategies to increase vaccination and support vaccination campaigns.
ARTICLE | doi:10.20944/preprints202202.0306.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; Twitter; Blood Clots; Social Media; Clots
Online: 24 February 2022 (09:35:35 CET)
After the first weeks of vaccination against the SARS-CoV-2, several cases of acute thrombosis were reported. These news reports began to be shared frequently across social media platforms. The aim of this study was to conduct an analysis of Twitter data related to the overall discussion. Data was retrieved from 14th March to 14th April using the keyword ‘blood clots’. A dataset with n=266,677 tweets was retrieved, and a systematic random sample of 5% of tweets (n=13,334) were entered into NodeXL for further analysis. Social network analysis was used to analyse the data by drawing upon the Clauset-Newman-Moore algorithm. Influential users were identified by drawing upon the betweenness centrality metric. Text analysis was applied to identify the key hashtags and websites used at this time. More than half of the network was comprised of retweets and the largest groups within the network were broadcast clusters where a number of key users were retweeted. The most popular narratives were around highlighting the low risk of obtaining a blood clot from a vaccine and highlighting higher blood clot risks in medicines commonly consumed. A wide-variety of actors drove the discussion on Twitter ranging from writers, physicians, the general public academics, celebrities, and journalists. Twitter was used to highlight the low potential of obtaining a blood clot from a vaccine and encouraged vaccinations among the public.
ARTICLE | doi:10.20944/preprints202209.0430.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: COVID-19 vaccines; menstruation; pregnancy outcomes; Influenza vaccines; VAERS
Online: 28 September 2022 (03:50:35 CEST)
Objectives: Assess rates of adverse events (AE) after COVID-19 vaccines experienced by women of reproductive age, focusing on pregnancy and menstruation, using data collected by the US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS) database. Design: Population based retrospective cohort study. Setting: US and global entries in US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS). Participants CDC VAERS entries from January 1, 1998 to June 30, 2022. Interventions: None. Main Outcome and Measures: A proportional reporting ratio analysis is performed using data in the VAERS system comparing adverse events (AE) reported post COVID-19 vaccines with that of post-Influenza vaccines. Results: COVID-19 vaccines, when compared to the Influenza vaccines are associated with a significant increase in AE with all proportional reporting ratios of > 2.0: menstrual abnormality, miscarriage, fetal chromosomal abnormalities, fetal malformation, fetal cystic hygroma, fetal cardiac disorders, fetal arrhythmia, fetal cardiac arrest, fetal vascular mal-perfusion, fetal growth abnormalities, fetal abnormal surveillance, fetal placental thrombosis, low amniotic fluid, and fetal death/stillbirth (all p values were much smaller than 0.05). When normalized by time-available, doses-given, or persons-received, all COVID-19 vaccine AE far exceed the safety signal on all recognized thresholds. Conclusions: Pregnancy and menstrual abnormalities are significantly more frequent following COVID-19 vaccinations than that of Influenza vaccinations. A worldwide moratorium on the use of COVID-19 vaccines in pregnancy is advised until randomized prospective trials document safety in pregnancy and long-term follow-up in offspring.
REVIEW | doi:10.20944/preprints202004.0005.v1
Subject: Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; Coronavirus; Pandemic; Viral Genomics
Online: 1 April 2020 (09:22:38 CEST)
The COVID-19 pandemic is due to infection caused by the novel SARS-CoV-2 that impacts the lower respiratory tract. The spectrum of symptoms ranges from asymptomatic infections to mild respiratory symptoms to the lethal form of COVID-19 which is associated with severe pneumonia, acute respiratory distress and fatality. At present, the global case fatality rate of COVID-19 laboratory confirmed cases is ~4.7% ranging from ~0.3-0.4% in Chile and Israel to ~10.8% in Italy. To address this global crisis, up-to-date information on the viral genomics and transcriptomics is crucial for understanding the origins and global dispersal of the virus, providing insight into viral pathogenicity, transmission and epidemiology, and enabling strategies for therapeutic interventions, drug discovery and vaccine development. Therefore, this review provides a comprehensive overview of COVID-19 epidemiology, genomic etiology, findings from recent transcriptomic map analysis, viral-human protein interactions, molecular diagnostics, and the current status of vaccine and novel therapeutic intervention development. Moreover, we provide an extensive list of resources that will help the scientific community access numerous types of databases related to SARS-CoV-2 OMICs and approaches to therapeutics related to COVID-19 treatment.
Subject: Life Sciences, Biochemistry Keywords: COVID-19; SARS-CoV-2; animal models; vaccines; future prospects
Online: 2 August 2021 (13:15:48 CEST)
The worldwide pandemic of coronavirus disease 2019 (COVID-19) has become an unprecedented challenge to global public health. With the intensification of the COVID-19 epidemic, the development of vaccines and therapeutic drugs against the etiological agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are also widespread. To prove the effectiveness and safety of these preventive vaccines and therapeutic drugs, available animal models that faithfully recapitulate clinical hallmarks of COVID-19 are urgently needed. Currently, animal models including mice, golden hamsters, ferrets, nonhuman primates and other susceptible animals have been involved in the study of COVID-19. 92 vaccine candidates have entered clinical trials after the primary evaluation in animal models, of which inactivated vaccines, subunit vaccines, virus-vectored vaccines and mRNA vaccines are promising vaccine candidates. In this review, we summarize the landscape of animal models and advanced vaccines with efficacy range from about 50% to more than 95%. In addition, we point out future directions for animal models and vaccine development, aiming at providing valuable information and accelerating the breakthroughs confronting SARS-CoV-2.
COMMUNICATION | doi:10.20944/preprints202012.0780.v1
Online: 31 December 2020 (09:25:54 CET)
With the arrival of SARS-CoV-2 vaccines, a new stage of the pandemic commenced, with new challenges ahead. During the coming months, countries will be implementing their COVID-19 vaccination programs depending on their implementation of vaccine availability and its prescription on risk stratification. Although children will not benefit from active immunization programs, now, with the beginning of the era of the anti-COVID19 vaccines, the suffering of children can no longer be ethically tolerated or neglected. The time has come to provide specific lasting strategies for children living in the COVID-19 era. Here we propose a child-focused indirect COVID-19 vaccination strategy.For better or worse, children depend on their natural caregivers (adults) and the rest of society for their well-being and achieving their full potential. We believe that including in the priority categories also those adults in close contact with children could ensure a safety net of child protection.A child-focused vaccination strategy would allow the faster return to "normality" for children and their families. Such an approach would not only enable the reopening and continuity of essential services for children but also would allow adults to return to their routine economic/productive activities.
ARTICLE | doi:10.20944/preprints202203.0169.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: COVID-19; adverse events; histamine intolerance; myocarditis; pericarditis; tachycardia
Online: 11 March 2022 (12:07:26 CET)
Rare cardiac adverse events are reported post vaccinations. For the SARS-CoV-2 vaccines, higher numbers of these cardiac adverse events are being reported with myocarditis disproportionately occurring in younger males. The etiology of these cardiac adverse events associated with vaccines including SARS-CoV-2 is unknown. The etiology of the higher frequency of these cardiac adverse events temporally associated with SARS-CoV-2 vaccines is also unknown. This article proposes that innate immune responses to vaccines cause elevated histamine levels post vaccination; the histamine level reached may exceed the vaccinees’ histamine tolerance level for several days. This article proposes that the elevated histamine level is causative for the reported cardiac adverse events. For myocarditis reported adverse events, this article proposes that elevated histamine levels induce cardiac capillary pericyte induced vasoconstrictions followed by localized ischemia and anoxia; this is followed by the release of troponin from myocyte cells affected by anoxia. This hypothesis is supported by the temporal onset timing of adverse events reported following SARS-CoV-2 vaccinations in the United States Department of Health and Human Services Vaccine Adverse Event Reporting System (VAERS). This model applies to multiple vaccines with innate immune response histamine levels generated varying by each vaccine and incidence frequencies correlate with vaccine reactogenicity.
REVIEW | doi:10.20944/preprints202011.0558.v1
Subject: Keywords: SARS-CoV-2; COVID-19; Adjuvants; Vaccine Production; Vaccine Delivery; Clinical Trials; Neutralizing Antibodies; Th1
Online: 22 November 2020 (11:57:51 CET)
With the COVID-19 pandemic now ongoing for close to a year, people all over the world are still waiting for a vaccine to become available. The initial focus of accelerated global research and development efforts to bring a vaccine to market as soon as possible was on novel platform technologies that promised speed but had limited history in the clinic. In contrast, recombinant protein vaccines, with numerous examples in the clinic for many years, missed out on the early wave of investments from government and industry. Emerging data are now surfacing suggesting that recombinant protein vaccines indeed might offer an advantage or complement to the nucleic acid or viral vector vaccines that will likely reach the clinic faster. Here, we summarize the current public information on the nature and on the development status of recombinant subunit antigens and adjuvants targeting SARS-CoV-2 infections.
Subject: Keywords: SARS-CoV-2; S-protein; RBD; COVID-19; neutralizing antibodies; serology; vaccines; animal models; Warp Speed
Online: 21 June 2020 (15:44:06 CEST)
In this review, we address issues that relate to the rapid “Warp Speed” development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of “Warp Speed” immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the “Warp Speed” vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.
ARTICLE | doi:10.20944/preprints202205.0228.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: COVID-19 vaccines; SARS-CoV2; lactation; mother-child dyads; reactogenicity
Online: 17 May 2022 (10:31:51 CEST)
The aims of the study are: a) Describe the reactogenicity of WHO-approved two mRNA (Pfizer-BioNTech, Moderna) and two non-RNA vaccines (Oxford-AstraZeneca, Sinovac) among lactating mother and baby pairs; and b) compare and contrast the reactogenicity between mRNA and non-mRNA vaccines. A cross-sectional, self-reported survey was conducted amongst 1784 lactating women who received COVID-19 vaccinations. The most common maternal adverse reaction was a local reaction at the injection site; the largest minority of respondents, 43.7% (780/1784), reported experiencing worse symptoms when receiving the second dose compared to the first dose. There were no major reported adverse effects or behavioural changes in the breastfed infants. Among the respondents who received non-mRNA COVID-19 vaccinations, a majority reported no change in lactation but those who did more commonly reported an increase in milk supply, decrease in milk supply and pain in the breast. The more commonly reported lactation changes (fluctuations in breastmilk supply and pain in the breast) for the non-mRNA vaccines were similar to that of respondents who received mRNA vaccines. Our study, with a large cohort and wide geographical and racial mix, further augments earlier reported findings that COVID-19 vaccines are safe for breastfeeding mothers and her children.
REVIEW | doi:10.20944/preprints202104.0468.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Vaccine Development; Clinical Trial; COVID-19; SARS-COV-2
Online: 19 April 2021 (12:04:31 CEST)
The COVID-19 pandemic is a devastating blow to the entire world community and changes the order of human life. All efforts and strategies are being carried out to contain and reduce the spread of the SARS-COV-2 virus, both by tightening the health protocol and using vaccines to the public. Currently, several vaccines are available and have passed phase 3 clinical trials, such as vector vaccines (Gamaleya Sputnik V Russia, University of Oxford/AstraZeneca, CanSino, and Janssen Pharmaceutical Companies), mRNA-based vaccines (Moderna/BioNTech/Fosun Pharma/Pfizer), inactivated vaccines (SinoVac and SinoPharm from China, Covaxin from Bharat Biotech India), and adjuvanted recombinant protein nanoparticles (Novavax from the USA) are expected to be able to suppress the spread of the virus and produce a minimum of 70 percent herd-immunity in a population. Each vaccine's efficacy varies from the lowest, namely the Sinovac vaccine (CoronaVac) 50% to the highest the Novavax vaccine (NVX-Cov2373) 96% effectivity value. Moreover, further rigorous research is still being carried out for the development of an effective and efficient vaccine.
REVIEW | doi:10.20944/preprints202106.0060.v1
Subject: Biology, Anatomy & Morphology Keywords: SARS-CoV-2; COVID-19; variants; vaccines; immune dysregulated; comorbidities; antibody; Spike protein; biomolecules; coronavirus
Online: 2 June 2021 (09:56:14 CEST)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic which has been a topic of major concern to global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7, B.1.351, P1 and, B.1.617., which show in-creased transmissibility and resistance towards vaccines and therapies. Importantly, the likelihood of susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response or comorbidities needs greater attention. Herein, we provide a comprehensive perspective regarding ongoing vaccine (mRNA, protein-based, viral vector based etc.) and therapeutic (mono-clonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.
REVIEW | doi:10.20944/preprints202004.0075.v1
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2; COVID-19; immunotherapeutics; therapeutics; vaccines
Online: 7 April 2020 (02:01:34 CEST)
A novel coronavirus (SARS-CoV-2), causing an emerging coronavirus disease (COVID-19), first detected in Wuhan City, Hubei Province, China has resulted in an outbreak in China which has taken a catastrophic turn with high toll rates in China and subsequently spreading across the globe. The rapid spread of this virus to more than 175 countries while affecting nearly 500,000 persons and causing more than 22,000 human deaths, it has resulted in a pandemic situation in the world. The SARS-CoV-2 virus belongs to the genus Betacoronavirus, like MERS-CoV and SARS-CoV, all of which originated in bats. It is highly contagious, causing symptoms like fever, dyspnea, asthenia and pneumonia, thrombocytopenia and the severely infected patients succumb to the disease. Coronaviruses (CoVs) among all known RNA viruses have the largest genomes ranging from 26 to 32 kb in length. Extensive research has been conducted to understand the molecular basis of the SARS-CoV-2 infection and evolution, develop effective therapeutics, antiviral drugs and vaccines, and to design rapid and confirmatory viral diagnostics as well as adopt appropriate prevention and control strategies. Till date, no clinically proclaimed, proven therapeutic antibodies or specific drugs and therapeutics, and vaccines have turned up. Several molecular diagnostic tests such as Real Time-PCR, isothermal loop-mediated amplification of coronavirus (i-LACO), full genome analysis by next-generation sequencing (NGS), multiplex nucleic acid amplification, and microarray-based assays are in use currently for the laboratory confirmation of this CoV infection. In this review article, we describe the basic molecular organization and phylogenetic analysis of the coronaviruses, including the SARS-CoV-2, and recent advances in diagnosis and vaccine development in brief and focusing mainly on developing potential therapeutic options that can be explored to manage this pandemic virus infection, which would help in valid countering of COVID-19.
ARTICLE | doi:10.20944/preprints202105.0447.v1
Subject: Keywords: Vaccine; Sentiment analysis; Public Sentiment Scenarios framework; COVID-19; Coronavirus; Twitter; Textual analytics; Public policy
Online: 19 May 2021 (13:51:57 CEST)
There exists a compelling need to better understand the temporal dynamics of public sentiment towards COVID-19 vaccines in the US on a national and state-wise level for facilitating appropriate public policy applications. Our analysis of social media data from early February of 2021 and late March of 2021 shows that in spite of overall strength of positive sentiment, and increasing numbers of Americans being fully vaccinated, negative sentiment about COVID-19 vaccines still persists among sections of people who are hesitant towards the vaccine. In this study, we performed sentiment analytics on vaccine tweets, studied changes in public sentiment over time, conducted vaccination sentiment validation using actual vaccination data from the US CDC and Household Pulse Survey (HPS), explored influence of maturity of Twitter user-accounts and generated geographic mapping of sentiments by location of Twitter users. Furthermore, we leverage the emotion polarity based Public Sentiment Scenarios (PSS) framework which was developed for COVID-19 sentiment analytics, to systematically analyze directions for public policy processes to potentially improve the administration of vaccines. Application of the PSS framework provides important time sensitive insights for state and federal government agencies and associated organizations to better implement public policy processes for healthcare management, communication, transparency, motivation and societal operational policies such as social distancing. These insights are expected to contribute to processes that can expedite the vaccination program and move closer to the cherished herd immunity goal.
REVIEW | doi:10.20944/preprints202005.0223.v1
Online: 13 May 2020 (05:10:48 CEST)
Abstract. The COVID-19 has turned in to a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in R&D by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are ‘rate-limiting’ and ‘time-consuming’, many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human ‘challenge experiments’ to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying ‘Quick fix’ and ‘short cuts’ can lead to errors with disastrous consequences.
BRIEF REPORT | doi:10.20944/preprints202007.0141.v3
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; pneumococcal vaccine; vaccination; cross-reactivity; protection; molecular mimicry; CRM197; rubella vaccine
Online: 4 September 2020 (10:45:26 CEST)
Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Hib and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.
REVIEW | doi:10.20944/preprints202004.0060.v1
Subject: Life Sciences, Immunology Keywords: COVID-19; coronavirus; cytokine storm; immunity; ADE; cross-reactive antibody; rapamycin; mTOR inhibotors
Online: 6 April 2020 (14:03:00 CEST)
COVID-19 has become a severe global public health concern. The critical illness has a mortality rate of 61.5%, and thus, reducing the severity and mortality is top priority. Currently, inflammatory storms are considered as the cause of critical illness and death due to COVID-19. However, After systematical review of the literature, we proposed that cross-reactive antibodies-associated antibody-dependent enhancement (ADE) may actually be the cause of cytokine storms. If the activation of memory B cells can be selectively inhibited in high-risk patients at an early stage of COVID-19 to reduce the production of cross-reactive antibodies of the virus, we speculate that the ADE can be avoided and severe symptoms can be prevented. The mammalian target of rapamycin (mTOR) inhibitors satisfy such conditions. We recommend that pharmaceutical companies conduct clinical trials urgently.
Subject: Keywords: SARS-CoV-2; S-protein; RBD; COVID-19; neutralizing antibodies; serology; T-cells; vaccines; animal models; Operation Warp Speed
Online: 27 October 2020 (11:25:32 CET)
Multiple preventive vaccines are being developed to counter the COVID-19 pandemic. The leading candidates have now been evaluated in non-human primates (NHPs) and human Phase 1 and/or Phase 2 clinical trials. Several vaccines have already advanced into Phase 3 efficacy trials, while others will do so before the end of 2020. Here, we summarize what is known of the antibody and T-cell immunogenicity of these vaccines in NHPs and humans. To the extent possible, we compare how the vaccines have performed, taking into account the use of different assays to assess immunogenicity and inconsistencies in how the resulting data are presented. We also summarize the outcome of SARS-CoV-2 challenge experiments in immunized macaques, while noting variations in the protocols used, including but not limited to the virus challenge doses.
ARTICLE | doi:10.20944/preprints202206.0116.v1
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV2; inactivated vaccine; mRNA vaccine; COVID-19; homologous vaccination; heterolo-gous vaccination; protectivity
Online: 8 June 2022 (05:39:30 CEST)
This prospective cohort study aimed to evaluate the efficacy of COVID-19 vaccine schemes, ho-mologous versus heterologous vaccine strategies, and vaccine-induced anti-S-RBD-IgG antibody response in preventing COVID-19 among 942 healthcare workers one year after vaccination with the inactivated and/or mRNA vaccines. All participants received the first two primary doses of vaccines, 13.6% of them lacked the dose-3, 50.5% the dose-4, and 90.3% the dose-5. Antibody lev-els increased with the increase in number of vaccine doses and also in heterologous vaccine regi-mens. In both inactive and mRNA vaccines, infection rates were significantly higher in 2-dose-receivers, but lower in 4- or 5-dose receivers and increasing the total number of vaccine doses resulted in more protection against infection: the 3-dose regimen yielded 4.71 times more protection, the 4-dose 11.76 times and 5-dose 38.46 times more protection from COVID-19 infec-tion, compared to any 2-dose vaccination regimens. Antibody levels at the end of the first year of 4- or 5-dose-receivers were significantly higher than 2- or 3-dose-receivers. To conclude; increased number of total vaccine doses and anti-S-RBD antibody levels increased the protection from COVID-19 infection. Therefore, four or more doses are recommended in one year, for effective protection, especially in risk groups.
REVIEW | doi:10.20944/preprints202004.0040.v3
Subject: 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)
Global severity maps of ongoing dengue epidemic and COVID-19 pandemic do not overlap. Countries with high dengue endemicity (>1.5 million cases/year) are observably less hit by COVID-19 in terms of infection, transmission and mortality. Based on non-overlap of dengue and COVID-19 severity maps and evidence of SARS-CoV-2 serological cross-reactions with dengue, we wonder whether immediate immunization of susceptible populations in Europe, North America and Asia (China, Iran) with available live-attenuated dengue vaccines, will cue the anti-viral immune response to thwart COVID-19 (viral interference). Risk of developing post-vaccination “Antibody-dependent Enhancement” is low as dengue is not endemic in the aforesaid regions.
SHORT NOTE | doi:10.20944/preprints202007.0526.v1
Subject: Social Sciences, Other Keywords: COVID-19; Unreported COVID-19 Death; Provisional COVID-19 Death; Death Reporting Discrepancy; Bangladesh
Online: 22 July 2020 (11:32:05 CEST)
Objective: We aim to assess the reporting discrepancy and the difference between confirmed and unreported COVID-19-like death counts.Study Design: The study is based on time-series data.Methods: We used publicly available data to explore the differences between confirmed death counts and deaths with Codiv-19 symptoms between March 8, 2020, and July 11, 2020, in Bangladesh.Results: During the week ending May 9, 2020, the unreported COVID-19-like death count was higher than the confirmed COVID-19 death count; however, it was lower in the following weeks. On average, unreported COVID-19-like death counts were similar to the confirmed COVID-19 death counts during the same period. However, the reporting authority neither considers these deaths nor adjusts for potential seasonal influenza or other related deaths, which might produce incomplete COVID-19 data and respective mortality rates. Conclusions: Documenting unreported deaths with COVID-19 symptoms needs to be included in provisional death counts because it is essential to estimate a robust COVID-19 mortality rate and to offer data-driven pandemic response strategies. An urgent initiative is needed to prepare an acceptable guideline for COVID-19 death reporting.
ARTICLE | doi:10.20944/preprints202208.0227.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: COVID-19; depression; anxiety; post-acute COVID-19 syndrome; post-COVID
Online: 12 August 2022 (04:56:33 CEST)
Background: This study aimed to examine the course of Depression and anxiety in COVID-19 survivors with a psychiatric history compared with those without a psychiatric history. Methods: A web-based cross-sectional survey for COVID-19 survivors was conducted from July to September 2021. 6016 COVID-19 survivors, the accuracy of whose responses was determined to be assured, were included in analyses. Exposures included psychiatric history and time since COVID-19 infection, and the main outcomes and measures included severity of depression and anxiety, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Results: Mean severity of PHQ-9 and GAD-7 were significantly higher in participants with a psychiatric history than in those without a psychiatric history. Two-way analysis of covariance for PHQ-9 showed a significant main effect of the presence of psychiatric history and a significant interaction effect of psychiatric history × time since infection. Two-way analysis of covariance for the GAD-7 score revealed a significant main effect of the presence of psychiatric history and time since COVID-19 infection and the interaction effect of these factors. Conclusions: The course of depression and anxiety was more severe in COVID-19 survivors with a psychiatric history than in those without a psychiatric history.
REVIEW | doi:10.20944/preprints202004.0361.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; pandemic; asymptomaticspread; early-stage COVID-19 mitigation
Online: 20 April 2020 (06:18:33 CEST)
Background: Early-stage interventions in a potential pandemic are important tounderstand as they can make the difference between runaway exponential growththat is hard to turn back and stopping the spread before it gets that far. COVID-19 is an interesting case study because there have been very different outcomesin different localities. These variations are best studied after the fact if precisionis the goal; while a pandemic is still unfolding less precise analysis is of value inattempting to guide localities in the early stages to learn lessons of those that pre-ceded them. Methods: I examine three factors that could differentiate strategy: asymptomaticspread, differences in use of the Bacillus Calmette-Guerin (BCG) tuberculosis vac-cine and cloth face masks.Results:Differences in disease progression as well as the possibility of alternativestrategies to prevent COVID-19 from entering the runaway phase or damping itdown later can be elucidated by a study of asymptomatic infection. A study todemonstrate not only what fraction are asymptomatic but how contagious they arewill also inform policy on universal mask wearing. Conclusions: While a COVID-19 outbreak is at a level that makes accurate trace-and test possible, investigation of asymptomatic transmission is viable and shouldbe attempted to enhance understanding of spread and variability in the disease aswell as policy options for slowing the spread.
ARTICLE | doi:10.20944/preprints202112.0413.v1
Online: 24 December 2021 (23:40:18 CET)
Background Recently, a surge of COVID 19 was observed globally, regionally and nationally. With increasing numbers of cases, the frequency of long COVID is on the rise. Management and control of long COVID depend on changes in respect of human behaviors and requires an understanding of knowledge, attitudes, and practices (KAP) regarding health threats. MethodsA descriptive cross sectional study using online survey to gather data on the socio-economic background, knowledge, attitudes and practices on long-term complications of COVID. Results: Out of 201 respondents, 89.2% participants have heard about long-term complications of COVID 19. Only 35.9% have demonstrated adequate knowledge in the questions relating to co-morbidities and risk factors of COVID-19. A total of 92.2% believe that they should adhere to preventive measures following vaccination. Less than 60 % were following the advice on avoiding unnecessary travel and crowded places. Further, less than 50% were following COVID preventive measures. ConclusionAlthough the majority of participants have heard about long-term complications and common symptoms, the knowledge regarding co-morbidities that can lead to severe disease and long COVID was not satisfactory. The attitudes of the participants indicated increasing concern about long COVID. Practices indicate lack of adherence to key measures such as avoiding crowded places. These findings highlight the need for further increasing of awareness.
Online: 21 July 2020 (13:46:45 CEST)
Today, we are all threatened by an unprecedented pandemic: COVID-19. How different is it from other coronaviruses? Will it be attenuated or become more virulent? Which animals may be its original host? In this study, we analyzed 377 publicly available complete genome sequences for the COVID-19 virus, the previously known flu-causing coronaviruses (HCov-229E, HCov-OC43, HCov-NL63 and HCov-HKU1) and the lethal, pathogenic P3/P4 viruses, SARS, MERS, Victoria, Lassa, Yamagata, Ebola, and Dengue. We found strong similarities between the current circulating COVID-19 and SARS and MERS, as well as COVID-19 in rhinolophines and pangolins. On the contrary, COVID-19 shares little similarity with the flu-causing coronaviruses and the other P3/P4 viruses. Strikingly, we observed divergence of COVID-19 strains isolated from human hosts has steadily increased from December 2019 to March 2020, suggesting COVID-19 is actively evolving in human hosts. From all existing human COVID-19 genome sequences, we calculated the first common model that represents the shared sequences of the human COVID-19 strains, which provides important information for vaccine and antibody development. Geographic and time-course analysis of the evolutionary trees of the human COVID-19 reveals possibly heterogeneous evolutional paths among strains from 21 countries. This finding has important implications to the management of COVID-19 and the development of vaccines.
CASE REPORT | doi:10.20944/preprints202006.0269.v1
Online: 21 June 2020 (11:59:21 CEST)
Understanding the clinical conditions and outcomes of Covid-19 infected patients with immunodeficiency like HIV will be an information for improving management and treatment modalities. It was reported a patient of HIV plus clinical confirmed Covid-19 in this presentation.
SHORT NOTE | doi:10.20944/preprints202003.0077.v4
The Ongoing COVID-19 Epidemic Curves Indicate Initial Point Spread in China With Log-Normal Distribution of New Cases per Day With a Predictable Last Date of the Outbreak Version 4: Predictions for Selected European Countries, USA and the World as a Whole and Try to Predict the End of the Outbreak Including a Discussion of a Possible “New Normal”
Online: 19 April 2020 (08:15:10 CEST)
During an epidemic outbreak it is useful for planners and responsible authorities to be able to plan ahead to estimate when an outbreak of an epidemic is likely to ease and when the last case can be predicted in their area of responsibility. Theoretically this could be done for a point source epidemic using epidemic curve forecasting. The extensive data now coming out of China makes it possible to test if this can be done using MS Excel a standard spreadsheet program available to most offices. The available data is divided up for whole China and the different provinces. This and the high number of cases makes the analysis possible. Data for new confirmed infections for Hubei, Hubei outside Wuhan, China excluding Hubei as well as Zhejiang and Fujian provinces all follow a log-normal distribution that can be used to make a rough estimate for the date of the last new confirmed cases in respective areas. In the version 2 continuation work, 9 additional days were added for the Chinese data to evaluate the previous predictions. The extra data then available from China follows the previous predicted trend supporting the usefulness of this simple technique. In the version 2 we also tested the feasibility for a non-specialist to make similar predictions using additional data from S Korea now available. In this third continuation the predictions for Version 2 are evaluated for S Korea and fits well the beginning of the decline but it seems to be difficult to bring down numbers of cases per day under about 100 new cases per day, potential reasons for this is discussed. To further evaluate when in a prediction becomes reliable the Chinese data was used to evaluate to make predictions for each day around the peak in number of cases and after2-3 consecutive days of decreasing new cases per day the prediction becomes reliable. In version 3 data for Italy just reaching this point was used to make further predictions for that country. A second new analysis was also added to use the fitted equation to detect when the acceleration of new cases per day stopped increasing exponentially. In the Chinese case this measured point coincides with the date of the complete Hubei lockdown and in the new Italian analysis it coincides with the mandatory Italian lockdown. Predicted dates for the end of the Italian outbreak is also added. In version 4 we expand the analysis to selected European countries, USA and the World as a whole and try to predict the end of the outbreak. We further discuss the apparent success of the used techniques that might work to introduce a “new normal” not very different to the previous to stop secondary outbreaks of COVID19 and future COVIDs that are sure to come.
REVIEW | doi:10.20944/preprints202103.0490.v1
Subject: Medicine & Pharmacology, Allergology 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)
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.
ARTICLE | doi:10.20944/preprints202209.0400.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: COVID 19; health personnel; Burnout, Psychological; COVID 19 stress syndrome
Online: 26 September 2022 (11:42:28 CEST)
Purpose: The healthcare pressure and emotional tension during the first year of the COVID 19 pandemic have been able to affect the health of healthcare personnel. Physical and psychological symptoms attributed to a work situation and or COVID 19 infection are describ ed in health professionals. Objective: to analyze the prevalence of physical and psychological symptoms directly or indirectly related to COVID 19 (occupational causes, illness or persistent COVID 19) after a 12 month pandemic. Methods: #COVID19PS is a cro ss sectional analytical study using an ad hoc questionnaire distributed through social media to record physical and psychological symptoms related to COVID 19 in health professionals. Variables: age, sex, geographical origin, profession, characteristics of the work environment, physical symptoms, Maslach test ( for health professionals. Univariate and bivariate statistical analysis using t distribution, Chi square, ANOVA using IBM SPSS v20®. Results: N=1.159 ( women, 21.8% men; 44.6% <35 years old, 23.9% between 35 45years); 96.5% Spaniards. Professions: 17.1% medicine, 12.7% nursing, 32% physiotherapy, 24.1% occupational therapy, 14.1% others; 47.5% belonged to direct care for COVID 19 patients. 28.2% had passed the disease and 3.7% had it acti ve. 61.6% had physical symptoms ( neurological, 31.7% musculoskeletal, 29.6% general, 20.9% gastrointestinal, 20.3% skin, 19.2% cardiovascular, 16% respiratory (p= 96.9% had a medium high Burnout index (p= 48.3% with high levels of Emot ional Exhaustion, 62.9% with medium high level of Depersonalization and 74% with medium low levels of Personal Accomplishment. Conclusion: all health professions present high rates of physical and burnout consequences of the first year of COVID 19 pandemic.
ARTICLE | doi:10.20944/preprints202205.0415.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; Coronavirus; Vaccine hesitancy; COVID-19 Vaccine; Saudi Arabia
Online: 31 May 2022 (09:22:49 CEST)
On 11th March 2020, the World Health Organization declared COVID-19 as a pandemic. Vaccination programs have advanced greatly in the global health period, despite widespread anti-vaccination attitudes and misinformation. Vaccine hesitancy of COVID-19 vaccine is currently a major issue in Saudi Arabia. This cross-sectional study was carried out from June 25, 2021 to October 2021 in order to investigate the knowledge levels of acceptance and hesitancy of COVID-19 vaccine among Saudi’s nationals. The data was collected through a close-ended structured questionnaire from a total of 565 respondents. Overall, 78.41% respondents were female, 62.48% having university level education and 61.06% were unemployed. Majority of the participants 82.30% (n=465) think that Pfizer vaccine has the highest efficiency against COVID-19. Our study concludes that majority of the participants have satisfactory knowledge about COVID-19 vaccination. Concerns over vaccine components, effectiveness of vaccine and possible side effects are among the key causes for vaccine hesitancy.
REVIEW | doi:10.20944/preprints202103.0416.v1
Online: 16 March 2021 (11:54:28 CET)
CoVID-19 is a multi-symptomatic disease which has made a global impact due to its ability to spread rapidly, and its relatively high mortality rate. Beyond the heroic efforts to develop vaccines, which we will not discuss, the response of scientists and clinicians to this complex problem has reflected the need to detect CoVID-19 rapidly, to diagnose patients likely to show adverse symptoms, and to treat severe and critical CoVID-19. Here we aim to encapsulate these varied and sometimes conflicting approaches and the resulting data in terms of chemistry and biology. In the process we highlight emerging concepts, and potential future applications that may arise out of this immense effort.
ARTICLE | doi:10.20944/preprints202006.0275.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: SARS-CoV-2; COVID-19; real-time RT-PCR; COVID-19 symptoms; COVID-19 hematological findings; Bangladesh
Online: 21 June 2020 (14:47:03 CEST)
Objective: SARS-Cov-2 infection or COVID-19 is a global pandemic. From the time of identification to till, multiple clinical symptoms and parameters have been identified by the researchers of various countries and regions regarding the diagnosis and presentations of COVID-19 disease. In this manuscript, we investigated the primary symptoms and basic hematological presentations of SARS-CoV-2 infection among the Bangladeshi patients. Methodology: We have collected the disease history of mild to moderate degree of COVID-19 patients; hematological and biochemical on admission reports of moderate degree COVID-19 patients. All of them were tested positive for SARS-CoV-2 by RT-PCR in different institutes in Bangladesh. Results: According to this study though COVID-19 patients in Bangladesh commonly presented with fever, cough, fatigue, shortness of breath, and sore throat, but symptoms like myalgia, diarrhea, skin rash, headache, Abdominal pain/cramp, nausea, vomiting, restlessness, and a higher temperature of >1000F have a greater presentation rate and more frequent than other published studies. CRP and Prothrombin time was found to increase in all the patients. Serum ferritin, ESR, SGPT, and D-Dimer were found increased among 53.85%, 80.43, 44%, and 25% patients respectively. 17.39% of the patients had leukocytosis and neutrophilia. 28.26% of patients presented with lymphocytopenia. 62.52% of patients had mild erythrocytopenia. Conclusion: Despite some similarities, our study has evaluated a different expression in presenting symptoms in the case of COVID-19 patients in Bangladesh. CRP, Prothrombin time, serum ferritin, ESR, SGPT, D-Dimer, erythrocytopenia, and lymphocytopenia can be initial diagnostic hematological findings and assessment for prognosis COVID-19 disease. Also, gender variations have a different scenario of clinical and laboratory appearance in this region.
REVIEW | doi:10.20944/preprints202009.0500.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; impact on society during COVID-19; behavioral impact of COVID-19; government policies against COVID-19; measures adopted by the government; COVID-19 Statistics; Infection rate and Data analysis
Online: 21 September 2020 (11:09:11 CEST)
Background: COVID-19 pandemic has pulled us all a few steps back, were we never shake hands or hug each other when we meet our friends and family after a gap, but instead we greet them by saying Namaste and joining our hands together. As we all know, COVID-19 spreads through air and the only way to shield ourselves is by maintaining a safe distance from one another. Methodology: In order to conduct a meta-analysis on the number of COVID-19 cases in Kerala and India, the data was retrieved from various sites hosted by the government bodies. The data for analysis was collected from May 2020 to July 2020. The average number of days required to reach every 5000 fresh cases were also calculated using this data. COVID-19 has affected all the economy holistically regardless of financial, behavioral, or societal aspects. Conclusion: Lifting of the lockdown in a step by step process keeping in mind the necessities for the nation was a thoughtful act, but the people who mistook this opportunity and did not remain in quarantine after coming from abroad was recognized as the reasons behind the sudden and uncontrolled rise in the number of COVID-19 cases in Kerala, India. The government authorities had no other option but to lift the restrictions to reduce the economic burdens that had already affected the daily wage worker and farmers prompting them to give up their lives.
ARTICLE | doi:10.20944/preprints202206.0024.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: second COVID-19 booster; vaccination; COVID-19; willingness; predictors; general population
Online: 2 June 2022 (04:07:07 CEST)
Given the concerns of waning immunity from the primary COVID-19 vaccines and the first booster dose, we conducted an on-line cross-sectional study in May 2022 to investigate willingness to receive a second COVID-19 booster dose or a new COVID-19 vaccine and its associated factors. Overall, 22.7% of participants were willing to be vaccinated, 39.3% were unsure, but tend to be willing, 25.8% were unsure, 4.9% were unsure, but tend to be unwilling, and 7.4% were unwilling to be vaccinated. The main reasons against accepting a second COVID‐19 booster dose or a new COVID-19 vaccine COVID-19 dose included concerns about the side effects, the opinion that further vaccination is unnecessary, and effectiveness uncertainties. Males, younger individuals, participants without a previous COVID-19 diagnosis, and those with good/very good self-perceived physical health were significantly more frequently willing to receive a second COVID‐19 booster dose or a new COVID-19 vaccine. Also, increased fear of the COVID-19, increased trust in COVID-19 vaccination and decreased fear of a second booster dose or a new COVID-19 vaccine were associated with increased willingness. Our results show some hesitancy and unwillingness toward further COVID-19 vaccination and indicate that fear of COVID-19 and trust in COVID-19 vaccination affect public opinion
ARTICLE | doi:10.20944/preprints202009.0619.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: COVID-19 Mexico; stress in healthcare professionals; COVID-19 stress scale
Online: 26 September 2020 (08:07:00 CEST)
The world is currently, subjected to the worst health crisis documented in modern history; an epidemic led by the novel coronavirus disease 2019 (COVID-19). At the epicenter of this crisis, healthcare professionals continue working to safeguard our well-being. To the regular high levels of stress, COVID new heights even more to healthcare professionals so depending on the area, specialty, and type of work. Here we investigated what are the tendencies, or areas most affected. Through an adaptation of the original COVID-stress scale, we developed a remote, fast test designed for healthcare professionals of the Northeastern part of Mexico, an important part of the country with economic and cultural ties to the US. Our results showed 4 key correlations as highly dependent: Work area – Xenophobia (p < 0.045), Work with COVID patients - Traumatic stress (p < 0.001) and Total number of COVID patients per day – Traumatic stress (p < 0.027), and Total number of COVID patients - Compulsive checking and reassurance. Overall concluding that normal levels of stress have increased (mild – moderate). Additionally, we further determine that the fear of being an asymptomatic patient (potential to spread without knowing) continues being a concern.
REVIEW | doi:10.20944/preprints202003.0378.v1
Subject: Medicine & Pharmacology, Other Keywords: China's COVID-19 Guide; Remdesivir; Xuebijing; Hydroxychloroquine; IL6 inhibitors; COVID-19
Online: 26 March 2020 (01:48:42 CET)
Currently, there is no specific treatment for COVID-19 proven by clinical trials. WHO and CDC guidelines therefore endorse supportive care only. However, frontline clinicians have been applying several virus-based and host-based therapeutics in order to combat SARS-CoV-2. Medications from COVID-19 case reports, observational studies and the COVID-19 Treatment Guideline issued by the China's National Health Commission (7th edition published March 3rd, 2020. Edited translation attached) are evaluated in this review. Key evidence from relevant in vitro researches, animal models and clinical studies in SARS-CoV-2, SARS-CoV and MERS-CoV are examined. Antiviral therapies remdesivir, lopinavir/ritonavir and umifenovir, if considered, could be initiated before the peak of viral replication for optimal outcomes. Ribavirin may be beneficial as an add-on therapy and is ineffective as a monotherapy. Corticosteroids use should be limited without indicating comorbidities. IVIG is not recommended due to lack of data in COVID-19. Xuebijing may benefit patients with complications of bacterial pneumonia or sepsis. The efficacy of interferon is unclear due to conflicting outcomes in SARS and MERS studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2 and may be beneficial as both prophylactic and treatment therapy. For patients who developed cytokine release syndrome, interleukin-6 inhibitors may be beneficial. Given the rapid disease spread and increasing mortality, active treatment with readily available medications may be considered timely prior to disease progression.
REVIEW | doi:10.20944/preprints202004.0007.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: nCov-19, COVID-19, coronavirus, SARS-CoV
Online: 1 April 2020 (09:30:00 CEST)
Coronaviruse disease (COVID-19) outbreak has created an emergency globally, and social distancing and isolation is the only solution to prevent its spread. Several countries have announced fully locked on to tackle this pandemic. The recent COVID-2019 has shaken the globe with incidence cases of more than half-million cases, and a mortality toll of more than twenty thousand to date. The coronavirus family is inclusive of pathogen of both – animal species and humans, encapsulating the isolated severe acute respiratory syndrome coronavirus (SARS-CoV). Researchers round the globe have been dexterously working to decode this lethal virus. Many mathematical frameworks have also been depicted which have helped to understand the dynamics of the COVID-19. Research on coronaviruses continues to explore various aspects of viral replication and pathogenesis to understanding the predilection of these viruses to switch between species, to develop an infection in a new host, and to identify significant reservoirs of coronaviruses will dramatically aid in our potential to prophesize when and where potential epidemics may occur. Many of the non-structural and accessory proteins encoded by the viruses remain unclear and unknown. This systematic review highlights the current situation of the pandemic, virus genomic composition, pathogenesis, symptomatology, diagnosis, and prognosis along with mathematical models of disease transmission and dynamics.
ARTICLE | doi:10.20944/preprints202106.0152.v1
Online: 7 June 2021 (08:29:46 CEST)
Fighting against the COVID-19 pandemic caused by the SARS-CoV-2 virus is one of the most critical challenges facing the global health system today. The possibility to identify the group of persons in the cohort of people under 50 years old, who are sensitive to the COVID-disease by non-invasive methods, is a very perspective approach for estimating the epidemiological state of the human population. The study aimed to identify the features of people's faces with COVID-19 that the most correlate with disease severity could serve as one of these approaches. For this aim, 525 photos of patients' faces with different outcomes of COVID-19 disease were analyzed using the Dlib face recognition convolutional neural network pre-trained for face recognition. Face descriptor vectors were obtained using the convolutional neural network. Facial features were found that predict a person's sensitivity to the SARS-CoV-2 virus (disease severity), and the contribution of each of the features to the risk of developing a severe form of COVID in a person was found. The accuracy of the binary classification of the individual severity of the COVID-19 course using the k-nearest neighbors algorithm on the test dataset was accuracy - 84%, AUC - 0.90.
Online: 17 May 2021 (17:06:31 CEST)
The most severe threat that the Covid-19 pandemic poses to the global economy is the need to choose between human lives and livelihoods. Bangladesh must assess the implications of such impacts on Bangladesh's macro-financial scenario to maintain the economy's current high growth trajectory. The paper outlines the major Covid-19 shock wave transmission channels to the four major sectors of the Bangladesh economy. Authorities around the world have taken every precaution possible to halt the spread of the pandemic. An aggregate transmission framework that includes these four sectors is required to contain the impact of Covid-19 can propagate through these sectors and eventually impact macro-financial stability.
ARTICLE | doi:10.20944/preprints202104.0139.v1
Online: 5 April 2021 (14:00:43 CEST)
Resilience is an adaptive coping mechanism needed by health workers, especially nurses who have longer working hours than other health workers to provide care to patients in the era of the Covid-19 pandemic which is a global health problem. The aim of this literature review is to identify the resilience of nurses during the covid-19 pandemic the 21 st century global nursing paradigm. This language method uses literature reviews which are summaries of 10 articles in the publication years of 2020-2021 on search 4 databased electronic searches contain namely Scopus, ProQuest, Pubmed, and Scient Direct. This review used prisms. The eligibility of these studies were from its title, abstract, research methodology, results and discussion. The results of the review were presented in narrative form. The results of a review of 10 articles found that the form of psychological factors during the covid-19 pandemic, mental distress and influencing factors in nurses caring for patients with COVID-19, resilience nurses during the covid-19 pandemic. Conclusion: The 21 st century global nursing paradigm, one of the global problems in the health sector, with the outbreak of the corona virus disease (Covid-19), the role of nurses as the front guard is needed by the community to provide health services in line with the increasing incidence of covid-19 cases. Strong nurses need an adaptive inner coping mechanism.
REVIEW | doi:10.20944/preprints202104.0078.v1
Online: 2 April 2021 (17:02:40 CEST)
Introduction: Corona Virus Disease 2019 causes health problems in the world in the form of a health crisis that results in psychological problems as fear and anxiety. The purpose of this study to determine the factors that influence psychological and stigma during the Covid-19 pandemic.Methods: This study is a literature review with five databases (Scopus, CINAHL, ScienceDirect, PubMed, and ProQuest), studies design used a cross-sectional or quasi-experimental, with a date of March 2021. The Center for Review and Dissemination and the JBI Guide are used to measure the Quality and Prism checklist for guide reviews. A feasibility study based on title, abstract, full text, and research methodology. The data analysis used narrative analysis based on the research findings.Results: Eleven articles met the predefined review inclusion criteria. Research is base on related factors psychology, related factors stigma, and factors related to psychological and stigma. Most of the factors associated with psychological conditions and stigma have a quasi-experimental and cross-sectional design. Participants averaged over a thousand for each study and discussed psychology factors related to the stigma. Conclusion: Factors related to psychological are age, education, symptoms and health conditions, gender, information, economy, exposure duration, and social support, while factors related to stigma are environment, history of comorbid diseases, discrimination, and public perceptions.
REVIEW | doi:10.20944/preprints202102.0066.v1
Online: 1 February 2021 (17:34:13 CET)
In critically ill patients with COVID-19, concomitant abnormalities of coagulation have been seen with an unusually high incidence. Standard coagulation tests are limited in their ability accurately to reflect the severity of the pro-thrombotic phenotype observed in severe COVID-19 infections. In this narrative review we consider the role of rotational thromboelastometry (ROTEM) as a near bedside test allowing a more comprehensive assessment of haemostatic function in the context of COVID-19 infection. Comprehensive literature search was conducted on PubMed, revealing 13 publications on the subject. The coagulopathy of this disease process appears to be insufficiently represented with often normal conventional coagulation test parameters. Whilst not the perfect substitute for in vivo coagulation, studies utilising rotational thromboelastometry assays in COVID-19 patients have demonstrated increased maximum clot firmness (consistent with hyper-coagulability) and reduced maximum lysis (consistent with “fibrinolytic shutdown”). ROTEM appears to be a possible tool for risk stratification and to monitor the potential modulation of fibrinogen-dependent coagulation processes with enhanced anti-coagulation strategies. Precisely how these coagulation abnormalities can be modified by optimum, individualised medical interventions to improve clinical outcome, however, remains unclear.
BRIEF REPORT | doi:10.20944/preprints202012.0607.v1
Online: 24 December 2020 (08:54:34 CET)
The Saudi government has undertaken rapid and swift actions, such as suspending Omrah and holding international flights. Such affirmative actions enhanced citizens and residents’ confidence in the government officials’ ability to fight the pandemic. However, there are more than 361,178 reported cases of Covid-19 with 6131 deaths as of December 22, 202. As nurses are the largest component of the health care workforce in Saudi Arabia, it is important that they are trained and have the skills and resources to adapt, whether on the frontline of a crisis or in a clinical environment. Nurses play a key function in fulfilling the needs of medical treatment by being the most important part of the health care delivery system.
REVIEW | doi:10.20944/preprints202012.0173.v1
Online: 7 December 2020 (15:36:05 CET)
Culture, gender and religion are closely linked each other’s, profoundly affect the role of each person within the Society, and also affect the ability to access to the health resources. We are now living a worldwide crisis due to the SARS-CoV-2 pandemic. In order to appropriately tackle it, an alliance between science, politics and citizens is needed. In this article, we summarize current evidences of how religions can represent, on one hand, a risk moment for spreading the virus (in relation with overcrowded events), on the other, a precious opportunity to engage people, and in particular minorities, in fighting the pandemic. To win this fight, we need a multicultural approach that takes into account every aspect of human life, and among these religion, which influences so much culture, everyday life and well-being.
Online: 19 July 2020 (15:11:24 CEST)
Severe COVID-19 disease is characterised by an exaggerated inflammatory response, called cytokine storm, accompanied by a condition of immune depression. Even sepsis is characterised by an exaggerated inflammatory response, called SIRS (Systemic Inflammatory Response Syndrome), accompanied by a condition of immune depression called CARS (compensatory anti-inflammatory response syndrome). Clinical studies reveal that most sepsis patients who did not die during the hyper inflammatory response (SIRS) subsequently succumbed to the condition of immune depression (CARS). Severe acute pancreatitis begins with local inflammation that induces systemic inflammatory response syndrome (SIRS), accompanied and followed by a compensatory anti-inflammatory response (CARS). In COVID-19 disease, the male response to SARS CoV-2 virus is typically characterised by a robust inflammatory response. Instead, a cell-mediated immune response is dominant in women. This means that the male sex tends to have a more robust hyper inflammatory response than the female one. Furthermore, in women the condition of immune depression is less represented, therefore they are more protected. Sepsis, severe acute pancreatitis and COVID-19 disease evolve between two fundamental aspects: hyper inflammation and immunodepression. The experience gained over years of studies of sepsis and severe acute pancreatitis suggests that therapies should be differentiated according to the evolutionary stage of the disease. The goal is to save the lives of most patients with COVID-19 disease. The identification of critical points, suitable for designing the windows of therapeutic opportunity, may allow the use of therapeutic interventions, in the COVID-19 disease, which are effective (there are no approved drugs yet), safe (without significant side effects), targeted (based on the evolutionary phase of the disease) personalized, (based on sex, co-morbidities, age, etc.) and timely (based on signs, symptoms, laboratory parameters and instrumental investigations).
ARTICLE | doi:10.20944/preprints202007.0228.v1
Online: 11 July 2020 (04:19:54 CEST)
Since the first confirmed case of COVID-19, information was spreading in large amounts over social media platforms. Information spreading about the COVID-19 pandemic can strongly influence people’s behavior. Therefore, identifying information superspreaders (or influencers) during the COVID-19 pandemic is an im- portant step towards understanding public reactions and information dissemination. In this work, we present an analysis over a large Arabic tweets collected during the COVID-19 pandemic. The presented study con- struct a network from users’ behaviors to identify information superspreaders during the month of March, 2020. We employed both HITS and PageRank algorithms to analyze the influence of information spreading, and compared the ranking of the users. The results show that both HITS and PageRank discovered a similar subset of superspreaders with 40% were found to be verified Twitter accounts.
ARTICLE | doi:10.20944/preprints202006.0009.v1
Online: 3 June 2020 (05:16:33 CEST)
Misinformation during the COVID-19 outbreak has shaped our perception of the disease. Some people thinkthe disease is a bioweapon while others are convinced that it is a hoax. Heightened anxiety often producesfearful rumors, some of which are absurd while others seem plausible and are laced with some truths. But, how does misinformation affect disease spread? In this paper, we construct a mathematical model parameterized by Ugandan data, to study the effect of misinformation on community COVID-19 spread. The analysis shows that misinformation leads to high number of COVID-19 cases in a community, and the effect is highest in the rumour initiators and spreaders. This analysis underscores the importance of addressing misinformation in COVID risk communication.
BRIEF REPORT | doi:10.20944/preprints202004.0424.v1
Online: 24 April 2020 (03:34:21 CEST)
The infected and fatal cases of Coronavirus Disease 2019 (COVID-19) keep increasing around the world, to explore the infection routes and pathogenesis of 2019-nCoV could be meaningful for prevention and treatment of COVID-19. Previous studies showed that the oral cavity is at potentially high risk of 2019-nCoV infection. The ACE2 receptor of 2019-nCoV was reported could express on oral epithelium and salivary glands, and 2019-nCoV could be detected in patients’ saliva. Recently, the amblygeustia were found to widely exist in the COVID-19 patients. To explore the potential mechanism of amblygeustia, we performed further analysis via independent in-house single-cell profiles. Our results showed that ACE2 was inclined to express in taste cells, which indicated that 2019-nCoV may invade into taste cells at the early stage of COVID-19, and lead to the amblygeustia of patients. Above findings about the 2019-nCoV and COVID-19 in oral cavity are valuable and enlightening for future epidemic prevention strategy.
BRIEF REPORT | doi:10.20944/preprints202004.0353.v1
Online: 19 April 2020 (16:54:43 CEST)
We have proposed a model considering two equally sized population (group A and group B) with low and high levels of disease tolerance. We have argued that in the more tolerant group (group B) the progression of the disease with respect to time will be slow with lower number of infections at any given time. We attribute this effect to the innate immunity which advantageously, can also be one of the major contributing factors for flattening the curve. We have compared the growth of Covid-19 disease in various countries to understand this effect.
DATASET | doi:10.20944/preprints202004.0263.v1
Online: 16 April 2020 (08:15:28 CEST)
The COVID-19 pandemic spread of the coronavirus across the globe has affected our lives on many different levels. The world we knew before the spread of the virus has become another one. Every country has taken preventive measures, including social distancing, travel restrictions, and curfew, to control the spread of the disease. With these measures implemented, people have shifted to social media platforms in the online sphere, such as Twitter, to maintain connections. In this paper, we describe a coronavirus data set of Arabic tweets collected from January 1, 2020, primarily from hashtags populated from Saudi Arabia. This data set is available to the research community to glean a better understanding of the societal, economical, and political effects of the outbreak and to help policy makers make better decisions for fighting this epidemic.
HYPOTHESIS | doi:10.20944/preprints202004.0013.v1
Online: 2 April 2020 (11:06:47 CEST)
The pharmacology of azithromycin, and the actions of certain bee products, suggest the possibility of overlap with the pathophysiology of COVID-19 at several points in the disease process. First, intercellular epithelial tight junctions of the respiratory tract serve as a critical barrier to invaders. Pathophysiological factors capable of disrupting this epithelial barrier include viral virulence factors such as those observed for other coronaviruses; virulence factors derived from potentially synergistic pathogens such as Candida albicans and Porphyramonas gingivalis; and imbalances in the host inflammatory response. Azithromycin, and to a lesser extent, certain bee products, appear to have actions that oppose such processes. Second, the matrikine PGP or its derivatives may contribute to risk in individuals at high risk for serious COVID-19 infection, especially during reactivation; but azithromycin is capable of modulating PGP in some contexts. Third, the most serious COVID-19 infections are associated with massive upregulation of inflammatory cytokines such as IL-6, TNF alpha, and other inflammatory cytokines. The anti inflammatory actions of azithromycin and bee derived products such as melittin are potentially capable of modulating these processes, as well. Azithromycin is already in current use as a treatment for COVID-19; however, it's utility as a protector of epithelial barrier function would be most likely to be realized in prophylactic context rather than in a treatment context. Similarly, since the anti inflammatory effects of bee products take time, their effectiveness of melittin and other bee products would be expected to be maximized in a prophylactic context. In the context of the current pandemic, prophylaxis with azithromycin, bee products, or both, might be warranted for individuals at high risk for serious COVID-19 infection.
ARTICLE | doi:10.20944/preprints202003.0308.v1
Online: 20 March 2020 (07:01:44 CET)
Novel coronavirus (COVID-19) can lead to multiple organ injuries such as acute respiratory distress syndrome (ARDS), acute renal injury (AKI) and so on. ACE2 is an important part of the renin-angiotensin system (RAS) and a key protein needed for COVID-19 to invade cells. First of all, we searched the HPA, GTEx and FANTOM5 Databases and found that the expression of ACE2 in kidney tissue was significantly higher than that in lung tissue. Then, by searching the Nephroseq Database, it is further verified that ACE2 is highly expressed in renal tissue and plays a protective role in renal tissue. However, current studies have found that the incidence of AKI caused by COVID-19 is much lower than that of ARDS. Because of this, we further searched the proteins interacting with ACE2 protein through the STING Database and analyzed the expression of tissue protein mRNA in the HPA Database. It was noted that AGTR2 mRNA was highly expressed in lung tissue, but low in kidney tissue, and hard tissue specificity in lung tissue. Through further research, it is found that AGTR2 plays a major role in the development of pulmonary fibrosis. Therefore, AGTR2 may be a key protein in COVID-19 pneumonia, and AGTR2 may be a potential new therapeutic target for the treatment of COVID-19 patients.
ARTICLE | doi:10.20944/preprints202104.0120.v1
Subject: Earth Sciences, Environmental Sciences Keywords: Pre-COVID-19; Post-COVID-19; Secondary Schools; Water Demand; Groundwater; Nigeria
Online: 5 April 2021 (12:22:37 CEST)
The prevalence of corona virus and the novel COVID-19 disease in the entire globe has exacerbated different impact on socioeconomic spectrum in the world, including water use pattern. Thus a research was conducted to examine the comparative use of water during pre- and post-COVID-19 lockdown pattern among post-primary schools in Iwo, Osun State, Nigeria. A survey was conducted among fifteen schools which were randomly selected, but with eight public and seven private schools for the investigation. Both descriptive and inferential statistical techniques were used in data analysis. The results revealed that the major source of water to the schools investigated is ground water which is obtained through hand-dug wells and boreholes. It was further discovered that there was increase in water use during post-COVID-19 lockdown era as a result of the directive by the government that clean water should be provided for hand-washing by all schools regardless of the owner to curtail the spread of COVID-19 disease in the country. One sample t-test also revealed that there was a significant difference in water use at (p<0.01) level. It is recommended that the government and other stakeholders in water sector to ensure that all-time and non-seasonal dependent source of water be provided rather than ground water source which is susceptible to variations in water yields from seasonal variations. This will enable continuous clean water supply, for all purposes, including COVID-19 protocols.
ARTICLE | doi:10.20944/preprints202103.0474.v1
Subject: Social Sciences, Accounting Keywords: COVID-19; fear of COVID-19; mental health; emotional distress; social effects
Online: 18 March 2021 (11:01:24 CET)
The aim of the article is to determine the predictors of mental health among Polish society. Research was conducted after the first wave of the pandemic. Due to such an approach, it was possible to determine whether secondary effects of the pandemic have impact on mental health, apart from socio-demographic and psychological factors. In order to gather the research material, the CAWI on-line survey method was applied and carried out within the framework of the Ariadna Research Panel on the sample of 1079 Poles aged 15 and over. The FCV-19S scale, which is used to measure the fear of COVID-19 was applied in the measurement. It is a verified diagnostic instrument used to measure mental health in a lot of countries. The results of a hierarchical regression analysis have shown that the factors which increase the level of fear of COVID-19 are demographic, social and psychological features as well as attitudes towards the pandemic. The results of research indicate the significance of social context in the analysis and explanation of the effects of disasters and cataclysms.
ARTICLE | doi:10.20944/preprints202208.0151.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: BNT162b2 mRNA COVID-19 vaccine; COVID-19 vaccine; cardiovascular effects; myocarditis; adolescents; Thailand
Online: 8 August 2022 (10:40:23 CEST)
This study focuses on cardiovascular effects, particularly myocarditis and pericarditis events, after BNT162b2 mRNA COVID-19 vaccine injection in Thai adolescents. This prospective cohort study enrolled students from two schools aged 13–18 years who received the second dose of the BNT162b2 mRNA COVID-19 vaccine. Data including demographics, symptoms, vital signs, ECG, echocardiography and cardiac enzymes were collected at baseline, Day 3, Day 7, and Day 14 (optional) using case record forms.We enrolled 314 participants; of these, 13 participants were lost to follow up, leaving 301 participants for analysis. The most common cardiovascular effects were tachycardia (7.64%), shortness of breath (6.64%), palpitation (4.32%), chest pain (4.32%), and hypertension (3.99%). Seven participants (2.33%) exhibited at least one elevated cardiac biomarker or positive lab assessments. Cardiovascular effects were found in 29.24% of patients, ranging from tachycardia, palpitation, and myopericarditis. Myopericarditis was confirmed in one patient after vaccination. Two patients had suspected pericarditis and four patients had suspected subclinical myocarditis. Conclusion: Cardiovascular effects in adolescents after BNT162b2 mRNA COVID-19 vaccination included tachycardia, palpitation, and myocarditis. The clinical presentation of myopericarditis after vaccination was usually mild, with all cases fully recovering within 14 days. Hence, adolescents receiving mRNA vaccines should be monitored for side effects. Clinical Trial Registration: NCT05288231
ARTICLE | doi:10.20944/preprints202206.0410.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: COVID-19 variants; COVID-19 vaccine; IBD; ulcerative colitis; Crohn’s disease; anti-TNF
Online: 29 June 2022 (15:02:36 CEST)
Management of inflammatory bowel disease (IBD) often relies on biological and immunomodulatory agents for remission through immunosuppression, raising concerns regarding the SARS-CoV-2 vaccine's effectiveness. The emergent variants have hindered the vaccine neutralization capacity, and whether the third vaccine dose has the capacity to neutralize SARS-CoV-2 variants in this population remains unknown. This study aims to evaluate the humoral response of SARS-CoV-2 variants in patients with IBD 60 days after the third vaccine dose [BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)].56 su bjects with IBD and 12 healthy subjects were recruited. 90% of patients with IBD (49/56) were receiving biologics and/or immunomodulatory therapy. 24 subjects with IBD did not develop effective neutralizing capability against the Omicron variant. 70% (17/24) of those subjects were receiving anti-Tumor Necrosis Factor therapy [10= adalimumab, 7= infliximab], two of them had a history of COVID-19 infection, and one subject did not develop immune neutralization against three other variants: Gamma, Epsilon, and Kappa. All subjects in the control group developed detectable antibodies and effective neutralization against all seven SARS-CoV-2 variants. Our study shows that patients with IBD might not be protected against SARS-CoV-2 variants, and larger studies are needed to evaluate optimal immunity.
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; with- COVID-19 age; infectious disease; local healthcare projects; healthcare systems
Online: 16 September 2021 (14:59:34 CEST)
Objectives: This study aimed to analyze the awareness of local residents regarding healthcare projects and to suggest some ideas for the revision of local ones. Methods: To delve into the opinions of local residents, the author of this study created a questionnaire composed of eight questions on the general characteristics of the respondents, eight questions on satisfaction with health centers, 16 questions on the awareness of healthcare projects, and 22 questions on local healthcare. The survey was conducted for 409 residents who visited public centers in Gimcheon from 15 March to 14 April 2021. Results: Data analysis revealed the following: The proportion of local residents who use health centers was 39.1%, and those users visit health centers, on average, 3.92 times a year. Among healthcare projects, the project known by the highest proportion of people was vaccinations (84.5%), which was also the project that was most used (38.1%). Among healthcare projects needed in the with-COVID-19 age, respondents awarded the highest score to vaccinations (4.15 points on a five-point Likert scale) and the second highest score to infectious disease management (4.12). Conclusions: For healthcare projects, central and local governments should focus on activating vaccinations, solving the problem of medical accessibility through untact remote treatment and establishing national infectious disease-specializing hospitals and local infectious disease management based on such national hospitals.
REVIEW | doi:10.20944/preprints202008.0597.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: COVID-19 detection; biosensor application; COVID-19 transmission styles; sensors interaction; artificial intelligence
Online: 27 August 2020 (08:01:55 CEST)
The global spread of coronavirus disease (COVID -19) worldwide has had a significant effect on social and economic growth. The contamination keeps on advancing quickly and eccentrically, representing a significant test to its recognition and conclusion. Coronaviruses are commonly recognized by seclusion from tests, regardless of whether natural or clinical, utilizing some atomic science procedures, which can take a few days. In this work an analytical review of virus transmission, methods of diagnosing COVID -19 using artificial intelligence techniques to classify images and types of biosensors. At long last, the deformities and points of interest of each kind of sensor are recognized and examined. This exploration gives an explanatory audit of the utilization of crown infection COVID-19 in 2019. Related examinations were led utilizing five dependable databases, for example, Science Direct, IEEE Xplore, Scopus, Web of Science, and PubMed. An acceptable investigation is remembered for this audit, which can be depended upon as a logical database to put resources into another technique for recognizing COIVD-19.
REVIEW | doi:10.20944/preprints202005.0411.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; Clinical Trials; disruption; non-COVID-19 clinical trials; drugs; therapeutic area
Online: 25 May 2020 (11:17:56 CEST)
COVID-19 is causing major turmoil around the globe, and the clinical trial industry is likely to face unprecedented challenges to health and business sectors. In an effort to find a suitable treatment and prevention options for COVID-19, several COVID-19 clinical trials are being planned and initiated, while a large number of clinical trials for non- COVID-19 indications are suffering delays. With over more than 1000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrolment. This analysis deals with the specific impacts of the COVID-19 pandemic on the clinical trial and pharmaceutical industry. The objective of this study is to provide an updated information of the disrupted clinical trials and its impact on various therapeutic areas and different drugs. Among the severely affected clinical trials, oncology and CNS trials are the hardest hit therapy areas.This article will certainly emphasize the need for advanced and innovative approaches to maintain the health of the clinical trial ecosystem by continuing the existing trials and the start of the new studies. We have to take and follow necessary actions to guarantee that the initiatives will not be locked during the COVID-19 pandemic, both for the treatment of patients and for the researchers to conduct decision-relevant clinical trials.
Subject: Keywords: COVID-19 infection; immunity; risk of COVID-19 infection; pandemics; outbreaks; voluntary infection
Online: 13 May 2020 (05:53:07 CEST)
Draconian defensive measures have been implemented to combat the COVID-19 pandemic outbreak. These important measures constitute a vital current priority but do little to increase communal immunity and avoid future outbreaks. A longer-term exit strategy for a sustainable return to normalcy has yet to be identified. The development of vaccines or effective therapeutics could largely solve the problem, but their timely development cannot be guaranteed. In this setting, and under the expected societal isolation fatigue from extended social distancing, we here propose the idea that at some point after the outbreak’s peak, hospitals, in addition to providing care for infected people who need it, could also be involved in the development of a controlled exit strategy designed to avoid future outbreaks. We postulate that controlled voluntary deliberate infection in a hospital setting and under continuous and close medical observation may offer a safer alternative compared to random en-masse exposure. We discuss potential risks and benefits, highlighting the need for careful consideration of the associated critical ethical issues.
ARTICLE | doi:10.20944/preprints202004.0527.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Radiation oncology; COVID-19; Radiation therapist COVID-19 policy; Radiation oncology departmental Policy
Online: 30 April 2020 (11:02:58 CEST)
Abstract: This brief policy is written after experience treating COVID-19 positive radiation therapy patients to reduce risk to therapy staff and patients in radiation oncology department. It is important to prioritize the safety of staff and non-infected patients while ensuring the continuation of radiation oncology services. Radiation therapists have sustained contact with covid-19 patients in an enclosed vault. Protocols for correct disinfecting of equipment and room and therapists following methods for less transmission of virus is crucial. This policy covers prevention methods from COVID-19 transmission from patient to patient, patient to staff, staff to patient and staff to staff as follows A.Risk reduction by screening and preparing staff and rooms B.Radiation Therapist Policy for COVID-19 positive patient with CCC (Critical Cancer Care)
REVIEW | doi:10.20944/preprints202004.0341.v1
Subject: Life Sciences, Virology Keywords: COVID-19; Outbreak; nCoV-19; Quinine; Chloroquine; Hydroxychloroquine
Online: 19 April 2020 (08:36:55 CEST)
Quinine and its less toxic derivatives have served humanity for decades as potent antimalarial drugs. Emergence of drug resistance has narrowed the usage of these drugs in malaria prevention and treatment. Fortunately, these drugs have roles in the treatment of other diseases as well including rheumatic disorders and viral infections. Quinine derivatives have proven antiviral effects, especially against human immunodeficiency virus (HIV), Zika virus (ZiKV), herpes simplex virus (HSV), Ebola virus and dengue virus (DENV). The prophylactic and therapeutic role of Chloroquine/hydroxychroquine has become a topic of interest after the recent outbreak of novel Corona virus-19 (nCoV-19). This virus is also named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and WHO has officially named this disease as Corona virus disease 2019 (COVID-19). This lethal virus has affected almost 186 countries of the world till to date just in a period of four months of its outbreak. No approved antiviral drug is existed for the treatment of COVID-19. Therefore, this review is focused on potential prophylactic and therapeutic role of chloroquine/hydroxychlroquine for COVID-19.
ARTICLE | doi:10.20944/preprints202205.0408.v2
Subject: Medicine & Pharmacology, General Medical Research Keywords: hesitancy; covid-19; post-covid; medical doctors; indonesia
Online: 13 September 2022 (05:13:14 CEST)
This study is a cross-sectional survey involving physicians around Indonesia aimed to explore physician hesitancy to treat COVID-19 patients after experiencing COVID-19 infection coupled with associated occupational risk factors. The questionnaire was distributed via contact information from the Indonesian Physician Association database. Out of 383 participants, 25.6% suffered from moderate symptoms of COVID-19 and 2.9% were admitted for critical care. Hesitancy to treat suspected, probable, or confirmed COVID-19 patients was found in 20.3% of physicians. A higher hesitancy rate was found in older physicians and those with less experience in treating COVID-19 patients. Specialist trainees and those who work in public hospitals were physicians with the lowest hesitancy in treating COVID-19 patients. There is a significant hesitancy in treating COVID-19 patients among physicians who have suffered from COVID-19 which calls for further action by management and policy makers.
COMMUNICATION | doi:10.20944/preprints202204.0196.v1
Online: 21 April 2022 (08:24:19 CEST)
The Omicron variant of SARS-CoV-2 is the latest pandemic lineage causing COVID-19. Despite having a vaccination rate ≥ 85% Ecuador recorded a high incidence of Omicron from December 2021 to March 2022. Since Omicron emerged it is evolving into multiple sublineages with distinct prevalence in different regions. In this work, we use all Omicron sequences from Ecuador available at GISAID until March 2022 and the software Nextclade and Pangolin to identify which lineages circulate in this country. We detected 12 different sublineages (BA.1, BA.1.1, BA.1.1.1, BA.1.1.14, BA.1.1.2, BA.1.14, BA.1.15, BA.1.16, BA.1.17, BA.1.6, BA.2, BA.2.3), which has been reported in Africa, America, Europe, and Asia suggesting multiple introduction events. Sublineages BA.1.1 and BA.1 were the most prevalent. Genomic surveillance must continue to evaluate the dynamic of current sublineages, early introduction of new ones and vaccine efficacy against evolving SARS-CoV-2.
ARTICLE | doi:10.20944/preprints202203.0076.v1
Online: 4 March 2022 (09:10:15 CET)
The COVID-19 pandemic has now become very severe as never before due to the overwhelming spread of Omicron. We found that Omicron outbreak can be effectively prevented by inactivated vaccines, which averted an outbreak of more than 1.6 million people in Hangzhou, China. The 36 mutations in the target spike protein of Omicron neutralizing antibody enable it to evade the immune protection afforded by vaccines. This is because that mRNA and adenovirus-vector vaccines are designed to recognize the spike (S) glycoprotein of the SARS-CoV-2 wild-type (WT) strain. However, Inactivated vaccines contain the whole viral antigens and remain stable in their recognition of newly emerging variants of SARS-CoV-2. Our study confirmed the advantage of inactivated vaccines in the face of highly mutated Omicron variant and provided a basis for the development of effective vaccines to prevent future long-term transmission, mutation and recurrence of SARS-CoV-2.
ARTICLE | doi:10.20944/preprints202111.0361.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: swimming; COVID-19; swim performance
Online: 19 November 2021 (14:34:46 CET)
The COVID-19 pandemic caused significant training disruptions during the 2020-21 season due to lockdowns, quarantines, and strict adherence to pandemic protocols. The main purpose of this study was to determine how pandemic training restrictions affected training volume and performance in one collegiate swim team. Cumulative training volume data, across a 28-week season, were compared between a pandemic (2020-2021) versus non-pandemic (2019-2020) season. Swimmers were categorized into three groups (Sprinters, Mid-Distance, and Long-Distance) based on training group. Performance times in 25 swimmers who competed in Regional Championships, during both the non-pandemic and pandemic year, were compared via 1-way ANOVA. 26 male and 22 female swimmers commenced the 2020-21 (pandemic) season, with 23% of swimmers voluntarily opting out. Three COVID-19 cases were confirmed (2%) by the medical staff with no long-term effects. Significant reductions in average swim volume were verified in Sprinters (32,867±10,135 vs.14,800±7,995yards;p<0.001), Mid-Distance (26,457±10,692 vs.17,054±9.923yards;p<0.001), and Long-Distance (37,600±14,430 vs.22,254±14,418yards;p<0.001) swimmers (non-pandemic vs. pandemic season, respectively). In the Regional performance analyses, the Sprinters swam faster (n=8;-0.5±0.6secs), while Mid-Distance (n=10;0.17±2.1secs) and Long-Distance (n=7;6.0±4.9secs) swimmers swam slower (F=11.76;p=0.0003;r2=0.52). Thus, the pandemic caused significant reductions in swim training volume, with Sprinters performing better and Long-Distance swimmers performing worse at Regional Championships.
CONCEPT PAPER | doi:10.20944/preprints202109.0162.v3
Subject: Life Sciences, Virology Keywords: epidemiological model; dwarf peak phenomenon; herd immunity; Covid-19
Online: 27 September 2022 (04:51:54 CEST)
Compartmental models that dynamically divide the host population in categories such as susceptible, infected and immune constitute the mainstream of epidemiological modelling. Effectively such models treat infection and immunity as binary variables. We constructed an individual based stochastic model that considers immunity as a continuous variable and incorporates factors that bring about small changes in immunity. The small immunity effects (SIE) comprise cross immunity by other infections, small increments in immunity by sub clinical exposures and slow decay in the absence of repeated exposure. The model makes qualitatively different epidemiological predictions including repeated waves without the need for new variants, dwarf peaks (peak and decline of a wave much before reaching herd immunity threshold), symmetry in the upward and downward slopes of a wave, endemic state, new surges after variable and unpredictable gaps, new surge after vaccinating majority of population. In effect the SIE model raises alternative possible causes of the universally observed dwarf and symmetric peaks and repeated surges, observed particularly well during the Covid-19 pandemic. We also suggest testable predictions to differentiate between the alternative causes for repeated waves. The model further shows complex interactions of different interventions that can be synergistic as well as antagonistic. The model suggests that interventions that are beneficial in the short run can also be hazardous in the long run.
ARTICLE | doi:10.20944/preprints202106.0310.v1
Online: 11 June 2021 (09:19:51 CEST)
Because of the covid-19 pandemic, world development has de-escalated, and some have come to a halt because there are many new problems that this era never faced before. Especially in Indonesia's education, every student in this millennial era who is already used to face-to-face lectures and teachers and professors are going through massive changes where every task will be done virtually. These actions are being done to prevent the spread of Covid-19. With online meetings, there will be many changes in the curriculum to find an effective way of studying, and the former curriculum will not fit because it was made for the offline lecture. Also adapting to it will take time. This article will bring up Indonesia’s education progress in this era while Covid-19 pandemic is happening and give an insight on how to anticipate this problem. Questions that arise from this topic are the effect of government effort on holding the pandemic, is it safe if school will be opened soon, and how education after this pandemic is. This research uses literature review methods where it’s done by search, gather, compile and interpret data that is being used. The data are from the latest research, namely from 2019 to 2021 published through Google Scholar, totaling 11 articles, and few online news to keep relevancy of the topic. The results of this study indicate that Covid-19 produces a change that is worse than the good. Even so, the government has allowed face-to-face and online learning according to the consent of students and parents. Thus, the community, especially students, teachers, and others, are expected to uphold education even though it is required to adapt according to existing protocols. From the research, literature review methods proved to be effective to study this topic while Covid-19 is happening to keep safety measures, but it does not give many details and specific information well. This method is recommended to researchers who don’t want to risk their life by being exposed to the pandemic.
BRIEF REPORT | doi:10.20944/preprints202105.0617.v1
Online: 25 May 2021 (15:06:40 CEST)
The harrowing second wave of COVID-19 in India has led to much discussion over the quality and timeliness of reporting of deaths attributed to the pandemic. In this brief report, we aim to present the existing evidence, as well as the broader complexities surrounding the mortality burden of COVID-19 in India. This article sheds light on the following epidemiological issues: (1) general and India-specific challenges to COVID-19 death reporting, (2) latest COVID-19 mortality estimates in India as of May 16, 2021, (3) the apparent scale of uncaptured COVID-19 deaths, and (4) the role of disaggregated historic mortality trends in quantification of excess deaths attributed to COVID-19. We conclude with a set of high-level policy recommendations for improving the vital surveillance system and tracking of causes of death in India. We encourage direct efforts to integrate health data and indirect strategies for cross-validation of registered deaths. Such system-wide advances would drastically aid epidemiological research efforts and strengthen India’s position to overcome future public health crises.
COMMUNICATION | doi:10.20944/preprints202102.0306.v1
Online: 12 February 2021 (14:39:16 CET)
The COVID-19 pandemic which have affected every part of the world have been deemed a public health concern and classified as a pandemic. The government imposing travel bans and quarantine measures have been found to be effective in preventing and reducing the spread of COVID-19. A reduction in physical activity and increase in the consumption of unhealthy foods have been observed to be some of the major implications of quarantine. Adequate physical activity and increased access to healthy foods would help in improving the psychological wellbeing of individuals thereby preventing the development of cardiovascular diseases.
ARTICLE | doi:10.20944/preprints202101.0153.v2
Online: 13 January 2021 (11:06:00 CET)
This study clearly shows that the corona pandemic has a significant impact on consumers’ eating habits. More food is eaten overall, and more convenience products such as ready meals and canned food with a longer shelf life are purchased. The consumption of alcohol and confectionery has also increased. In return, the consumption of fresh fruit and vegetables has declined. It becomes clear that families who are financially affected by the pandemic represent a vulnerable group. With the increasing duration of the pandemic, repeated lockdowns, corona-related closings of schools and kindergartens, health consequences are to be expected in the medium to long term, especially for this population group.
ARTICLE | doi:10.20944/preprints202009.0242.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COPD; COVID-19; prevalence; prognosis
Online: 11 September 2020 (05:47:59 CEST)
Patients with COPD have a higher prevalence of coronary ischemia and other factors that put them at risk for COVID-19-related complications. We aimed to explore the impact of COVID-19 in a large population-based sample of patients with COPD in Castilla-La Mancha, Spain. We analyzed clinical data in electronic health records from January 1st to May 10th, 2020 by using Natural Language Processing through the SAVANA Manager® clinical platform. Out of 31,633 COPD patients, 793 had a diagnosis of COVID-19. The proportion of patients with COVID-19 in the COPD population (2,51%; CI95% 2,33 – 2,68) was significantly higher than in the general population aged > 40 years (1,16%; 95%CI 1,14 – 1,18); P < .001. Compared with COPD-free individuals, COPD patients with COVID-19 showed significantly poorer disease prognosis, as evaluated by hospitalizations (31,1 % vs 39,8%: OR 1,57; 95%CI 1,14 – 1,18) and mortality (3,4% vs 9,3%: OR 2,93; 95%CI 2,27 – 3,79). Patients with COPD and COVID-19 were significantly older (75 vs. 66 years), predominantly male (83% vs 17%), smoked more frequently, and had more comorbidities than their non-COPD counterparts. Pneumonia was the most common diagnosis among COPD patients hospitalized due to COVID-19 (59%); 19% of patients showed pulmonary infiltrates suggestive of pneumonia and heart failure. Mortality in COPD patients with COVID-19 was associated with older age and prevalence of heart failure (P<0.05). COPD patients with COVID-19 showed higher rates of hospitalization and mortality, mainly associated with pneumonia. This clinical profile is different from exacerbations caused by other respiratory viruses in the winter season.
Online: 4 September 2020 (12:32:58 CEST)
As part of a plethora of global efforts to minimize the negative effects of the SARS-CoV2 (COVID-19) pandemic, we developed two different mechanisms that, after further development, could potentially be of use in the future in order to increase the capacity of ventilators with low-cost devices based on single-use-bag-valve mask systems. We describe the concept behind the devices and report a characterization of them. Finally, we make a description of the solved and unsolved challenges and propose a series of measures in order to better cope with future contingencies.
ARTICLE | doi:10.20944/preprints202007.0129.v1
Online: 7 July 2020 (16:26:57 CEST)
The effect of the COVID-19 pandemic in a developing country like Bangladesh is enormous. A research conducted by South Asian network of Economic Modelling predicted that the pandemic could double the poverty. But it is not that only the socioeconomic condition is dropping in Bangladesh, the impact of COVID-19 pandemic is manifold. The poor condition of Bangladesh's health sector has also been exposed due to the pandemic. People are not getting proper treatment due to lack of isolation beds, oxygen, ICU etc. The health sector of Bangladesh is not much developed and now with this pandemic it has become impossible to provide treatment facility for all the patients. Education sector, which is the backbone of a country,has also been greatly affected by the pandemic. We know that different types of cultural occasions are an inherited tradition of Bangladesh, COVID-19 have not even spared these traditions, all the cultural programes and festivals have been cancelled due to this pandemic.In this paper, our aim is to present the present status of all these sectors.
ARTICLE | doi:10.20944/preprints202006.0309.v1
Online: 26 June 2020 (12:14:21 CEST)
This paper uses resilience as a lens through which to analyse disasters and other major threats to patterns of criminal behaviour. A set of indicators and mathematical models are introduced that aim to quantitatively describe changes in crime levels in comparison to what could otherwise be expected, and what might be expected by way of adaptation and subsequent resumption of those patterns. The validity of the proposed resilience assessment tool is demonstrated using commercial theft data from the COVID-19 pandemic period. A 64 per cent reduction in crime was found in the studied city (China) during an 83-day period, before daily crime levels bounced back to higher than expected values. The proposed resilience indicators are recommended as benchmarking instruments for evaluating and comparing the global impact of COVID-19 policies on crime and public safety.
CASE REPORT | doi:10.20944/preprints202006.0282.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; mesenteric vein thrombosis
Online: 21 June 2020 (16:44:51 CEST)
Since its inception in December 2019, Covid-19 has challenged the global scientific community. Some treatments were used in this infection, but doubts still persist regarding the use of medications 1. More severe cases complicate with endothelial dysfunction, excess thrombin synthesis and decreased fibrinolysis which, associated with hypoxemia, lead to a hypercoagulability state 2 and some authors indicate the use of anticoagulants for these 3. For mild cases, doubts remain regarding this indication. We will report the case of a patient with mild symptoms of covid-19, complicated by inferior mesenteric vein thrombosis.
ARTICLE | doi:10.20944/preprints202003.0366.v3
Subject: Earth Sciences, Environmental Sciences Keywords: COVID-19; coronavirus; temperature; solutions
Online: 21 June 2020 (16:19:26 CEST)
This article investigated whether the atmospheric temperature had any role in the spread and vulnerability to COVID-19 worldwide and how that knowledge can be utilized to contain the fast-spreading disease. It highlighted that temperature was an important factor in transmitting the virus, and a moderately cool environment was the most favourable state for its susceptibility. In fact, the risk from the virus is reduced significantly in high temperature environment. Warm countries and places were likely to be less vulnerable. We identified various degrees of vulnerability based on temperature and specified countries for March and April. The maximum reported case, as well as death, was noted when the temperature was in the range of around 275°K (2°C) to 290°K (17°C). Countries like the USA, UK, Italy and Spain belonged to this category. The vulnerability was moderate when the temperature was less than around 275°K (2°C) and countries in that category were Russia, parts of Canada and few Scandinavian countries. For temperature 300°K (27°C) and above, a significantly lesser degree of vulnerability was noted. Countries from SAARC, South East Asia, the African continent and Australia fell in that category. In fact, when the temperature was more than 305°K (32°C), there was a unusually low number of reported cases and deaths. For warm countries, further analyses on the degree of vulnerability were conducted for the group of countries from SAARC and South East Asia and individual countries were compared. We also showed countries can switch from one vulnerability state to another based on the variability of temperature. We provided maps of temperature to identify countries of different vulnerability states in different months of the year. That influence of temperature on the virus and previous results of clinical trials with similar viruses gave us a useful insight that regulating the level of temperature can provide remarkable results to arrest and stop the outbreak. Based on that knowledge, some urgent solutions are proposed, which are practically without side effects and very cost-effective too.
ARTICLE | doi:10.20944/preprints202006.0029.v1
Online: 4 June 2020 (08:03:48 CEST)
On the 9th March 2020, the first patient with COVID-19 was admitted to ICU in the Royal Gwent Hospital, Newport, Wales. We prospectively recorded the rate of ICU admissions of 52 patients with COVID-19 over 60 days, focusing on the epidemiology of ethnicity and deprivation. Patients were 65% (34 of 52) male and had a median (IQR) age of 55 (48-62) years. Prevalent comorbidities included obesity (52%); diabetes (33%), and asthma (23%). COVID-19 hospital and ICU inpatient numbers peaked on days 23 and 39, respectively – a lag of 16 days. The ICU mortality rate was 33% (17 of 52). Black, Asian and Minority Ethnics (BAME) population represented 35% of ICU COVID-19 admissions (18 of 52) and 35% of deaths (6 of 17). Within the BAME group, 72% (13 of 18) were found to reside in geographical areas representing the 20% most deprived in Wales, versus 27% of Caucasians (9 of 33). Less than 5% of the population within the hospital catchment area are of BAME descent, yet they represent a disproportionately high proportion of patients with ICU admission and mortality suffering from COVID-19. The interplay between ethnicity and deprivation, which is complex, may be a factor in our findings. This in turn could be related to an increased prevalence of co-morbidities; higher community exposure; or genetic polymorphisms.
COMMUNICATION | doi:10.20944/preprints202005.0395.v1
Online: 24 May 2020 (18:19:02 CEST)
We present a modification of the logistic model of epidemics that takes into account the possibility that an epidemic can develop from multiple physically-distinct hot spots with a range of starting times. This produces an improved understanding of the time evolution of the COVID-19 epidemic taking place in the United States in the spring of 2020.
CONCEPT PAPER | doi:10.20944/preprints202005.0298.v1
Online: 18 May 2020 (08:01:52 CEST)
COVID-19 Pandemic management has become the top priority of Government Institutions globally, which is justifiable seeing the high mortality of the disease. In India, Lockdowns by National, State and Local level administrations have greatly reduced the spread of the SARS COV-2 Virus. Some areas with a greater proportion of COVID-19 patients have been declared hotspots with increased restrictions on public activities through law enforcement. But quite often delay in identification of these hotspots leads to community transmission of the Virus thus aggravating the problem. A method to identify the areas which are at risk of becoming the next hotspot for the disease is the need of the hour. In this Research document we will find the probable risk factors and make an appropriate scale to measure the vulnerability of an area, identified by its Postal code. To help with this a Pan India survey by the title of “Survey on General Indian population on the level of preparedness for COVID-19 pandemic” was launched and received around 1250 submissions, with the acquired data we will evaluate the risk factors and make appropriate scale to identify ‘pre-hotspots’.
HYPOTHESIS | doi:10.20944/preprints202005.0262.v1
Online: 16 May 2020 (04:19:07 CEST)
COVID-19 is frequently associated with a coagulopathy with severe consequences. The mechanisms leading to a pro-coagulant state in these patients is multifactorial, including tissue destruction and inflammatory mechanisms. Based on the analysis of publicly available interactomes, we propose that SARS-CoV-2 infection causes a deficiency in C1 esterase inhibitor (C1-INH), a pathogen-specific mechanism that may help explain the pro-coagulant state in COVID-19 patients.
REVIEW | doi:10.20944/preprints202005.0178.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: COVID-19; estrogen; RAGE; ACE2
Online: 10 May 2020 (17:46:13 CEST)
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has provoked major stresses on the health care systems of several countries, and caused the death of more than a quarter of a million people globally, mainly in the elderly population with pre-existing pathologies. Previous studies with coronavirus (SARS-CoV) point to gender differences in infection and disease progression with increased susceptibility in male patients, indicating that estrogens may be associated with physiological protection against the coronavirus. Therefore, the objectives of this work are threefold. First, we aim to summarize the SARS-CoV-2 infection pathway and the roles both the virus and patient play in COVID-19 (Coronavirus disease 2019) progression, clinical symptomology, and mortality. Second, we detail the effect estrogen has on viral infection and host infection response, including its role in both the regulation of key viral receptor expression and the mediation of inflammatory activity. Finally, we describe how ERs (estrogen receptors) and RAGE (receptor for advanced glycation end-products) play a critical role in metabolic pathways, which we envisage could maintain a close interplay with SARS-CoV and COVID-19 mortality rates, despite a current lack of research directly determining how. Taken together, we present the current state of the field regarding SARS-CoV-2 research and illuminate where research is needed to better define the role both estrogen and metabolic comorbidities have in the COVID-19 disease state, which can be key in screening potential therapeutic options as the search for effective treatments continue.
ARTICLE | doi:10.20944/preprints202005.0161.v1
Online: 9 May 2020 (10:08:24 CEST)
Background: Corona virus disease was first reported in Wuhan City, Hubei province, China. Soon the corona virus disease has spread to many countries. World health organization has described the situation as Pandemic. By 12 March 2020, corona virus disease has affected 125 countries around the world. Corona virus was first confirmed in Iran on 19 February 2020. Objective: The aim of writing this small article is to determine the mortality rate of corona virus disease in different cities of Iran. This article will give readers an idea of different ways to control spread of corona virus disease in Iran. Methods: Author has collected the data of daily confirmed cases from different diagnostic centers and hospitals across the country from 19 February 2020 to 1 April 2020. Results: Mortality rate of corona virus disease is roughly 4%. Conclusions: Mortality rate could rise if COVID 19 infection is not controlled.
CASE REPORT | doi:10.20944/preprints202004.0531.v1
Online: 30 April 2020 (13:49:58 CEST)
Severe outbreaks of infectious disease occur throughout the world with some reaching the level of an international pandemic: Coronavirus (COVID-19) is the most recent to do so. As such pandemics cause extensive loss of lives, hamper industrial operations, and cause economic losses in both developing and developed countries, it is critical to establish common standards of accuracy in the determination and reporting of cases. In particular, there are current concerns that countries are hiding or incorrectly reporting cases of COVID-19. In this paper, we set out a mechanism for using Zipf's law to establish the accuracy of international reporting of COVID-19 cases via a determination of whether an individual country's COVID-19 reporting follows a power-law for confirmed, recovered, and death cases. We observe that the probability of Zipf's law (P-values) for COVID-19 confirmed cases show that Uzbekistan has the highest P-value of 0.940, followed by Belize (0.929), and Qatar (0.897). For COVID-19 recovered cases, Iraq had the highest P-value of 0.901, followed by New Zealand (0.888), and Austria (0.884). Furthermore, for COVID-19 death cases, Bosnia and Herzegovina had the highest P-value of 0.874, followed by Lithuania (0.843), and Morocco (0.825). China, where the COVID-19 pandemic began, is a significant outlier in recording P-values lower than 0.1 for the confirmed, recovered, and death cases. This raises important questions, not only for China but also any country whose data exhibits P-values below this threshold. The main application of this work is to serve as an early warning for the World Health Organization (WHO) and other health regulatory bodies to perform more investigations in countries where COVID-19 datasets deviate significantly from Zipf's law. To this end, we also provide a tool for illustrating Zipf's law P-values on a global map in order to report anomalies.
ARTICLE | doi:10.20944/preprints202004.0497.v1
Online: 28 April 2020 (10:23:16 CEST)
Objectives: The impact of COVID-19 in metropolitan areas has been extensively studied. The geographic spread to smaller cities is of great concern and may follow hierarchical influence of urban centers. With that in mind, we investigated factors that affect vulnerability of inner municipalities in São Paulo State, Brazil, an area with 24 million inhabitants. Methods: Surveillance data for confirmed COVID-19 cases and admissions for severe acute respiratory disease (SARD) up to April 18th were recorded for each of 604 municipalities that lay outside São Paulo metropolitan area. Vulnerability was assessed in Multivariable models, including sociodemographic indexes, road distance to the State Capital and the municipalities classification proposed by the Brazilian Institute of Geography and Statistics. Municipalities of great regional relevance were used as reference category for that classification. The outcome of interest for Cox regression was having COVID-cases, with time counting from the first report in São Paulo State. For binomial negative regression models, the outcomes of interest were rates of confirmed COVID-19 cases and admissions for SARD.Results: A total of 198 (32.8%) municipalities had autochthonous COVID-19 cases. In Cox models, affected municipalities were likely to have greater population density (Hazard Ratio[HR] for each 100 inhabitants per square kilometer, 1.07; 95% Confidence Interval [CI], (1.05-1.10)), proportion of inhabitants in urban area (HR, 1.02; 95%CI, 1.00-1.04), higher human development index (HDI, HR for 1%, 1.06; 95%CI, 1.00-1.13) and Gini Index for Inequality of income (HR for 1%, 1.04, 95% CI, 1.00-1.07). On the other hand, distance from the Capital was protective (HR for each 100Km, 0.82; 95%CI, 0.74-0.90). The HR95%[95%CI] also varied negatively according to the categories of influence of major centers (0.41 [0.22-0.77], 0.16 [0.09-0.32], 0.07 [0.03-0.15]). The binomial negative regression models for COVID-19 incidence also detected positive association with population density (Incidence Rate Ratio[IRR], 1.13; 95%CI, 1.07-1.18) and proportion of urban population (IRR, 1.04; 95%CI, 1.01-1.05), protection for cities distant to the Capital (IRR=0.73; 95%CI, 0.68-0.81) and increasing negative association for categories of influence (0.19 [0.09-0.42], 0.07 [0.03-0.15] and 0.03 [0.02-0.08]). Similar findings were detected when we used SARD incidence as outcome.Conclusion: Municipalities with greater population, density and regional influence were more likely to be affected earlier and more intensely by COVID-19. Non-pharmacological measures should be strengthened in those areas of greater risk.
ARTICLE | doi:10.20944/preprints202004.0438.v1
Online: 24 April 2020 (10:53:36 CEST)
COVID-19 breakout in Italy has caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection very few information are available about liver involvement in COVID-19 infection, that could possibly evocate a systemic disease targeting a lot of organs. Since now there are no reports of large series of histological evaluation of liver morphology in this setting. Knowledge of histological liver findings connected to clinical data is crucial in management of this disease.Post-mortem wedge liver biopsies from 48 patients died for COVID-19 infection were available from two main hospitals located in northern Italy, Lombardy; all sample were obtained during autopsies. No patient has a significant clinical complain of liver disease or signs of liver failure before and during hospitalization; for each of them laboratory data focused on liver were available. All liver samples showed minimal inflammation features; on the other side, many histological pictures compatible with vascular alterations were observed, characterized by portal vein braches number increase associated with lumen massive dilatation, partial or complete recent luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally severely enlarged and fibrotic. Our preliminary results concerning histological liver involvement in COVID-19 infection confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage; histopatological findings are highly suggestive for marked alteration of intrahepatic blood vessel network secondary to systemic alterations induced by virus that could target, besides lung parenchyma, cardiovascular system, coagulation cascade or endothelial layer of blood vessels.
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: SARS; Covid-19; Vitamins; Therapy
Online: 23 April 2020 (05:44:52 CEST)
In December 2019 a novel human-infecting coronavirus, named SARS-CoV-2 has been recognized to cause a pneumonia epidemic outbreak with different degree of severity in Wuhan, Hubei Province in China. Since then this epidemic spread worldwide an in the last week Europe and Italy also have been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, SARS-CoV-2 has been isolated only recently, therefore a few studies concerning its immunopathogenesis and tretament are available. Therefore, on the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82% of genome homology) and that its characteristics, like the modality of transmission, the route of infection, the organ localization, the type of the immune response it may stimulate, the morbidity and the mortality rates are still poor-known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analysed: 1) the structure of SARS CoV-2 and SARS CoV; 2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the Cytokine Release Syndrome; 3) the modification of the cell microRNome and of the immune response in patients with SARS infection; 4) the possible role of some liposoluble compounds (such as vitamin A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.
HYPOTHESIS | doi:10.20944/preprints202004.0348.v3
Subject: Medicine & Pharmacology, General Medical Research Keywords: hydroxychloroquine; COVID-19; pneumonia; prophylaxis; treatment
Online: 12 May 2020 (08:06:55 CEST)
According to current literature and preliminary data, hydroxychloroquine (HCQ) seems potentially effective in the treatment of patients with Covid-19 pneumonia. The concentrations of HCQ in lungs might be well above that of plasma. Most likely, this property of HCQ provides effective drug concentrations in lungs. HCQ has a gradual onset of action in the treatment of rheumatic diseases. This could be valid for the treatment of Covid-19 pneumonia. It was suggested that regular HCQ administration in animals for a certain time might result in gradual accumulation of HCQ in tissues. Reduced perfusion, somewhat distorted architecture of lung tissue, edema and, suggested gradual accumulation of HCQ in lung tissue might cause reduced HCQ concentrations in pneumonic areas of the lungs in Covid-19 pneumonia. Patients with Covid-19 pneumonia and extensive lung involvement might have less HCQ concentrations in their lungs than patients having limited lung involvement. Furthermore, patients with Covid-19 pneumonia and extensive lung involvement might have more viral load than patients having limited lung involvement. That’s why treatment of patients with advanced Covid-19 pneumonia using HCQ might result in treatment failure, however HCQ might be effective in the treatment of patients with mild and moderate Covid-19 pneumonia. Using HCQ in Covid-19 pneumonia prophylaxis seems logical since providing enough accumulation of HCQ in the healthy lungs, before the arrival of the SARS-CoV-2 virus, might prevent Covid-19 pneumonia. However, the purpose of this paper is not to recommend using or not using HCQ for the treatment or for the prophylaxis of Covid-19 pneumonia. The purpose of this paper is only to try to bring a new perspective on the role of HCQ in the treatment or in the prophylaxis of Covid-19 pneumonia. This paper proposes only hypotheses, which need further researches to be confirmed.
ARTICLE | doi:10.20944/preprints202004.0281.v2
Online: 7 September 2020 (04:15:59 CEST)
Spike (S) protein of Coronaviruses help in receptor attachment and virus entry into the host cells. While S protein is required for virus entry, it is also important as an immunogen as it is the most accessible part of the virus architecture. S protein form knob like structures (viral spikes) protruding outwards in the form of homotrimers containing an S1 and S2 as monomers. Mutations in structural proteins of virus play crucial role in determining virulence and also in many instances influencing emergence of antibody escape variants and cellular tropism. In this paper we have performed in depth analyses of spike protein sequences from various parts of the world and tried to correlate the data with possible functional relevance of such mutations.
ARTICLE | doi:10.20944/preprints202004.0219.v1
Online: 14 April 2020 (08:50:30 CEST)
The article revisits previous viruses such as Ebola to extrapolate the socio-economic implications of the COVID-19. Using secondary sources and the Sustainable Livelihoods Framework (SLF) to guide understanding, the article argues that unless measures are put in place to safeguard smallholder activities in Zimbabwe, COVID-19 has the potential to reproduce the same catastrophic implications created by Ebola in West African countries where peasant food systems where shattered and livelihoods strategies maimed. With a perceptible withdrawal of the government from small-scale farming towards large-scale capital intensive operations, smallholders could now be even more vulnerable. The article concludes that social assistance should now be intensified to protect its vulnerable population from the ravages of COVID-19.
COMMUNICATION | doi:10.20944/preprints202004.0130.v1
Online: 8 April 2020 (12:03:43 CEST)
In response to the COVID-19 pandemic, the Philippines placed the majority of the country under enhanced community quarantine, restricting the movement of most of its 100 million plus population. These aggressive measures were initiated on March 15, 2020 and intensified on March 17. According to official data, the number of confirmed COVID-19 cases has exponentially increased during this period, but it is important to note that the number of patients tested also substantially increased during the same period. It is not conclusive that widespread transmission of COVID-19 only started in March and our analysis suggests that community transmission was happening earlier. In discussing extended quarantine measures, it is important to properly understand the trends and recognize the limitations of the data. The unintended consequences on the population, especially in lower-middle income countries with fragile health systems like the Philippines, must be carefully considered.
REVIEW | doi:10.20944/preprints202004.0128.v1
Online: 8 April 2020 (11:49:56 CEST)
Coronavirus disease 2019 (COVID-19) has been declared a global pandemic by the World Health Organization on March 11, 2020. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov-2). Although primarily a respiratory disease, cardiovascular complications of COVID-19 have been increasingly recognized. In addition, higher fatality has been reported in COVID-19 patients with underlying cardiovascular diseases. Cancer survivors have a considerably increased risk for premature cardiovascular diseases, mainly due to cardiotoxic cancer treatments. Therefore, it is foreseeable that cancer survivors will be more vulnerable to cardiovascular complications caused by COVID-19. In this review, three scenarios for increased cardiovascular complications of COVID-19 in cancer patients are proposed. In the first scenario, cardiotoxic cancer treatment and COVID-19 synergize to exacerbate direct myocardial damage. In the second scenario, cardiotoxic cancer treatment leads to a reduced cardiac reserve in cancer survivors, making them more vulnerable to COVID-19 in a “two-hit” model. The third scenario suggests that several shared risk factors may aggravate cardiovascular complications caused by both cancer treatment and COVID-19. Taken together, cancer survivors may be more vulnerable to cardiovascular complications when challenged by the COVID-19, and special cardiovascular care should be given to these patients.
HYPOTHESIS | doi:10.20944/preprints202004.0101.v1
Online: 7 April 2020 (12:07:22 CEST)
On March 11, 2020, the World Health Organization declared the coronavirus outbreak a pandemic. Since December 2019, the world has experienced an outbreak of coronavirus disease 2019 (COVID-19). Epidemiology, risk factors, and clinical characteristics of patients with COVID-19 have been reported but the factors affecting the immune system against COVID-19 have not been well described. In this article, we provide a novel hypothesis to describe how an increase in cellular adenosine triphosphate (c-ATP) can potentially improve the efficiency of innate and adaptive immune systems to either prevent and fight off COVID-19.
Online: 27 April 2020 (09:55:03 CEST)
Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2 or SARS-CoV-2) is the cause of the respiratory infection known as COVID-19. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce an increase in a variety of T-helper 1 (Th1) and inflammatory cytokines and chemokines including interleukins IL-1, IL-6, CCL2 protein and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 symptoms and severity. This report briefly describes four unconventional but commercially accessible immunomodulatory agents that could be employed in clinical trials to evaluate their effectiveness at alleviating disease symptoms and severity: Low-dose oral interferon-alpha, microdose DNA, low-dose thimerosal and phytocannabinoids.
Online: 31 March 2020 (22:41:36 CEST)
There is an urgent need to advance safe and affordable COVID-19 vaccines for low- and middle-income countries of Asia, Africa and Latin America. Such vaccines rely on proven technologies such as recombinant protein-based vaccines to facilitate its transfer for emerging market vaccine manufacturers. Our group is developing a two-pronged approach to advance recombinant protein-based vaccines to prevent COVID-19 caused by SARS CoV2 and other coronavirus infections. One vaccine is based on a yeast-derived (Pichia pastoris) recombinant protein comprised of the receptor binding domain (RBD) of the SARS-CoV formulated on alum and referred to as the CoV RBD219-N1 Vaccine. Potentially this vaccine could be used as a heterologous vaccine against COVID-19. A second vaccine specific for COVID-19 is also being advanced using the corresponding RBD of SARS-CoV-2. The first antigen has already undergone cGMP manufacture and is therefore “shovel ready” for advancing into clinical trials, following vialing and required GLP toxicology testing. Evidence for its potential efficacy to cross-protect against SARS-CoV-2 includes cross-neutralization and binding studies using polyclonal and monoclonal antibodies. Evidence in support of its safety profile include our internal assessments in a mouse challenge model using a lethal mouse adapted SARS strain, which show that SARS-CoV RBD 291N1 (when adsorbed to Alhydrogel®) does not elicit eosinophilic lung pathology. Together these findings suggest that recombinant protein-based vaccines based on the RBD warrant further development to prevent SARS, COVID-19 or other coronaviruses of pandemic potential.
BRIEF REPORT | doi:10.20944/preprints202003.0436.v1
Online: 29 March 2020 (11:31:15 CEST)
Novel Coronavirus infection mediated pandemic started in China in December 2019 and is still killing 1000s of people throughout the world. The second most populous country, India too is fighting against this infectious disease. The country is taking effective measures to curb the pandemic by exerting extensive campaigning on sanitation and strict social distancing measures to quell the explosion of the infection rate. The future of the COVID-19 infections in India still remain unpredictable, so precautionary methods need to be continued until the growth rate of new cases drop below one.
HYPOTHESIS | doi:10.20944/preprints202003.0392.v1
Online: 26 March 2020 (14:58:35 CET)
SARS-CoV 2 also known as COVID-19 is a fast spreading coronavirus related disease that emerged from China in December 2019 and is currently attained the status of a pandemic. There are currently no drugs/ vaccines against the same and moreover limited diagnostic tests to identify the infection. Additionally, these tests are expensive and hence are exclusive for very highly suspected cases of the disease especially in developing countries. This is causing an under-diagnosis which is an alarming state of affairs, as even a single missed SARS-CoV 2 case would spread the disease exponentially and keep it in the community. Through this entirely in silico study, we have developed a cheaper and faster diagnostic method based on simple PCR and restriction enzyme digestion, commonly used in restriction fragment length polymorphism (RFLP) tests. Through comparative genomics, we found the closest neighbours of SARS-CoV 2 then found the highly conserved regions of the genome which were absent in SARS-CoV 1, its closest neighbour. Then we found restriction sites for various enzymes followed by designing of PCR primers flanking those sites. We have found the primer pair to produce a 401 bp amplicon and when digested by SwaI enzyme, it produces two fragments of lengths 216 bp and 185 bp. As an internal control, GAPDH primers are pooled with the SARS-CoV 2 primers as the patient sample will also include human RNA mixed with the viral RNA. This primer pair gives an amplicon of 131 bp and hence a negative sample should show a single band of 131 bp while a positive digested sample will give three bands of 401 bp, 216 bp and 131 bp. The primers are specific to SARS-CoV 2 only and can additionally be used for SYBR green based real time quantification of viral load. The developed tests have not yet been tested in vitro due to stressed out working hours in the only pathogenic virus handling laboratory in our institute. Nonetheless, this study works as a head start for other laboratories to rapidly test the suggested protocols in vitro and make available a cheaper alternative test for SARS-CoV 2 which would especially be beneficial for the lower to middle income countries.
Online: 9 March 2020 (10:34:58 CET)
An outbreak caused by coronavirus disease 2019 (COVID-19) occurred in Wuhan City, Hubei Province, China, in December 2019. Up to March 2, 2020, at least 80180 cases have been reported. Most of the patients had a history of visiting Hubei Province or contacting with people who had ever stayed in or passed by Hubei Province, or exposed to symptoms. Some patients got infected only from asymptomatic contacts. This study aimed to report the epidemic features and lab identification of a patient confirmed with COVID-19 infection only from asymptomatic contact.
REVIEW | doi:10.20944/preprints202002.0283.v1
Online: 19 February 2020 (11:58:13 CET)
The latest emergence of a novel coronavirus (COVID-19) had caused an outbreak of respiratory virus infections in Wuhan, China, and other countries so that the world health organization (WHO) declared the COVID-19 epidemic as a Public Health Emergency of International Concern (PHEIC) on January 31, 2020. At present, it is the fact that we have identified the bats as the host, the route of respiratory droplets, contact, and aerosol can accelerate the transmission from person to person. However, it is not well known about the intermediator and other approaches. Identifying and characterizing the origin and host(s) of COVID-19 can help us to evaluate the potential risk of COVID-19 for transmission among humans or cross-species.