Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Severity of COVID-19 at elevated exposure to perfluorinated alkylates

    Authors: Philippe Grandjean; Clara Amalie Gade Timmermann; Marie Kruse; Flemming Nielsen; Pernille Just Vinholt; Lasse Boding; Carsten Heilmann; Kaare Molbak; Peter F.M. Teunis; Jean-Louis Mege; Jean-Marc Busnel; Joana Vitte

    doi:10.1101/2020.10.22.20217562 Date: 2020-10-26 Source: medRxiv

    Background The course of coronavirus disease MESHD 2019 (COVID-19) seems to be aggravated by air pollution, and some industrial chemicals, such as the perfluorinated alkylate substances (PFASs), are immunotoxic and may contribute as well. Methods From Danish biobanks, we obtained plasma SERO samples from 323 subjects aged TRANS 30-70 years with known SARS-CoV-2 infection MESHD. The PFAS concentrations measured at the background exposures included five PFASs known to be immunotoxic. Register data was obtained to classify disease status, other health information, and demographic variables. We used ordinal and ordered logistic regression analyses to determine associations between PFAS concentrations and disease outcome. Results Plasma SERO-PFAS concentrations were higher in males TRANS, in subjects with Western European background, and tended to increase with age TRANS, but were not associated with the presence of chronic disease MESHD. Of the study population, 108 (33%) had not been hospitalized, and of those hospitalized, 53 (16%) had been in intensive care or were deceased. Among the five PFASs considered, perfluorobutanoic acid (PFBA) showed an odds ratio (OR) of 2.19 (95% confidence interval, CI, 1.39-3.46) for increasing severities of the disease, although the OR decreased to 1.77 (95% CI, 1.09, 2.87) after adjustment for age TRANS, sex, sampling site and interval between blood SERO sampling and diagnosis. Conclusions Measures of individual exposures to immunotoxic PFASs MESHD included PFBA that accumulates in the lungs. Elevated plasma SERO-PFBA concentrations were associated with an increased risk of more severe course of CIVID-19. Given the low background exposure levels in this study, the role of PFAS exposure in COVID-19 needs to be ascertained in populations with elevated exposures.

    SARS-CoV-2 specific memory T lymphocytes from COVID-19 convalescent donors: identification, biobanking and large scale production for Adoptive Cell Therapy

    Authors: Cristina Ferreras; Barbara Pascual-Miguel; Carmen Mestre-Duran; Alfonso Navarro-Zapata; Laura Clares-Villa; Carla Martin-Cortazar; Raquel De Paz; Antonio Marcos; Jose Luis Vicario; Antonio Balas; Felix Garcia-Sanchez; Cristina Eguizabal; Carlos Solano; Marta Mora-Rillo; Bernat Soria; Antonio Perez-Martinez

    doi:10.1101/2020.10.23.352294 Date: 2020-10-26 Source: bioRxiv

    SARS-CoV-2 is causing a second outbreak so the hope for its complete eradication is far from happening. In the absence of effective vaccines, it is mandatory to find effective treatments with low adverse effects able to treat hospitalized patients with COVID-19 disease. In this work, we determined the existence of SARS-CoV-2 specific T cells within the CD45RA- T memory cells from the blood SERO of convalescent donors. Memory T cells can respond quickly to the infection MESHD and provide long-term immune protection to reduce the severity of the COVID-19 symptoms. Also, CD45RA- memory T cells confer protection from other pathogens the donors encountered in their life. This is vital to clear other secondary infections usually developed in hospitalized COVID-19 patients. SARS-CoV-2 specific memory T cells were found within all the CD45RA- subsets CD3+, CD4+, CD8+, and in the central memory and effector memory subpopulations. The procedure to obtain the cells is feasible, easy to implement for small scale manufacture, quick and cost-effective involving minimal manipulation, and without GMP condition requirements. This biobank of specific SARS-CoV-2 memory T MESHD cells would be immediately available off-the-shelf to treat moderate/severe cases of COVID-19 increasing the therapeutic options available for these patients.

    SARS-CoV-2 antibodies SERO in the Southern Region of New Zealand, 2020

    Authors: Alyson Craigie; Reuben McGregor; Alana Whitcombe; Lauren Carlton; David Harte; Michelle Sutherland; Matthew Parry; Erasmus Smit; Gary McAuliffe; James Ussher; Nicole Moreland; Susan Jack; Arlo Upton; Danielle Skinner; Ken Hirata; Sungjun Beck; Aaron F Carlin; Alex E. Clark; Laura Berreta; Daniel Maneval; Felix Frueh; Brett L Hurst; Hong Wang; Klaudia I Kocurek; Frank M Raushel; Jair L. Siqueira-Neto; Thomas D Meek; James H McKerrow

    doi:10.1101/2020.10.20.20215616 Date: 2020-10-23 Source: medRxiv

    Background: During New Zealand's first outbreak in early 2020 the Southern Region had the highest per capita SARS-CoV-2 infection MESHD rate. PCR testing was initially limited by a narrow case definition and limited laboratory capacity, so cases may have been missed. Objectives: To evaluate the Abbott SARS-CoV-2 MESHD IgG nucleocapsid assay, alongside spike-based assays, and to determine the frequency of antibodies SERO among PCR-confirmed and probable cases, contacts, and higher risk individuals in the Southern Region of NZ. Study design: Pre-pandemic sera (n=300) were used to establish assay specificity and sera from PCR-confirmed SARS-CoV-2 patients (n=78) to establish sensitivity SERO. For prevalence SERO analysis, all samples (n=1214) were tested on the Abbott assay, and all PCR- confirmed cases TRANS (n=78), probable cases (n=9), and higher risk individuals with grey-zone (n=14) or positive results (n=11) were tested on four additional SARS-CoV-2 serological assays SERO. Results: The median time from infection MESHD onset to serum SERO collection for PCR- confirmed cases TRANS was 14 weeks (range 11-17 weeks). The Abbott assay demonstrated a specificity of 99.7% (95% CI, 98.2%-99.99%) and a sensitivity SERO of 76.9% (95% CI, 66.0%-85.7%). Spike-based assays demonstrated superior sensitivity SERO ranging 89.7-94.9%. Nine previously undiagnosed sero-positive individuals were identified, and all had epidemiological risk factors. Conclusions: Spike-based assays demonstrated higher sensitivity SERO than the Abbott IgG assay, likely due to temporal differences in antibody SERO persistence. No unexpected SARS-CoV-2 infections MESHD were found in the Southern region of NZ, supporting the elimination status of the country at the time this study was conducted.

    Emergency Response for Evaluating SARS-CoV-2 Immune Status, Seroprevalence SERO and Convalescent Plasma SERO in Argentina

    Authors: Diego Ojeda; Maria Mora Gonzalez Lopez Ledesma; Horacio Palleres; Guadalupe Costa Navarro; Lautaro Sanchez; Beatriz Perazzi; Sergio Villordo; Diego Alvarez; - BioBanco Working Group; Marcela Echavarria; Kasopefoluwa Y. Oguntuyo; Christian Stevens; Benhur Lee; Jorge Carradori; Julio Caramelo; Marcelo Yanovsky; Andrea Gamarnik; Bart N Lambrecht; Lynda Coughlan; Adolfo Garcia-Sastre; Bruno G De Geest; Michael Schotsaert; Marion Yger; Bertrand Degos; Louise-Laure Mariani; Christophe Bouche; Nathalie Dzierzynski; Bruno Oquendo; Flora Ketz; An-Hung Nguyen; Aurelie Kas; Jean-Yves Delattre; Jean-Christophe Corvol

    doi:10.1101/2020.10.21.20216960 Date: 2020-10-23 Source: medRxiv

    We report the emergency development and application of a robust serologic test SERO to evaluate acute and convalescent antibody SERO responses to SARS-CoV-2 in Argentina. The assays, COVIDAR IgG and IgM, which were produced and provided for free to health authorities, private and public health institutions and nursing homes, use a combination of a trimer stabilized spike protein and the receptor binding domain (RBD) in a single enzyme-linked immunosorbent assay SERO ( ELISA SERO) plate. Over half million tests have already been distributed to detect and quantify antibodies SERO for multiple purposes, including assessment of immune responses in hospitalized patients and large seroprevalence SERO studies in neighborhoods, slums and health care workers, which resulted in a powerful tool for asymptomatic TRANS detection and policy making in the country. Analysis of antibody SERO levels and longitudinal studies of symptomatic and asymptomatic TRANS SARS-CoV-2 infections MESHD in over one thousand patient samples provided insightful information about IgM and IgG seroconversion time and kinetics, and IgM waning profiles. At least 35% of patients showed seroconversion within 7 days, and 95% within 45 days of symptoms onset TRANS, with simultaneous or close sequential IgM and IgG detection. Longitudinal studies of asymptomatic TRANS cases showed a wide range of antibody SERO responses with median levels below those observed in symptomatic patients. Regarding convalescent plasma SERO applications, a protocol was standardized for the assessment of end point IgG antibody SERO titers with COVIDAR with more than 500 plasma SERO donors. The protocol showed a positive correlation with neutralizing antibody SERO titers, and was used to assess antibody SERO titers for clinical trials and therapies across the country. Here, we demonstrate the importance of providing a robust and specific serologic assay for generating new information about antibody SERO kinetics in infected individuals and mitigation policies to cope with pandemic needs.

    Early use of nitazoxanide in mild Covid-19 disease: randomized, placebo-controlled trial

    Authors: Patricia Rieken Macedo Rocco; Pedro Leme Silva; Fernanda Ferreira Cruz; Marco Antonio C.M. Junior; Paulo Fernando Guimaraes Morando Marzocchi Tierno; Marcos de Assis Moura; Luis Frederico Gerbase De Oliveira; Cristiano Cleidson Lima; Ezequiel Aparecido Dos Santos; Walter Freitas Junior; Ana Paula Salles Moura Fernandes; Kleber Gomes Franchini; Erick Magri; Nara Franzin de Moraes; Jose Mario de Jesus Goncalves; Melanie Nogueira Carbonieri; Ivonise Sampaio Dos Santos; Natalia de Fatima Paes; Paula Veronica Martini Maciel; Raissa Prado Rocha; Alex Fiorini de Carvalho; Pedro Augusto Alves; Jose Luiz Proenca Modena; Artur Torres Cordeiro; Daniela Barreto Barbose Trivella; Rafael Elias Marques; Ronir R Luiz; Paolo Pelosi; Jose Roberto Lapa e Silva

    doi:10.1101/2020.10.21.20217208 Date: 2020-10-23 Source: medRxiv

    The antiparasitic drug nitazoxanide is widely available and exerts broad-spectrum antiviral activity in vitro. However, there is no evidence of its impact on SARS-CoV-2 infection MESHD. In a multicenter, randomized, double-blind, placebo-controlled trial, adult TRANS patients who presented up to 3 days after onset of Covid-19 symptoms ( dry cough MESHD cough HP, fever HP fever MESHD, and/or fatigue HP fatigue MESHD) were enrolled. After confirmation of SARS-CoV2 infection MESHD by RT-PCR on nasopharyngeal swab, patients were randomized 1:1 to receive either nitazoxanide (500 mg) or placebo, TID, for 5 days. The primary outcome was complete resolution of symptoms. Secondary outcomes were viral load, general laboratory tests, serum SERO biomarkers of inflammation MESHD, and hospitalization rate. Adverse events were also assessed. From June 8 to August 20, 2020, 1,575 patients were screened. Of these, 392 (198 placebo, 194 nitazoxanide) were analyzed. Median time from symptom onset TRANS to first dose of study drug was 5 (4-5) days. At the 5-day study visit, symptom resolution did not differ between the nitazoxanide and placebo arms. However, at the 1-week follow-up, 78% in the nitazoxanide arm and 57% in the placebo arm reported complete resolution of symptoms (p=0.048). Swabs collected were negative for SARS-CoV-2 in 29.9% of patients in the nitazoxanide arm versus 18.2% in the placebo arm (p=0.009). Viral load was also reduced after nitazoxanide compared to placebo (p=0.006). No serious adverse events were observed. In patients with mild Covid-19, symptom resolution did not differ between the nitazoxanide and placebo groups after 5 days of therapy. However, early nitazoxanide therapy was safe and reduced viral load significantly.

    Clinical correlations of SARS-CoV-2 antibody SERO responses in patients with COVID-19 infection MESHD

    Authors: Mia DeSimone; Daimon P Simmons; Nicole Tolan; Stacy Melanson; Athena Petrides; Milenko Tanasijevic; Peter Schur; Jill Hakim; Keirstinne Turcios; Lee Atkinson-McEvoy; Raphael Hirsch; Roberta L Keller; Theodore Ruel; Auritte Cohen-Ross; Araceli Leon; Naomi Bardach; Aaron F Carlin; Alex E. Clark; Laura Berreta; Daniel Maneval; Felix Frueh; Brett L Hurst; Hong Wang; Klaudia I Kocurek; Frank M Raushel; Jair L. Siqueira-Neto; Thomas D Meek; James H McKerrow

    doi:10.1101/2020.10.22.20213207 Date: 2020-10-23 Source: medRxiv

    Coronavirus disease 19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2). Understanding the clinical correlations of antibodies SERO produced by infected individuals will be critical for incorporating antibody SERO results into clinical management. This study was an observational cohort study to evaluate antibody SERO responses in individuals with PCR-confirmed COVID-19, including 48 hospitalized patients diagnosed with COVID-19 by real-time polymerase chain reaction (RT-PCR) at a large tertiary care medical center. Serum samples SERO were obtained from patients at various time points during the disease course and tested for IgM and IgG antibodies SERO against SARS-CoV-2. Medical records were reviewed, and antibody SERO levels were compared with clinical and laboratory findings. Patients did not have high levels of antibodies SERO within one week of symptoms, but most had detectable IgM and IgG antibodies SERO between 8 and 29 days after onset of symptoms TRANS. Some individuals did not develop measurable levels of IgM or IgG antibodies SERO. IgM antibodies SERO were associated with elevated ALT, but there were no other significant associations. We did not observe significant associations of SARS-CoV-2 antibodies SERO with clinical outcomes, including intubation and death MESHD. SARS-CoV-2 IgM MESHD IgM and IgG antibodies SERO were unlikely to be detected in the first week of infection or in severely HP infection or in severely MESHD immunocompromised individuals. Although we did not observe associations with clinical outcomes, IgM antibodies SERO were associated with higher ALT levels. Antibody SERO production reflects the virus-specific immune response, which is important for immunity but also drives pathology, and antibody SERO levels may be important for guiding treatment of individuals with COVID-19.

    Prevalence SERO of antibodies to SARS-CoV-2 SERO in healthy blood SERO donors in New York

    Authors: Kathy Kamath; Elisabeth Baum-Jones; Gregory Jordan; Winston Haynes; Rebecca Waitz; John Shon; Steve Kujawa; Lyn Fitzgibbons; Debra Kessler; Larry L Luchsinger; - Yale IMPACT Team; Patrick Daugherty; Shershah Assadullah; Matthew Leung; Aisling O'Neill; Chhaya Popat; Radhika Kumar; Thomas J Humphries; Rebecca Talbutt; Sarika Raghunath; Philip L Molyneaux; Miriam Schechter; Jeremy Lowe; Andrew Barlow

    doi:10.1101/2020.10.19.20215368 Date: 2020-10-21 Source: medRxiv

    ABSTRACT Despite the high level of morbidity and mortality worldwide, there is increasing evidence for asymptomatic TRANS carriers TRANS of the novel coronavirus SARS-CoV-2. We analyzed blood SERO specimens from 1,559 healthy blood SERO donors, collected in the greater New York metropolitan area between the months of March and July 2020 for antibodies to SARS-CoV-2 SERO virus. Using our proprietary technology, SERA ( Serum SERO Epitope Repertoire Analysis), we observed a significant increase in SARS-CoV-2 seropositivity rates over the four-month period, from 0% [95% CI: 0 - 1.5%] (March) to 11.6% [6.0 - 21.2%] (July). Follow-up ELISA SERO tests using S1 and nucleocapsid viral proteins confirmed most of these results. Our findings are consistent with seroprevalence SERO studies within the region and with reports that SARS-COV-2 infections MESHD can be asymptomatic TRANS or cause only mild symptoms. IMPORTANCE The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has caused vast morbidity and mortality worldwide, yet several studies indicate that there may be a significant number of infected people MESHD who are asymptomatic TRANS or exhibit mild symptoms. In this study, samples were collected from healthy blood SERO donors in a region of rapidly increasing disease burden (New York metropolitan area) and we hypothesized that a subset would be seropositive to SARS-CoV-2. People who experienced mild or no symptoms during SARS-CoV-2 infection MESHD may represent a source for convalescent plasma SERO donors.

    High-throughput detection of antibodies SERO targeting the SARS-CoV-2 Spike MESHD in longitudinal convalescent plasma SERO samples

    Authors: Sai Priya Anand; Jeremie Prevost; Jonathan Richard; Josee Perreault; Tony Tremblay; Mathieu Drouin; Marie-Josee Fournier; Antoine Lewin; Renee Bazin; Andres Finzi; Daniel Hurdiss; Olalekan Daramola; Frank Grosveld; Frank van Kuppeveld; Bart Haagmans; Luis Enjuanes; Dubravka Drabek; Berend-Jan Bosch; Gabriel Umaji Oka; Natalia Fernanda Bueno; Fausto K Ferraris; Mariana TQ de Magalhaes; Renata J Medeiros; Juliana MM Gomes; Mara Souza Junqueira; Katia Conceicao; Leticia G. Pontes; Antonio Condino Neto; Andrea C Perez; Leonardo G Barcellos; Jose Dias Correa Junior; Erick Gustavo Dorlass; Niels OS Camara; Edison Luiz Durigon; Fernando Q Cunha; Rafael H Nobrega; Glaucia M Machado-Santelli; Chuck S Farah; Flavio P Veras; Jorge Galindo-Villegas; Leticia Costa-Lotufo; Thiago M Cunha; Roger Chammas; Luciani R. Carvalho; Cristiane R. Guzzo; Ives Charlie-Silva

    doi:10.1101/2020.10.20.346783 Date: 2020-10-20 Source: bioRxiv

    Background: The SARS-CoV-2 virus is the cause of the ongoing coronavirus disease MESHD 2019 (COVID-19) pandemic, infecting millions of people and causing more than a million deaths. The SARS-CoV-2 Spike glycoproteins mediate viral entry and represent the main target for antibody SERO responses. Humoral responses were shown to be important for preventing and controlling infection by coronaviruses. A promising approach to reduce the severity of COVID-19 is the transfusion of convalescent plasma SERO. However, longitudinal studies revealed that the level of antibodies SERO targeting the receptor-binding domain (RBD) of the SARS-CoV-2 Spike declines MESHD rapidly after the resolution of the infection MESHD. Study Design and Methods: To extend this observation beyond the RBD domain, we performed a longitudinal analysis of the persistence of antibodies SERO targeting the full-length SARS-CoV-2 Spike in the plasma SERO from 15 convalescent donors. We generated a 293T cell line constitutively expressing the SARS-CoV-2 Spike and used it to develop a high-throughput flow cytometry-based assay to detect SARS-CoV-2 Spike specific antibodies SERO in the plasma SERO of convalescent donors. Results and Conclusion: We found that the level of antibodies SERO targeting the full-length SARS-CoV-2 Spike declines MESHD gradually after the resolution of the infection MESHD. This decline was not related to the number of donations, but strongly correlated with the decline of RBD-specific antibodies SERO and the number of days post- symptom onset TRANS. These findings help to better understand the decline of humoral responses against the SARS-CoV-2 Spike MESHD and provide important information on when to collect plasma SERO after recovery from active infection for convalescent plasma SERO transfusion.

    Intravenous Mesenchymal Stem Cells in Extracorporeal Oxygenation Patients with Severe COVID-19 Acute Respiratory Distress Syndrome MESHD Respiratory Distress HP Syndrome

    Authors: Sunjay Kaushal; Aisha Khan; Kristopher Deatrick; Derek K Ng; Abigail Snyder; Aakash Shah; Lina V Caceres; Ketty Bacallao; Melania Bembea; Allen Everett; Jie Zhu; David Kaczorowski; Ronson Madathil; Ali Tabatabai; Geoffrey Rosenthal; Adriana Brooks; Bangon Longsomboon; Rachana Mishra; Progyaparamita Saha; Yvenie Desire; Russell Saltzman; Kim G Hankey; Sixto A Arias; Folusakin Ayoade; Jairo A. Tovar; Rejane Lamazares; Hayley B Gershengorn; Fontaine J Magali; Matthias Loebe; Kristin Mullins; Muthukumar Gunasekaran; Vela Karakeshishyan; Dushyantha T Jayaweera; Anthony Atala; Ali Ghodsizad; Joshua M Hare

    doi:10.1101/2020.10.15.20122523 Date: 2020-10-20 Source: medRxiv

    Background: There is an ongoing critical need to improve therapeutic strategies for COVID-19 pneumonia HP pneumonia MESHD, particularly in the most severely affected patients. Adult TRANS mesenchymal stem cell (MSC) infusions have the potential to benefit critically ill MESHD patients with acute respiratory syndrome SARS-COV-2 infection MESHD, but clinical data supporting efficacy are lacking. Methods: We conducted a case-control study of critically ill MESHD patients with laboratory-confirmed COVID-19, severe acute respiratory distress HP respiratory distress MESHD syndrome ( ARDS MESHD). To evaluate clinical responsiveness in the most critically ill patient we examined outcomes in a sub-group of those requiring extracorporeal membrane oxygenation (ECMO) support. Patients (n=9) were administered with up to 3 infusions of intravenous (IV) MSCs and compared to a local ECMO control group (n=31). The primary outcome was safety, and the secondary outcomes were all-cause mortality (or rate of hospital discharge), cytokine levels, and viral clearance. Findings: MSC infusions (12 patients) were well tolerated and no side effects occurred. Of ECMO patients receiving MSC infusions, 2 out of 9 died (22.2%; 95%CI: 2.8%, 60.0%) compared with a mortality of 15 of 31 (48.4%; 95%CI: 30.2%, 66.9%; p = 0.25) in the ECMO control group. Isolated plasma SERO exosomes containing the SARS-COV-2 Spike protein decreased after MSC infusions between day 14 or 21 after administration (p=0.003 and p=0.005, respectively) and was associated with a decrease in COVID-19 IgG Spike protein titer at same time points (p = 0.006 and p=0.007, respectively). Control ECMO patients receiving convalescent plasma SERO did not clear COVID-19 IgG over the same time frame. Interpretation: Together these findings suggest that MSC IV infusion is well tolerated in patients with a broad range of severity including the most severe COVID-19 ARDS requiring ECMO. These data also raise the possibility that MSCs, in addition to exerting an immunomodulatory effect, contribute to viral clearance and strongly support the conduct of randomized placebo-controlled trial.

    Impact of clade specific mutations on structural fidelity of SARS-CoV-2 proteins

    Authors: Souradip Basu; Suparba Mukhopadhyay; Rajdeep Das; Sarmishta Mukhopadhyay; Pankaj Kumar Singh; Arun C. Habermann; Taylor S. Adams; Jonas C. Schupp; Sergio Poli; Lance M. Peter; Chase J. Taylor; Jessica B. Blackburn; Bradley W. Richmond; Andrew G. Nicholson; Doris Rassl; William A. Wallace; Ivan O. Rosas; R. Gisli Jenkins; Naftali Kaminski; Jonathan A. Kropski; Nicholas E. Banovich; - Human Cell Atlas Lung Biological Network

    doi:10.1101/2020.10.20.347021 Date: 2020-10-20 Source: bioRxiv

    The SARS-CoV-2 is a positive stranded RNA virus with a genome size of ~29.9 kilobase pairs which spans 29 open reading frames. Studies have revealed that the genome encodes about 16 non-structural proteins (nsp), four structural proteins, and six or seven accessory proteins. Based on prevalent knowledge on SARS-CoV MESHD and other coronaviruses, functions have been assigned for majority of the proteins. While, researchers across the globe are engrossed in identifying a potential pharmacological intervention to control the viral outbreak, none of the work has come up with new antiviral drugs or vaccines yet. One possible approach that has shown some positive results is by treating infected MESHD patients with the plasma SERO collected from convalescent COVID-19 patients. Several vaccines around the world have entered their final trial phase in humans and we expect that these will in time be available for application to worldwide population to combat the disease. In this work we analyse the effect of prevalent mutations in the major pathogenesis related proteins of SARS-COV2 and attempt to pinpoint the effects of those mutations on the structural stability of the proteins. Our observations and analysis direct us to identify that all the major mutations have a negative impact in context of stability of the viral proteins under study and the mutant proteins suffer both structural and functional alterations as a result of the mutations. Our binary scoring scheme identifies L84S mutation in ORF8 as the most disruptive of the mutations under study. We believe that, the virus is under the influence of an evolutionary phenomenon similar to Muller s ratchet where the continuous accumulation of these mutations is making the virus less virulent which may also explain the reduction in fatality rates worldwide. Keywords: SARS-COV2, Covid19, Mutations, Structural Analysis

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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