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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (1492)

ProteinN (428)

NSP5 (315)

ComplexRdRp (187)

ProteinE (102)


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SARS-CoV-2 Proteins
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    Machine Learning Identifies Ponatinib as a Potent Inhibitor of SARS-CoV2-induced Cytokine Storm

    Authors: Marina Chan; Siddharth Vijay; M. Juliana McElrath; Eric C Holland; Taranjit S Gujral

    doi:10.1101/2021.04.07.438871 Date: 2021-04-09 Source: bioRxiv

    Although 15-20% of COVID-19 MESHD patients experience hyper-inflammation MESHD induced by massive cytokine production, cellular triggers of this process and strategies to target them remain poorly understood. Here, we show that the N-terminal domain ( NTD HGNC) of the spike protein PROTEIN from the SARS-CoV-2 and emerging variants B1.1.7 and B.1.351 substantially induces multiple inflammatory molecules in human monocytes and PBMCs. Further, we identified several protein kinases, including JAK1 HGNC, EPHA7 HGNC, IRAK1 HGNC, MAPK12 HGNC, and MAP3K8 HGNC, as essential downstream mediators of NTD HGNC-induced cytokine release. Additionally, we found that the FDA-approved, multi-kinase inhibitor Ponatinib is a potent inhibitor of the NTD HGNC-mediated cytokine storm. Taken together, we propose that agents targeting multiple kinases required for the SARS-CoV-2-mediated cytokine storm, such as Ponatinib, may represent an attractive therapeutic option for treating moderate to severe COVID-19 MESHD.

    An extended SEIARD model for COVID-19 MESHD vaccination in Mexico: analysis and forecast

    Authors: Ángel G. C. Pérez; David Adeyemi Oluyori

    doi:10.1101/2021.04.06.21255039 Date: 2021-04-09 Source: medRxiv

    In this study, we propose and analyze an extended SEIARD model with vaccination. We compute the control reproduction number Rc of our model and study the stability of equilibria. We show that the set of disease-free equilibria is locally asymptotically stable when Rc<1 HGNC and unstable when Rc>1, and we provide a sufficient condition for its global stability. Furthermore, we perform numerical simulations using the reported data of COVID-19 MESHD infections and vaccination in Mexico to study the impact of different vaccination, transmission and efficacy rates on the dynamics of the disease.

    The demographic and geographic impact of the COVID pandemic in Bulgaria and Eastern Europe in 2020

    Authors: Antoni Rangachev; Georgi Marinov; Mladen Mladenov

    doi:10.1101/2021.04.06.21254958 Date: 2021-04-09 Source: medRxiv

    Background: The COVID-19 pandemic MESHD followed a unique trajectory in Eastern Europe compared to other heavily affected regions, with most countries there only experiencing a major surge of cases and deaths towards the end of 2020 after a relatively uneventful first half of the year. However, the consequences of that surge have not received as much attention as the situation in Western countries. Bulgaria, even though it has been one of the most heavily affected countries, has been one of those neglected cases. Methods: We use mortality and mobility data from Eurostat, official governmental and other sources to examine the development and impact of the COVID-19 pandemic MESHD in Bulgaria and other European countries. Results: We find a very high level of excess mortality in Eastern European countries measured by several metrics including excess mortality rate (EMR), P-scores and potential years of life lost. By the last metric Eastern Europe emerges as the hardest hit region by the pandemic in Europe in 2020. With a record EMR at ~0.25% and a strikingly large and mostly unique to it mortality rate in the working age demographics, Bulgaria emerges as one of the most affected countries in Eastern Europe. The high excess mortality in Bulgaria correlates with insufficient intensity of testing and with delayed imposition of lockdown measures. We also find major geographic and demographic disparities within the country, with considerably lower mortality observed in major cities relative to more remote areas (likely due to disparities in the availability of medical resources). Analysis of the course of the epidemic revealed that individual mobility measures were predictive of the eventual decline in cases and deaths. However, while mobility declined as a result of the imposition of a lockdown, it already trended downwards before such measures were introduced, which resulted in a reduction of deaths independent of the effect of restrictions. Conclusions: Large excess mortality and high numbers of potential years of life lost are observed as a result of the COVID pandemic in Bulgaria, as well as in several other countries in Eastern Europe. Significant delays in the imposition of stringent mobility-reducing measures combined with a lack of medical resources likely caused a substantial loss of life, including in the working age population.

    Improved diagnosis of SARS-CoV-2 by using Nucleoprotein PROTEIN and Spike protein PROTEIN fragment 2 in quantitative dual ELISA tests

    Authors: Carolina De Marco Verissimo; Carol O'Brien; Jesus Lopez Corrales; Amber Dorey; Krystyna Cwiklinski; Richard Lalor; Jack M Doyle; Stephen Field; Claire Masterson; Eduardo Ribes Martinez; Gerry Hughes; Colm Bergin; Kieran Walshe; Bairbre McNicholas; John Laffey; John P Dalton; Colm Kerr; Sean Doyle

    doi:10.1101/2021.04.07.21255024 Date: 2021-04-09 Source: medRxiv

    The novel Coronavirus, SARS-CoV-2, is the causative agent of the 2020 worldwide coronavirus pandemic. Antibody testing is useful for diagnosing historic infections of a disease in a population. These tests are also a helpful epidemiological tool for predicting how the virus spreads in a community, relating antibody levels to immunity and for assessing herd immunity. In the present study, SARS-CoV-2 viral proteins were recombinantly produced and used to analyse serum from individuals previously exposed, or not, to SARS-CoV-2. The nucleocapsid (Npro) and Spike subunit 2 (S2Frag) proteins were identified as highly immunogenic, although responses to the former were generally greater. These two proteins were used to develop two quantitative ELISA assays that when used in combination resulted in a highly reliable diagnostic test. Npro and S2Frag-ELISAs could detect at least 10% more true positive COVID-19 MESHD cases than the commercially available ARCHITECT test (Abbott). Moreover, our quantitative ELISAs also show that specific antibodies to SARS-CoV-2 proteins tend to wane rapidly even in patients that had developed severe disease. As antibody tests complement COVID-19 MESHD diagnosis and determine population-level surveillance during this pandemic, the alternative diagnostic we present in this study could play a role in controlling the spread of the virus.

    Performance Comparison of a Flow Cytometry-based and Two Commercial Chemiluminescent Immunoassays for Detection and Quantification of Antibodies Binding to SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN Protein

    Authors: Arantxa Valdivia; Fabián Tarín; María Jesús Alcaraz; Paula Piñero; Ignacio Torres; Francisco Marco; Eliseo Albert; David Navarro

    doi:10.1101/2021.04.06.21254995 Date: 2021-04-09 Source: medRxiv

    The performance of a laboratory-developed quantitative IgG/IgA flow cytometry-based immunoassay (FCI) using Jurkat T cells stably expressing full-length native S protein PROTEIN was compared against Elecsys(R) electrochemiluminiscent (ECLIA) Anti-SARS-CoV-2 S (Roche Diagnostics, Pleasanton, CA, USA), and LIAISON(R) SARS-CoV-2 TrimericS IgG chemiluminiscent assay (CLIA) ( Diasorin S.p MESHD.a, Saluggia, IT) for detection and quantitation of SARS-CoV-2-specific antibodies. A total of 225 serum/plasma specimens from 120 acute or convalescent COVID-19 MESHD individuals were included. Overall, IgG/IgA-FCI yielded the highest number of positives (n=179), followed by IgA-FCI (n=177), Roche ECLIA (n=175), IgG-FCI (n=172) and Diasorin CLIA (n=154). Positive percent agreement between FCI and compared immunoassays was highest for Roche ECLIA, ranging from 96.1% (IgG/IgA-FCI) to 97.7% (IgG-FCI), whereas negative percent agreement was higher between FCI and Diasosin CLIA, regardless of antibody isotype. A strong correlation (Rho:0.6-0.8) was found between IgG-FCI or IgA-FCI levels and antibodies quantified by Roche ECLIA and Diasorin CLIA. The trajectory of antibody levels delineated by the different immunoassays in 22 of patients with sequential specimens (>=3) was frequently discordant, with the exception of IgG and IgA determined by FCI assay and to a lesser extent antibodies quantified by Roche ECLIA and Diasorin CLIA. The data suggest that FCI may outperform Roche ECLIA and Diasorin CLIA in terms of clinical sensitivity for serological diagnosis of SARS-CoV-2 infection MESHD.

    Correcting COVID-19 MESHD PCR Prevalence for False Positives in the Presence of Vaccination Immunity

    Authors: Michael Halem

    doi:10.1101/2021.04.06.21255029 Date: 2021-04-09 Source: medRxiv

    Many public health authority reports on COVID-19 MESHD cases confound positive test results with population prevalence. As the population prevalence approaches the PCR test false positive rate (FPR), for example during a vaccination campaign, it is necessary to adjust the the raw test results for the false positive rate. This paper provides a technique for estimating the test false positive rate and making the correction to test population prevalence in the absence of accurate and definitive specificity. Using current data providing by the Public Health England as of the most recent complete data, a false positive rate of 1.16% (95% CI 1.09 - 1.23% ) was found for the PHE PCR test for the period 1 January through 29 March 2021. During this period, the test population prevalence is decreasing, starting at a decay rate estimated as 3.0% per day (CI 2.79 - 3.14%). This rate of decay increased to an estimated 14.7% by the end of the period (CI 13.30 - 16.16%) Finally, mean test population prevalence was estimated at 14.3% (CI 13.75 - 14.87%) on 1 January and is estimated to have declined significantly to 0.06% (CI 0.00 - 0.13%). If PCR test positivity are used without the application of the false positive rate, the percent positive PCR tests will eventually "flatline" at the false positive rate, and produce a false positive bias even if test population prevalence should fall to zero.

    Evaluating and optimizing COVID-19 MESHD vaccination policies: a case study of Sweden

    Authors: Henrik Sjodin; Joacim Rocklov; Tom Britton

    doi:10.1101/2021.04.07.21255026 Date: 2021-04-09 Source: medRxiv

    We evaluate the efficiency of vaccination scenarios for COVID-19 MESHD by analysing a data-driven mathematical model. Healthcare demand and incidence are investigated for different scenarios of transmission and vaccination schemes. Our results suggest that reducing the transmission rate affected by invading virus strains, seasonality and the level of prevention, is most important. Second to this is timely vaccine deliveries and expeditious vaccination management. Postponing vaccination of antibody-positive individuals reduces also the disease burden, and once risk groups have been vaccinated, it is best to continue vaccinating in a descending age order.

    Neutralization of SARS-CoV-2 variants by convalescent and vaccinated serum

    Authors: Timothy A. Bates; Hans C Leier; Zoe L Lyski; Savannah K McBride; Felicity J Coulter; Jules B Weinstein; James R Goodman; Zhengchun Lu; Sarah A. R. Siegel; Peter Sullivan; Matt Strnad; Amanda E Brunton; David X Lee; Marcel E Curlin; William B Messer; Fikadu G Tafesse

    doi:10.1101/2021.04.04.21254881 Date: 2021-04-09 Source: medRxiv

    We tested human sera from large, demographically balanced cohorts of BNT162b2 vaccine recipients (n=51) and COVID-19 MESHD patients (n=44) for neutralizing antibodies against SARS-CoV-2 variants B.1.1.7 and B.1.351. Although the effect is more pronounced in the vaccine cohort, both B.1.1.7 and B.1.351 show significantly reduced levels of neutralization by vaccinated and convalescent sera. Age is negatively correlated with neutralization in vaccinee, and levels of variant-specific RBD antibodies are proportional to neutralizing activities.

    Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals

    Authors: Talia Kustin; Noam Harel; Uriah Finkel; Shay Perchik; Sheri Harari; Maayan Tahor; Itamar Caspi; Rachel Levy; Michael Leschinsky; Shifra Ken Dror; Galit Bergerzon; Hala Gadban; Faten Gadban; Eti Eliassian; Orit Shimron; Loulou Saleh; Haim Ben-Zvi; Doron Amichay; Anat Ben-Dor; Dana Sagas; Merav Strauss; Yonat Shemer Avni; Amit Huppert; Eldad Kepten; Ran D Balicer; Doron Nezer; Shay Ben-Shachar; Adi Stern

    doi:10.1101/2021.04.06.21254882 Date: 2021-04-09 Source: medRxiv

    The SARS-CoV-2 pandemic has been raging for over a year, creating global detrimental impact. The BNT162b2 mRNA vaccine has demonstrated high protection levels, yet apprehension exists that several variants of concerns (VOCs) can surmount the immune defenses generated by the vaccines. Neutralization assays have revealed some reduction in neutralization of VOCs B.1.1.7 and B.1.351, but the relevance of these assays in real life remains unclear. Here, we performed a case-control study that examined whether BNT162b2 vaccinees with documented SARS-CoV-2 infection MESHD were more likely to become infected with B.1.1.7 or B.1.351 compared with unvaccinated individuals. Vaccinees infected at least a week after the second dose were disproportionally infected with B.1.351 (odds ratio of 8:1). Those infected between two weeks after the first dose and one week after the second dose, were disproportionally infected by B.1.1.7 (odds ratio of 26:10), suggesting reduced vaccine effectiveness against both VOCs under different dosage/timing conditions. Nevertheless, the B.1.351 incidence in Israel to-date remains low and vaccine effectiveness remains high against B.1.1.7, among those fully vaccinated. These results overall suggest that vaccine breakthrough infection MESHD is more frequent with both VOCs, yet a combination of mass-vaccination with two doses coupled with non-pharmaceutical interventions control and contain their spread.

    Detecting Pathogen-Associated RNA via Piecewise Isothermal Testing achieving Sample-to-Result Integration

    Authors: Saptarshi Banerjee; Sujay Kumar Biswas; Nandita Kedia; Rakesh Sarkar; Aratrika De; Suvrotoa Mitra; Subhanita Roy; Aditya Bandopadhyay; Indranath Banerjee; Ritobrata Goswami; Shanta Dutta; Mamta Chawla-Sarkar; Suman Chakraborty; Arindam Mondal

    doi:10.1101/2021.04.06.21254740 Date: 2021-04-09 Source: medRxiv

    We report a novel piece-wise isothermal nucleic acid test (PINAT) for diagnosing pathogen-associated RNA that embeds an exclusive DNA-mediated specific probing reaction with the backbone of an isothermal reverse-transcription cum amplification protocol as a unified single-step procedure. This single step sample-to-result test method has been seamlessly integrated in an inexpensive, scalable, pre-programmable and portable instrument, resulting in a generic platform technology for detecting nucleic acid from a wide variety of pathogens. The test exhibited high sensitivity and specificity of detection of SARS-CoV-2 infection MESHD when assessed using 200 double-blind patient samples, conducted by the Indian Council of Medical Research (ICMR), reporting a positive and negative percent agreement of 94.6% and 98% respectively. We also established its efficacy in detecting Influenza-A virus infection MESHD, performing the diagnosis at the point of collection with uncompromised detection rigor. The envisaged trade-off between advanced laboratory-based procedures with the elegance of common rapid tests renders the innovation to be ideal for deployment in resource-limited settings towards catering the needs of the underserved.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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