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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (547)

ProteinS (185)

ComplexRdRp (33)

ProteinE (33)

ORF1ab (27)


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SARS-CoV-2 Proteins
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    T-cell receptor sequencing identifies prior SARS-CoV-2 infection MESHD and correlates with neutralizing antibody titers and disease severity

    Authors: Rebecca Elyanow; Thomas M. Snyder; Sudeb C. Dalai; Rachel M. Gittelman; Jim Boonyaratanakornkit; Anna Wald; Stacy Selke; Mark H. Wener; Chihiro Morishima; Alex L. Greninger; Michael R. Holbrook; Ian M. Kaplan; H. Jabran Zahid; Jonathan M. Carlson; Lance Baldo; Thomas Manley; Harlan S. Robins; David M. Koelle

    doi:10.1101/2021.03.19.21251426 Date: 2021-03-22 Source: medRxiv

    Measuring the adaptive immune response to SARS-CoV-2 can enable the assessment of past infection as well as protective immunity and the risk of reinfection. While neutralizing antibody (nAb) titers are one measure of protection, such assays are challenging to perform at a large scale and the longevity of the SARS-CoV-2 nAb response is not fully understood. Here, we apply a T-cell receptor (TCR) sequencing assay that can be performed on a small volume standard blood sample to assess the adaptive T-cell response to SARS-CoV-2 infection MESHD. Samples were collected from a cohort of 302 individuals recovered from COVID-19 MESHD up to 6 months after infection. Previously published findings in this cohort showed that two commercially available SARS-CoV-2 serologic assays correlate well with nAb testing. We demonstrate that the magnitude of the SARS-CoV-2-specific T-cell response strongly correlates with nAb titer, as well as clinical indicators of disease severity including hospitalization, fever MESHD, or difficulty breathing. While the depth and breadth of the T-cell response declines during convalescence, the T-cell signal remains well above background with high sensitivity up to at least 6 months following initial infection. Compared to serology tests detecting binding antibodies to SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN and nucleoprotein PROTEIN, the overall sensitivity of the TCR-based assay across the entire cohort and all timepoints was approximately 5% greater for identifying prior SARS-CoV-2 infection MESHD. Notably, the improved performance of T-cell testing compared to serology was most apparent in recovered individuals who were not hospitalized and were sampled beyond 150 days of their initial illness, suggesting that antibody testing may have reduced sensitivity in individuals who experienced less severe COVID-19 MESHD illness and at later timepoints. Finally, T-cell testing was able to identify SARS-CoV-2 infection MESHD in 68% (55/81) of convalescent samples having nAb titers below the lower limit of detection, as well as 37% (13/35) of samples testing negative by all three antibody assays. These results demonstrate the utility of a TCR-based assay as a scalable, reliable measure of past SARS-CoV-2 infection MESHD across a spectrum of disease severity. Additionally, the TCR repertoire may be useful as a surrogate for protective immunity with additive clinical value beyond serologic or nAb testing methods.

    First wastewater surveillance-based city zonation for effective COVID-19 pandemic MESHD preparedness powered by early warning: A study of Ahmedabad, India

    Authors: Manish Kumar; Madhvi Joshi; Anil V Shah; Vaibhav Srivastava; Shyamnarayan Dave

    doi:10.1101/2021.03.18.21253898 Date: 2021-03-20 Source: medRxiv

    Following the proven concept, capabilities, and limitations of detecting the RNA of Severe Acute Respiratory Coronavirus MESHD 2 (SARS-CoV-2) in wastewater, it is pertinent to understand the utility of wastewater surveillance data on various scale. In the present work, we put forward the first wastewater surveillance-based city zonation for effective COVID-19 MESHD pan-demic preparedness. A three-month data of Surveillance of Wastewater for Early Epidemic Prediction (SWEEP) was generated for the world heritage city of Ahmedabad, Gujarat, India. In this expedition, one hundred sixteen wastewater samples were analyzed to detect SARS-CoV-2 RNA, from September 3rd to November 26th, 2020. A total of 111 samples were detected with at least two out of three SARS-CoV-2 genes (N PROTEIN, ORF 1ab, and S). Monthly variation depicted a significant decline in all three genes copies in October compared to September 2020, followed by a sharp increment in November 2020. Correspondingly, the descending order of average genome concentration was: November (~10729 copies/ L) > September (~3047 copies/ L) > October (~454 copies/ L). Monthly variation of SARS-CoV-2 RNA in the wastewater samples may be ascribed to a decline of 19.3% in the total number of active cases in October 2020 and a rise of 1.82% in November 2020. Also, the monthly recovery rate of patients was 16.61, 19.31, and 15.58% in September, October, and Novem-ber 2020, respectively. The percentage change in the genome concentration was observed in the lead of 1-2 weeks with respect to the provisional figures of confirmed cases. SWEEP data-based city zonation was matched with the heat map of the overall COVID-19 MESHD infected population in Ahmedabad city, and month-wise effective RNA concentration variations are shown on the map. The results expound on the potential of WBE surveillance of COVID-19 MESHD as a city zonation tool that can be meaningfully interpreted, predicted, and propagated for community preparedness through advance identification of COVID-19 MESHD hotspots within a given city.

    Epitope-resolved serology test differentiates the clinical outcome of COVID-19 MESHD and identifies defects in antibody response in SARS-CoV-2 variants

    Authors: Courtney Voss; Sally Esmail; Xuguang Liu; Michael Knauer; Suzanne Ackloo; Tomonori Kaneko; Lori Lowes; Peter Stogios; Almagul Seitova; Ashley Hutchinson; Farhad Yusifov; Tatiana Skarina; Elena Evdokimova; Peter Loppnau; Pegah Ghiabi; Taraneh Haijian; Shanshan Zhong; Husam Abdoh; Benjamin Hedley; Vipin Bhayana; Claudio Martin; Marat Slessarev; Benjamin Chin-Yee; Douglas Fraser; Ian Chin-Yee; Shawn Li

    doi:10.1101/2021.03.16.21253716 Date: 2021-03-20 Source: medRxiv

    BACKGROUND. The role of humoral immunity in the coronavirus disease 2019 MESHD ( COVID-19 MESHD) is not fully understood owing, in large part, to the complexity of antibodies produced in response to the SARS-CoV-2 infection MESHD. There is a pressing need for serology tests to assess patient-specific antibody response and predict clinical outcome. METHODS. Using SARS-CoV-2 proteome and peptide microarrays, we screened 146 COVID-19 MESHD patients plasma samples to identify antigens and epitopes. This enabled us to develop a master epitope array and an epitope-specific agglutination assay to gauge antibody responses systematically and with high resolution. RESULTS. We identified 54 linear epitopes from the Spike (S) and Nucleocapsid (N) protein PROTEIN and showed that epitopes enabled higher resolution antibody profiling than protein antigens. Specifically, we found that antibody responses to the S(811-825), S(881-895) and N(156-170) epitopes negatively or positively correlated with clinical severity or patient survival. Moreover, we found that the P681H and S235F mutations associated with the coronavirus variant B.1.1.7 altered the specificity of the corresponding epitopes. CONCLUSIONS. Epitope-resolved antibody testing not only offers a high-resolution alternative to conventional immunoassays to delineate the complex humoral immunity to SARS-CoV-2 and differentiate between neutralizing and non-neutralizing antibodies, it may also be used as predictor of clinical outcome. The epitope peptides can be readily modified to detect antibodies against variants in both the peptide array and latex agglutination formats. FUNDING. Ontario Research Fund (ORF)- COVID-19 MESHD Rapid Research Fund, the Toronto COVID-19 MESHD Action Fund, Western University, the Lawson Health Research Institute, the London Health Sciences Foundation, and the AMOSO Innovation Fund.

    Structural basis of anti-SARS-CoV-2 activity of hydroxychloroquine: specific binding to NTD HGNC/CTD and disruption of LLPS of N protein PROTEIN

    Authors: Mei Dang; Jianxing Song

    doi:10.1101/2021.03.16.435741 Date: 2021-03-17 Source: bioRxiv

    SARS-CoV-2 is the coronavirus causing the catastrophic pandemic which already led to >120 millions of infections and >2.6 millions of deaths. Hydroxychloroquine (HCQ) has been shown to own promising potential in clinically combating SARS-CoV-2 but the underlying mechanisms still remain almost unknown. So far, all action sites are proposed on the host cells, and in particular no specific viral target protein has been experimentally identified. In this study, by use of DIC microscopy and NMR spectroscopy, for the first time we have decoded that HCQ specifically binds to both N-terminal domain ( NTD HGNC) and C-terminal domain (CTD) of SARS-CoV-2 nucleocapsid (N) protein PROTEIN to inhibit their interactions with nucleic acids (NAs), as well as to disrupt its NA-induced liquid-liquid phase separation ( LLPS MESHD) essential for the viral life cycle including the package of gRNA and N protein PROTEIN into new virions. These results suggest that HCQ may achieve its anti-SARS-CoV-2 activity by interfering in several key steps of the viral life cycle. The study not only provides a structural basis for the anti-SARS-CoV-2 activity of HCQ, but also indicates that SARS-CoV-2 N protein PROTEIN and its LLPS represent key targets for further optimization and development of anti-SARS-CoV-2 drugs.

    Multiplexed Flow Cytometric Approach for Detection of Anti-SARS-CoV-2 IgG, IgM and IgA Using Beads Covalently Coupled to the Nucleocapsid Protein PROTEIN

    Authors: Ingrid Fatima Zattoni; Luciano F. Huergo; Edileusa C. M. Gerhardt; Jeanine M. Nardin; Alexia Marques Fernandes dos Santos; Fabiane Gomes de Moraes Rego; Geraldo Picheth; Vivian Rotuno Moure; Glaucio Valdameri

    doi:10.26434/chemrxiv.14219999.v1 Date: 2021-03-17 Source: ChemRxiv

    Flow cytometry has emerged as a promising technique for detection of SARS-CoV-2 antibodies. In this study, we described a new methodology to detect simultaneously IgG, IgM and IgA of SARS-CoV-2 nucleocapsid protein PROTEIN in human serum by flow cytometry. The Nucleocapsid protein PROTEIN was covalently bound on functional beads surface applying sulfo-SMCC chemistry. BUV395 anti-IgG, BB515 anti-IgM, biotinylated anti- IgA1 HGNC/IgA2 and BV421 streptavidin were used as fluorophore conjugated secondary antibodies. Serum and antibodies reaction conditions were optimized for each antibody isotype detection and a multiplexed detection assay was developed. This new cell-free multiplex approach based on flow cytometry was able to efficiently discriminate COVID-19 MESHD negative and positive samples. The simultaneous detection of IgG, IgM and IgA showed a sensibility of 88.5-96.2% and specificity of 100%. The combined detection of antibody isotypes offers greater spectrum for detection and monitoring of COVID-19 MESHD vaccines and seroconversion. This novel strategy opens a new avenue for flow cytometry-based diagnosis.

    SARS-CoV-2 spike PROTEIN protein induces inflammation MESHD via TLR2 HGNC-dependent activation of the NF-κB pathway

    Authors: Shahanshah Khan; Mahnoush S. Shafiei; Christopher Longoria; John Schoggins; Rashmin C. Savani; Hasan Zaki

    doi:10.1101/2021.03.16.435700 Date: 2021-03-17 Source: bioRxiv

    Pathogenesis of COVID-19 MESHD is associated with a hyperinflammatory response; however, the precise mechanism of SARS-CoV-2-induced inflammation MESHD is poorly understood. Here we investigated direct inflammatory functions of major structural proteins of SARS-CoV-2. We observed that spike (S) protein PROTEIN potently induces inflammatory cytokines and chemokines including IL-6 HGNC, IL-1b HGNC, TNFa HGNC, CXCL1 HGNC, CXCL2 HGNC, and CCL2 HGNC, but not IFNs in human and mouse macrophages. No such inflammatory response was observed in response to membrane (M), envelope (E), and neucleocapsid ( N) proteins PROTEIN. When stimulated with extracellular S protein PROTEIN, human lung epithelial cells A549 also produce inflammatory cytokines and chemokines. Interestingly, epithelial cells expressing S protein PROTEIN intracellularly are non-inflammatory, but elicit an inflammatory response in macrophages when co-cultured. Biochemical studies revealed that S protein PROTEIN triggers inflammation MESHD via activation of the NF-kB pathway in a MyD88 HGNC-dependent manner. Further, such an activation of the NF-kB pathway is abrogated in Tlr2 HGNC-deficient macrophages. Consistently, administration of S protein PROTEIN induces IL-6, TNF-a, and IL-1b in wild-type, but not Tlr2-deficient mice. Together these data reveal a mechanism for the cytokine storm during SARS-CoV-2 infection MESHD and suggest that TLR2 could be a potential therapeutic target for COVID-19 MESHD.

    Longitudinal characterization of humoral and cellular immunity in hospitalized COVID-19 MESHD patients reveal immune persistence up to 9 months after infection

    Authors: John Tyler Sandberg; Renata Varnaitė; Wanda Christ; Puran Chen; Jagadeeswara Rao Muvva; Kimia T Maleki; Marina García; Majda Dzidic; Elin Folkesson; Magdalena Skagerberg; Gustaf Ahlén; Lars Frelin; Matti Sällberg; - The Karolinska COVID-19 Study Group; Lars I Eriksson; Olav Rooyackers; Anders Sönnerborg; Marcus Buggert; Niklas K Björkström; Soo Aleman; Kristoffer Strålin; Jonas Klingström; Hans-Gustaf Ljunggren; Kim Blom; Sara Gredmark-Russ

    doi:10.1101/2021.03.17.435581 Date: 2021-03-17 Source: bioRxiv

    Background: Insights into early, specific humoral and cellular responses to infection with SARS-CoV-2, as well as the persistence and magnitude of resulting immune memory is important amidst the ongoing pandemic. The combination of humoral and cellular immunity will most likely contribute to protection from reinfection or severe disease. Methods: Here, we conducted a longitudinal study on hospitalized moderate and severe COVID-19 MESHD patients from the acute phase of disease into convalescence at five- and nine-months post symptom onset. Utilizing flow cytometry, serological assays as well as B cell and T cell FluoroSpot assays, we assessed the magnitude and specificity of humoral and cellular immune memory during and after human SARS-CoV-2 infection MESHD. Findings: During acute COVID-19 MESHD, we observed an increase in germinal center activity, a substantial expansion of antibody-secreting cells, and the generation of SARS-CoV-2-neutralizing antibodies. Despite gradually decreasing antibody levels, we show persistent, neutralizing antibody titers as well as robust specific memory B cell responses and polyfunctional T cell responses at five- and nine-months after symptom onset in both moderate and severe COVID-19 MESHD patients. Long-term SARS-CoV-2 specific responses were marked by preferential targeting of spike over nucleocapsid protein PROTEIN. Conclusions: Our findings describe the initiation and, importantly, persistence of cellular and humoral SARS-CoV-2 specific immunological memory in hospitalized COVID-19 MESHD patients long after recovery, likely contributing towards protection against reinfection.

    Durability of SARS-CoV-2-specific IgG responses in saliva for up to 8 months after infection

    Authors: Pranay R. Randad; Nora Pisanic; Kate Kruczynski; Tyrone Howard; Magdielis Gregory Rivera; Kristoffer Spicer; Annukka A.R. Antar; Tristan Penson; David L. Thomas; Andrew Pekosz; Nelson Ndahiro; Lateef Aliyu; Michael J. Betenbaugh; Hannah Manley; Barbara Detrick; Morgan Katz; Sara Cosgrove; Claire Rock; Israel Zyskind; Jonathan I. Silverberg; Avi Z. Rosenberg; Priya Duggal; Yukari C. Manabe; Matthew H. Collins; Christopher D. Heaney

    doi:10.1101/2021.03.12.21252149 Date: 2021-03-15 Source: medRxiv

    We evaluated the durability of IgG responses specific to SARS-CoV-2 nucleocapsid (N PROTEIN), receptor binding domain (RBD), and spike (S) antigens in saliva up to 8 months after RT-PCR-confirmed COVID-19 MESHD using a multiplex salivary assay. We estimated a half-life of 64 days (d) (95% CI: 49, 80 d) for N, 100 d for RBD (95% CI: 58, 141 d), and 148 d (95% CI: 62, 238 d) for S IgG responses in saliva, consistent with half-life estimates previously reported in blood. Saliva can serve as an alternative to blood to monitor humoral immune responses on a large scale following natural SARS-CoV-2 infection MESHD and vaccination for surveillance and assessment of population immunity.

    An In-House ELISA for SARS-CoV-2 RBD MESHD uncovers elevatedimmune response at higher altitudes

    Authors: Rodrigo Tomas Grau; Diego Ploper; Cesar Luis Avila; Esteban Vera Pingitore; Carolina Maldonado; Silvina Chaves; Sergio Benjamin Socias; Agustin Stagnetto; Silvia Navarro; Rossana Chahla; Monica Aguilar; Conrado Llapur; Patricia Aznar; Malena Alcorta; Dardo Costas; Isolina Flores; Gabriela Apfelbaum; Dar Heinze; Raul Mostoslavsky; Gustavo Mostoslavsky; Gabriela Perdigon; Silvia Cazorla; Rosana Chehin

    doi:10.1101/2021.03.10.21252711 Date: 2021-03-12 Source: medRxiv

    The severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2) first reported in Wuhan has caused a global pandemic with dramatic health and socioeconomic consequences. The Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) associated represents a challenge for health systems that had to quickly respond developing new diagnostic and therapeutic strategies. In the present work, we developed an In House ELISA with high sensitivity (92.2 %), specificity (100%) and precision (93.9%), with an area under the ROC curve (AUC) of 0.991, rendering the assay as an excellent serological test to correctly discriminate between SARS-COv-2 infected MESHD and non-infected individuals and study population seroprevalence. Among 758 patients evaluated for SARS-CoV-2 diagnosis in the province of Tucuman, Argentina, we found a Pearson correlation coefficient of 0.5048 between antibodies elicited against the RBD and the nucleocapsid (N PROTEIN) antigen. Additionally, 33.6% of individuals diagnosed with COVID-19 MESHD displayed mild levels of RBD-IgG antibodies, while 19% of the patients showed high antibody titers. Interestingly, patients with SARS-COV-2 infection MESHD over 60 years old elicited significantly higher levels of IgG antibodies against RBD compared to younger ones, while no difference was found between women and men. Surprisingly, individuals from a high altitude village displayed statistically significant higher and longer lasting anti-RBD antibodies compared to those from a city at a lower altitude, suggesting that a hypobaric hypoxia MESHD-adapted mechanism may act as a protective factor for COVID-19 MESHD. To our knowledge, this is the first report correlating altitude with increased humoral immune response against SARS-Cov-2 infection MESHD.

    SARS-CoV-2 Serology Status Detected by Commercialized Platforms Distinguishes Previous Infection and Vaccination Adaptive Immune Responses

    Authors: Raymond T Suhandynata; Nicholas J Bevins; Jenny T Tran; Deli Huang; Melissa A Hoffman; Kyle Lund; Michael J Kelner; Ronald W McLawhon; Steven L Gonias; David Nemazee; Robert L Fitzgerald

    doi:10.1101/2021.03.10.21253299 Date: 2021-03-12 Source: medRxiv

    Background. The severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2) has infected over 110 million individuals and led to 2.5 million deaths worldwide. As more individuals are vaccinated, the clinical performance and utility of SARS-CoV-2 serology platforms needs to be evaluated. Methods. The ability of four commercial SARS-CoV-2 serology platforms to detect previous infection or vaccination were evaluated using a cohort of 53 SARS-CoV-2 PCR-positive patients, 89 SARS-CoV-2-vaccinated healthcare workers (Pfizer or Moderna), and 127 SARS-CoV-2 negative patients. Serology results were compared to a cell based SARS-CoV-2 pseudovirus (PSV) neutralizing antibodies assay. Results. The Roche S-(spike) antibody and Diazyme neutralizing antibodies (NAbs) assays detected adaptive immune response in 100.0% and 90.1% of vaccinated individuals who received two-doses of vaccine (initial and booster), respectively. The Roche N-(nucleocapsid PROTEIN) antibody assay and Diazyme IgG assay did not detect adaptive immune response in vaccinated individuals. The Diazyme Nabs assay correlated with the PSV SARS-CoV-2 MESHD ID50 neutralization titers (R2= 0.70), while correlation of the Roche S-antibody assay was weaker (R2= 0.39). Median PSV SARS-CoV-2 MESHD ID50 titers more than doubled in vaccinated individuals who received two-doses of the Moderna vaccine (ID50: 597) compared to individuals that received a single dose (ID50: 284). Conclusions. The Roche S-antibody and Diazyme NAbs assays robustly detected adaptive immune responses in SARS-CoV-2 vaccinated individuals and SARS-CoV-2 infected MESHD individuals. The Diazyme NAbs assay strongly correlates with the PSV SARS-CoV-2 MESHD NAbs in vaccinated individuals. Understanding the reactivity of commercially available serology platforms is important when distinguishing vaccination response versus natural infection.

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MeSH Disease
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SARS-CoV-2 Proteins


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