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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

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    Identification of SARS-CoV-2-specific immune alterations in acutely ill patients

    Authors: Rose-Marie Rebillard; Marc Charabati; Camille Grasmuck; Abdelali Filali-Mouhim; Olivier Tastet; Nathalie Brassard; Audrey Daigneault; Lyne Bourbonniere; Renaud Balthazard; Ana Carmena Moratalla; Yves Carpentier Solorio; Negar Farzam-kia; Antoine Philippe Fournier; Elizabeth Gowing; Helene Jamann; Florent Lemaitre; Victoria Hannah Mamane; Karine Thai; Jean-Franois Cailhier; Nicolas Chomont; Andres Finzi; Michael Chasse; Madeleine Durand; Nathalie Arbour; Daniel E Kaufmann; Alexandre Prat; Catherine Larochelle

    doi:10.1101/2020.12.21.20248642 Date: 2020-12-22 Source: medRxiv

    Dysregulated immune profiles have been described in symptomatic SARS-CoV-2-infected MESHD patients. Whether the reported immune alterations are specific to SARS-CoV-2 infection MESHD or also triggered by other acute illnesses remains unclear. We performed flow cytometry analysis on fresh peripheral blood from a consecutive cohort of i) patients hospitalized with acute SARS-CoV-2 infection MESHD; ii) patients of comparable age/sex hospitalized for other acute disease MESHD (SARS-CoV-2 negative); and iii) healthy controls. Using both data-driven and hypothesis-driven analyses, we found several dysregulations in immune cell subsets (e.g. decreased proportion of T cells) that are similarly associated with acute SARS-CoV-2 infection MESHD and non- COVID-19 MESHD related acute illnesses. In contrast, we identified specific differences in myeloid and lymphocyte subsets that are associated with SARS-CoV-2 status (e.g. elevated proportion of ICAM-1 HGNC+ mature/activated neutrophils, ALCAM HGNC+ monocytes, and CD38 HGNC+CD8+ T cells). A subset of SARS-CoV-2-specific immune alterations correlated with disease severity, disease outcome at 30 days and mortality. Our data provides novel understanding of the immune dysregulation that are specifically associated with SARS-CoV-2 infection MESHD among acute care hospitalized patients. Our study lays the foundation for the development of specific biomarkers to stratify SARS-CoV-2+ patients at risk of unfavorable outcome and uncover novel candidate molecules to investigate from a therapeutic perspective.

    Suboptimal SARS-CoV-2-specific CD8 HGNC+ T-cell response associated with the prominent HLA-A HGNC*02:01 phenotype

    Authors: Jennifer R Habel; Thi H O Nguyen; Carolien E van de Sandt; Jennifer A Juno; Priyanka Chaurasia; Kathleen Wragg; Marios Koutsakos; Luca Hensen; Brendon Chua; Wuji Zhang; Hyon Xhi Tan; Katie L Flanagan; Denise Doolan; Joseph Torresi; Weisan Chen; Linda Wakim; Allen Cheng; Jan Petersen; Jamie Rossjohn; Adam K Wheatley; Stephen Kent; Louise Rowntree; Katherine Kedzierska

    doi:10.1101/2020.08.17.20176370 Date: 2020-08-19 Source: medRxiv

    An improved understanding of human T-cell-mediated immunity in COVID-19 MESHD is important if we are to optimize therapeutic and vaccine strategies. Experience with influenza shows that infection primes CD8 HGNC+ T-cell memory to shared peptides presented by common HLA types like HLA-A2. Following re-infection, cross-reactive CD8 HGNC+ T-cells enhance recovery and diminish clinical severity. Stimulating peripheral blood mononuclear cells from COVID-19 MESHD convalescent patients with overlapping peptides from SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD, Nucleocapsid and Membrane proteins led to the clonal expansion of SARS-CoV-2-specific CD8 HGNC+ and CD4 HGNC+ T-cells in vitro, with CD4 HGNC+ sets being typically robust. For CD8 HGNC+ T-cells taken directly ex vivo, we identified two HLA-A HGNC*02:01-restricted SARS-CoV-2 epitopes, A2/S269-277 and A2/Orf1ab3183-3191. Using peptide-HLA tetramer enrichment, direct ex vivo assessment of the A2/S269+ CD8 HGNC+ and A2/Orf1ab3183+ CD8 HGNC+ populations indicated that the more prominent A2/S269+ CD8 HGNC+ set was detected at comparable frequency (1.3x10-5) in acute and convalescent HLA-A HGNC*02:01+ patients. But, while the numbers were higher than those found in uninfected HLA-A HGNC*02:01+ donors (2.5x10-6), they were low when compared with frequencies for influenza-specific (A2/M158) and EBV-specific (A2/BMLF1280) (1.38x10-4) populations. Phenotypic analysis ex vivo of A2/S269+ CD8 HGNC+ T-cells from COVID-19 MESHD convalescents showed that A2/S269+ CD8 HGNC+ T-cells were predominantly negative for the CD38 HGNC, HLA-DR, PD-1 HGNC and CD71 HGNC activation markers, although the majority of total CD8 HGNC+ T-cells were granzyme and/or perforin-positive. Furthermore, the bias towards naive, stem cell memory and central memory A2/S269+ CD8 HGNC+ T-cells rather than effector memory populations suggests that SARS-CoV2 infection MESHD may be compromising CD8 HGNC+ T-cell activation. Priming with an appropriate vaccine may thus have great value for optimizing protective CD8 HGNC+ T-cell immunity in COVID-19 MESHD.

    Presence of SARS-CoV-2 reactive T cells in COVID-19 MESHD patients and healthy donors

    Authors: Julian Braun; Lucie Loyal; Marco Frentsch; Daniel Wendisch; Philipp Georg; Florian Kurth; Stefan Hippenstiel; Manuela Dingeldey; Beate Kruse; Florent Fauchere; Emre Baysal; Maike Mangold; Larissa Henze; Roland Lauster; Marcus Mall; Kirsten Beyer; Jobst Roehmel; Juergen Schmitz; Stefan Miltenyi; Marcel A Mueller; Martin Witzenrath; Norbert Suttorp; Florian Kern; Ulf Reimer; Holger Wenschuh; Christian Drosten; Victor M Corman; Claudia Giesecke-Thiel; Leif-Erik Sander; Andreas Thiel

    doi:10.1101/2020.04.17.20061440 Date: 2020-04-22 Source: medRxiv

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a rapidly unfolding pandemic, overwhelming health care systems worldwide1. Clinical manifestations of Corona-virus-disease 2019 ( COVID-19 MESHD) vary broadly, ranging from asymptomatic infection to acute respiratory failure MESHD and death2, yet the underlying physiological conditions and mechanisms for this high variability are still unknown. Also, the role of host immune responses in viral clearance and its involvement in pathogenesis remains unresolved. For SARS-CoV MESHD (2002/03), however, CD4+ T cell responses are generally associated with positive outcomes3,4, while cellular immune responses to SARS-CoV-2 have not yet been investigated. Here we describe an assay that allows direct detection and characterization of SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN glycoprotein (S PROTEIN)-reactive CD4+ T cells in peripheral blood. We demonstrate the presence of S-reactive CD4+ T cells in 83% of COVID-19 MESHD patients, as well as in 34% of SARS-CoV-2 seronegative healthy donors, albeit at lower frequencies. Strikingly, in COVID-19 MESHD patients S-reactive CD4+ T cells equally targeted both N-terminal and C-terminal parts of S whereas in healthy donors S-reactive CD4+ T cells reacted almost exclusively to the Cterminal part that is a) characterized by higher homology to spike glycoprotein PROTEIN of human endemic "common cold" coronaviruses, and b) contains the S2 subunit of S with the cytoplasmic peptide (CP), the fusion peptide (FP), and the transmembrane domain (TM) but not the receptor-binding domain (RBD). S-reactive CD4+ T cells from COVID-19 MESHD patients were further distinct to those from healthy donors as they co-expressed higher levels of CD38 HGNC and HLA-DR, indicating their recent in vivo activation. Our study is the first to directly measure SARS-CoV-2-reactive T cell responses providing critical tools for large scale testing, in depth epitope MESHD mapping and characterization of potential cross-reactive cellular immunity to SARS-CoV-2. The presence of pre-existing SARS-CoV-2-reactive T cells in healthy donors is of high interest but larger scale prospective cohort studies are needed to assess whether their presence is a correlate of protection or pathology. Results of such studies will be key for a mechanistic understanding of the SARS-CoV-2 pandemic, adaptation of containment methods and to support vaccine development.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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