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      Next Generation Sequencing of T and B cell receptor repertoires from COVID-19 patients showed signatures associated with severity of disease

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          Summary

          We profiled adaptive immunity in COVID-19 patients with active infection or after recovery and created a repository of currently >14 million B and T cell receptor (BCR, TCR) sequences from blood of these patients. The B cell response showed converging IGHV3-driven BCR clusters closely associated with SARS-CoV-2 antibodies. Clonality and skewing of TCR repertoires was associated with interferon type I and III responses, early CD4+ and CD8+ T cell activation and counterregulation by the coreceptors BTLA, Tim-3, PD-1, TIGIT and CD73. Tfh, Th17-like and nonconventional (but not classical anti-viral) Th1 cell polarizations were induced. SARS-CoV-2-specific T cell responses were driven by TCR clusters shared between patients with a characteristic trajectory of clonotypes and traceability over the disease course. Our data provide fundamental insight into adaptive immunity to SARS-CoV-2 with the actively updated repository providing a resource for the scientific community urgently needed to inform therapeutic concepts and vaccine development.

          Highlights

          • Convergent B cell responses to SARS-CoV-2 epitopes are predominantly naïve

          • Shared T cell clusters emerge over disease course in recovering COVID-19 patients

          • A receptor sequence repository from COVID-19 patients is established for public use

          Abstract

          It is unclear how immune responses to Sars-CoV-2 differ in patients with mild versus severe COVID-19 disease. Schultheiß et al. define specific immune receptor sequences associated with different disease courses and established an actively updated sequence repository for public use.

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          Author and article information

          Contributors
          Journal
          Immunity
          Immunity
          Immunity
          Elsevier Inc.
          1074-7613
          1097-4180
          30 June 2020
          30 June 2020
          Affiliations
          [1 ]Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany
          [2 ]Department of Neurosurgery, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany
          [3 ]Infectious Diseases, Department of Internal Medicine II, University Hospital Frankfurt, 60596 Frankfurt am Main, Germany
          [4 ]First Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Department for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany
          [5 ]Department of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
          [6 ]Mid-German Heart Center, Department of Cardiology and Intensive Care Medicine, University Hospital, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany
          [7 ]Institute of Medical Virology, University Hospital, Goethe University Frankfurt, 60596 Frankfurt am Main, Germany; Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Branch Translational Medicine und Pharmacology, 60596 Frankfurt am Main, Germany; German Center for Infection Research (DZIF), External partner site Frankfurt, 60596 Frankfurt am Main, Germany
          Author notes
          []Lead contact: Mascha Binder, MD, Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Straße 40, 06120 Halle (Saale), Germany , Phone (+) 49-345-557-4972, Fax (+) 49-345-557-2950 E Mascha.Binder@ 123456uk-halle.de
          [#]

          These authors contributed equally.

          Article
          S1074-7613(20)30279-X
          10.1016/j.immuni.2020.06.024
          7324317
          32668194
          d5b4de24-6fb9-4fcc-a0f6-3fcb08331378
          © 2020 Elsevier Inc.

          Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

          History
          : 27 May 2020
          : 19 June 2020
          : 26 June 2020
          Categories
          Article

          Immunology
          Immunology

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