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Dynamics of B-cell repertoires and emergence of cross-reactive responses in COVID-19 patients with different disease severity.

Authors
  • Montague, Zachary1
  • Lv, Huibin2
  • Otwinowski, Jakub3
  • DeWitt, William S4, 5
  • Isacchini, Giulio3, 6
  • Yip, Garrick K2
  • Ng, Wilson W2
  • Tsang, Owen Tak-Yin7
  • Yuan, Meng8
  • Liu, Hejun8
  • Wilson, Ian A8, 9
  • Peiris, J S Malik2
  • Wu, Nicholas C10, 11, 12
  • Nourmohammad, Armita1, 3, 5
  • Mok, Chris Ka Pun2
  • 1 Department of Physics, University of Washington, 3910 15th Ave Northeast, Seattle, WA 98195, USA.
  • 2 HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. , (China)
  • 3 Max Planck Institute for Dynamics and Self-organization, Am Faßberg 17, 37077 Göttingen, Germany. , (Germany)
  • 4 Department of Genome Sciences, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, USA.
  • 5 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA.
  • 6 Laboratoire de physique de l'ecole normale supérieure (PSL University), CNRS, Sorbonne Université, and Université de Paris, 75005 Paris, France. , (France)
  • 7 Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong. , (Hong Kong SAR China)
  • 8 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • 9 The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • 10 Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
  • 11 Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
  • 12 Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Type
Published Article
Journal
medRxiv : the preprint server for health sciences
Publication Date
Apr 05, 2021
Identifiers
DOI: 10.1101/2020.07.13.20153114
PMID: 32699862
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

COVID-19 patients show varying severity of the disease ranging from asymptomatic to requiring intensive care. Although a number of SARS-CoV-2 specific monoclonal antibodies have been identified, we still lack an understanding of the overall landscape of B-cell receptor (BCR) repertoires in COVID-19 patients. Here, we used high-throughput sequencing of bulk and plasma B-cells collected over multiple time points during infection to characterize signatures of B-cell response to SARS-CoV-2 in 19 patients. Using principled statistical approaches, we determined differential features of BCRs associated with different disease severity. We identified 38 significantly expanded clonal lineages shared among patients as candidates for specific responses to SARS-CoV-2. Using single-cell sequencing, we verified reactivity of BCRs shared among individuals to SARS-CoV-2 epitopes. Moreover, we identified natural emergence of a BCR with cross-reactivity to SARS-CoV-1 and SARS-CoV-2 in a number of patients. Our results provide important insights for development of rational therapies and vaccines against COVID-19.

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