Dynamics of B-Cell Repertoires and Emergence of Cross-Reactive Responses in COVID-19 Patients with Different Disease Severity

Zachary Montague, Hejun Liu, Ian Wilson, J.S. Malik Peiris, Nicholas C. Wu, Armita Nourmohammad, Chris Ka Pun Mok, Huibin Lv, Jakub Otwinowski, William S. DeWitt, Giulio Isacchini, Garrick K. Yip, Wilson W. Ng, Owen Tak-Yin Tsang, Meng Yuan

Research output: Working paper

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.
Original languageEnglish (US)
Number of pages59
DOIs
StateSubmitted - Dec 17 2020

Publication series

NameCELL-REPORTS-D-20-06009

Keywords

  • SARS-CoV-2
  • COVID-19
  • B-cell repertoires
  • cross-reactivity

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