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

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

Research output: Contribution to journalArticlepeer-review


Individuals with the 2019 coronavirus disease (COVID-19) show varying severity of the disease, ranging from asymptomatic to requiring intensive care. Although monoclonal antibodies specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified, we still lack an understanding of the overall landscape of B cell receptor (BCR) repertoires in individuals with COVID-19. We use high-throughput sequencing of bulk and plasma B cells collected at multiple time points during infection to characterize signatures of the B cell response to SARS-CoV-2 in 19 individuals. Using principled statistical approaches, we associate differential features of BCRs with different disease severity. We identify 38 significantly expanded clonal lineages shared among individuals as candidates for responses specific to SARS-CoV-2. Using single-cell sequencing, we verify the reactivity of BCRs shared among individuals to SARS-CoV-2 epitopes. Moreover, we identify the natural emergence of a BCR with cross-reactivity to SARS-CoV-1 and SARS-CoV-2 in some individuals. Our results provide insights important for development of rational therapies and vaccines against COVID-19.
Original languageEnglish (US)
Article number109173
JournalCell Reports
Issue number8
Early online dateMay 9 2021
StatePublished - May 25 2021


  • SARS-CoV-2
  • COVID-19
  • B-cell repertoires
  • cross-reactivity
  • BCR selection
  • antibody
  • B cell clonal expansion
  • BCR sharing
  • B cell repertoires

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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