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

Cell Rep. 2021 May 25;35(8):109173. doi: 10.1016/j.celrep.2021.109173. Epub 2021 May 9.


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.

Keywords: B cell clonal expansion; B cell repertoires; BCR selection; BCR sharing; COVID-19; SARS-CoV-2; antibody; cross-reactivity.

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • B-Lymphocytes / immunology*
  • COVID-19 / genetics
  • COVID-19 / immunology*
  • Cross Reactions*
  • Epitopes
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Receptors, Antigen, B-Cell / genetics*
  • Receptors, Antigen, B-Cell / immunology*
  • SARS-CoV-2 / immunology*
  • Severity of Illness Index
  • Sf9 Cells
  • Single-Cell Analysis
  • Spike Glycoprotein, Coronavirus / immunology


  • Antibodies, Viral
  • Epitopes
  • Receptors, Antigen, B-Cell
  • Spike Glycoprotein, Coronavirus