  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.
