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COVID-19 patients show varying severity of the disease ranging fromasymptomatic to requiring intensive care. Although a number of SARS-CoV-2specific monoclonal antibodies have been identified, we still lack anunderstanding of the overall landscape of B-cell receptor (BCR) repertoires inCOVID-19 patients. Here, we used high-throughput sequencing of bulk and plasmaB-cells collected over multiple time points during infection to characterizesignatures of B-cell response to SARS-CoV-2 in 19 patients. Using principledstatistical approaches, we determined differential features of BCRs associatedwith different disease severity. We identified 38 significantly expanded clonallineages shared among patients as candidates for specific responses toSARS-CoV-2. Using single-cell sequencing, we verified reactivity of BCRs sharedamong individuals to SARS-CoV-2 epitopes. Moreover, we identified naturalemergence of a BCR with cross-reactivity to SARS-CoV-1 and SARS-CoV-2 in anumber of patients. Our results provide important insights for development ofrational therapies and vaccines against COVID-19.

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