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

Patients with COVID-19 show varying severity of the disease ranging from asymptomatic to requiring intensive care. Although 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 patients with COVID-19. We use high-throughput sequencing of bulk and plasma B-cells collected over multiple time points during infection to characterize signatures of the B-cell response to SARS-CoV-2 in 19 patients. Using principled statistical approaches, we can associate differential features of BCRs with different disease severity. We identify 38 significantly expanded clonal lineages shared among patients 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 patients. Our results provide important insights for the development of rational therapies and vaccines against COVID-19.