Summary 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. Graphical abstract Highlights • Analysis of B cell repertoires with SARS-CoV-2 epitope-sorted B cell receptors • Differential sequence features of B cell receptors are associated with disease severity • Expansion of B cell clonal lineages in response to SARS-CoV-2 • Shared B cell receptors emerge with cross-reactivity to SARS-CoV-1 and SARS-CoV-2 It is unclear how the dynamics of the humoral immune response to SARS-CoV-2 vary across individuals with different disease severity. Montague et al. develop a principled statistical approach based on time-course, high-throughput B cell repertoire sequences to identify shared, expanding, rare clonal B cell lineages as candidates for responses specific to SARS-CoV-2.
【저자키워드】 COVID-19, SARS-CoV-2, antibody, cross-reactivity, B cell repertoires, BCR selection, BCR sharing, B cell clonal expansion, 【초록키워드】 Vaccine, coronavirus, therapy, intensive care, severity, disease severity, monoclonal antibody, Sequencing, Infection, SARS-CoV-1, B cell, Asymptomatic, response, Lineage, 2019 coronavirus disease, humoral immune response, receptor, expansion, single-cell, SARS-CoV-2 epitopes, BCR, B cell receptor, B cell response, acute respiratory syndrome, Abstract, approaches, individual, sequence, candidate, approach, feature, statistical, identify, lack, collected, develop, significantly, the disease, individuals, reactivity, individuals with COVID-19, plasma B cell, 【제목키워드】 severity, Dynamics, B cell, response, Patient, cross-reactive,