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

TL;DR

This study characterizes B-cell receptor repertoires in COVID-19 patients, revealing disease severity-associated features, shared clonal lineages, and cross-reactive responses to SARS-CoV-2 and SARS-CoV-1, informing vaccine and therapy development.

Contribution

It provides a comprehensive analysis of B-cell responses in COVID-19, identifying shared clonal lineages and cross-reactive BCRs across patients with different disease severities.

Findings

Shared clonal BCR lineages among patients

Identification of cross-reactive BCRs to SARS-CoV-1 and SARS-CoV-2

BCR features associated with disease severity

Abstract

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.