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

Ian A. Wilson,William S. DeWitt,Hejun Liu,Garrick K. Yip,Armita Nourmohammad,Zachary Montague,J.S. Malik Peiris,Wilson W. Ng,Huibin Lv,Jakub Otwinowski,Giulio Isacchini,Chris Ka Pun Mok,Owen Tak-Yin Tsang,Meng Yuan,Nicholas C. Wu

doi:10.1016/j.celrep.2021.109173

Abstract

SummaryIndividuals 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.

Highlights

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the 2019 coronavirus disease (COVID-19), has spread to 223 countries and caused more than 143 million infections with a mortality rate around 2.2% (World Health Organization, 2021)
immunoglobulin G (IgG) heavy chains of B cell repertoires were sequenced by next-generation sequencing, and the statistics of the collected B cell receptor (BCR) read data from each sample are shown in Data S1
Statistical models were applied to analyze the length of the HCDR3 region, IGHV or IGHJ gene usage, and expansion and sharing of clonal lineages (Figure 1)

Summary

Introduction

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the 2019 coronavirus disease (COVID-19), has spread to 223 countries and caused more than 143 million infections with a mortality rate around 2.2% (World Health Organization, 2021). Individuals with COVID-19 show varying disease severity, ranging from asymptomatic to requiring intensive care. Shedding light on signatures of a protective immune response against SARS-CoV-2 infection can help elucidate the nature of COVID-19 and guide therapeutic agent development as well as vaccine design and assessment. Adaptive immunity is considered one of the core protective mechanisms of humans against infectious diseases.

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