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

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

doi:10.1016/j.celrep.2021.109173

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

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Otwinowski, Jakub
Max Planck Research Group Statistical physics of evolving systems, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society;

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Isacchini, Giulio
Max Planck Research Group Statistical physics of evolving systems, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society;

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Nourmohammad, Armita
Max Planck Research Group Statistical physics of evolving systems, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society;

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Citation

Montague, Z., Lv, H., Otwinowski, J., DeWitt, W. S., Isacchini, G., Yip, G. K., et al. (2021). Dynamics of B cell repertoires and emergence of cross-reactive responses in patients with different severities of COVID-19. Cell Reports, 35: 109173. doi:10.1016/j.celrep.2021.109173.

Cite as: https://hdl.handle.net/21.11116/0000-0008-C034-4

Abstract

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 singlecell 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.