@article{e02c237f27714f10bfe6d1658a521ca4,
title = "Dynamics of B cell repertoires and emergence of cross-reactive responses in patients with different severities of COVID-19",
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 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.",
keywords = "SARS-CoV-2, COVID-19, B-cell repertoires, cross-reactivity, BCR selection, antibody, B cell clonal expansion, BCR sharing, B cell repertoires",
author = "Zachary Montague and Huibin Lv and Jakub Otwinowski and DeWitt, {William S.} and Giulio Isacchini and Yip, {Garrick K.} and Ng, {Wilson W.} and Tsang, {Owen Tak-Yin} and Meng Yuan and Hejun Liu and Ian Wilson and Peiris, {J.S. Malik} and Wu, {Nicholas C.} and Armita Nourmohammad and Mok, {Chris Ka Pun}",
note = "Funding Information: We are grateful for discussions with Maria Ruiz Ortega on selection inference in BCR repertoires. This work was supported by Deutsche Forschungsgemeinschaft grant ( SFB1310 ) on Predictability in Evolution (to A.N., Z.M., J.O., and G.I.); MPRG funding from the Max Planck Society (to A.N., Z.M., J.O., and G.I.); the Royalty Research Fund at the University of Washington (to A.N. and Z.M.); NIH NIAID F31AI150163 (to W.S.D.); a Calmette and Yersin scholarship from the Pasteur International Network Association (to H.L.); Bill and Melinda Gates Foundation OPP1170236 (to I.A.W.); a startup fund at the University of Illinois at Urbana-Champaign (to N.C.W.); the National Institutes of Health (contract HHSN272201400006C to J.S.M.P.); the National Natural Science Foundation of China (NSFC)/Research Grants Council (RGC) Joint Research Scheme ( N_HKU737/18 to C.K.P.M. and J.S.M.P.); and the Research Grants Council of the Hong Kong Special Administrative Region, China (project T11-712/19-N to J.S.M.P.). We acknowledge support from the clinicians who facilitated this study, including Drs. Wai Shing Leung, Jacky Man Chun Chan, Thomas Shiu Hong Chik, Chris Yau Chung Choi, John Yu Hong Chan, Daphne Pui-Lin Lau, and Ying Man Ho; the dedicated clinical team at the Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong; and the individuals who kindly consented to participate in this investigation. We also thank the Center for PanorOmic Sciences (CPOS), LKS Faculty of Medicine, and University of Hong Kong for support with next-generation sequencing and acknowledge use of the computational infrastructure provided by the Hyak supercomputer system funded by the Student Technology Fund (STF) at the University of Washington . Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = may,
day = "25",
doi = "10.1016/j.celrep.2021.109173",
language = "English (US)",
volume = "35",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",
}