@techreport{e02c237f27714f10bfe6d1658a521ca4,
title = "Dynamics of B-Cell Repertoires and Emergence of Cross-Reactive Responses in COVID-19 Patients with Different 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. ",
keywords = "SARS-CoV-2, COVID-19, B-cell repertoires, cross-reactivity",
author = "Zachary Montague and Hejun Liu and Ian Wilson and Peiris, {J.S. Malik} and Wu, {Nicholas C.} and Armita Nourmohammad and Mok, {Chris Ka Pun} 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",
note = "Funding: This work was supported by DFG grant (SFB1310) on Predictability in Evolution (A.N., Z.M., J.O., G.I.), the Max Planck Society through MPRG funding (A.N., Z.M., J.O., G.I.), Department of Physics at the University of Washington (A.N., Z.M.), Royalty Research Fund at the University of Washington (A.N., Z.M.), NIH NIAID F31AI150163 (WSD), Calmette and Yersin scholarship from the Pasteur International Network Association (H.L.), Bill and Melinda Gates Foundation OPP1170236 (I.A.W.), a startup fund at the University of Illinois at Urbana-Champaign (N.C.W.), US National Institutes of Health (contract no. HHSN272201400006C) (J.S.M.P), National Natural Science Foundation of China (NSFC)/Research Grants Council (RGC) Joint Research Scheme(N_HKU737/18) (C.K.P.M. and J.S.M.P) and the Research Grants Council of the Hong Kong Special Administrative Region, China (Project no. T11-712/19-N) (J.S.M.P). ",
year = "2020",
month = dec,
day = "17",
doi = "10.2139/ssrn.3751051",
language = "English (US)",
series = "CELL-REPORTS-D-20-06009",
type = "WorkingPaper",
}