@article{aef0eb1752244047aed4b9fe022dde3e,
title = "Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity",
abstract = "Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4+ and CD8+ T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4+ and CD8+ T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals ≥ 65 years old. Scarcity of naive T cells was also associated with aging and poor disease outcomes. A parsimonious explanation is that coordinated CD4+ T cell, CD8+ T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.",
keywords = "CD4, CD8, CXCL10, IP-10, Spike, T cells, adaptive immunity, antibody, coronavirus, epitopes, neutralizing antibodies",
author = "{Rydyznski Moderbacher}, Carolyn and Ramirez, {Sydney I.} and Dan, {Jennifer M.} and Alba Grifoni and Hastie, {Kathryn M.} and Daniela Weiskopf and Simon Belanger and Abbott, {Robert K.} and Christina Kim and Jinyong Choi and Yu Kato and Crotty, {Eleanor G.} and Cheryl Kim and Rawlings, {Stephen A.} and Jose Mateus and Tse, {Long Ping Victor} and April Frazier and Ralph Baric and Bjoern Peters and Jason Greenbaum and {Ollmann Saphire}, Erica and Smith, {Davey M.} and Alessandro Sette and Shane Crotty",
note = "Funding Information: We would like to express our deepest thanks to the study subjects and their families for their participation and their altruistic desires to forward our scientific understanding of COVID-19 and other diseases. This study would not be possible without their generous donations. We would also like to thank LJI flow cytometry core facility, specifically Denise Hinz, for outstanding expertise, and the LJI clinical core, specifically Gina Levi RN and Brittany Schwan, for healthy donor enrollment and sample procurement. This work was funded by the NIH NIAID, United States, under awards AI142742 (Cooperative Centers for Human Immunology) (A.S. and S.C.), NIH contract Nr. 75N9301900065 (D.W. and A.S.), NIH NIAID AI100625 (R.B.), and U19 AI118626 (A.S. and B.P.). The BD FACSymphony S6 purchase was partially funded by the Bill and Melinda Gates Foundation, United States, (S.C.) and LJI Institutional Funds (S.C. and A.S.). This work was additionally supported in part by the Johnathan and Mary Tu Foundation (D.M.S.); the NIAID under K08 award AI135078 (J.M.D.), K99 award AI145762 (R.K.A.), UCSD T32s AI007036, and AI007384 Infectious Diseases Division (S.I.R. and S.A.R.); and the Bill and Melinda Gates Foundation, United States, INV-006133 from the Therapeutics Accelerator, also supported by Mastercard, Wellcome, and private philanthropic contributions (K.H. E.O.S. B.P. and S.C.). J.M. was supported by PhD student fellowships from the Departamento Administrativo de Ciencia, Tecnolog{\'i}a e Innovaci{\'o}n (COLCIENCIAS) and Pontificia Universidad Javeriana, Colombia (Convocatoria 727 Doctorados Nacionales). Conceptualization, A.S. and S.C.; Investigation, C.R.M. S.I.R. J.M.D. A.G. K.M.H. S.B. R.K.A. Christina Kim, J.C. Y.K. Cheryl Kim, J.M. and L.P.V.T.; Formal Analysis, C.R.M. S.I.R. J.M.D. E.G.C. B.P. J.G. and S.C.; Patient Recruitment and Samples, S.I.R. D.W. A.F. S.A.R. D.M.S.; Material Resources, R.B. E.O.S. A.S. and S.C.; Data Curation, C.R.M. S.I.R. J.A.G. E.G.C. and B.P.; Writing, C.R.M. S.I.R. J.M.D. A.S. and S.C.; Supervision, S.C. Project Administration, A.F.; Funding Acquisition, J.M.D. S.I.R. R.K.A. D.W. J.M. D.M.S. B.P. S.A.R. R.B. E.O.S. A.S. and S.C. A.S. is a consultant for Gritstone, Flow Pharma, and Avalia. S.C. is a consultant for Avalia. Funding Information: We would like to express our deepest thanks to the study subjects and their families for their participation and their altruistic desires to forward our scientific understanding of COVID-19 and other diseases. This study would not be possible without their generous donations. We would also like to thank LJI flow cytometry core facility, specifically Denise Hinz, for outstanding expertise, and the LJI clinical core, specifically Gina Levi RN and Brittany Schwan, for healthy donor enrollment and sample procurement. This work was funded by the NIH NIAID , United States, under awards AI142742 (Cooperative Centers for Human Immunology) (A.S. and S.C.), NIH contract Nr. 75N9301900065 (D.W. and A.S.), NIH NIAID AI100625 (R.B.), and U19 AI118626 (A.S. and B.P.). The BD FACSymphony S6 purchase was partially funded by the Bill and Melinda Gates Foundation , United States, (S.C.) and LJI Institutional Funds (S.C. and A.S.). This work was additionally supported in part by the Johnathan and Mary Tu Foundation (D.M.S.); the NIAID under K08 award AI135078 (J.M.D.), K99 award AI145762 (R.K.A.), UCSD T32s AI007036 , and AI007384 Infectious Diseases Division (S.I.R. and S.A.R.); and the Bill and Melinda Gates Foundation, United States, INV-006133 from the Therapeutics Accelerator, also supported by Mastercard, Wellcome, and private philanthropic contributions (K.H., E.O.S., B.P., and S.C.). J.M. was supported by PhD student fellowships from the Departamento Administrativo de Ciencia , Tecnolog{\'i}a e Innovaci{\'o}n (COLCIENCIAS) and Pontificia Universidad Javeriana , Colombia (Convocatoria 727 Doctorados Nacionales). Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = nov,
day = "12",
doi = "10.1016/j.cell.2020.09.038",
language = "English (US)",
volume = "183",
pages = "996--1012.e19",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}