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Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity.
Cell. 2020 11 12; 183(4):996-1012.e19.Cell

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.

Authors+Show Affiliations

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.Flow Cytometry Core Facility, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.Department of Epidemiology, UNC Chapel Hill School of Public Health, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.Department of Epidemiology, UNC Chapel Hill School of Public Health, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA. Electronic address: alex@lji.org.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA. Electronic address: shane@lji.org.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33010815

Citation

Rydyznski Moderbacher, Carolyn, et al. "Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations With Age and Disease Severity." Cell, vol. 183, no. 4, 2020, pp. 996-1012.e19.
Rydyznski Moderbacher C, Ramirez SI, Dan JM, et al. Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity. Cell. 2020;183(4):996-1012.e19.
Rydyznski Moderbacher, C., Ramirez, S. I., Dan, J. M., Grifoni, A., Hastie, K. M., Weiskopf, D., Belanger, S., Abbott, R. K., Kim, C., Choi, J., Kato, Y., Crotty, E. G., Kim, C., Rawlings, S. A., Mateus, J., Tse, L. P. V., Frazier, A., Baric, R., Peters, B., ... Crotty, S. (2020). Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity. Cell, 183(4), 996-e19. https://doi.org/10.1016/j.cell.2020.09.038
Rydyznski Moderbacher C, et al. Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations With Age and Disease Severity. Cell. 2020 11 12;183(4):996-1012.e19. PubMed PMID: 33010815.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity. AU - Rydyznski Moderbacher,Carolyn, AU - Ramirez,Sydney I, AU - Dan,Jennifer M, AU - Grifoni,Alba, AU - Hastie,Kathryn M, AU - Weiskopf,Daniela, AU - Belanger,Simon, AU - Abbott,Robert K, AU - Kim,Christina, AU - Choi,Jinyong, AU - Kato,Yu, AU - Crotty,Eleanor G, AU - Kim,Cheryl, AU - Rawlings,Stephen A, AU - Mateus,Jose, AU - Tse,Long Ping Victor, AU - Frazier,April, AU - Baric,Ralph, AU - Peters,Bjoern, AU - Greenbaum,Jason, AU - Ollmann Saphire,Erica, AU - Smith,Davey M, AU - Sette,Alessandro, AU - Crotty,Shane, Y1 - 2020/09/16/ PY - 2020/08/06/received PY - 2020/08/21/revised PY - 2020/09/11/accepted PY - 2020/10/5/pubmed PY - 2020/11/26/medline PY - 2020/10/4/entrez KW - CD4 KW - CD8 KW - CXCL10 KW - IP-10 KW - Spike KW - T cells KW - adaptive immunity KW - antibody KW - coronavirus KW - epitopes KW - neutralizing antibodies SP - 996 EP - 1012.e19 JF - Cell JO - Cell VL - 183 IS - 4 N2 - 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. SN - 1097-4172 UR - https://www.unboundmedicine.com/medline/citation/33010815/Antigen_Specific_Adaptive_Immunity_to_SARS_CoV_2_in_Acute_COVID_19_and_Associations_with_Age_and_Disease_Severity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(20)31235-6 DB - PRIME DP - Unbound Medicine ER -