Cell
Volume 183, Issue 4, 12 November 2020, Pages 996-1012.e19
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Article
Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity

https://doi.org/10.1016/j.cell.2020.09.038Get rights and content
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Highlights

  • Adaptive immune responses limit COVID-19 disease severity

  • Multiple coordinated arms of adaptive immunity control better than partial responses

  • CXCL10 may be a biomarker of impaired T cell responses in acute COVID-19

  • Aging and scarcity of naive T cells may be linked risk factors for severe COVID-19

Summary

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

coronavirus
CD4
CD8
T cells
antibody
neutralizing antibodies
adaptive immunity
CXCL10
IP-10
Spike
epitopes

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These authors contributed equally

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