Abstract
SummaryLimited 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.
Highlights
The ongoing COVID-19 pandemic has resulted in the infection of nearly 18 million people worldwide within 8 months, with over 4.5 million cases in the United States (World Health Organization)
We measured SARS-CoV-2-specific antibodies, SARS-CoV-2-specific CD4+ T cells, and SARS-CoV-2-specific CD8+ T cells in all individuals in a new cohort, with an emphasis on including acute cases across a range of COVID-19 disease severities. 54 subjects were enrolled in this study, 24 subjects with acute COVID-19
T cells were only detected in 50% of acute COVID-19 samples
Summary
The ongoing COVID-19 pandemic has resulted in the infection of nearly 18 million people worldwide within 8 months, with over 4.5 million cases in the United States (World Health Organization). Severe cases can progress to respiratory failure associated with diffuse alveolar damage and acute respiratory distress syndrome (ARDS) (Grasselli et al, 2020; Richardson et al, 2020), similar to what was observed for SARS (Rockx et al, 2020). The relative role(s) played by the immune response to SARS-CoV-2 versus direct viral effects in the respiratory system and other organ systems has been questioned, with the possibility of immunopathogenesis being a major causal component of severe COVID-19 (McKechnie and Blish, 2020; Vabret et al, 2020).
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