The disease spectrum of coronavirus disease 2019 (COVID-19) ranges from no symptoms to multisystem failure and death. Characterization of virus-specific immune responses to severe acute respiratory coronavirus 2 (SARS–CoV-2) is key to understanding disease pathogenesis, but few studies have evaluated T cell immunity. In this issue of the JCI, Sattler and Angermair et al. sampled blood from subjects with COVID-19 and analyzed the activation and function of virus antigen–specific CD4+ T cells. T cells that failed to respond to peptides from the membrane, spike, or nucleocapsid proteins were more common in subjects who died. In those whose T cells had the capacity to respond, older patients with comorbidity had larger numbers of activated T cells compared with patients who had fewer risk factors, but these cells showed impaired IFN-γ production. This cross-sectional study relates activated T cell responses to patient risk factors and outcome. However, T cell response trajectory over the disease course remains an open question.
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