T‐cell recovery and evidence of persistent immune activation 12 months after severe COVID‐19

BACKGROUND: T‐cell lymphopenia and functional impairment is a hallmark of severe acute coronavirus disease 2019 (COVID‐19). How T‐cell numbers and function evolve at later timepoints after clinical recovery remains poorly investigated. METHODS: We prospectively enrolled and longitudinally sampled 173 individuals with asymptomatic to critical COVID‐19 and analyzed phenotypic and functional characteristics of T cells using flow cytometry, 40‐parameter mass cytometry, targeted proteomics, and functional assays. RESULTS: The extensive T‐cell lymphopenia observed particularly in patients with severe COVID‐19 during acute infection had recovered 6 months after infection, which was accompanied by a normalization of functional T‐cell responses to common viral antigens. We detected persisting CD4(+) and CD8(+) T‐cell activation up to 12 months after infection, in patients with mild and severe COVID‐19, as measured by increased HLA‐DR and CD38 expression on these cells. Persistent T‐cell activation after COVID‐19 was independent of administration of a COVID‐19 vaccine post‐infection. Furthermore, we identified a subgroup of patients with severe COVID‐19 that presented with persistently low CD8(+) T‐cell counts at follow‐up and exhibited a distinct phenotype during acute infection consisting of a dysfunctional T‐cell response and signs of excessive pro‐inflammatory cytokine production. CONCLUSION: Our study suggests that T‐cell numbers and function recover in most patients after COVID‐19. However, we find evidence of persistent T‐cell activation up to 12 months after infection and describe a subgroup of severe COVID‐19 patients with persistently low CD8(+) T‐cell counts exhibiting a dysregulated immune response during acute infection.