Transient and durable T cell reactivity after COVID-19.

Martner, Anna; Grauers Wiktorin, Hanna; Törnell, Andreas; Ringlander, Johan; Arabpour, Mohammad; Lindh, Magnus; Lagging, Martin; Nilsson, Staffan et al. · Proc Natl Acad Sci U S A · 2022

basic_science · Level V

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Abstract

This study analyzed whole blood samples (<i>n</i> = 56) retrieved from 30 patients at 1 to 21 (median 9) mo after verified COVID-19 to determine the polarity and duration of antigen-specific T cell reactivity against severe acute respiratory syndrome coronavirus 2-derived antigens. Multimeric peptides spanning the entire nucleocapsid protein triggered strikingly synchronous formation of interleukin (IL)-4, IL-12, IL-13, and IL-17 ex vivo until ∼70 d after confirmed infection, whereafter this reactivity was no longer inducible. In contrast, levels of nucleocapsid-induced IL-2 and interferon-γ remained stable and highly correlated at 3 to 21 mo after infection. Similar cytokine dynamics were observed in unvaccinated, convalescent patients using whole-blood samples stimulated with peptides spanning the N-terminal portion of the spike 1 protein. These results unravel two phases of T cell reactivity following natural COVID-19: an early, synchronous response indicating transient presence of multipolar, antigen-specific T helper (T<sub>H</sub>) cells followed by an equally synchronous and durable T<sub>H</sub>1-like reactivity reflecting long-lasting T cell memory.

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