Whether and how baseline immune states may be altered by viral infections remains unclear. In Nature, Tsang and colleagues evaluated the immune responses to vaccination against influenza in healthy people who had not been vaccinated against COVID-19 and had recovered from non-severe COVID-19 (COVR; n = 33) versus those of age- and sex-matched control participants who had never had COVID-19 (HC; n = 44). Up to 150 days after COVID-19, monocyte frequencies were higher in male COVR participants than in female COVR or male HC participants, whereas male and female COVR participants had higher transcriptional signatures of T cell activation and lower expression of innate immune receptors in monocytes than those of HC participants. After vaccination against influenza, male COVR participants had stronger inflammatory responses, in particular interferon-γ-related transcriptional responses, and stronger influenza-specific antibody responses than those of male HC or female COVR participants, which correlated with enrichment for effector memory GPR56+CD8+ T cells that make interferon-γ in response to the cytokines IL-15, IL-12 and IL-18 (possibly in an antigen-independent manner) in male COVR participants before vaccination. Vaccination against influenza normalized the innate immune receptor transcriptional signature in monocytes, especially in female COVR participants, although the functional relevance of this change remains to be determined.

Credit: [Radoslav Zilinsky]/[Moment]/Getty

Original reference: Nature https://doi.org/10.1038/s41586-022-05670-5 (2023)