Immunosenescence Profile Is Associated With Increased Susceptibility to Severe COVID ‐19

In this study, we tested the hypothesis that the immunosenescence profile could account for the disproportional susceptibility of the elderly to severe forms of COVID‐19. The immunological profiles of volunteers residing in endemic and non‐endemic areas for chronic infectious diseases were analyzed at the early stage of SARS‐CoV‐2 infection. A unique signature of inflammatory plasma mediators was identified in COVID‐19 volunteers when compared to individuals with other flu‐like syndromes. COVID‐19 severity correlated with high levels of inflammatory mediators; among them, CXCL9, a serum marker of aging. Patients who progressed to hospitalization displayed high frequencies of CD8 ⁺ and CD4 ⁺ T cells expressing exhaustion and senescence markers and showed reduced and more mature B cell repertoires, which are typical of senescence. They also had an acceleration of epigenetic age measured by DNA methylation. Therefore, severe COVID‐19 correlated with phenotypic, functional, and epigenetic features of accelerated immunosenescence at the onset of infection.