Immunosenescence profile is associated with increased susceptibility to severe COVID-19

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Abstract

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 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 onset of infection.

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