Age-related decline of de novo T cell responsiveness as a cause of COVID-19 severity

Adults and the elderly experience higher mortality rate of coronavirus disease 2019 (COVID-19) and are also more at risk of developing very serious symptoms and death. Comorbidities sand the progressive accumulation of senescent cells during life that generate many inflammatory cytokines (e.g., interleukin-6) and contributes to the basal hyperinflammatory status may play a role in the vulnerability of old people to COVID-19. In a population never previously exposed, as in case of SARS-CoV-2, the induction of de novo immune responses against relies on the recognition by naïve T cells that decrease with age. This condition may contribute to the age-dependent development of the disease and to the greater severity of symptoms and death in the elderly. The Authors reviewed some data from animal and human studies that highlighted the importance of T cell responses for CoV control. The decreased number of naïve T cells and the impaired responses against neoantigens in elderly people can contribute to the age-related severity of emerging SARS-CoV-2. The enhancement of virus-specific T cell responses by immunotherapeutics avoiding unspecific activation and inflammation may be important in already infected patients before the onset of severe symptoms to prevent disease exacerbation and promote viral clearance. Special attention should be paid to mechanisms that impair SARS-CoV-2-specific immune responses, as the same mechanisms could negatively affect the effectiveness of future COVID-19 vaccines in these populations.