Pulmonary infection by SARS-CoV-2 induces senescence accompanied by an inflammatory phenotype in severe COVID-19: possible implications for viral mutagenesis

In patients with severe COVID-19, alveolar type II (AT2) cells that are infected with SARS-CoV-2 undergo senescence accompanied also by an inflammatory phenotype. In vitro recapitulation of SARS-CoV-2 infection in two-dimensional (2D) cellular systems and in a three-dimensional alveosphere system derived from alveolar type 2 (AT2) cells, also induced senescence and inflammation. Importantly, infected cells can act as a source of mutagenesis for SARS-CoV-2, since they exhibit increased levels of the APOBEC deaminating enzymes, which can mediate viral mutations. Overall these findings support that SARS-CoV-2 induced senescence may be an important driver of COVID-19 severity, disease persistence and the emergence of new viral strains. Finally, SARS-CoV-2-induced senescence may justify the implementation of senotherapeutics for the treatment of COVID-19 patients and possibly for long-COVID syndrome.