Virus-induced senescence is a central pathogenic principle and therapeutic target in COVID-19 disease

SARS-CoV-2 infection accounts for COVID-19 lung disease and other organ manifestations. Increasing evidence points towards an inflammatory cytokine network as the underlying driver of actual organ damage and severity of the clinical course. Here we show that SARS-CoV-2, like a broad spectrum of other viruses, evokes cellular senescence as a primary stress response in infected cells, among them respiratory epithelial cells, which is – indistinguishably from other forms of cellular senescence – characterized by typical morphological and cell-cycle arrest features, and accompanied by the massive secretion of largely pro-inflammatory cytokines, termed senescence-associated secretory phenotype (SASP). Overall design: Examine differentially expressed gene transcripts of senescent cells induced by direct virus infection or conditioned medium from virus-induced senescent cells.