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.

VG New

Prof. Vassilis G. Gorgoulis

Laboratory of Histology-Embryology
Molecular Carcinogenesis Group
Medical School
National and Kapodistrian University of Athens



Chair of Clinical Molecular Pathology,

Ninewells Hospital and School of Medicine


University of Dundee, Dundee, UK


Biomedical Research Foundation of the Academy of Athens


Faculty Institute for Cancer Sciences, University of Manchester,
Manchester Academic Health Science Centre, Manchester, UK

Manchester Centre for Cellular Metabolism,
University of Manchester, Manchester Academic Health Science Centre, Manchester


EMBO member


European Academy
of Cancer Sciences member


Academia Europaea member


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E-mail: vgorg@med.uoa.gr


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