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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Fax: 0030 210-7462340
E-mail: vgorg@med.uoa.gr

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