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Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters

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Delval, Lou | Hantute-Ghesquier, Aline | Sencio, Valentin | Flaman, Jean Michel | Robil, Cyril | Angulo, Fabiola Silva | Lipskaia, Larissa | Çobanoğlu, Ozmen | Lacoste, Anne-Sophie | Machelart, Arnaud | Danneels, Adeline | Corbin, Mathieu | Deruyter, Lucie | Heumel, Séverine | Idziorek, Thierry | Séron, Karin | Sauve, Florent | Bongiovanni, Antonino | Prévot, Vincent | Wolowczuk, Isabelle | Belouzard, Sandrine | Saliou, Jean-Michel | Gosset, Philippe | Bernard, David | Rouillé, Yves | Adnot, Serge | Duterque-Coquillaud, Martine | Trottein, François

Edité par CCSD ; Nature -

International audience. Older age is one of the strongest risk factors for severe COVID-19. In this study, we determined whether age-associated cellular senescence contributes to the severity of experimental COVID-19. Aged golden hamsters accumulate senescent cells in the lungs, and the senolytic drug ABT-263, a BCL-2 inhibitor, depletes these cells at baseline and during SARS-CoV-2 infection. Relative to young hamsters, aged hamsters had a greater viral load during the acute phase of infection and displayed higher levels of sequelae during the post-acute phase. Early treatment with ABT-263 lowered pulmonary viral load in aged (but not young) animals, an effect associated with lower expression of ACE2, the receptor for SARS-CoV-2. ABT-263 treatment also led to lower pulmonary and systemic levels of senescence-associated secretory phenotype factors and to amelioration of early and late lung disease. These data demonstrate the causative role of age-associated pre-existing senescent cells on COVID-19 severity and have clear clinical relevance.

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