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

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.

• Delval, L.
• Hantute-Ghesquier, A.
• Sencio, V.
• Flaman, J. M.
• Robil, C.
• Angulo, F. S.
• Lipskaia, L.
• Çobano
• Lacoste, A. S.
• Machelart, A.
• Danneels, A.
• Corbin, M.
• Deruyter, L.
• Heumel, S.
• Idziorek, T.
• S
• Sauve, F.
• Bongiovanni, A.
• Prévot, V.
• Wolowczuk, I.
• Belouzard, S.
• Saliou, J. M.
• Gosset, P.
• Bernard, D.
• Rouillé, Y.
• Adnot, S.
• Duterque-Coquillaud, M.
• Trottein, F.