Virus-induced senescence is driver and therapeutic target in COVID-19

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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  • Soyoung Lee
  • Yong Yu
  • Jakob Trimpert
  • Fahad Benthani
  • Mario Mairhofer
  • Paulina Richter-Pechanska
  • Emanuel Wyler
  • Dimitri Belenki
  • Sabine Kaltenbrunner
  • Maria Pammer
  • Lea Kausche
  • Theresa C. Firsching
  • Kristina Dietert
  • Michael Schotsaert
  • Carles Martínez-Romero
  • Gagandeep Singh
  • Séverine Kunz
  • Daniela Niemeyer
  • Riad Ghanem
  • Helmut J. F. Salzer
  • Christian Paar
  • Michael Mülleder
  • Melissa Uccellini
  • Edward G. Michaelis
  • Amjad Khan
  • Andrea Lau
  • Martin Schönlein
  • Anna Habringer
  • Josef Tomasits
  • Julia M. Adler
  • Susanne Kimeswenger
  • Achim D. Gruber
  • Wolfram Hoetzenecker
  • Herta Steinkellner
  • Bettina Purfürst
  • Reinhard Motz
  • Francesco Di Pierro
  • Bernd Lamprecht
  • Markus Landthaler
  • Christian Drosten
  • Adolfo García-Sastre
  • Rupert Langer
  • Markus Ralser
  • Roland Eils
  • Maurice Reimann
  • Dorothy N. Y. Fan
  • Clemens A. Schmitt


Original languageEnglish
Pages (from-to)283–289
Journal / PublicationNature
Issue number7884
Online published13 Sept 2021
Publication statusPublished - 11 Nov 2021


Derailed cytokine and immune cell networks account for organ damage and clinical severity of COVID-191–4. Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and accompanied by a senescence-associated secretory phenotype (SASP), composed of pro-inflammatory cytokines, extracellular matrix-active factors and pro-coagulatory mediators5–7. COVID-19 patients displayed markers of senescence in their airway mucosa in situ and elevated serum levels of SASP factors. Mirroring COVID-19 hallmark features such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue1,8,9, in vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, neutrophil extracellular trap (NET) formation as well as activation of platelets and the clotting cascade in response to supernatant of VIS cells, including SARS-CoV-2-induced senescence. Senolytics such as Navitoclax and Dasatinib/Quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-driven hamster and mouse models. Our findings mark VIS as pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest senolytic targeting of virus-infected cells as a novel treatment option against SARS-CoV-2 and perhaps other viral infections.

Citation Format(s)

Virus-induced senescence is driver and therapeutic target in COVID-19. / Lee, Soyoung; Yu, Yong; Trimpert, Jakob et al.
In: Nature, Vol. 599, No. 7884, 11.11.2021, p. 283–289.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review