Derailed cytokine and immune cell networks account for the organ damage and the clinical severity of COVID-19 (refs. ^1,2,3,4). 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 is accompanied by a senescence-associated secretory phenotype (SASP), which comprises pro-inflammatory cytokines, extracellular-matrix-active factors and pro-coagulatory mediators^5,6,7. Patients with COVID-19 displayed markers of senescence in their airway mucosa in situ and increased serum levels of SASP factors. In vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, which mirrored hallmark features of COVID-19 such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue^1,8,9. Moreover, supernatant from VIS cells, including SARS-CoV-2-induced senescence, induced neutrophil extracellular trap formation and activation of platelets and the clotting cascade. Senolytics such as navitoclax and a combination of dasatinib plus quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-infected hamsters and mice. Our findings mark VIS as a pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest that senolytic targeting of virus-infected cells is a treatment option against SARS-CoV-2 and perhaps other viral infections.

脱轨的细胞因子和免疫细胞网络导致器官损伤和 COVID-19 的临床严重程度（参考文献^{1、2、3、4}）。在这里，我们表明 SARS-CoV-2 与其他病毒一样，会引起细胞衰老，这是受感染细胞的主要应激反应。病毒诱导的衰老 (VIS) 与其他形式的细胞衰老没有区别，并伴有衰老相关分泌表型 (SASP)，其中包括促炎细胞因子、细胞外基质活性因子和促凝血介质^{5,6 ,7}. COVID-19 患者在原位气道粘膜中显示出衰老标志物，并且血清 SASP 因子水平升高。体外试验证明了巨噬细胞激活，伴有 SASP 记忆分泌、补体裂解和 SASP 放大内皮细胞继发性衰老，这反映了 COVID-19 的标志性特征，例如受影响肺组织中的巨噬细胞和中性粒细胞浸润、内皮损伤和广泛血栓形成^{1， 8,9}. 此外，来自 VIS 细胞的上清液，包括 SARS-CoV-2 诱导的衰老，诱导了中性粒细胞胞外陷阱的形成和血小板的激活以及凝血级联反应。navitoclax 等 Senolytics 和达沙替尼加槲皮素的组合选择性地消除了 VIS 细胞，减轻了 COVID-19 相关的肺部疾病，并减少了感染 SARS-CoV-2 的仓鼠和小鼠的炎症。我们的研究结果将 VIS 标记为 COVID-19 相关细胞因子升高和器官损伤的致病触发因素，并表明对病毒感染细胞的衰老靶向是针对 SARS-CoV-2 和其他病毒感染的治疗选择。