SARS-CoV-2 infection can lead to various types of cell death including apoptosis, necroptosis and pyroptosis. Liang et al. report the dynamics and features of cell death in infected human airway epithelial cells, the primary target cell type that hosts SARS-CoV-2 replication.

The authors first showed that SARS-CoV-2 infection in ACE2-expressing lung epithelial cells initially induced apoptosis and necroptosis, followed by GSDME-mediated pyroptosis only at a later stage. They also observed apoptosis in bystander cells without infection. At the molecular level, they discovered that ZBP1 sensed viral Z-RNA and triggered necroptosis after SARS-CoV-2 infection. Notably, when compared with the Omicron variant, infection with the Delta strain enhanced ZBP1 interaction with Z-RNA and caused aggravated necroptosis, suggesting a correlation between variants of concern and disease severity.

SARS-CoV-2感染可导致多种类型的细胞死亡，包括细胞凋亡、坏死性凋亡和焦亡。梁等人。报告了受感染的人气道上皮细胞的细胞死亡动态和特征，这是承载 SARS-CoV-2 复制的主要靶细胞类型。

作者首先表明，表达 ACE2 的肺上皮细胞中的 SARS-CoV-2 感染最初会诱导细胞凋亡和坏死性凋亡，随后仅在后期诱导 GSDME 介导的细胞焦亡。他们还观察到未感染的旁观者细胞的凋亡。在分子水平上，他们发现 ZBP1 感知病毒 Z-RNA 并在 SARS-CoV-2 感染后引发坏死性凋亡。值得注意的是，与 Omicron 变体相比，Delta 菌株的感染增强了 ZBP1 与 Z-RNA 的相互作用，并导致坏死性凋亡加剧，这表明所关注的变体与疾病严重程度之间存在相关性。