Apart from cytokine storm and pyroptosis observed in highly pathogenic HCoVs, other cell death programmes such as apoptosis and necrosis might also contribute to pathogenesis. Apoptosis was detected in various HCoV-infected samples derived from not only the respiratory tract, but also extrapulmonary sites. Autopsy studies on SARS casualties revealed massive apoptosis in multiple organs including the liver and thyroid gland [78]. MERS-CoV induces apoptosis in the kidney, lung, and primary T lymphocytes, plausibly through induction of Smad7 and FGF2 [21]. To delineate how CoVs might activate apoptosis, pathway analysis was performed with CoV proteins. ORF3a, ORF3b, ORF7a, ORF8a, ORF9b, and E proteins of SARS-CoV are pro-apoptotic [79]. SARS-CoV ORF7a protein activates the intrinsic pathway of apoptosis through an interaction with anti-apoptotic protein Bcl-XL in the endoplasmic reticulum, thereby sequestering a key suppressor of apoptosis. MERS-CoV infection activates both intrinsic and extrinsic pathways of apoptosis, exacerbating viral pathogenesis [21]. Other than apoptosis, SARS-CoV induces RIP3-mediated necrosis through induction of ORF3a oligomerization [80]. Generally, highly pathogenic HCoVs are capable of activating different cell death programmes more efficiently. In this regard, it will be of great interest to see whether and how the lower pathogenicity and higher human-to-human transmissibility of SARS-CoV-2 might be linked to its abilities to modulate inflammasome activation and cell death programmes selectively.