Two years after the emergence of SARS-CoV-2, our understanding of COVID-19 disease pathogenesis is still incomplete. Despite unprecedented global collaborative scientific efforts and rapid vaccine development, an uneven vaccine roll-out and the emergence of novel variants of concern such as omicron underscore the critical importance of identifying the mechanisms that contribute to this disease. Overt inflammation and cell death have been proposed to be central drivers of severe pathology in COVID-19 patients and their pathways and molecular components therefore present promising targets for host-directed therapeutics. In our review, we summarize the current knowledge on the role and impact of diverse programmed cell death (PCD) pathways on COVID-19 disease. We dissect the complex connection of cell death and inflammatory signaling at the cellular and molecular level and identify a number of critical questions that remain to be addressed. We provide rationale for targeting of cell death as potential COVID-19 treatment and provide an overview of current therapeutics that could potentially enter clinical trials in the near future.

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程序性细胞死亡：导致严重 COVID-19 的途径？

在 SARS-CoV-2 出现两年后，我们对 COVID-19 疾病发病机制的理解仍然不完整。尽管前所未有的全球协作科学努力和快速的疫苗开发，但疫苗的不平衡推出和诸如 omicron 等新的关注变体的出现强调了确定导致这种疾病的机制的关键重要性。已提出明显的炎症和细胞死亡是 COVID-19 患者严重病理的主要驱动因素，因此它们的途径和分子成分为宿主导向治疗提供了有希望的目标。在我们的综述中，我们总结了当前关于不同程序性细胞死亡 (PCD) 途径对 COVID-19 疾病的作用和影响的知识。我们在细胞和分子水平上剖析了细胞死亡和炎症信号之间的复杂联系，并确定了许多有待解决的关键问题。我们提供了将细胞死亡作为潜在 COVID-19 治疗的基本原理，并概述了当前可能在不久的将来进入临床试验的治疗方法。