Int J Biol Sci 2022; 18(15):5827-5848. doi:10.7150/ijbs.77561 This issue

Review

Pyroptotic cell death in SARS-CoV-2 infection: revealing its roles during the immunopathogenesis of COVID-19

Man Wang, Wenguang Chang, Lei Zhang, Yuan Zhang

Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, 38 Dengzhou Road, Qingdao 266021, China.

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Citation:
Wang M, Chang W, Zhang L, Zhang Y. Pyroptotic cell death in SARS-CoV-2 infection: revealing its roles during the immunopathogenesis of COVID-19. Int J Biol Sci 2022; 18(15):5827-5848. doi:10.7150/ijbs.77561. Available from https://www.ijbs.com/v18p5827.htm

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Abstract

Graphic abstract

The rapid dissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), remains a global public health emergency. The host immune response to SARS-CoV-2 plays a key role in COVID-19 pathogenesis. SARS-CoV-2 can induce aberrant and excessive immune responses, leading to cytokine storm syndrome, autoimmunity, lymphopenia, neutrophilia and dysfunction of monocytes and macrophages. Pyroptosis, a proinflammatory form of programmed cell death, acts as a host defense mechanism against infections. Pyroptosis deprives the replicative niche of SARS-CoV-2 by inducing the lysis of infected cells and exposing the virus to extracellular immune attack. Notably, SARS-CoV-2 has evolved sophisticated mechanisms to hijack this cell death mode for its own survival, propagation and shedding. SARS-CoV-2-encoded viral products act to modulate various key components in the pyroptosis pathways, including inflammasomes, caspases and gasdermins. SARS-CoV-2-induced pyroptosis contriubtes to the development of COVID-19-associated immunopathologies through leakage of intracellular contents, disruption of immune system homeostasis or exacerbation of inflammation. Therefore, pyroptosis has emerged as an important mechanism involved in COVID-19 immunopathogenesis. However, the entangled links between pyroptosis and SARS-CoV-2 pathogenesis lack systematic clarification. In this review, we briefly summarize the characteristics of SARS-CoV-2 and COVID-19-related immunopathologies. Moreover, we present an overview of the interplay between SARS-CoV-2 infection and pyroptosis and highlight recent research advances in the understanding of the mechanisms responsible for the implication of the pyroptosis pathways in COVID-19 pathogenesis, which will provide informative inspirations and new directions for further investigation and clinical practice. Finally, we discuss the potential value of pyroptosis as a therapeutic target in COVID-19. An in-depth discussion of the underlying mechanisms of COVID-19 pathogenesis will be conducive to the identification of potential therapeutic targets and the exploration of effective treatment measures aimed at conquering SARS-CoV-2-induced COVID-19.

Keywords: SARS-CoV-2, COVID-19, cytokine storm, pyroptosis, inflammasomes, immunopathogenesis, therapeutic targets