Involvement of NLRP3 Inflammasome in SARS-Cov-2-Induced Multiorgan Dysfunction in Patients with COVID-19: A Review of Molecular Mechanisms

Nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome is a critical component of the innate immune system. The inflammasome activation is correlated with the COVID-19 severity. Furthermore, the underlying conditions are accompanied by hyperactivation of NLRP3 inflammasome and poor outcomes. Herein, we presented the involvement of NLRP3 inflammasome in the pathogenies of SARS-CoV-2-induced multiorgan dysfunction and potential therapeutics. Overexpression of NLRP3 inflammasome components and subsequently increased levels of cytokines following viral infection leads to the cytokine storm and indirectly affects the organ functions. Besides, invading host cells via SARS-CoV-2 further activates the NLRP3 inflammasome and induces pyroptosis in immune cells, resulting in the secretion of higher levels of proinflammatory cytokines into the extracellular matrix. These events continued by induction of fibrosis and organ dysfunction following infection with SARS-CoV-2 in critically ill patients. This condition can be observed in individuals with comorbidities (e.g., diabetes, obesity, etc.) due to a primed state of immunity, which can cause severe disease or death in this population. Therefore, understanding the mechanisms underlying host-SARS-CoV-2 interaction may help to clarify the pathophysiology of SARS-CoV-2-induced multiorgan dysfunction and introduce potential therapeutic strategies.