Evidence of their involvement can b

Evidence of their involvement can be found in the observation of high levels of circulating IL-1β, IL1-Ra, and IL-18[23,26]and synergistic upregulation of IL1 and IL1RN genes in the lung[34].Indeed, some NLRs are able to assemble a multimolecular platform termed inflammasome(via recruiting the adaptor ASC, apoptosis-associated speck-like protein containing a CARD), which in turn activates the proinflammatory caspase-1.Caspase-1 cleaves and activates IL-1β and IL-18, and induces a hyperinflammatory form of cell death, termed pyroptosis, through the cleavage of the pore-forming gasdermin-D[32,35].IL-1 family cytokines include IL-1α, IL-1β, IL-18 and their bioavailability is regulated by soluble antagonists(IL-1Ra, IL-18BP)of either endogenous origin or resulting from therapeutic intervention[36,37].The most frequently studied inflammasome sensor, NLRP3, drives inflammation during SARS-CoV infection through several activating pathways[38–41].Given the similarities between SARS-CoV and SARS-CoV-2, comparable mechanisms likely intervene during the acute phase of COVID-19.