The known role of NLRP3 in hyperinflammatory ARDS and CRS, documented NLRP3 involvement in MERS-CoV and SARS-CoV severity, and apparent efficacy of anti-NLRP3 therapeutics in SARS-CoV and SARS-CoV-2 clinical trials and animal models strongly indicate that NLRP3 is a central mediator of severe COVID-19. Here, NLRP3 is linked to congenital rubella syndrome.