Elevated NET levels are found in COVID-19 patients [96]. NET formation is considered as a driver of COVID-19, since NET formation may contribute to tissue damage, organ injury, and mortality as indicated by autopsy specimens from COVID-19 patients [97]. The by-product of NETs, such as elastase, is involved in the pathogenesis of COVID-19 by facilitating SARS-CoV-2 entry and causing hypertension, thrombosis, and vasculitis [98–100]. The tissue damage leading to excessive oxidative stress creates a vicious cycle by increasing NET formation and distressing adaptive immunity [101]. Increased NETs are associated with hyperinflammation and in COVID-19 patients they amplify the severity and mortality associated with the disease. Targeting NETs and its feedback loop, with elastase, DNase-1, or inhibitory peptides as well as IL-1β, are potential therapeutic interventions for reducing the severity of COVID-19 [102,103].