The elimination of viruses by autophagy (sometimes termed as virophagy) has been well described for a variety of viral infections [8,84,85,137]. Although, the virus has multiple ways of entry into the cell, autophagy augmentation provides strategic advantage in reducing viral load by promoting its clearance [90,137]. As a proof of concept, recent study demonstrated the utility of three different autophagy-inducing drugs, spermidine, MK02206, and niclosamide, in restricting SARS-CoV-2 propagation [138]. Autophagy induction and related upregulation of overall immunity helps combat exacerbations and is suggested as an immunity boosting strategy as a preventive measure against COVID-19 [139]. In addition to boosting immunity, dampening viral load, and allowing SARS-COV2 clearance, autophagy induction may provide strategic advantage in the treatment of COVID-19 and prevention of negative outcomes, which makes it a subject of ongoing studies. In support of this, autophagy inhibiting drugs, such as hydroxychloroquine (HCQ) that help dampen the immune response in rheumatoid arthritis, malaria, and other illnesses but weakens cellular ability for viral clearance by the critical homeostatic process autophagy. Despite early claims that HCQ may provide benefit in treating COVID-19 [90,91,92], it has since been deemed unsafe for use in COVID-19 treatment by the FDA based on randomized double blind placebo control trials [140,141]. In addition, earlier studies on Middle East respiratory syndrome (MERS) coronavirus [50] provide proof-of-concept data on therapeutic potential of autophagy modulating drugs to combat SARS-COV2 infection, cytokine storm, and the pathogenesis of severe ARDS-like COVID-19 fatal lung disease. Prior studies showing a protective role of autophagy induction in other models of ARDS demonstrate the scope of autophagy augmenting strategies in combating SARS-CoV-2 infections (Figure 1) and thus is part of ongoing validation and rapid clinical development studies that may help limit the burden and spread of this novel virus.