COVID-19 is a deadly pandemic and has resulted in a huge loss of money and life in the past few months. It is well known that the SARS-CoV-2 gene mutates relatively slowly as compared to other viruses but still may create hurdles in developing vaccines. Therefore, there is a need to develop alternative routes for its management and treatment of COVID-19. Based on the severity of viral infection in COVID-19 patients, critically ill patients (∼5%, with old age, and comorbidities) are at high risk of morbidities. The reason for this severity in such patients is attributed to "misleading cytokine storm", which produces ARDS and results in the deaths of critically ill patients. In this connection, ethyl pyruvate (EP) controls these cytokines/chemokines, is an antiinflammatory agent, and possesses a protective effect on the lungs, brain, heart, and mitochondria against various injuries. Considering these facts, we propose that the site-selective EP formulations (especially aerosols) could be the ultimate adjuvant therapy for the regulation of misleading cytokine storm in severely affected COVID-19 patients and could reduce the mortalities.