The coronavirus disease of 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is turning out to be one of the most devastating global pandemics in the history of humankind. There is a shortage of effective therapeutic strategies or preventative vaccines for this disease to date. A rigorous investigation is needed for identifying and developing more effective therapeutic strategies for COVID-19. Angiotensin converting enzyme 2 (ACE2), a crucial factor in COVID-19 pathogenesis, has been identified as a potential target for COVID-19 treatment. Smoking and vaping are potential risk factors for COVID-19 which are also shown to upregulate ACE2 expression. In this review, we have discussed the pathobiology of COVID-19 in the lungs and brain and the role of ACE2 in the transmission and pathobiology of this disease. Further, we have shown possible interactions between nicotine/smoking and ACE2 in the lungs and brain which could aggravate the transmission and pathobiology of COVID-19 resulting in a poor disease outcome. Significance Statement This review addresses the present global pandemic COVID-19 with respect to its pathobiology in the lungs and brain. It focuses on the potential negative impact of tobacco and nicotine exposure on the outcomes of this disease by interaction with the ACE2 receptor. It adds to the time-sensitive and critically important growing knowledge about the risk factors, transmission, pathobiology, and prognosis of COVID-19.

Keywords: Lung; angiotensin converting enzyme (ACE); brain/CNS; nicotine.