Air pollution by NO₂ and PM_2.5 explains COVID-19 infection severity by overexpression of angiotensin-converting enzyme 2 in respiratory cells: a review

Many major cities that witnessed heavy air pollution by nitrogen dioxide (NO₂) and particulate matter (PM) have experienced a high rate of infection and severity of the coronavirus disease pandemic (COVID-19). This phenomenon could be explained by the overexpression of the angiotensin converting enzyme 2 (ACE-2) on epithelial cell surfaces of the respiratory tract. Indeed, ACE-2 is a receptor for coronaviruses including the severe acute respiratory syndrome coronavirus 1 and 2 (SARS-CoV), and ACE-2 is overexpressed under chronic exposure to air pollution such as NO₂ and PM_2.5. In this review, we explain that ACE-2 acts as the sole receptor for the attachment of the SARS-CoV-2 via its spike protein. The fact that respiratory and vascular epithelial cells express ACE-2 has been previously observed during the 2003 epidemic of the SARS-CoV-1 in China, and during the 2012 Middle East respiratory syndrome in Saudi Arabia. High ACE-2 expression in respiratory epithelial cells under air pollution explains the positive correlation between the severity in COVID-19 patients and elevated air pollution, notably high NO₂ and PM_2.5 levels. Specific areas in India, China, Italy, Russia, Chile and Qatar that experience heavy air pollution also show high rates of COVID-19 infection and severity. Overall, we demonstrate a link between NO₂ emissions, PM_2.5 levels, ACE-2 expression and COVID-19 infection severity. Therefore, air pollution should be reduced in places where confirmed cases of COVID-19 are unexpectedly high.