Severe air pollution links to higher mortality in COVID-19 patients: The “double-hit” hypothesis

•Some regions of the world have higher infection rates from SARS-CoV-2 and with a higher mortality.•These regions have high concentration of air pollutants, especially PM 2.5 and NO2.•Chronic exposure, especially to PM 2.5, correlates with alveolar ACE-2 receptor overexpression leading to more severe COVID-19 infection.•High ambient NO2 may be responsible for the extensive lung injury in COVID-19 pneumonia associated with a worse outcome. In areas of SARS-CoV-2 outbreak worldwide mean air pollutants concentrations vastly exceed the maximum limits. Chronic exposure to air pollutants have been associated with lung ACE-2 over-expression which is known to be the main receptor for SARS-CoV-2. The aim of this study was to analyse the relationship between air pollutants concentration (PM 2.5 and NO2) and COVID-19 outbreak, in terms of transmission, number of patients, severity of presentation and number of deaths. COVID-19 cases, ICU admissions and mortality rate were correlated with severity of air pollution in the Italian regions. The highest number of COVID-19 cases were recorded in the most polluted regions with patients presenting with more severe forms of the disease requiring ICU admission. In these regions, mortality was two-fold higher than the other regions. From the data available we propose a “double-hit hypothesis”: chronic exposure to PM 2.5 causes alveolar ACE-2 receptor overexpression. This may increase viral load in patients exposed to pollutants in turn depleting ACE-2 receptors and impairing host defences. High atmospheric NO2 may provide a second hit causing a severe form of SARS-CoV-2 in ACE-2 depleted lungs resulting in a worse outcome. [Display omitted]