PM2.5 AND SARS-CoV-2: BIO-INTERACTIONS AND MOLECULAR MECHANISMS UNDERLYING THE EFFECTS AT PULMONARY LEVEL

The hypothesis that particulate matter (PM) may promote SARS-CoV-2 infection is of great interest. PM has been suggested to act either as a “carrier” of SARS-CoV-2 or by reducing the cellular defenses and making people more susceptible to infections. PM ability to induce a state of chronic lung inflammation, characterized by the over-expression of the angiotensin 2 converting enzyme (ACE2), for which SARS-CoV-2 has a high affinity, is currently under evaluation1,2. Thus, understanding how ACE2-related pathways in pulmonary epithelial cells could be perturbed by PM and exploited by SARS-CoV-2 infection can help in suggesting new strategies to prevent/mitigate the effects of COVID-19 pandemic. This project proposes to evaluate the in vitro interactions between SARS-CoV-2 and PM2.5, using human alveolar epithelial cells (A549) to define if and how PM facilitates virus entry and to identify biological markers of exposure and risk. PM2.5 was collected in Milan during winter 2021. Cells were firstly treated for 72h with PM2.5 in combination or not with SARS-CoV-2 inactivated form. Successively cells were exposed only to PM for 72h, afterward SARS-CoV-2 was added for additional 24h to mimic a sub-chronic exposure to air pollution. The activation of the inflammatory response was studied at biochemical and molecular level. The endosomal pathway was also explored as parameter for the internalization of viral particles. Results demonstrated that exposure to PM2.5 induced an ACE2 over-expression in A549 cells, even in absence of SARS-CoV-2. Moreover, PM/SARS-CoV-2 co-exposure promoted an increase of the pro-inflammatory cytokine IL-6 release. Preliminary data suggested that co-exposure might facilitate the virus entry within the endosomal route. Our data support the hypothesis that the mechanism by which PM exposure can contribute to enhancing SARS-CoV-2 infection and consequent COVID-19 severity is related to an increase in the basal level of the ACE2 receptor in lung epithelial cells and in the inflammatory status.