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Airborne pathogens represents a topic of great scientific relevance, especially considering the recent COVID-19 pandemic. Air pollutant such as Particulate Matter (PM) can in fact be associated with an increased incidence of respiratory viral diseases.1 To provide useful insights into the mechanisms by which PM could be involved into infection, we exposed human lung cells to fine PM (PM2.5) and SARS-CoV-2, in order to evaluate different particles cytotoxicological properties and the molecular pathways activated after 72 hours of treatment. We also explored the combined effects of PM2.5 and SARS-CoV-2, to verify the possibility that PM2.5 may play a role in facilitating SARS-CoV-2 infection. Results demonstrated that inflammation is the key process involved in the cell response to PM2.5 and viral particles, albeit with differences. Interestingly, the harmful effects are increased when SARS-CoV-2 and PM2.5 are combined. We also found that PM2.5 induces an over-expression of the angiotensin 2 converting enzyme (ACE2), a preferential entry for the viral particles into respiratory host cells.2 We then verified the possibility that a sub-chronic exposure to PM could induce a reduction of cellular defenses, thus making people more susceptible to infection. Cells were treated with PM2.5 for 72 hours, afterward SARS-CoV-2 was added for additional 2 and 24 hours. Data showed that pre-treatment with PM2.5 facilitates virus entry within the endosomal route already after 2 hours of exposure to SARS-CoV-2. We also demonstrated that the cells exposed to PM and successively treated with virus for 24 hours, respond with an intensified inflammatory state. Taken together, these results showed that PM2.5 appears to facilitate the virus entry in the lung, besides worsening the potency of the inflammatory response to viral infection. The times we are living in, solicit the urgency to carry out a more in-depth investigation, to provide useful elements for understanding the different mecha

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 epitheli