Shedding light on the cellular mechanisms involved in the combined adverse effects of fine particulate matter and SARS-CoV-2 on human lung cells.

Airborne pathogens represent a topic of scientific relevance, especially considering the recent COVID-19 pandemic. Air pollution, and particulate matter (PM) in particular, has been proposed as a possible risk factor for the onset and spread of pathogen-driven respiratory diseases. Regarding SARS-CoV-2 infection, exposure to fine PM (PM, particles with an aerodynamic diameter < 2.5 μm) has been associated with increased incidence of the COVID-19 disease. To provide useful insights into the mechanisms through which PM might be involved in infection, we exposed human lung cells (A549) to PM and SARS-CoV-2, to evaluate the toxicological properties and the molecular pathways activated when airborne particles are combined with viral particles. Winter PM was collected in a metropolitan urban area and its physico-chemical composition was analyzed. A549 cells were exposed to SARS-CoV-2 concomitantly or after pre-treatment with PM. Inflammation, oxidative stress and xenobiotic metabolism were the main pathways investigated. Results showed that after 72 h of exposure PM significantly increased the expression of the angiotensin-converting enzyme 2 (ACE2) receptor, which is one of the keys used by the virus to infect host cells. We also analyzed the endosomal route in the process of internalization, by studying the expression of RAB5 and RAB7. The results show that in cells pre-activated with PM and then exposed to SARS-CoV-2, RAB5 expression is significantly increased. The activation of the inflammatory process was then studied. Our findings show an increase of pro-inflammatory markers (NF-kB and IL-8) in cells pre-activated with PM for 72 h and subsequently exposed to the virus for a further 24 h, further demonstrating that the interaction between PM and SARS-CoV-2 determines the severity of the inflammatory responses in lung epithelial cells. In conclusion, the study provides mechanistic biological evidence of PM contribution to the onset and progression of viral respiratory diseases in exposed populations.