Particulate matter exposure potentiates SARS-CoV-2 Delta variant infection by suppressing epithelial antiviral responses

Supasek Kongsomros^1,2*Jiraporn Paha³Phayungsap Prasara-a³Sopita Visamol³Pinnakarn Techapichetvanich²Apisada Jiso^2,4Kwanchanok Uppakara²Ardythe Morrow¹Somchai Chutipongtanate^1,2,5Phisit Khemawoot²Arunee Thitithanyanont^3*

• ¹University of Cincinnati Department of Environmental & Public Health Sciences, Cincinnati, United States
• ²Chakri Naruebodin Medical Institute, Bang Phli District, Thailand
• ³Mahidol University Faculty of Science, Bangkok, Thailand
• ⁴Chiang Mai University Faculty of Pharmacy, Chiang Mai, Thailand
• ⁵Mahidol University Faculty of Medicine Ramathibodi Hospital Department of Pediatrics, Bangkok, Thailand

Airborne particulate matter (PM), particularly fine (PM2.5) and coarse (PM10) particles, is a major environmental health concern linked to increased respiratory morbidity and mortality. During the COVID-19 pandemic, epidemiological studies suggested that PM exposure may worsen SARS-CoV-2 infection outcomes; however, cellular mechanisms underlying this association remain incompletely understood. Here, we investigated how pre-exposure to PM2.5 and PM10 impacts SARS-CoV-2 infection dynamics in Calu-3 human epithelial cells. Cells were pre-exposed to PM for 72 h prior to infection with either the wild-type Wuhan strain or the more virulent Delta variant for additional 48 h. Our results show that PM10, but not PM2.5, enhanced Delta variant infection, increasing the proportion of infected cells by 13.7% and viral titers by 2.6-fold compared with controls. This enhancement was not attributable to changes in ACE2 receptor expression or viral entry efficiency but instead impaired antiviral defenses. PM10 pre-exposure suppressed apoptosis and reduced the expression of pro-inflammatory cytokines including IFN-γ, IP-10, and TNF-α during Delta infection. These findings suggest that PM10 compromise epithelial antiviral response by dampening apoptotic cell clearance and inflammatory responses, thereby creating a cellular condition more permissive to viral replication. Our study provides a mechanistic basis by which particulate air pollution may amplify SARS-CoV-2 pathogenicity in a variant-specific manner. These results underscore further validation in physiologically relevant systems and highlight the potential public health implications of air pollution during viral pandemics.