Kongsomros S.Paha J.Prasara-a P.Visamol S.Techapichetvanich P.Jiso A.Uppakara K.Morrow A.L.Thorman A.W.Chutipongtanate S.Khemawoot P.Thitithanyanont A.Mahidol University2026-02-062026-02-062026-01-01Frontiers in Cellular and Infection Microbiology Vol.15 (2026)https://repository.li.mahidol.ac.th/handle/123456789/114663Introduction: Airborne particulate matter (PM), particularly fine (PM<inf>2.5</inf>) and coarse (PM<inf>10</inf>) 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 PM<inf>2.5</inf> and PM<inf>10</inf> impacts SARS-CoV-2 infection dynamics in Calu-3 human epithelial cells. Methods: Calu-3 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. Viral infection, receptor expression, apoptosis and cytokine responses were assessed. Results: PM<inf>10</inf>, but not PM<inf>2.5</inf>, 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. Discussion: These findings suggest that PM<inf>10</inf> 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.MedicineImmunology and MicrobiologyArticleSCOPUS10.3389/fcimb.2025.16940502-s2.0-1050278855842235298841561095