An overlooked health risk of PM2.5: Elevated respiratory viral susceptibility revealed by assessing inflammatory and antiviral responses to chemical constituents

Abstract

Epidemiological evidence linked PM_2.5 exposure to increased virus transmission, yet the impact of chemical composition of PM_2.5 on viral susceptibility remains unclear. We characterized the constituents of water-soluble matters (WSM) in PM_2.5 from urban Guangzhou and their association with pseudotyped SARS-CoV-2 infectivity, inflammatory and antiviral responses in A549 cells. Chemical analysis revealed considerable variability in chemical composition across all samples, although all samples were dominated by inorganic ions (e.g., NO₃⁻, SO₄²⁻, NH₄⁺) and WSOM (e.g., lipids, oxy-aromatics), with metals constituted ∼1.2 %, primarily Cu, Fe, and Al. WSM exposure elevated viral infectivity (1.3–5.6-fold), IL-8 and TNF-α generation (1.2–5.2-fold), and suppressed IFN-β by 24 %–74 %, with minimal effects on IFN-α and surfactant proteins. An explainable machine learning analysis indicated that transition metals (e.g., Ni, V, Mn, Fe), inorganic ions (e.g., SO₄²⁻, Na⁺, K⁺), highly unsaturated oxy-aromatics (Xc ≥ 2.5, DBE ≥6) and protein1 with 0.2 < O/C ≤ 0.6 and 0.9 < H/C < 2.5 were positively linked to IL-8 and TNF-α induction, whereas trace metals (e.g., Cr, Al) and protein2 with 0.6 < O/C ≤ 1 and 1.2 < H/C < 2.5 were both associated with enhanced infectivity and IFN-β inhibition. Notably, viral infectivity remained uncorrelated with inflammatory cytokines but showed an inverse correlation with IFN-β expression consistently observed during WSM-only and WSM + virus co-exposure, suggesting that PM_2.5 may impair interferon-mediated defenses to exacerbate viral susceptibility. Our study uncovers an overlooked health risk of PM_2.5 thereby filling a critical gap in understanding the multifaceted health effect of PM_2.5 exposure.