Environmentally persistent free radicals enhance SARS-CoV-2 replication in respiratory epithelium
Epidemiological evidence links lower air quality with increased incidence and severity of COVID-19; however, mechanistic data have yet to be published. We hypothesized air pollution-induced oxidative stress in the nasal epithelium increased viral replication and inflammation. Nasal epithelial cells (NECs), collected from healthy adults, were grown into a fully differentiated epithelium. NECs were infected with the ancestral strain of SARS-CoV-2. An oxidant combustion by-product found in air pollution, the environmentally persistent free radical (EPFR) DCB230, was used to mimic pollution exposure four hours prior to infection. Some wells were pretreated with antioxidant, astaxanthin, for 24 hours prior to EPFR-DCB230 exposure and/or SARS-CoV-2 infection. Outcomes included viral replication, epithelial integrity, surface receptor expression (, ), cytokine mRNA expression (, ), intracellular signaling pathways, and oxidative defense enzymes. SARS-CoV-2 infection induced a mild phenotype in NECs, with some cell death, upregulation of the antiviral cytokine , but had little effect on intracellular pathways or oxidative defense enzymes. Prior exposure to EPFR-DCB230 increased SARS-CoV-2 replication, upregulated expression, increased secretion of the proinflammatory cytokine , inhibited expression of the mucus producing gene, upregulated expression of (apoptosis pathway), (mitophagy pathway), and reduced levels of antioxidant enzymes. Pretreatment with astaxanthin reduced SARS-CoV-2 replication, downregulated expression, and prevented most, but not all EPFR-DCB230 effects. Our data suggest that oxidant damage to the respiratory epithelium may underly the link between poor air quality and increased COVID-19. The apparent protection by antioxidants warrants further research.
Publication Source (Journal or Book title)
Experimental biology and medicine (Maywood, N.J.)
Yamamoto, A., Sly, P. D., Chew, K. Y., Khachatryan, L., Begum, N., Yeo, A. J., Vu, L. D., & Short, K. R. (2023). Environmentally persistent free radicals enhance SARS-CoV-2 replication in respiratory epithelium. Experimental biology and medicine (Maywood, N.J.), 15353702221142616. https://doi.org/10.1177/15353702221142616