Urban Particulate Matter Impairment of Airway Surface Liquid–Mediated Coronavirus Inactivation

Stapleton, Emma M.; Welch, Jennifer L.; Ubeda, Erika A; Xiang, Jinhua; Zabner, Joseph; Thornell, Ian M.; Nonnenmann, Matthew W.; Stapleton, Jack T.; Comellas, Alejandro P.

doi:10.1093/infdis/jiab545

Cited by 5 publications

(6 citation statements)

References 14 publications

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“…It has been proposed that vitamin D deficiency increases the risk of COVID-19 incidence and severity [ 40 ]. We recapitulated our previous work demonstrating ASL to be virucidal [ 41 ], however, we found no difference in ASL-mediated 229E-CoV viral inactivation between calcitriol-treated and untreated hAEC ASL. This is consistent with a recent finding from the United Kingdom where blood 25(OH)D concentrations did not correlate with COVID-19 infection risk [ 42 ].…”

Section: Discussionsupporting

confidence: 87%

Vitamin D-mediated effects on airway innate immunity in vitro

et al. 2022

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Introduction Vitamin D supplementation has been suggested to enhance immunity during respiratory infection season. We tested the effect of active vitamin D (calcitriol) supplementation on key airway innate immune mechanisms in vitro. Methods Primary human airway epithelial cells (hAECs) grown at the air liquid interface were supplemented with 10−7 M calcitriol for 24 hours (or a time course) and their antimicrobial airway surface liquid (ASL) was tested for pH, viscoscity, and antibacterial and antiviral properties. We also tested hAEC ciliary beat frequency (CBF). Next, we assessed alterations to hAEC gene expression using RNA sequencing, and based on results, we measured neutrophil migration across hAECs. Results Calcitriol supplementation enhanced ASL bacterial killing of Staphylococcus aureus (p = 0.02) but did not enhance its antiviral activity against 229E-CoV. It had no effect on ASL pH or viscosity at three timepoints. Lastly, it did not affect hAEC CBF or neutrophil migration, although there was a trend of enhanced migration in the presence of a neutrophil chemokine (p = 0.09). Supplementation significantly altered hAEC gene expression, primarily of AMP-related genes including CAMP and TREM1. Conclusion While vitamin D supplementation did not have effects on many airway innate immune mechanisms, it may provide a useful tool to resolve respiratory bacterial infections.

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Section: Discussionsupporting

confidence: 87%

Vitamin D-mediated effects on airway innate immunity in vitro

et al. 2022

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“…Furthermore, since many of the genes assayed in this study are involved in general antiviral host defense, these results may translate to other viral pathogens of public health importance. Recently, urban PM was shown to impair antiviral properties of airway epithelial cultures toward SARS-CoV-2 and 229E-CoV, which causes the common cold ( 64 ).…”

Section: Discussionmentioning

confidence: 99%

Woodsmoke particle exposure prior to SARS-CoV-2 infection alters antiviral response gene expression in human nasal epithelial cells in a sex-dependent manner

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et al. 2022

American Journal of Physiology-Lung Cellular and Molecular Phys

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Inhalational exposure to particulate matter (PM) derived from natural or anthropogenic sources alters gene expression in the airways and increases susceptibility to respiratory viral infection. Woodsmoke-derived ambient PM from wildfire events during 2020 was associated with higher COVID-19 case rates in the western US. We hypothesized that exposure to suspensions of woodsmoke particles (WSP) or diesel exhaust particles (DEP) prior to SARS-CoV-2 infection would alter host immune gene expression at the transcript level. Primary human nasal epithelial cells (hNECs) from both sexes were exposed to WSP or DEP (22 μg/cm2) for 2 h, followed by infection with SARS-CoV-2 at a multiplicity of infection of 0.5. Forty-six genes related to SARS-CoV-2 entry and host response were assessed. Particle exposure alone minimally affected gene expression, while SARS-CoV-2 infection alone induced a robust transcriptional response in hNECs, upregulating type I and III interferons, interferon-stimulated genes, and chemokines by 72 h p.i. This upregulation was higher overall in cells from male donors. However, exposure to WSP prior to infection dampened expression of antiviral, interferon, and chemokine mRNAs. Sex-stratification of these results revealed that WSP exposure downregulated gene expression in cells from females more so than males. We next hypothesized that hNECs exposed to particles would have increased apical viral loads compared to unexposed cells. While apical viral load was correlated to expression of host response genes, viral titer did not differ between groups. These data indicate that WSP alter epithelial immune responses in a sex-dependent manner, potentially suppressing host defense to SARS-CoV-2 infection.

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“…As recently discussed (Woodby et al, 2021), virus incubation with urban PM decreased infectivity for enveloped bacteriophage Φ6 but enhanced infection by nonenveloped Φ174, possibly due to PM damage of lipid membranes in enveloped viruses (Groulx et al, 2018). In a recent mechanistic study, Stapleton et al (2022) demonstrated that urban PM affects SARS-CoV-2 and human common cold alphacoronavirus 229E (CoV-229E) infectivity by decreasing viral viability while impairing viral inactivation by primary human epithelial cells airway surface liquid (ASL). The results showed for the first time that urban PM consistently inactivated both coronaviruses in vitro, thereby decreasing ambient viral titers before inhalation (Stapleton et al, 2022).…”

Section: Resultsmentioning

confidence: 91%

“…In a recent mechanistic study, Stapleton et al (2022) demonstrated that urban PM affects SARS-CoV-2 and human common cold alphacoronavirus 229E (CoV-229E) infectivity by decreasing viral viability while impairing viral inactivation by primary human epithelial cells airway surface liquid (ASL). The results showed for the first time that urban PM consistently inactivated both coronaviruses in vitro, thereby decreasing ambient viral titers before inhalation (Stapleton et al, 2022).…”

Section: Resultsmentioning

confidence: 99%