Epigenetics at the Intersection of COVID-19 Risk and Environmental Chemical Exposures

Abstract

Purpose of Review Several environmental contaminants have been implicated as contributors to COVID-19 susceptibility and severity. Immunomodulation and epigenetic regulation have been hypothesized as mediators of this relationship, but the precise underlying molecular mechanisms are not well-characterized. This review examines the evidence for epigenetic modification at the intersection of COVID-19 and environmental chemical exposures. Recent Findings Numerous environmental contaminants including air pollutants, toxic metal(loid)s, per- and polyfluorinated substances, and endocrine disrupting chemicals are hypothesized to increase susceptibility to the SARS-CoV-2 virus and the risk of severe COVID-19, but few studies currently exist. Drawing on evidence that many environmental chemicals alter the epigenetic regulation of key immunity genes and pathways, we discuss how exposures likely perturb host antiviral responses. Specific mechanisms vary by contaminant but include general immunomodulation as well as regulation of viral entry and recognition, inflammation, and immunologic memory pathways, among others. Summary Associations between environmental contaminants and COVID-19 are likely mediated, in part, by epigenetic regulation of key immune pathways involved in the host response to SARS-CoV-2.

Sex-Specific Associations between Prenatal Exposure to Di(2-ethylhexyl) Phthalate, Epigenetic Age Acceleration, and Susceptibility to Early Childhood Upper Respiratory Infections

“…Given the potential sensitivity of the developing immune system to early phthalate exposure, researchers have called for critical policy reforms and stricter regulations on phthalates such as DEHP to protect healthy development in children. The limited evidence on potential biological mechanisms through which phthalates may adversely affect immune system development may be one of the reasons that these chemicals are still considered safe exposures for pregnant women and children [80,81]. This was the first study to examine infant epigenetic age as a potential biomolecular mediator of the immunosuppressive effects of prenatal exposure to DEHP, and future well-powered investigations are needed to replicate and validate the present findings.…”

“…A recent epigenome-wide investigation indicated that prenatal exposure to phthalates may program the activity and signaling pathways of immune cells and sex steroid hormones in infants [76], both of which have important implications for sex differences in the capacity to cope with infections and the later development of inflammatory conditions and autoimmune disorders [84,85]. Additional work is needed to understand how prenatal DEHP exposure contributes to developmental immunotoxicity [80,81] and the biological (e.g., immunological, epigenetic) mechanisms that transmit risk in young girls and boys.…”

Individual blood concentrations of persistent organic pollutants and chemical elements, and COVID-19: A prospective cohort study in Barcelona

“…The results should encourage translational research from the observations we made in a real human population to the clinic and the laboratory ( Porta et al, 2014b ); that is, they can inspire clinical and laboratory research on mechanisms through which the environmental agents we studied may influence immune processes and contribute to general immunomodulation, hypersensitivity, inappropriate enhancement, immunosuppression, autoimmunity, viral entry and recognition, endocrine and metabolic disruption, glucose metabolism, cytokine production, inflammation, host susceptibility to infection and disease severity, epigenetic modification of immunomodulatory genes, and immunologic memory pathways, among others ( Weaver et al, 2022 ; Gore et al, 2015 ; Dietert et al, 2010 ; Germolec et al, 2022 ; International Programme on Chemical Safety, 2012 ; Alper and Sawyer, 2019 ; Bulka et al, 2022 ; Kostoff et al, 2023 ; Clerbaux et al, 2022 ; Courtin and Vineis, 2021 ). Several of these pathways overlap with those involved in the host response to the SARS-CoV-2 virus and may contribute to explain the associations we report.…”

“…Numerous environmental chemicals are immunoactive and cause a range of adverse clinical effects ( Karachaliou et al, 2021 ; Kogevinas et al, 2021 ; Weaver et al, 2022 ; Gore et al, 2015 ; Dietert et al, 2010 ; Germolec et al, 2022 ; International Programme on Chemical Safety, 2012 ; Alper and Sawyer, 2019 ; Bulka et al, 2022 ; Franza and Cianci, 2021 ). It has been hypothesized that some agents, including persistent organic pollutants (POPs) and chemical elements, might also affect the risk of COVID-19 across multiple systems and pathways ( Weaver et al, 2022 ; Bulka et al, 2022 ; Rayasam et al, 2022 ; Kostoff et al, 2023 ; Clerbaux et al, 2022 ). However, uncertainties abound, particularly for the so-called rare earth elements and other chemical elements (including some metals, essential trace elements, and minority elements).…”

Long-Term Exposure to Air Pollution and COVID-19 Vaccine Antibody Response in a General Population Cohort (COVICAT Study, Catalonia)

“… 12 – 14 The negative impact of chronic inflammation on vaccines efficacy has been seen mainly in the elderly and in chronic inflammatory conditions. 15 In relation to COVID-19, air pollutants may alter several immune pathways also mediated by epigenetic regulation 16 that are involved in the development and severity of the disease and could also affect vaccine efficacy.…”