Cross-sectional associations of maternal PFAS exposure on SARS-CoV-2 IgG antibody levels during pregnancy.

BACKGROUND: Perfluoroalkylated substances (PFAS) are man-made, persistent organic compounds with immune-modulating potentials. Given that pregnancy itself represents an altered state of immunity, PFAS exposure-related immunotoxicity is an important environmental factor to consider in SARS-CoV-2 infection during pregnancy as it may further affect humoral immune responses. AIM: To investigate the relationship between maternal plasma PFAS concentrations and SARS-CoV-2 antibody levels in a NYC-based pregnancy cohort. METHODS: Maternal plasma was collected from 72 SARS-CoV-2 IgG + participants of the Generation C Study, a birth cohort established at the beginning of the COVID-19 pandemic in New York City. Maternal SARS-CoV-2 anti-spike IgG antibody levels were measured using ELISA. A panel of 16 PFAS congeners were measured in maternal plasma using a targeted UHPLC-MS/MS-based assay. Spearman correlations and linear regressions were employed to explore associations between maternal IgG antibody levels and plasma PFAS concentrations. Weighted quantile sum (WQS) regression was also used to evaluate mixture effects of PFAS. Models were adjusted for maternal age, gestational age at which SARS-CoV-2 IgG titer was measured, COVID-19 vaccination status prior to IgG titer measurement, maternal race/ethnicity, parity, type of insurance and pre-pregnancy BMI. RESULTS: Our study population is ethnically diverse with an average maternal age of 32 years. Of the 16 PFAS congeners measured, nine were detected in more than 60% samples. Importantly, all nine congeners were negatively correlated with SARS-CoV-2 anti-spike IgG antibody levels; n-PFOA and PFHxS, PFHpS, and PFHxA reached statistical significance (p < 0.05) in multivariable analyses. When we examined the mixture effects using WQS, a quartile increase in the PFAS mixture-index was significantly associated with lower maternal IgG antibody titers (beta [95% CI] = -0.35 [-0.52, -0.17]). PFHxA was the top contributor to the overall mixture effect. CONCLUSIONS: Our study results support the notion that PFAS, including short-chain emerging PFAS, act as immunosuppressants during pregnancy. Whether such compromised immune activity leads to downstream health effects, such as the severity of COVID-19 symptoms, adverse obstetric outcomes or neonatal immune responses remains to be investigated.

Exposure to a mixture of per-and polyfluoroalkyl substances modulates pulmonary expression of ACE2 and circulating hormones and cytokines.

Genetic and environmental factors impact on the interindividual variability of susceptibility to communicable and non-communicable diseases. A class of ubiquitous chemicals, Per- and polyfluoroalkyl substances (PFAS) have been linked in epidemiological studies to immunosuppression and increased susceptibility to viral infections, but possible mechanisms are not well elucidated. To begin to gain insight into the role of PFAS in susceptibility to one such viral infection, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), male and female C57BL/6 J mice were exposed to control water or a mixture of 5 PFAS (PFOS, PFOA, PFNA, PFHxS, Genx) for 12 weeks and lungs were isolated for examination of expression of SARS-CoV-2-related receptors Angiotensin-Converting Enzyme 2 (ACE2) and others. Secondary analyses included circulating hormones and cytokines which have been shown to directly or indirectly impact on ACE2 expression and severity of viral infections. Changes in mRNA and protein expression were analyzed by RT-qPCR and western blotting and circulating hormones and cytokines were determined by ELISA and MESO QuickPlex. The PFAS mixture decreased Ace2 mRNA 2.5-fold in male mice (p < 0.0001), with no significant change observed in females. In addition, TMPRSS2, ANPEP, ENPEP and DPP4 (other genes implicated in COVID-19 infection) were modulated due to PFAS. Plasma testosterone, but not estrogen were strikingly decreased due to PFAS which corresponded to PFAS-mediated repression of 4 representative pulmonary AR target genes; hemoglobin, beta adult major chain (Hbb-b1), Ferrochelatase (Fech), Collagen Type XIV Alpha 1 Chain (Col14a1), 5'-Aminolevulinate Synthase 2 (Alas2). Finally, PFAS modulated circulating pro and anti-inflammatory mediators including IFN-γ (downregulated 3.0-fold in females; p = 0.0301, 2.1-fold in males; p = 0.0418) and IL-6 (upregulated 5.6-fold in males; p = 0.030, no change in females). In conclusion, our data indicate long term exposure to a PFAS mixture impacts mechanisms related to expression of ACE2 in the lung. This work provides a mechanistic rationale for important future studies of PFAS exposure and subsequent viral infection.

Antibody response to COVID-19 vaccines among workers with a wide range of exposure to per- and polyfluoroalkyl substances.

Per- and polyfluoroalkyl substances (PFAS) are a broad class of synthetic chemicals; some are present in most humans in developed countries. Several studies have shown associations between certain PFAS, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), and reduced antibody concentration after vaccination against diseases such as Tetanus. Recent studies have reported associations between COVID-19 occurrence and exposure to certain types of PFAS. However, studies of antibody concentration after COVID-19 vaccination in relation to PFAS serum concentrations have not been reported. We examined COVID-19 antibody responses to vaccines and PFAS serum concentrations among employees and retirees from two 3M facilities, one of which historically manufactured PFOS, PFOA, and perfluorohexane sulfonic acid (PFHxS). Participants completed enrollment and follow-up study visits in the Spring of 2021, when vaccines were widely available. In total 415 participants with 757 observations were included in repeated measures analyses. Log-transformed concentrations of anti-spike IgG and neutralizing antibodies were modeled in relation to concentration of PFAS at enrollment after adjusting for antigenic stimulus group (9 groups determined by COVID-19 history and number and type of vaccination) and other variables. The fully adjusted IgG concentration was 3.45 percent lower (95% CI -7.03, 0.26) per 14.5 ng/mL (interquartile range) increase in PFOS; results for neutralizing antibody and PFOS were similar. For PFOA, PFHxS, and perfluorononanoic acid (PFNA), the results were comparable to those for PFOS, though of smaller magnitude. In our study data, the fully adjusted coefficients relating concentration of vaccine-induced antibodies to COVID-19 and interquartile range difference in serum concentration of PFOS, PFOA, PFHxS, and PFNA were inverse but small with confidence intervals that included zero. Our analysis showed that the coefficient for the four PFAS examined in detail was considerably affected by adjustment for antigenic stimulus group.

A Participatory Science Approach to Evaluating Factors Associated with the Occurrence of Metals and PFAS in Guatemala City Tap Water

Limited information is available regarding chemical water quality at the tap in Guatemala City, preventing individuals, water utilities, and public health authorities from making data-driven decisions related to water quality. To address this need, 113 participants among households served by a range of water providers across the Guatemala City metropolitan area were recruited as participatory scientists to collect first-draw and flushed tap water samples at their residence. Samples were transported to the U.S. and analyzed for 20 metals and 25 per- and polyfluoroalkyl substances (PFAS). At least one metal exceeded the Guatemalan Maximum Permissible Limit (MPL) for drinking water in 63% of households (n = 71). Arsenic and lead exceeded the MPL in 33.6% (n = 38) and 8.9% (n = 10) of samples, respectively. Arsenic was strongly associated with groundwater while lead occurrence was not associated with location, water source, or provider. One or more PFAS were detected in 19% of samples (n = 21, range 2.1–64.2 ppt). PFAS were significantly associated with the use of plastic water storage tanks but not with location, water source, or provider. Overall, the high prevalence of arsenic above the MPL in Guatemala City tap water represents a potential health risk that current water treatment processes are not optimized to remove. Furthermore, potential contaminants from premise plumbing and storage, including lead and PFAS, represent additional risks requiring further investigation and public engagement.

Influence of Perfluoroalkyl Substances on Occurrence of Coronavirus Disease 2019.

Epidemiologic evidence indicates exposure to polyfluoroalkyl substances (PFAS) influences immunosuppression, with diminished vaccination response. The relationship between PFAS blood levels and coronavirus disease 2019 (COVID-19) occurrence by age warrants further examination. This assessment identified blood PFAS exposure levels in discrete populations. Recent PFAS population studies summarizing age and gender results were identified and included. Geographically corresponding COVID-19 incidence data were determined for selected counties in North Carolina (NC) and Ohio (OH), and the state of New Jersey (NJ). Centers for Disease Control and Prevention COVID-19 databases were accessed for national incidence data by age groupings. We assessed associations between blood PFAS concentrations, COVID-19 incidence rates, and key demographic characteristics, within subpopulations. COVID-19 incidence counts and blood PFAS concentration were obtained for each age group, along with estimated U.S. Census total population. A general trend observed is higher PFAS levels in older age groups. Younger age groups contained fewer COVID-19 cases. Global COVID-19 mortality is highest in elderly populations with hospitalization and death greatly increasing from age 50. PFAS exposures occurring early in life may cause deleterious health effects later in life, including decreased antibody response and reduced disease resistance. Highest levels of both PFAS exposure and COVID-19 were found in the oldest populations. While this does not determine causality, such associations should help promote further study.

Per- and Polyfluoroalkyl Substances (PFAS) in Facemasks: Potential Source of Human Exposure to PFAS with Implications for Disposal to Landfills

Facemasks are important tools for fighting against disease spread, including Covid-19 and its variants, and some may be treated with per- and polyfluoroalkyl substances (PFAS). Nine facemasks over a range of prices were analyzed for total fluorine and PFAS. The PFAS compositions of the masks were then used to estimate exposure and the mass of PFAS discharged to landfill leachate. Fluorine from PFAS accounted only for a small fraction of total fluorine. Homologous series of linear perfluoroalkyl carboxylates and the 6:2 fluorotelomer alcohol indicated a fluorotelomer origin. Inhalation was estimated to be the dominant exposure route (40%-50%), followed by incidental ingestion (15%-40%) and dermal (11%-20%). Exposure and risk estimates were higher for children than adults, and high physical activity substantially increased inhalation exposure. These preliminary findings indicate that wearing masks treated with high levels of PFAS for extended periods of time can be a notable source of exposure and have the potential to pose a health risk. Despite modeled annual disposal of 29-91 billion masks, and an assuming 100% leaching of individual PFAS into landfill leachate, mask disposal would contribute only an additional 6% of annual PFAS mass loads and less than 11 kg of PFAS discharged to U.S. wastewater. © 2022 American Chemical Society.

Identifying environmental factors that influence immune response to SARS-CoV-2: Systematic evidence map protocol.

BACKGROUND: Widespread environmental contamination can directly interact with human immune system functions. Environmental effects on the immune system may influence human susceptibility to respiratory infections as well as the severity of infectious diseases, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, the efficacy of vaccines to respiratory diseases may be impacted by environmental exposures through immune perturbations. Given the quick pace of research about COVID-19 and associated risk factors, it is critical to identify and curate the streams of evidence quickly and effectively. OBJECTIVE: We developed this systematic evidence map protocol to identify and organize existing human and animal literature on high-priority environmental chemical classes (Per- and polyfluoroalkyl substances, pesticides, phthalates, quaternary ammonium compounds, and air pollutants) and their potential to influence three key outcomes: (1) susceptibility to respiratory infection, including SARS-CoV-2 (2) severity of the resultant disease progression, and (3) impact on vaccine efficacy. The result of this project will be an online, interactive database which will show what evidence is currently available between involuntary exposures to select environmental chemicals and immune health effects, data gaps that require further research, and data rich areas that may support further analysis. SEARCH AND STUDY ELIGIBILITY: We will search PubMed for epidemiological or toxicological literature on select toxicants from each of the chemical classes and each of the three outcomes listed above. STUDY APPRAISAL AND SYNTHESIS OF METHODS: For each study, two independent reviewers will conduct title and abstract screening as well as full text review for data extraction of study characteristics. Study quality will not be evaluated in this evidence mapping. The main findings from the systematic evidence map will be visualized using a publicly available and interactive database hosted on Tableau Public.

Environmental Health Literacy as Knowing, Feeling, and Believing: Analyzing Linkages between Race, Ethnicity, and Socioeconomic Status and Willingness to Engage in Protective Behaviors against Health Threats.

This study investigates the relationships between environmental health literacy, the characteristics of people (race, ethnicity, and socioeconomic status) associated with health disparities, and people's willingness to engage in protective behaviors against environmental health threats. Environmental health literacy is a framework for capturing the continuum between the knowledge of environmental impacts on public health, and the skills and decisions needed to take health-protective actions. We pay particular attention to three dimensions of environmental health literacy: factual knowledge (knowing the facts), knowledge sufficiency (feeling ready to decide what to do), and response efficacy (believing that protective behaviors work). In June 2020, we collected survey data from North Carolina residents on two topics: the viral infection COVID-19 and industrial contaminants called per- and polyfluoroalkyl substances (PFAS). We used their responses to test stepwise regression models with willingness to engage in protective behaviors as a dependent variable and other characteristics as independent variables, including environmental health literacy. For both topics, our results indicated that no disparities emerged according to socioeconomic factors (level of education, household income, or renting one's residence). We observed disparities in willingness according to race, comparing Black to White participants, but not when comparing White to American Indian, Alaska Native, Asian, Native Hawaiian, or Pacific Islander participants nor Hispanic to non-Hispanic participants. The disparities in willingness between Black and White participants persisted until we introduced the variables of environmental health literacy, when the difference between these groups was no longer significant in the final regression models. The findings suggest that focusing on environmental health literacy could bridge a gap in willingness to protect oneself based on factors such as race/ethnicity and socioeconomic status, which have been identified in the environmental health literature as resulting in health disparities.

Legal Extension Strategies to Increase Awareness of Drinking Water Contaminant Regulatory Framework

It is important for stakeholders, scientists, industry, lawyers, and decision-makers to understand the varying approaches to regulating drinking water contaminants. To increase awareness and understanding among stakeholder audiences of the legal framework for drinking water protection, the National Sea Grant Law Center (NSGLC) at the University of Mississippi School of Law has developed and implemented research and extension projects for lead, nitrates, and per-and polyfluorinated substances (PFAS). The NSGLC's mission is to encourage a well-informed constituency by providing legal information and analysis to the Sea Grant community, policy makers, and the general public through a variety of products and services. For each contaminant, the NSGLC conducted legal research to identify relevant laws, regulations, policies, and court decisions to gain an in-depth understanding of the existing legal framework. The NSGLC then translated its information on the current legal framework, identified gaps, and potential solutions into a variety of outreach programming. For each of the relevant drinking water contaminants, the NSGLC has taken different outreach approaches. For lead, the NSGLC has worked with an interdisciplinary academic team to conduct community-based research and outreach directly to families. With nitrates, the NSGLC has focused more on professional development for attorneys, natural resource managers, and other policy makers. With PFAS, the NSGLC is proposing a hybrid approach, drawing on lessons learned from its previous projects and the COVID-19 pandemic, to disseminate information to both professionals and communities. This case study will synthesize key findings on the legal overview, potential legal issues, and outreach efforts for lead, nitrates, and PFAS.

How to investigate human health effects related to exposure to mixtures of per- and polyfluoroalkyl substances: A systematic review of statistical methods.

BACKGROUND: Humans are exposed to several per- and polyfluoroalkyl substances (PFAS) daily; however, most previous studies have focused on individual PFAS. Although attention to effects of exposure to mixtures of PFAS has grown in recent years, there is no consensus on the appropriate statistical methods that can be used to assess their combined effect on human health. OBJECTIVES: We aim to perform a comprehensive review of the statistical methods used in the existing studies which evaluate the association between exposure to mixtures of PFAS and any adverse human health effect. METHODS: The online databases PubMed, Embase and Scopus were searched for eligible studies, published during the last ten years (last search performed on April 08, 2021). Covidence software was used by two different reviewers to perform a title/abstract screening, followed by a full text revision of the selected papers. RESULTS: A total of 3640 papers were identified, and after the screening process, 53 papers were included in the current review. Most of the studies were published between 2019 and 2021 and were conducted mainly in North America and Europe; more than half of the studies (28 out of 53) were conducted on mother and child pairs. WQS (Weighted Quantile Sum) Regression and BKMR (Bayesian Kernel Machine Regression) were used in 36 out of 53 papers to model mixtures' effects. Health outcomes included in the studies are immunotoxicity (n = 8), fetal development (n = 7), neurodevelopment (n = 9), reproductive hormones (n = 6), thyroid hormones (n = 7), outcomes related to metabolic pathways (n = 16). CONCLUSION: Studies on human exposure to PFAS as complex mixtures and health consequences have substantially increased in the last few years. Based on our findings, we propose that addressing risk from PFAS mixtures will likely require combinations of approaches and implementation of constantly evolving statistical methods. Specific guidelines and tools for quality assessment and publication of mixture observational studies are warranted.

Susceptibility to COVID-19 after High Exposure to Perfluoroalkyl Substances from Contaminated Drinking Water: An Ecological Study from Ronneby, Sweden.

There is concern that immunotoxic environmental contaminants, particularly perfluoroalkyl substances (PFAS), may play a role in the clinical course of COVID-19 and epidemiologic studies are needed to answer if high-exposed populations are especially vulnerable in light of the ongoing pandemic. The objective was, therefore, to determine if exposure to highly PFAS-contaminated drinking water was associated with an increased incidence of COVID-19 in Ronneby, Sweden, during the first year of the pandemic. We conducted an ecological study determining the sex- and age-standardized incidence ratio (SIR) in the adult population relative to a neighboring reference town with similar demographic characteristics but with only background levels of exposure. In Sweden, COVID-19 is subject to mandatory reporting, and we retrieved aggregated data on all verified cases until 3 March 2021 from the Public Health Agency of Sweden. The SIR in Ronneby was estimated at 1.19 (95% CI: 1.12; 1.27). The results suggest a potential link between high PFAS exposure and susceptibility to COVID-19 that warrants further research to clarify causality.

Perfluorobutanoic acid (PFBA): No high-level accumulation in human lung and kidney tissue.

Perfluorobutanoic acid (PFBA) belongs to the complex group of synthetic perfluoroalkyl substances (PFAS) which have led to ubiquitous environmental contamination. While some of the long-chain compounds accumulate in the human body, the short-chain compound PFBA was found to have a relatively short half-life in blood of a few days, in agreement with relatively low PFBA serum/plasma levels of roughly 0.01 ng/ml in European studies. Surprisingly, very high median levels of PFBA of 807 and 263 ng/g tissue for human lung and kidney autopsy samples, respectively, were reported in a paper of Pérez et al. (2013). This would question the concept of PFAS blood analysis reflecting the body burden of these compounds. To verify the results of high PFBA tissue accumulation in humans, we have analyzed PFBA in a set of 7 lung and 9 kidney samples from tumor patients with a different method of quantification, using high-resolution mass spectrometry with the accurate mass as analytical parameter. The only human sample with a quantifiable amount of PFBA (peak area more than twice above the analytical background signals) contained approximately 0.17 ng/g lung tissue. In the light of our results and considering the analytical problems with the short-chain compound PFBA exhibiting only one mass fragmentation, it appears to be likely that PFBA is not accumulating on a high level in human lung and kidney tissue. In general, the analysis of short-chain PFAS in complex matrices like food or tissue is very challenging with respect to instrumental quantification and possible sample contamination.

Exposure to Perfluoroalkyl Substances and Mortality for COVID-19: A Spatial Ecological Analysis in the Veneto Region (Italy).

BACKGROUND: In the context of the COVID-19 pandemic, there is interest in assessing if per- and polyfluoroalkyl substances (PFAS) exposures are associated with any increased risk of COVID-19 or its severity, given the evidence of immunosuppression by some PFAS. The objective of this paper is to evaluate at the ecological level if a large area (Red Zone) of the Veneto Region, where residents were exposed for decades to drinking water contaminated by PFAS, showed higher mortality for COVID-19 than the rest of the region. METHODS: We fitted a Bayesian ecological regression model with spatially and not spatially structured random components on COVID-19 mortality at the municipality level (period between 21 February and 15 April 2020). The model included education score, background all-cause mortality (for the years 2015-2019), and an indicator for the Red Zone. The two random components are intended to adjust for potential hidden confounders. RESULTS: The COVID-19 crude mortality rate ratio for the Red Zone was 1.55 (90% Confidence Interval 1.25; 1.92). From the Bayesian ecological regression model adjusted for education level and baseline all-cause mortality, the rate ratio for the Red Zone was 1.60 (90% Credibility Interval 0.94; 2.51). CONCLUSION: In conclusion, we observed a higher mortality risk for COVID-19 in a population heavily exposed to PFAS, which was possibly explained by PFAS immunosuppression, bioaccumulation in lung tissue, or pre-existing disease being related to PFAS.

Drinking water pollutants may affect the immune system: concerns regarding COVID-19 health effects.

The current coronavirus pandemic is leading to significant impacts on the planet, changing our way of life. Although the COVID-19 virus mechanisms of action and pathogenesis are still under extensive research, immune system effects are evident, leading, in many cases, to respiratory distress. Although apparent pollution reduction has been noticed by the population, environmental and human health impacts due to the increased use of plastic waste and disinfectants is concerning. One of the main routes of human exposure to pollutants is through drinking water. Thus, this point of view discusses some major contaminants in drinking water known to be immunotoxic, exploring sources and drinking water routes and emphasizing the known mechanisms of action that could likely compromise the effective immune response of humans, particularly raising concerns regarding people exposed to the COVID-19 virus. Based on a literature review, metals, plastic components, plasticizers, and per- and polyfluoroalkyl substances may display the potential to exacerbate COVID-19 respiratory symptoms, although epidemiological studies are still required to confirm the synergistic effects between these pollutants and the virus.