Dataset Information

Association between urinary per- and poly-fluoroalkyl substances and COVID-19 susceptibility.

ABSTRACT:

Background and objective

The growing impact of the COVID-19 pandemic has heightened the urgency of identifying individuals most at risk of infection. Per- and poly-fluoroalkyl substances (PFASs) are manufactured fluorinated chemicals widely used in many industrial and household products. The objective of this case-control study was to assess the association between PFASs exposure and COVID-19 susceptibility and to elucidate the metabolic dysregulation associated with PFASs exposure in COVID-19 patients.

Methods

Total 160 subjects (80 COVID-19 patients and 80 symptom-free controls) were recruited from Shanxi and Shandong provinces, two regions heavily polluted by PFASs in China. Twelve common PFASs were quantified in both urine and serum. Urine metabolome profiling was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).

Results

In unadjusted models, the risk of COVID-19 infection was positively associated with urinary levels of perfluorooctanesulfonic acid (PFOS) (Odds ratio: 2.29 [95% CI: 1.52-3.22]), perfluorooctanoic acid (PFOA) (2.91, [1.95-4.83], and total PFASs (∑ (12) PFASs) (3.31, [2.05-4.65]). After controlling for age, sex, body mass index (BMI), comorbidities, and urine albumin-to-creatinine ratio (UACR), the associations remained statistically significant (Adjusted odds ratio of 1.94 [95% CI: 1.39-2.96] for PFOS, 2.73 [1.71-4.55] for PFOA, and 2.82 [1.97-3.51] for ∑ (12) PFASs). Urine metabolome-PFASs association analysis revealed that 59% of PFASs-associated urinary endogenous metabolites in COVID-19 patients were identified to be produced or largely regulated by mitochondrial function. In addition, the increase of PFASs exposure was associated with the accumulation of key metabolites in kynurenine metabolism, which are involved in immune responses (Combined β coefficient of 0.60 [95% CI: 0.25-0.95, P = 0.001]). Moreover, alternations in PFASs-associated metabolites in mitochondrial and kynurenine metabolism were also correlated with clinical lab biomarkers for mitochondrial function (serum growth/differentiation factor-15) and immune activity (lymphocyte percentage), respectively.

Conclusion

Elevated exposure to PFASs was independently associated with an increased risk of COVID-19 infection. PFASs-associated metabolites were implicated in mitochondrial function and immune activity. Larger studies are needed to confirm our findings and further understand the underlying mechanisms of PFASs exposure in the pathogenesis of SARS-CoV2 infection.

SUBMITTER: Ji J

PROVIDER: S-EPMC7972714 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Human ingestion of per- and polyfluoroalkyl substances (PFAS) from contaminated food and water is linked to the development of several cancers, birth defects and other illnesses. The complete mineralisation of aqueous PFAS by ultrasound (sonolysis) into harmless inorganics has been demonstrated in many studies. However, the range and interconnected nature of reaction parameters (frequency, power, temperature etc.), and variety of reaction metrics used, limits understanding of degradation mechanisms and parametric trends. This work summarises the state-of-the-art for PFAS sonolysis, considering reaction mechanisms, kinetics, intermediates, products, rate limiting steps, reactant and product measurement techniques, and effects of co-contaminants. The meta-analysis showed that mid-high frequency (100 - 1,000 kHz) sonolysis mechanisms are similar, regardless of reaction conditions, while the low frequency (20 - 100 kHz) mechanisms are specific to oxidative species added, less well understood, and generally slower than mid-high frequency mechanisms. Arguments suggest that PFAS degradation occurs via adsorption (not absorption) at the bubble interface, followed by headgroup cleavage. Further mechanistic steps toward mineralisation remain to be proven. For the first time, complete stoichiometric reaction equations are derived for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) sonolysis, which add H2 as a reaction product and consider CO an intermediate. Fluorinated intermediate products are derived for common, and more novel PFAS, and a naming system proposed for novel perfluoroether carboxylates. The meta-analysis also revealed the transition between pseudo first and zero order PFOA/S kinetics commonly occurs at 15 - 40 µM. Optimum values of; ultrasonic frequency (300 - 500 kHz), concentration (>15 - 40 μM), temperature (≈20 °C), and pH range (3.2 - 4) for rapid PFOX degradation are derived by evaluation of prior works, while optimum values for the dilution factor applied to PFAS containing firefighting foams and applied power require further work. Rate limiting steps are debated and F- is shown to be rate enhancing, while SO42- and CO2 by products are theorised to be rate limiting. Sonolysis was compared to other PFAS destructive technologies and shown to be the only treatment which fully mineralises PFAS, degrades different PFAS in order of decreasing hydrophobicity, is parametrically well studied, and has low-moderate energy requirements (several kWh g-1 PFAS). It is concluded that sonolysis of PFAS in environmental samples would be well incorporated within a treatment train for improved efficiency.

Project description:Seafood consumption has been identified as one of the major contributors of per- and poly(fluoroalkyl) substances (PFASs) to the human diet. To assess dietary exposure, highly consumed seafood products in the United States were selected for analysis. The analytical method previously used for processed food was extended to include four additional long-chain perflurocarboxylic acids (PFCAs), which have been reported in seafood samples. This method was single-lab-validated, and method detection limits were reported at 345 ng kg-1 for perfluorobutanoic acid (PFBA) and 207 ng kg-1 for perfluoropentanoic acid (PFPeA) and below 100 ng kg-1 for the rest of the PFAS analytes. The 81 seafood samples (clams, crab, tuna, shrimp, tilapia, cod, salmon, pollock) were analyzed for 20 PFASs using the updated analytical method. Most of the seafood packaging was also analyzed by Fourier transform infrared-attenuated total reflectance (FTIR-ATR) to identify packaging potentially coated with PFASs. None of the packaging samples in this study were identified as having PFASs. A wide range of concentrations was observed among the seafood samples, ranging from below the method detection limit to the highest concentration of 23 μg kg-1 for the sum of PFASs in one of the canned clam samples. Such a wide range is consistent with those reported in previous studies. The highest concentrations were reported in clams and crabs, followed by cod, tuna, pollock, tilapia, salmon, and shrimp. Technical perfluorooctanoic acid (PFOA) dominated the profile of the clam samples, which has been consistently found in other clam samples, especially in Asia. Long-chain PFCAs, specifically perfluoroundecanoic (PFUdA) and perfluorododecanoic (PFDoA), were the most frequently detected analytes across all seafood samples. The trends observed are comparable with those in the literature where benthic organisms tend to have the highest PFAS concentrations, followed by lean fish, fatty fish, and aquaculture. The results from this study will be used to prioritize future studies and to inform steps to reduce consumer exposure to PFASs.

Project description:BackgroundPer- and poly-fluoroalkyl substances (PFAS) exposure can occur through ingestion of contaminated food and water, and inhalation of indoor air contaminated with these chemicals from consumer and industrial products. Prenatal PFAS exposures may confer risk for pregnancy-related outcomes such as hypertensive and metabolic disorders, preterm birth, and impaired fetal development through intermediate metabolic and inflammation pathways.ObjectiveEstimate associations between maternal pregnancy PFAS exposure (individually and as a mixture) and bioactive lipids.MethodsOur study included pregnant women in the Environmental influences on Child Health Outcomes Program: Chemicals in our Bodies cohort (CiOB, n=73), Illinois Kids Developmental Study (IKIDS, n=287), and the ECHO-PROTECT cohort (n=54). We measured twelve PFAS in serum and 50 plasma bioactive lipids (parent fatty acids and eicosanoids derived from cytochrome p450, lipoxygenase, and cyclooxygenase) during pregnancy (median 17 gestational weeks). Pairwise associations across cohorts were estimated using linear mixed models and meta-analysis. Associations between the PFAS mixture and individual bioactive lipids were estimated using quantile g-computation.ResultsPFDeA, PFOA, and PFUdA were associated (p<0.05) with changes in bioactive lipid levels in all three enzymatic pathways (cyclooxygenase [n=6 signatures]; cytochrome p450 [n=5 signatures]; lipoxygenase [n=7 signatures]) in at least one combined cohort analysis. The strongest signature indicated that a doubling in PFOA corresponded with a 24.3% increase (95% CI [7.3%, 43.9%]) in PGD2 (cyclooxygenase pathway) in the combined cohort. In the mixtures analysis, we observed nine positive signals across all pathways associated with the PFAS mixture. The strongest signature indicated that a quartile increase in the PFAS mixture was associated with a 34% increase in PGD2 (95% CI [8%, 66%]), with PFOS contributing most to the increase.ConclusionsBioactive lipids were revealed as biomarkers of PFAS exposure and could provide mechanistic insights into PFAS' influence on pregnancy outcomes, informing more precise risk estimation and prevention strategies.

Project description:BackgroundPrenatal exposure to per- and poly-fluoroalkyl substances (PFAS) and psychosocial stressors has been associated with adverse pregnancy outcomes, including preterm birth. Previous studies have suggested that joint exposure to environmental chemical and social stressors may be contributing to disparities observed in preterm birth. Elevated corticotropin-releasing hormone (CRH) during mid-gestation may represent one biologic mechanism linking chemical and nonchemical stress exposures to preterm birth.MethodsUsing data from a prospective birth cohort (N = 497), we examined the cross-sectional associations between five individual PFAS (ng/mL; PFNA, PFOA, PFOS, PFHxS, and Me-PFOSA-AcOH) and CRH (pg/mL) using linear regression. PFAS and CRH were measured during the second trimester in serum and plasma, respectively. Coefficients were standardized to reflect change in CRH associated with an interquartile range (IQR) increase in natural log-transformed PFAS. We additionally examined if the relationship between PFAS and CRH was modified by psychosocial stress using stratified models. Self-reported depression, stressful life events, perceived stress, food insecurity, and financial strain were assessed using validated questionnaires during the second trimester and included as binary indicators of psychosocial stress.ResultsAn IQR increase in PFNA was associated with elevated CRH (β = 5.17, 95% confidence interval [CI] = 1.79, 8.55). Increased concentrations of PFOA were also moderately associated with CRH (β = 3.62, 95% CI = -0.42, 7.66). The relationship between PFNA and CRH was stronger among women who experienced stressful life events, depression, food insecurity, and financial strain compared to women who did not experience these stressors.ConclusionsThis cross-sectional study is the first to examine the relationship between PFAS exposure and CRH levels in mid-gestation. We found that these associations were stronger among women who experienced stress, which aligns with previous findings that chemical and nonchemical stressor exposures can have joint effects on health outcomes.