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.

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

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 ß 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.