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Eliana Ferroni,1 Paolo Giorgi Rossi,2 Stefania Spila Alegiani,3 Gianluca Trifirò,4 Gisella Pitter,1 Olivia Leoni,5 Danilo Cereda,5 Massimiliano Marino,2 Michele Pellizzari,1 Massimo Fabiani,6 Flavia Riccardo,6 Janet Sultana,4 Marco Massari3 On behalf of The ITA-COVID Working Group1Azienda Zero of the Veneto Region, Padua, Italy; 2Azienda Unità Sanitaria Locale – IRCCS, Reggio Emilia, Italy; 3National Center for Drug Research and Evaluation, Istituto Superiore Di Sanità, Rome, Italy; 4Department of Biomedical and Dental Sciences and Morphofunctional Imaging – University of Messina, Messina, Italy; 5Department of Health of Lombardy Region, Milan, Italy; 6Department of Infectious Diseases, Istituto Superiore Di Sanità, Rome, ItalyCorrespondence: Stefania Spila AlegianiIstituto Superiore Di Sanità, Viale Regina Elena, 299, Rome 00161, ItalyTel +39 0649904249Fax +39 0649904248Email stefania.spila@iss.itPaolo Giorgi RossiAzienda Unità Sanitaria Locale – IRCCS, Reggio Emilia, via Amendola 2, Reggio Emilia 42122, ItalyTel +39 0522335490Email paolo.giorgirossi@ausl.re.itIntroduction: COVID-19 case fatality rate in hospitalized patients varies across countries and studies. Reliable estimates, specific for age, sex, and comorbidities, are needed to monitor the epidemic, to compare the outcome in different settings, and to correctly design trials for COVID-19 interventions. The aim of this study was to provide population-based survival curves of hospitalized COVID-19 patients.Materials and Methods: A cohort study was conducted in three areas of Northern Italy, heavily affected by SARS-CoV-2 infection (Lombardy and Veneto Regions, and Reggio Emilia province), using a loco-regional COVID-19 surveillance system, linked to hospital discharge databases. We included all patients testing positive for SARS-CoV-2 RNA by RT-PCR on nasopharyngeal/throat swab samples who were hospitalized from 21 February to 21 April 2020. Kaplan–Meier survival estimates were calculated at 14 and 30 days for death in any setting, stratifying by age, sex, and the Charlson Index.Results: Overall, 42,926 hospitalized COVID-19 patients were identified. Patients’ median age was 69 years (IQR: 57– 79), 62.6% were males, and 6.0% had a Charlson Index ≥ 3. Survival curves showed that 22.0% (95% CI 21.6– 22.4) of patients died within 14 days and 27.6% (95% CI 27.2– 28.1) within 30 days from hospitalization. Survival was higher in younger patients and in females. The negative impact of comorbidities on survival was more pronounced in younger age groups.Conclusion: The high fatality rate observed in the study (28% at 30 days) suggests that studies should focus on death as primary endpoint during a follow-up of at least one month.Keywords: COVID-19, survival, cohort study, hospitalized patients, Italy

Introduction: Perfluoroalkyl substances (PFAS) are widely used, ubiquitous and highly persistent man-made chemicals. Previous cross-sectional studies have consistently linked PFAS exposure to alterations in lipid profiles. However, longitudinal investigations are preferred to mitigate issues related to reverse causation and confounding. Hence, we aimed to investigate the association between changes in serum PFAS and changes in serum lipids, while shedding light on potential modifiers of the examined relationships., Methods: We used data from a health surveillance program offered to residents of a vast area of the Veneto Region (North-Eastern Italy), who had been exposed to PFAS via contaminated drinking water until 2013. We included subjects aged ≥20 years who provided two blood samples over an average 4-year interval (n = 8101). We examined the relationships between changes in PFOA, PFOS and PFHxS and changes in total cholesterol (TC), high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol (LDL-C). Linear models were fitted for change in the natural logarithm (ln) of each lipid in relation to the change in the ln of PFAS. From the estimated regression coefficients, we calculated the predicted percentage change in the response for a ln-decrease in PFAS serum concentrations., Results: Overall concentrations of PFOA, PFOS, PFHxS fell by 62.1 %, 24.4 % and 35.4 % from baseline, while small increases in lipids were observed. Declines in PFAS concentrations were associated with decreases in all lipids. For a ln-decrease in PFOA HDL-C decreased by 1.99 % (95 % CI: 1.28, 2.70), TC by 1.49 % (95 % CI: 0.88, 2.10), and LDL-C by 1.40 % (95 % CI: 0.45, 2.37)., Conclusions: We found a positive association between changes in PFAS concentrations and changes in cholesterol levels, observing the most marked contrasts across sexes and age groups. Our findings support the reversibility of the associations identified in cross-sectional analyses, emphasizing the importance of water treatment measures in mitigating adverse health effects., (Copyright © 2024. Published by Elsevier B.V.)

Background: Perfluoroalkyl substances (PFAS) are widely used, ubiquitous, and highly persistent man-made chemicals. Groundwater of a vast area of the Veneto Region (northeastern Italy) was found to be contaminated by PFAS from a manufacturing plant active since the late 1960s. As a result, residents were overexposed to PFAS through drinking water until 2013, mainly to perfluorooctanoic acid (PFOA)., Objectives: The aim of the present study was to estimate the rates of decline in serum PFOA and their corresponding serum half-lives, while characterizing their determinants., Methods: We investigated 5,860 subjects more than 14 years of age who enrolled in the second surveillance round of the regional health surveillance program. Two blood samples were collected between 2017 and 2022 (average time between measurements: 4 years). Serum PFOA excretion rates and half-lives were estimated based on linear mixed effect models, modeling subject-specific serum PFOA concentrations over time and correcting for background concentrations. For modeling determinants of half-life [age, sex, body mass index (BMI), smoking-habit, alcohol consumption, and estimated glomerular filtration rate (eGFR)], we added interaction terms between each covariate and the elapsed time between measurements. Perfluorooctanesulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) apparent half-lives were also estimated. A separate analysis was conducted in children ( n = 480 ). All analyses were stratified by sex., Results: Median initial serum concentrations of PFOA was 49  ng / mL (range: 0.5-1,090), with a median reduction of 62.45%. The mean estimated PFOA half-life was 2.36 years [95% confidence interval (CI): 2.33, 2.40], shorter in women (2.04; 95% CI: 2.00, 2.08) compared to men (2.83; 95% CI: 2.78, 2.89). Half-lives varied when stratified by some contributing factors, with faster excretion rates in nonsmokers and nonalcohol drinkers (especially in males)., Conclusions: This study, to our knowledge the largest on PFOA half-life, provides precise estimates in young adults whose exposure via drinking water has largely ceased. For other PFAS, longer half-lives than reported in other studies can be explained by some ongoing exposure to PFAS via other routes. https://doi.org/10.1289/EHP13152.

Background: Knowledge about the dynamics of transmission of SARS-CoV-2 and the clinical aspects of COVID-19 has steadily increased over time, although evidence of the determinants of disease severity and duration is still limited and mainly focused on older adult and fragile populations., Methods: The present study was conceived and carried out in the Emilia-Romagna (E-R) and Veneto Regions, Italy, within the context of the EU's Horizon 2020 research project called ORCHESTRA (Connecting European Cohorts to increase common and effective response to SARS-CoV-2 pandemic) (www.orchestra-cohort.eu). The study has a multicenter retrospective population-based cohort design and aimed to investigate the incidence and risk factors of access to specific healthcare services (outpatient visits and diagnostics, drug prescriptions) during the post-acute phase from day-31 to day-365 after SARS-CoV-2 infection, in a healthy population at low risk of severe acute COVID-19. The study made use of previously recorded large-scale healthcare data available in the administrative databases of the two Italian Regions. The statistical analysis made use of methods for competing risks. Risk factors were assessed separately in the two Regions and results were pooled using random effects meta-analysis., Results: There were 35,128 subjects in E-R and 88,881 in Veneto who were included in the data analysis. The outcome (access to selected health services) occurred in a high percentage of subjects in the post-acute phase (25% in E-R and 21% in Veneto). Outpatient care was observed more frequently than drug prescriptions (18% vs. 12% in E-R and 15% vs. 10% in Veneto). Risk factors associated with the outcome were female sex, age greater than 40 years, baseline risk of hospitalization and death, moderate to severe acute COVID-19, and acute extrapulmonary complications., Conclusion: The outcome of interest may be considered as a proxy for long-term effects of COVID-19 needing clinical attention. Our data suggest that this outcome occurs in a substantial percentage of cases, even among a previously healthy population with low or mild severity of acute COVID-19. The study results provide useful insights into planning COVID-19-related services., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gagliotti, Banchelli, De Paoli, Buttazzi, Narne, Ricchizzi, Schievano, Bellio, Pitter, Tonon, Canziani, Rolli, Tacconelli, Berti, Russo and Moro.)

Since the beginning of the COVID-19 pandemic, wastewater-based epidemiology (WBE) has been depicted as a promising environmental surveillance tool and early warning system. Predictive models for the estimate of COVID-19 cases from wastewater viral loads also earned lot of interest and are currently under development. Hereby a pilot study that compares WBE surveillance data with confirmed cases, total hospitalizations, doses of vaccine administered and predominance of coronavirus variants. Composite 24hrs wastewater samples were collected weekly between September 2021 and July 2022 from Padua wastewater treatment plant. Samples were processed following a previously published method. One-step RT-qPCR was performed for quantification, adapting an Orf1b-nsp14 gene assay. Variant replacement was derived from the monthly bulletins of the Italian National Health Institute. Aggregate data on vaccine doses administered and on COVID-19 prevalence and hospitalizations were retrieved from official reports. Eighty-two samples were processed. Viral loads highlighted 3 major peaks in January, April and July 2022. Quantitation of SARS-CoV-2 in wastewater and clinical surveillance resulted temporally juxtaposable. However, variation of the two curves is not proportional. SARS-CoV-2 showed its highest peak in April, whereas maximum COVID-19 prevalence was achieved in January. Total hospitalizations followed the prevalence trend. Omicron BA.1 started to replace the Delta variant in December 2021. Subsequently, the shift towards Omicron BA.2 occurred between February and April 2022. Finally, BA.4/5 attested around June, somehow preceding the summer peak. Emergence of Omicron BA.1 over Delta could be a possible driver of the increase in both clinical cases and wastewater viral load in January 2022. In late March 2022, Omicron BA.2 replaced BA.1: this reflected in a steep increase of wastewater viral load, but not of COVID-19 confirmed cases. When a dramatic drop in the testing capacity of clinical surveillance occurred, WBE was possibly capable of detecting a substantial increase in viral circulation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: We examined differences in blood pressure (BP) levels between first-generation immigrants and natives in adult residents in Northeast Italy, and investigated the role of lifestyle behaviors, body mass index (BMI), and education as potentially modifiable mediating factors., Methods: We included 20-69-year-old participants from the Health Surveillance Program of the Veneto Region (n = 37,710). Immigrants born in a high migratory pressure country (HMPC) were further grouped into geographical macro-areas. The outcomes were systolic BP (SBP) and hypertension. Multiple mediation analyses were performed to determine the contribution of each mediator of the SBP/migrant status association., Results: Of the 37,380 subjects included, 8.7% were born in an HMPC. BMI, education, alcohol, sweets and meat consumption were included as potential mediators. A small advantage in SBP was seen for immigrants compared to natives (β =  - 0.71,95%CI  - 1.30;  - 0.10). The direct effect (net of the covariates) of immigrant status on SBP was a reduction of 1.62 mmHg (95%CI  - 2.25;  - 0.98). BMI played the highest suppressive role (β = 1.14,95%CI 0.99; 1.35), followed by education. Alcohol consumption amplified the health advantage of immigrants. The suppressing effect of BMI was particularly evident among women and North Africans compared to natives. Similar results were seen for hypertension rates., Conclusions: Although causation cannot be proven given the cross-sectional design, our findings identify BMI as the most effective target to preserve the health advantage of immigrants with respect to BP levels., (© 2023. The Author(s).)

Introduction: The health condition of immigrants traditionally follows a transition from a low disease occurrence to the epidemiological profile of the deprived groups in the host country. In the Europe, studies examining differences in biochemical and clinical outcomes among immigrants and natives are lacking. We examined differences in cardiovascular risk factors between first-generation immigrants and Italians, and how migration pattern variables could affect health outcomes., Material and Methods: We included participants between 20 and 69 years recruited from a Health Surveillance Program of the Veneto Region. Blood pressure (BP), total cholesterol (TC) and LDL cholesterol levels were measured. Immigrant status was defined by being born in a high migratory pressure country (HMPC) and subdivided by geographical macro-areas. We used generalized linear regression models to investigate differences between these outcomes among immigrants compared to native-born, adjusting for age, sex, education, BMI, alcohol consumption, smoking status, food consumption, salt consumption in the BP analysis and the laboratory in charge for cholesterol analysis. Within immigrant subjects, the results were stratified by variables of the migration pattern: age at immigration and length of residence in Italy., Results: Thirty seven thousand three hundred and eighty subjects were included in the analysis, 8.6% were born in an HMPC. Heterogeneous results were seen by the macro-areas of origin and sex, with male immigrants from CE Europe (β = 8.77 mg/dl) and Asia (β = 6.56 mg/dl) showing higher levels of TC than native-born, while female immigrants from Northern Africa showed lower levels of TC (β = -8.64 mg/dl). BP levels were generally lower among immigrants. Immigrants residing in Italy for more than 20 years had lower levels of TC (β = -2.9 mg/dl) than native-born. In contrast, immigrants who arrived <20 years ago or arrived older than 18 years had higher levels of TC. This trend was confirmed for CE Europeans and was inverted for Northern Africans., Conclusions: The large heterogeneity in the results depending on sex and macro-area of origin indicates the need for targeted intervention in each specific immigrant group. The results confirm that acculturation leads to a convergence toward the epidemiological profile of the host population that depends on the starting condition of the immigrant group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dalla Zuanna, Batzella, Pitter, Russo, Spadea and Canova.)

Background: Residents of a large area in the Veneto Region (Northeastern Italy) were exposed to drinking water contaminated by perfluoroalkyl substances (PFAS) for decades. While exposure to PFAS has been consistently associated with elevated serum lipids, combined exposures to multiple PFASs have been poorly investigated. Utilising different statistical approaches, we examine the association between chemical mixtures and lipid parameters., Methods: Cross-sectional data from the regional health surveillance program (34,633 individuals aged 20-64 years) were used to examine the combined effects of PFAS mixture (Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS)) on total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Weighted Quantile Sum (WQS) regression, Quantile-based G-computation (Q-Gcomp) and Bayesian Kernel Machine Regression (BKMR) were used based on their ability to handle highly correlated chemicals., Results: We observed that each quartile increase in the WQS index was associated with an increase in the levels of TC (β: 4.09, 95% CI: 3.47-4.71), HDL-C (β: 1.13, 95% CI: 0.92-1.33) and LDL-C (β: 3.14, 95% CI: 2.65-3.63). Q-Gcomp estimated that a quartile increase in the PFAS mixture was associated with increased TC (ψ: 4.04, 95% CI 3.5-4.58), HDL-C (ψ: 1.07, 95% CI 20.87-1.27) and LDL-C (ψ: 2.71, 95% CI 2.23-3.19). In the BKMR analysis, the effect of PFAS mixture on serum lipids increased significantly when their concentrations were at their 75th percentiles or above, compared to those at their 50th percentile. All methods revealed a major contribution of PFOS and PFNA, although the main exposure was due to PFOA. We found suggestive evidence that associations varied when stratified by gender., Conclusions: The PFAS mixture was positively associated with lipid parameters, regardless of the applied method. Very similar results obtained from the three methods may be attributed to the linear positive association with the outcomes and no interaction between each PFAS.

Background: Perfluoroalkyl substances (PFAS) have been consistently associated with cardio-metabolic traits. Occupational exposures to multiple PFAS with health outcomes have been poorly investigated. The aim of the present study was to examine these associations among former workers involved in PFAS production., Methods: We considered 232 male ex-employees who had worked in a factory (Trissino, Veneto Region, Italy), which produced PFAS and other chemicals during 1968-2018. Out of twelve serum PFAS, only four (PFOA, PFOS, PFHxS, and PFNA) were quantifiable in at least 50% of samples. Non-fasting serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. The associations between serum PFAS mixture and considered outcomes were assessed through linear regression mixed models and Weighted Quantile Sum (WQS) regression, adjusting for potential confounders., Results: PFOA was detected at the highest level, with a median concentration (in ng/mL) of 80.8 (min-max: 0.35-13,033), followed by PFOS (median: 8.55, min-max: 0.35-343), PFHxS (median: 6.8, min-max: 0.35-597) and PFNA (median: 0.8, min-max: 0.35-5). We observed that each A quartile increase in the WQS index was positively associated with the levels of TC (β: 8.41, 95% IC: 0.78-16.0), LDL-C (β: 8.02, 95% IC: 1-15.0) and SBP (β: 3.21, 95% IC: 0.82-5.60). No association of serum PFAS concentration on HDL cholesterol and DBP emerged. WQS analyses revealed a major contribution of PFNA and PFHxS for the cholesterol levels, although PFOA reported the highest concentration. PFOA and PFOS emerged as chemicals of concern regarding the association with SBP., Conclusions: The results showed a clear association between serum PFAS levels and markers of cardiovascular risk and support the importance of clinical surveillance of cardiovascular risk factors in population with a high exposure to PFAS, especially in the occupational setting., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Per- and poly-fluoroalkyl substances (PFAS) are persistent and widespread environmental pollutants. People living in Veneto Region (Italy) have been exposed from the late 1970s to 2013 to elevated concentrations of PFAS through drinking water. The effect of PFAS on thyroid function is still controversial and studies focusing on thyroid stimulating hormone (TSH) have shown inconsistent results. The aim of this study was to evaluate the association between serum PFAS and TSH levels and its dose-response relationship in a large population of highly exposed individuals., Methods: A cross-sectional study was conducted on 21,424 individuals aged 14-39 living in the contaminated area. In the main analysis, participants with prevalent thyroid disease and pregnant women were excluded. Serum levels of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) were measured. Generalized Additive Models were used to evaluate the association between TSH levels and serum PFAS, using thin plate spline smooth terms to model the potential non-linear relationship. Models were stratified by sex and age group and adjusted for potential confounders. A secondary analysis was conducted to evaluate the association between PFAS with prevalent self-reported thyroid disorders., Results: We found no association between TSH and any type of PFAS among adolescents or women. A decrease in TSH concentration was observed in association with an IQR increase in PFHxS and a mild decrease in TSH at low levels of PFOA, PFOS and PFHxS among male adults. Self-reported thyroid disease was more common among women with higher levels of PFNA concentrations, whereas all other PFAS were not associated with thyroid diseases regardless of sex or age., Conclusions: Overall there is no evidence of an association between TSH and PFAS. However, some results are suggestive of a possible inverse association of TSH with PFOA, PFOS and PFHxS among adult males., (Copyright © 2021. Published by Elsevier Inc.)

Background: Residents of a large area of north-eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Despite the large amount of evidence in adults of a positive association between serum PFAS and metabolic outcomes, studies focusing on children and adolescents are limited. We evaluated the associations between serum PFAS concentrations that were quantifiable in at least 40% of samples and lipid profile, blood pressure (BP) and body mass index (BMI) in highly exposed adolescents and children., Methods: A cross-sectional analysis was conducted in 6669 adolescents (14-19 years) and 2693 children (8-11 years) enrolled in the health surveillance program of the Veneto Region. Non-fasting blood samples were obtained and analyzed for perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides. Low-density lipoprotein cholesterol (LDL-C) was calculated. Systolic and diastolic BP were measured, and BMI z-score accounting for age and sex was estimated. The associations between ln-transformed PFAS (and categorized into quartiles) and continuous outcomes were assessed using generalized additive models. The weighted quantile sum regression approach was used to assess PFAS-mixture effects for each outcome. Analyses were stratified by gender and adjusted for potential confounders., Results: Among adolescents, significant associations were detected between all investigated PFAS and TC, LDL-C, and to a lesser extent HDL-C. Among children, PFOS and PFNA had significant associations with TC, LDL-C and HDL-C, while PFOA and PFHxS had significant associations with HDL-C only. Higher serum concentrations of PFAS, particularly PFOS, were associated with lower BMI z-score. No statistically significant associations were observed between PFAS concentrations and BP. These results were confirmed by the multi-pollutant analysis., Conclusions: Our study supports a consistent association between PFAS concentration and serum lipids, stronger for PFOS and PFNA and with a greater magnitude among children compared to adolescents, and a negative association of PFAS with BMI.

Exposure to per- and polyfluoroalkyl substances (PFAS), ubiquitous persistent environmental contaminants, has led to substantial global concern due to their potential environmental and human health effects. Several epidemiological studies have assessed the possible association between PFAS exposure and risk of metabolic syndrome (MetS), however, the results are ambiguous. The aim of this study was to assess the current human epidemiologic evidence on the association between exposure to PFAS and MetS. We performed a systematic search strategy using three electronic databases (PubMed, Scopus, and Web of Science) for relevant studies concerning the associations of PFAS with MetS and its clinical relevance from inception until January 2021. We undertook meta-analyses where there were five or more studies with exposure and outcomes assessments that were reasonably comparable. The pooled odd ratios (ORs) were calculated using random effects models and heterogeneity among studies was assessed by I2 index and Q test. A total of 12 cross-sectional studies (10 studies on the general population and two studies in the occupational settings) investigated the association between PFAS exposure and MetS. We pooled data from seven studies on the general population for perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) and five studies for perfluorohexanesulfonate (PFHxS) and perfluorononanoic acid (PFNA). Predominately, most studies reported no statistically significant association between concentrations of PFAS and MetS. In the meta-analysis, the overall measure of effect was not statistically significant, showing no evidence of an association between concentrations of PFOA, PFOS, PFNA, and PFHxS and the risk of MetS. Based on the results of the meta-analysis, current small body of evidence does not support association between PFAS and MetS. However, due to limited number of studies and substantial heterogeneity, results should be interpreted with caution. Further scrutinizing cohort studies are needed to evaluate the association between various and less well-known PFAS substances and their mixture with MetS and its components in both adults and children in different settings., (© 2021 Maryam Zare Jeddi et al., published by De Gruyter, Berlin/Boston.)

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.