Endocrine disrupting chemicals and COVID-19 relationships: a computational systems biology approach

Wu, Qier; Coumoul, Xavier; Grandjean, Philippe; Barouki, Robert; Audouze, Karine

doi:10.1101/2020.07.10.20150714

Cited by 8 publications

(8 citation statements)

References 51 publications

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“…8,9 In addition to immunotoxicity, major PFASs can potentially interfere with major pathways that are predictive of a serious clinical outcome of the infection. 14 An association of PFAS exposure with disease severity therefore appears biologically plausible.…”

Section: Discussionmentioning

confidence: 99%

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Severity of COVID-19 at elevated exposure to perfluorinated alkylates

Grandjean

Timmermann²,

Kruse

et al. 2020

Preprint

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Background The course of coronavirus disease 2019 (COVID-19) seems to be aggravated by air pollution, and some industrial chemicals, such as the perfluorinated alkylate substances (PFASs), are immunotoxic and may contribute as well. Methods From Danish biobanks, we obtained plasma samples from 323 subjects aged 30-70 years with known SARS-CoV-2 infection. The PFAS concentrations measured at the background exposures included five PFASs known to be immunotoxic. Register data was obtained to classify disease status, other health information, and demographic variables. We used ordinal and ordered logistic regression analyses to determine associations between PFAS concentrations and disease outcome. Results Plasma-PFAS concentrations were higher in males, in subjects with Western European background, and tended to increase with age, but were not associated with the presence of chronic disease. Of the study population, 108 (33%) had not been hospitalized, and of those hospitalized, 53 (16%) had been in intensive care or were deceased. Among the five PFASs considered, perfluorobutanoic acid (PFBA) showed an odds ratio (OR) of 2.19 (95% confidence interval, CI, 1.39-3.46) for increasing severities of the disease, although the OR decreased to 1.77 (95% CI, 1.09, 2.87) after adjustment for age, sex, sampling site and interval between blood sampling and diagnosis. Conclusions Measures of individual exposures to immunotoxic PFASs included PFBA that accumulates in the lungs. Elevated plasma-PFBA concentrations were associated with an increased risk of more severe course of CIVID-19. Given the low background exposure levels in this study, the role of PFAS exposure in COVID-19 needs to be ascertained in populations with elevated exposures.

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Section: Discussionmentioning

confidence: 99%

“…11-13 Further, major PFASs are suspected interfering with proteins involved in critical pathways associated with severe clinical outcomes of the COVID-19 infection. 14…”

Section: Introductionmentioning

confidence: 99%

Severity of COVID-19 at elevated exposure to perfluorinated alkylates

Grandjean

Timmermann²,

Kruse

et al. 2020

Preprint

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“…Moreover, receptors which directly mediate BPA effects, such as the membrane-bound oestrogen receptor GPR30, are widely distributed in human tissues and may co-localise with SARS-CoV-2 infection mediators (e.g., co-localisation of GPR30 with TMPRSS2 and CTSL in the lung), potentially affecting their local tissue expression. Therefore, it becomes evident that there might be potential implications of exposure to BPA and other common EDCs on the risk of SARS-CoV-2 infection and the severity of COVID-19 [ 11 , 12 ]. This is a developing topic and clearly further in vitro, computational, preclinical, and in vivo studies are needed to elucidate any such direct links between BPA and COVID-19 and clarify the molecular mechanisms that may be involved.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, a recent review has further proposed that long-term exposure to chemicals in mixtures, as well as lifestyle habits, may be linked to compromised immunity and predispose to the complications observed in patients with severe COVID-19 [ 10 ]. Moreover, a computational systems biology approach revealed that a number of signalling pathways which are dysregulated by EDCs (e.g., Th17 and advanced glycation end-products (AGE)/receptor for AGE (RAGE), AGE/RAGE, pathways) might also be related to the severity of COVID-19 [ 11 ]. As these detrimental effects of EDCs overlap with key risk factors for severe COVID-19, the hypothesis that exposure to EDCs may be also linked to the severity of COVID-19 merits further investigation [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Is There a Link between Bisphenol A (BPA), a Key Endocrine Disruptor, and the Risk for SARS-CoV-2 Infection and Severe COVID-19?

Zahra

Sisu

Silva

et al. 2020

JCM

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Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the causative agent of a new disease (COVID-19). The risk of severe COVID-19 is increased by certain underlying comorbidities, including asthma, cancer, cardiovascular disease, hypertension, diabetes, and obesity. Notably, exposure to hormonally active chemicals called endocrine-disrupting chemicals (EDCs) can promote such cardio-metabolic diseases, endocrine-related cancers, and immune system dysregulation and thus, may also be linked to higher risk of severe COVID-19. Bisphenol A (BPA) is among the most common EDCs and exerts its effects via receptors which are widely distributed in human tissues, including nuclear oestrogen receptors (ERα and ERβ), membrane-bound oestrogen receptor (G protein-coupled receptor 30; GPR30), and human nuclear receptor oestrogen-related receptor gamma. As such, this paper focuses on the potential role of BPA in promoting comorbidities associated with severe COVID-19, as well as on potential BPA-induced effects on key SARS-CoV-2 infection mediators, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Interestingly, GPR30 appears to exhibit greater co-localisation with TMPRSS2 in key tissues like lung and prostate, suggesting that BPA exposure may impact on the local expression of these SARS-CoV-2 infection mediators. Overall, the potential role of BPA on the risk and severity of COVID-19 merits further investigation.

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“…In a separate report, it was revealed that exposure to toxic substances played vital roles in the COVID-19 pandemic [ 18 , 19 ]. Similarly, a computational systems biology approach identified Th17 and AGE/RAGE signaling pathways as links between EDCs and COVID-19 severity [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Endocrine-Disrupting Chemicals and Infectious Diseases: From Endocrine Disruption to Immunosuppression

Adegoke

Rahman

Park

et al. 2021

IJMS

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Endocrine-disrupting chemicals (EDCs) are hormonally active compounds in the environment that interfere with the body’s endocrine system and consequently produce adverse health effects. Despite persistent public health concerns, EDCs remain important components of common consumer products, thus representing ubiquitous contaminants to humans. While scientific evidence confirmed their contribution to the severity of Influenza A virus (H1N1) in the animal model, their roles in susceptibility and clinical outcome of the coronavirus disease (COVID-19) cannot be underestimated. Since its emergence in late 2019, clinical reports on COVID-19 have confirmed that severe disease and death occur in persons aged ≥65 years and those with underlying comorbidities. Major comorbidities of COVID-19 include diabetes, obesity, cardiovascular disease, hypertension, cancer, and kidney and liver diseases. Meanwhile, long-term exposure to EDCs contributes significantly to the onset and progression of these comorbid diseases. Besides, EDCs play vital roles in the disruption of the body’s immune system. Here, we review the recent literature on the roles of EDCs in comorbidities contributing to COVID-19 mortality, impacts of EDCs on the immune system, and recent articles linking EDCs to COVID-19 risks. We also recommend methodologies that could be adopted to comprehensively study the role of EDCs in COVID-19 risk.

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Endocrine disrupting chemicals and COVID-19 relationships: a computational systems biology approach

Cited by 8 publications

References 51 publications

Severity of COVID-19 at elevated exposure to perfluorinated alkylates

Severity of COVID-19 at elevated exposure to perfluorinated alkylates

Is There a Link between Bisphenol A (BPA), a Key Endocrine Disruptor, and the Risk for SARS-CoV-2 Infection and Severe COVID-19?

Endocrine-Disrupting Chemicals and Infectious Diseases: From Endocrine Disruption to Immunosuppression

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