Severity of COVID-19 at elevated exposure to perfluorinated alkylates

  1. Philippe Grandjean
  2. Clara Amalie Gade Timmermann
  3. Marie Kruse
  4. Flemming Nielsen
  5. Pernille Just Vinholt
  6. Lasse Boding
  7. Carsten Heilmann
  8. Kåre Mølbak

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Abstract

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 to an association with disease severity.

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 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 unadjusted odds ratio (OR) of 2.19 (95% confidence interval, CI, 1.39–3.46) for increasing severities of the disease. Among those hospitalized, the fully adjusted OR for getting into intensive care or expiring was 5.18 (1.29, 20.72) when based on plasma samples obtained at the time of diagnosis or up to one week before.

Conclusions

Measures of individual exposures to immunotoxic PFASs included short-chain PFBA known to accumulate in the lungs. Elevated plasma-PFBA concentrations were associated with an increased risk of a more severe course of COVID-19. Given the low background exposure levels in this study, the role of exposure to PFASs in COVID-19 needs to be ascertained in populations with elevated exposures.

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  1. ScreenIT

    SciScore for 10.1101/2020.10.22.20217562: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: The protocol was approved by the Regional Committee on Health Research Ethics (S-20200064), which also allowed the project to proceed without seeking informed consent from the subjects identified for study participation.
    Consent: The protocol was approved by the Regional Committee on Health Research Ethics (S-20200064), which also allowed the project to proceed without seeking informed consent from the subjects identified for study participation.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    In regard to limitations, the study population is not representative of corona-positive subjects, as inclusion in the study depended solely on the existence of plasma from diagnostic blood samples at the hospitals. Thus, subjects with chronic disease or more severe COVID-19 likely had more frequent hospital visits or longer admissions and thereby a greater chance of having plasma available for inclusion in this study. With a corona-related fatality rate of Danish blood donors below 70 years of age at 89 per 100,000 infections,36 the presence of 17 deaths in the present material (i.e., against 0.3 deaths expected) confirms that the blood samples represent a highly selected population. Still, a total of 108 subjects were known to have been infected, though not hospitalized. In many cases, their plasma had been stored on previous occasions, and the PFAS concentrations may reflect slightly higher exposures in the recent past.8 Although adjustment for the time interval since sample collection was included in the analyses, its impact on the results was negligible. The study population included relatively older subjects who were more frequently male, and a large proportion of foreign-born subjects and second-generation immigrants (Table 3), thereby possibly also deviating from the background population of corona-infected patients in Denmark. Still, such biases will not necessarily affect the PFAS exposure and its association with COVID-19 outcomes. Among immigrants, adverse associat...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a protocol registration statement.

    About SciScore

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  2. Version published to 10.1371/journal.pone.0244815
  3. Version published to 10.1101/2020.10.22.20217562v1 on medRxiv