Angiotensin II receptor I auto-antibodies following SARS-CoV-2 infection

  1. Yonghou Jiang
  2. Fergal Duffy
  3. Jennifer Hadlock
  4. Andrew Raappana
  5. Sheila Styrchak
  6. Ingrid Beck
  7. Fred D. Mast
  8. Leslie R. Miller
  9. William Chour
  10. John Houck
  11. Blair Armistead
  12. Venkata R. Duvvuri
  13. Winnie Yeung
  14. Micaela Haglund
  15. Jackson Wallner
  16. Julie A. Wallick
  17. Samantha Hardy
  18. Alyssa Oldroyd
  19. Daisy Ko
  20. Ana Gervassi
  21. Kim M. Murray
  22. Henry Kaplan
  23. John D. Aitchison
  24. James R. Heath
  25. D. Noah Sather
  26. Jason D. Goldman
  27. Lisa Frenkel
  28. Whitney E. Harrington

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Abstract

Coronavirus disease 2019 ( COVID-19 ) is associated with endothelial activation and coagulopathy, which may be related to pre-existing or infection-induced pro-thrombotic autoantibodies such as those targeting angiotensin II type I receptor ( AT1R-Ab ).

Methods

We compared prevalence and levels of AT1R-Ab in COVID-19 cases with mild or severe disease to age and sex matched negative controls utilizing multivariate logistic and quantile regression adjusted for comorbidities including hypertension, diabetes, and heart disease.

Results

There were trends toward increased prevalence (50% vs. 33%, p = 0.1) and level of AT1R-Ab (median 9.8 vs. 6.1 U/mL, p = 0.06) in all cases versus controls. When considered by COVID-19 disease severity, there was a trend toward increased prevalence of AT1R-Ab (55% vs. 31%, p = 0.07), as well as significantly higher AT1R-Ab levels (median 10.7 vs. 5.9 U/mL, p = 0.03) amongst individuals with mild COVID-19 versus matched controls. In contrast, the prevalence (42% vs. 37%, p = 0.9) and level (both medians 6.7 U/mL, p = 0.9) of AT1R-Ab amongst those with severe COVID-19 did not differ from matched controls.

Conclusions

These findings support an association between COVID-19 and AT1R-Ab, emphasizing that vascular pathology may be present in individuals with mild COVID-19 as well as those with severe disease.

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  1. Version published to 10.1371/journal.pone.0259902
  2. ScreenIT

    SciScore for 10.1101/2021.06.30.21259796: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants provided written informed consent.
    Sex as a biological variablenot detected.
    RandomizationAnti-SARS-CoV-2 Spike, Receptor Binding Domain, and Nucleocapsid Protein ELISAs: In order to investigate potential cross-reactivity between AT1R-Ab and SARS-CoV-2 Spike, we tested plasma from AT1R-Ab positive control subjects and randomly selected AT1R-Ab negative controls for reactivity against SARS-CoV-2 Spike trimer (including both S1 and S2 domains), as previously published (12).
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-AT1R Antibody Screening: The concentration of AT1R-Ab in plasma was measured with a quantitative ELISA (Celltrend, Luckenwalde, Germany) using the entire AT1R protein, with assays performed according to the manufacturer’s instructions.
    Anti-AT1R
    suggested: None
    After washing, AT1R-Ab was detected with HRP-labelled anti-human IgG antibody followed by enzymatic substrate reaction.
    anti-human IgG
    suggested: None
    Distribution of HLA and SARS-CoV-2 antibody responses were compared with the Chi-square test.
    SARS-CoV-2
    suggested: None

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.06.30.21259796v1 on medRxiv