Antibodies against type-I Interferon: detection and association with severe clinical outcome in COVID-19 patients

  1. Goncalves David
  2. Mezidi Mehdi
  3. Bastard Paul
  4. Perret Magali
  5. Saker Kahina
  6. Fabien Nicole
  7. Pescarmona Rémi
  8. Lombard Christine
  9. Walzer Thierry
  10. Casanova Jean-Laurent
  11. Belot Alexandre
  12. Richard Jean-Christophe
  13. Trouillet-Assant Sophie

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Abstract

Objectives

Impairment of type I interferon (IFN-I) immunity has been reported in critically-ill COVID-19 patients. This defect can be explained in a subset of patients by the presence of circulating autoantibodies (auto-Abs) against IFN-I. We set out to improve the detection and the quantification of IFN-I auto-Abs in a cohort of critically-ill COVID-19 patients, in order to better evaluate the prevalence of these Abs as the pandemic progresses, and how they correlate with the clinical course of the disease.

Methods

The concentration of anti - IFN-α 2 Abs was determined in the serum of 84 critically-ill COVID-19 patients who were admitted to ICU in Hospices Civils de Lyon , France using a commercially available kit (Thermo-Fisher, Catalog #BMS217).

Results

A total of 21/84 (25%) critically-ill COVID-19 patients had circulating anti-IFN-α 2 Abs above cut-off (>34 ng.mL -1 ). Among them, 15/21 had Abs with neutralizing activity against IFN-α 2 , i . e . 15/84 (18%) of critically-ill patients. In addition, we noticed an impairment of the IFN-I response in the majority of patients with neutralizing anti-IFN-α 2 Abs. There was no significant difference in the clinical characteristics or outcome of with or without neutralizing anti-IFN-α 2 auto-Abs. We detected anti-IFN-α 2 auto-Abs in COVID-19 patients’ sera throughout their ICU stay. Finally, we also found auto-Abs against multiple subtypes of IFN-I including IFN-ω.

Conclusions

We reported that 18% of critically-ill COVID-19 patients were positive for IFN-I auto-Abs, confirming that the presence of these antibodies is associated with higher risk of developing a criticall COVID-19 form.

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  1. ScreenIT

    SciScore for 10.1101/2021.04.02.21253262: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    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: 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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04341142RecruitingAssessment of Serological Techniques for Screening Patients …

    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.

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  2. Version published to 10.1101/2021.04.02.21253262 on medRxiv
  3. Version published to 10.1002/cti2.1327