Anticardiolipin and other antiphospholipid antibodies in critically ill COVID-19 positive and negative patients

  1. Uriel Trahtemberg
  2. Robert Rottapel
  3. Claudia C Dos Santos
  4. Arthur S Slutsky
  5. Andrew Baker
  6. Marvin J Fritzler

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Abstract

Reports of severe COVID-19 being associated with thrombosis, antiphospholipid antibodies (APLA), and antiphospholipid syndrome have yielded disparate conclusions. Studies comparing patients with COVID-19 with contemporaneous controls of similar severity are lacking.

Methods

22 COVID-19 + and 20 COVID-19 – patients with respiratory failure admitted to intensive care were studied longitudinally. Demographic and clinical data were obtained from the day of admission. APLA testing included anticardiolipin (aCL), anti-β2glycoprotien 1 (β2GP1), antidomain 1 β2GP1 and antiphosphatidyl serine/prothrombin complex. Antinuclear antibodies (ANAs) were detected by immunofluorescence and antibodies to cytokines by a commercially available multiplexed array. Analysis of variance was used for continuous variables and Fisher’s exact test was used for categorical variables with α=0.05 and the false discovery rate at q=0.05.

Results

APLAs were predominantly IgG aCL (48%), followed by IgM (21%) in all patients, with a tendency towards higher frequency among the COVID-19 + . aCL was not associated with surrogate markers of thrombosis but IgG aCL was strongly associated with worse disease severity and higher ANA titres regardless of COVID-19 status. An association between aCL and anticytokine autoantibodies tended to be higher among the COVID-19 + .

Conclusions

Positive APLA serology was associated with more severe disease regardless of COVID-19 status.

Trial registration number

NCT04747782

Article activity feed

  1. Version published to 10.1136/annrheumdis-2021-220206
  2. ScreenIT

    SciScore for 10.1101/2021.02.19.21252113: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Michael’s Hospital (Toronto, ON, Canada), as approved by the Research Ethics Board (REB# 20-078).
    Consent: Informed consent was obtained from all patients or their legal surrogates.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Detailed methods are available (online supplement), including methods for detection of anti-nuclear autoantibodies (ANA) by HEp-2 immunofluorescence assay (IFA) (Inova Diagnostics, San Diego, CA USA), and antigen-specific autoantibodies (TheraDiag, Paris, France) and anti-cytokine autoantibodies (Millipore, Oakville, ON, Canada) using addressable laser bead immunoassays.
    anti-nuclear
    suggested: None
    antigen-specific
    suggested: None
    anti-cytokine
    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: We detected the following sentences addressing limitations in the study:
    The main limitation of our study is the small sample size. The strengths of our study include its prospective, contemporaneous COVID- cohort with similar severity of disease. Importantly, we tested a broad APLA serological panel longitudinally, providing a more robust assessment of its true prevalence and incidence than in other reported studies; this is particularly relevant for such acutely ill patients with dynamic clinical courses. Finally, our use of an extensive serological panel allowed us to better characterize the broad phenotype associated with aCL.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04747782RecruitingCOVID-19 Longitudinal Biomarkers in Lung Injury

    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.

    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 10.1101/2021.02.19.21252113v1 on medRxiv