Generation of Inhibitory Autoantibodies to ADAMTS13 in Coronavirus Disease 2019

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Abstract

Objectives

It has recently been shown that von Willebrand factor (vWf) multimers may be a key driver of immunothrombosis in Coronavirus disease 2019 (COVID-19). Since COVID-19 is associated with an increased risk of autoreactivity, the present study investigates, whether the generation of autoantibodies to ADAMTS13 contributes to this finding.

Design

Observational prospective controlled multicenter study.

Setting

Blood samples and clinical data of patients with COVID-19 were collected regularly during hospitalization in the period from April to November 2020.

Patients

90 patients with confirmed COVID-19 of mild to critical severity and 30 healthy controls participated in this study.

Measuerements and Main Results

Antibodies to ADAMTS13 occurred in 31 (34.4%) patients with COVID-19. Generation of ADAMTS13 antibodies was associated with a significantly lower ADAMTS13 activity (56.5%, interquartile range (IQR) 21.25 vs. 71.5%, IQR 24.25, p=0.0041), increased disease severity (severe or critical disease in 90% vs. 62.3%, p=0.0189), and a trend to a higher mortality (35.5% vs. 18.6%, p=0.0773). Median time to antibody development was 11 days after first positive SARS-CoV-2-PCR specimen.

Conclusion

The present study demonstrates for the first time, that generation of antibodies to ADAMTS13 is a frequent finding in COVID-19. Generation of these antibodies is associated with a lower ADAMTS13 activity and an increased risk of an adverse course of the disease suggesting an inhibitory effect on the protease. These findings provide a rationale to include ADAMTS13 antibodies in the diagnostic workup of SARS-CoV-2 infections.

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  1. SciScore for 10.1101/2021.03.18.21253869: (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: 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.

    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.