Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies
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Abstract
Purpose
Six to 19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable strategy for early identification of IFN-AAB-positive patients for potential subsequent clinical interventions.
Methods
We analyzed sera of 430 COVID-19 patients from four hospitals for presence of IFN-AABs by ELISA. Binding specificity and neutralizing activity were evaluated via competition assay and virus-infection-based neutralization assay. We defined clinical parameters associated with IFN-AAB positivity. In a subgroup of critically ill patients, we analyzed effects of therapeutic plasma exchange (TPE) on the levels of IFN-AABs, SARS-CoV-2 antibodies and clinical outcome.
Results
The prevalence of neutralizing AABs to IFN-α and IFN-ω in COVID-19 patients from all cohorts was 4.2% (18/430), while being undetectable in an uninfected control cohort. Neutralizing IFN-AABs were detectable exclusively in critically affected (max. WHO score 6–8), predominantly male (83%) patients (7.6%, 18/237 for IFN-α-AABs and 4.6%, 11/237 for IFN-ω-AABs in 237 patients with critical COVID-19). IFN-AABs were present early post-symptom onset and at the peak of disease. Fever and oxygen requirement at hospital admission co-presented with neutralizing IFN-AAB positivity. IFN-AABs were associated with lower probability of survival (7.7% versus 80.9% in patients without IFN-AABs). TPE reduced levels of IFN-AABs in three of five patients and may increase survival of IFN-AAB-positive patients compared to those not undergoing TPE.
Conclusion
IFN-AABs may serve as early biomarker for the development of severe COVID-19. We propose to implement routine screening of hospitalized COVID-19 patients for rapid identification of patients with IFN-AABs who most likely benefit from specific therapies.
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SciScore for 10.1101/2021.11.12.21266249: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: Study cohorts and data collection: Patients were recruited and data and sample collection was performed within one of four prospective observational studies conducted at Charité - Universitätsmedizin Berlin, Germany (Cohort A, (Kurth et al. 2020)), Inselspital Universitätsspital Bern, Switzerland (Cohort B), Universitätsklinikum Freiburg, Germany (Cohort C) and Universitätsklinikum Heidelberg, Germany (Cohort D). Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Cytokine AABs were detected using a monoclonal mouse antibody … SciScore for 10.1101/2021.11.12.21266249: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: Study cohorts and data collection: Patients were recruited and data and sample collection was performed within one of four prospective observational studies conducted at Charité - Universitätsmedizin Berlin, Germany (Cohort A, (Kurth et al. 2020)), Inselspital Universitätsspital Bern, Switzerland (Cohort B), Universitätsklinikum Freiburg, Germany (Cohort C) and Universitätsklinikum Heidelberg, Germany (Cohort D). Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Cytokine AABs were detected using a monoclonal mouse antibody to human IgG (D20JL-6, MSD). human IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources Virus infection-based neutralization assays: Calu-3 cells were pre-incubated with 1% human serum in the presence or absence of 200-400 IU/ml IFN-α2a (Roferon®-A, Roche) or 20-50 ng/ml IFN-ω (PeproTech). Calu-3suggested: BCRJ Cat# 0264, RRID:CVCL_0609)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:
Identifier Status Title NCT04510012 Recruiting Characterizing the Immune Response and Neuronal Damage in CO… 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.
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Results from scite Reference Check: We found no unreliable references.
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