Internet Archive Scholar

Early and rapid identification of COVID-19 patients with neutralizing type I-interferon auto-antibodies by an easily implementable algorithm [article]

Bengisu Akbil, Tim Meyer, Paula Stubbemann, Charlotte Thibeault, Olga Staudacher, Daniela Niemeyer, Jenny Jansen, Barbara Muehlemann, Jan-Moritz Doehn, Christoph Tabeling, Christian Nusshag, Cedric Hirzel (+27 others)
2021 medRxiv   pre-print

Preserved Fulltext

fulltext thumbnail
Web Archive Capture PDF (3.8 MB)
https://web.archive.org/web/20220116182329/https://www.medrxiv.org/content/medrxiv/early/2021/11/17/2021.11.12.21266249.full.pdf

A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2022; you can also visit the original URL. The file type is application/pdf.

Purpose Six-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 analysed sera of 430 COVID-19 patients with severe and critical disease from four hospitals for presence of IFN-AABs by ELISA. Binding specificity and neutralizing activity were evaluated via competition
more » ... ay 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 was 4.2% (18/430), while being undetectable in an uninfected control cohort. Neutralizing IFN-AABs were detectable exclusively in critically affected, predominantly male (83%) patients (7.6% IFN-α and 4.6% IFN-ω in 207 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 higher mortality (92.3% versus 19.1 % 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 development of severe COVID-19. We propose to implement routine screening of hospitalized COVID-19 patients according to our algorithm for rapid identification of patients with IFN-AABs who most likely benefit from specific therapies.
doi:10.1101/2021.11.12.21266249 fatcat:glnkm7elzbgdffs6gi5vbj7bzu
Citation

Bengisu Akbil, Tim Meyer, Paula Stubbemann, Charlotte Thibeault, Olga Staudacher, Daniela Niemeyer, Jenny Jansen, Barbara Muehlemann, Jan-Moritz Doehn, Christoph Tabeling, Christian Nusshag, Cedric Hirzel, David Soekler Sanchez, Alexandra Nieters, Achim Lother, Daniel Duerschmied, Nils Schallner, Jan Nikolaus Lieberum, Dietrich August, Siegbert Rieg, Valeria Falcone, Hartmut Hengel, Uwe Koelsch, Nadine Unterwalder, Ralf-Harto Huebner, Terry C. Jones, Norbert Suttorp, Christian Drosten, Klaus Warnatz, Thibaud Spinetti, Joerg C. Schefold, Thomas Doerner, Leif Sander, Victor M Corman, Uta Merle, Florian Kurth, Horst von Bernuth, Christian Meisel, Christine Goffinet. "Early and rapid identification of COVID-19 patients with neutralizing type I-interferon auto-antibodies by an easily implementable algorithm." medRxiv (2021)