• Media type: E-Article
  • Title: Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies
  • Contributor: Akbil, Bengisu; Meyer, Tim; Stubbemann, Paula; Thibeault, Charlotte; Staudacher, Olga; Niemeyer, Daniela; Jansen, Jenny; Mühlemann, Barbara; Doehn, Jan; Tabeling, Christoph; Nusshag, Christian; Hirzel, Cédric; Sanchez, David Sökler; Nieters, Alexandra; Lother, Achim; Duerschmied, Daniel; Schallner, Nils; Lieberum, Jan Nikolaus; August, Dietrich; Rieg, Siegbert; Falcone, Valeria; Hengel, Hartmut; Kölsch, Uwe; Unterwalder, Nadine; [...]
  • imprint: Springer Science and Business Media LLC, 2022
  • Published in: Journal of Clinical Immunology
  • Language: English
  • DOI: 10.1007/s10875-022-01252-2
  • ISSN: 0271-9142; 1573-2592
  • Origination:
  • Footnote:
  • Description: <jats:title> Abstract </jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>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.</jats:p> </jats:sec>