| Autor: |
Ralf-Harto Huebner, Christoph Tabeling, Nils Schallner, Christian Drosten, Terry Jones, Siegbert Rieg, Horst von Bernuth, Uta Merle, Leif E. Sander, Daniel Duerschmied, Barbara Muehlemann, Christine Goffinet, Dietrich August, Victor M. Corman, Norbert Suttorp, JM Doehn, Uwe Koelsch, Olga Staudacher, Achim Lother, Nadine Unterwalder, Charlotte Thibeault, Bengisu Akbil, Daniela Niemeyer, Cédric Hirzel, Alexandra Nieters, Florian Kurth, Christian Nusshag, Tim Meyer, Thomas Doerner, Paula Stubbemann, David Sanchez, Jenny Jansen, Joerg C. Schefold, Valeria Falcone, Thibaud Spinetti, Klaus Warnatz, Christian Meisel, Jan Nikolaus Lieberum, Hartmut Hengel |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.11.12.21266249 |
| Popis: |
PurposeSix-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.MethodsWe 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 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.ResultsThe 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.ConclusionIFN-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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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