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Here, we establish a clinically applicable strategy for early identification of IFN-AAB-positive patients for potential subsequent clinical interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <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>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The prevalence of neutralizing AABs to IFN-\u03b1 and IFN-\u03c9 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\u20138), predominantly male (83%) patients (7.6%, 18\/237 for IFN-\u03b1-AABs and 4.6%, 11\/237 for IFN-\u03c9-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>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <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>\n                  <\/jats:sec>","DOI":"10.1007\/s10875-022-01252-2","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T04:17:23Z","timestamp":1651724243000},"page":"1111-1129","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon 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Furthermore, the authors affirm that human research participants provided written informed consent for publication of their demographic, clinical and laboratory data.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent to Participate and to Publish"}},{"value":"V.M.C is named together with Euroimmun GmbH on a patent application filed recently regarding the diagnostic of SARS-CoV-2 by antibody testing. Technische Universit\u00e4t Berlin, Freie Universit\u00e4t Berlin, and Charit\u00e9\u2014Universit\u00e4tsmedizin have filed a patent application for siRNAs inhibiting SARS-CoV-2 replication with D.N. as co-author. J.C.S, T.S. (full departmental disclosure): the department of Intensive Care Medicine has\/had research and\/or development\/consulting contracts with (full disclosure) Orion Corporation, Abbott Nutrition International, B. Braun Medical AG, CSEM SA, Edwards Lifesciences Services GmbH\/SA, Kenta Biotech Ltd, Maquet Critical Care AB, Omnicare Clinical Research AG, Phagenesis Ltd, Cytel, and Nestl\u00e9. No personal financial gains resulted from respective development\/consulting contracts and\/or educational grants.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}