Akbil, BengisuBengisuAkbilMeyer, TimTimMeyerStubbemann, PaulaPaulaStubbemannThibeault, CharlotteCharlotteThibeaultStaudacher, OlgaOlgaStaudacherNiemeyer, DanielaDanielaNiemeyerJansen, JennyJennyJansenMühlemann, BarbaraBarbaraMühlemannDoehn, JanJanDoehnTabeling, ChristophChristophTabelingNusshag, ChristianChristianNusshagHirzel, CédricCédricHirzel0000-0002-7870-912XSanchez, David SöklerDavid SöklerSanchezNieters, AlexandraAlexandraNietersLother, AchimAchimLotherDuerschmied, DanielDanielDuerschmiedSchallner, NilsNilsSchallnerLieberum, Jan NikolausJan NikolausLieberumAugust, DietrichDietrichAugustRieg, SiegbertSiegbertRiegFalcone, ValeriaValeriaFalconeHengel, HartmutHartmutHengelKölsch, UweUweKölschUnterwalder, NadineNadineUnterwalderHübner, Ralf-HartoRalf-HartoHübnerJones, Terry CTerry CJonesSuttorp, NorbertNorbertSuttorpDrosten, ChristianChristianDrostenWarnatz, KlausKlausWarnatzSpinetti, ThibaudThibaudSpinettiSchefold, Jörg ChristianJörg ChristianSchefoldDörner, ThomasThomasDörnerSander, Leif ErikLeif ErikSanderCorman, Victor MVictor MCormanMerle, UtaUtaMerleKurth, FlorianFlorianKurthvon Bernuth, HorstHorstvon BernuthMeisel, ChristianChristianMeiselGoffinet, ChristineChristineGoffinet2024-10-092024-10-092022-08https://boris-portal.unibe.ch/handle/20.500.12422/70580PURPOSE 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.enAutoantibodies COVID-19 SARS-CoV-2 Type I interferon600 - Technology::610 - Medicine & healtharticle10.48350/1697673551131410.1007/s10875-022-01252-2