期刊
JOURNAL OF CLINICAL IMMUNOLOGY
卷 42, 期 6, 页码 1111-1129出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10875-022-01252-2
关键词
COVID-19; SARS-CoV-2; Type I interferon; Autoantibodies
类别
资金
- Charite - Universitatsmedizin Berlin
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [422681845]
- Deutsche Forschungsgemeinschaft (DFG) [SCHA1838/4-2]
- Berlin Institute of Health
6-19% of critically ill COVID-19 patients carry auto-antibodies against type I interferons (IFN-AABs), which may serve as early biomarkers for severe COVID-19. This study establishes a clinically applicable strategy for identifying IFN-AAB-positive patients and providing targeted therapies.
Purpose 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-alpha and IFN-omega 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-alpha-AABs and 4.6%, 11/237 for IFN-omega-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.
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