Early and rapid identification of COVID-19 patients with neutralizing type I-interferon auto-antibodies by an easily implementable algorithm

Abstract

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.

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

“…These findings established the crucial role of type I IFNs in fending off SARS-CoV-2 (13). Moreover, autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml in plasma diluted 1/10) of IFN-2 and/or IFN- were found in at least 10% of individuals with critical COVID-19 (14), an observation replicated in various regions of the world (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). Patients with autoimmune polyendocrine syndrome type I (APS-1) harbor these neutralizing auto-Abs from early childhood and are at high risk of life-threatening COVID-19 (24,25).…”

Multisystem inflammatory syndrome in children (MIS-C): Implications for long COVID

“…It is also possible to specifically test during the early stages of COVID-19 because more targeted treatments—like IFNβ, neutralizing monoclonal antibodies against SARS-CoV-2, or plasma exchange—could be beneficial in patients with autoantibody positive patients (Zhang et al 2022a ). Clinically relevant approaches are being developed to quickly recognize people with positive interferon antibody responses so that subsequent clinical interventions can be administered (Akbil et al 2021 ).…”