Neutralizing auto-Abs against type I IFNs in children with life-threatening COVID-19. (A) Gyros (high-throughput automated ELISA) results for auto-Abs against IFN-α2 for positive controls (n = 4), pediatric patients (n = 188), and healthy controls (n = 16). (B) Plot of anti–IFN-α2 auto-Ab IgG levels, as determined by Gyros, against their neutralization capacity at 10 ng/ml in the luciferase assay. For plasma from each patient, luciferase activity was normalized against the mean induction of control plasma tested on the same day in the luciferase assay. The horizontal dotted line indicates the threshold of neutralization, defined as the level of induction below 15% of the mean value for controls tested on the same day. (C–J) Proportion by age of pediatric and adult patients from the general population positive for neutralizing auto-Abs (in plasma 1:10) against (C) IFN-α2 at 10 ng/ml, for both sexes; (D) IFN-α2, at 10 ng/ml, for men or women; (E) IFN-ω, at 10 ng/ml, for both sexes; (F) IFN-ω, at 10 ng/ml, for men or women; (G) IFN-β, at 10 ng/ml, for both sexes; (H) IFN-β, at 10 ng/ml, for men or women; (I) IFN-α2 and IFN-ω, at 10 ng/ml, for both sexes; and (J) IFN-α2 and IFN-ω, at 10 ng/ml, for men or women.