Abstract
Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia.
Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN- ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia.
The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 x 10-5), especially those <70 yr old (OR = 139.9, P = 3.1 x 10-10).
We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for TILDE OPERATOR+D915% of cases of life-threatening influenza pneumonia in patients <70 yr old.