Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia

Autoantibodies (AABs) neutralizing type I interferons (IFN) underlie about 15% of cases of critical coronavirus disease 2019 (COVID-19) pneumonia. The impact of autoimmunity toward type III IFNs remains unexplored. We included samples from 1,002 patients with COVID-19 (50% with severe disease) and 1,489 SARS-CoV-2naive individuals. We studied the prevalence and neutralizing capacity of AABs toward IFN? and IFNa. Luciferase-based immunoprecipitation method was applied using pooled IFNa (subtypes 1, 2, 8, and 21) or pooled IFN?1-IFN?3 as antigens, followed by reporter cell-based neutralization assay. In the SARS-CoV-2naive cohort, IFN? AABs were more common (8.5%) than those targeting IFNa2 (2.9%) and were related with older age. In the COVID-19 cohort the presence of autoreactivity to IFN? did not associate with severe disease [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.40-1.73], unlike to IFNa (OR 4.88; 95% CI 2.40-11.06; P<0.001). Most IFN? AAB-positive COVID-19 samples (67%) did not neutralize any of the 3 IFN? subtypes. Pan-IFN? neutralization occurred in 5 patients (0.50%), who all suffered from severe COVID-19 pneumonia, and 4 of them neutralized IFNa2 in addition to IFN?. Overall, AABs to type III IFNs are rarely neutralizing, and do not seem to predispose to severe COVID-19 pneumonia on their own.

Automated summary

Autoantibodies neutralizing type I interferons are present in 15% of critical COVID-19 cases, while the impact of autoimmunity toward type III interferons remains unexplored. In a study of COVID-19 patients and SARS-CoV-2naive individuals, it was found that autoantibodies targeting interferon-alpha were more common and associated with older age, while autoreactivity to interferon-gamma did not correlate with severe disease in COVID-19 patients.