December 16, 2020
Reviewed by Daniel Mendoza, M.D., Ph.D.
Human inborn errors of type I interferons (IFNs) predispose to severe viral respiratory diseases. In an international study published by Bastard et al. in Science, the investigators hypothesized that neutralizing auto-antibodies (auto-Abs) against type I IFNs may underlie critical COVID-19. They searched for auto-Abs against type I IFNs in 987 patients with life-threatening COVID-19 whose samples were collected during the acute phase of disease, 663 patients with asymptomatic or mildly symptomatic COVID-19, and 1,227 healthy controls whose samples were collected before the pandemic.
The investigators found that 101 of 987 (10.2%) patients with life-threatening COVID-19 had auto-IgG against IFN-ω (13 patients), against the 13 types of IFN-α (36 patients), or against both (52 patients) during critical disease. By contrast, these auto-Abs were absent from 663 individuals with asymptomatic or mild COVID-19, and they were present in 4 of 1,227 (0.33%) healthy individuals. Ninety-five of the 101 (94%) patients with auto-Abs were male. The auto-Abs neutralized high concentrations of the corresponding type I IFN, including their ability to block SARS-CoV-2 infection in vitro. All patients with auto-Abs had low or undetectable serum levels of IFN-α during acute disease.
The results are important as they suggest that errors of type I IFN immunity can explain the development of life-threatening COVID-19 in some individuals. However, it is important to note that the majority of patients (89.8%) with critical COVID-19 did not have auto-Abs, therefore the findings do not explain the pathogenesis underlying critical disease in most patients. In addition, the results do not establish causality, as the vast majority of samples were collected during the acute phase of disease. For instance, for Italian patients, samples were collected at a median of 10 days after hospital admission. Overall, this study advances our understanding of potential immune pathways underlying life-threatening COVID-19.