RE: Eric Topol Again24 Sep 2020 22:59
Conclusion of the papers -
We report here that at least 10% of patients with life-threatening COVID-19 pneumonia have neutralizing auto-Abs against type I IFNs. With our accompanying description of patients with inborn errors of type I IFNs and life-threatening COVID-19 (18), this study highlights the crucial role of type I IFNs in protective immunity against SARS-CoV-2. These auto-Abs against type I IFNs were clinically silent until the patients were infected with SARS-CoV-2, which is a poor inducer of type I IFNs (28), suggesting that the small amounts of IFNs induced by the virus are important for protection against severe disease. The neutralizing auto-Abs against type I IFNs, like inborn errors of type I IFN production, tip the balance in favor of the virus, resulting in devastating disease, with insufficient, and even perhaps deleterious, innate and adaptive immune responses.
Our findings have direct clinical implications. First, SARS-CoV-2-infected patients can be screened to identify individuals with auto-Abs at risk of developing life-threatening pneumonia. Such patients recovering from life-threatening COVID-19 should also be excluded from donating convalescent plasma for ongoing clinical trial, or at least tested before their plasma donations are accepted (29). Second, this unexpected finding paves the way for therapeutic intervention, including plasmapheresis, monoclonal Abs depleting plasmablasts, and the specific inhibition of type I IFN-reactive B cells (30). Finally, in this patient group, early treatment with IFN-a is unlikely to be beneficial. However, treatment with injected or nebulized IFN-ß may have beneficial effects, as auto-Abs against IFN-ß appear to be rare in patients with auto-Abs against type I IFNs.
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