Thread by @casanova_lab

We report @JExpMed an international survey of SARS-CoV-2-infected APS-1 patients and show that they are at very high risk of life-threatening, critical C-19 pneumonia due to preexisting auto-Abs neutralizing type I IFNs (urldefense.proofpoint.com/v2/url?u=https…)

APS-1 patients typically carry bi-allelic mutations in 𝘈𝘐𝘙𝘌, which controls thymic expression of peripheral antigens, thereby governing central T cell tolerance (science.sciencemag.org/content/298/55…).

They have multiple autoimmune endocrinopathies, and mucocutaneous candidiasis because of auto-Abs to IL-17 cytokines (rupress.org/jem/article/20…, rupress.org/jem/article/20…).

These patients were also shown from 2006 onward to carry auto-Abs against type I IFN (journals.plos.org/plosmedicine/a…) but these auto-Abs were thought to be clinically silent, in the apparent absence of severe viral illnesses in the patients.

Our study is important for APS-1 patients, who should be vaccinated against C-19 ASAP, albeit not with an attenuated Yellow Fever Virus 17D backbone, as they are vulnerable to YFV-17D vaccine link.springer.com/article/10.100….

Upon infection, these patients may be given anti-viral mAb and IFN-beta if diagnosed early enough (link.springer.com/article/10.100…), and steroids if pneumonia is diagnosed, while considering the potential help of plasma exchange (link.springer.com/article/10.100…; jacionline.org/article/S0091-…).

This study is also important beyond APS-1, as it provides proof-of-principle that auto-Abs to type I IFN found in >10% of patients with critical C-19 are preexisting, and causal of disease, as opposed to triggered by the virus (science.sciencemag.org/content/370/65…, science.sciencemag.org/content/370/65…).

Huge thanks to co-authors: @LevyRomain, @JRosain, @PhilippotQ, @ALNeehus, @MelanieMigaud, @kai_kisand, @ShenYingZhang1, @crow_lab, @ldnotar, @JouanguyE, @BenedicteNeven, @anne_puel, @LionakisLab, @LionakisLab, and other co-authors not yet on Twitter 🤗