Inborn errors of immunity (IEIs) often increase susceptibility to severe and/or recurrent infection, but also autoimmunity, autoinflammation, allergy, and cancer. At the beginning of the COVID-19 pandemic, patients with IEIs were considered to be at risk for severe COVID-19. Recent studies however report that most patients with IEIs had silent infection with SARS-CoV-2 or mild COVID-19, as seen in the general population [1, 2]. However, the COVID-19-related mortality rates among IEI patients in global and Brazilian studies were higher than those of the general population [1, 2]. In this context, patients with autoimmune polyglandular syndrome type 1 (APS-1), which results from pathogenic variants in the AIRE gene, produce autoantibodies (auto-Abs) against type I interferons (IFNs) from early childhood onwards, which predispose them to life-threatening COVID-19 pneumonia [3, 4]. We report two Brazilian brothers, 13 yo (P1) and 7 yo (P2), born to third-degree consanguineous parents of Italian and Polish descent. The boys presented with life-threatening COVID-19 pneumonia, which led to their diagnosis of APS-1.

P1 first exhibited fever and wheezing after contact with his father who had tested positive for SARS-CoV-2 and developed mild COVID-19 (Fig. 1A). With a history of asthma, P1 was prescribed azithromycin, prednisone, antipyretics, and a bronchodilator. Two days later, P1 presented to a metropolitan field hospital, near to the capital of Parana State in Brazil, with worsening respiratory pattern, cough,