Patients with the monogenic immune dysregulatory syndrome autoimmune 
polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), which is caused by 
loss-of-function mutations in the autoimmune regulator (AIRE) gene, uniformly 
carry neutralizing autoantibodies directed against type-I interferons (IFNs) and 
many develop autoimmune pneumonitis, both of which place them at high risk for 
life-threatening COVID-19 pneumonia. Bamlanivimab and etesevimab are monoclonal 
antibodies (mAbs) that target the SARS-CoV-2 spike protein and block entry of 
SARS-CoV-2 in host cells. The use of bamlanivimab and etesevimab early during 
infection was associated with reduced COVID-19-associated hospitalization and 
death in patients at high risk for progressing to severe disease, which led the 
US Food and Drug Administration to issue an emergency use authorization for 
their administration in non-hypoxemic, non-hospitalized high-risk patients. 
However, the safety and efficacy of these mAbs has not been evaluated in APECED 
patients. We enrolled two siblings with APECED on an IRB-approved protocol 
(NCT01386437) and admitted them prophylactically at the NIH Clinical Center for 
evaluation of mild-to-moderate COVID-19. We assessed the safety and clinical 
effects of early treatment with bamlanivimab and etesevimab. The administration 
of bamlanivimab and etesevimab was well tolerated and was associated with 
amelioration of COVID-19 symptoms and prevention of invasive ventilatory 
support, admission to the intensive care, and death in both patients without 
affecting the production of antibodies to the nucleocapsid protein of 
SARS-CoV-2. If given early in the course of COVID-19 infection, bamlanivimab and 
etesevimab may be beneficial in APECED and other high-risk patients with 
neutralizing autoantibodies directed against type-I IFNs.