Fungal Pathogenesis Section, LCIM, NIAID, NIH, Bethesda, MD, United States.
Immunopathogenesis Section, LCIM, NIAID, NIH, Bethesda, MD, United States.
Front Immunol. 2021 Aug 24;12:720205. doi: 10.3389/fimmu.2021.720205. eCollection 2021.
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 () 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.
患有单基因免疫失调综合征自身免疫性多内分泌腺病-念珠菌病-外胚层营养不良（APECED）的患者，其病因是自身免疫调节（）基因的功能丧失性突变，均携带针对 I 型干扰素（IFN）的中和自身抗体，许多患者会发展为自身免疫性肺炎，这使他们面临罹患危及生命的 COVID-19 肺炎的高风险。巴姆单抗和埃特司韦单抗是靶向 SARS-CoV-2 刺突蛋白的单克隆抗体（mAb），可阻止 SARS-CoV-2 进入宿主细胞。在感染早期使用巴姆单抗和埃特司韦单抗与降低高危患者 COVID-19 相关住院率和死亡率相关，这促使美国食品和药物管理局发布了在非低氧血症、非住院高危患者中使用的紧急使用授权。然而，这些 mAb 在 APECED 患者中的安全性和疗效尚未得到评估。我们根据机构审查委员会（IRB）批准的方案（NCT01386437）招募了两名患有 APECED 的兄弟姐妹，并在 NIH 临床中心预防性收治，以评估他们轻度至中度 COVID-19 的病情。我们评估了早期使用巴姆单抗和埃特司韦单抗的安全性和临床效果。巴姆单抗和埃特司韦单抗的给药耐受良好，并改善了 COVID-19 症状，预防了侵入性通气支持、入住重症监护病房和死亡，而不影响对 SARS-CoV-2 核衣壳蛋白的抗体产生。如果在 COVID-19 感染的早期给予，巴姆单抗和埃特司韦单抗可能对 APECED 和其他针对 I 型 IFN 的中和自身抗体的高危患者有益。
