SARS-CoV-2 Spike Protein-Directed Monoclonal Antibodies May Ameliorate COVID-19 Complications in APECED Patients.
SARS-CoV-2 Spike Protein-Directed Monoclonal Antibodies May Ameliorate COVID-19 Complications in APECED Patients.
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DOI：
10.3389/fimmu.2021.720205
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发表时间：
2021
影响因子：
7.3
通讯作者：
Lionakis MS
中科院分区：
文献类型：
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作者：
Ferré EMN;Schmitt MM;Ochoa S;Rosen LB;Shaw ER;Burbelo PD;Stoddard JL;Rampertaap S;DiMaggio T;Bergerson JRE;Rosenzweig SD;Notarangelo LD;Holland SM;Lionakis MS
患有单基因免疫失调综合征自身免疫性多内分泌病-念珠菌病-外胚层营养不良症 (APECED) 的患者是由自身免疫调节器 (AIRE) 基因功能丧失突变引起的，均携带针对 I 型干扰素 (IFN) 的中和性自身抗体，许多患者会发展为自身免疫性肺炎，这两种情况都使他们面临危及生命的 COVID-19 肺炎的高风险。 Bamlanivimab 和 etesevimab 是单克隆抗体 (mAb)，靶向 SARS-CoV-2 刺突蛋白并阻止 SARS-CoV-2 进入宿主细胞。在感染早期使用 bamlanivimab 和 etesevimab 与进展为严重疾病的高风险患者中与 COVID-19 相关的住院和死亡减少有关，这导致美国食品和药物管理局发布紧急使用授权，将其用于非低氧血症、非住院高风险患者。然而，这些单克隆抗体的安全性和有效性尚未在 APECED 患者中进行评估。我们根据 IRB 批准的方案 (NCT01386437) 将两名兄弟姐妹纳入 APECED，并预防性地将他们收入 NIH 临床中心，以评估轻至中度的 COVID-19。我们评估了 bamlanivimab 和 etesevimab 早期治疗的安全性和临床效果。 bamlanivimab 和 etesevimab 的给药耐受性良好，与改善 COVID-19 症状、预防有创通气支持、入住重症监护室和死亡相关，且不影响 SARS-CoV-2 核衣壳蛋白抗体的产生。如果在 COVID-19 感染过程的早期给予，bamlanivimab 和 etesevimab 可能对 APECED 和其他具有针对 I 型 IFN 的中和自身抗体的高危患者有益。
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.