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SARS-CoV-2 Spike Protein-Directed Monoclonal Antibodies May Ameliorate COVID-19 Complications in APECED Patients.
- Source :
-
Frontiers in immunology [Front Immunol] 2021 Aug 24; Vol. 12, pp. 720205. Date of Electronic Publication: 2021 Aug 24 (Print Publication: 2021). - Publication Year :
- 2021
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Abstract
- 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.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2021 Ferré, Schmitt, Ochoa, Rosen, Shaw, Burbelo, Stoddard, Rampertaap, DiMaggio, Bergerson, Rosenzweig, Notarangelo, Holland and Lionakis.)
- Subjects :
- Adult
COVID-19 complications
COVID-19 genetics
COVID-19 immunology
Female
Humans
Interferons genetics
Interferons immunology
Male
Mutation
Polyendocrinopathies, Autoimmune complications
Polyendocrinopathies, Autoimmune genetics
Polyendocrinopathies, Autoimmune immunology
SARS-CoV-2 genetics
Spike Glycoprotein, Coronavirus genetics
Transcription Factors genetics
Transcription Factors immunology
AIRE Protein
Antibodies, Monoclonal, Humanized administration & dosage
Polyendocrinopathies, Autoimmune drug therapy
SARS-CoV-2 immunology
Spike Glycoprotein, Coronavirus immunology
COVID-19 Drug Treatment
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34504497
- Full Text :
- https://doi.org/10.3389/fimmu.2021.720205