Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report

Matthew S. Buckland (), James B. Galloway, Caoimhe Nic Fhogartaigh, Luke Meredith, Nicholas M. Provine, Stuart Bloor, Ane Ogbe, Wioleta M. Zelek, Anna Smielewska, Anna Yakovleva, Tiffeney Mann, Laura Bergamaschi, Lorinda Turner, Frederica Mescia, Erik J. M. Toonen, Carl-Philipp Hackstein, Hossain Delowar Akther, Vinicius Adriano Vieira, Lourdes Ceron-Gutierrez, Jimstan Periselneris, Sorena Kiani-Alikhan, Sofia Grigoriadou, Devan Vaghela, Sara E. Lear, M. Estée Török, William L. Hamilton, Joanne Stockton, Josh Quick, Peter Nelson, Michael Hunter, Tanya I. Coulter, Lisa Devlin, John R. Bradley, Kenneth G. C. Smith, Willem H. Ouwehand, Lise Estcourt, Heli Harvala, David J. Roberts, Ian B. Wilkinson, Nick Screaton, Nicholas Loman, Rainer Doffinger, Paul A. Lyons, B. Paul Morgan, Ian G. Goodfellow, Paul Klenerman, Paul J. Lehner, Nicholas J. Matheson () and James E. D. Thaventhiran ()
Additional contact information
Matthew S. Buckland: Department of Clinical Immunology, Barts Health
James B. Galloway: Centre for Rheumatic Diseases, King’s College London
Caoimhe Nic Fhogartaigh: Department of Infection, Barts Health NHS Trust
Luke Meredith: Department of Pathology, University of Cambridge, Addenbrooke’s Hospital
Nicholas M. Provine: Peter Medawar Building for Pathogen Research
Stuart Bloor: Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
Ane Ogbe: Peter Medawar Building for Pathogen Research
Wioleta M. Zelek: Systems Immunity Institute and Dementia Research Institute, Cardiff University
Anna Smielewska: Division of Virology, Department of Pathology, University of Cambridge, Addenbrookes Hospital
Anna Yakovleva: Department of Pathology, University of Cambridge, Addenbrooke’s Hospital
Tiffeney Mann: Medical Research Council Toxicology Unit, University of Cambridge
Laura Bergamaschi: Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
Lorinda Turner: Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
Frederica Mescia: Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
Erik J. M. Toonen: R&D Department, Hycult Biotechnology
Carl-Philipp Hackstein: Peter Medawar Building for Pathogen Research
Hossain Delowar Akther: Peter Medawar Building for Pathogen Research
Vinicius Adriano Vieira: Peter Medawar Building for Pathogen Research
Lourdes Ceron-Gutierrez: Department of Clinical Biochemistry and Immunology, Addenbrooke’s Hospital
Jimstan Periselneris: Respiratory Department, King’s College Hospital NHS Foundation Trust, UK. Department of Clinical Virology
Sorena Kiani-Alikhan: Department of Clinical Immunology, Barts Health
Sofia Grigoriadou: Department of Clinical Immunology, Barts Health
Devan Vaghela: Department of Infectious Diseases, Cambridge University Hospitals NHS Trust
Sara E. Lear: Department of Immunology, Cambridge University Hospitals NHS Trust
M. Estée Török: Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
William L. Hamilton: Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
Joanne Stockton: Institute of Microbiology and Infection, University of Birmingham
Josh Quick: Institute of Microbiology and Infection, University of Birmingham
Peter Nelson: Belfast Health and Social Care Trust
Michael Hunter: Belfast Health and Social Care Trust
Tanya I. Coulter: Belfast Health and Social Care Trust
Lisa Devlin: Belfast Health and Social Care Trust
John R. Bradley: NIHR BioResource and NIHR Cambridge Biomedical Research Centre, Cambridge Biomedical Campus
Kenneth G. C. Smith: Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
Willem H. Ouwehand: Department of Haematology, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus
Lise Estcourt: NHS Blood and Transplant
Heli Harvala: NHS Blood and Transplant
David J. Roberts: NHS Blood and Transplant
Ian B. Wilkinson: Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus
Nick Screaton: Radiology, Papworth Hospital
Nicholas Loman: Institute of Microbiology and Infection, University of Birmingham
Rainer Doffinger: Respiratory Department, King’s College Hospital NHS Foundation Trust, UK. Department of Clinical Virology
Paul A. Lyons: Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
B. Paul Morgan: Systems Immunity Institute and Dementia Research Institute, Cardiff University
Ian G. Goodfellow: Department of Pathology, University of Cambridge, Addenbrooke’s Hospital
Paul Klenerman: Peter Medawar Building for Pathogen Research
Paul J. Lehner: Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
Nicholas J. Matheson: Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
James E. D. Thaventhiran: Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.

Date: 2020
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DOI: 10.1038/s41467-020-19761-2

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