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

Author

Listed:
  • Matthew S. Buckland

    (Department of Clinical Immunology, Barts Health
    UCL GOSH Institute of Child Health Division of Infection and Immunity, Section of Cellular and Molecular Immunology)

  • 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
    Nuffield Department of Clinical Medicine, University of Oxford)

  • Stuart Bloor

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
    Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus)

  • Ane Ogbe

    (Peter Medawar Building for Pathogen Research
    Nuffield Department of Clinical Medicine, University of Oxford)

  • 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
    PHE – Public Health England Laboratory, Cambridge. Box 236, Cambridge University Hospitals NHS Foundation Trust)

  • 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
    Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus)

  • Lorinda Turner

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
    Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus)

  • Frederica Mescia

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
    Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus)

  • Erik J. M. Toonen

    (R&D Department, Hycult Biotechnology)

  • Carl-Philipp Hackstein

    (Peter Medawar Building for Pathogen Research
    Nuffield Department of Clinical Medicine, University of Oxford)

  • Hossain Delowar Akther

    (Peter Medawar Building for Pathogen Research
    Nuffield Department of Clinical Medicine, University of Oxford)

  • Vinicius Adriano Vieira

    (Peter Medawar Building for Pathogen Research
    Nuffield Department of Clinical Medicine, University of Oxford)

  • 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
    Cambridge University Hospitals NHS Foundation Trust, Department of Microbiology)

  • William L. Hamilton

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
    Cambridge University Hospitals NHS Foundation Trust)

  • 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
    Regional Immunology Service, Belfast Health and Social Care Trust)

  • Lisa Devlin

    (Belfast Health and Social Care Trust
    Regional Immunology Service, 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
    Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus)

  • Willem H. Ouwehand

    (Department of Haematology, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus
    NHS Blood and Transplant, Cambridge Biomedical Campus)

  • Lise Estcourt

    (NHS Blood and Transplant)

  • Heli Harvala

    (NHS Blood and Transplant)

  • David J. Roberts

    (NHS Blood and Transplant
    Radcliffe Department of Medicine and BRC Haematology Theme, University of Oxford, John Radcliffe Hospital)

  • 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
    Department of Medicine, University of Cambridge School of Clinical Medicine, 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
    Nuffield Department of Clinical Medicine, University of Oxford)

  • Paul J. Lehner

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
    Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus
    Department of Infectious Diseases, Cambridge University Hospitals NHS Trust)

  • Nicholas J. Matheson

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
    Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus
    Department of Infectious Diseases, Cambridge University Hospitals NHS Trust
    NHS Blood and Transplant, Cambridge Biomedical Campus)

  • James E. D. Thaventhiran

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus
    Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus
    Medical Research Council Toxicology Unit, University of Cambridge
    Cancer Research UK Cambridge Institute, Cambridge Biomedical Campus)

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.

Suggested Citation

  • 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 , 2020. "Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19761-2
    DOI: 10.1038/s41467-020-19761-2
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    Cited by:

    1. Juan Carlos Yam-Puc & Zhaleh Hosseini & Emily C. Horner & Pehuén Pereyra Gerber & Nonantzin Beristain-Covarrubias & Robert Hughes & Aleksei Lulla & Maria Rust & Rebecca Boston & Magda Ali & Katrin Fis, 2023. "Age-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Sebastian Weigang & Jonas Fuchs & Gert Zimmer & Daniel Schnepf & Lisa Kern & Julius Beer & Hendrik Luxenburger & Jakob Ankerhold & Valeria Falcone & Janine Kemming & Maike Hofmann & Robert Thimme & Ch, 2021. "Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants," Nature Communications, Nature, vol. 12(1), pages 1-12, December.

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