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Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report.
Buckland, Matthew S; Galloway, James B; Fhogartaigh, Caoimhe Nic; Meredith, Luke; Provine, Nicholas M; Bloor, Stuart; Ogbe, Ane; Zelek, Wioleta M; Smielewska, Anna; Yakovleva, Anna; Mann, Tiffeney; Bergamaschi, Laura; Turner, Lorinda; Mescia, Frederica; Toonen, Erik J M; Hackstein, Carl-Philipp; Akther, Hossain Delowar; Vieira, Vinicius Adriano; Ceron-Gutierrez, Lourdes; Periselneris, Jimstan; Kiani-Alikhan, Sorena; Grigoriadou, Sofia; Vaghela, Devan; Lear, Sara E; Török, M Estée; Hamilton, William L; Stockton, Joanne; Quick, Josh; Nelson, Peter; Hunter, Michael; Coulter, Tanya I; Devlin, Lisa; Bradley, John R; Smith, Kenneth G C; Ouwehand, Willem H; Estcourt, Lise; Harvala, Heli; Roberts, David J; Wilkinson, Ian B; Screaton, Nick; Loman, Nicholas; Doffinger, Rainer; Lyons, Paul A; Morgan, B Paul; Goodfellow, Ian G; Klenerman, Paul; Lehner, Paul J; Matheson, Nicholas J; Thaventhiran, James E D.
  • Buckland MS; Department of Clinical Immunology, Barts Health, London, UK. m.buckland@ucl.ac.uk.
  • Galloway JB; UCL GOSH Institute of Child Health Division of Infection and Immunity, Section of Cellular and Molecular Immunology, London, UK. m.buckland@ucl.ac.uk.
  • Fhogartaigh CN; Centre for Rheumatic Diseases, King's College London, London, UK.
  • Meredith L; Department of Infection, Barts Health NHS Trust, London, UK.
  • Provine NM; Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
  • Bloor S; Peter Medawar Building for Pathogen Research, South Parks Rd, Oxford, OX1 3SY, UK.
  • Ogbe A; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
  • Zelek WM; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.
  • Smielewska A; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.
  • Yakovleva A; Peter Medawar Building for Pathogen Research, South Parks Rd, Oxford, OX1 3SY, UK.
  • Mann T; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
  • Bergamaschi L; Systems Immunity Institute and Dementia Research Institute, Cardiff University, Cardiff, UK.
  • Turner L; Division of Virology, Department of Pathology, University of Cambridge, Addenbrookes Hospital, Cambridge, UK.
  • Mescia F; PHE - Public Health England Laboratory, Cambridge. Box 236, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, UK.
  • Toonen EJM; Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
  • Hackstein CP; Medical Research Council Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge, CB2 1QW, UK.
  • Akther HD; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.
  • Vieira VA; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.
  • Ceron-Gutierrez L; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.
  • Periselneris J; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.
  • Kiani-Alikhan S; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.
  • Grigoriadou S; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.
  • Vaghela D; R&D Department, Hycult Biotechnology, Frontstraat 2A, 5405 PB, Uden, The Netherlands.
  • Lear SE; Peter Medawar Building for Pathogen Research, South Parks Rd, Oxford, OX1 3SY, UK.
  • Török ME; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
  • Hamilton WL; Peter Medawar Building for Pathogen Research, South Parks Rd, Oxford, OX1 3SY, UK.
  • Stockton J; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
  • Quick J; Peter Medawar Building for Pathogen Research, South Parks Rd, Oxford, OX1 3SY, UK.
  • Nelson P; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
  • Hunter M; Department of Clinical Biochemistry and Immunology, Addenbrooke's Hospital, Cambridge, UK.
  • Coulter TI; Respiratory Department, King's College Hospital NHS Foundation Trust, UK. Department of Clinical Virology, Addenbrookes, UK.
  • Devlin L; Department of Clinical Immunology, Barts Health, London, UK.
  • Bradley JR; Department of Immunology, Cambridge University Hospitals NHS Trust, Cambridge, UK.
  • Smith KGC; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.
  • Ouwehand WH; Cambridge University Hospitals NHS Foundation Trust, Department of Microbiology, Cambridge, UK.
  • Estcourt L; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.
  • Harvala H; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
  • Roberts DJ; Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK.
  • Wilkinson IB; Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK.
  • Screaton N; Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
  • Loman N; Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
  • Doffinger R; Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
  • Lyons PA; Regional Immunology Service, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
  • Morgan BP; Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
  • Goodfellow IG; Regional Immunology Service, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
  • Matheson NJ; NIHR BioResource and NIHR Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, Cambridge, UK.
  • Thaventhiran JED; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.
Nat Commun ; 11(1): 6385, 2020 12 14.
Article in English | MEDLINE | ID: covidwho-977267
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Adenosine Monophosphate / Alanine / Immunity, Humoral / SARS-CoV-2 Type of study: Case report / Observational study / Prognostic study Limits: Adult / Humans / Male Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2020 Document Type: Article Affiliation country: S41467-020-19761-2

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Adenosine Monophosphate / Alanine / Immunity, Humoral / SARS-CoV-2 Type of study: Case report / Observational study / Prognostic study Limits: Adult / Humans / Male Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2020 Document Type: Article Affiliation country: S41467-020-19761-2