Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report.
| Title: | Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report. |
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| Authors: | Buckland MS; Department of Clinical Immunology, Barts Health, London, UK. m.buckland@ucl.ac.uk.; UCL GOSH Institute of Child Health Division of Infection and Immunity, Section of Cellular and Molecular Immunology, London, UK. m.buckland@ucl.ac.uk.; Galloway JB; Centre for Rheumatic Diseases, King's College London, London, UK.; Fhogartaigh CN; Department of Infection, Barts Health NHS Trust, London, UK.; Meredith L; Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.; Provine NM; Peter Medawar Building for Pathogen Research, South Parks Rd, Oxford, OX1 3SY, UK.; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.; Bloor S; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.; Ogbe A; Peter Medawar Building for Pathogen Research, South Parks Rd, Oxford, OX1 3SY, UK.; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.; Zelek WM; Systems Immunity Institute and Dementia Research Institute, Cardiff University, Cardiff, UK.; Smielewska A; Division of Virology, Department of Pathology, University of Cambridge, Addenbrookes Hospital, Cambridge, UK.; PHE - Public Health England Laboratory, Cambridge. Box 236, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, UK.; Yakovleva A; Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.; Mann T; Medical Research Council Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge, CB2 1QW, UK.; Bergamaschi L; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.; Turner L; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.; Mescia F; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.; Toonen EJM; R&D Department, Hycult Biotechnology, Frontstraat 2A, 5405 PB, Uden, The Netherlands.; Hackstein CP; Peter Medawar Building for Pathogen Research, South Parks Rd, Oxford, OX1 3SY, UK.; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.; Akther HD; Peter Medawar Building for Pathogen Research, South Parks Rd, Oxford, OX1 3SY, UK.; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.; Vieira VA; Peter Medawar Building for Pathogen Research, South Parks Rd, Oxford, OX1 3SY, UK.; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.; Ceron-Gutierrez L; Department of Clinical Biochemistry and Immunology, Addenbrooke's Hospital, Cambridge, UK.; Periselneris J; Respiratory Department, King's College Hospital NHS Foundation Trust, UK. Department of Clinical Virology, Addenbrookes, UK.; Kiani-Alikhan S; Department of Clinical Immunology, Barts Health, London, UK.; Grigoriadou S; Department of Clinical Immunology, Barts Health, London, UK.; Vaghela D; Department of Infectious Diseases, Cambridge University Hospitals NHS Trust, Cambridge, UK.; Lear SE; Department of Immunology, Cambridge University Hospitals NHS Trust, Cambridge, UK.; Török ME; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.; Cambridge University Hospitals NHS Foundation Trust, Department of Microbiology, Cambridge, UK.; Hamilton WL; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Stockton J; Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK.; Quick J; Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK.; Nelson P; Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.; Hunter M; Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.; Coulter TI; Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.; Regional Immunology Service, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.; Devlin L; Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.; Regional Immunology Service, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.; Bradley JR; NIHR BioResource and NIHR Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, Cambridge, UK.; Smith KGC; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.; Ouwehand WH; Department of Haematology, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.; NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK.; Estcourt L; NHS Blood and Transplant, Oxford, UK.; Harvala H; NHS Blood and Transplant, London, UK.; Roberts DJ; NHS Blood and Transplant, Oxford, UK.; Radcliffe Department of Medicine and BRC Haematology Theme, University of Oxford, John Radcliffe Hospital, Oxford, UK.; Wilkinson IB; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.; Screaton N; Radiology, Papworth Hospital, Cambridge, UK.; Loman N; Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK.; Doffinger R; Respiratory Department, King's College Hospital NHS Foundation Trust, UK. Department of Clinical Virology, Addenbrookes, UK.; Lyons PA; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.; Morgan BP; Systems Immunity Institute and Dementia Research Institute, Cardiff University, Cardiff, UK.; Goodfellow IG; Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.; Klenerman P; Peter Medawar Building for Pathogen Research, South Parks Rd, Oxford, OX1 3SY, UK.; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.; Lehner PJ; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.; Department of Infectious Diseases, Cambridge University Hospitals NHS Trust, Cambridge, UK.; Matheson NJ; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK. njm25@cam.ac.uk.; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK. njm25@cam.ac.uk.; Department of Infectious Diseases, Cambridge University Hospitals NHS Trust, Cambridge, UK. njm25@cam.ac.uk.; NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK. njm25@cam.ac.uk.; Thaventhiran JED; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK. jedt2@cam.ac.uk.; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK. jedt2@cam.ac.uk.; Medical Research Council Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge, CB2 1QW, UK. jedt2@cam.ac.uk.; Cancer Research UK Cambridge Institute, Cambridge Biomedical Campus, Cambridge, UK. jedt2@cam.ac.uk. |
| Corporate Authors: | CITIID-NIHR COVID-19 BioResource Collaboration; MRC-Toxicology Unit COVID-19 Consortium |
| Source: | Nature communications [Nat Commun] 2020 Dec 14; Vol. 11 (1), pp. 6385. Date of Electronic Publication: 2020 Dec 14. |
| Publication Type: | Case Reports; Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Nature Pub. Group |
| MeSH Terms: | Adenosine Monophosphate/*analogs & derivatives ; Alanine/*analogs & derivatives ; Immunity, Humoral/*drug effects ; SARS-CoV-2/*drug effects; Adenosine Monophosphate/therapeutic use ; Alanine/therapeutic use ; Antiviral Agents/therapeutic use ; COVID-19/virology ; Fever/prevention & control ; Immunity, Humoral/immunology ; SARS-CoV-2/immunology ; SARS-CoV-2/physiology ; Adult ; Humans ; Lymphocyte Count ; Male ; Treatment Outcome |
| 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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| Grant Information: | RG95376 United Kingdom MRC_ Medical Research Council; MR/S035362/1 United Kingdom MRC_ Medical Research Council; United Kingdom DH_ Department of Health; MR/M501621/1 United Kingdom MRC_ Medical Research Council; 206298/B/17/Z United Kingdom WT_ Wellcome Trust; MR/J014370/1 United Kingdom MRC_ Medical Research Council; 109965/Z/15/Z United Kingdom WT_ Wellcome Trust; WT109965MA United Kingdom WT_ Wellcome Trust; MR/V011561/1 United Kingdom MRC_ Medical Research Council; 200871/Z/16/Z United Kingdom WT_ Wellcome Trust; 207498/Z/17/Z United Kingdom WT_ Wellcome Trust; MR/V028448/1 United Kingdom MRC_ Medical Research Council; 210688/Z/18/Z United Kingdom WT_ Wellcome Trust; MR/P008801/1 United Kingdom MRC_ Medical Research Council; MR/L006197/1 United Kingdom MRC_ Medical Research Council; MC_UU_00025/12 United Kingdom MRC_ Medical Research Council; HF-19-1595 United Kingdom HCRW_ HCRW_; MC_EX_MR/S300011/1 United Kingdom MRC_ Medical Research Council |
| Substance Nomenclature: | 0 (Antiviral Agents); 3QKI37EEHE (remdesivir); 415SHH325A (Adenosine Monophosphate); OF5P57N2ZX (Alanine) |
| Entry Date(s): | Date Created: 20201215 Date Completed: 20201225 Latest Revision: 20250530 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC7736571 |
| DOI: | 10.1038/s41467-020-19761-2 |
| PMID: | 33318491 |
| Database: | MEDLINE |
Case Reports; Journal Article; Research Support, Non-U.S. Gov't