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

Matthew Buckland(Barts Health NHS Trust), James Galloway(King's College London), Caoimhe Nic Fhogartaigh(Barts Health NHS Trust), Luke W. Meredith(University of Cambridge), Nicholas M. Provine(University of Oxford), Stuart Bloor(University of Cambridge), Ane Ogbe(University of Oxford), Wioleta M. Zelek(UK Dementia Research Institute), Anna Smielewska(University of Cambridge), Anna Yakovleva(University of Cambridge), Tiffeney Mann(University of Cambridge), Laura Bergamaschi(University of Cambridge), Lorinda Turner(University of Cambridge), Frederica Mescia(University of Cambridge), Erik J. M. Toonen(Hycult Biotech (Netherlands)), Carl-Philipp Hackstein(University of Oxford), Hossain Delowar Akther(University of Oxford), Vinícius Vieira(University of Oxford), Lourdes Ceron‐Gutierrez(Addenbrooke's Hospital), Jimstan Periselneris(King's College Hospital NHS Foundation Trust), Sorena Kiani‐Alikhan(Barts Health NHS Trust), Sofia Grigoriadou(Barts Health NHS Trust), Devan Vaghela(Cambridge University Hospitals NHS Foundation Trust), Sara Lear(Cambridge University Hospitals NHS Foundation Trust), M. Estée Török(Cambridge University Hospitals NHS Foundation Trust), William L. Hamilton(Cambridge University Hospitals NHS Foundation Trust), Joanne Stockton(University of Birmingham), Josh Quick(University of Birmingham), Peter H. Nelson(Belfast Health and Social Care Trust), Michael Hunter(Belfast Health and Social Care Trust), Tanya Coulter(Belfast Health and Social Care Trust), Lisa Devlin(Belfast Health and Social Care Trust), John R. Bradley(NIHR Cambridge Biomedical Research Centre), Kenneth G. C. Smith(University of Cambridge), Willem H. Ouwehand(NHS Blood and Transplant), Lise J Estcourt(NHS Blood and Transplant), Heli Harvala(NHS Blood and Transplant), David J. Roberts(NHS Blood and Transplant), Ian B. Wilkinson(University of Cambridge), Nick Screaton(Papworth Hospital), Nicholas J. Loman(University of Birmingham), Rainer Döffinger(King's College Hospital NHS Foundation Trust), Paul Lyons(University of Cambridge), B. Paul Morgan(UK Dementia Research Institute), Ian Goodfellow(University of Cambridge), Paul Klenerman(University of Oxford), Paul J. Lehner(University of Cambridge), Nicholas J. Matheson(NHS Blood and Transplant), James Thaventhiran(MRC Laboratory of Molecular Biology)
Nature Communications
December 14, 2020
Cited by 130Open Access
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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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