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Nat Commun
. 2020 Dec 14;11(1):6385.
doi: 10.1038/s41467-020-19761-2.
Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report
Matthew S Buckland 1 2 , James B Galloway 3 , Caoimhe Nic Fhogartaigh 4 , Luke Meredith 5 , Nicholas M Provine 6 7 , Stuart Bloor 8 9 , Ane Ogbe 6 7 , Wioleta M Zelek 10 , Anna Smielewska 11 12 , Anna Yakovleva 5 , Tiffeney Mann 13 , Laura Bergamaschi 8 9 , Lorinda Turner 8 9 , Frederica Mescia 8 9 , Erik J M Toonen 14 , Carl-Philipp Hackstein 6 7 , Hossain Delowar Akther 6 7 , Vinicius Adriano Vieira 6 7 , Lourdes Ceron-Gutierrez 15 , Jimstan Periselneris 16 , Sorena Kiani-Alikhan 17 , Sofia Grigoriadou 17 , Devan Vaghela 18 , Sara E Lear 19 , M Est?e T?r?k 8 20 , William L Hamilton 8 21 , Joanne Stockton 22 , Josh Quick 22 , Peter Nelson 23 , Michael Hunter 23 , Tanya I Coulter 23 24 , Lisa Devlin 23 24 , CITIID-NIHR COVID-19 BioResource Collaboration; MRC-Toxicology Unit COVID-19 Consortium; John R Bradley 25 , Kenneth G C Smith 8 9 , Willem H Ouwehand 26 27 , Lise Estcourt 28 , Heli Harvala 29 , David J Roberts 28 30 , Ian B Wilkinson 9 , Nick Screaton 31 , Nicholas Loman 22 , Rainer Doffinger 16 , Paul A Lyons 8 9 , B Paul Morgan 10 , Ian G Goodfellow 5 , Paul Klenerman 6 7 , Paul J Lehner 8 9 18 , Nicholas J Matheson 32 33 34 35 , James E D Thaventhiran 36 37 38 39
Affiliations
- PMID: 33318491
- DOI: 10.1038/s41467-020-19761-2
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.