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

10.1038/s41467-020-19761-2

Nature Communications

14th December 2020

Contributing to research themes:

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.

Author list:

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, Laura Bergamaschi, Lorinda Turner, Frederica Mescia, Erik J. M. Toonen, Carl-Philipp Hackstein, Hossain Delowar Akther, Vinicius Adriano Vieira, Lourdes Ceron-Gutierrez, Jimstan Periselneris, Sorena Kiani-Alikhan, Sofia Grigoriadou, Devan Vaghela, Sara E. Lear, M. Estée Török, William L. Hamilton, Joanne Stockton, Josh Quick, Peter Nelson, Michael Hunter, Tanya I. Coulter, Lisa Devlin, CITIID-NIHR COVID-19 BioResource Collaboration, MRC-Toxicology Unit COVID-19 Consortium, John R. Bradley, Kenneth G. C. Smith, Willem H. Ouwehand, Lise Estcourt, Heli Harvala, David J. Roberts, Ian B. Wilkinson, Nick Screaton, Nicholas Loman, Rainer Doffinger, Paul A. Lyons, B. Paul Morgan, Ian G. Goodfellow, Paul Klenerman, Paul J. Lehner, Nicholas J. Matheson & James E. D. Thaventhiran