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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. and Thaventhiran, James E. D. 2020. Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report. Nature Communications 11 (1) , 6385. 10.1038/s41467-020-19761-2

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Nature Research
ISSN: 2041-1723
Date of First Compliant Deposit: 21 January 2021
Date of Acceptance: 27 October 2020
Last Modified: 22 Jan 2021 13:45

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