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

Author:

Buckland Matthew S.ORCID, ,Galloway James B.,Fhogartaigh Caoimhe Nic,Meredith Luke,Provine Nicholas M.,Bloor Stuart,Ogbe AneORCID,Zelek Wioleta M.,Smielewska Anna,Yakovleva Anna,Mann Tiffeney,Bergamaschi Laura,Turner Lorinda,Mescia FredericaORCID,Toonen Erik J. M.ORCID,Hackstein Carl-Philipp,Akther Hossain Delowar,Vieira Vinicius AdrianoORCID,Ceron-Gutierrez Lourdes,Periselneris Jimstan,Kiani-Alikhan SorenaORCID,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.ORCID,Estcourt Lise,Harvala Heli,Roberts David J.,Wilkinson Ian B.,Screaton Nick,Loman Nicholas,Doffinger Rainer,Lyons Paul A.ORCID,Morgan B. Paul,Goodfellow Ian G.,Klenerman Paul,Lehner Paul J.ORCID,Matheson Nicholas J.ORCID,Thaventhiran James E. D.ORCID,

Abstract

AbstractThe 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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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