Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-020-19761-2
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Funding
- MRC [RG95376, MC_UU_00025/12]
- MRC (CSF) [MR/P008801/1]
- NHSBT [WPA15-02]
- Wellcome Trust [PRF 210688/Z/18/Z, 207498/Z/17/Z]
- Wellcome [WT109965MA, 200871/Z/16/Z]
- ARTIC Network Collaborative Award [206298/B/17/Z]
- EU H2020 research and innovation program [668036]
- NIHR Oxford Biomedical Research Centre
- Oxford Immunology Network COVID-19 Response T cell Consortium
- NIHR Cambridge Biomedical Research Centre
- UKRI/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC)
- COVID-19 Genomics UK - Medical Research Council, UK Research and Innovation
- National Institute of Health Research, and Genome Research
- H2020 Societal Challenges Programme [668036] Funding Source: H2020 Societal Challenges Programme
- Wellcome Trust [206298/B/17/Z, 200871/Z/16/Z] Funding Source: Wellcome Trust
- MRC [MR/J014370/1, MR/P008801/1, MR/V028448/1] Funding Source: UKRI
- UKRI [MR/S035362/1] Funding Source: UKRI
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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.
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