Treatment of COVID-19 with remdesivir in the absence of humoral immunity, a case report
Morgan, B Paul
Adriano Vieira, Vinicius
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Thaventhiran, J., Matheson, N., Lehner, P., Klenerman, P., Goodfellow, I., Morgan, B. P., Lyons, P., et al. Treatment of COVID-19 with remdesivir in the absence of humoral immunity, a case report. Nature Communications https://doi.org/10.17863/CAM.58548
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.
JEDT is supported by the MRC (RG95376 and MC_UU_00025/12). NJM is supported by the MRC (CSF MR/P008801/1) and NHSBT (WPA15-02). PJL is supported by the Wellcome Trust (PRF 210688/Z/18/Z). PK is a Wellcome Investigator (WT109965MA). IG is supported by the Wellcome Trust (Senior Fellowship 207498/Z/17/Z and ARTIC Network Collaborative Award 206298/B/17/Z). KGCS is a Wellcome Investigator (200871/Z/16/Z). PAL and KGCS are additionally supported by the EU H2020 research and innovation programme under grant agreement 668036 (RELENT). This work was supported by the NIHR Oxford Biomedical Research Centre, Oxford Immunology Network COVID-19 Response T cell Consortium and the NIHR Cambridge Biomedical Research Centre. This work was partly funded by UKRI/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC). The viral sequencing was funded by COVID-19 Genomics UK, which is supported by funding from the Medical Research Council part of UK Research and Innovation, the National Institute of Health Research, and Genome Research, operating as the Wellcome Sanger Institute.
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This record's DOI: https://doi.org/10.17863/CAM.58548
This record's URL: https://www.repository.cam.ac.uk/handle/1810/311455
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