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

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-...

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Autores principales: 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., Thaventhiran, James E. D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736571/
https://www.ncbi.nlm.nih.gov/pubmed/33318491
http://dx.doi.org/10.1038/s41467-020-19761-2
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author 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.
Thaventhiran, James E. D.
author_facet 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.
Thaventhiran, James E. D.
author_sort Buckland, Matthew S.
collection PubMed
description 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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spelling pubmed-77365712020-12-28 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. Thaventhiran, James E. D. Nat Commun Article 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. Nature Publishing Group UK 2020-12-14 /pmc/articles/PMC7736571/ /pubmed/33318491 http://dx.doi.org/10.1038/s41467-020-19761-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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.
Thaventhiran, James E. D.
Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report
title Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report
title_full Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report
title_fullStr Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report
title_full_unstemmed Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report
title_short Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report
title_sort treatment of covid-19 with remdesivir in the absence of humoral immunity: a case report
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736571/
https://www.ncbi.nlm.nih.gov/pubmed/33318491
http://dx.doi.org/10.1038/s41467-020-19761-2
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