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

by Yakovleva, Anna , Bradley, John R. , Smielewska, Anna , Hamilton, William L. , Estcourt, Lise , Provine, Nicholas M. , Bergamaschi, Laura , Harvala, Heli , Lyons, Paul A. , Galloway, James B. , Loman, Nicholas , Stockton, Joanne , Akther, Hossain Delowar , Wilkinson, Ian B. , Quick, Josh , Periselneris, Jimstan , Toonen, Erik J. M. , Hunter, Michael , Smith, Kenneth G. C. , Kiani-Alikhan, Sorena , Doffinger, Rainer , Lehner, Paul J. , Török, M. Estée , Bloor, Stuart , Ceron-Gutierrez, Lourdes , Mescia, Frederica , Ogbe, Ane , Buckland, Matthew S. , Turner, Lorinda , Vaghela, Devan , Meredith, Luke , Klenerman, Paul , Zelek, Wioleta M. , Mann, Tiffeney , Thaventhiran, James E. D. , Morgan, B. Paul , Grigoriadou, Sofia , Screaton, Nick , Goodfellow, Ian G. , Matheson, Nicholas J. , Vieira, Vinicius Adriano , Lear, Sara E. , Fhogartaigh, Caoimhe Nic , Devlin, Lisa , Roberts, David J. , Hackstein, Carl-Philipp , Nelson, Peter , Ouwehand, Willem H. , Coulter, Tanya I.

in 13/1 / 13/31 / 631/326/596/1296 / 631/326/596/4130 / 692/699/249/2512 / 692/699/255/2514 / Adenosine Monophosphate - analogs & derivatives / Adenosine Monophosphate - therapeutic use / Adult / Alanine - analogs & derivatives / Alanine - therapeutic use / Antibodies / Antiviral agents / Antiviral Agents - therapeutic use / Antiviral drugs / Case reports / Cell activation / Clinical trials / Complement activation / Coronaviridae / Coronaviruses / COVID-19 / COVID-19 - virology / Drug resistance / Fever - prevention & control / Health services / Humanities and Social Sciences / Humans / Humoral immunity / Immunity, Humoral - drug effects / Immunity, Humoral - immunology / Lymphocyte Count / Lymphocytes / Lymphocytes T / Male / multidisciplinary / Pandemics / Patients / Pneumonitis / Respiratory diseases / SARS-CoV-2 - drug effects / SARS-CoV-2 - immunology / SARS-CoV-2 - physiology / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Treatment Outcome / Viral diseases

2020

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

2020

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2020

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Journal Article

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

Yakovleva, Anna,

Bradley, John R.,

Smielewska, Anna,

Hamilton, William L.,

Estcourt, Lise,

Provine, Nicholas M.,

Bergamaschi, Laura,

Harvala, Heli,

Lyons, Paul A.,

Galloway, James B.,

Loman, Nicholas,

Stockton, Joanne,

Akther, Hossain Delowar,

Wilkinson, Ian B.,

Quick, Josh,

Periselneris, Jimstan,

Toonen, Erik J. M.,

Hunter, Michael,

Smith, Kenneth G. C.,

Kiani-Alikhan, Sorena,

Doffinger, Rainer,

Lehner, Paul J.,

Török, M. Estée,

Bloor, Stuart,

Ceron-Gutierrez, Lourdes,

Mescia, Frederica,

Ogbe, Ane,

Buckland, Matthew S.,

Turner, Lorinda,

Vaghela, Devan,

Meredith, Luke,

Klenerman, Paul,

Zelek, Wioleta M.,

Mann, Tiffeney,

Thaventhiran, James E. D.,

Morgan, B. Paul,

Grigoriadou, Sofia,

Screaton, Nick,

Goodfellow, Ian G.,

Matheson, Nicholas J.,

Vieira, Vinicius Adriano,

Lear, Sara E.,

Fhogartaigh, Caoimhe Nic,

Devlin, Lisa,

Roberts, David J.,

Hackstein, Carl-Philipp,

Nelson, Peter,

Ouwehand, Willem H.,

Coulter, Tanya I.

2020

Overview

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. Remdesivir is under evaluation for treatment of COVID-19 in clinical trials. Here, the authors report results of remdesivir treatment in a patient with COVID-19 and the genetic antibody deficiency XLA. They show a temporally correlated clinical and virological response, suggesting that remdesivir can reduce SARS-CoV-2 replication in patients.

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Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

/ 13/31

/ Adenosine Monophosphate - analogs & derivatives