Remdesivir failure with SARS-CoV-2 RNA-dependent RNA-polymerase mutation in a B-cell immunodeficient patient with protracted Covid-19

Martin Martinot; Aude Jary; Samira Fafi-Kremer; Valentin Leducq; Heloise Delagreverie; Marc Garnier; Jérôme Pacanowski; Arsène Mékinian; France Pirenne; Pierre Tiberghien; Vincent Calvez; Catherine Humbrecht; Anne-Geneviève Marcelin; Karine Lacombe

doi:10.1093/cid/ciaa1474

Remdesivir failure with SARS-CoV-2 RNA-dependent RNA-polymerase mutation in a B-cell immunodeficient patient with protracted Covid-19

Clin Infect Dis. 2020 Sep 28;ciaa1474. doi: 10.1093/cid/ciaa1474. Online ahead of print.

Authors

Affiliations

¹ Infectious diseases Department, Hôpitaux Civils de Colmar, Colmar, France.
² Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Pitié-Salpêtrière Hospital, Department of Virology, Paris, France.
³ Virology Laboratory, Strasbourg University Hospital, Strasbourg, France Strasbourg University, INSERM, IRM UMR-S, Strasbourg, France.
⁴ Sorbonne Université, GRC, APHP, DMU DREAM, Anesthesiology and Intensive Care Department, Saint-Antoine Hospital - Paris, France.
⁵ Infectious diseases Department, Saint-Antoine Hospital, APHP - Sorbonne Université, Paris - France.
⁶ Sorbonne Université, Internal Medicine Department, Inflammation-Immunopathology-Biotherapy Department (DMU i3D), Saint-Antoine Hospital, AP-HP,Paris - France.
⁷ Etablissement Français du Sang, La Plaine St-Denis - France.
⁸ Institut Mondor de Recherche Biomédicale, Unité, Equipe: Transfusion et Maladies du Globule Rouge, INSERM, EFS, Université Paris-Est Créteil, Créteil - France.
⁹ UMR 1098 RIGHT Inserm Université de Franche-Comté Etablissement Français du Sang, Besançon.
¹⁰ Etablissement Français du sang Grand Est, Strasbourg, France.
¹¹ Sorbonne Université, Inserm IPLESP, Infectious Diseases Department, Saint-Antoine Hospital, APHP, Paris - France.

Abstract

SARS-CoV-2 is a new pandemic virus for which Remdesivir is the only antiviral available. We report the occurrence of a mutation in the RdRP (D484Y) following failure of remdesivir in a 76-year-old woman with a post-rituximab B-cell immunodeficiency and persistent SARS-CoV-2 viremia. Cure was reached after supplementation with convalescent plasma.

Keywords: COVID-19; CoVID-19 convalescent plasma; Remdesivir; SARS-CoV-2; SARS-CoV-2 RNA-dependent RNA-polymerase mutation.