Title :

Effect of Remdesivir on Viral Dynamics in COVID-19 Hospitalized Patients: A Modelling Analysis of the Randomized, Controlled, Open-Label DisCoVeRy Trial

Author(s) :

Bouscambert-Duchamp, Maude [Auteur]
Virology and human respiratory Pathologies - Virology and human respiratory Pathologies [CIRI] [VirPath]
Hospices Civils de Lyon [HCL]
Centre International de Recherche en Infectiologie [CIRI]
Lingas, Guillaume [Auteur]
Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)]
Néant, Nadège [Auteur]
Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)]
Gaymard, Alexandre [Auteur]
Virology and human respiratory Pathologies - Virology and human respiratory Pathologies [CIRI] [VirPath]
Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] [CNR - laboratoire associé]
Institut des Agents Infectieux [Lyon] [IAI]
Belhadi, Drifa [Auteur]
Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Peytavin, Gilles [Auteur]
Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Hites, Maya [Auteur]
Université libre de Bruxelles [ULB]
Staub, Thérèse [Auteur]
Centre Hospitalier de Luxembourg [Luxembourg] [CHL]
Greil, Richard [Auteur]
Paracelsus Medizinische Privatuniversität = Paracelsus Medical University [PMU]
Paiva, José-Artur [Auteur]
Poissy, Julien [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Peiffer-Smadja, Nathan [Auteur]
Services de Maladies Infectieuses et Tropicales [CHU Bichat]
Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)]
Imperial College London
Costagliola, Dominique [Auteur]
Institut Pierre Louis d'Epidémiologie et de Santé Publique [iPLESP]
Yazdanpanah, Yazdan [Auteur]
CIC - CHU Bichat
Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)]
Wallet, Florent [Auteur]
Centre Hospitalier Lyon Sud [CHU - HCL] [CHLS]
Gagneux-Brunon, Amandine [Auteur]
Centre International de Recherche en Infectiologie [CIRI]
Mentré, France [Auteur]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Ader, Florence [Auteur]
Centre International de Recherche en Infectiologie [CIRI]
Université Claude Bernard Lyon 1 [UCBL]
Burdet, Charles [Auteur]
Emergence de la résistance bactérienne in vivo [EA3964]
Guedj, Jérémie [Auteur]
Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)]

Journal title :

Journal of Antimicrobial Chemotherapy

Pages :

1404--1412

Publisher :

Oxford University Press (OUP)

Publication date :

2022

ISSN :

0305-7453

HAL domain(s) :

Sciences du Vivant [q-bio]/Médecine humaine et pathologie

English abstract : [en]

Abstract Background The antiviral efficacy of remdesivir in COVID-19 hospitalized patients remains controversial. Objectives To estimate the effect of remdesivir in blocking viral replication. Methods We analysed nasopharyngeal ...
Show more >Abstract Background The antiviral efficacy of remdesivir in COVID-19 hospitalized patients remains controversial. Objectives To estimate the effect of remdesivir in blocking viral replication. Methods We analysed nasopharyngeal normalized viral loads from 665 hospitalized patients included in the DisCoVeRy trial (NCT 04315948; EudraCT 2020-000936-23), randomized to either standard of care (SoC) or SoC + remdesivir. We used a mathematical model to reconstruct viral kinetic profiles and estimate the antiviral efficacy of remdesivir in blocking viral replication. Additional analyses were conducted stratified on time of treatment initiation (≤q7 or >7\hspace0.25emdays since symptom onset) or viral load at randomization (< or ≥q3.5 log10 copies/104 cells). Results In our model, remdesivir reduced viral production by infected cells by 2-fold on average (95% CI: 1.5\textendash 3.2-fold). Model-based simulations predict that remdesivir reduced time to viral clearance by 0.7\hspace0.25emdays compared with SoC, with large inter-individual variabilities (IQR: 0.0\textendash 1.3\hspace0.25emdays). Remdesivir had a larger impact in patients with high viral load at randomization, reducing viral production by 5-fold on average (95% CI: 2.8\textendash 25-fold) and the median time to viral clearance by 2.4\hspace0.25emdays (IQR: 0.9\textendash 4.5\hspace0.25emdays). Conclusions Remdesivir halved viral production, leading to a median reduction of 0.7\hspace0.25emdays in the time to viral clearance compared with SoC. The efficacy was larger in patients with high viral load at randomization.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Glycobiology in fungal Pathogenesis and Clinical Applications

Submission date :

2024-02-27T16:21:04Z