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Systematic review and patient-level meta-analysis of SARS-CoV-2 viral dynamics to model response to antiviral therapies

Gastine, S; Pang, J; Boshier, FAT; Carter, SJ; Lonsdale, DO; Cortina-Borja, M; Hung, IFN; ... Standing, JF; + view all (2021) Systematic review and patient-level meta-analysis of SARS-CoV-2 viral dynamics to model response to antiviral therapies. Clinical Pharmacology and Therapeutics , 110 (2) pp. 321-333. 10.1002/cpt.2223. Green open access

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Abstract

SARS-CoV-2 viral loads change rapidly following symptom onset so to assess antivirals it is important to understand the natural history and patient factors influencing this. We undertook an individual patient-level meta-analysis of SARS-CoV-2 viral dynamics in humans to describe viral dynamics and estimate the effects of antivirals used to-date. This systematic review identified case reports, case series and clinical trial data from publications between 1/1/2020 and 31/5/2020 following PRISMA guidelines. A multivariable Cox proportional hazards regression model (Cox-PH) of time to viral clearance was fitted to respiratory and stool samples. A simplified four parameter nonlinear mixed-effects (NLME) model was fitted to viral load trajectories in all sampling sites and covariate modelling of respiratory viral dynamics was performed to quantify time dependent drug effects. Patient-level data from 645 individuals (age 1 month-100 years) with 6316 viral loads were extracted. Model-based simulations of viral load trajectories in samples from the upper and lower respiratory tract, stool, blood, urine, ocular secretions and breast milk were generated. Cox-PH modelling showed longer time to viral clearance in older patients, males and those with more severe disease. Remdesivir was associated with faster viral clearance (adjusted hazard ratio (AHR) = 9.19, p<0.001), as well as interferon, particularly when combined with ribavirin (AHR = 2.2, p=0.015; AHR = 6.04, p = 0.006). Combination therapy should be further investigated. A viral dynamic dataset and NLME model for designing and analysing antiviral trials has been established.

Type: Article
Title: Systematic review and patient-level meta-analysis of SARS-CoV-2 viral dynamics to model response to antiviral therapies
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/cpt.2223
Publisher version: https://doi.org/10.1002/cpt.2223
Language: English
Additional information: © 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: COVID-19, SARS-CoV-2, pharmacodynamics, viral dynamics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10123735
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