Gastine, S; Pang, J; Boshier, FAT; Carter, SJ; Lonsdale, DO; Cortina-Borja, M; Hung, IFN; Breuer, J; Kloprogge, F; Standing, JF
(2021)
Systematic Review and Patient-Level Meta-Analysis of SARS-CoV-2 Viral Dynamics to Model Response to Antiviral Therapies.
Clin Pharmacol Ther, 110 (2).
pp. 321-333.
ISSN 1532-6535
https://doi.org/10.1002/cpt.2223
SGUL Authors: Lonsdale, Dagan
Abstract
Severe acute respiratory syndrome-coronavirus 2 (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 January 1, 2020, and May 31, 2020, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A multivariable Cox proportional hazards (Cox-PH) regression model 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 modeling of respiratory viral dynamics was performed to quantify time-dependent drug effects. Patient-level data from 645 individuals (age 1 month to 100 years) with 6,316 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 modeling showed longer time to viral clearance in older patients, men, 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 analyzing antiviral trials has been established.
Item Type: |
Article
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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 (http://creativecommons.org/licenses/by/4.0/), 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, COVID-19, SARS-CoV-2, pharmacodynamics, viral dynamics, 1115 Pharmacology and Pharmaceutical Sciences, Pharmacology & Pharmacy |
SGUL Research Institute / Research Centre: |
Academic Structure > Institute of Medical & Biomedical Education (IMBE) |
Journal or Publication Title: |
Clin Pharmacol Ther |
ISSN: |
1532-6535 |
Language: |
eng |
Dates: |
Date | Event |
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26 July 2021 | Published | 1 May 2021 | Published Online | 22 February 2021 | Accepted |
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Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
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PubMed ID: |
33641159 |
Web of Science ID: |
WOS:000624500100143 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/113162 |
Publisher's version: |
https://doi.org/10.1002/cpt.2223 |
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