Systematic Review and Patient-Level Meta-Analysis of SARS-CoV-2 Viral Dynamics to Model Response to Antiviral Therapies.
Clin Pharmacol Ther
; 110(2): 321-333, 2021 08.
Article
in English
| MEDLINE | ID: covidwho-1103289
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Viral Load
/
COVID-19
/
COVID-19 Drug Treatment
Type of study:
Prognostic study
/
Randomized controlled trials
/
Reviews
/
Systematic review/Meta Analysis
Topics:
Long Covid
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
English
Journal:
Clin Pharmacol Ther
Year:
2021
Document Type:
Article
Affiliation country:
Cpt.2223
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