File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Systematic Review and Patient‐Level Meta‐Analysis of SARS‐CoV‐2 Viral Dynamics to Model Response to Antiviral Therapies

TitleSystematic Review and Patient‐Level Meta‐Analysis of SARS‐CoV‐2 Viral Dynamics to Model Response to Antiviral Therapies
Authors
Issue Date2021
PublisherAmerican Society for Clinical Pharmacology and Therapeutics. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1532-6535/issues
Citation
Clinical Pharmacology and Therapeutics, 2021, v. 110 n. 2, p. 321-333 How to Cite?
AbstractSevere 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.
Persistent Identifierhttp://hdl.handle.net/10722/307682
ISSN
2023 Impact Factor: 6.3
2023 SCImago Journal Rankings: 1.988
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGastine, S-
dc.contributor.authorPang, J-
dc.contributor.authorBoshier, FAT-
dc.contributor.authorCarter, SJ-
dc.contributor.authorLonsdale, DO-
dc.contributor.authorCortina-Borja, M-
dc.contributor.authorHung, FNI-
dc.contributor.authorBreuer, J-
dc.contributor.authorKloprogge, F-
dc.contributor.authorStanding, JF-
dc.date.accessioned2021-11-12T13:36:16Z-
dc.date.available2021-11-12T13:36:16Z-
dc.date.issued2021-
dc.identifier.citationClinical Pharmacology and Therapeutics, 2021, v. 110 n. 2, p. 321-333-
dc.identifier.issn0009-9236-
dc.identifier.urihttp://hdl.handle.net/10722/307682-
dc.description.abstractSevere 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.-
dc.languageeng-
dc.publisherAmerican Society for Clinical Pharmacology and Therapeutics. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1532-6535/issues-
dc.relation.ispartofClinical Pharmacology and Therapeutics-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleSystematic Review and Patient‐Level Meta‐Analysis of SARS‐CoV‐2 Viral Dynamics to Model Response to Antiviral Therapies-
dc.typeArticle-
dc.identifier.emailHung, FNI: ivanhung@hkucc.hku.hk-
dc.identifier.authorityHung, FNI=rp00508-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1002/cpt.2223-
dc.identifier.pmid33641159-
dc.identifier.pmcidPMC8014833-
dc.identifier.scopuseid_2-s2.0-85104363136-
dc.identifier.hkuros330094-
dc.identifier.volume110-
dc.identifier.issue2-
dc.identifier.spage321-
dc.identifier.epage333-
dc.identifier.isiWOS:000645941200001-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats