Evidence map›Paper›PMID 33641159›Full record

SynthesisClinical pharmacology and therapeutics2021

Systematic Review and Patient-Level Meta-Analysis of SARS-CoV-2 Viral Dynamics to Model Response to Antiviral Therapies.

Silke Gastine, Juanita Pang, Florencia A T Boshier, Simon J Carter, Dagan O Lonsdale, Mario Cortina-Borja, Ivan F N Hung, Judy Breuer, Frank Kloprogge, Joseph F Standing

Registry-linked trialOpen access · hybridAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Clinical pharmacology and therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05852873 (PAxlovid loNg cOvid-19 pRevention triAl With recruitMent In the Community in Norway), which is not on this map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05852873 phase3active not recruitingnot on this mapstarted 2023, after this paper: background citation

PAxlovid loNg cOvid-19 pRevention triAl With recruitMent In the Community in Norway

TypeinterventionalSponsorHaukeland University HospitalRan2023 to 2027Enrolled2,000ConditionsPost COVID-19 Condition, Unspecified, SARS-CoV2 Infection, COVID-19ArmsNirmatrelvir/ritonavir, Placebo
3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

  1. Pooled it
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  7. Review
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  18. Observational
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 3 countries.

Silke GastineInfection, Immunity and Inflammation Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London, UK.
Juanita PangDivision of Infection and Immunity, University College London, London, UK.
Florencia A T BoshierDivision of Infection and Immunity, University College London, London, UK.
Simon J CarterInfection, Immunity and Inflammation Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London, UK.
Dagan O LonsdaleDepartment of Clinical Pharmacology, St George's University of London, London, UK.
Mario Cortina-BorjaPopulation, Policy and Practice Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London, UK.
Ivan F N HungDivision of Infectious Diseases, Department of Medicine, The University of Hong Kong, Hong Kong, China.
Judy BreuerDivision of Infection and Immunity, University College London, London, UK.
Frank KloproggeInstitute for Global Health, University College London, London, UK.
Joseph F StandingInfection, Immunity and Inflammation Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London, UK.
University College London · GBGreat Ormond Street Hospital · GBInstitute of Infection and Immunity · CASt George's, University of London · GBUniversity of Hong Kong · HK

Funding

Medical Research Council M008665Medical Research Council MR/M008665/1Medical Research Council MR/P014534/1Medical Research Council P014534Wellcome Trust 203268
6 · The paper itself

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.

Indexed as

COVID-19 Drug TreatmentAdenosine MonophosphateAdultAlanineAntiviral AgentsClinical Trials as TopicCOVID-19Drug Therapy, CombinationFemaleHumansInterferonsMaleMiddle AgedProportional Hazards ModelsSARS-CoV-2Viral LoadAdenosine MonophosphateAlanineAntiviral AgentsInterferonsremdesivir

Identifiers

PMID33641159
PMCPMC8014833
OpenAlexW3134241111

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.