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Record W3194251718 · doi:10.1002/jmv.27285

Evolution of viral variants in remdesivir‐treated and untreated SARS‐CoV‐2‐infected pediatrics patients

2021· article· en· W3194251718 on OpenAlexaff
Florencia A. T. Boshier, Juanita Pang, Justin Penner, Matthew Parker, Nele Alders, Alasdair Bamford, Louis Grandjean, Stephanie Grünewald, James Hatcher, Timothy Best, Caroline Dalton, Patricia Dyal Bynoe, Claire Frauenfelder, Jutta Köeglmeier, Phoebe Myerson, Sunando Roy, Rachel Williams, Thushan I. de Silva, Richard A. Goldstein, Judith Breuer

Bibliographic record

VenueJournal of Medical Virology · 2021
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsInstitute of Infection and Immunity
FundersMedical Research CouncilJohn Black Charitable FoundationUniversity College London Hospitals NHS Foundation TrustBiotechnology and Biological Sciences Research CouncilRosetrees TrustAction Medical ResearchUK Research and InnovationAcademy of Medical SciencesWellcome TrustNational Institute for Health and Care ResearchGilead Sciences
KeywordsViral loadSuperinfectionVirologyPopulationMedicineBiologyViral replicationVirusImmunology

Abstract

fetched live from OpenAlex

Detailed information on intrahost viral evolution in SARS-CoV-2 with and without treatment is limited. Sequential viral loads and deep sequencing of SARS-CoV-2 from the upper respiratory tract of nine hospitalized children, three of whom were treated with remdesivir, revealed that remdesivir treatment suppressed viral load in one patient but not in a second infected with an identical strain without any evidence of drug resistance found. Reduced levels of subgenomic RNA during treatment of the second patient, suggest an additional effect of remdesivir on viral replication. Haplotype reconstruction uncovered persistent SARS-CoV-2 variant genotypes in four patients. These likely arose from within-host evolution, although superinfection cannot be excluded in one case. Although our dataset is small, observed sample-to-sample heterogeneity in variant frequencies across four of nine patients suggests the presence of discrete viral populations in the lung with incomplete population sampling in diagnostic swabs. Such compartmentalization could compromise the penetration of remdesivir into the lung, limiting the drugs in vivo efficacy, as has been observed in other lung infections.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.005
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.062
Threshold uncertainty score0.589

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.005
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.021
GPT teacher head0.329
Teacher spread0.308 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations20
Published2021
Admission routes1
Has abstractyes

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Same venueJournal of Medical VirologySame topicSARS-CoV-2 and COVID-19 ResearchFrench-language works237,207