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Record W4309639772 · doi:10.1101/2022.11.20.22282552

Use of whole genome sequencing to identify low-frequency mutations in COVID-19 patients treated with remdesivir

2022· preprint· en· W4309639772 on OpenAlexafffund
Kuganya Nirmalarajah, Finlay Maguire, Winfield Yim, Patryk Aftanas, Angel X. Li, Altynay Shigayeva, Lily Yip, Xi Zhong, Allison McGeer, Samira Muberka, Robert Kozak

Bibliographic record

VenuemedRxiv · 2022
Typepreprint
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsToronto General HospitalSinai Health SystemDalhousie UniversityUniversity of TorontoSunnybrook Health Science Centre
FundersSocial Sciences and Humanities Research Council of CanadaNatural Sciences and Engineering Research Council of CanadaUniversity of TorontoCanadian Institutes of Health ResearchDalhousie University
KeywordsMedicineCoronavirus disease 2019 (COVID-19)MutationBiologyVirologyInternal medicineGeneDiseaseGeneticsInfectious disease (medical specialty)

Abstract

fetched live from OpenAlex

Abstract Background We investigate the effects of remdesivir (RDV) treatment on intra-host SARS-CoV-2 diversity and low-frequency mutations in moderately ill hospitalized COVID-19 patients and compare them to patients without RDV treatment. Methods Sequential collections of nasopharyngeal and mid-turbinate swabs were obtained from 16 patients with and 31 patients without RDV treatment. A total of 113 samples were sequenced and mutation analyses were performed. Results We did not identify any drug resistant mutations during RDV therapy. In genes encoding and associated with the replication complex, low-frequency minority variants that do not reach fixation within the sampling period were detected in 6/16 (37.5%) and 14/31 (45%) patients with and without RDV treatment respectively. We did not detect significant differences in within-host diversity and positive selection between the RDV-treated and untreated groups. Conclusions Minimal intra-host variability and stochastic low-frequency variants detected in moderately ill patients suggests little selective pressure in patients receiving short courses of RDV. Patients undergoing short regimens of RDV therapy should continue to be monitored.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.002
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

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

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 head0.093
GPT teacher head0.376
Teacher spread0.283 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2022
Admission routes2
Has abstractyes

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