Evidence map›Paper›PMID 37752062›Full record

ArticleInfluenza and other respiratory viruses2023

Use of whole genome sequencing to identify low-frequency mutations in SARS-CoV-2 patients treated with remdesivir.

Kuganya Nirmalarajah, Winfield Yim, Patryk Aftanas, Angel X Li, Altynay Shigayeva, Lily Yip, Zoe Zhong, Allison J McGeer, Finlay Maguire, Samira Mubareka and 1 more

Open access · goldAbstract read
In one paragraph

Article in Influenza and other respiratory viruses, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.0field-weighted citation impact, top 25% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
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

11 authors at 5 institutions in 1 country.

Kuganya NirmalarajahSunnybrook Research Institute, Toronto, Ontario, Canada.ORCID 0000-0002-8226-7969
Winfield YimSunnybrook Research Institute, Toronto, Ontario, Canada.
Patryk AftanasShared Hospital Laboratory, Toronto, Ontario, Canada.
Angel X LiSinai Health System, Toronto, Ontario, Canada.
Altynay ShigayevaSinai Health System, Toronto, Ontario, Canada.
Lily YipSunnybrook Research Institute, Toronto, Ontario, Canada.ORCID 0000-0002-7387-0387
Zoe ZhongSinai Health System, Toronto, Ontario, Canada.
Allison J McGeerDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0001-5647-6137
Finlay MaguireFaculty of Computer Science, Dalhousie University, Halifax, Nova Scotia, Canada.
Samira MubarekaSunnybrook Research Institute, Toronto, Ontario, Canada.ORCID 0000-0001-5012-2311
Robert KozakSunnybrook Research Institute, Toronto, Ontario, Canada.ORCID 0000-0002-6159-9972
University of Toronto · CASinai Health System · CASunnybrook Hospital · CADalhousie University · CAToronto General Hospital · CA

Funding

CIHR 174925CIHR 177701CIHR 480722
6 · The paper itself

Abstract

backgroundRemdesivir (RDV) has been shown to reduce hospitalization and mortality in COVID-19 patients. Resistance mutations caused by RDV are rare and have been predominantly reported in patients who are on prolonged therapy and immunocompromised. We investigate the effects of 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.

methodsFrom March 2020 to April 2022, sequential collections of nasopharyngeal and mid-turbinate swabs were obtained from 14 patients with and 30 patients without RDV treatment. Demographic and clinical data on all patients were reviewed. A total of 109 samples were sequenced and mutation analyses were performed.

resultsPreviously reported drug resistant mutations in nsp12 were not identified during short courses of RDV therapy. In genes encoding and surrounding the replication complex (nsp6-nsp14), low-frequency minority variants were detected in 7/14 (50%) and 18/30 (60%) 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.

conclusionsMinimal intra-host variability and stochastic low-frequency variants detected in moderately ill patients suggests little selective pressure in patients receiving short courses of RDV. The barrier to RDV resistance is high in patients with moderate disease. Patients undergoing short regimens of RDV therapy should continue to be monitored.

Indexed as

COVID-19SARS-CoV-2Adenosine MonophosphateAlanineCOVID-19 Drug TreatmentHumansMutationWhole Genome SequencingAdenosine MonophosphateAlanineremdesivirantiviral resistanceremdesivirSARS-CoV-2whole genome sequencing

Identifiers

PMID37752062
PMCPMC10522481
OpenAlexW4387035006

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.