Evidence map›Paper›PMID 33826681›Full record

ArticlePLoS pathogens2021

Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts.

Andrew L Valesano, Kalee E Rumfelt, Derek E Dimcheff, Christopher N Blair, William J Fitzsimmons, Joshua G Petrie, Emily T Martin, Adam S Lauring

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 1 pooled it
7.0field-weighted citation impact, top 2% 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

83 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.

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23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Andrew L ValesanoDivision of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-3649-8352
Kalee E RumfeltDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0001-5128-0274
Derek E DimcheffDivision of Hospital Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0001-7509-322X
Christopher N BlairDivision of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
William J FitzsimmonsDivision of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-0997-1108
Joshua G PetrieDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-5696-965X
Emily T MartinDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-5771-8895
Adam S LauringDivision of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0003-2906-8335
University of Michigan · USMichigan United · US

Funding

MICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3M
US Hospital Vaccine Effectiveness (VE) Network - SupplementU01IP000974 · IP · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MONTO, ARNOLD S · 2015 to 2019
$4.5M
Fidelity, robustness, and diversity in RNA virus evolution and pathogenesisR01AI118886 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LAURING, ADAM · 2016 to 2020
$2.0M
Hospital-Associated Respiratory Virus Infections: Molecular Epidemiology, Clinical Outcomes, and Cost-Effectiveness of Interventions - COVID-19 Administrative SupplementK01AI141579 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PETRIE, JOSHUA GLENN · 2019 to 2023
$634k
Mutation rates and transmission dynamics of influenza B virusR21AI141832 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LAURING, ADAM · 2019 to 2020
$429k
NCIRD CDC HHS U01 IP000974NIAID NIH HHS K01 AI141579NIAID NIH HHS R01 AI118886NIAID NIH HHS R21 AI141832NIGMS NIH HHS T32 GM007863NIH HHS K01 AI41579
6 · The paper itself

Abstract

Analysis of SARS-CoV-2 genetic diversity within infected hosts can provide insight into the generation and spread of new viral variants and may enable high resolution inference of transmission chains. However, little is known about temporal aspects of SARS-CoV-2 intrahost diversity and the extent to which shared diversity reflects convergent evolution as opposed to transmission linkage. Here we use high depth of coverage sequencing to identify within-host genetic variants in 325 specimens from hospitalized COVID-19 patients and infected employees at a single medical center. We validated our variant calling by sequencing defined RNA mixtures and identified viral load as a critical factor in variant identification. By leveraging clinical metadata, we found that intrahost diversity is low and does not vary by time from symptom onset. This suggests that variants will only rarely rise to appreciable frequency prior to transmission. Although there was generally little shared variation across the sequenced cohort, we identified intrahost variants shared across individuals who were unlikely to be related by transmission. These variants did not precede a rise in frequency in global consensus genomes, suggesting that intrahost variants may have limited utility for predicting future lineages. These results provide important context for sequence-based inference in SARS-CoV-2 evolution and epidemiology.

Indexed as

Mutation AccumulationAgedBase SequenceCOVID-19FemaleGenetic VariationGenome, ViralHost Microbial InteractionsHumansMaleMiddle AgedMutationPhylogenyRNA, ViralSARS-CoV-2Sequence Analysis, RNARNA, Viral

Identifiers

PMID33826681
PMCPMC8055005
OpenAlexW3147222942

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.