Evidence map›Paper›PMID 34387545›Full record

ArticleeLife2021

Patterns of within-host genetic diversity in SARS-CoV-2.

Gerry Tonkin-Hill, Inigo Martincorena, Roberto Amato, Andrew R J Lawson, Moritz Gerstung, Ian Johnston, David K Jackson, Naomi Park, Stefanie V Lensing, Michael A Quail and 31 more

Abstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed
–field-weighted citation impact
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

127 citing papers in PubMed.

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

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

41 authors.

Gerry Tonkin-Hill *Wellcome Sanger Institute, Hinxton, United Kingdom.ORCID https://orcid.org/0000-0003-4397-2224
Inigo Martincorena *Wellcome Sanger Institute, Hinxton, United Kingdom.
Roberto AmatoWellcome Sanger Institute, Hinxton, United Kingdom.
Andrew R J LawsonWellcome Sanger Institute, Hinxton, United Kingdom.
Moritz GerstungEuropean Bioinformatics Institute, Hinxton, United Kingdom.
Ian JohnstonWellcome Sanger Institute, Hinxton, United Kingdom.
David K JacksonWellcome Sanger Institute, Hinxton, United Kingdom.ORCID http://orcid.org/0000-0002-8090-9462
Naomi ParkWellcome Sanger Institute, Hinxton, United Kingdom.
Stefanie V LensingWellcome Sanger Institute, Hinxton, United Kingdom.
Michael A QuailWellcome Sanger Institute, Hinxton, United Kingdom.
Sónia GonçalvesWellcome Sanger Institute, Hinxton, United Kingdom.
Cristina ArianiWellcome Sanger Institute, Hinxton, United Kingdom.
Michael Spencer ChapmanWellcome Sanger Institute, Hinxton, United Kingdom.ORCID http://orcid.org/0000-0002-5320-8193
William L HamiltonDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.ORCID http://orcid.org/0000-0002-3330-353X
Luke W MeredithDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Grant HallDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.ORCID http://orcid.org/0000-0003-3928-3979
Aminu S JahunDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.ORCID http://orcid.org/0000-0002-4585-1701
Yasmin ChaudhryDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Myra HosmilloDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.ORCID http://orcid.org/0000-0002-3514-7681
Malte L PinckertDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Iliana GeorganaDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.ORCID http://orcid.org/0000-0002-8976-1177
Anna YakovlevaDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Laura G CallerDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Sarah L CaddyDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.ORCID http://orcid.org/0000-0002-9790-7420
Theresa FeltwellDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Fahad A KhokharDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.
Charlotte J HouldcroftDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.ORCID http://orcid.org/0000-0002-1833-5285
Martin D CurranPublic Health England, Cambridge, United Kingdom.
Surendra ParmarPublic Health England, Cambridge, United Kingdom.
COVID-19 Genomics UK (COG-UK) Consortium
Alex AldertonWellcome Sanger Institute, Hinxton, United Kingdom.
Rachel NelsonWellcome Sanger Institute, Hinxton, United Kingdom.
Ewan M HarrisonWellcome Sanger Institute, Hinxton, United Kingdom.
John SillitoeWellcome Sanger Institute, Hinxton, United Kingdom.
Stephen D BentleyWellcome Sanger Institute, Hinxton, United Kingdom.
Jeffrey C BarrettWellcome Sanger Institute, Hinxton, United Kingdom.
M Estee TorokDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.ORCID http://orcid.org/0000-0001-9098-8590
Ian G GoodfellowDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.ORCID http://orcid.org/0000-0002-9483-510X
Cordelia LangfordWellcome Sanger Institute, Hinxton, United Kingdom.
Dominic KwiatkowskiWellcome Sanger Institute, Hinxton, United Kingdom.
Wellcome Sanger Institute COVID-19 Surveillance Team

Funding

Cancer Research UK 21777Medical Research Council MC_PC_19027Medical Research Council MR/S00291X/1Wellcome Trust 204016/Z/16/ZWellcome Trust 204911/Z/16/ZWellcome Trust 207498/Z/17/Z
6 · The paper itself

Abstract

Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world. The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of transmission chains from consensus genome sequences, but within-host genetic diversity could theoretically help identify close contacts. Here we describe the patterns of within-host diversity in 1181 SARS-CoV-2 samples sequenced to high depth in duplicate. 95.1% of samples show within-host mutations at detectable allele frequencies. Analyses of the mutational spectra revealed strong strand asymmetries suggestive of damage or RNA editing of the plus strand, rather than replication errors, dominating the accumulation of mutations during the SARS-CoV-2 pandemic. Within- and between-host diversity show strong purifying selection, particularly against nonsense mutations. Recurrent within-host mutations, many of which coincide with known phylogenetic homoplasies, display a spectrum and patterns of purifying selection more suggestive of mutational hotspots than recombination or convergent evolution. While allele frequencies suggest that most samples result from infection by a single lineage, we identify multiple putative examples of co-infection. Integrating these results into an epidemiological inference framework, we find that while sharing of within-host variants between samples could help the reconstruction of transmission chains, mutational hotspots and rare cases of superinfection can confound these analyses.

Indexed as

Genetic VariationGenome, ViralMutationBase SequenceCOVID-19Host-Pathogen InteractionsHumansPandemicsPhylogenySARS-CoV-2epidemiologygeneticsgenomicsglobal healthmutational spectrumSARS-CoV-2transmissionwithin-host

Identifiers

PMID34387545
PMCPMC8363274

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.