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

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...

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Autores principales:	Andrew L Valesano, Kalee E Rumfelt, Derek E Dimcheff, Christopher N Blair, William J Fitzsimmons, Joshua G Petrie, Emily T Martin, Adam S Lauring
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f846ab6774994d9eac586b53433405fa
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spelling	oai:doaj.org-article:f846ab6774994d9eac586b53433405fa2021-12-02T20:00:18ZTemporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts.1553-73661553-737410.1371/journal.ppat.1009499https://doaj.org/article/f846ab6774994d9eac586b53433405fa2021-04-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009499https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Analysis 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.Andrew L ValesanoKalee E RumfeltDerek E DimcheffChristopher N BlairWilliam J FitzsimmonsJoshua G PetrieEmily T MartinAdam S LauringPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 4, p e1009499 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Andrew L Valesano Kalee E Rumfelt Derek E Dimcheff Christopher N Blair William J Fitzsimmons Joshua G Petrie Emily T Martin Adam S Lauring Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts.
description	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.
format	article
author	Andrew L Valesano Kalee E Rumfelt Derek E Dimcheff Christopher N Blair William J Fitzsimmons Joshua G Petrie Emily T Martin Adam S Lauring
author_facet	Andrew L Valesano Kalee E Rumfelt Derek E Dimcheff Christopher N Blair William J Fitzsimmons Joshua G Petrie Emily T Martin Adam S Lauring
author_sort	Andrew L Valesano
title	Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts.
title_short	Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts.
title_full	Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts.
title_fullStr	Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts.
title_full_unstemmed	Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts.
title_sort	temporal dynamics of sars-cov-2 mutation accumulation within and across infected hosts.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/f846ab6774994d9eac586b53433405fa
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Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts.

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