Hannah Goldswain, Rebekah Penrice-Randal, I'ah Donovan-Banfield, Craig W Duffy, Xiaofeng Dong, Nadine Randle, Yan Ryan, Aleksandra M Rzeszutek, Jack Pilgrim, Emma Keyser, Simon A Weller, Emma J Hutley, Catherine Hartley, Tessa Prince, Alistair C Darby, Niall Aye Maung, Henry Nwume, Julian A Hiscox, Stevan R Emmett
{"title":"SARS-CoV-2 population dynamics in immunocompetent individuals in a closed transmission chain shows genomic diversity over the course of infection.","authors":"Hannah Goldswain, Rebekah Penrice-Randal, I'ah Donovan-Banfield, Craig W Duffy, Xiaofeng Dong, Nadine Randle, Yan Ryan, Aleksandra M Rzeszutek, Jack Pilgrim, Emma Keyser, Simon A Weller, Emma J Hutley, Catherine Hartley, Tessa Prince, Alistair C Darby, Niall Aye Maung, Henry Nwume, Julian A Hiscox, Stevan R Emmett","doi":"10.1186/s13073-024-01360-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>SARS-CoV-2 remains rapidly evolving, and many biologically important genomic substitutions/indels have characterised novel SARS-CoV-2 lineages, which have emerged during successive global waves of the pandemic. Worldwide genomic sequencing has been able to monitor these waves, track transmission clusters, and examine viral evolution in real time to help inform healthcare policy. One school of thought is that an apparent greater than average divergence in an emerging lineage from contemporary variants may require persistent infection, for example in an immunocompromised host. Due to the nature of the COVID-19 pandemic and sampling, there were few studies that examined the evolutionary trajectory of SARS-CoV-2 in healthy individuals.</p><p><strong>Methods: </strong>We investigated viral evolutionary trends and participant symptomatology within a cluster of 16 SARS-CoV-2 infected, immunocompetent individuals with no co-morbidities in a closed transmission chain. Longitudinal nasopharyngeal swab sampling allowed characterisation of SARS-CoV-2 intra-host variation over time at both the dominant and minor genomic variant levels through Nimagen-Illumina sequencing.</p><p><strong>Results: </strong>A change in viral lineage assignment was observed in individual infections; however, there was only one indel and no evidence of recombination over the period of an acute infection. Minor and dominant genomic modifications varied between participants, with some minor genomic modifications increasing in abundance to become the dominant viral sequence during infection.</p><p><strong>Conclusions: </strong>Data from this cohort of SARS-CoV-2-infected participants demonstrated that long-term persistent infection in an immunocompromised host was not necessarily a prerequisite for generating a greater than average frequency of amino acid substitutions. Amino acid substitutions at both the dominant and minor genomic sequence level were observed in immunocompetent individuals during infection showing that viral lineage changes can occur generating viral diversity.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"16 1","pages":"89"},"PeriodicalIF":10.4000,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251137/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genome Medicine","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13073-024-01360-1","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: SARS-CoV-2 remains rapidly evolving, and many biologically important genomic substitutions/indels have characterised novel SARS-CoV-2 lineages, which have emerged during successive global waves of the pandemic. Worldwide genomic sequencing has been able to monitor these waves, track transmission clusters, and examine viral evolution in real time to help inform healthcare policy. One school of thought is that an apparent greater than average divergence in an emerging lineage from contemporary variants may require persistent infection, for example in an immunocompromised host. Due to the nature of the COVID-19 pandemic and sampling, there were few studies that examined the evolutionary trajectory of SARS-CoV-2 in healthy individuals.
Methods: We investigated viral evolutionary trends and participant symptomatology within a cluster of 16 SARS-CoV-2 infected, immunocompetent individuals with no co-morbidities in a closed transmission chain. Longitudinal nasopharyngeal swab sampling allowed characterisation of SARS-CoV-2 intra-host variation over time at both the dominant and minor genomic variant levels through Nimagen-Illumina sequencing.
Results: A change in viral lineage assignment was observed in individual infections; however, there was only one indel and no evidence of recombination over the period of an acute infection. Minor and dominant genomic modifications varied between participants, with some minor genomic modifications increasing in abundance to become the dominant viral sequence during infection.
Conclusions: Data from this cohort of SARS-CoV-2-infected participants demonstrated that long-term persistent infection in an immunocompromised host was not necessarily a prerequisite for generating a greater than average frequency of amino acid substitutions. Amino acid substitutions at both the dominant and minor genomic sequence level were observed in immunocompetent individuals during infection showing that viral lineage changes can occur generating viral diversity.
期刊介绍:
Genome Medicine is an open access journal that publishes outstanding research applying genetics, genomics, and multi-omics to understand, diagnose, and treat disease. Bridging basic science and clinical research, it covers areas such as cancer genomics, immuno-oncology, immunogenomics, infectious disease, microbiome, neurogenomics, systems medicine, clinical genomics, gene therapies, precision medicine, and clinical trials. The journal publishes original research, methods, software, and reviews to serve authors and promote broad interest and importance in the field.