SARS-CoV-2 population dynamics in immunocompetent individuals in a closed transmission chain shows genomic diversity over the course of infection

DOI record: { "DOI": "10.1186/s13073-024-01360-1", "ISSN": [ "1756-994X" ], "URL": "http://dx.doi.org/10.1186/s13073-024-01360-1", "abstract": "<jats:title>Abstract</jats:title><jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec>", "alternative-id": [ "1360" ], "article-number": "89", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "23 September 2023" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "4 July 2024" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "16 July 2024" }, { "group": { "label": "Declarations", "name": "EthicsHeading" }, "name": "Ethics", "order": 1 }, { "group": { "label": "Ethics approval and consent to participate", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "During the early phase of the COVID-19 pandemic emergency public health and workforce protection measures were in place, so health surveillance was undertaken to prevent and manage transmission risk and morbidity. As part of these health surveillance measures, subjects consented to routine nasopharyngeal swab COVID-19 analysis and regular self-report of symptoms and signs such that disease outbreak could be prevented or controlled. In the UK, such public health surveillance measures do not require Research Ethics Committee review (UK Health Research Agency Guidance (hra-decisiontools.org.uk)). The Senior Medical Advisor is the sample database owner; all samples and clinical data were fully anonymised to the research team. All samples and data were GDPR compliant and the study conformed to the principles defined in the Declaration of Helsinki as adopted at the 64th WMA General Assembly at Fortaleza, Brazil in October 2013." }, { "group": { "label": "Consent for publication", "name": "EthicsHeading" }, "name": "Ethics", "order": 3, "value": "Not applicable." }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 4, "value": "The authors declare that they have no competing interests." } ], "author": [ { "affiliation": [], "family": "Goldswain", "given": "Hannah", "sequence": "first" }, { "affiliation": [], "family": "Penrice-Randal", "given": "Rebekah", "sequence": "additional" }, { "affiliation": [], "family": "Donovan-Banfield", "given": "I’ah", "sequence": "additional" }, { "affiliation": [], "family": "Duffy", "given": "Craig W.", "sequence": "additional" }, { "affiliation": [], "family": "Dong", "given": "Xiaofeng", "sequence": "additional" }, { "affiliation": [], "family": "Randle", "given": "Nadine", "sequence": "additional" }, { "affiliation": [], "family": "Ryan", "given": "Yan", "sequence": "additional" }, { "affiliation": [], "family": "Rzeszutek", "given": "Aleksandra M.", "sequence": "additional" }, { "affiliation": [], "family": "Pilgrim", "given": "Jack", "sequence": "additional" }, { "affiliation": [], "family": "Keyser", "given": "Emma", "sequence": "additional" }, { "affiliation": [], "family": "Weller", "given": "Simon A.", "sequence": "additional" }, { "affiliation": [], "family": "Hutley", "given": "Emma J.", "sequence": "additional" }, { "affiliation": [], "family": "Hartley", "given": "Catherine", "sequence": "additional" }, { "affiliation": [], "family": "Prince", "given": "Tessa", "sequence": "additional" }, { "affiliation": [], "family": "Darby", "given": "Alistair C.", "sequence": "additional" }, { "affiliation": [], "family": "Aye Maung", "given": "Niall", "sequence": "additional" }, { "affiliation": [], "family": "Nwume", "given": "Henry", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-6582-0275", "affiliation": [], "authenticated-orcid": false, "family": "Hiscox", "given": "Julian A.", "sequence": "additional" }, { "affiliation": [], "family": "Emmett", "given": "Stevan R.", "sequence": "additional" } ], "container-title": "Genome Medicine", "container-title-short": "Genome Med", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2024, 7, 16 ] ], "date-time": "2024-07-16T11:02:23Z", "timestamp": 1721127743000 }, "deposited": { "date-parts": [ [ 2024, 7, 16 ] ], "date-time": "2024-07-16T11:10:35Z", "timestamp": 1721128235000 }, "funder": [ { "DOI": "10.13039/100000038", "award": [ "75F40120C00085" ], "doi-asserted-by": "publisher", "name": "U.S. Food and Drug Administration" }, { "DOI": "10.13039/501100000265", "award": [ "MR/W005611/1", "MR/Y004205/1" ], "doi-asserted-by": "publisher", "name": "Medical Research Council" } ], "indexed": { "date-parts": [ [ 2024, 7, 17 ] ], "date-time": "2024-07-17T00:25:10Z", "timestamp": 1721175910088 }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2024, 7, 16 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2024, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 7, 16 ] ], "date-time": "2024-07-16T00:00:00Z", "timestamp": 1721088000000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 7, 16 ] ], "date-time": "2024-07-16T00:00:00Z", "timestamp": 1721088000000 } } ], "link": [ { "URL": "https://link.springer.com/content/pdf/10.1186/s13073-024-01360-1.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/article/10.1186/s13073-024-01360-1/fulltext.html", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/content/pdf/10.1186/s13073-024-01360-1.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1186", "published": { "date-parts": [ [ 2024, 7, 16 ] ] }, "published-online": { "date-parts": [ [ 2024, 7, 16 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1038/s41586-020-2012-7", "author": "P Zhou", "doi-asserted-by": "publisher", "first-page": "270", "journal-title": "Nature", "key": "1360_CR1", "unstructured": "Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, Si H-R, Zhu Y, Li B, Huang C-L, et al. 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