Combined analyses of within-host SARS-CoV-2 viral kinetics and information on past exposures to the virus in a human cohort identifies intrinsic differences of Omicron and Delta variants.
The emergence of successive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) during 2020 to 2022, each exhibiting increased epidemic growth relative to earlier circulating variants, has created a need to understand the drivers of such growth. However, both path...
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002463&type=printable |
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| author | Timothy W Russell Hermaleigh Townsley Sam Abbott Joel Hellewell Edward J Carr Lloyd A C Chapman Rachael Pung Billy J Quilty David Hodgson Ashley S Fowler Lorin Adams Chris Bailey Harriet V Mears Ruth Harvey Bobbi Clayton Nicola O'Reilly Yenting Ngai Jerome Nicod Steve Gamblin Bryan Williams Sonia Gandhi Charles Swanton Rupert Beale David L V Bauer Emma C Wall Adam J Kucharski |
| author_facet | Timothy W Russell Hermaleigh Townsley Sam Abbott Joel Hellewell Edward J Carr Lloyd A C Chapman Rachael Pung Billy J Quilty David Hodgson Ashley S Fowler Lorin Adams Chris Bailey Harriet V Mears Ruth Harvey Bobbi Clayton Nicola O'Reilly Yenting Ngai Jerome Nicod Steve Gamblin Bryan Williams Sonia Gandhi Charles Swanton Rupert Beale David L V Bauer Emma C Wall Adam J Kucharski |
| author_sort | Timothy W Russell |
| collection | DOAJ |
| description | The emergence of successive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) during 2020 to 2022, each exhibiting increased epidemic growth relative to earlier circulating variants, has created a need to understand the drivers of such growth. However, both pathogen biology and changing host characteristics-such as varying levels of immunity-can combine to influence replication and transmission of SARS-CoV-2 within and between hosts. Disentangling the role of variant and host in individual-level viral shedding of VOCs is essential to inform Coronavirus Disease 2019 (COVID-19) planning and response and interpret past epidemic trends. Using data from a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening, we developed a Bayesian hierarchical model to reconstruct individual-level viral kinetics and estimate how different factors shaped viral dynamics, measured by PCR cycle threshold (Ct) values over time. Jointly accounting for both interindividual variation in Ct values and complex host characteristics-such as vaccination status, exposure history, and age-we found that age and number of prior exposures had a strong influence on peak viral replication. Older individuals and those who had at least 5 prior antigen exposures to vaccination and/or infection typically had much lower levels of shedding. Moreover, we found evidence of a correlation between the speed of early shedding and duration of incubation period when comparing different VOCs and age groups. Our findings illustrate the value of linking information on participant characteristics, symptom profile and infecting variant with prospective PCR sampling, and the importance of accounting for increasingly complex population exposure landscapes when analysing the viral kinetics of VOCs. Trial Registration: The Legacy study is a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening for SARS-CoV-2 at University College London Hospitals or at the Francis Crick Institute (NCT04750356) (22,23). The Legacy study was approved by London Camden and Kings Cross Health Research Authority Research and Ethics committee (IRAS number 286469). The Legacy study was approved by London Camden and Kings Cross Health Research Authority Research and Ethics committee (IRAS number 286469) and is sponsored by University College London Hospitals. Written consent was given by all participants. |
| format | Article |
| id | doaj-art-cfe2aa3e3c23488697cdd2e92920d429 |
| institution | OA Journals |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-cfe2aa3e3c23488697cdd2e92920d4292025-08-20T02:22:59ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852024-01-01221e300246310.1371/journal.pbio.3002463Combined analyses of within-host SARS-CoV-2 viral kinetics and information on past exposures to the virus in a human cohort identifies intrinsic differences of Omicron and Delta variants.Timothy W RussellHermaleigh TownsleySam AbbottJoel HellewellEdward J CarrLloyd A C ChapmanRachael PungBilly J QuiltyDavid HodgsonAshley S FowlerLorin AdamsChris BaileyHarriet V MearsRuth HarveyBobbi ClaytonNicola O'ReillyYenting NgaiJerome NicodSteve GamblinBryan WilliamsSonia GandhiCharles SwantonRupert BealeDavid L V BauerEmma C WallAdam J KucharskiThe emergence of successive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) during 2020 to 2022, each exhibiting increased epidemic growth relative to earlier circulating variants, has created a need to understand the drivers of such growth. However, both pathogen biology and changing host characteristics-such as varying levels of immunity-can combine to influence replication and transmission of SARS-CoV-2 within and between hosts. Disentangling the role of variant and host in individual-level viral shedding of VOCs is essential to inform Coronavirus Disease 2019 (COVID-19) planning and response and interpret past epidemic trends. Using data from a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening, we developed a Bayesian hierarchical model to reconstruct individual-level viral kinetics and estimate how different factors shaped viral dynamics, measured by PCR cycle threshold (Ct) values over time. Jointly accounting for both interindividual variation in Ct values and complex host characteristics-such as vaccination status, exposure history, and age-we found that age and number of prior exposures had a strong influence on peak viral replication. Older individuals and those who had at least 5 prior antigen exposures to vaccination and/or infection typically had much lower levels of shedding. Moreover, we found evidence of a correlation between the speed of early shedding and duration of incubation period when comparing different VOCs and age groups. Our findings illustrate the value of linking information on participant characteristics, symptom profile and infecting variant with prospective PCR sampling, and the importance of accounting for increasingly complex population exposure landscapes when analysing the viral kinetics of VOCs. Trial Registration: The Legacy study is a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening for SARS-CoV-2 at University College London Hospitals or at the Francis Crick Institute (NCT04750356) (22,23). The Legacy study was approved by London Camden and Kings Cross Health Research Authority Research and Ethics committee (IRAS number 286469). The Legacy study was approved by London Camden and Kings Cross Health Research Authority Research and Ethics committee (IRAS number 286469) and is sponsored by University College London Hospitals. Written consent was given by all participants.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002463&type=printable |
| spellingShingle | Timothy W Russell Hermaleigh Townsley Sam Abbott Joel Hellewell Edward J Carr Lloyd A C Chapman Rachael Pung Billy J Quilty David Hodgson Ashley S Fowler Lorin Adams Chris Bailey Harriet V Mears Ruth Harvey Bobbi Clayton Nicola O'Reilly Yenting Ngai Jerome Nicod Steve Gamblin Bryan Williams Sonia Gandhi Charles Swanton Rupert Beale David L V Bauer Emma C Wall Adam J Kucharski Combined analyses of within-host SARS-CoV-2 viral kinetics and information on past exposures to the virus in a human cohort identifies intrinsic differences of Omicron and Delta variants. PLoS Biology |
| title | Combined analyses of within-host SARS-CoV-2 viral kinetics and information on past exposures to the virus in a human cohort identifies intrinsic differences of Omicron and Delta variants. |
| title_full | Combined analyses of within-host SARS-CoV-2 viral kinetics and information on past exposures to the virus in a human cohort identifies intrinsic differences of Omicron and Delta variants. |
| title_fullStr | Combined analyses of within-host SARS-CoV-2 viral kinetics and information on past exposures to the virus in a human cohort identifies intrinsic differences of Omicron and Delta variants. |
| title_full_unstemmed | Combined analyses of within-host SARS-CoV-2 viral kinetics and information on past exposures to the virus in a human cohort identifies intrinsic differences of Omicron and Delta variants. |
| title_short | Combined analyses of within-host SARS-CoV-2 viral kinetics and information on past exposures to the virus in a human cohort identifies intrinsic differences of Omicron and Delta variants. |
| title_sort | combined analyses of within host sars cov 2 viral kinetics and information on past exposures to the virus in a human cohort identifies intrinsic differences of omicron and delta variants |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002463&type=printable |
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