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.
Creators: name: Russell, Timothy W
name: Townsley, Hermaleigh
name: Abbott, Sam
name: Hellewell, Joel
name: Carr, Edward J
name: Chapman, Lloyd AC
name: Pung, Rachael
name: Quilty, Billy J
name: Hodgson, David
name: Fowler, Ashley S
name: Adams, Lorin
name: Bailey, Chris
name: Mears, Harriet V
name: Harvey, Ruth
name: Clayton, Bobbi
name: O'Reilly, Nicola
name: Ngai, Yenting
name: Nicod, Jerome
name: Gamblin, Steve
name: Williams, Bryan
name: Gandhi, Sonia
name: Swanton, Charles
name: Beale, Rupert
name: Bauer, David LV
name: Wall, Emma C
name: Kucharski, Adam J
Publisher: name: The Francis Crick Institute
Year: 2024
Subjects: classificationCode: Tumour Biology
subject: Tumour Biology
classificationCode: Stem Cells
subject: Stem Cells
classificationCode: Signalling & Oncogenes
subject: Signalling &amp; Oncogenes
classificationCode: Chemical Biology & High Throughput
subject: Chemical Biology &amp; High Throughput
classificationCode: Ecology,Evolution & Ethology
subject: Ecology,Evolution &amp; Ethology
classificationCode: Infectious Disease
subject: Infectious Disease
classificationCode: Immunology
subject: Immunology
subject: FOS: Clinical medicine
classificationCode: Genetics & Genomics
subject: Genetics &amp; Genomics
classificationCode: Metabolism
subject: Metabolism
classificationCode: Computational & Systems Biology
subject: Computational &amp; Systems Biology
classificationCode: Genome Integrity & Repair
subject: Genome Integrity &amp; Repair
classificationCode: Neurosciences
subject: Neurosciences
classificationCode: Human Biology & Physiology
subject: Human Biology &amp; Physiology
classificationCode: Model organisms
subject: Model organisms
classificationCode: Structural Biology & Biophysics
subject: Structural Biology &amp; Biophysics
classificationCode: Cell Biology
subject: Cell Biology
classificationCode: Imaging
subject: Imaging
classificationCode: Cell Cycle & Chromosomes
subject: Cell Cycle &amp; Chromosomes

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.