Lineage replacement and evolution captured by three years of the United Kingdom Covid Infection Survey

The Office for National Statistics COVID-19 Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced samples collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors. The sweeps also generated an alternating pattern in which most samples had either S-gene target failure (SGTF) or non- SGTF over time. Evolution was characterised by steadily increasing divergence and diversity within lineages, but with step increases in divergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens, particularly in the current phase of the pandemic with routine RT-PCR testing now ended in the community. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The CIS is funded by the Department of Health and Social Care with in-kind support from the Welsh Government, the Department of Health on behalf of the Northern Ireland Government and the Scottish Government. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) [grant code: MC\_PC\_19027], and Genome Research Limited, operating as the Wellcome Sanger Institute. The authors acknowledge the support of the NHS Test and Trace Genomics Programme through sequencing of SARS-CoV-2 genomes analysed in this study. ASW is supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford in partnership with the UK Health Security Agency (UK HSA) (NIHR200915) and the NIHR Oxford Biomedical Research Centre, and is an NIHR Senior Investigator. TH is supported by the Royal Society and Alan Turing Institute for Data Science and Artificial Intelligence. KAL is supported by the Royal Society and the Wellcome Trust (107652/Z/15/Z) and the Li Ka Shing Foundation. The views expressed are those of the authors and not necessarily those of the National Health Service, NIHR, Department of Health, or UKHSA. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study received ethical approval from the South Central Berkshire B Research Ethics Committee (20/SC/0195) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes A privacy preserving version of the lineage dataset is available from ons.gov.uk. The sequences are publicly available via the COG-UK project on the ENA. A table (SampleInfo.csv) has been uploaded to Katrina Lythgoe's Github with the COG-UK ids, enabling them to be identified and downloaded. The table also gives their collection dates, pangolin designation, major lineage, and whether they were included in the phylogenetic analysis. The weekly aggregated ONS-CIS testing data (TestingInfo.csv) is also available here. The full description and code for the growth rate analysis is on Thomas House's github. We have permission from the ONS to make this data publicly available.