Wastewater genomic surveillance tracks the spread of the SARS-CoV-2 Omicron variant across England

Background Many countries have moved into a new stage of managing the SARS-CoV-2 pandemic with minimal restrictions and reduced testing in the population, leading to reduced genomic surveillance of virus variants in individuals. Wastewater-based epidemiology (WBE) can provide an alternative means of tracking virus variants in the population but is lacking verifications of its comparability to individual testing data. Methods We analysed more than 19,000 samples from 524 wastewater sites across England at least twice a week between November 2021 and February 2022, capturing sewage from >70% of the English population. We used amplicon-based sequencing and the phylogeny based de-mixing tool Freyja to estimate SARS-CoV-2 variant frequencies and compared these to the variant dynamics observed in individual testing data from clinical and community settings. Findings We show that wastewater data can reconstruct the spread of the Omicron variant across England since November 2021 in close detail and aligns closely with epidemiological estimates from individual testing data. We also show the temporal and spatial spread of Omicron within London. Our wastewater data further reliably track the transition between Omicron subvariants BA1 and BA2 in February 2022 at regional and national levels. Interpretation Our demonstration that WBE can track the fast-paced dynamics of SARS-CoV-2 variant frequencies at a national scale and closely match individual testing data in time shows that WBE can reliably fill the monitoring gap left by reduced individual testing in a more affordable way. Funding Department of Health and Social Care, UK, Natural Environmental Research Council, UK, COG-UK Evidence before this study Genomic monitoring of wastewater for SARS-CoV-2 variants has been introduced in several countries and shown to effectively detect the spread of known variants in multiple studies. However, verification of its alignment with individual testing data at a national scale has so far been reported only for Austria, where sampling covered around 5.4million people. Further and larger scale verifications of the reliability of wastewater-based epidemiology (WBE) are needed to increase confidence in its use for public health monitoring. Added value of this study We provide evidence that WBE was able to closely track the spread of the emerging SARS-CoV-2 variant Omicron, as well as its sub lineage dynamics, at a regional and national scale across England. Our sampling covered >70% of the English population, equivalent to 39.4 million people. We thereby demonstrate the scalability of our approach to national levels. We also show how WBE is able to track dynamics in different regions of the UK and at a finer scale within London. Its close alignment, in estimated epidemiological timings, with results from intensive individual testing in the same timeframe provides evidence that wastewater-based monitoring can be a reliable alternative when large scale data from individual testing is not available. Implications of all the available evidence Altogether, evidence is accumulating that WBE is a reliable approach for monitoring SARS-CoV-2 variant dynamics and informing public health measures across spatial scales. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement Funding was provided by DHSC UK (2020\_097) and NERC (NE/V003860/1). This report is independent research funded by the Department of Health and Social Care. 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 use of data generated through the COVID-19 Genomics Programme funded by the Department of Health and Social Care. The views expressed are those of the authors and not necessarily those of the Department of Health and Social Care 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: Use of surplus nucleic acid derived from routine diagnostics and associated patient data was approved through the COG-UK consortium by the Public Health England Research Ethics and Governance Group (R&D NR0195). 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 Wastewater sequencing data are publicly available on the European Nucleotide Archive under Study ID PRJEB55313. The clinical case data used in this study are visualised at . A filtered, privacy conserving version of the lineage-LTLA-week dataset is publicly available online () and gives access to almost all used data, despite a small number of cells having been suppressed to conserve patient privacy.