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UNIVERSITYhttps://www.ebi.ac.uk/ena/browser/view/PRJEB42191SARS-CoV-2 and the resulting COVID-19 pandemic represents one of the greatest recent threats to human health, wellbeing and economic growth. Wastewater-based epidemiology (WBE) of human viruses represents a useful tool for population-scale monitoring of SARS-CoV-2 prevalence and epidemiology to help prevent further spread of the disease, particularly within urban centres. Here we present a longitudinal analysis (March-July, 2020) of SARS-CoV-2 RNA prevalence in sewage across six major urban centres in the UK (total population equivalent 3 million) by q(RT-)PCR and viral genome sequencing. Our results demonstrate that levels of SARS-CoV-2 RNA generally correlated with the abundance of clinical cases recorded within the community in large urban centres, with a marked decline in SARS-CoV-2 RNA abundance following the implementation of lockdown measures. The strength of this association was weaker in areas with lower confirmed COVID-19 case numbers. The genetic diversity of SARS-CoV-2 from wastewater suggests that multiple genetically distinct clusters were co-circulating in the local populations covered by our sample sites, and that the genetic variants observed in wastewater reflect similar SNPs observed in contemporaneous samples from cases tested in clinical diagnostic laboratories. Although greater understanding of the factors that affect SARS-CoV-2 RNA concentration in wastewater are needed for the full integration of WBE data into outbreak surveillance, we demonstrate how WBE can be used for both community-level detection and tracking of SARS-CoV-2 prevalence, and can inform public health policy decisions. In conclusion, our results lend support to the use of routine WBE to monitor SARS-CoV-2 and other human pathogenic viruses circulating in the population and to assess the effectiveness of disease control measures.xref:EuropePMC:PMC8105641covid19ENAfalseNorthwest UK SARS-CoV-2 wastewater sequencingMonitoring SARS-CoV-2 in municipal wastewater to evaluate the success of lockdown measures for controlling COVID-19 in the UK2021-01-112020-12-28PRJEB42191