Wastewater-based epidemiology has emerged as a powerful public health tool to trace new outbreaks, detect trends in infection, and provide an early warning of COVID-19 community spread. Here, we investigated the spread of SARS-CoV-2 infections across Utah by characterizing lineages and mutations detected in wastewater samples. We sequenced over 1,200 samples from 32 sewersheds collected between November 2021 and March 2022. Wastewater sequencing confirmed the presence of Omicron (B.1.1.529) in Utah in samples collected on November 19, 2021, up to 10 days before its corresponding detection via clinical sequencing. Analysis of diversity of SARS-CoV-2 lineages revealed Delta as the most frequently detected lineage during November 2021 (67.71%), but it started declining in December 2021 with the onset of Omicron (B.1.1529) and its sublineage BA.1 (6.79%). The proportion of Omicron increased to ~58% by January 4, 2022, and completely displaced Delta by February 7, 2022. Wastewater genomic surveillance revealed the presence of Omicron sublineage BA.3, a lineage that was not identified from Utah's clinical surveillance. Interestingly, several Omicron-defining mutations began to appear in early November 2021 and increased in prevalence across sewersheds from December to January, aligning with the surge in clinical cases. Our study highlights the importance of tracking epidemiologically relevant mutations in detecting emerging lineages in the early stages of an outbreak. Wastewater genomic epidemiology provides an unbiased representation of community-wide infection dynamics and is an excellent complementary tool to SARS-CoV-2 clinical surveillance, with the potential of guiding public health action and policy decisions. IMPORTANCE SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has had a significant impact on public health. Global emergence of novel SARS-CoV-2 variants, shift to at-home tests, and reduction in clinical tests demonstrate the need for a reliable and effective surveillance strategy to contain COVID-19 spread. Monitoring of SARS-CoV-2 viruses in wastewater is an effective way to trace new outbreaks, establish baseline levels of infection, and complement clinical surveillance efforts. Wastewater genomic surveillance, in particular, can provide valuable insights into the evolution and spread of SARS-CoV-2 variants. We characterized the diversity of SARS-CoV-2 mutations and lineages using whole-genome sequencing to trace the introduction of lineage B.1.1.519 (Omicron) in Utah. Our data showed that Omicron appeared in Utah on November 19, 2021, up to 10 days prior to its detection in patient samples, indicating that wastewater surveillance provides an early warning signal. Our findings are important from a public health perspective as timely identification of communities with high COVID-19 transmission could help guide public health interventions.
Keywords: Omicron; SARS-CoV-2; genomics; mutation of interest; public health; wastewater surveillance.