First seen in local wastewater – Novel virus variants observed weeks prior to routine surveillance underscore the potential of wastewater-based epidemiology

Wastewater-based epidemiology (WBE) is a valuable approach for the early detection and monitoring of infectious diseases at the population level. By rapidly sequencing pathogenic genetic material extracted from wastewater, local and regional virus surveillance can be enhanced, enabling earlier identification of emerging variants than routine clinical testing typically allows – an especially critical advantage for immune-evasive pathogens. In this study, we employed a cost-effective sequencing and sensitive analysis strategy to monitor SARS-CoV-2 variants in the metropolitan Ruhr area of Germany, combining pathogen-specific tiled amplification, established analytical tools and a customized method for enhanced sensitivity. Samples were taken bi-weekly over six weeks, resulting in 55 samples from five sampling sites. As expected, our findings demonstrate earlier detection for emerging variants of concern (VOCs) in wastewater, compared to patient-based genomic surveillance. However and particularly notable, XBB.1.5 was identified in local wastewater from intra-urban sewersheds two weeks before its appearance in patient samples and XBB.1.9 several months prior to its local clinical manifestation. We further corroborate ours and other's prior reports that local sampling sites can extend the early-warning horizon for novel variants when compared to wastewater treatment plants (WWTPs), likely due to lower dilution and closer proximity to infection sources. Overall, these results underscore the utility of sequencing-based WBE in delivering timely, actionable insights to healthcare providers and authorities. Such methodologies represent a promising expansion of current surveillance infrastructures and quantitative frameworks, offering practical benefits for optimizing environmental viral monitoring and support improved public health responses.