Whole genome sequencing of SARS-CoV-2 from wastewater links to individual cases in catchments

Highlights

• Understanding the resolution of wastewater SARS-CoV-2 genomics has been hampered by rapid increases in case numbers.

• SARS-CoV-2 wastewater sequences were compared to COVID-19 patient sequences when case numbers were low and cases were known.

• Wastewater COVID-19 sequences could be linked to individual active cases in a catchment size of 250,000 population.

• Potential contribution cases can be identified using genomic profiles in wastewater given enough nucleotide differences.

• Wastewater genomic epidemiology can provide very high resolution for informing outbreak management and disease surveillance.

Abstract

After a limited first wave of community transmission in March 2020 and until 2022, Western Australia was largely free of COVID-19, with cases restricted to hotel quarantine, commercial vessels, and small, infrequent community clusters. Despite the low case load setting, sequencing of wastewater samples from large municipal treatment plants produced SARS-CoV-2 genomes with coverage up to 99.7 % and depth to 4000×, which was sufficient to link wastewater sequences to those of active cases in the catchment at the time. This study demonstrates that ≤5 positive individuals can be enough to produce high genomic coverage (>90 %) assemblies even in catchments of up to a quarter of a million people. Genomic analysis of wastewater contemporaneous with clinical cases can also be used to rule out transmission between cases in different catchments, when their SARS-CoV-2 genomes have distinguishing nucleotide polymorphisms. These findings reveal a greater potential of wastewater WGS to inform outbreak management and disease surveillance than previously recognized.