Early detection and surveillance of SARS-CoV-2 genomic variants in wastewater using COJAC

• DOI: 10.1038/s41564-022-01185-x
• Publication Date: 2022-07-18T16:21:46Z
• Authors: Katharina Jahn; David Dreifuss; Ivan Topolsky; Anina Kull; Pravin Ganesanand...; Xavier Fernandez-...; Carola Bänziger; Alexander J. Devaux; Elyse Stachler; Lea Caduff; Federica Cariti; Alex Tuñas Corzón; Lara Fuhrmann; Chaoran Chen; Kim Philipp Jablo...; Sarah Nadeau; Mirjam Feldkamp; Christian Beisel; Catharine Aquino; Tanja Stadler; Christoph Ort; Tamar Kohn; Timothy R. Julian; Niko Beerenwinkel
• Keywords: Microbiology (medical); 0301 basic medicine; Coronaviruses; Immunology; 610 Medicine & health; 10071 Functional Genomics Center Zurich; Wastewater; Applied Microbiology and Biotechnology; Microbiology; 2726 Microbiology (medical); Article; 1307 Cell Biology; 03 medical and health sciences; 1311 Genetics; Aigües residuals; Genetics; 2402 Applied Microbiology and Biotechnology; Humans; 2403 Immunology; 0303 health sciences; Sewage; SARS-CoV-2; 2404 Microbiology; COVID-19; Cell Biology; Genomics; 6. Clean water; 3. Good health; Coronavirus; 570 Life sciences; biology

AbstractThe continuing emergence of SARS-CoV-2 variants of concern and variants of interest emphasizes the need for early detection and epidemiological surveillance of novel variants. We used genomic sequencing of 122 wastewater samples from three locations in Switzerland to monitor the local spread of B.1.1.7 (Alpha), B.1.351 (Beta) and P.1 (Gamma) variants of SARS-CoV-2 at a population level. We devised a bioinformatics method named COJAC (Co-Occurrence adJusted Analysis and Calling) that uses read pairs carrying multiple variant-specific signature mutations as a robust indicator of low-frequency variants. Application of COJAC revealed that a local outbreak of the Alpha variant in two Swiss cities was observable in wastewater up to 13 d before being first reported in clinical samples. We further confirmed the ability of COJAC to detect emerging variants early for the Delta variant by analysing an additional 1,339 wastewater samples. While sequencing data of single wastewater samples provide limited precision for the quantification of relative prevalence of a variant, we show that replicate and close-meshed longitudinal sequencing allow for robust estimation not only of the local prevalence but also of the transmission fitness advantage of any variant. We conclude that genomic sequencing and our computational analysis can provide population-level estimates of prevalence and fitness of emerging variants from wastewater samples earlier and on the basis of substantially fewer samples than from clinical samples. Our framework is being routinely used in large national projects in Switzerland and the UK.