Viral genetic variability in wastewater predicts changes in community infection levels

Sequencing viruses found in community wastewater facilitates the study of diversity in circulating viruses at the population level. By analyzing 12,290 wastewater samples collected between January 2023 and April 2025 in New York State, USA from 196 sampling sites across 57 counties, we assessed the diversity of the SARS-CoV-2 genome and how it changed over time compared to changes in COVID-19 infections and hospitalizations. We calculated three measures of SARS-CoV-2 genome diversity across all samples: nucleotide diversity ( π ), Shannon diversity (H), and viral variant count. We found that diversity increased with a rise in COVID-19 incidence and hospitalizations for all three measures (with a Spearman ρ > 0.8, p<0.001). The genetic diversity of the spike protein region had the highest correlation with the incidence of cases ( ρ = 0.92, p<0.001 for π, ρ = 0.91, p <0.001 for H), and the statewide count of virus variants had a correlation coefficient of ρ = 0.85 (p<0.001) with case incidence. Additionally, the genetic diversity of the spike protein predicted 90.1 percent of the variance of COVID-19 case incidence. Our results demonstrate the potential for viral diversity analysis from wastewater in predicting epidemiological outcomes.