Background Since early in the COVID-19 pandemic, SARS-CoV-2 wastewater concentration has been measured as a surrogate for community prevalence. However, our knowledge remains limited regarding wastewater concentration and effects of the COVID-19 vaccination on overall disease burden as measured by hospitalization rates. Methods We used weekly SARS-CoV-2 wastewater concentration with a stratified random sampling of seroprevalence, and spatially linked vaccination and hospitalization data, from April to August 2021. Our susceptible (S), vaccinated (V), variant-specific infected (I1 and I2), recovered (R), and seropositive (T) model (SVI2RT) tracked prevalence longitudinally. This was related to wastewater concentration for a spatial analysis of strain mutation, vaccination effect, and overall hospitalization burden. Findings We found strong linear association between wastewater concentration and estimated community prevalence (r=0.916). Based on the corresponding regression model, the 64% county vaccination rate translated into about 57% decrease in SARS-CoV-2 incidence. During the study period, the estimated effect of SARS-CoV-2 Delta variant emergence was seen as an over 7-fold increase of infection counts, which corresponded to over 12-fold increase in wastewater concentration. Hospitalization burden and wastewater concentration had the strongest correlation (r=0.963) at 1 week lag time. We estimated the community vaccination campaign resulted in about 63% reduction in the number of daily admissions over the study period. This protective effect was counteracted by the emergence of SARS-CoV-2 Delta strain mutation. Interpretation Wastewater samples can be used to estimate the effects of vaccination and hospitalization burden. Our study underscores the importance of continued environmental surveillance post-vaccine and provides a proof of concept for environmental epidemiology monitoring.