Parallel wastewater-based surveillance of SARS-CoV-2 and the antiviral drug combination nirmatrelvir/ritonavir (Paxlovid)

Abstract

Wastewater-based epidemiology is a well-established method for tracking COVID-19 outbreaks and prevalence through SARS-CoV-2 quantification in influent wastewater. This study evaluated chemical monitoring as a complementary tool for assessing disease burden and community response by targeting the antiviral drug combination nirmatrelvir/ritonavir (Paxlovid®), recommended in Austria for adults at high risk of severe COVID-19. Wastewater samples were collected from Innsbruck (Tyrol, Austria) between January 2022 and November 2024. SARS-CoV-2 concentrations were determined in 701 samples (2–7 per week), and nirmatrelvir and ritonavir in 152 samples (1 per week). SARS-CoV-2 RNA and ritonavir were detectable in all samples, while nirmatrelvir appeared only after mid-March 2022, following European Medicines Agency authorization. The sensitive analytical method enabled detection even when very few patients were treated pharmacologically (as few as 1 in 200,000). Time series of viral and chemical signals correlated significantly with each other and with hospitalization data (R = 0.62–0.91), reflecting the same underlying population-level dynamics. Changes over time in chemical-to-viral load ratios suggest that monitoring antivirals can provide additional insights into alterations of treatment coverage and disease severity. These findings highlight the potential of wastewater-based chemical monitoring to complement and extend the capabilities of viral surveillance for public health decision-making.