Complementing RNA Detection with Pharmaceutical Monitoring for Early Warning of Viral Outbreaks through Wastewater-Based Epidemiology

Wastewater-based epidemiology using viral nucleic acids to predict community viral outbreaks has many challenges, including differences in viral shedding of infected individuals and interference from the wastewater matrix. In this study, we demonstrate that monitoring pharmaceutical residues in untreated sewage provides complementary information that correlates with future occurrences of viral outbreaks. We monitored 63 pharmaceutically active compounds, including antivirals used to treat COVID-19 and influenza and over-the-counter drugs commonly used to relieve the symptoms of infection. Weekly sampling was conducted at four municipal sewage treatment plants in Western New York. Residues of drugs associated with managing COVID-19 symptoms were detected, including azithromycin (1.99-5.00 μg/L), chloroquine (0.01-33.00 μg/L), hydroxychloroquine (0.05-30.54 μg/L), and lopinavir (13.75-181.20 μg/L). A significant correlation (p < 0.001) was observed between the total COVID-19-related drugs detected and the 5-day rolling averages of reported cases. Acetaminophen concentrations spiked approximately 2.5 weeks before a spike in SARS-CoV-2 RNA copies in all wastewater treatment plants sampled. The results suggest over-the-counter analgesic concentrations, in particular, acetaminophen in raw sewage to be used to complement viral RNA data as an early warning system for effective management of viral outbreaks at the community level.