Pharmaceutical-driven disinfection by-products formation and antibiotic resistance gene enrichment under intensified chlorination during pandemic.

Intensified chlorine disinfection during pandemic is widely implemented in hospital and municipal wastewaters to inactivate pathogens. However, high concentrations of residual chlorine in treated wastewaters might bring secondary environmental risks. This study investigated the impacts of intensified chlorine disinfection on disinfection by-product (DBP) formation from six commonly used pandemic-related drugs and antibiotic resistance gene (ARG) enrichment in sewage. Results showed that high chlorine dosage of 2000 µmol/L led to DBP yields and estimated toxicity that were 1-2 orders of magnitude higher than those under normal chlorine dosage of 40-100 µmol/L. Intensified chlorine disinfection and drug overuse during the pandemic evidently increased the contribution of drugs as precursors to DBPs formation (29.2 %-78.8 %) in sewage. Two antibiotics emerged as major dichloroacetonitrile precursors, two bromine expectorants dominated haloacetic acids and Br-DBP formation, while two ICMs were critical precursors of iodinated acetamides. These DBPs were the main contributors to the estimated toxicity of the chlorinated drugs. Bromine expectorants produced DBPs with yields and estimated toxicity 1-2 orders of magnitude greater than other drugs. Metagenomic sequencing results showed that low chlorine up-regulated ARGs and related mobile genetic elements, driving ARGs enrichment and horizontal transfer. High chlorine in short term inhibited the total ARGs, but enriched the multidrug resistance gene subtypes related to the efflux/mutation pathway and transfer, thereby selected highly chlorine-resistant bacteria with strong antibiotic resistance. These findings reveal the environmental risks of intensified chlorine disinfection and suggest that optimizing chlorine dosage is crucial to mitigate these environmental risks and protect public health.