Tracing COVID-19 drugs in the environment: Are we focusing on the right environmental compartment?

The Coronavirus Disease 2019 (COVID-19) pandemic led to over 770 million confirmed cases, straining public healthcare systems and necessitating extensive and prolonged use of synthetic chemical drugs around the globe for medical treatment and symptom relief. Concerns have arisen regarding the massive release of active pharmaceutical ingredients (APIs) and their metabolites into the environment, particularly through domestic sewage. While discussions surrounding this issue have primarily centered on their discharge into aquatic environments, particularly through treated effluent from municipal wastewater treatment plants (WWTPs), one often overlooked aspect is the terrestrial environment as a significant receptor of pharmaceutical-laden waste. This occurs through the disposal of sewage sludge, for instance, by applying biosolids to land or non-compliant disposal of sewage sludge, in addition to the routine disposal of expired and unused medications in municipal solid wastes. In this article, we surveyed sixteen approved pharmaceuticals for treating COVID-19 and bacterial co-infections, along with their primary metabolites. For this, we delved into their physiochemical properties, ecological toxicities, environmental persistence, and fate within municipal WWTPs. Emphasis was given on lipophilic substances with log K_ow >3.0, which are more likely to be found in sewage sludge at significant factions (25.2%-75.0%) of their inputs in raw sewage and subsequently enter the terrestrial environment through land application of biosolids, e.g., 43% in the United States and as high as 96% in Ireland or non-compliant practices of sewage sludge disposal in developing communities, such as open dumping and land application without prior anaerobic digestion. The available evidence underscores the importance of adequately treating and disposing of sewage sludge before its final disposal or land application in an epidemic or pandemic scenario, as mismanaged sewage sludge could be a significant vector for releasing pharmaceutical compounds and their metabolites into the terrestrial environment.