Fate, environmental impact and treatability of favipiravir and surveillance of sars-cov-2 RNA: Comparison with Covid-19 cases

Abstract

Pharmaceutical substances, such as antiviral drugs, antibiotics, antidepressants, anti-inflammatory drugs, antipyretics, beta-blockers and lipid regulators have become more common in both human and animal healthcare to enhance quality of life and prolong lifespan. This increase in pharmaceutical usage has become a significant global environmental concern in recent years. Therefore, the extensive use of these substances worldwide requires attentive monitoring to manage their contamination and environmental impact of water sources. In the second and third chapter, two reviews aimed to provide a comprehensive discussion of the physicochemical properties, analytical detection methods, removal techniques, and ecotoxicological impacts of antiviral drugs. Also, combined assessment of antiviral drugs and virus discharged in the environment were reviewed. These reviews address the challenges faced and explores future opportunities in this field of study. Special emphasis was placed on the occurrence of antiviral drugs employed in the treatment of COVID-19 in water and wastewater. In the fourth chapter, the long-term presence of favipiravir in influent, effluent wastewater, and sludge samples from two WWTPs in Istanbul were investigated. Additionally, the potential environmental risks of favipiravir were assessed using two model organisms. The study determined the mass balance, removal efficiency, and seasonal variations in favipiravir concentrations. The correlation between the number of confirmed COVID-19 cases and favipiravir concentrations in influent wastewater was also analyzed. Furthermore, the impact of drug concentration on the microbial community in sludge from various WWTPs during the pandemic was compared with post-pandemic sludge. The results demonstrate that favipiravir is partially removed (<50%) in WWTPs, with the majority of its removal mechanism being attributed to biodegradation. Additionally, a significant statistical correlation was observed between the concentration of favipiravir and the incidence of COVID-19 in Istanbul, with p-values of 0.025 and 0.039 for WWTP-1 and WWTP-2, respectively. The microbiological distribution was found to vary significantly between sludge samples taken during the COVID-19 pandemic and those from the post-pandemic period. The fifth chapter presents that the presence and quantification of SARS-CoV-2 RNA in raw wastewater, treated effluents, and secondary sludge samples were monitored between June 2021 and January 2022 at two different WWTPs in Istanbul, Turkey. The obtained data were compared with the number of COVID-19 cases and deaths in Istanbul. Additionally, the seasonal variations of SARS-CoV-2 and its relationship with TN, TP, and COD parameters were analyzed using PCA. The results indicated that secondary treatment effectively reduces SARS-CoV-2 levels, thereby mitigating the associated risks from wastewater. This study highlights a moderate correlation between the concentration of SARS-CoV-2 genes and the number of reported COVID-19 cases and deaths in Istanbul. Furthermore, a correlation was observed between the amounts of gene copies and the levels of TP and COD for both the N1 and N2 genes at the two wastewater treatment plants. In the sixth chapter, degradation kinetics of favipiravir under UV, UV/H₂O₂, and UV/Co-doped ZnS processes was investigated. The influence of initial favipiravir concentration, pH, and water matrices (distilled water, tap water, and WWTP effluent) on the degradation kinetics of favipiravir in these processes were assessed. The ecotoxicity risks of favipiravir using algae with treated solutions containing various initial FAV concentrations were evaluated. The degradation of favipiravir after 45 min was observed to be 77.3%, 100%, 89.8%, and 100% for the UV, UV/H₂O₂, UV/Co-doped ZnS, and UV/H₂O₂/Co-doped ZnS processes, respectively. In the seventh chapter was to examine how initial concentrations of antiviral drugs and sludge retention time (SRT) affect favipiravir removal efficiency in membrane bioreactor (MBR) systems. The biotransformation kinetics of favipiravir were also investigated to understand the relationship between biokinetic coefficients, initial drug concentration and SRT. Additionally, an environmental risk assessment was carried out to assess the potential risks associated with favipiravir. Favipiravir was eliminated >99% regardless of its initial concentration in MBR systems. The removal efficiency of favipiravir improved from 48.9% to 86.4% as the sludge retention time (SRT) increased from 15 days to 45 days.