The occurrence of emerging compounds in real urban wastewater before and after the COVID-19 pandemic in Cali, Colombia

Abstract

The COVID-19 pandemic is considered one of the most significant global disasters in the last years. The rapid increase in infections, deaths, treatment, and the vaccination process has resulted in the excessive use of pharmaceuticals that have entered the environment as micropollutants. Considering the prior information about the presence of pharmaceuticals found in the wastewater of Cali, Colombia, which was collected from 2015 to 2022. The data monitored after the COVID-19 pandemic showed an increase in the concentration of analgesics and anti-inflammatory drugs of up to 91%. This increase was associated with the consumption of pharmaceuticals for mild symptoms, such as fever and pain. Moreover, the increase in concentration of pharmaceuticals poses a highly ecological threat, which was up to 14 times higher than that reported before of COVID-19 pandemic. These results showed that the COVID-19 had not only impacted human health but also had an effect on environmental health.

Graphical abstract

Introduction

Urban wastewater consists of a complex combination of contaminants, including micropollutants which are chemical substances with concentrations ranging from μgL⁻¹ to ngL⁻¹. Micropollutants and their presence in the water sources have become an environmental issue of global relevance. Pharmaceuticals are the most concerning micropollutants, as they can be excreted in their original form through urine and feces or as metabolites and are often resistant to degradation [1].

In Colombia, pharmaceutical compounds have been found in drinking water, surface water, and wastewater of cities, such as Bogotá, Medellín, and Cali [2, 3∗∗, 4]. Their presence is related to the self-medicating of people, and to the broad marketing of over-the-counter pharmaceuticals, particularly analgesics and anti-inflammatory compounds.

The COVID-19 pandemic has been one of the most concerning disasters in recent years. It placed the medical, scientific, and political circles on high alert due to the rapid increase in contagion and deaths. In Colombia, the first recorded case of COVID-19 was reported in March 2020, and subsequently, the number of positive cases quickly rose to an accumulated total of more than six million, resulting in almost 142,000 deaths up until November 2022 [5].

According to the World Health Organization, the most common symptoms of COVID-19 include fever, cough, tiredness, headache, and muscle aches, as well as in severe cases, shortness of breath. Therefore, symptom management requires the prescription of different pharmaceuticals, including antiviral, antibiotics, and analgesics/anti-inflammatory pharmaceuticals. Moreover, in Colombia, the vaccination process started in 2021, and around 71% of the population was vaccinated up until November 2022 [6]. Some mild symptoms were reported after vaccination, such as tiredness, myalgia, fever, headache, pain at the injection site, joint pain, nausea, and diarrhea [7, 8]. Some analgesics/anti-inflammatory pharmaceuticals are also recommended for the treatment of vaccination-related symptoms.

The increase in the presence of antiviral drugs and antibiotics has been reported by Morales-Paredes et al. [9], who stated that these compounds were detected in the water bodies at concentrations higher than 70% during the pandemic compared to previous years. In Colombia, only a few pharmaceutical compounds used to treat mild COVID-19 symptoms have been previously detected in urban wastewater, including paracetamol, ibuprofen, naproxen, diclofenac, and the antibiotic azithromycin all at average concentrations of up to 29.66, 2.72, 5.84, 0.34, and 3.99 μgL⁻¹, respectively. However, there is no literature reporting data on the presence and concentration of these compounds during the COVID-19 pandemic.

Taking into account the impact of COVID-19 and the need for medication to treat both the disease and the mild symptoms associated with the vaccination, the aim of this paper is to analyze the changes in some pharmaceutical compounds present in Santiago de Cali’ wastewater, based on collected data, before and after the-COVID-19 pandemic, and evaluate their potential impact on aquatic biota using an ecological hazard methodology.

Geographical location

Data were collected from the effluent of the Santiago de Cali, Colombia, wastewater treatment plant (WWTP-C), which serves 82.7% of the population, equivalent to 1,847,773 people. The plant uses chemically enhanced primary treatment (CEPT) methods, including coagulation, flocculation, and sedimentation processes. The plant is located at the geographic coordinates 3°28′10.345″ N - 76°28′30.593″ W (refer to the location map in Figure S1 of the supplementary material).

Occurrence of pharmaceutical compounds

A combination of spot and composite samplings was conducted to obtain 42 samples in 2015, 2016, 2018, 2019, 2021, and 2022. The composite samples were taken at hourly intervals for 12 h. These samples were stored in amber-colored glass containers, refrigerated at 4 °C, filtered with 0.45 μm cellulose membranes, and analyzed using high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS-MS) to detect pharmaceutical compounds, following the methodology outlined by Jiménez-Bambague et al. [10]. The HPLC/MS-MS process is detailed in the supplementary material. A total of 21 pharmaceutical compounds were measured in the WWTP-C effluent. The sampling was arbitrarily alternated between rainy and dry periods, where no significant differences were identified, which is characteristic of Colombia's tropical climate.

The therapeutic groups evaluated were as follows: antiepileptics such as 10,11-Dihydro-10,11-dihydroxy carbamazepine (CBZ-Diol), carbamazepine, gabapentin, lamotrigine, and primidone; hypolipidemic drugs such as bezafibrate, clofibric acid, etofibrate, fenofibrate, fenofibric acid, and gemfibrozil; analgesics and anti-inflammatory drugs such as diclofenac, fenoprofen, ibuprofen, indomethacin, ketoprofen, naproxen, and paracetamol; and tranquilizers such as diazepam, oxazepam, and pentoxyfilline. Lastly, the limit of quantification (LOQ) of the pharmaceutical compounds in HPLC/MS-MS was 0.050 μgL⁻¹.

The effluent of the WWTP-C associated with CEPT was not designed to effectively remove these pharmaceutical compounds, leading to a low removal efficiency of less than 30% for the majority of these compounds [11]. Previous studies have shown that the coagulation-flocculation process has low efficiency for removing compounds, such as paracetamol, naproxen, ibuprofen, diclofenac, and carbamazepine [12, 13, 14]. Carballa et al. [13] found that the hydrophobic and acid properties of some compounds affect their fixation in the solid fraction, leading to a better removal of contaminants through the coagulation-flocculation process. However, most pharmaceuticals found in WWTP-C are hydrophilic or weakly hydrophobic. Moreover, although acidic pharmaceuticals (except carbamazepine) may interact better with the solids in the wastewater at acidic pH, their adsorption tends to decrease at neutral pH. This is because the negatively charged pharmaceuticals produce a repelling effect with the negatively charged solids in the wastewater, reducing the efficiency of the coagulation-flocculation process [14,15]. Therefore, the low removal efficiency of pharmaceutical compounds in WWTP-C can also be attributed to the circumneutral pH values (6.5 and 7.4) of its effluent, which is necessary to comply with regulations.

Eleven pharmaceutical compounds above LOQ have been detected since 2015, and these consist of four antiepileptics, including CBZ-Diol, carbamazepine, gabapentin, and lamotrigine; two hypolipidemic drugs including fenofibric acid (the active form of fenofibrate) and gemfibrozil; and five analgesics and anti-inflammatory drugs including diclofenac, ibuprofen, ketoprofen, naproxen, and paracetamol. Figure 1 shows the pharmaceutical concentration for every year of the periods that were studied.

Figure 1.

Minimum, average, and maximum concentrations of pharmaceutical compounds.

The analgesics and anti-inflammatory drugs were of the highest concentrations, and paracetamol was found to have the highest value of 180 μgL⁻¹. Similarly, this therapeutic drug group showed a higher concentration increase in the post-COVID period than other compounds. These increases were 89%, 70%, 48%, and 91% for diclofenac, ibuprofen, naproxen, and paracetamol, respectively. This sharp increase in concentration could be attributed to these compounds being used to treat mild symptoms of COVID-19 and the effects of vaccination to prevent it [16]. In addition, according to Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA), they are over-the-counter pharmaceuticals, which means they are much more easily acquired in drugstores, supermarket chains, and small shops.

In another study, Galani et al. [17] found a drop in the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) of 27% and an increase of 198% in the consumption of paracetamol. These results were likely related to the common practice of doctors recommending the use of paracetamol instead of NSAIDs for treating COVID-19 symptoms. This is because NSAIDs have been found to increase the risk of respiratory tract infections [18]. NSAIDs include diclofenac, ibuprofen, naproxen, and ketoprofen. Paracetamol is not an NSAID because it is an analgesic and antipyretic, with limited anti-inflammatory effects.

Despite doctors advising patients to avoid using NSAIDs, their increase in Santiago de Cali's wastewater can be associated with users self-medicating, particularly in cases where users did not receive medical attention. It can also be attributed to the misinformation on social networks where incorrect medical advice is frequently given.

The COVID-19 pandemic is also the indirect cause of mental health problems, particularly because of isolation [19]. However, the results did not show a significant increase in antiepileptic drug and tranquilizer concentration. Only the antiepileptic drug lamotrigine had a concentration increase above LOQ and a greater detection frequency (8% in the pre-pandemic period vs. 94% between 2021 and 2022). According to Asadi-Pooya et al. [20], COVID-19 treatment in people with epilepsy may be complicated as antiepileptic drug doses often require adjusting. Van der Lee et al. [21] showed that the interaction between lopinavir/ritonavir (antiviral drugs used for treating COVID-19 patients) with lamotrigine might require a dose increment of 200%. Therefore, the need to increase the dose by said amount could lead to a higher consumption of lamotrigine, thus increasing its concentration in wastewater. This lamotrigine increase remains a problem because it is a persistent compound found in wastewater and brings with it complex degradation as carried out through conventional treatments. In some studies, these conventional treatments have resulted in an increase in lamotrigine concentration, which has been associated with a transformation of metabolite 5-desamino 5-Oxo-2,5-dihydro Lamotrigine back to lamotrigine [22].

Hypolipidemic drugs, such as fenofibric acid and gemfibrozil, maintained a similar trend in pre and post-pandemic periods. However, some studies have shown that these compounds can serve as effective treatments for COVID-19 infections. Fenofibric acid is the active form of fenofibrate which demonstrates that it could become a potential therapeutic agent for preventing contagions and reducing the severity of COVID-19-infected patients [23].

Determination of ecological hazard pre and post-COVID-19 pandemic

The ecological hazard was estimated using the hazard quotient (HQ) method, according to Equation (1) [24].

$$HQ=\frac{MEC}{PNEC}$$ (1)

where MEC is the measured environmental concentration (μgL⁻¹), PNEC is the predicted no-effect concentration that refers to the highest concentration at which there are no adverse effects on an indicator organism (μgL⁻¹). PNEC is determined according to Equation (2).

$$PNEC=\frac{Mostsensitivetoxicitydatum\left(NOECorEC50\right)}{AF}$$ (2)

The PNEC value was calculated by applying assessment factors (AF) based on available long-term no observed effects concentration (NOEC) toxicity data on fish, daphnias, and algae, or short-term EC50 data [24]. The ecotoxicological data were taken from The ECOTOXicology Knowledgebase (ECOTOX). It was created and is now maintained by the United States Environmental Protection Agency, which can be viewed via the following link: https://cfpub.epa.gov/ecotox/help.cfm.

HQ is interpreted as follows: no hazard when HQ < 0.1; insignificant hazard but potential adverse effects should be considered when between 0.1 and 1.0; medium hazard with moderate effects when between 1.0 and 10; and high hazard when HQ > 10.

Table 1 presents the ecotoxicological data of indicator organisms for each pharmaceutical compound. No ecotoxicological data were found for CBZ-Diol, while for lamotrigine, the HQ was applied from the PNEC value, as reported in previous studies [25]. HQ was determined from the maximum concentrations of pharmaceutical compounds (MEC) for each year between 2015 and 2022. The Literature data for the calculation of the HQ of each compound are included in the final part of Table 1.

Table 1.

Determination of the ecological hazard of pharmaceutical compounds [23, 24, 25, 26, 27, 28∗∗, 29, 30∗∗, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46∗∗].

The results of HQ study show that gemfibrozil, ibuprofen, and naproxen had a consistently high ecological hazard throughout the duration of the study. Additionally, diclofenac and paracetamol demonstrated medium to high HQ values, but saw a significant increase in their post-COVID HQ values, ranging from 2 to 14 times higher than the average pre-COVID HQ values. It is noteworthy that diclofenac saw the largest increase among these drugs.

These results raise concern due to the negative impact of these compounds on the aquatic biota of the recipient water body. In relation to this, Erhunmwunse et al. [46] reported that 10 μgL⁻¹ of paracetamol can produce teratogenic, neurotoxic, and cardiotoxic effects in the embryo and larvae of Clarias gariepinus. This level of paracetamol concentration is less than the highest value reported in this study, which was up to 180 μgL⁻¹ (Figure 1). In addition, ibuprofen and naproxen have been related to fish reproduction issues and are, therefore, considered endocrine disruptors [47,48]. Diclofenac has also shown toxic effects on aquatic organisms including hormonal disorders in crustaceans at concentrations of 0.25 μgL⁻¹ [49]. This concentration is 34 times lower than the maximum value found in this study. Gemfibrozil is also considered to pose a threat to embryonic development due to its potential to cause genotoxicity and toxic effects [36,50,51].

The HQ results indicate that carbamazepine has a medium potential to affect the aquatic biota, which is a cause of concern due to some alterations observed in aquatic organisms. A recent study reported that environmental concentrations of carbamazepine could induce oxidative DNA damage in the livers of Chinese minnows, with notable effects when concentrations were at 0.91 μgL⁻¹ [28]. This concentration level is slightly higher when compared to the highest concentration levels found in Santiago de Cali's wastewater.

According to the results which were obtained between 2015 and 2022, it is possible to conclude that the COVID-19 pandemic may have had a negative impact on the aquatic biota of the Cauca River. This result is primarily due to the increased consumption of analgesics and anti-inflammatory drugs, such as diclofenac, ibuprofen, naproxen, and paracetamol. These findings may provide an indirect measurement of COVID-19's impact on Santiago de Cali and serve as a warning to public health and environmental entities regarding the potential consequences of excessive use of over-the-counter medication.

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fiderman Machuca reports financial support was provided by Ibero-American Program of Science and Technology for Development.

This review comes from a themed issue on Environmental Technologies 2023: Eco-Friendly and Advanced Technologies for Pollutant Remediation and Management

Edited by Palanivel Sathishkumar, Abirami Ramu Ganesan, Tony Hadibarata and Thava Palanisami

Appendix A. Supplementary data

The followings are the supplementary data to this article.

WWTP location.tif.

Data availability

Data will be made available on request.