key: cord-0967380-ej2ri76h
authors: Bandala, Erick R.; Kruger, Brittany R.; Cesarino, Ivana; Leao, Alcides L.; Wijesiri, Buddhi; Goonetilleke, Ashantha
title: Impacts of COVID-19 pandemic on the wastewater pathway into surface water: A review
date: 2021-02-05
journal: Sci Total Environ
DOI: 10.1016/j.scitotenv.2021.145586
sha: 31ae0485b66c24a9eb445532af166bc4279e1177
doc_id: 967380
cord_uid: ej2ri76h

With global number of cases 100 million and death toll surpassing 2.16 million as of late-January 2021, the COVID-19 pandemic is certainly one of the major threats that humankind have faced in modern history. As the scientific community navigates through the overwhelming avalanche of information on the multiple health impacts caused by the pandemic, new reports start to emerge on significant ancillary effects associated with the treatment of the virus. Besides the evident health impacts, other emerging impacts related to the COVID-19 pandemic, such as water-related impacts, merits in-depth investigation. This includes strategies for the identification of these impacts and technologies to mitigate them, and to prevent further impacts not only in water ecosystems, but also in relation to human health. This paper has critically reviewed currently available knowledge on the most significant potential impacts of the COVID-19 pandemic on the wastewater pathway into surface water, as well as technologies that may serve to counteract the major threats posed, key perspectives and challenges. Additionally, current knowledge gaps and potential directions for further research and development are identified. While the COVID-19 pandemic is an ongoing and rapidly evolving situation, compiling current knowledge of potential links between wastewater and surface water pathways as related to environmental impacts and relevant associated technologies, as presented in this review, is a critical step to guide future research in this area.

Worldwide, the impacts on public health and the economic impact of the COVID-19 pandemic have become more evident as scientific information starts to flow, providing a better understanding of its complexity (Pulido et al., 2020) . In recent studies, evidence of emerging side effects of the pandemic besides the regrettable global amount of infection cases and deaths is of increasing concern (Abbas et al., 2020; Wu et al., 2020b; Xu et al., 2020b; Zhao et al., 2015) .

The emerging impacts of the COVID-19 pandemic on the environment, however, remain unelucidated at present, which is a significant knowledge gap requiring further investigation (Zambrano-Monserrate et al., 2020) . Despite the fact that some studies report positive changes such as the reduction in pollution indices in highly populated regions including cleaner beaches, environmental noise reduction, and the reduction in greenhouse gas emissions to the atmosphere (Muhammad et al., 2020; Wang and Su, 2020) , there are also other studies reporting on negative environmental consequences such as the increase in domestic solid residues, reduction in recycling, and the generation of long lasting plastic materials used for personal protection equipment (Klemes et al., 2020; Saadat et al., 2020; Sharma et al., 2020) .

Similar trends have been observed in relation to the aquatic environment, with some studies demonstrating improvements in some water quality parameters (e.g., total dissolved solids, nutrients, suspended particulate matter) in water bodies in urban areas when the concentrations behavior of droplets can change depending on temperature and humidity which are found to influence droplet properties such as size, expanding the critical size of small and large droplets to 50-150 µm Mittal et al., 2020) . In fact, a recent study reports that the increase in temperature and humidity can lead to increased number of COVID-19 infections as evident from caseloads from China and Indonesia, while noting the likelihood of rapid transmission due to high population density and mobility, particularly in urban areas (Barcelo, 2020) .

Moreover, the association between air quality and the dispersion of SARS-Cov-2 have been shown. Some Italian cities, where the air pollution limits set for PM10 were exceeded for periods less than 100 days/year, reported more than 1,000 infections. This figure increased to more than 3,000 infections when the air quality remained poor for more than 100 days/year (Coccia, 2020) .

In a study about the relationship between temperature and caseloads to determine the linear and nonlinear relationship between annual average temperature compensation and confirmed cases, the results have shown that temperature had a negative linear relationship with the number of confirmed cases with the curve flattening at a threshold of 25.8 °C. However, no evidence was found supporting that the curve declined for temperatures above 25.8 °C (Prata et al., 2020) .

Meteorological parameters have also been shown to influence infectious disease propagation, and mathematical relationships have been investigated to assess the impact of this parameter on COVID-19 spread. For example, Yielding et al. (Yueling et al., 2020 ) developed an additive model considering the effect of temperature, humidity and diurnal temperature range and the daily death counts of COVID-19. The study reported a positive association of COVID-19 daily deaths with diurnal temperature range, but negative association with relative humidity, concluding that temperature and humidity variation were significant factors on mortality rates.

Variation in environmental temperature has been suggested to influence the surface stability of J o u r n a l P r e -p r o o f Journal Pre-proof SARS-CoV-2, and temperature-dependent differences in SARS-CoV-2 stability in solution were reported recently (Kratzel et al., 2020) .

These early findings provide important base knowledge and insight into potential links between environmental parameters and SARS-CoV-2/COVID-19 impacts, but additional research is needed on the effect of seasonal changes, usually accompanied by temperature fluctuations, on virus stability. This lack of information is identified as a significant knowledge gap which merits timely consideration as seasonal changes progress and the number of cases is increasing or stable, but high in many regions. A better understanding of the effects of environmental temperature on the stability or infection potential of the SARS-CoV-2 virus will certainly serve to more accurately model, predict, and mitigate the immediate term occurrence of new cases.

In addition to virus transmission via respiratory droplets, there is increasing concern about the potential spread of SARS-CoV-2 to environmental surface water Cuevas-Ferrando et al., 2020; Randazzo et al., 2020) , a potential exposure pathway that is so far largely under-studied. Some viruses (e.g. fish and crustacean viruses such as infectious haematopoietic necrosis virus, (Oidtmann et al., 2017) ) are well known to remain viable and infectious, at least temporarily, in natural freshwater environments including lakes and streams, in manufactured environments such as wastewater treatment plants, and in sewage-polluted waters. Therefore, similar to other harmful viruses and pathogens, it is possible that an environmental exposure risk from SARS-CoV-2 exists via contact with such surface waters, and this represents another knowledge gap requiring further study. Conventional risk methodology identifies three exposure pathways when considering the wastewater to surface water pathway, namely, inhalation, dermal contact, and ingestion of polluted water (Foladori et al., 2020) .

It is well established that the release of under-treated or untreated sewage into surface waterways poses an epidemiological risk and can lead to the spread of disease through the 'fecal-oral' transmission route. Exposure to surface water where there is a sewage spill or release of inadequately treated wastewater increases the risk of ingesting fecal-borne pathogens such as E.

coli, giardia, and hepatitis (Chung et al., 2015) . Evidence suggest that SARS-CoV-2 may also be shed from human hosts via fecal matter expulsion for weeks after respiratory symptoms abate.

For example, (Cheung et al., 2020) have reported that 48.1% of 4,243 patients, (Wu et al., 2020a) reported that 55% of 74 patients, had fecal samples positive for the virus. It follows that SARS-CoV-2 may be a candidate for fecal-oral transmission (Arslan et al., 2020; Yeo et al., 2020) .

Furthermore, other coronaviruses have been shown to exhibit survival for many days in natural and wastewaters (Grundy et al., 2009 ). As such, despite the fact that dilution may keep the risk low, it is conceivable that high concentrations of water-borne SARS-CoV-2 may occur as the virus is shed from fecal matter as infection rates peak. Whether such environmental viral loads could represent a risk to humans coming into contact with contaminated water sources is unknown, and requires further study. The lack of information on the ability of the SARS-CoV-2 virus to remain viable in these wastewaters and in environmental surface water, and the lack of information about infectivity of detected SARS-CoV-2 from environmental samples, are significant gaps in knowledge which merit further investigation. Currently, it is not clear whether While the risk to human health associated with SARS-CoV-2 exposure from environmental samples is unknown, it is important to note that if fecal-oral transmission of COVID-19 is determined to be a concern, this issue would be particularly significant in areas with poor sanitation and/or where diagnostic capacity might be limited such as, for example, in developing countries (Lodder and de Roda Husman, 2020; Street et al., 2020) . A number of very recent studies have reported an increased number of cases where SARS-CoV-2 has been found in feces and/or urine of infected patients Xiao et al., 2020; Xu et al., 2020a) , although the mechanism of COVID-19-induced gastrointestinal symptoms remains unknown . As such, wastewater monitoring has been proposed as part of the SARS-CoV-2 surveillance strategy and has the potential to combat the disease through early detection. Along with Wastewater-Based Epidemiology (WBE), this can evolve into a potential highly costeffective approach to the current wide scale screening resulting in reduced resource costs (Mao et al., 2020; Street et al., 2020) . In fact, this approach would help to identify the presence asymptomatic individuals in the community who may be carriers of the virus with the ability to infect other people, but not show the symptoms themselves. However several factors may affect the detection of SARS-CoV-2 in wastewater samples and the subsequent implementation of wastewater based epidemiology approaches.

Detection and monitoring of the SARS-CoV-2 virus in wastewater is challenging due to dilution , thus requiring concentration of viral particles in water samples for accurate quantification (Bofill-Mas and Rusinol, 2020; Kitajima et al., 2020; La Rosa et al., 2020) . A recent review by Lu et al. (2020) identified the several approaches for effective primary J o u r n a l P r e -p r o o f Journal Pre-proof concentration of SARS-CoV-2 virions from wastewater. Concentration would be even more difficult in surface water bodies such as lakes and rivers, where the potential discharge of virus carrying wastewater is further diluted. In a recent review paper, Kitajima et al. (2020) suggested that the limited information on the presence of SARS-CoV-2 in wastewater is mainly because of the lack of past research focused on the virus, and the initial information proposing person-toperson as the only spread mechanisms. Importantly, they also found that other studies have suggested that standard virus concentration methods are inefficient for recovering enveloped viruses from water samples. Nevertheless, a study from 2013 reported the detection of coronaviruses in wastewater (Wong et al., 2013) , and studies of the SARS outbreak in 2004 (caused by the enveloped coronavirus SARS-CoV) showed virus RNA being detected in 100% of untreated and 30% of disinfected wastewater samples collected from a hospital in Beijing, China (Wang et al., 2005) . The presence of SARS-CoV-2 has already been reported in wastewater in Australia, France, the Netherlands, and USA Gonzalez et al., 2020; Hata and Honda, 2020; Kitajima et al., 2020; Lodder and de Roda Husman, 2020; Medema et al., 2020) , confirming that it can be concentrated from and detected in varied wastewater environments.

Bogler et al. (Bogler et al., 2020) identified three main approaches for the detection and monitoring of SARS-CoV-2 in wastewater, namely, qualitative, quantitative molecular, and in- RT-qPCR (Lodder and de Roda Husman, 2020) . The technique was deemed effective in detecting the virus in wastewater even within a week after the first reported cases of COVID-19.

However, this method of gene fragment identification does not provide information about the viability or infectivity of the virus from such environments. One study (Rimolldi et al., 2020) found that SARS-CoV-2 viral particles isolated from wastewater did not appear to infect VERO E6 cells (a kidney cell line from African green monkeys) when cultured together. However, caution must be excercised when interpreting such outcomes, as in vitro experimental conditions are rarely representative of the precise biological host conditions that may foster infection and disease development. Therefore, we identify the lack of information about the viability and infectivity of SARS-CoV-2 particles from wastewater and other environmental reservoirs as a significant knowledge gap requiring further research.

As evidence builds on the occurrence of SARS-CoV-2 in wastewater (Collivignarelli et al., 2020; Nemudryi et al., 2020) , there is a significant need to identify the feasibility of testing and detection methodology for broad scale implementation, to understand the main environmental pathways and fate of the virus, as well as to assess SARS-CoV-2 infection capacity as a function of time and the related inactivation mechanisms implemented during wastewater treatment.

Some studies have suggested monitoring wastewater to identify the transmission of the virus within entire communities, suggesting well-established approaches such as Wastewater-Based Epidemiology could be implemented to identify fragment biomarkers of the virus that represent a particular community (Daughton, 2020). For example, a recent study investigated the efficiency of computational analysis for SARS-CoV-2/COVID-19 surveillance (Hart and Halden, 2020) . It was found that one infected individual is detectable (at least in theory) among 100-2,000,000 persons through wastewater monitoring, meaning that 2.1 billion people could be monitored J o u r n a l P r e -p r o o f Journal Pre-proof globally in 105,600 sewage treatment plants, potentially saving billions of dollars. However, in their study, Hart and Halden (2020) did not incorporate field-based data because relatively few studies have quantified the SARS-CoV-2 virus in wastewater effluent. This lack of field-based information represents another significant knowledge gap worth exploration, because validation of the computational analysis with field results presents the best opportunity for optimized model accuracy, thereby creating the highest likelihood of cost effective COVID-19 monitoring.

It is important to note that the use of WBE or other epidemiology approaches does not indicate risk of disease development associated with exposure to sewage contaminated waters.

Complementary clinical testing campaigns would be required to accomplish this, because SARS-CoV-2 RNA detection in wastewater using RT-qPCR is not necessarily indicative of viable or transmissible virus load. Rather, the use of WBE may have benefits over clinical testing as an indicator of community spread because one wastewater treatment plant is potentially able to provide an estimate of SARS-CoV-2 incidence within a large population.

Because the risks to human health associated with exposure to wastewater which contains indicators of SARS-CoV-2 genes has not been quantified, it is important to assess the effectiveness of current wastewater treatment practices in removing or deactivating viruses in wastewater. It is expected that many conventional sewage treatment methods including disinfection are able to inactivate the SARS-CoV-2 virus. Regrettably, in some developing countries or in rural areas of developed countries such sewage treatment practices are not prevalent. As some developing countries are already susceptible to the COVID-19 pandemic because of the limitations in basic sanitation and environmental conditions that can favor the virus spread (Usman et al., 2020) , it is important to understand the environmental factors that could affect the transmission and virus survival after release in wastewater. It has been suggested J o u r n a l P r e -p r o o f that SARS-CoV-2 virus is capable of surviving for several days in untreated sewage, and for a much longer period in low-temperature regions. While this scenario is not yet been well studied, it is imperative that more work is done to understand this potential exposure risk since around 1.8 billion people worldwide are estimated to be using sewage contaminated drinking water sources (Bhowmick and Dhar, 2019) .

Is has also been suggested that in some cases conventional wastewater treatment processes may not be capable of completely removing SARS-CoV-2 (Lesimple et al., 2020; , and is such situations pretreatment techniques are suggested to minimize the entry of the virus into wastewater due to the unknown infectivity of SARS-CoV-2 from such environments. These include, membrane filtration, virus inactivation using ultraviolet radiation and chlorination.

Further, the incorporation of effective monitoring tools has been recommended for wastewater treatment plants, in order to identify any increase in the virus load which may accompany outbreaks or re-emergence after control measures to stop the spread of the disease are lifted (Venugopal et al., 2019) . It is important to note that advanced monitoring and treatment of wastewater would be especially limited in resource-constrained regions such as low income countries which had capacity to treat only about 8% of wastewater in 2015 (Street et al., 2020) . Some recent studies have also reported the presence of pathogenic microorganisms in wastewater plumbing systems, confirming that even in countries where conventional wastewater treatment is prevalent, the potential for disease transmission may exist (Gormley et al., 2020) . For example, empty U-bends in bathrooms were noted as a potentially hazardous SARS-CoV-2 virus propagation mechanism in a study by Gormley et al. (2020) . They found that U-bends in bathrooms draws contaminated air into the room, highlighting the need for more studies on the transmission role of wastewater plumbing systems. Based on all this evidence, if SARS-CoV-2 proves to remain viable and infective in wastewater environments, the risk of disease spread from wastewater exposure would be much higher in regions which lack access to effective wastewater treatment relative to regions where conventional wastewater treatment is widely available (Nwobodo and Chukwu, 2020) . In contrast to wastewater, research is yet to investigate virus prevalence in surface waters. In fact, a recent study noted the lack of research into the presence of not only the current SARS-CoV-2 virus, but also other types of coronaviruses in surface water (La Rosa et al., 2020) . Some studies have found limited evidence via RT-qPCR techniques of various coronaviruses in river, lake, and reservoir water (Alexyuk et al., 2017; Blanco et al., 2019) . Despite these studies reporting low detection rates (number of positive samples), their findings suggest the possibility of surface water contamination with coronaviruses via discharge of poorly treated wastewater.

Therefore, extensive field-based investigations are necessary to understand SARS-CoV-2 virus prevalence not only in raw and treated wastewater, but also in receiving surface waters. These investigations should include assessment of virus viability and infectivity, if detected. This will J o u r n a l P r e -p r o o f generate knowledge required for quantitative risk assessment and to assist in monitoring outbreaks within communities.

It is clear that an accurate, low-cost, and easy-to-use SARS-CoV-2 monitoring system can support the strategies adopted by the authorities to reduce the economic and social impacts of the COVID-19 pandemic. This is particularly important since different countries around the world are at widely varying stages of the pandemic. In this sense, electrochemical sensors have several advantages because they can be miniaturized and allow in situ analysis (Rocha et al., 2020) .

Several biosensors combined with nanotechnology, especially those that use reduced graphene J o u r n a l P r e -p r o o f 

Electrochemical immunosensor

The device uses specific envelop protein antibody as recognition element, possesses a dynamic range of 0.001 to 100 ng/mL, and detection limit of 1 pg/mL Laboratory scale (Layqah and Eissa, 2019) *Technology maturity status= Laboratory scale: Technology concept and/or application formulated; Bench scale: Component and/or breadboard validation in laboratory environment; Field application: System prototype demonstration in a space environment.

Viruses in general are considered to have relatively higher resistance to conventional water disinfection process compared to bacteria (Garcia-Gil et al., 2020) , which highlights the significance of the search for novel, cost-effective methodologies for viral inactivation in water (Adelodun et al., 2020; . Usually, it is assumed that predatory microorganisms (e.g., protozoa) in wastewater can inactivate a significant proportion of the viruses present (Yang et al., 2005) . Conventional secondary wastewater treatment processes are capable of removing 2-3 log 10 -cycles of virus content through adsorption to the solid particles of activated sludge . Membrane technologies (e.g., ultra, nano-filtration, reverse osmosis) have also proven to be another efficient approach towards the removal of viruses and/or solid-associated viruses, achieving removal efficiencies in the range from 0.2 log 10 -to 6.5 log 10cycles for ultra-filtration and reverse osmosis, respectively (Bhowmick and Dhar, 2019) . The use of any of these technologies for the removal of viruses involves only mechanical separation, but not the inactivation of the viruses. In this regard, tertiary treatment processes have been reported to be effective for virus inactivation with variable efficiency , and several different technologies have been tested for the inactivation of different viruses in water. Table 2 shows a selected overview of recent studies which have reported on the use of conventional and non-conventional methodologies for the inactivation of viruses in water. Table 2 , it is important to note that different advanced oxidation processes (AOPs) have been tested and identified as having great potential and provides a variety of alternatives for virus inactivation. For example, the use of either solar disinfection, ozonation, wet oxidation, or even cold plasma to generate reactive oxygen species (ROS) have shown significant potential for inactivation not only of bacteria and other pathogenic J o u r n a l P r e -p r o o f microorganisms (Huesca-Espitia et al., 2017) , but also virus inactivation. Other methodologies have been reported, including conventional chlorination procedures, the use of alternative disinfectants (Garcia et al., 2019; Rachmadi et al., 2020) , and the application of high temperature CO 2 injection in water for viruses inactivation (Sanchis et al., 2019) . No studies on the inactivation or removal of SARS-CoV-2 in water are available, probably because of the reported very low survival of the virus in surface water, wastewater, sludge and biosolids at temperatures higher than 20°C, and the higher inactivation rate of Coronavirus when compared with others such as enteric viruses (e.g., Adenoviridae, Astroviridae, Caliciviridae) considered by WHO as a concern in relation to water (Carraturo et al., 2020; La Rosa et al., 2020) . However, the virus poses high risks due to its highly infectious nature and resistance to conventional water and wastewater treatment technologies (Garcia-Gil et al., 2020; Haleem et al., 2020) . Assessing the time elapsed since the start of the outbreak and the release of active or inactive virus into receiving water bodies is a further interesting research area which merits exploration, because it is only in the last few months that the virus has gained attention and there has not been adequate time to undertake studies on its mobility through various pathways such as sewers, water treatment plants and surface water bodies.

It is also important to note the use, in some cases, of bacteriophage viruses such as MS2 or ΦX174 to run experiments in water as a surrogate of other human pathogenic viruses.

Bacteriophages have been reported as a surrogate also for SARS-CoV-2 for testing inactivation using UV-C lamps because of their similar envelope and size to coronavirus (Cadnum et al., 2020; Carducci et al., 2020) . However, very little is known about other characteristics that may be different between bacteriophage viruses and SARS-CoV-2. For example, bacteriophage is known to possess a double stranded RNA genome which means greater stability compared to J o u r n a l P r e -p r o o f single-stranded RNA genome in coronaviruses . Usually the difference may be considered appropriate from an inactivation perspective, as bacteriophages may serve as a conservative surrogate for SARS-CoV-2, but further studies are required to robustly assess these differences and their potential influence in relation to the use of surrogates. This presents a significant knowledge gap which merits further investigation.

Another interesting pending research avenue is the role potentially played by nanomaterials in the inactivation of SARS-CoV-2 in water (Sportelli et al., 2020) . Nanotechnology has been used in the past for the production of contamination-safe personnel protection equipment based on the significant antimicrobial and antiviral properties of some specific nanomaterials (Chen et al., 2016) . In a recent review, Kokkinos et al. (2020) provided information on the outstanding capacity of nanomaterials for the removal and inactivation of different viruses in water (Kokkinos et al., 2020) . These researchers collated knowledge demonstrating the disinfection potential of doped-TiO 2 nanofibers, Fe 3 O 4 -SiO 2 -NH 2 nanoparticles, Ag-doped TiO 2 , Bi 2 WO 6 , and NeTiO 2 for the inactivation of a wide variety of viruses including bacteriophage MS2, f2, and poliovirus-1 in water with highly encouraging results.

Nevertheless, the reported nanomaterials are just a few compared to the wide variety of nanoparticles, nanotubes, nanosheets, nanorods, nanocages, nanobranches, and several other engineered nanomaterials (ENMs) reported in literature with different and versatile characteristics and potential for application in virus inactivation (Bandala and Berli, 2019) .

However, the use of nanomaterials for water treatment needs to be considered with caution due to the potential toxic nature of some of these materials which can be concerning (Gardea-Torresdey et al., 2014; Nowack et al., 2015) . The interactions between ENMs and biological systems is known to be complex and with considerable inherent difficulties in monitoring of their (Chen et al., 2017) J o u r n a l P r e -p r o o f ZnO, and Fe 3 O 4 *Technology maturity status= Laboratory scale: Technology concept and/or application formulated; Bench scale: Component and/or breadboard validation in laboratory environment; Field application: System prototype demonstration in a space environment.

J o u r n a l P r e -p r o o f 6. COVID-19 related pharmaceuticals in wastewater pathways into surface water

Additional to the risk of the potential release of SARS-CoV-2 virus to surface water, wastewater also possess the potential for carrying chemical contaminants harmful to the aquatic ecosystem and potentially dangerous to human health. Among many different chemical compounds, pharmaceuticals are the most significant because of the threat posed by their biological activity, persistence, and mobility in the environment (Bandala and Rodriguez-Narvaez, 2019) .

Consequently, the effort of controlling the adverse health effects caused by COVID-19 may also have significant adverse repercussions on the water ecosystem. As an example, one of the common symptoms of COVID-19, and any other viral upper respiratory tract infection, is fever.

As the number of COVID-19 infections and hospitalization cases peak, it would be expected that the amount of drugs being used to control fever, dyspnea, or other related symptoms will correspondingly increase.

Usually, only a small part of these drugs are metabolized within the human body with a significant fraction being released from the patient organism through their feces and urine which will eventually end up in sewage (Zeidman et al., 2020) . It is well-known that conventional wastewater treatment is not capable of degrading most of these pharmaceuticals, and many are instead released back into receiving water bodies (Rodriguez-Narvaez et al., 2017) . Many of these pharmaceuticals are considered to be endocrine disrupting compounds able to generate health impacts even at trace concentrations in water. Therefore, their quantification in water and associated risk is fundamental research as well as assessing the correlation between the amounts of pharmaceuticals being released into surface water and the development of cost effective technologies for their degradation and removal (Rodríguez-Narvaez et al., 2020) .

The medical community have devoted a significant amount of effort identifying allopathic drugs, natural products, and homeopathic products with treatment potential against COVID-19 symptoms (Dong et al., 2020) . Either in agreement with WHO or otherwise, at least 12 potential COVID-19 treatments are currently being widely tested/used, including drugs used for HIV and malaria such as chloroquine, and experimental antiviral drugs (Colson et al., 2020; Kupferschmidt and Cohen, 2020) . As result, a significant amount of active ingredients and their metabolized relatives are being released into the sewer on a daily basis (Bensalah et al., 2020) .

The significant presence of these compounds in water bodies and drinking water sources highlights the need for cost-effective treatment as their non-or low-biodegradable characteristics leads to their persistence in water and potential health and environmental risks (Zaied et al., 2020) .

The lack of information about the type and amount of COVID-19-related active principal and metabolites being released into sewage, arriving in the wastewater influent, or being released with the wastewater treatment plant effluent into receiving water bodies is a highly significant knowledge gap which merits further investigation because of the known and unknown biological activity of these chemicals and the potential effects these may have on aquatic species and/or human health. Very little is known about the mass balance for COVID-19-related drugs or their metabolites in wastewater treatment plants. Therefore, the efficacy of the water treatment processes on their elimination cannot be assessed solely using the currently available knowledge.

Consequently, this can also be highlighted as an important research avenue. Further, knowledge creation about the persistence, bioaccumulation, bioconcentration, biomagnification and/or environmental fate of the active principal and/or metabolites after their release into aquatic ecosystems is another challenging research avenue which requires attention.

J o u r n a l P r e -p r o o f

In the last decades, the wastewater treatment sector has been facing several different technology challenges related with the increased water stress, wastewater reuse in agriculture and other industrial applications (Gómez-López et al., 2009) . Additionally, the improvement in analytical technologies used for water analysis have shown that many of the conventional wastewater treatments currently used do not suffice to eliminate some pollutants generated from anthropogenic activities (Krzeminski et al., 2019) . Further, the reuse of wastewater effluent without appropriate treatment can lead to the dispersion of these pollutants in soil and water matrices (Medrano-Rodríguez et al., 2020). One of the major outcomes of the dispersion of pollutants from poorly or improperly treated wastewater is the detection of organic molecules of anthropogenic origin (pharmaceuticals and personal care products) at trace levels (ng/L-µg/L) in water bodies (Blanchet et al., 2017; Reis et al., 2019; Wang et al., 2018) . These pollutants, also called contaminants of emerging concern (CECs), are considered as a proxy for anthropogenic activity and in many cases have served as tracers to assess their level of consumption in the Due to the stress caused by the pandemic, people have resorted to using non-prescribed drugs as a form of COVID-19 prevention. Although chloroquine (CQ) and hydroxychloroquine (HCQ) present an unproven hypothesis to treat COVID-19, the consumption of these and other drugs has increased considerably in recent months. Consequently, significant quantities of wastewater J o u r n a l P r e -p r o o f contaminated with CQ and HCQ being released into the environment is a distinct possibility.

Considering this scenario, the generation of methodologies for the degradation of these drugs, as well as protocols for their determination in wastewater effluent and surface water resources is a significant research need.

A recent state-of-the-art review (Saka, 2020) into the detection techniques and quantitative determination methods of CQ and its related metabolites found that the main methods used for CQ analysis are liquid chromatography, capillary electrophoresis, electroanalytical, spectrophotometric, and ELISA-based methods. In most of the studies, detection and quantification of CQ were performed in pharmaceutical dosage formulations and biological matrices and the most frequently used technique is high performance liquid chromatography (HPLC). In this case, the potential use of electroanalytical methods emerges as highly significant for the determination of CQ, HCQ, and other pharmaceuticals in wastewater effluent and surface water because of their ability to make in situ analysis possible. Some carbon-based electrochemical sensors, particularly carbon nanotubes and graphene have been successfully used in the analysis of CECs. For example, sensors based on rGO-metal nanoparticles have been used for estriol hormone and glyphosate detection in water samples (Cesarino et al., 2015; Donini et al., 2018; Setznagl and Cesarino, 2020) , where the devices yielded low limits of detection for the target analytes.

Among the metallic nanoparticles studied, copper nanoparticles were found showing the best results when compared to the other nanoparticles. Figure 3 illustrates a schematic overview of the preparation procedure of a sensor based on rGO-CuNPs composite that could be used in the analysis of COVID-19-relevant pharmaceuticals in wastewater effluent and surface water using differential pulse voltammetry (DPV) technique. As shown, the preparation procedure is simple J o u r n a l P r e -p r o o f Journal Pre-proof and uses relatively inexpensive materials, but the resulting sensors possess wide applicability for environmental sample analysis. For example, a recent study reported the development of a sensor based on reduced graphene oxide for tetracycline determination that uses just 10 µL of the sample and generates highly selective results within 6 minutes (Lorenzetti et al., 2020) . Another study used a graphene-oxide-based electrochemical sensor for selective, highly sensitive (0.6 µAµM -1 cm -2 ), and strong anti-interference capacity for detection of naproxen (Qian et al., 2020) . One of the common characteristic of this type of sensors, however, is they are usually disposable after use which make them convenient for field applications, but may also imply some drawbacks considering the accumulation in the environment of the base materials used for their manufacture. As noted earlier, there is an increasing concern about unknown and undesirable interaction of nanomaterial with the environment after their release into water or soil. In this J o u r n a l P r e -p r o o f regard, the development of re-usable sensors emerges as a very interesting research avenue worthy of consideration to increase the life cycle of the technology and to avoid the release of nanoparticles into the environment. Until now, very few studies on the development of reusable electrochemical sensors are available, and even fewer devoted to the detection of pharmaceuticals in water (Costa-Rama et al., 2020) which makes this a significant knowledge gap worthy of further exploration.

In this paper, a review of the most significant potential impacts of the COVID-19 pandemic on the wastewater pathway into surface water, as well as different technologies that may serve to counteract the major threats posed, key perspectives and challenges was undertaken. The following are the main findings:

 Besides the best understood spreading of the SARS-CoV-2 virus through droplets and aerosols in airborne dispersion, very little is known about the effect of environmental conditions, such as temperature or humidity, on the transmissibility of the virus. This is identified as a significant knowledge gap as the climate moves towards fall/winter season.

 Fecal-oral transmission of the SARS-CoV-2 virus has been reported. However, there is a significant lack of information on the role wastewater effluent may play in such infection pathways, in the spread of COVID-19 resulting from the release of poorly or untreated wastewater effluents into freshwater bodies, or in the factors that may influence the transmission and survival of the virus in aquatic ecosystems.

 Additional to the identification and quantification of the SARS-CoV-2 in water and wastewater using conventional methodologies such as RT-PCR, other emerging J o u r n a l P r e -p r o o f approaches such as wastewater-based epidemiology (WBE) have been suggested to complement information and identify fragment biomarkers of the virus. The use of WBE as a preventative and monitoring measure has been found to be particularly appealing for application in developing countries and/or rural communities where scattered population and lack of resources limits widespread application of RT-PCR technology.

 The need for accurate, low-cost, and easy-to-use sensors for either SARS-CoV-2 monitoring or related pharmaceuticals in wastewater pathways into surface water was identified as a significant knowledge gap which merits further exploration in order to reduce not only economic and social impacts of the COVID-19 pandemic, but also other undesirable impacts on the aquatic environment.

 Virus inactivation and/or degradation of COVID-19 related pharmaceuticals in water was found to be not only important, but also a challenging scientific task because of the relatively high resistance of the virus to conventional water disinfection processes compared to bacteria and the known and unknown biological activity of some pharmaceuticals. Different technologies have been proposed and successfully tested, but most of these have significant drawbacks such as high cost, the involvement of phase change separation without inactivation/degradation of the viruses/pharmaceuticals, or the risk to the environment from the release of potentially toxic compounds during treatment.

The search for novel, cost-effective methodologies for virus inactivation and pharmaceuticals degradation in water is also identified as an important future research avenue worthy of consideration.

This work was partially supported by Nevada Water Resources Research Institute (Grant No J o u r n a l P r e -p r o o f G16AP00069).

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☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

Technically robust, low cost technologies for virus identification, quantification and inactivation needed specifically for wastewater J o u r n a l P r e -p r o o f