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Official websites use. Share sensitive information only on official, secure websites. Corresponding author. Elsevier hereby grants permission to make all its COVIDrelated research that is available on the COVID resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. The abuse of legal and illegal drugs is a global public health problem, also affecting the social and economic well-being of the population. Thus, there is a significant interest in monitoring drug consumption. Relevant epidemiological information on lifestyle habits can be obtained from the chemical analysis of urban wastewater. In this work, passive sampling using polar organic chemical integrative samplers POCIS was used to quantify licit and illicit drugs biomarkers in wastewater for the application of wastewater-based epidemiology WBE. In this WBE study, a small urban community of approximately inhabitants was monitored from 18 March to 3 March , covering the mobility restriction and flexibilization periods of the COVID pandemic in Brazil. Our study is the first long-term drug consumption evaluation during the COVID pandemic, with continuous sampling for almost a whole year. The observed reduction in consumption of both licit and illicit drugs is probably associated with stay-at-home orders and reduced access, which can be due to the closure of commercial facilities during some time of the evaluated period, smaller drug supply, and reduced income of the population due to the shutdown of companies and unemployment. The assay described in this study can be used as a complementary and cost-effective tool to the long-term monitoring of drug use biomarkers in wastewater, a relevant epidemiological strategy currently limited to short collection times. In addition, the use of some licit drug compounds, such as tobacco, has relevant impacts on the population's health Gao et al. In this context, the knowledge of the illicit and licit drug consumption behavior of a given population is of paramount importance for the planning and monitoring of demand and damage reduction activities, as well as for law enforcement intelligence Bannwarth et al. Classic monitoring of the consumption of drugs at the population level is based on epidemiological, sociological, and criminological indicators EMCDDA, Considering the complexity and inherent uncertainty of these indicators, the analysis of wastewater was proposed as a more objective and representative strategy for the estimation of drug consumption by a population served by a wastewater treatment plant WWTP. In this approach, named wastewater-based epidemiology WBE , concentrations of biomarkers of drug use in wastewater are measured and the amount of drug intake by the population is estimated through retrospective calculations Daglioglu et al. Several WBE studies were already reported, mainly focused on illicit drugs Huizer et al. The first European study on illicit drug use by analyzing wastewater biomarkers was carried out in Thomas et al. A biomarker must also be sufficiently stable in wastewater Gracia-Lor et al. COC consumption is estimated using benzoylecgonine BZE wastewater concentrations, which is relatively stable in wastewater Gracia-Lor et al. Amphetamine stimulants are generally monitored as the parent compounds Gracia-Lor et al. Caffeine CAF can be monitored as the parent compound Senta et al. The retrospective calculation of drug consumption in WBE requires the knowledge of the average concentration of the biomarker along the 24 h of the day. The large majority of the reported WBE studies used composite active sampling to obtain representative wastewater concentrations Hahn et al. This sampling strategy demands the use of expensive automatic samplers, properly installed with environmental protection and power supply Allan et al. A cost-effective alternative to automatic composite sampling is the use of passive samplers, particularly the polar organic chemical integrative sampler POCIS Alvarez et al. POCIS samplers are less affected by short-term fluctuations of biomarker concentrations in wastewater and allow pre-concentration of the analytes, leading to very low quantification limits Fedorova et al. Criquet et al. The concentrations measured with POCIS were, in general, between the maximum and minimum levels measured in the composite samples. Bishop et al. However, the POCIS membrane occlusion sampled over 30 days reported by the authors may have affected the performance of the sampling device. The initial control of the spread of the disease was based on non-pharmacological measures, and more than Countries instated personal mobility restrictions Reinstadler et al. The impact of these measures on the demand and supply in the illicit drug market is still unknown. Cannabis use appeared to have been less affected during the pandemic mobility restriction periods. However, this study was based on sampling performed during only one week in most evaluated cities SCORE, In this context, this study describes a WBE study evaluating all priority SCORE drugs during a whole year in — in a Brazilian mid-size city, comparing the estimated drug consumption with human mobility reports. Methanol, acetonitrile, and dichloromethane were purchased from Merck Darmstadt, Germany. Formic acid and ammonium formate were bought from Sigma-Aldrich. The extracts were analyzed in an Acquity I-Class chromatograph coupled to a TQ-S Micro triple quadrupole mass spectrometer, both purchased from Waters. The initial mobile phase composition was held for 0. This latter composition was held until 7. The total chromatographic run was 11 min. The mobile phase flow rate was 0. The mass spectrometer was operated in both positive and negative electrospray ionization mode, at multiple reaction monitoring MRM mode. Compound-specific acquisition parameters and retention times are presented in the supplementary material table S1. All calibrators contained a mixture of deuterated internal standards, with the concentrations of 0. Weighted linear regression curves were obtained relating the nominal concentration of the analytes to the area ratio of the target compound to the respective internal standard. This latter compound presented an ion enhancement effect in the range of Positive and negative controls were also processed. The samplers were exposed to the water containing the analytes for 8 days, with daily aliquots used for the quantification of the compounds. R s values were confirmed by the mass balance of the amount of the analyte accumulated in the POCIS at the end of the calibration study Li et al. The R s values of the analytes were calculated by the water concentration decrease method, using a linear regression that describes the loss of a compound from the water as the result of absorption by the POCIS over the days of the calibration study duration. The R s for each analyte was calculated by multiplying k u by the water volume present in the experimental vessel. R s values were 0. Details of the calibration experiment were described by Hahn et al. This WWTP serves an average estimated urban population of people, according to the hydro chemical parameter biological oxygen demand over five days BOD5. Measurements of BOD5 in each sampling period allowed the use of a dynamic population size marker. The values ranged from to inhabitants served by the WWTP during the evaluation period. The sampling campaign started in March and finished in March After removal from the wastewater, the samplers were briefly washed with tap water and transferred to plastic bags. The samplers were disassembled, and the sorbent was extracted on the same day of removal from the wastewater. Data on wastewater inflow, temperature, and pH were provided by the sanitation company responsible for the WWTP. The result of this multiplication is divided by the number of people served by the WWTP and multiplied by , to obtain a normalized value van Nuijs et al. The correction factors used in the study are presented in Table 1. Considering the low estimated mean residence time of the wastewater in the investigated sewer system 0. Evaluated drugs, consumption biomarkers, and correction factors used for the estimation of population drug consumption. Ratio between the molecular mass of the drug and the biomarker. Report insights are created with aggregated and anonymized datasets from users who have enabled the location history setting. The reports presented data on mobile phone mobility through city locations related to different human activities, classified as workplaces, supermarkets and pharmacies, parks, residential, public transport, and retail and recreation. The evaluated time range included the introduction of the first human mobility reduction measures during the COVID pandemic in the evaluated region, where the first stay-at-home recommendations by local authorities were stated on 16 March , and the period of easing of mobility restrictions, after 3 August The parks and public transport mobility data were not evaluated due to incomplete data. The normality of the drug consumption data was tested using the Kolmogorov-Smirnov test. Parametric tests for correlation and regression analyses and group comparisons were used due to data normality. For the multiple linear regression, the estimated consumption of each drug was related to all location categories at the same time. In addition, consumption data were divided into 2 groups, before and after the flexibilization period decreed in the city of Novo Hamburgo. The pre-flexibilization period was from 18 March to 5 August and the post-flexibility period was from 5 August to 3 March To evaluate whether there are differences between these two groups, the Student's t -test for independent samples was used. Wastewater sampling using POCIS is a useful alternative for WBE studies in resource-limited settings, once more sofisticated automatic composite samplers are not required. Particularly in Brazil, only composite sampling was reported, with short-term evaluations, for COC da Silva et al. In this study, a sampling campaing of almost a whole year was applied. Long-term WBE studies can provide a valuable outline of the drug consumption profile of a locality and are less affected by point variabilities Krizman-Matasic et al. The lack of standardization of POCIS calibration procedures and influence of environmental factors can result in significantly different R s values for the same compounds even when similar sorbents are used Baz-Lomba et al. The wide variation of R s values observed in the literature characterize the high dependency of experimental calibration conditions and the semi-quantitative nature of drug consumption estimation using POCIS Hahn et al. The wastewater was sampled in a WWTP from a mid-sized Brazilian city from 18 March to 3 March , with 24 sampling periods of two weeks. Table 3 summarizes the estimated C TWA and amount of consumed drug for all sampling periods of the study. Among the monitored compounds, only MAMP was not detected in any sampling period. AEME was detected in only 4 sampling periods. CAF monitoring started in 27 May To date, the majority of WBE studies for illicit drugs were performed using composite sampling, with sampling campaigns of up to one week Hahn et al. The long-term profiling of consumption behavior of licit and illicit drugs was reported only by few studies. Among the compounds evaluated in this study, Harman et al. Important to note that AMP can be present in wastewater as a metabolite of drugs such as fenproporex, used illegally in Brazil as an appetite suppressant and as a stimulant by truck drivers Leyton et al. This finding indicates the use of COC in the form of crack by the evaluated population, but in a small proportion of the overall consumption. The low frequency of AEME detection and the very high proposed correction factor described in the literature to estimate crack consumption, which leads to significant uncertainty, prevented us to use this marker for consumption estimates Baker et al. In this context, we used the correction factor of 3. The estimates of consumption presented in Table 3 correspond to the amounts of active drugs taken. The actual amount of pure drug in a consumption unit is not easily estimated due to wide variations in the patterns of use and varying purity of the street products Zuccato et al. The consumption of COC in Brazilian cities was previously estimated, using 24 h composite sampling performed over 1—8 days da Silva et al. Important to note that POCIS sampling provides an average concentration over the sampling period and is less affected by point variation in the use of a given drug. Also, differences on the socio-economical, cultural, and demographic characteristics of the evaluated populations could also affect the consumption estimates. Similar observation was made regarding tobacco use, where the estimated consumption of 1. These differences in the estimates of CAF and NIC consumption could be attributed to the reduced income of the population during the mobility reduction period due to the COVID pandemic and to the demographic characteristics of the population served by the WWTP, with an unknown percentage of children. The COVID pandemic resulted in the enforcement of human mobility restrictions in most countries of the world. The state of health emergency in the city of Novo Hamburgo, Brazil, was declared on 18 March by the city mayor. Soon after, on 23 March , the state of public calamity was instated, with mandatory closure of all workplaces, commercial, and educational facilities, excluding essential activities. Different levels of restrictions in human mobility were effective since then, until 3 August , when non-essential activities were authorized to reopen partially. The human distancing levels do not depend only on government recommendations, but also on individual decisions. The level of human mobility in an urban location can be derived from cellular phone mobility, as applied in other studies Reinstadler et al. Drug consumption and human mobility in different location categories during the WBE sampling study 18 March to 3 March In this study, wastewater was sampled from 18 March to 3 March , covering the period of most severe mobility restrictions and the period where some of the restrictions were lifted, what happened just after the middle of the year of There is very limited data about the drug consumption of the evaluated population before COVID mobility restrictions Hahn et al. The results of the simple and multiple correlation analyses relating to the amount of consumed drug and human mobility reduction during the study are summarized in Table 4 , Table 5 , respectively. No significant correlations were observed for AMP consumption, in both analyses, the drug less consumed among the evaluated compounds. In addition, COC daily consumption also had a positive significant correlation with retail and recreation mobility in simple correlation analysis, and a negative correlation with workplaces mobility on multivariate analysis. In both tests, we observe that the contribution regression slope of the residence mobility category is much greater than the other significant variables to the consumption of COC. So, even if the circulation in the workplace and recreation and leisure locations has increased over time, the major impact in the increase of COC consumption was probably the reduction of the permanence of the population in their residences. Particularly, COC consumption presented a trend to increase along with the increase of mobility in public activities, markedly after the end of August This observation was confirmed by the finding of the correlation analyses, characterizing that the longer people stayed at home, lesser COC was consumed. Reduced consumption in the end-of-year holidays is probably associated with people temporally moving away from their homes in this period. CAF daily consumption also presented a positive significant correlation with supermarket and pharmacies mobilities in the multiple regression analysis. These data indicate that CAF consumption was affected by overall mobility and not by modifications in particular human activity. Both CAF and NIC consumption presented a strong negative correlation with the human mobility level at residential locations and positive significant correlations with retail and recreation. As these compounds are originated from licit consumed products, the reduction in consumption is probably associated with reduced access, which can be due to the closure of commercial facilities during some time of the evaluated period, but also to the reduced income of the population due to the shutdown of companies and unemployment. The smaller NIC consumption when people were mostly at home may also be due to respect for family members who do not smoke. Thus, the decrease in the population's permanence in residential locations due to the flexibility of stay-at-home recommendations during had a greater impact on the increase in the consumption of licit and illicit drugs than the change of mobility in other location categories. In general, we observed that overall drug consumption was reduced during the stay-at-home period. In the evaluation of the period before and after the mobility flexibilization, significant higher drug consumption was observed, except for AMP, as presented in Table 6. From the 4 sampling periods of the pre-pandemic period, the consumption averages were 7. Even considering the limited amount of data available from pre-pandemic drug consumption estimates, we can observe an increase in consumption after easing mobility restrictions when compared to the pre-pandemic period, except for THC, which presented similar behavior in both periods. Significant difference between the compared periods are presented in bold. Reinstadler et al. Been et al. However, an increase in drug consumption was observed in other locations, like an increase in COC consumption in Milan. Montgomery et al. The study performed sampling of wastewater for 4 periods of 10 consecutive days and compared the estimated drug consumption of June with March , during the lockdown period. Bade et al. Authors suggest that the observed changes in consumption were possibly linked to reduced supply of imported substances, with increased use of locally produced drugs. Our study is the first long-term continuous drug consumption evaluation during the COVID pandemic. We hypothesize that the observed reduction of the consumption of both drugs of illicit and licit compounds in the low-income community monitoring in this study, differently from the study performed in Developed Countries, was mostly related to reduced availably of financial resources of the population. The increase in consumption was probably due to the relaxation and return of recreational activities, with the reduction in permanence in residential locations. The consumption of illicit and licit drugs by the population served by the WWTP was correlated with the human mobility, estimated by mobile phone data. The reduction in consumption, observed for both licit and illicit drugs, is probably associated with stay-at-home recommendations and reduced access, which can be due to the closure of commercial facilities during some time of the evaluated period, but also to the reduced income of the population due to the shutdown of companies and unemployment. The reduction of the permanence of the population in the residential locations was associated with an increase in the consumption of drugs. Marcos Frank Bastiani: Investigation, Data curation. Anelise Schneider: Investigation. Isabela Caroline da Silva Moreira: Investigation. Yasmin Fazenda Meireles: Investigation. Mariana Freitas Viana: Investigation. 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. RL is recipient of a CNPq research scholarship. Authors thank Prof. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. Find articles by Roberta Zilles Hahn. Find articles by Marcos Frank Bastiani. Find articles by Lilian de Lima Feltraco Lizot. Find articles by Anelise Schneider. Find articles by Isabela Caroline da Silva Moreira. Find articles by Yasmin Fazenda Meireles. Find articles by Mariana Freitas Viana. Find articles by Carlos Augusto do Nascimento. Find articles by Rafael Linden. All rights reserved. Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Gracia-Lor et al. Baselt Castiglioni et al.

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