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Official websites use. Share sensitive information only on official, secure websites. 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 coronavirus disease COVID has developed into a serious pandemic with millions of cases diagnosed worldwide. To fight COVID pandemic, over countries instituted either a full or partial lockdown, affecting billions of people. In Tyrol, first lockdown measures were taken on 10 March On 16 March , a curfew went into force which ended on 1 May On 19 March , Tyrol as a whole was placed in quarantine which ended on 7 April The governmental actions helped reducing the spread of COVID at the cost of significant effects on social life and behaviour. Accordingly, to provide a comprehensive picture of the population health status not only input from medical and biological sciences is required, but also from other sciences able to provide lifestyle information such as drug use. Herein, wastewater-based epidemiology was used for studying temporal trends of licit and illicit drug consumption during lockdown and quarantine in the area of the Tyrolean capital Innsbruck , inhabitants. On 35 days between 12 March and 15 April , loads of 23 markers were monitored in wastewater. Loads determined on days between March and January served as reference. During lockdown, changes in the consumption patterns of recreational drugs i. For illicit drugs and alcohol, it is very likely that observed changes were linked to the shutdown of the hospitality industry and event cancelation which led to a reduced demand of these compounds particularly on weekends. For the pharmaceuticals, further work will be necessary to clarify if the observed declines are indicators of improved population health or of some kind of restraining effect that reduced the number of consultations of medical doctors and pharmacies. Wastewater-based epidemiology WBE is a well-established technique that provides information on human consumption and exposure to chemical residues at a community level. Commonly analysed chemicals include illicit drugs, ingredients of food, drink and tobacco, pharmaceuticals, pesticides, personal care products, and pollutants Choi et al. WBE involves systematically sampling of wastewater at the influent of wastewater treatment plants WWTPs and quantitation of informative markers therein. Useful markers include the consumed chemicals as well as biotransformation products thereof. The per capita consumption of specific compounds can be estimated by converting wastewater concentrations into loads, correcting for compound-specific pharmacokinetics, and normalizing to the size of the contributing population Jones et al. WBE has been particularly successful in studying spatial and temporal trends of illicit drug use Gonzalez-Marino et al. Spatial analysis can provide insights into the prevalence of drug use in different countries. For example, WBE results identify cocaine as the most prevalent and most frequently seized illicit stimulant in Southern and Western Europe, whereas amphetamines are reported as the most frequently consumed stimulants in northern and eastern countries Gonzalez-Marino et al. Temporal analysis is able to identify changes in drug use over time. For instance, in many European cities population-normalized mass loads of benzoylecgonine increased significantly between and indicating changes in cocaine consumption over years that might be related to changes in prevalence, consumption habits or drug purity Gonzalez-Marino et al. Generally, wastewater composition is a mirror of the society. WBE provides insights in population lifestyle, behaviour and health. Recent studies have linked WBE results with sociodemographic and socioeconomic descriptors and changes Choi et al. WBE was also able to detect and monitor changes induced by the Greek socioeconomic crisis Thomaidis et al. Thus, in the current crisis triggered by the coronavirus disease COVID pandemic, WBE holds the promise to support governments, health authorities, and other relevant stakeholders in understanding the diseases and its impact on different communities as well as in finding options going through and forward after the COVID pandemic Adam, To fight COVID pandemic, over countries worldwide had instituted either a full or partial lockdown, affecting billions of people. And many others had recommended restricted movement for some or all of their citizens. In the wake of the lockdown, a disturbance of the equilibrium of the market was expected. Disruption of demand and supply chains should have particularly affected the illicit drug market UNODC, Due to the shutdown of the hospitality industry and the cancelation of all kinds of events, changes in alcohol and tobacco consumption are also likely to occur. Additionally, based on lessons learned from the financial crisis, it is hypothesized that the COVID crisis will have further effects on public health, especially on mental health Brooks et al. Indeed, first reports from China Qiu et al. Changes are likely to alter wastewater compositions and loads of biomarkers that are analysed by WBE. Thus, the object of this work is to use the tools offered by WBE to identify direct and indirect effects of the current crisis on public health. In particular this study aims to identify trends in the use patterns of illicit and licit drugs during COVID lockdown and quarantine in the Tyrolean capital Innsbruck. This is one of the first studies addressing this research question by WBE. In order to achieve the aforementioned objective, the main illicit drugs together with important licit drugs, including alcohol, nicotine, caffeine as well as representatives of the classes of anaesthetics, antidepressants, anticonvulsants, anxiolytics, antihypertensives, analgesics and antibiotics, were investigated. Concentrations were converted to population normalized mass loads PNLs to identify temporal trends during the monitoring campaign. PNLs determined on days between March and January served as reference. The study included analysis of markers for the consumption of caffeine, tobacco and alcohol, for illicit drug use, as well as for the intake of prescription or non-prescription medications. The targeted compounds are summarized in Table 1. Overview on studied compounds including information on the correction factors used to calculate drug consumption. The correction factors were taken from the literature Castiglioni et al. Formic acid was purchased from Merck Darmstadt, Germany. Calibrators and internal standards were prepared daily from the individual solutions. Innsbruck was selected as model city to evaluate the usefulness of WBE for identifying changes in licit and illicit drug consumption. Innsbruck is the capital city of Austria's federal state Tyrol and the fifth-largest city of Austria, and has an actual population of about , inhabitants. The wastewater is collected in the city by a combined sewer system. Additionally, fourteen surrounding communities drain into the sewer system of Innsbruck, which is served by one WWTP. The total number of registered inhabitants in the catchment area is , Raw h composite wastewater samples were collected following a common protocol Castiglioni et al. The mode of sampling was volume-proportional. Sewer system characteristics and key parameters of the influent wastewater are summarized in Supplementary materials Table S1. Between and , samples were collected in seventeen sampling series covering 7—22 consecutive days each Supplementary materials Table S2. This allows investigating of temporal trends throughout the week, over the studied periods and particularly the lockdown period. Compound quantification was accomplished with five validated workflows Fig. Splitting was necessary to cover the range of compound concentrations and compound characteristics. Overview on the five validated analytical workflows used for quantification of 23 targeted compounds in raw h composite wastewater samples. Isotopically labelled analogues were used as internal standards Supplementary materials Table S3. After addition of internal standard solutions, aliquots of the raw wastewater samples were processed by either centrifugation EtS, caffeine, acetaminophen , evaporation cotinine , or solid-phase extraction SPE methods Fig. Details of the applied analytical methods are provided in Section S2 of the Supplementary material. All methods were validated in influent wastewater according to published guidelines Peters et al. Internal quality control included analysis of blank and spiked samples every 10 samples. External quality control involved the successful participation to inter-laboratory exercises van Nuijs et al. The reduced number of days covered by the later biomarkers is due to the fact that the corresponding analytical methods were introduced at a later stage of the monitoring process. Daily mass loads of biomarkers were calculated by multiplying their concentrations in the h composite samples with the corresponding daily flows of wastewater. Different hydrochemical parameters were evaluated for characterizing the WWTP catchment population. Details of this evaluation are provided in Section S4 of the Supplementary material. As COD is a routine, economical, and daily available parameter and the studied WWTP mainly receives wastewater from residential areas, we decided to use this parameter for real-time estimates of catchment population size. The mobility trends covered the following categories: a residential, b workplaces, c retail and recreation e. In this study, Innsbruck was selected as model city to evaluate the usefulness of WBE for identifying changes in licit and illicit drug consumption. Innsbruck and fourteen surrounding communities are served by one WWTP. Thus, the total number of registered inhabitants in the catchment area of the WWTP is , Because of the availability of a comprehensive set of WBE data, Innsbruck was perfectly suited for studying changes of lifestyle and behaviour during COVID pandemic. WBE of Innsbruck's wastewater started in March Until January , monitoring covered days organized in seventeen series. The available monitoring data served as baseline for evaluating the impact of lockdown and quarantine on licit and illicit drug consumption of the population living in the area of Innsbruck. Parts of the data have been submitted to the yearly international wastewater monitoring study focusing on the spatial comparison of drug consumption in Europe Gonzalez-Marino et al. This study indicates that Innsbruck's patterns are similar to those observed in other Western and Southern European cities. An overview on the ranges of compound-specific population normalized mass loads obtained during baseline monitoring March to January is given in Fig. The loads spanned 5 orders of magnitude. Caffeine was the most abundant compound tested, followed by acetaminophen, EtS and cotinine. Methamphetamine, and MDA were found on the lower end of the concentration range. MAM was not detected at all. Population normalized loads observed for the 23 targeted compounds between March and January The variability of the mass loads during the reference period can be expressed by the relative standard deviations RSD. The RSDs ranged from Large RSD values suggest the occurrence of changes in consumption over time, either weekly, seasonally or yearly trends, and these were mainly observed for the biomarkers of illicit drugs e. A time line covering the first two months of the COVID pandemic in Innsbruck including information on the wastewater sampling period and the temporal distribution of active cases, is provided in Fig. Timeline of the COVID lockdown in Tyrol, including information on a the wastewater sampling period to , b important government interventions, and c the number of acute cases. Beginning from 1 March , authorities in different European countries began identifying the Tyrolean ski resorts as major coronavirus hotspots. On 10 March , first steps towards lockdown were taken. On 16 March , the Austrian government implemented a lockdown to contain further spread of the disease. A nationwide curfew went into force. On 19 March , Tyrol as a whole was placed in quarantine. This quarantine ended on 7 April The nationwide curfew ended on 1 May The number of active cases started to raise exponentially at the beginning of March. The peak of the number of active cases was reached on 2 April By the end of April less than 0. Wastewater was sampled from 12 March to 15 April Thus, the study started four days before the lockdown began, covered the full quarantine period, and ended when the first steps to exit the lockdown were taken. Community mobility reports are a useful source of information to evaluate the impact of governmental interventions on social life and behaviour. The available data sets summarized the percent changes in visits to either places of residence, workplaces, places of retail and recreation, or places like grocery markets and pharmacies in March and April Supplementary materials Fig. As expected the governmental interventions i. All events were cancelled. Restaurants, bars, cafes and all kind of shops were closed. Only groceries and pharmacies were open. Inhabitants were not allowed to leave their main residences. Many companies introduced short-time working hours, and employees switched to home-based telework arrangements. Thus, Tyrolians were forced to spend more time at home. Traffic at workplaces, places of retail and recreation, as well as groceries and pharmacies was significantly reduced. It was expected that the described changes in social life and mobility would have affected consumption of licit and illicit drugs as well, and this should be detectable by WBE. Temporal trends in population normalized loads of a benzoylecgonine, b amphetamine, c MDMA, and d methamphetamine between March and April Coloured lines are representing the lockdown period. For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article. Weekly patterns in population normalized loads of a benzoylecgonine, b amphetamine, c MDMA, d ethyl sulfate, e cotinine, and f lidocaine during lockdown and the reference period March to January Like in other European cities Gonzalez-Marino et al. The largest growth rate was observed in A reduction was mainly observed during weekends Fig. Amphetamine use increased during Fig. The average PNL of amphetamine was During lockdown, the average PNL of amphetamine decreased to Consumption was reduced on all weekdays Fig. The largest effects were observed on weekends. PNLs of methamphetamine were found to be lower than 4. During lockdown, however, an average PNL of 5. Per capita intakes and consumed quantities are indicators for sales volumes on the illicit drug market. They are derived from PNLs. The results are summarized in Table 2. Cocaine was the most used illicit stimulant in Innsbruck. This is followed by amphetamine and MDMA. Methamphetamine was hardly consumed before lockdown. During lockdown, sales of cocaine, amphetamine and MDMA were reduced by 6. Consumed quantities of methamphetamine, on the other hand, were more than doubled. It is very likely that this compound was used as substitute for other stimulants. For the stimulants, the equilibrium of the market was disturbed during lockdown. Due to the shutdown of the hospitality industry and the cancelation of all kinds of events, a reduced demand for drug use in recreational settings was observed, and this affected sales of MDMA, cocaine, and amphetamine. Additionally, difficulties with the delivery e. With WBE, the consumption of other important illicit drugs, including cannabis, heroin and methadone, was studied as well. On the community level, lockdown had no effect on the consumed quantities of these compounds. Cannabis was the most used illicit drug in Innsbruck. During the complete sampling campaign, the average per capita intake of THC was MAM was used as biomarker for heroin consumption. Due to the facts that this compound is excreted in low amounts and shows limited stability in wastewater, we were not able to detect MAM in the collected samples. Methadone and EDDP served as biomarker for methadone consumption. The lockdown had no clear effect on methadone consumption. This observation is quite reasonable, as this drug is primarily used in opioid maintenance treatment. As expected, the results of Amsterdam and Castellon de la Plana were in line with our findings. In Helsinki, situation was different. WBE indicated that a record amount of amphetamine was being used during lockdown. By comparison, no major changes were observed for methamphetamine use. Known to mankind for several centuries, alcohol, tobacco and coffee have become an important part of culture, serving as a vehicle for social interaction, and shaping the urban landscape with dedicated places for sales and consumption. In western societies, ethanol, nicotine and caffeine are among the most prevalent psychotropic drugs. Their consumption can be studied with WBE. The weekly patterns of ethyl sulfate and cotinine are shown in Fig. Ethyl sulfate was used as biomarker for estimating alcohol consumption. This compound is stable and detectable in wastewater Reid et al. For Innsbruck, a strong weekly consumption pattern was observed Fig. PNL-values of ethyl sulfate were higher during weekend than during weekdays. Alcohol consumption was reduced on all weekdays. Cotinine served as biomarker for estimating nicotine and tobacco consumption, respectively Castiglioni et al. There was no statistically significant difference in PNLs between weekdays and sampling periods Fig. For the complete sampling campaign, the average nicotine intake was calculated to be 4. The wastewater data correlates well to Austrian sales figures. According to official data provided by the Austrian Statistical Office, 3. By using the average amount of cotinine excreted by a smoker, the share of smokers in Innsbruck's population can be assessed. If a smoker excretes about 2. From to , the average PNL of caffeine was During lockdown, the PNL slightly increased to The difference, however, was not statistically significant. Temporal trends in population normalized loads of a caffeine, b oxazepam, c morphine, d codeine e acetaminophen, and f trimethoprim during lockdown. The population normalized loads determined between March and January were used as reference. Regarding the consumption of alcohol, nicotine and caffeine, the governmental interventions during lockdown mainly affected consumption of alcohol. With the shutdown of the hospitality industry, the cancelation of all kinds of events and the prohibition of any kind of social interaction with non-family members, common places and occasions for social drinking of alcoholic beverages were not available during quarantine. In Austria, social drinking accounts for approximately one third of the total amount of consumed alcohol Bachmayer et al. Consumed quantities of tobacco and coffee were hardly affected. Maybe, for these two licit drugs, reduced social consumption was compensated by an increased use in the private setting. Ten biomarkers of pharmaceutical compounds were quantified in the collected wastewater samples. These included oxazepam, venlafaxine, carbamazepine, metoprolol, morphine, tramadol, lidocaine, acetaminophen, codeine, and trimethoprim. The patterns of use for the monitored compounds between the different sampling periods were evaluated. The weekly pattern of lidocaine is shown in Fig. Lidocaine is primarily used as local anaesthetic. The efficacy profile of lidocaine is characterized by a rapid onset of action and intermediate duration of efficacy. Therefore, lidocaine is suitable for infiltration, block, and surface anaesthesia as single dose applications. Lidocaine is commonly used in dentistry. As the working week of dentists usually ends on Friday, a strong weekly consumption pattern was observed Fig. There was no statistically significant difference in PNLs between sampling periods. The average PNLs of lidocaine were Oxazepam, venlafaxine, carbamazepine were regarded as markers for changes in mental health treatment during lockdown. Oxazepam is a benzodiazepine that is used in the treatment of anxiety and insomnia. Furthermore, it is a metabolite of diazepam, prazepam, and temazepam. Venlafaxine is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class that is used in the treatment of major depressive disorder, generalized anxiety disorder, panic disorder, and social phobia. Carbamazepine is an anticonvulsant that is primarily used in the treatment of epilepsy and neuropathic pain. Furthermore, it is used in schizophrenia along with other medications and as a second-line agent in bipolar disorder. However, such measures pose a challenge for mental health Pfefferbaum and North, Especially, people who contract the disease, those at heightened risk for it, people with pre-existing psychiatric problems, and health care providers are vulnerable to emotional distress. Possible emotional outcomes include stress, depression, insomnia, fear, anger, and frustration Brooks et al. Nevertheless, WBE provided no evidence for increased use of nervous system drugs in Innsbruck during the early weeks of lockdown. Nevertheless, individual PNL-values during lockdown did not follow a trend. There is evidence that lockdown and quarantine had an impact on mental health of both individuals and communities. Nevertheless, at least during quarantine, WBE results for Innsbruck did not support this hypothesis. An explanation for the observed discrepancy was provided recently. In the early weeks of the COVID lockdown in Austria, the total number of patients treated on average per week was lower than in the months before Probst et al. The indicated undersupply of psychotherapy might have prevented rise of prescribed drug consumption at the community level. Metoprolol is a beta blocking agent that is used for a number of conditions, including hypertension, angina, acute myocardial infarction, supraventricular tachycardia, ventricular tachycardia, congestive heart failure, and prevention of migraine headaches. In this study, metoprolol was regarded as marker for changes in the treatment of cardiovascular diseases during lockdown. No statistically significant difference in PNLs before and during lockdown was observed. Furthermore, no trend could be identified over time for the PNL of metoprolol during lockdown monitoring. Acetaminophen, codeine, tramadol and morphine are analgesics. Codeine is a step 2 medication. Step 2 adds a moderate opioid agonist in combination with non-opioids e. They are used to treat moderate-severe and often chronic pain. Morphine is further applied for drug maintenance therapy in opioid-dependent individuals. As the PNL of morphine showed no trend during quarantine monitoring Fig. Tramadol is the other step 3 analgesic monitored. Codeine and acetaminophen represent analgesics that are used for a limited duration. The PNL graphs of these two compounds showed specific characteristics Fig. It is unclear whether the higher demand was directly linked with the COVID crisis or with another seasonal disease e. An interesting observation was that the PNLs showed a decline during the quarantine period. WBE indicates a decline of the consumption of analgesics used for short-term pain management during the quarantine period. An important class of this type of medication is nonsteroidal anti-inflammatory drugs, such as aspirin and ibuprofen. Their use has been associated with potentially serious dose-dependent gastrointestinal complications such as upper gastrointestinal bleeding Butt et al. Interestingly, a recent report from Austria indicated that national lockdown resulted a decrease in upper gastrointestinal bleeding events Schmiderer et al. The authors speculated that reduced visits to emergency departments as well as reduced stress factors could have played a role. Our results provided an additional explanation: reduced consumption of analgesics. Trimethoprim is an antibiotic that is mainly used to treat urinary tract infections. WBE showed that the use of pharmaceuticals for short-term application i. For pharmaceuticals in long-term use i. Community mobility reports demonstrated that traffic at pharmacies was significantly reduced during quarantine Supplementary materials Fig. The different indicators provided evidence for an impact of lockdown and quarantine on drug consumption patterns. Further work will be necessary to clarify if these changes are linked with the population health status. Currently, it cannot be answered whether people stayed at home with various diseases which would have required treatments or in contrast change in lifestyle during lockdown with social distancing resulted in less disease. This study is a first attempt to investigate the impact of COVID lockdown and quarantine on use patterns of illicit drugs, ingredients of drinks and tobacco, as well as pharmaceuticals with WBE. Certain limitations are noted with respect to the interpretation of results. Various sources of uncertainty are associated in each step of the analytical process: sampling, chemical analysis, wastewater flow measurement, excretion rate, and population estimation. Systematic uncertainties, e. COD-values were used for population size estimation. COD is a routine, economical, and daily available parameter. There are hints that COD-derived values might overestimate population size see Section S4 of the Supplementary material. As the population size was used for normalization, calculated per capita loads and consumptions might have been underestimated. Nevertheless, based on the outcome of this and other studies Gao et al. The impact of in-sewer processes leading to an underestimation of drug loads is not known for all chemicals tested in this study. We have applied optimized and validated analytical workflows. Nevertheless, without the availability of reference material, the occurrence of systematic errors caused by environmental factors, sample preparation and analyses cannot completely be ruled out, and this was recently demonstrated for WBE of cannabis Causanilles et al. Unconsumed drugs dumped into sewers would lead to elevated loads. Dumping was indicated by unexpected high loads on a certain day in comparison to all other monitored days as well as by shifts of parent drug to metabolite ratios e. MDMA, cocaine, and methadone. Such data points were removed from statistical analysis. Random uncertainties may affect the assessment of temporal changes. This problem, however, should have been overcome by using a sufficient number of monitoring days to characterize drug consumption before and during lockdown. The load of a biomarker in wastewater does not give insight into the prevalence of its excretion in the population sampled. Identical loads can either result from the same number of people exposed to the chemical at the same level or a fewer number of people exposed at a higher level. This is a limitation of the method but it is an advantage from an ethical viewpoint to ensure the anonymity of individuals in the catchment area. Temporal trends were identified by determining PNLs of 23 markers. Particularly, changes in the consumption patterns of recreational drugs and pharmaceuticals for short-term application were detected. Consumption patterns of drugs for long-term application i. Due to the shutdown of the hospitality industry and the cancelation of all kinds of events, a reduced demand for drug use in recreational settings was observed, and this affected sales of alcohol, cocaine, MDMA, and amphetamine. Additionally, difficulties with the delivery of stimulants e. The observed decline in the use of pharmaceuticals for short-term application i. Clearly, the results demonstrate that WBE can be used to identify quarantine-induced changes in lifestyle, behaviour and health that are associated with the consumption of specific chemicals or food components. HO elaborated conception and design of this study. All authors contributed to data acquisition and analysis. VR and HO wrote a first version of the manuscript. All authors were involved in drafting and revising the manuscript. All authors have read and approved the final manuscript. 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. This manuscript is dedicated to Klemens Geiger who was an important promotor of the local WBE initiative. 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. Sci Total Environ. Find articles by Vera Reinstadler. Find articles by Verena Ausweger. Find articles by Anna-Lena Grabher. Find articles by Marco Kreidl. Find articles by Susanne Huber. Find articles by Julia Grander. Find articles by Sandra Haslacher. Find articles by Klaus Singer. Find articles by Michael Schlapp-Hackl. Find articles by Manuel Sorg. Find articles by Harald Erber. Find articles by Herbert Oberacher. Open in a new tab. Amphetamine Amphetamine 3. Carbamazepine Carbamazepine 7. Morphine Morphine n. Tramadol Tramadol n. Trimethoprim Trimethoprim n. Venlafaxine Venlafaxine n. Compound Average per capita intake before lockdown Average per capita intake during lockdown Average quantities consumedbefore lockdown Average quantities consumedduring lockdown Cocaine 1. 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.