key: cord-0968303-rlfhpzpe authors: Shah, Shimoni; Gwee, Sylvia Xiao Wei; Ng, Jamie Qiao Xin; Lau, Nicholas; Koh, Jiayun; Pang, Junxiong title: Wastewater surveillance to infer COVID-19 transmission: A systematic review date: 2021-09-08 journal: Sci Total Environ DOI: 10.1016/j.scitotenv.2021.150060 sha: 986761f2a1f56611c9442f497574e5d6bc907438 doc_id: 968303 cord_uid: rlfhpzpe Successful detection of SARS-COV-2 in wastewater suggests the potential utility of wastewater-based epidemiology (WBE) for COVID-19 community surveillance. This systematic review aims to assess the performance of wastewater surveillance as early warning system of COVID-19 community transmission. A systematic search was conducted in PubMed, Medline, Embase and the WBE Consortium Registry according to PRISMA guidelines for relevant articles published until 31st July 2021. Relevant data were extracted and summarized. Quality of each paper was assessed using an assessment tool adapted from Bilotta et al.'s tool for environmental science. Of 763 studies identified, 92 studies distributed across 34 countries were shortlisted for qualitative synthesis. A total of 26,197 samples were collected between January 2020 and May 2021 from various locations serving population ranging from 321 to 11,400,000 inhabitants. Overall sample positivity was moderate at 29.2% in all examined settings with the spike (S) gene having maximum rate of positive detections and nucleocapsid (N) gene being the most targeted. Wastewater signals preceded confirmed cases by up to 63 days, with 13 studies reporting sample positivity before the first cases were detected in the community. At least 50 studies reported an association of viral load with community cases. While wastewater surveillance cannot replace large-scale diagnostic testing, it can complement clinical surveillance by providing early signs of potential transmission for more active public health responses. However, more studies using standardized and validated methods are required along with risk analysis and modelling to understand the dynamics of viral outbreaks. Wastewater surveillance, commonly used to monitor the epidemiology of poliovirus and noroviruses, is a potential approach for community surveillance of COVID-19 1 . Established evidence on fecal shedding of SARS-COV-2 by patients and successful virus genomic detection in wastewater studies suggest the applicability of this surveillance technique 2 . Monitoring of sewage for detecting pathogens has been ongoing for over 40 years especially for poliovirus 3 . Past studies have established that small outbreaks and epidemics of enterovirus and adenovirus disease within a community can be predicted by monitoring a community"s sewage 3 . Virus during a Coxsackievirus B5 outbreak was detected 10 days before clinical cases were detected while the Public Health Laboratories of Israel have been conducting an environmental surveillance of sewage to assess the spread of wild type poliovirus, on a monthly basis since 1989 4, 5 . This helped in the detection of the most recent outbreak of wild poliovirus type 1 in 2013-14 in Rahat, Israel 6 . Sensitivity of sewage surveillance has also been validated in Mumbai, India wherein the wild type poliovirus was detected three months before any clinical cases were observed 7 . Viruses causing gastroenteritis can also be detected in wastewater with only a few infected people. Hellmer et al., concluded that detection of pathogenic viruses in sewage provided early warnings of Hepatitis A virus and Norovirus outbreaks even before the causative pathogens were recognized in health care 8, 9 . Wastewater surveillance can also help predict The ongoing COVID-19 pandemic is caused by newly diagnosed SARS-CoV-2 virus, which has been detected in feces and urine of infected patients 11 . One of the public health challenges in this pandemic has been to implement high coverage and timely COVID-19 testing on populations, and the mainstay has been to conduct laboratory-based diagnostic testing on individuals, whether be it with Polymerase Chain Reaction (PCR) or serological tests. The use of wastewater surveillance as an early warning system to monitor the appearance and resurgence of COVID-19 is commonly suggested along with its use is in tailoring containment and mitigation measures and determining target populations for testing 12 . Wastewater surveillance has a potential advantage of being able to predict the overall status of a given catchment area and being able to include asymptomatic individuals with much less effort compared to clinical surveillance. Given the median duration of virus persistence in feces exceeds that in respiratory samples 2 , the probability of viral RNA detection in wastewater may be greater than clinical testing. Wastewater surveillance can complement the surveillance pyramid by providing mass monitoring via a low-cost, efficient and non-invasive approach. It can also shed light on prevalence rates "hidden" by asymptomatic infections, poor health-seeking behaviour as well as in settings with low diagnostic capacity 13 . There is still limited systematic synthesis of the progress made in applying wastewater surveillance to monitor COVID-19 trends exclusively, but rather reviews on the different methodologies used by various research groups and application of wastewater surveillance for SARS-CoV-2 along with other waterborne pathogens 14, 15 . While we came across 22 reviews in our search, only one review by Li. et al was a systematic review conducted until Jan 2021. 16 , This systematic review can complement Li et al."s work and assess the performance of wastewater surveillance in conducting qualitative or quantitative risk assessment of COVID-19 community cases until July 2021, to help understand the potential of wastewater surveillance in driving public health decisions. positive samples. Three papers that examined samples from aviation settings, specifically two from aircrafts and one from airport, found 34 positive samples from 212 samples 76, 77, 91 . In the sole paper that sampled cruise ships, Ahmed samples; 89.5%) was targeted, this should be interpreted with caution as the data was only obtained from two studies 67, 90 . N genes remain the most commonly used gene targets in samples taken from settings outside of the conventional sewage system. Maximum sample positivity outside of the conventional sewage system was seen in ORF1ab (12/20; 42 ,500,000 inhabitants as well as targeted areas like university, residential area, cruise, airlines and hospitals. Although the performance of wastewater surveillance in settings outside conventional sewage system was better (34.8% vs. 28 .9%) than conventional sewage system, number of samples in the latter were far more that the former (24,862 vs. 1,335) . On the note of ethical considerations, wastewater surveillance seems better suited for larger catchment areas as focusing on targeted and high risk areas allows population to be easily identified 14 . In case of wastewater surveillance for pharmaceuticals, it is generally accepted that populations over > 10,000 can be considered to give anonymity and posing no risk to smaller groups of people 111 . However, targeting confined sub-populations within high-risk facilities may provide clearer indication of infection source as opposed to widespread geographical testing. Key high-risk facilities such as schools, dormitories, nursing homes that entail frequent prolonged close interactions between individuals have been shown to promote COVID-19 outbreaks [112] [113] [114] . In this study, SARS-CoV-2 was detected in the targeted surveillance of hospitals (65.1%), university settings (27.7%), residential buildings/regions (63.6%) and nursing home (33.3%) . Notably, in their study on hospital wastewater, Gonçalves et al. reported positive signals in wastewater in the presence of only one hospitalised COVID-19 case 80 . Persistent positive signals were detected in the hospital"s wastewater throughout the study period, which saw only a maximum of four hospitalised COVID-19 patients at its peak, 80 suggesting high sensitivity of facility based sewage sampling. Similar findings were reported by Betancourt et al. and Xu et al., which detected the presence of SARS-CoV-2 even before the first case surfaced in the facilities 24, 73 . Targeted surveillance of living facilities can also sieve out sub-populations underserved by healthcare due to unavailability of healthcare services or avoidance in seeking healthcare 112 . Given that sewage can be diluted by rain or industrial discharge running into the sewer network 115 , infection prevalence deduced from WWTP samples may be underestimated J o u r n a l P r e -p r o o f without proper accountancy of these factors during analysis. Nevertheless, it would still be challenging to interpret the wastewater samples tested positive as potential transmission when there are known reported recovered cases who have returned back into these targeted non-healthcare facilities 2, 68 . Inadequate sewage infrastructure in developing countries can hinder the application of wastewater surveillance, further stunting surveillance efforts in the very countries that ought to reap the most benefit from this cost-effective surveillance approach. Several constraints in sanitation infrastructure of developing countries challenge the representativeness of wastewater surveillance, such as high proportions of households not being connected to the sewage network, underperformance of WWTP, dysfunctional operational facilities, and mismanagement of sewage. Surveillance approaches that typically begin with sampling influent of WWTP is not representative of actual disease prevalence in developing countries [116] [117] [118] . Despite several studies based in developing countries, these limitations were insufficiently addressed. Only a single paper included in this review focused on SARS-CoV-2 surveillance in low sanitation settings, detecting three positive samples out of three samples collected from rivers receiving untreated sewage in Ecuador. Approaches should be contextualized to consider both areas served and not-served by sewage networks to present an accurate picture of estimated prevalence 119 . More investigation of wastewater surveillance approach in developing/low-income settings is warranted. Positive samples were detected as early as two months before the first case was clinically identified 120 . Virus shedding in feces is suggested to occur five days prior to symptom onset and last up to 17.2 days 121, 122 . COVID-19 has a short serial interval of 3-8 days, given that SARS-CoV-2 reportedly has an incubation period of 5.6 days, it suggests that transmission typically occurred before or near symptom onset [123] [124] [125] [126] . In this review, Kuryntseva et al. J o u r n a l P r e -p r o o f detected SARS-CoV-2 in wastewater discharged from Kazan Federal University Buildings when nobody reported illness, five days before the first COVID-19 case was registered 87 while dormitories in the USA and residential buildings in Hong Kong reported positive samples 2-4 days before the first case surfaced. Four cases were detected within seven days after investigation, demonstrating fecal shedding of virus in pre-symptomatic individuals. Studies included in this review typically reported anticipation of COVID-19 cases 16 days prior to clinical detection (≤10 days; 24 studies, ≥14 days; 8 studies), which provides adequate time for containment measures to be put in place to prevent an imminent cluster/outbreak given the short serial interval of COVID-19. However, there were studies that did not report any positive detection before cases were clinically reported in the community 91, 99, 103 , or detection was only observed when there were higher incidence rate reported 84, 92, 94, 105 . This phenomenon may be due to the fact that only about 50% of the infected cases would shed viruses in the excreta 127 . Reports of SARS-CoV-2 signals in wastewater at the beginning of the COVID-19 pandemic should be interpreted with caution given the initial delay in establishing targeted assays and laboratory surveillance for a novel virus. All papers reported SARS-CoV-2 detection with viral load ranging from 1 to 4.8 x 10 9 gene copies per liter of wastewater, overall sample positivity was relatively low at 29.2%. Detection of SARS-CoV-2 signals in wastewater depends on viral load present and sensitivity of detection assays. Hata et al. reported that SARS-CoV-2 was detectable in WWT if one in 100,000 persons sheds 10 9 copies/g-feces in 200 g of feces, and the success of wastewater surveillance is dependent on the viral load in feces and the detection limit of the method of analysis, estimated as 2 copies/mL in wastewater using the RT-qPCR assay 120 . Evidence from two meta-analyses demonstrated pooled virus detection in stool of 40.5% and 48.1% of patients respectively 128, 129 . Higher detection rates were also reported in females, those with J o u r n a l P r e -p r o o f gastrointestinal symptoms and more severe disease 130 . Such differential viral shedding profiles in feces further challenge the representation of disease prevalence deduced by wastewater surveillance. On this note, targeting endogenous biomarkers instead of utilizing clinical diagnostic testing platforms can potentially mitigate the aforementioned limitations 112 . The accuracy of disease prevalence captured can be potentially improved with the identification of infection markers that are more likely to be universally excreted in either urine or feces. An example of its potential is provided by a preprint published on medRxiv, which reported heighted sensitivity by assaying viral proteins using Multiplex Pairedantibody Amplified Detection 131 . Since significant inflammation is typically induced in severe patients, the identification of appropriate endogenous markers warrant deeper biomarker evaluation 116 , especially for universal indicators applicable to mild cases. Apart from cost reduction from lowered reliance on SARS-CoV-2 immuno-and molecular assays 112 , false negativity caused by low viral load falling below assay detection and analytical limits can be mitigated. Other plausible benefits include earlier alerts supplemented by infection indicators and simplified sampling and processing workflow from using biomarkers present in urine 112 . Process efficiency is a major challenge as little is known of the recovery efficiency of SARS-CoV-2 132 . Beyond proving SARS-CoV-2 detection in wastewater, several studies were driven by the need to propose an adequate workflow to optimise recovery efficiency, comparing the use of different concentration methods adapted from surveillance of other pathogenic viruses, primers and probes for detection 104, 105 . Nineteen studies included in this review trialed more than one virus concentration protocol to evaluate performance differences. The most commonly used approaches were ultrafiltration (34 studies) and polyethylene glycol (PEG) precipitation (31 studies 31 . This suggests that wastewater surveillance can potentially serve as an "early warning system" to monitor trends of SARS-CoV-2 transmission; however, more papers need to look at sensitivity and positive predictive value to allow a meta-analysis providing more robust evidence. Finally, this review piloted the first tool to assess the risk of bias in wastewater surveillance studies across the domains of study design, outcome measurement and clarity/publication bias. Our risk of bias assessment highlighted the urgent need for more well-established J o u r n a l P r e -p r o o f guidance in the aspects of study design, execution and interpretation of wastewater surveillance studies for use globally and to allow robust meta-review. The importance of such an assessment lies in its potential to explain heterogeneity in findings and the ability to grade the strength of evidence presented by studies, which can influence the interpretation of results synthesized 137 . This assessment tool can 1) provide a platform to guide the consistency of future research design and presentation, which can help strengthen the conclusions made by future systematic reviews; 2) can act as a foundation for the refinement of future risk of bias assessments. This review is limited by the usage of solely qualitative synthesis due to the largely descriptive nature of existing literature. Units in which the viral load in various papers were presented were inconsistent and did not allow for meta-analysis. It is recommended to present it in terms of the daily loads per capita (mg/day/1000 inhabitants) to allow comparisons between cities in different geographic locations, and to be able to normalize the findings 120 . Furthermore, there is also no consistent guidance on the definition of a positive wastewater result, either based on a significantly high viral load cut-off value and/or a consecutive number of days with wastewater sampling tested positive. There is a lack of systematic methods in existing literature to assess association between COVID-19 cases and wastewater signals as well as the accuracy of this wastewater testing over a fixed period of time. Ideally, the association between COVID-19 incidence and wastewater signals should be based on daily regular surveillance of the wastewater and the weekly PCR nasopharyngeal swab test of the susceptible (naïve) population of interest. Though funnel plot analysis for publication bias assessment was not feasible in this review, it would be prudent to assume that most, if not all, J o u r n a l P r e -p r o o f studies with negative findings on their wastewater testing and its association with COVID-19 incidences, would be challenging to publish when making interpretation from this review. Sample positivity was moderately high with respect to the nucleocapsid gene amidst low rates of sample positivity seen amongst studies overall. While wastewater surveillance omits the factors of time consumption, cost, exposure risk, and avoids the biases of epidemiological indicators arising from limitations in the healthcare system, such as diagnostic testing capacity, symptomatic testing and hospitalization lags, it does not provide a true quantitative estimation of the number of people who are infected in the population. More studies using accurate and validated methods are required along with risk analysis and modelling to understand the dynamics of viral outbreaks. Future studies need to present their findings in a more consistent mannerprovide clarity of sampling approach and sampling sites, virus detection and quantification process, use of laboratory controls and genetic targets in addition to mere reporting of sample positivity so as to guide and enable valid comparisons of study design. Guidance should also be provided on analysis methods to enable standardized, statistically robust association of findings with community/clinical data. As countries embrace the emerging SARS-CoV-2 variant of concerns, wastewater surveillance can complement clinical surveillance by providing signs of potential transmission for more active public health responses. It is clear that an increase in SARS-CoV-2 concentration has been consistently associated with an increased number of COVID-19 infections (weekly). (Model) An increase in the SARS-CoV-2 concentration in the current week implies a steadily increase in the COVID-19 cases in the following three weeks and with the maximum impact occur in the third week. Then the impact will go down and eventually disappear after 6 weeks in the future. An increase in the SARS-CoV-2 concentration in the current week implies a steadily increase in the COVID-19 cases in the following three weeks, peaking in the third week. The index case (Case 1) returned from the healthcare facility on 8 July 2020 after clinical recovery. Therefore, wastewater signals detected on 9 July 2020 could be either due to viral shedding from the newly identified case (Case 10) or from the returned index case. SARS-CoV-2 levels declined after the newly identified case was conveyed to a healthcare facility (1100-39,400 to 600-1700 RNA copies/L sewage from 10 to 13 July 2020). SARS-CoV-2 levels increased again during 15-16 July 2020 (3900-28,300 RNA copies/L sewage) and was attributed to two recovered cases who returned on 14 July 2020. SARS-CoV-2 levels were not detected from the evening of 19 July 2020, corroborating the viral shedding pattern of recovered cases and the cessation of active virus transmission in the building. Wastewater viral titers generally mirrored trends in disease incidence: an exponential rise from March to mid-April, a decline through July, a slow increase over the summer, followed by a sharper increase in the fall and second peak in the winter. Trends in wastewater data differed from clinical data after some key events; a short peak in wastewater viral titers at the start of August, which was only slightly reflected in the clinical data; after colleges and universities welcomed students back in late August/early September, we observed another peak in wastewater viral titers, but not in clinical cases; after the start of Phase 3 Step 2 reopening, wastewater viral titers increased steeply, while clinical cases had a shallower slope. WW data more sensitive than clinical data. 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wastewaters and rivers SARS-CoV-2 RNA in wastewater anticipated COVID-19 occurrence in a low prevalence area Metropolitan wastewater analysis for COVID-19 epidemiological surveillance Preliminary results of SARS-CoV-2 detection in sewerage system in Niterói municipality Measurement of SARS-CoV-2 RNA in wastewater tracks community infection dynamics Temporal Detection and Phylogenetic Assessment of SARS-CoV-2 in Municipal Wastewater Presence of SARS-Coronavirus-2 RNA in Sewage and Correlation with Reported COVID-19 Prevalence in the Early Stage of the Epidemic in The Netherlands Tracking SARS-CoV-2 in Sewage: Evidence of Changes in Virus Variant Predominance during COVID-19 Pandemic SARS-CoV-2 has been circulating in northern Italy since First detection of SARS-CoV-2 in untreated wastewaters in Italy A simplified approach to monitoring the COVID-19 epidemiologic situation using waste water analysis and its application in Russia First proof of the capability of wastewater surveillance for COVID-19 in India through detection of genetic material of SARS-CoV-2 Sentinel™ Wastewater Test Provide Early Warning of a potential COVID-19 outbreak Detection of SARS-CoV-2 in wastewater in Japan during a COVID-19 outbreak Detection and quantification of SARS-CoV-2 RNA in wastewater and treated effluents: Surveillance of COVID-19 epidemic in the United Arab Emirates First environmental surveillance for the presence of SARS-CoV-2 RNA in wastewater and river water in Japan SARS-CoV-2 in river water: Implications in low sanitation countries COVID-19 surveillance in Southeastern Virginia using wastewater-based epidemiology The presence of SARS-CoV-2 RNA in human sewage in Santa Catarina, Brazil Quantitative analysis of SARS-CoV-2 RNA from wastewater solids in communities with low COVID-19 incidence and prevalence Sewage surveillance for the presence of SARS-CoV-2 genome as a useful wastewater based epidemiology (WBE) tracking tool in India First confirmed detection of SARS-COV-2 in untreated municipal and aircraft wastewater in Dubai, UAE: The use of wastewater based epidemiology as an early warning tool to monitor the prevalence of COVID-19 Detection of SARS-CoV-2 RNA in commercial passenger aircraft and cruise ship wastewater: a surveillance tool for assessing the presence of COVID-19 infected travellers First confirmed detection of SARS-CoV-2 in untreated wastewater in Australia: A proof of concept for the wastewater surveillance of COVID-19 in the community Detection of SARS-CoV-2 RNA in hospital wastewater from a low COVID-19 disease prevalence area A multicenter study investigating SARS-CoV-2 in tertiary-care hospital wastewater. viral burden correlates with increasing hospitalized cases as well as hospital-associated transmissions and outbreaks Longterm monitoring of SARS-CoV-2 RNA in wastewater of the Frankfurt metropolitan area in Southern Germany SARS-CoV-2 RNA monitoring in wastewater as a potential early warning system for COVID-19 transmission in the 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of COVID-19 in the Metropolitan Area of Assessing sensitivity and reproducibility of RT-ddPCR and RT-qPCR for the quantification of SARS-CoV-2 in wastewater Development of Wastewater Pooled Surveillance of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) from Congregate Living Settings Catching a resurgence: Increase in SARS-CoV-2 viral RNA identified in wastewater 48 h before COVID-19 clinical tests and 96 h before hospitalizations Wastewater monitoring outperforms case numbers as a tool to track COVID-19 incidence dynamics when test positivity rates are high SARS-CoV-2 in Human Sewage and River Water from a Remote and Vulnerable Area as a Surveillance Tool in Brazil Early-pandemic wastewater surveillance of SARS-CoV-2 in Southern Nevada: Methodology, occurrence, and incidence/prevalence considerations Implementing building-level SARS-CoV-2 wastewater surveillance on a university campus Monitoring of SARS-CoV-2 RNA in wastewater as an epidemiological surveillance tool in Mendoza, Argentina SARS-CoV-2 RNA in Wastewater Settled Solids Is Associated with COVID-19 Cases in a Large Urban Sewershed Monitoring SARS-CoV-2 in municipal wastewater to evaluate the success of lockdown measures for controlling COVID-19 in the UK The detection and stability of the SARS-CoV-2 RNA biomarkers in wastewater influent in Helsinki, Finland Estimating the minimum number of SARS-CoV-2 infected cases needed to detect viral RNA in wastewater: To what extent of the outbreak can surveillance of wastewater tell us? Qualitative and quantitative detection of SARS-CoV-2 RNA in untreated wastewater in Western Cape Province, South Africa High-Throughput Wastewater SARS-CoV-2 Detection Enables Forecasting of Community Infection Dynamics in San Diego County Efficient detection of SARS-CoV-2 RNA in the solid fraction of wastewater Wastewater monitoring as a supplementary surveillance tool for capturing SARS-COV-2 community spread. A case study in two Greek municipalities Unravelling the early warning capability of wastewater surveillance for COVID-19: A temporal study on SARS-CoV-2 RNA detection and need for the escalation Wastewater surveillance-based city zonation for effective COVID-19 pandemic preparedness powered by early warning: A perspectives of temporal variations in SARS-CoV-2-RNA in Ahmedabad Fine-Scale Temporal Dynamics of SARS-CoV-2 RNA Abundance in Wastewater during A COVID-19 Lockdown Predictive power of SARS-CoV-2 wastewater surveillance for diverse populations across a large geographical range A direct capture method for purification and detection of viral nucleic acid enables epidemiological surveillance of SARS-CoV-2 Assessing spatial distribution of COVID-19 prevalence in Brazil using decentralised sewage monitoring Monitoring changes in COVID-19 infection using wastewater-based epidemiology: A South African perspective Wastewater-based epidemiology as a useful tool to track SARS-CoV-2 and support public health policies at municipal level in Brazil Moore swab performs equal to composite and outperforms grab sampling for SARS-CoV-2 monitoring in wastewater Ahead of the second wave: Early warning for COVID-19 by wastewater surveillance in Hungary Monitoring waves of the COVID-19 pandemic: Inferences from WWTPs of different sizes Surveillance of wastewater revealed peaks of SARS-CoV-2 preceding those of hospitalized patients with COVID-19 COVID-19 (SARS-CoV-2) outbreak monitoring using wastewater-based epidemiology in Qatar Targeted wastewater surveillance of SARS-CoV-2 on a university campus for COVID-19 outbreak detection and mitigation SARS-CoV-2 detection in sewage samples: Standardization of method & preliminary observations Feasibility of neighborhood and building scale wastewater-based genomic epidemiology for pathogen surveillance The first detection of SARS-CoV-2 RNA in the wastewater of Tehran SARS-CoV-2 RNA detected in urban wastewater from Porto, Portugal: Method optimization and continuous 25-week monitoring Tracking COVID-19 with wastewater to understand asymptomatic transmission Correlation of SARS-CoV-2 RNA in wastewater with COVID-19 disease burden in sewersheds Co-quantification of crAssphage increases confidence in wastewaterbased epidemiology for SARS-CoV-2 in low prevalence areas Rapid Increase of SARS-CoV-2 Variant B.1.1.7 Detected in Sewage Samples from England between Non-intrusive wastewater surveillance for monitoring of a residential building for COVID-19 cases Wastewater surveillance of SARS-CoV-2 across 40 U.S. states from Viral RNA in City Wastewater as a Key Indicator of COVID-19 Recrudescence and Containment Measures Effectiveness Evaluation of lockdown effect on SARS-CoV-2 dynamics through viral genome quantification in waste water Metrics to relate COVID-19 wastewater data to clinical testing dynamics The first case study of wastewaterbased epidemiology of COVID-19 in Hong Kong City-level SARS-CoV-2 sewage surveillance COVID-19 WEEKLY SURVEILLANCE IN NSW -EPIDEMIOLOGICAL WEEK 40 COVID-19 WEEKLY SURVEILLANCE IN NSW -EPIDEMIOLOGICAL WEEK 41 COVID-19 WEEKLY SURVEILLANCE IN NSW -EPIDEMIOLOGICAL WEEK 42 COVID-19 WEEKLY SURVEILLANCE IN NSW -EPIDEMIOLOGICAL WEEK 43