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Open accessJournal ArticleDOI: 10.1128/MSYSTEMS.00045-21

High-Throughput Wastewater SARS-CoV-2 Detection Enables Forecasting of Community Infection Dynamics in San Diego County

02 Mar 2021-Vol. 6, Iss: 2, pp 02
Abstract: Large-scale wastewater surveillance has the ability to greatly augment the tracking of infection dynamics especially in communities where the prevalence rates far exceed the testing capacity. However, current methods for viral detection in wastewater are severely lacking in terms of scaling up for high throughput. In the present study, we employed an automated magnetic-bead-based concentration approach for viral detection in sewage that can effectively be scaled up for processing 24 samples in a single 40-min run. The method compared favorably to conventionally used methods for viral wastewater concentrations with higher recovery efficiencies from input sample volumes as low as 10 ml and can enable the processing of over 100 wastewater samples in a day. The sensitivity of the high-throughput protocol was shown to detect 1 asymptomatic individual in a building of 415 residents. Using the high-throughput pipeline, samples from the influent stream of the primary wastewater treatment plant of San Diego County (serving 2.3 million residents) were processed for a period of 13 weeks. Wastewater estimates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral genome copies in raw untreated wastewater correlated strongly with clinically reported cases by the county, and when used alongside past reported case numbers and temporal information in an autoregressive integrated moving average (ARIMA) model enabled prediction of new reported cases up to 3 weeks in advance. Taken together, the results show that the high-throughput surveillance could greatly ameliorate comprehensive community prevalence assessments by providing robust, rapid estimates.IMPORTANCE Wastewater monitoring has a lot of potential for revealing coronavirus disease 2019 (COVID-19) outbreaks before they happen because the virus is found in the wastewater before people have clinical symptoms. However, application of wastewater-based surveillance has been limited by long processing times specifically at the concentration step. Here we introduce a much faster method of processing the samples and show its robustness by demonstrating direct comparisons with existing methods and showing that we can predict cases in San Diego by a week with excellent accuracy, and 3 weeks with fair accuracy, using city sewage. The automated viral concentration method will greatly alleviate the major bottleneck in wastewater processing by reducing the turnaround time during epidemics.

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Topics: Wastewater (52%)
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28 results found


Open accessPosted ContentDOI: 10.1101/2021.04.29.21255961
Jana S. Huisman1, Jana S. Huisman2, Jérémie Scire1, Jérémie Scire2  +19 moreInstitutions (7)
30 Apr 2021-medRxiv
Abstract: The effective reproductive number, Re, is a critical indicator to monitor disease dynamics, inform regional and national policies, and estimate the effectiveness of interventions. It describes the average number of new infections caused by a single infectious person through time. To date, Re estimates are based on clinical data such as observed cases, hospitalizations, and/or deaths. Here we show that the dynamics of SARS-CoV-2 RNA in wastewater can be used to estimate Re in near real-time, independent of clinical data and without associated biases stemming from clinical testing and reporting strategies. The method to estimate Re from wastewater is robust and applicable to data from different countries and wastewater matrices. The resulting estimates are as similar to the Re estimates from case report data as Re estimates based on observed cases, hospitalizations, and deaths are among each other. We further provide details on the effect of sampling frequency and the shedding load distribution on the ability to infer Re. To our knowledge, this is the first time Re has been estimated from wastewater. This method provides a low cost, rapid, and independent way to inform SARS-CoV-2 monitoring during the ongoing pandemic and is applicable to future wastewater-based epidemiology targeting other pathogens. Significance statementThe effective reproductive number, Re, is widely used during the COVID-19 pandemic to track disease dynamics, inform regional and national policies, and estimate the effectiveness of interventions. Re is typically estimated from clinical case data, and can be biased by e.g. changes in testing and reporting. We show longitudinal measurements of SARS-CoV-2 RNA in wastewater can be used to estimate Re, across different regions, and provide an independent assessment of the dynamics of COVID-19. Given widespread wastewater sampling during this pandemic, these Re estimates are directly applicable as a rapid, low-cost method to inform public health policy. The method can be adapted to other pathogens, including those for which clinical data is not available.

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13 Citations


Open accessJournal ArticleDOI: 10.1016/J.ENVRES.2021.111373
Abstract: The recent spread of severe acute respiratory syndrome coronavirus (SAR-CoV-2) and the accompanied coronavirus disease 2019 (COVID-19) has continued ceaselessly despite the implementations of popular measures, which include social distancing and outdoor face masking as recommended by the World Health Organization. Due to the unstable nature of the virus, leading to the emergence of new variants that are claimed to be more and rapidly transmissible, there is a need for further consideration of the alternative potential pathways of the virus transmissions to provide the needed and effective control measures. This review aims to address this important issue by examining the transmission pathways of SARS-CoV-2 via indirect contacts such as fomites and aerosols, extending to water, food, and other environmental compartments. This is essentially required to shed more light regarding the speculation of the virus spread through these media as the available information regarding this is fragmented in the literature. The existing state of the information on the presence and persistence of SARS-CoV-2 in water-food-environmental compartments is essential for cause-and-effect relationships of human interactions and environmental samples to safeguard the possible transmission and associated risks through these media. Furthermore, the integration of effective remedial measures previously used to tackle the viral outbreaks and pandemics, and the development of new sustainable measures targeting at monitoring and curbing the spread of SARS-CoV-2 were emphasized. This study concluded that alternative transmission pathways via human interactions with environmental samples should not be ignored due to the evolving of more infectious and transmissible SARS-CoV-2 variants.

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10 Citations


Open accessPosted ContentDOI: 10.1101/2021.03.16.21253652
Aaron Bivins1, Devin North1, Zhenyu Wu1, Marlee Shaffer1  +2 moreInstitutions (2)
24 Mar 2021-medRxiv
Abstract: Wastewater surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is being used to monitor Coronavirus Disease 2019 (COVID-19) trends in communities; however, within-day variation in primary influent concentrations of SARS-CoV-2 RNA remain largely uncharacterized. In the current study, grab sampling of primary influent was performed every 2 hours over two different 24-hour periods at two wastewater treatment plants (WWTPs) in northern Indiana, USA. In primary influent, uncorrected, recovery-corrected, and pepper mild mottle virus (PMMoV)-normalized SARS-CoV-2 RNA concentrations demonstrated ordinal agreement with increasing clinical COVID-19 positivity, but not COVID-19 cases. Primary influent SARS-CoV-2 RNA concentrations exhibited greater variation than PMMoV RNA concentrations as expected for lower shedding prevalence. The bovine respiratory syncytial virus (BRSV) process control recovery efficiency was low (mean: 0.91%) and highly variable (coefficient of variation: 51% - 206%) over the four sampling events with significant differences between the two WWTPs (p <0.0001). The process control recovery was similar to the independently assessed SARS-CoV-2 RNA recovery efficiency, which was also significantly different between the two WWTPs (p <0.0001). Recovery-corrected SARS-CoV-2 RNA concentrations better reflected within-day changes in primary influent flow rate and fecal content, as indicated by PMMoV concentrations. These observations highlight the importance of assessing the process recovery efficiency, which is highly variable, using an appropriate process control. Despite large variations, both recovery-corrected and PMMoV-normalized SARS-CoV-2 RNA concentrations in primary influent demonstrate potential for monitoring COVID-19 positivity trends in WWTPs serving peri-urban and rural areas.

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9 Citations


Open accessJournal ArticleDOI: 10.1016/J.WATRES.2021.117438
Kyle Bibby1, Aaron Bivins1, Zhenyu Wu1, Devin North1Institutions (1)
01 Sep 2021-Water Research
Abstract: Wastewater-based epidemiology (WBE) has emerged as a useful tool in the fight to track and contain COVID-19 spread within communities. One of the motives behind COVID-19 WBE efforts is the potential for 'early warning' of either the onset of disease in a new setting or changes in trends in communities where disease is endemic. Many initial reports of the early warning potential of WBE have relied upon retrospective sample analysis, and delays in WBE analysis and reporting should be considered when evaluating the early warning potential of WBE that enable public health action. Our purpose in this manuscript is to establish a framework to critique the potential of WBE to serve as an early warning system, with special attention to the onset of viral shedding and the differential between results reporting for WBE and clinical testing. While many uncertainties remain regarding both COVID-19 clinical presentation and technical factors influencing WBE results, our analysis suggests at most a modest lead time interval ranging from six days for clinical testing to four days for WBE during community-level wastewater surveillance where clinical testing is accessible on-demand with a rapid time to results. This potential lead time for WBE subsequently increases in settings with limited clinical testing capacity or utilization. Care should be taken when reporting 'early detection' of COVID-19 disease trends via WBE to consider underlying causes (e.g., clinical testing lag or delayed result reporting) to avoid misrepresenting WBE potential.

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Topics: Early warning system (51%)

6 Citations


Journal ArticleDOI: 10.1021/ACSESTWATER.1C00178
Aaron Bivins1, Devin North1, Zhenyu Wu1, Marlee Shaffer1  +2 moreInstitutions (2)
10 Sep 2021-
Abstract: Wastewater surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is being used to monitor Coronavirus Disease 2019 (COVID-19) trends in communities;however, within- and between-day variation of SARS-CoV-2 RNA concentration in primary influent remains largely uncharacterized. In the current study, grab sampling of primary influent was performed every 2 h over two 24-h periods at two wastewater treatment plants (WWTPs) in northern Indiana, USA. The recovery efficiency of endogenous SARS-CoV-2 RNA in wastewater was confirmed to be similar to the recovery efficiency of the process control, bovine respiratory syncytial virus (BRSV). Recovery-corrected SARS-CoV-2 RNA concentrations in primary influent indicate diurnal loading patterns and confirm monitoring dependent on grab samples should target daytime periods with high fecal loading. Importantly, manual compositing performed at the WWTP resulted in concentrations that were consistently lower than grab sample averages indicating potential bias. Uncorrected, recovery-corrected, and pepper mild mottle virus (PMMoV)-normalized SARS-CoV-2 RNA concentrations demonstrated an ordinal agreement with increasing clinical COVID-19 positivity but not COVID-19 cases. In areas where geolocated COVID-19 case data are not available, the COVID-19 positivity rate could provide a useful county-level metric for comparison with wastewater. Nonetheless, large variation both within- and between-days may preclude robust quantitative analyses beyond correlation.

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5 Citations


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7 results found


Open accessJournal ArticleDOI: 10.1016/J.SCITOTENV.2020.138764
Warish Ahmed1, Nicola Angel2, Janette Edson2, Kyle Bibby3  +14 moreInstitutions (4)
Abstract: Infection with SARS-CoV-2, the etiologic agent of the ongoing COVID-19 pandemic, is accompanied by the shedding of the virus in stool. Therefore, the quantification of SARS-CoV-2 in wastewater affords the ability to monitor the prevalence of infections among the population via wastewater-based epidemiology (WBE). In the current work, SARS-CoV-2 RNA was concentrated from wastewater in a catchment in Australia and viral RNA copies were enumerated using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) resulting in two positive detections within a six day period from the same wastewater treatment plant (WWTP). The estimated viral RNA copy numbers observed in the wastewater were then used to estimate the number of infected individuals in the catchment via Monte Carlo simulation. Given the uncertainty and variation in the input parameters, the model estimated a median range of 171 to 1,090 infected persons in the catchment, which is in reasonable agreement with clinical observations. This work highlights the viability of WBE for monitoring infectious diseases, such as COVID-19, in communities. The work also draws attention to the need for further methodological and molecular assay validation for enveloped viruses in wastewater.

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Topics: Population (52%), Wastewater (51%)

735 Citations


Open accessJournal ArticleDOI: 10.1021/ACS.ESTLETT.0C00357
Abstract: In the current COVID-19 pandemic, a significant proportion of cases shed SARS-Coronavirus-2 (SARS-CoV-2) with their faeces. To determine if SARS-CoV-2 RNA was present in sewage during the emergence...

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550 Citations


Open accessJournal ArticleDOI: 10.1038/S41587-020-0684-Z
Abstract: We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA concentrations in primary sewage sludge in the New Haven, Connecticut, USA, metropolitan area during the Coronavirus Disease 2019 (COVID-19) outbreak in Spring 2020. SARS-CoV-2 RNA was detected throughout the more than 10-week study and, when adjusted for time lags, tracked the rise and fall of cases seen in SARS-CoV-2 clinical test results and local COVID-19 hospital admissions. Relative to these indicators, SARS-CoV-2 RNA concentrations in sludge were 0–2 d ahead of SARS-CoV-2 positive test results by date of specimen collection, 0–2 d ahead of the percentage of positive tests by date of specimen collection, 1–4 d ahead of local hospital admissions and 6–8 d ahead of SARS-CoV-2 positive test results by reporting date. Our data show the utility of viral RNA monitoring in municipal wastewater for SARS-CoV-2 infection surveillance at a population-wide level. In communities facing a delay between specimen collection and the reporting of test results, immediate wastewater results can provide considerable advance notice of infection dynamics. Testing sewage for the novel coronavirus reveals epidemiological trends.

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Topics: Specimen collection (60%)

271 Citations


Open accessJournal ArticleDOI: 10.1093/JAMIA/OCAA037
Abstract: Objective To describe the implementation of technological support important for optimizing clinical management of the COVID-19 pandemic. Materials and methods Our health system has confirmed prior and current cases of COVID-19. An Incident Command Center was established early in the crisis and helped identify electronic health record (EHR)-based tools to support clinical care. Results We outline the design and implementation of EHR-based rapid screening processes, laboratory testing, clinical decision support, reporting tools, and patient-facing technology related to COVID-19. Discussion The EHR is a useful tool to enable rapid deployment of standardized processes. UC San Diego Health built multiple COVID-19-specific tools to support outbreak management, including scripted triaging, electronic check-in, standard ordering and documentation, secure messaging, real-time data analytics, and telemedicine capabilities. Challenges included the need to frequently adjust build to meet rapidly evolving requirements, communication, and adoption, and to coordinate the needs of multiple stakeholders while maintaining high-quality, prepandemic medical care. Conclusion The EHR is an essential tool in supporting the clinical needs of a health system managing the COVID-19 pandemic.

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213 Citations


Open accessJournal ArticleDOI: 10.1016/J.SCITOTENV.2020.139960
Warish Ahmed1, Paul M. Bertsch1, Aaron Bivins2, Kyle Bibby2  +13 moreInstitutions (8)
Abstract: There is currently a clear benefit for many countries to utilize wastewater-based epidemiology (WBE) as part of ongoing measures to manage the coronavirus disease 2019 (COVID-19) global pandemic. Since most wastewater virus concentration methods were developed and validated for nonenveloped viruses, it is imperative to determine the efficiency of the most commonly used methods for the enveloped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Municipal wastewater seeded with a human coronavirus (CoV) surrogate, murine hepatitis virus (MHV), was used to test the efficiency of seven wastewater virus concentration methods: (A-C) adsorption-extraction with three different pre-treatment options, (D-E) centrifugal filter device methods with two different devices, (F) polyethylene glycol (PEG 8000) precipitation, and (G) ultracentrifugation. MHV was quantified by reverse-transcription quantitative polymerase chain reaction and the recovery efficiency was calculated for each method. The mean MHV recoveries ranged from 26.7 to 65.7%. The most efficient methods were adsorption-extraction methods with MgCl2 pre-treatment (Method C), and without pre-treatment (Method B). The third most efficient method used the Amicon® Ultra-15 centrifugal filter device (Method D) and its recovery efficiency was not statistically different from the most efficient methods. The methods with the worst recovery efficiency included the adsorption-extraction method with acidification (A), followed by PEG precipitation (F). Our results suggest that absorption-extraction methods with minimal or without pre-treatment can provide suitably rapid, cost-effective and relatively straightforward recovery of enveloped viruses in wastewater. The MHV is a promising process control for SARS-CoV-2 surveillance and can be used as a quality control measure to support community-level epidemic mitigation and risk assessment.

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193 Citations