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      Invited Perspective: The Promise of Wastewater Monitoring for Infectious Disease Surveillance

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      Environmental Health Perspectives
      Environmental Health Perspectives

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          Abstract

          Wastewater provides a naturally composited biological sample that includes pathogens shed in feces, urine, blood, sputum, and vomit and that can be used to infer information about disease occurrence in the community. Early in the COVID-19 pandemic, it was noted that SARS-CoV-2 RNA is regularly shed in the feces of infected people, and monitoring of wastewater to estimate disease occurrence became an attractive option. 1,2 Wastewater monitoring has been used previously, mostly for enteric diseases such as polio 3 and salmonellosis, 4 but a significant investment in research and implementation has elevated the approach as part of the COVID-19 response and measurements of SARS-CoV-2 RNA in wastewater have been consistently highly associated with reported COVID-19 cases. 2,5 The U.S. Centers for Disease Control and Prevention began the National Wastewater Surveillance System (NWSS) to support and aggregate data from wastewater nationwide, the first such program in the United States. There is a growing acceptance of wastewater monitoring. A depth of research indicates the strength of its performance as a surveillance tool that public health officials and media have begun to include in their reports on the pandemic, but there are challenges around the coordination of its protocol and policies. Now, there is a further need to document the impact of specific public health actions that have been taken based on this data, as in Deng et al., 6 and to examine the ethical considerations and sustainability concerns around these programs. Deng et al. describe not only a large-scale program monitoring wastewater for SARS-CoV-2 in Hong Kong but also a close relationship with public health intervention. 6 Wastewater was sampled from within the sewer network, capturing populations ranging from tens of thousands of people down to groups as small as 17 individuals. Based on positive wastewater test results, compulsory testing was triggered, and during the study period, 62 cases were identified during individual testing following a positive wastewater sample. Some of these cases were asymptomatic or presymptomatic; these cases may not have been identified, especially in a timely manner, without wastewater guiding the investigation. The study by Deng et al. 6 is a compelling example of wastewater monitoring working together with public health interventions at a large scale, but it also raises questions about both sustainable use cases for wastewater and the importance of ensuring that these emerging tools are used appropriately. Use cases for wastewater monitoring for public health action are largely dependent on the scale (and frequency) at which samples are taken, and sustainability may depend on the geographic scale and frequency of sampling. Monitoring can be done using samples from treatment plants that represent large segments of towns and cities, or from within a sewer network or building outflow to monitor smaller, targeted communities (as in Deng et al. 6 ). Treatment plant samples provide information about a larger community with a single sample and can usually be collected by existing treatment plant staff and in many cases with existing equipment, making costs lower and coordination simpler than collecting samples from within a sewer network that may provide more detailed information. It is important to match testing to the level of possible intervention—for example, citywide monitoring provides information at an appropriate level to inform policies and forecast needs that are managed at this level, such as hospital staffing. City-level monitoring can also be used to detect the introduction of rare new targets, such as emerging SARS-CoV-2 variants, 7 and provide an overall picture of the outbreak in a region. 8 For smaller segments of communities, and as shown in Deng et al., 6 the focus is often on determining where to target additional testing, and this can also be done for other services, such as vaccination. In the United States, wastewater monitoring has been widely used on college campuses, sometimes alongside additional testing for those associated with positive wastewater tests. 9–11 Wastewater monitoring programs should also address important ethical considerations. An advantage of wastewater monitoring is that samples are naturally collected and aggregated such that individuals are not directly identifiable. However, monitoring small populations raises privacy concerns, and even if individuals cannot be identified they may be impacted by responsive interventions. Others have noted that wastewater monitoring should be used only in populations that are large enough to ensure the anonymity of those monitored. 12–14 People who are represented in a wastewater sample are, for the most part, not able to opt out of their participation. In Deng et al. populations as small as 17 people were monitored. 6 It is notable that although Deng et al. 6 monitored small populations with the explicit purpose of implementing compulsory testing based on the results, it does not appear that any ethical review board was consulted. Smaller-scale testing can inform planning for testing and vaccination clinics or guide policies in schools or other institutions, but it is also more resource intensive and has unique ethical considerations. Programs should carefully consider the size and vulnerability of the populations monitored when evaluating the ethics of monitoring, and public health officials should avoid responses that are unduly burdensome or punitive. 14 All actions based on monitoring should operate based on principles of protection for individuals, including their privacy, and should acknowledge limitations in interpreting results. Deng et al. note, for example, that there is still uncertainty about the timing and magnitude of fecal shedding of SARS-CoV-2, and that in some cases positive signals were likely a result of convalescing cases. 6 This is a particularly important limitation of the method when data is used to request or require individuals to take action based on the results. Wastewater monitoring will continue to guide responses to the COVID-19 pandemic and other disease outbreaks. Sampling at the treatment plant level is a sustainable approach to monitoring communities for infectious diseases because the cost and labor for the few samples needed is relatively low. Although monitoring at the community level as described by Deng et al. 6 is much more resource intensive, there are many cases in which monitoring at the small community, institution, or building level is desirable and worth an investment to support the targeted protection of public health. Existing and developing ethical guidelines should be considered when these programs are implemented, especially for smaller community sites. Schools, correctional facilities, and many businesses are all places where relatively consistent groups of people intermingle and where early identification of an outbreak could allow for responsive action to prevent further illness. Sustainable and ethical implementation of wastewater monitoring at both treatment plant and smaller community levels will enable further use of wastewater data for the protection of public health using a tool that is less biased by health care access than traditional surveillance. Programs that balance these considerations and work with the community can produce data that can not only guide public health interventions but can also be used by communities to advocate for their needs and help shape interventions to appropriately and effectively limit the spread of disease.

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          Most cited references13

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          Virological assessment of hospitalized patients with COVID-2019

          Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.
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            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

            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 of COVID-19 in The Netherlands, sewage samples of six cities and the airport were tested using four qRT-PCR assays, three targeting the nucleocapsid gene (N1–N3) and one the envelope gene (E). No SARS-CoV-2 RNA was detected on February 6, 3 weeks before the first Dutch case was reported. On March 4/5, one or more gene fragments were detected in sewage of three sites, in concentrations of 2.6–30 gene copies per mL. In Amersfoort, N3 was detected in sewage 6 days before the first cases were reported. As the prevalence of COVID-19 in these cities increased in March, the RNA signal detected by each qRT-PCR assay increased, for N1–N3 up to 790–2200 gene copies per mL. This increase correlated significantly with the increase in reported COVID-19 prevalence. The detection of the virus RNA in sewage, even when the COVID-19 prevalence is low, and the correlation between concentration in sewage and reported prevalence of COVID-19, indicate that sewage surveillance could be a sensitive tool to monitor the circulation of the virus in the population.
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              Measurement of SARS-CoV-2 RNA in wastewater tracks community infection dynamics

              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.
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                Author and article information

                Journal
                Environ Health Perspect
                Environ Health Perspect
                EHP
                Environmental Health Perspectives
                Environmental Health Perspectives
                0091-6765
                1552-9924
                12 May 2022
                May 2022
                : 130
                : 5
                : 051302
                Affiliations
                [ 1 ]Rollins School of Public Health, Emory University , Atlanta, Georgia, USA
                Author notes
                Address correspondence to Marlene K. Wolfe, Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Rd., Atlanta, GA 30322 USA. Telephone: (617) 583-2401. Email: marlene.wolfe@ 123456emory.edu
                Author information
                https://orcid.org/0000-0002-6476-0450
                Article
                EHP11151
                10.1289/EHP11151
                9097954
                35549718
                84661ddc-989d-4eed-b54f-3cb4479082fb

                EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.

                History
                : 23 February 2022
                : 04 April 2022
                : 11 April 2022
                Categories
                Invited Perspective

                Public health
                Public health

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