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      Letter to the Editor: Wastewater-Based Epidemiology Can Overcome Representativeness and Stigma Issues Related to COVID-19

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          Abstract

          We read with great interest the Viewpoint by Mao et al., “Can a Paper-Based Device Trace COVID-19 Sources with Wastewater-Based Epidemiology?” 1 We agree regarding the benefits of a wastewater-based epidemiology (WBE) approach in predicting the spread of the COVID-19 infection by analyzing the presence of the virus in wastewater. Concentrations of the norovirus in wastewater samples collected every week accurately reflect the infection in the watershed, suggesting that this approach can serve as a warning of a public outbreak. 2 We suggest additional advantages to this approach and call for a wastewater collection campaign involving international cooperation between environmental researchers, wastewater workers, and public health specialists, aimed at preventing the spread of COVID-19. The WBE approach to testing for COVID-19 has potential advantages over testing the public. First, virus concentrations in wastewater represent the overall status of the watershed, while the number of COVID-19 cases involving infected people is possibly biased. Testing of the public seldom involves complete enumeration or even randomized sampling, because these sampling methods tend to overwhelm or collapse the medical care system, have the disadvantage of false-positives, and are time and labor intensive. The WBE approach is effective in identifying temporal changes in the infection status in the watershed without selection bias. Its second advantage relates to the issue of the stigma that can result from a COVID-19 outbreak. Infected people, or those diagnosed with a false-positive, together with their families, are potentially harmed by stigma and discrimination as well as social isolation. 3 This is one of the disadvantages of testing in complete enumeration or randomized sampling of the entire population. So far, WBE may not have been preferred due to potential regional stigma; however, WBE has proved its value by avoiding individual stigmatization. By contrast, in the current context of a worldwide outbreak of COVID-19, details of the number of cases in a particular region, and sometimes identifying details of infected individuals, are already being broadcast. Detection of SARS-CoV-2 in urban wastewater has been reported in The Netherlands where RT-qPCR tests have been used, 4 although these tests still need more careful investigation regarding their sensitivity and specificity. The necessary analytical techniques must be developed, and in the meantime, wastewater samples should be collected and frozen regularly for future validation of the method and reconstruction of the temporal trends of the infection. Meeting this challenge could provide a perspective on preventing the continuing spread of the COVID-19 pandemic.

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          Mental health care for international Chinese students affected by the COVID-19 outbreak

          Coronavirus disease 2019 (COVID-19), first identified in Wuhan, Hubei province, China in December, 2019, has received substantial attention globally. As of Feb 12, 2020, many countries in which numerous Chinese students pursue their academic studies announced travel restrictions on foreign nationals to contain COVID-19. International Chinese students are living with the fear that their families in China are susceptible and at risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for COVID-19. They also face discrimination and isolation in some countries due to being deemed as potential SARS-CoV-2 carriers. 1 Some media outlets have used derogatory headlines, perpetuating stereotypes and prejudices about Chinese people. This coverage fuels public fear, alienation, and discrimination. Consequently, such students are at risk of hate crimes, especially when individuals consider them contagious. This situation can lead to mental health problems, such as denial, stress, anxiety, and fear. 2 Hence, we urgently need to address the mental health needs of international Chinese students. Some universities have sent messages of solidarity to international Chinese students, offering support and resources to respond to the crisis. Although these universities provide counselling services, such centres are often understaffed, and long waiting times might aggravate students' mental health problems. Mental health care for international Chinese students requires improvement. First, a walk-in triage system can assist university counselling centres in differentiating urgent and routine problems; 3 meanwhile, the triage coordinator needs to be aware of international Chinese students' specific mental health concerns involving COVID-19. Second, counselling training clinics are essential assets because they present avenues for collaboration with university counselling centres to address pressing understaffing issues. 4 Free counselling services in training clinics can also ease anxiety among international Chinese students experiencing distress. Third, departments such as student affairs, international programmes, and student health centres should rally to support affected students by advocating for non-discrimination and coordinating the health response to the crisis. Advice services provided by these departments can help students address academic and financial issues, and other concerns causing distress. Education is also needed to inform the public about the facts of COVID-19 to protect international Chinese students from hate crimes. Care and advocacy serve a crucial role in promoting mental health. 5 Thus, building institutional and societal awareness of international Chinese students' needs for mental health care can be the lynchpin of supporting them. With the experience attained working with these students in this crisis, universities and communities should be well positioned to provide timely appropriate mental health care for other students experiencing natural or ecological disasters if required, in the future.
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            Can a Paper-Based Device Trace COVID-19 Sources with Wastewater-Based Epidemiology?

            A recent outbreak of novel coronavirus pneumonia (COVID-19) caused by SARS-CoV-2 infection has spread rapidly around the globe, with cases now confirmed in 130 countries worldwide. Although public health authorities are racing to contain the spread of COVID-19 around the world, the situation is still grim. About 158 111 confirmed cases and 5946 cumulative deaths (81 059 confirmed cases and 3204 cumulative deaths from China) have been reported around the globe as of March 15, 2020. Some clinical cases have found that some carriers of the virus may be asymptomatic, with no fever, and no, or only slight symptoms of infection. Without the ability to screen these asymptomatic patients quickly and effectively, these unsuspecting carriers have the potential to increase the risk of disease transmission if no early effective quarantine measures are implemented. Therefore, to trace unknown COVID-19 sources, fast and accurate screening of potential virus carriers and diagnosis of asymptomatic patients is a crucial step for intervention and prevention at the early stage. It remains a highly challenging logistical exercise for medical professionals to practically and effectively screen suspected infectious cases from individual households. Such a massive undertaking is time-consuming and labor intensive and is constrained by the availability of testing technologies at this extremely critical time. However, an alternative method utilizing wastewater-based epidemiology (WBE), may provide an effective approach to predict the potential spread of the infection by testing for infectious agents in wastewater, which has been approved as an effective way to trace illicit drugs, and obtain information on health, disease, and pathogens. 1 Faeces and urine from disease carriers in the community will contain many biomarkers that can enter the sewer system. A recent study demonstrated that live SARS-CoV-2 was isolated from the faeces and urine of infected people, 2 which would then enter the wastewater treatment system. A further study has shown that SARS-CoV-2 can typically survive for up to several days in an appropriate environment after exiting the human body. There is potential, therefore, that the analysis of SARS-CoV-2 in community wastewater could trace COVID-19 sources through sewage pipe networks and determine whether there are potential SARS-CoV-2 carriers in certain local areas. If SARS-CoV-2 can be monitored in the community at the early stage through WBE, effective intervention can be taken as early as possible to restrict the movements of that local population, working to minimize the pathogen spread and threat to public health. Using a WBE approach in developing an early warning system and consequent effective intervention system will require a rapid analytical method for the on-site detection of viruses at the wastewater collection point. Currently, the most direct method for the detection of SARS-CoV-2 is a nucleic acid–based polymerase chain reaction(PCR) assay, which is also a means for confirmation of COVID-19 patients throughout China. Although PCR has high sensitivity and specificity, requirements for complicated sample handling in the laboratory, skilled personnel, and a long period of data processing and analysis (4–6 h) are not conducive to real-time and effective monitoring of samples on location. Therefore, it is critical to develop efficient transportable and robust analytical tools to accurately and quickly trace low-level SARS-CoV-2 sources through WBE to confirm these suspected cases and screen asymptomatic infected cases without centralized laboratories. Paper analytical devices have emerged as powerful tools for the rapid diagnosis of pathogens and determination of infection transmission. 3 The paper-based device is a small analytical tool with different functional areas printed with a wax printer that integrates all processes (extraction, enrichment, purification, elution, amplification, and visual detection) required for nucleic acid testing into an inexpensive paper material. The whole testing process can be completed through simple folding of a paper-based device in different ways in different steps without a pump or power supply, which overcomes the limitation of PCR and avoids multiple processes. Paper analytical devices enable multiplexed, sensitive assays that rival PCR laboratory assays and provide high-quality, fast precision diagnostics for pathogens. For example, a recent work has demonstrated that the multiplexed determination of malaria from whole blood using a paper-based device in rural Uganda. 4 The test could sensitively analyze multiplexed nucleic acid sequences of pathogens within 50 min, which gave a higher-quality and faster precision diagnosis for malaria than PCR. In addition, paper analytical devices are easy to stack, store, and transport because they are thin, lightweight, and of different thicknesses. Visual analysis is made simple due to the strong contrast with a colored substrate. Paper-based devices can also be incinerated after use, reducing the risk of further contamination. Although wastewater is a complex matrix, paper-based devices have shown the potential to detect pathogens in wastewater. We have developed a fast “sample-to-answer” analysis method that can provide quantitative monitoring of nucleic acids and genetic information through the analysis of sewage, 5 which was confirmed with a robust electrophoresis and agarose gel image assay, showing promising reliability for wastewater analysis. Additional paper-based devices have also been fabricated for infectious diseases and pathogens determination as shown in Table 1 . Table 1 Examples of Paper-Based Devices for Infectious Diseases and Pathogens Determination infectious diseases/pathogens characteristics of paper-based devices detection method malaria paper device combined vertical flow sample-processing steps visual UV/lateral flow device rotavirus A integrated nucleic acid test on a single paper device, including extraction, amplification, and on-site detection naked eye Zika virus wax-printed paper devices utilizing isothermal amplification smartphone human papillomavirus paper device in a foldable system allowing for fully integrated operation from sample to result lateral flow device HIV paper devices fabricated with cellulose paper and flexible plastic plate electrochemistry Neisseria meningitides versatile paper devices integrated with isothermal amplification visual fluorescence Listeria monocytogenes loop-mediated isothermal amplification (LAMP)-based paper devices visual fluorescence Cochlodinium polykrikoides paper devices based on LAMP visual fluorescence Staphylococcus aureus self-priming paper devices visual fluorescence Vibrio parahemolyticus self-priming paper devices visual fluorescence Mycobacterium smegmatis paper devices combined thermal lysis and isothermal amplification into a single step visual fluorescence Bacillus subtilis a wax-printed cellulose paper device colorimetry Salmonella paper devices integrated with purification, amplification, and on-site detection colorimetry Escherichia coli foldable paper devices with the ability of long-term reagents storage colorimetry   paper devices based on isothermal amplification and on-chip detection visual fluorescence   paper machine integrated sample preparation and isothermal amplification with end point detection visual UV/camera   paper devices integrated extraction, purification, amplification and detection smartphone/naked eye   paper devices combined thermal lysis and isothermal amplification visual fluorescence bovine infectious reproductive diseases multiplexed and point-of-care paper-analytical device visual UV/smartphone highly pathogenic strain of porcine reproductive and respiratory syndrome virus (HP-PRRSV) paper devices fabricated with filter paper and plastic chip colorimetry In summary, the paper-based device has the potential to be used as a small, portable device to detect SARS-CoV-2 in wastewater on site and to track virus carriers in the community. Such an approach could provide near real-time and continuous data and serve as an early warning sensing system to help local governments and agencies make effective interventions to isolate potential virus carriers and prevent the spread of epidemics. We believe that in the case of asymptomatic infections in the community or people are not sure whether they are infected or not, rapid and real-time community sewage detection through paper analytical devices can determine whether there are SARS-CoV-2 carriers in the area in a timely manner to enable rapid screening, quarantine, and prevention. The potentially infected patient will also benefit from paper analytical device tracing SARS-CoV-2 sources with WBE, providing information for the correct and timely treatment of COVID-19.
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              Presence of SARS-Coronavirus-2 in sewage

              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 is present in sewage during the emergence of COVID-19 in the Netherlands, sewage samples of 7 cities and the airport were tested using RT-PCR against three fragments of the nucleocapsid protein gene (N1-3) and one fragment of the envelope protein gene (E). No SARS-CoV-2 was detected in samples of February 6, three weeks before the first case was reported in the Netherlands on February 27. On March 5, the N1 fragment was detected in sewage of five sites. On March 15/16, the N1 fragment was detected in sewage of six sites, and the N3 and E fragment were detected at 5 and 4 sites respectively. This is the first report of detection of SARS-CoV-2 in sewage. The detection of the virus in sewage, even when the COVID-19 incidence is low, indicates that sewage surveillance could be a sensitive tool to monitor the circulation of the virus in the population.
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                Author and article information

                Journal
                Environ Sci Technol
                Environ. Sci. Technol
                es
                esthag
                Environmental Science & Technology
                American Chemical Society
                0013-936X
                1520-5851
                22 April 2020
                : acs.est.0c02172
                Affiliations
                []Department of Health Risk Communication, Fukushima Medical University School of Medicine , Fukushima 960-1295, Japan
                []Department of Environmental and Civil Engineering, Faculty of Engineering, Toyama Prefectural University , Imizu 939-0398, Japan
                [§ ]Faculty of Geosciences and Civil Engineering, Kanazawa University , Kanazawa 920-1192, Japan
                []Department of Food, Life and Environmental Sciences, Yamagata University , Tsuruoka 997-8555, Japan
                Author notes
                Article
                10.1021/acs.est.0c02172
                7182141
                32323978
                b42f50b9-d180-4b03-868d-565bde039f8c
                Copyright © 2020 American Chemical Society

                This article is made available via the PMC Open Access Subset for unrestricted RESEARCH re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 07 April 2020
                : 10 April 2020
                Categories
                Letter to the Editor
                Custom metadata
                es0c02172
                es0c02172

                General environmental science
                General environmental science

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