Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel member of the Coronaviridae family, has been identified as the etiologic agent of an ongoing pandemic of severe pneumonia known as COVID-19.(1) To date there have been millions of cases of COVID-19 diagnosed in 184 countries with case fatality rates ranging from 1.8% in Germany to 12.5% in Italy.(2) Limited diagnostic testing capacity and asymptomatic and oligosymptomatic infections result in significant uncertainty in the estimated extent of SARS-CoV-2 infection.(3) Recent reports have documented that infection with SARS-CoV-2 is accompanied by persistent shedding of virus RNA in feces in 27%(4) to 89% of patients at densities from 0.8 to 7.5 log₁₀ gene copies per gram.(5) The presence of SARS-CoV-2 RNA in feces raises the potential to survey sewage for virus RNA to inform epidemiological monitoring of COVID-19, which we refer to as wastewater-based epidemiology (WBE),(6) but is also known as environmental surveillance.(7) Several studies have reported the detection of SARS-CoV-2 RNA in wastewater in the early stages of local outbreaks, further supporting the technical viability of WBE.(8−10) WBE could be especially informative given that asymptomatic and oligosymptomatic infections are unlikely to be detected during clinical surveillance. In such instances, WBE can be used to determine the burden of undiagnosed infections at the population level, which is critical to refining estimates of case-fatality rates. Additionally, wastewater offers an aggregate sample from an entire community that is more easily accessible than pooled clinical samples.(11) Along with clinical data and other technological approaches, such as contact tracing, WBE could provide critical monitoring of SARS-CoV-2 transmission within a community including the beginning, tapering, or re-emergence of an epidemic (Figure 1). This approach mirrors previous efforts in environmental monitoring, for example poliovirus RNA, to inform mechanistic models of pathogen transmission dynamics.(12) Figure 1. In wastewater-based epidemiology (WBE), the prevalence of SARS-CoV-2 infections in a community could be estimated by enumerating the virus RNA in that community’s sewage and performing mass balances on virus shedding using population and sewage flow rate data. Such information can then inform public health responses to the outbreak. The ongoing pandemic provides a meaningful opportunity to field-test the hypothesis that WBE can be used to detect and manage infectious disease transmission in communities. Many research groups across the globe are mobilizing to monitor wastewater for SARS-CoV-2 RNA for this purpose. However, the quantitative relationship between RNA densities in sewage and human infection prevalence is dependent on many spatial and temporal variables. Importantly, these relationships must be examined in both urban settings with centralized wastewater facilities and rural and low-income settings with decentralized wastewater infrastructure. Assessing variation and uncertainty across such diverse settings requires the systematic harmonization and validation of methodologies across research groups. Therefore, to maximize the potential of the diverse WBE efforts underway, we propose a global effort to coordinate methodologies and data-sharing to maximize the yields of WBE for the current and future outbreaks of disease. The community will also benefit from including appropriate quantitative controls and standards as described previously by Bustin et al.(13) to ensure cross laboratory comparability and data defensibility. Efficient harmonization of sampling, quality control, and analysis methods in the near term and, in the future, widespread dissemination of the resulting data sets and publications will help to ensure a high-quality evaluation of WBE. In partnership with the Sewage Analysis CORe group Europe (SCORE) network and the Global Water Pathogen Project, we have launched the COVID-19 WBE Collaborative (https://www.covid19wbec.org/) as a hub to coordinate and promote the efforts of research groups undertaking WBE for COVID-19. The Web site will include content such as press releases, commentaries, and media content for public outreach and will be used to solicit participation in the collaborative and advertise events relevant to WBE. In the future, the site could also be used to host data sets and promulgate publications and presentations that result from the COVID-19 WBE Collaborative. We are pleased to invite our colleagues to join this effort at a level commensurate with their discretion. The Web site also links to two important platforms for ongoing collaboration. The first is a protocols.io workshare platform for methodological coordination. Research groups currently undertaking wastewater surveillance for SARS-CoV-2 RNA are invited to share their protocols to help produce comparable results across geographies and time scales. Important details include, but are not limited to, the timing, frequency, location, and volume of sampling, relevant metadata, sample storage, means of concentration, extraction, and quantification of nucleic acids and observed processing recoveries. As previously mentioned, harmonization in the execution, or at a minimum, the reporting of relevant details, will greatly enhance the robustness of resulting data sets for analyzing transmission dynamics at various spatial and temporal levels. The second platform linked through the Web site is a Slack workspace for informal communication regarding COVID-19 WBE. The ongoing COVID-19 pandemic continues to evolve rapidly; therefore, any collaborative effort must include a platform for rapid communication. As we work to sample sewage in the midst of this pandemic, biosafety remains paramount. Beyond protocols for sample analysis, we encourage all interested parties to work together to ensure appropriate biosafety measures while conducting this important work. Additionally, we ask funding agencies and the wastewater industry to consider funding for collaborative research related to COVID-19 WBE. The ongoing COVID-19 pandemic requires engineers and scientists to collaborate with population-based scientists, including epidemiologists, mathematical modelers and public health agencies. A multidisciplinary approach on a global scale is required for timely and high impact results to help society. To that end, we have established the COVID-19 WBE Collaborative to facilitate such collaboration and we encourage all interested parties to join us. The authors declare no competing financial interest. This article references 13 other publications.

中文翻译：

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基于废水的流行病学：全球合作，最大限度地为抗击 COVID-19 做出贡献。

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 是冠状病毒科的一种新成员，已被确定为持续大流行的严重肺炎（称为 COVID-19）的病原体。(1) 迄今为止，已发现184 个国家诊断出数百万例 COVID-19 病例，病死率从德国的 1.8% 到意大利的 12.5%。(2) 有限的诊断检测能力以及无症状和寡症状感染导致 SARS 的估计范围存在很大的不确定性。 CoV-2 感染。(3) 最近的报告表明，27%(4) 至 89% 的患者感染 SARS-CoV-2 时，粪便中病毒 RNA 持续脱落，粪便密度为 0.8 至 7.5 log ₁₀(5) 粪便中 SARS-CoV-2 RNA 的存在提高了调查污水中病毒 RNA 的潜力，为 COVID-19 的流行病学监测提供信息，我们将其称为基于废水的流行病学 (WBE)， (6) 但也称为环境监测。(7) 多项研究报告在当地疫情爆发的早期阶段在废水中检测到了 SARS-CoV-2 RNA，进一步支持了 WBE 的技术可行性。(8−10)鉴于在临床监测过程中不太可能检测到无症状和寡症状感染，WBE 的信息尤其丰富。在这种情况下，WBE 可用于确定人群水平上未确诊感染的负担，这对于完善病死率的估计至关重要。此外，废水提供了来自整个社区的汇总样本，比汇集的临床样本更容易获取。(11) 除了临床数据和接触者追踪等其他技术方法外，WBE 还可以对 SARS-CoV-2 传播提供关键监测社区内的风险，包括流行病的开始、逐渐减少或重新出现（图 1）。这种方法反映了之前在环境监测方面的努力，例如脊髓灰质炎病毒 RNA，为病原体传播动态的机制模型提供信息。(12) 图 1. 在基于废水的流行病学 (WBE) 中，社区中 SARS-CoV-2 感染的流行情况可以通过计算该社区污水中的病毒 RNA 并使用人口和污水流量数据对病毒脱落进行质量平衡来估计。这些信息可以为公共卫生应对疫情的措施提供信息。持续的大流行提供了一个有意义的机会来现场测试 WBE 可用于检测和管理社区传染病传播的假设。为此，全球许多研究小组正在动员起来监测废水中的 SARS-CoV-2 RNA。然而，污水中 RNA 密度与人类感染流行率之间的定量关系取决于许多空间和时间变量。重要的是，必须在具有集中式废水设施的城市环境和具有分散式废水基础设施的农村和低收入环境中审查这些关系。评估如此不同环境中的变化和不确定性需要跨研究小组对方法进行系统协调和验证。因此，为了最大限度地发挥正在进行的各种 WBE 努力的潜力，我们建议全球努力协调方法和数据共享，以最大限度地提高 WBE 针对当前和未来疾病爆发的效果。社区还将受益于包括 Bustin 等人之前描述的适当的定量控制和标准(13)，以确保跨实验室的可比性和数据的可靠性。近期内有效协调采样、质量控制和分析方法，未来，广泛传播由此产生的数据集和出版物将有助于确保对 WBE 进行高质量的评估。我们与欧洲污水分析 CORe 集团 (SCORE) 网络和全球水病原体项目合作，启动了 COVID-19 WBE 协作组织 (https://www.covid19wbec.org/)，作为协调和促进相关工作的中心的研究小组针对 COVID-19 进行 WBE。该网站将包括新闻稿、评论和公共宣传媒体内容等内容，并将用于招揽参与与 WBE 相关的合作和广告活动。将来，该网站还可以用于托管数据集并发布 COVID-19 WBE 协作的出版物和演示文稿。我们很高兴邀请我们的同事根据自己的判断力参与这项工作。该网站还链接到两个重要的持续合作平台。第一个是用于方法协调的protocols.io 工作共享平台。目前正在对 SARS-CoV-2 RNA 进行废水监测的研究小组受邀分享他们的方案，以帮助产生跨地域和时间尺度的可比结果。重要细节包括但不限于采样的时间、频率、位置和体积、相关元数据、样品存储、核酸浓缩、提取和定量的方法以及观察到的处理回收率。如前所述，执行中的协调，或者至少是相关细节报告的协调，将大大增强用于分析各种空间和时间层面的传输动态的结果数据集的稳健性。通过网站链接的第二个平台是 Slack 工作区，用于有关 COVID-19 WBE 的非正式沟通。正在发生的 COVID-19 大流行继续迅速发展；因此，任何协作努力都必须包括一个快速沟通的平台。当我们在这场大流行期间对污水进行采样时，生物安全仍然至关重要。除了样本分析协议之外，我们鼓励所有感兴趣的各方共同努力，在开展这项重要工作的同时确保采取适当的生物安全措施。此外，我们要求资助机构和废水行业考虑资助与 COVID-19 WBE 相关的合作研究。正在进行的 COVID-19 大流行需要工程师和科学家与流行病学家、数学建模师和公共卫生机构等基于人群的科学家合作。需要在全球范围内采取多学科方法才能及时取得高影响力的成果来帮助社会。为此，我们建立了 COVID-19 WBE 协作组织来促进此类协作，并鼓励所有感兴趣的各方加入我们。作者声明不存在竞争性经济利益。本文引用了其他 13 篇出版物。广泛传播由此产生的数据集和出版物将有助于确保对 WBE 进行高质量的评估。我们与欧洲污水分析 CORe 集团 (SCORE) 网络和全球水病原体项目合作，启动了 COVID-19 WBE 协作组织 (https://www.covid19wbec.org/)，作为协调和促进相关工作的中心的研究小组针对 COVID-19 进行 WBE。该网站将包括新闻稿、评论和公共宣传媒体内容等内容，并将用于招揽参与与 WBE 相关的合作和广告活动。将来，该网站还可以用于托管数据集并发布 COVID-19 WBE 协作的出版物和演示文稿。我们很高兴邀请我们的同事根据自己的判断力参与这项工作。该网站还链接到两个重要的持续合作平台。第一个是用于方法协调的protocols.io 工作共享平台。目前正在对 SARS-CoV-2 RNA 进行废水监测的研究小组受邀分享他们的方案，以帮助产生跨地域和时间尺度的可比结果。重要细节包括但不限于采样的时间、频率、位置和体积、相关元数据、样品存储、核酸浓缩、提取和定量的方法以及观察到的处理回收率。如前所述，执行中的协调，或者至少是相关细节报告的协调，将大大增强用于分析各种空间和时间层面的传输动态的结果数据集的稳健性。通过网站链接的第二个平台是 Slack 工作区，用于有关 COVID-19 WBE 的非正式沟通。正在发生的 COVID-19 大流行继续迅速发展；因此，任何协作努力都必须包括一个快速沟通的平台。当我们在这场大流行期间对污水进行采样时，生物安全仍然至关重要。除了样本分析协议之外，我们鼓励所有感兴趣的各方共同努力，在开展这项重要工作的同时确保采取适当的生物安全措施。此外，我们要求资助机构和废水行业考虑资助与 COVID-19 WBE 相关的合作研究。正在进行的 COVID-19 大流行需要工程师和科学家与流行病学家、数学建模师和公共卫生机构等基于人群的科学家合作。需要在全球范围内采取多学科方法才能及时取得高影响力的成果来帮助社会。为此，我们建立了 COVID-19 WBE 协作组织来促进此类协作，并鼓励所有感兴趣的各方加入我们。作者声明不存在竞争性经济利益。本文引用了其他 13 篇出版物。广泛传播由此产生的数据集和出版物将有助于确保对 WBE 进行高质量的评估。我们与欧洲污水分析 CORe 集团 (SCORE) 网络和全球水病原体项目合作，启动了 COVID-19 WBE 协作组织 (https://www.covid19wbec.org/)，作为协调和促进相关工作的中心的研究小组针对 COVID-19 进行 WBE。该网站将包括新闻稿、评论和公共宣传媒体内容等内容，并将用于招揽参与与 WBE 相关的合作和广告活动。将来，该网站还可以用于托管数据集并发布 COVID-19 WBE 协作的出版物和演示文稿。我们很高兴邀请我们的同事根据自己的判断力参与这项工作。该网站还链接到两个重要的持续合作平台。第一个是用于方法协调的protocols.io 工作共享平台。目前正在对 SARS-CoV-2 RNA 进行废水监测的研究小组受邀分享他们的方案，以帮助产生跨地域和时间尺度的可比结果。重要细节包括但不限于采样的时间、频率、位置和体积、相关元数据、样品存储、核酸浓缩、提取和定量的方法以及观察到的处理回收率。如前所述，执行中的协调，或者至少是相关细节报告的协调，将大大增强用于分析不同空间和时间层面的传输动态的结果数据集的稳健性。通过网站链接的第二个平台是 Slack 工作区，用于有关 COVID-19 WBE 的非正式沟通。正在发生的 COVID-19 大流行继续迅速发展；因此，任何协作努力都必须包括一个快速沟通的平台。当我们在这场大流行期间对污水进行采样时，生物安全仍然至关重要。除了样本分析协议之外，我们鼓励所有感兴趣的各方共同努力，在开展这项重要工作的同时确保采取适当的生物安全措施。此外，我们要求资助机构和废水行业考虑资助与 COVID-19 WBE 相关的合作研究。正在进行的 COVID-19 大流行需要工程师和科学家与流行病学家、数学建模师和公共卫生机构等基于人群的科学家合作。需要在全球范围内采取多学科方法才能及时取得高影响力的成果来帮助社会。为此，我们建立了 COVID-19 WBE 协作组织来促进此类协作，并鼓励所有感兴趣的各方加入我们。作者声明不存在竞争性经济利益。本文引用了其他 13 篇出版物。