G L O B A L I N F L U E N Z A P R O G R A M M E INTERIM GUIDANCE 8 NOVEMBER 2020 Maintaining surveillance of influenza and monitoring SARS-CoV-2 adapting Global Influenza Surveillance and Response System (GISRS) and sentinel systems during the COVID-19 pandemic GISRS COVID –19 IN FL U EN ZA SURVEILLA N CE maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance ii WHO/2019-nCoV/Adapting_GISRS/2020.1 © World Health Organization 2020 Some rights reserved. This work is available under the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/ licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. 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In no event shall WHO be liable for damages arising from its use. ii world health organization iii Acknowledgements WHO wishes to acknowledge the experts and country representatives who contributed to the development of the interim guidance before, during and after the WHO Consultation to Adapt Influenza Sentinel Surveillance Systems for Including COVID-19 held virtually from 6 to 8 October 2020. Contribution is acknowledged from experts of the influenza/SARS-CoV-2 interface working groups. Experts of case definitions group include Luzhao Feng, Siri Hague, Jean-Michel Heraud, Gianfranco Spiteri, Sheena Sullivan, and Weigong Zhou. Experts of epidemiology considerations group include Cornelia Adlhoch, Yuzo Arima, Imad Cherkaoui, Cheryl Cohen, and Sonja Olsen. Experts of laboratory considerations group include Ian Barr, Eeva Broberg, Rodrigo Fasce, Erik Karlsson, Rebecca Kondor, Angeliki Melidou, Catherine Thompson, Dominic NC Tsang, Sylvie van der Werf, Xiyan Xu, and Thedi Ziegler. Acknowledgements go to the following experts and institutions that contributed data in the pre-consultation workshop: Departamento de Epidemiología, de la División de Planificación Sanitaria del Ministerio de Salud de Chile, Hospitales Centinelas para la vigilancia de IRAG y el Instituto de Salud Pública, Chile; Ministerio de Salud de Costa Rica, INCIENSA, CCSS, Costa Rica; Ministerio de Salud Pública de Paraguay; Sibongile Walaza, Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, South Africa; Andrew Hayward, Institute of Epidemiology and Health Care, University College London, UK; Thulani Ashcroft, Emma Gillette, Durga Kulkarni, and You Li, Usher Institute, University of Edinburgh, UK; Scott A. Nabity, Centers for Disease Control and Prevention, USA. Special thanks to the consultation chair, Rahman Mahmudur, and co-chairs, Ian Barr and Cheryl Cohen; to Thedi Ziegler and Shoshanna Goldin who served as meeting rapporteur and to all presenters and discussion leads. The following WHO staff and consultants are gratefully acknowledged for their support in the preparation of the consultation and contributions to the development and finalization of the interim guidance: Abdinasir Abubakar, Maya Allan, Tomas John Allen, Amal Barakat, Silvia Bertagnolio, Paula Couto, Vanessa Cozza, Janet Diaz, Hien Doan, Amgad A. Elkholy, Julia Fitzner, Aspen Hammond, Siddhivinayak Shriram Hirve, Belinda L. Herring, Francis Inbanathan, Jorge Jara, Kazunobu Kojima, Frank Konings, Henry Laurenson-Schafer, Sandra Jackson, Juliana Leite, Maja Lievre, Bikram Maharjan, Awandha Mamahit, Marie-jo Medina, Ann Moen, Piers Andrew Nicholas Mook, Karen Nahapetyan, Richard Pebody, Dmitriy Pereyaslov, Anne Perrocheau, Angel Rodriguez, Magdi Samaan, Soe Soe Thwin, Katelijn A.H. Vandemaele, Andrea Vicari, Karen Von Eije, Pushpa Wijesinghe, and Wenqing Zhang. The technical editing of this document was performed by Judith Ann Mandelbaum-Schmid. maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance iv The threat of influenza epidemics and pandemics persists. It is imperative for the GISRS to maintain meaningful surveillance of influenza worldwide and for countries to remain vigilant while adapting to meet COVID-19 surveillance objectives. world health organization 1 Overview 3 Key points 3 Introduction 5 Background 5 Extending objectives of influenza sentinel surveillance to COVID-19 6 Influenza surveillance case definitions for COVID-19 7 Rapid situation assessment of the status of the sentinel surveillance system 9 Rapid situation assessment 9 Evaluate changes in healthcare seeking behaviour 10 Addressing disruptions in influenza sentinel surveillance systems 10 Addressing specific disruptions 10 Practical considerations for extending influenza sentinel surveillance to COVID-19 11 Expansion of the of sentinel system 11 Case detection and data collection at sentinel sites 11 Sampling strategy and sample size considerations 12 Laboratory considerations – sentinel surveillance specimens 13 Clinical specimens 13 Storage of clinical specimens at the sentinel site 13 Transport of clinical specimens to the laboratory 13 Handling of clinical specimens in the laboratory 14 Algorithms for surveillance testing of influenza and SARS-CoV-2 14 Selection of influenza positive clinical specimens and virus isolates to forward to a WHO CC 17 Laboratory techniques for the detection of influenza and SARS-CoV-2 17 Biosafety and Biosecurity 18 Data reporting, analysis and interpretation 19 Monitoring and evaluation 20 Translating evidence to policy 20 References 22 Content maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance 2 Supplementary Table S1: Glossary of commonly used case definitions for influenza and COVID-19 26 Supplementary Table S2: Source and heterogeneity of data analysed to estimate performance characteristics for ILI, ARI and SARI case definitions for COVID-19 27 Supplementary Table S3: Influenza like illness (ILI) performance characteristics for COVID-19 29 Supplementary Table S4: ARI performance characteristics for COVID-19 30 Supplementary Table S5: SARI performance characteristics for COVID-19 31 Annex 1. Strengths and limitations of ILI / ARI / SARI surveillance to address COVID-19 objectives 32 Annex 2. Rapid situation assessment of surveillance system attributes and example questions 36 Annex 3. Addressing disruptions in sentinel syndromic surveillance for influenza 37 Annex 4. Addressing disruptions in sentinel virologic surveillance for influenza 40 Annex 5. Changes to sentinel site case reporting form and reasons for inclusion 42 Annex 6. Influenza surveillance data and objectives and limitations to interpretation 43 Annex 7. How and what to report 46 Annex 8. Monitoring and evaluation of influenza sentinel surveillance systems 48 Annexes world health organization 3 The threat of influenza epidemics and pandemics persists. It is imperative for the GISRS to maintain meaningful surveillance of influenza worldwide and for countries to remain vigilant while adapting to meet COVID-19 surveillance objectives. Countries are advised to first assess and address disruptions to the influenza sentinel surveillance systems when implementing sentinel surveillance of COVID-19. Specimens from sentinel sites should be tested for both influenza and SARS-CoV-2 viruses. If possible, multiplex PCR assays for the simultaneous detection of influenza and SARS-CoV-2 viruses should be selected for efficient use of reagents, consumables and hands-on time. It is important to ship timely representative influenza viruses and/ or clinical specimens from positive specimens to WHO Collaborating Centres, according to existing WHO guidance. Reporting of weekly aggregated sentinel surveillance is a critical component of surveillance. Despite its great challenges, the COVID-19 pandemic provides an opportunity to strengthen core surveillance capacities that can deliver public health benefits during and well beyond this emergency. Overview This document is an update of the interim guidance entitled Operational considerations for COVID-19 surveillance using GISRS, published on 26 March 2020, and of the interim guidance Preparing GISRS for the upcoming influenza seasons during the COVID-19 pandemic – practical considerations, published on 26 May 2020. The document incorporates additional considerations for assessing and addressing disruptions in influenza sentinel surveillance systems and for extending influenza sentinel surveillance to COVID-19. It also includes the updated algorithms for surveillance testing of influenza and SARS-CoV-2, which would enable the monitoring of the potential co-circulation of these respiratory viruses during the upcoming influenza season 2020/2021 and the detection of co-infections with SARS-CoV-2 and influenza or other respiratory viruses. This version is based on the most recent published evidence and country lessons learnt for leveraging the Global Influenza Surveillance and Response System (GISRS) for COVID-19 surveillance compiled before and during a virtual consultation in October 2020. KEY POINTS maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance 4 Despite its great challenges, the COVID-19 pandemic provides an opportunity to strengthen core surveillance capacities that can deliver public health benefits during and well beyond this emergency. world health organization 5 Introduction This document is intended for public health professionals involved in disease and laboratory surveillance at the national level. It is also a guide for WHO staff involved in influenza and COVID-19 pandemic surveillance and response. It provides interim guidance for adapting and sustaining influenza sentinel surveillance systems that ensure continued influenza surveillance and complement COVID-19 surveillance wherever possible during the ongoing pandemic. Background Since the emergence of SARS-CoV-2, the Global Influenza Surveillance and Response System (GISRS) (1) and its network of public health laboratories (National Influenza Centers (NICs), WHO H5 Reference Laboratories, WHO Collaborating Centers) in 125 countries have been at the forefront of a concerted global and national response for the detection and containment of SARS-CoV-2 transmission. A survey conducted by GISRS in May 2020 indicated that more than 90% of NICs, WHO H5 reference laboratories and other public health laboratories in the GISRS network are conducting testing for SARS-CoV-2. Existing GISRS influenza reporting systems have become the primary platforms for sharing COVID-19 data at regional and global levels. A rapid global external quality assessment programme for COVID-19 was built on the influenza mechanism of GISRS with 164 countries (233 labs) participating in the programme. Sharing of genetic sequence data of SARS-COV-2 rapidly took place globally through a publicly accessible database in GISAID (2). The GISRS infectious substance shipping mechanism was used for the shipping of SARS-CoV-2 virus materials to WHO COVID-19 reference laboratories. Furthermore, since March 2020, countries have started sentinel surveillance of COVID-19, through testing of sentinel samples for SARS-CoV-2 from influenza surveillance systems to monitor community transmission, following WHO guidance on operational considerations for leveraging influenza surveillance systems to incorporate COVID-19 testing (3). However, while responding to the exponential surge in demand for COVID-19 testing, influenza surveillance systems have been overwhelmed and faced significant disruptions and resource challenges due to the changes in healthcare seeking behavior and delivery. In many countries, weekly reporting of influenza surveillance data has been delayed, infrequent or ceased altogether. In those countries that were able to test and report, influenza activity was low and below the epidemic threshold during the 2020 southern hemisphere season compared to past years. It is essential for countries to continue vigilance for the emergence of non-seasonal influenza viruses of pandemic potential and prepare for the upcoming 2020/2021 northern hemisphere influenza season during the ongoing COVID-19 pandemic. WHO supports country readiness and response by providing evidence-based guidance for active case finding, care and isolation, contact tracing and quarantine (4). As part of the response efforts, the Emergency Committee of the International Health Regulations (IHR 2005) advised WHO to provide guidance on monitoring disease trends using severe acute respiratory infection (SARI) and influenza-like illness (ILI) surveillance systems in anticipation of the co-circulation of influenza and SARS-CoV-2 viruses. It continues to advise State Parties to share with WHO all data (including SARI and ILI where available) necessary to conduct global risk assessments through data platforms, such as the GISRS and the IHR mechanism (5, 6). maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance 6 Surveillance systems should be based on clear objectives, which guide what kind of data should be collected and the selection of sites for surveillance that will provide the most appropriate data. The objectives of routine influenza sentinel surveillance are to provide timely and high-quality epidemiological data and viral isolates to describe the seasonality, signal the start and end of the influenza season, provide candidate viruses for vaccine production, monitor the antigenic and genetic evolution of circulating viruses, monitor groups at high risk of severe disease, assess severity, estimate disease burden, monitor antiviral susceptibility and detect unusual and unexpected events and outbreaks. The approach of routine influenza sentinel surveillance system is not to capture all suspected cases of influenza but only a systematic subset of influenza cases. Early detection of cases for isolation, testing, contact tracing, quarantine and rapid control of clusters and outbreaks are not the primary objectives of sentinel surveillance systems for seasonal influenza (7). Existing influenza surveillance systems, using global standards and approaches and coordinated through the GISRS system are in a unique position to contribute to pandemic surveillance and monitoring, especially considering the likely co-circulation of influenza and SARS-CoV-2 viruses. The potential of the existing sentinel systems meeting the following objectives is, however, dependent on the evolving SARS-CoV-2 transmission situation in the country. COVID-19 objectives that are likely to be addressed through influenza sentinel systems: Monitoring long term epidemiological trends and evolution of SARS-CoV-2 viruses Detecting the co-circulation of influenza and SARS-CoV-2 viruses. COVID-19 objectives that influenza sentinel surveillance can likely contribute to include: Early detection of community transmission of SARS-CoV-2 Evaluation of the impact of COVID-19 on healthcare systems Informing the implementation and adjustment of targeted public health and social measures. COVID-19 objectives that are unlikely to be addressed include: Early detection and containment of COVID-19 outbreaks. The strengths and limitations of primary care-based (ILI/ARI) and hospital-based (SARI) sentinel surveillance systems for addressing COVID-19 objectives are described in Annex 1. Several countries are using other surveillance systems to monitor trends for influenza, such as universal monitoring of ICD 10 codes for acute respiratory diseases, excess mortality surveillance and participatory surveillance. These systems are not discussed in this document but should also be leveraged in the context of COVID surveillance (8). Despite the challenges, the COVID-19 pandemic provides an opportunity to strengthen core surveillance capacities that can deliver public health benefits during and well beyond this emergency. Surveillance capacities built by countries during the pandemic would serve as a basis for resilient systems that can respond more effectively and rapidly to public health threats in the future. Extending objectives of influenza sentinel surveillance to COVID-19 world health organization 7 Influenza surveillance case definitions for COVID-19 Determining optimal thresholds for sensitivity and specificity for a case definition is always a balance based on needs and objectives of surveillance for influenza, COVID-19 and other respiratory infections with similar and non-discriminatory clinical characteristics (9). A non- sensitive case definition could result in the failure to detect activity early enough or incorrectly estimate disease severity. By contrast, an overly sensitive case definition may signal false alerts for the onset of the epidemic due to a higher number of false positives from other causes, and consequently demand more resources (10). ILI, ARI and SARI for influenza ILI and SARI case definitions, as defined in the WHO global influenza surveillance standards, are commonly used by national influenza surveillance systems globally, though sometimes with minor adaptations (Box 1). Acute respiratory infection (ARI) case definition is also used in some countries for influenza and other respiratory virus surveillance and is included in the WHO Regional Office for Europe guidance for influenza surveillance in humans (11). The ILI case definition (Table 1) has a high specificity (85 – 95%) but lower sensitivity (45 – 55%) for detecting influenza in primary care consultations (12). By contrast, the broader ARI case definition is more sensitive (94%) but less specific (27%) for influenza than the ILI case definition. Similarly, the SARI case definition has a specificity and sensitivity that ranges between 45 and 70% (13, 14). ILI, ARI and SARI for COVID-19 WHO has regularly updated the case definitions for COVID-19 to integrate increasing knowledge on the most common and predictive symptoms, clinical and radiographic signs and known transmission dynamics (supplementary Table S1) (15). Part A of the suspected COVID-19 case definition requires acute onset fever and cough (same as for ILI and SARI) or acute onset of at least three of a range of symptoms that are broader (gastro-intestinal, altered mental status, myalgia, general weakness/fatigue, headache) than that required for any case definition for influenza. Part B of the suspected COVID-19 case definition requires acute onset of fever (measured or reported), cough and hospitalization and are the same as for the SARI case definition for influenza. The epidemiological link required for a COVID-19 case (e.g., contact with a known COVID-19 case, history of travel to COVID-19 affected areas) is relevant when a country is not yet in a community transmission phase. ILI symptoms onset within past 10 days AND measured fever of 38˚C or more AND respiratory infection (cough) ARI at least one of cough, sore throat, shortness of breath, runny nose with or without fever AND a clinician’s judgement that the illness is due to an infection SARI severe (hospitalization) AND acute (symptoms onset within past 10 days) AND fever (reported or measured 38˚C or more AND respiratory infection (cough) Box 1: Influenza surveillance case definitions maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance 8 A recent systematic review on the clinical characteristics of COVID-19 commissioned by WHO in September 2020 found fever (83%) and cough (60%) as the most common symptoms associated with COVID-19 in persons with illness, followed by loss of smell or taste (41%), fatigue (31%) and loss of appetite (30%) (16). The review was mainly based on symptoms in hospitalized cases, and it is therefore possible that community or primary cases would have milder symptom profiles. Little is known about the prevalence of ILI, ARI or SARI among COVID-19 cases from published literature and meta-analysis of patient-level data from different geographical and severity settings. It would be necessary to explore the different combinations of symptoms to optimally capture COVID-19 cases. SARS-CoV-2 positivity in ILI / ARI and SARI surveillance ranged between 1.8% and 25.6% and was highest in the elderly and lowest in children (17-19). A review of seven ecological studies found positive correlation between excess ILI / ARI and COVID-19 cases or influenza- negative cases, indirectly supporting the use of ILI, ARI and SARI case definitions for COVID-19 surveillance (16, 20). Supplementary tables S2-S5 describe the source and heterogeneity of data and results from countries that have contributed to the WHO assessment of ILI, ARI and SARI case definitions performance for COVID-19. Further in-depth analysis is needed on extensive data sourced from different geographic and population settings, and different stages of the COVID-19 pandemic. In the interim, influenza surveillance systems should continue to use existing WHO ILI and SARI case definitions to test for influenza and wherever possible, for COVID-19. Countries with high testing capacities may continue to use the more sensitive but less specific ARI case definition. ILI ARI SARI Sensitivity (%) 45 – 55 94 45 – 70 Sensitivity (%) 20 – 51 86 40 – 55 Specificity (%) 85 – 95 27 45 – 70 Specificity (%) 60 – 90 23 33 – 60 INFLUENZA COVID-19 Table 1: Summary of performance characteristics of ILI, ARI and SARI case definitions for influenza and COVID-19 world health organization 9 Rapid situation assessment of the status of the sentinel surveillance system Well-established influenza surveillance uses a network of sentinel sites for the collection of clinical specimens from suitable patients according to the case definitions. These sites include public and private medical offices and clinics as well as hospitals. The current situation has had variable effects on routine influenza surveillance systems. Some aspects of influenza surveillance have benefited from the rapid capacity building and training efforts during the response to COVID-19. Other parts of the surveillance system have been disrupted, affecting routine influenza surveillance activities. Within a country, the type and degree of disruptions may vary between regions and sentinel sites and over time with fluctuations in SARS-CoV-2 and influenza transmission intensities affecting national and local capacities. Disruptions to existing sentinel influenza surveillance systems may be the result of changes in healthcare delivery (including resource limitations and changing priorities) and healthcare seeking behaviour and can influence the utility of the surveillance system in meeting its objectives. Disruptions can disproportionally affect one sentinel system over another (e.g. outpatient surveillance may be more severely disrupted compared to inpatient surveillance systems). Additional survey methods can be considered for a detailed assessment of changes in healthcare seeking behaviour. Rapid situation assessment The rapid situation assessment described below is a quick approach to documenting and describing the potential opportunities for and disruptions to sentinel surveillance for influenza to inform possible interventions in the context of the COVID-19 pandemic. The assessment does not replace recommended regular in-depth scored evaluations or routine monitoring. A rapid assessment is meant to be used when limited time and resources make a broad evaluation difficult and when interventions need to be considered immediately. The rapid assessment aims to achieve the following objectives: To identify strengths, challenges and gaps in surveillance program implementation, as well as opportunities and threats relevant to sustaining influenza surveillance and incorporating the surveillance of COVID-19 in the sentinel system. To use the assessment findings to assess the degree of disruptions and take appropriate, targeted actions for sustaining influenza surveillance and incorporating the surveillance of COVID-19 in the sentinel system. Consider including the following activities: Collect information on sentinel site attributes, focusing on changes in trends, policies, system processes and data quality that may have taken place in the context of the COVID-19 pandemic response. Example questions are given in Annex 2 but should be adapted for the national situation. Sources of information may include in-depth interviews with key sentinel site and laboratory personnel, direct observation and desk review of key documents. Summarize the findings and prepare a brief report on the degree of disruptions to the sentinel surveillance system, including specific disruptions and affected attributes. The report can also include interim recommendations on actions for improvement if needed to sustain influenza sentinel surveillance. maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance 10 Evaluate changes in healthcare seeking behaviour To better understand changes in healthcare seeking behavior and how this affects the data and interpretation, the information below could be useful: Policy documents Are patients with respiratory symptoms redirected to special screening centers? Are patients with SARI referred to designated hospitals? A cross-sectional survey of participants identified through random or systematic sampling, who self-complete a tool that collects data including sociodemographic information Participatory surveillance systems for influenza and influenza-like illness Subjective anecdotal information from clinical networks. If there are major disruptions, determine what influenza objectives should be prioritized realistically for the next 6-12 months and what resources and capacity are available in order to make adaptations to meet these priority objectives. Priority objectives would include: understanding when, where and in whom (e.g. age groups) influenza activity is occurring to inform clinical management recommendations and public health response activities at national and subnational levels submitting representative samples to inform the global vaccine composition selection decision contributing to the understanding of trends and impact at subnational, national, regional and global levels If some disruptions are identified in the rapid assessment, address the specific disruptions to maintain influenza surveillance. Consider adding SARS-CoV-2 as a virus under surveillance in the existing system. If resources allow, test all samples collected in sentinel sites for influenza and SARS-CoV-2. If no disruptions are noted, consider adding SARS-CoV-2 as a virus under surveillance in the existing system. If resources allow, test all samples collected in sentinel sites for influenza and SARS-COV-2 Addressing specific disruptions Disruptions to existing influenza sentinel surveillance systems may vary by country, and the underlying reasons are diverse. They may occur as a result of changes in healthcare delivery, especially primary care health services including telephone first policies, teleconsultations, redirection of patients to specialized triage / testing / treatment clinics or centres and changes to sentinel sites and staff (repurposed for the COVID-19 response) and case definitions (e.g. from ILI to ARI). Detailed considerations for sustaining influenza surveillance are provided in Annex 3 (syndromic surveillance) and Annex 4 (virologic surveillance) with associated opportunities and constraints. Any changes made to sentinel surveillance should be recorded and monitored closely to understand if they have addressed the issues identified. Addressing disruptions in influenza sentinel surveillance systems world health organization 11 Practical considerations for extending influenza sentinel surveillance to COVID-19 Countries should consider the following before implementing sentinel surveillance for COVID-19 in the influenza surveillance systems: presence of a national or subnational surveillance system governed by national health authorities results of the surveillance system evaluation and the assessment of the degree of disruption to the system potential (if there is capacity in place) to pilot sentinel surveillance of COVID-19 at a select proportion of well-functioning sentinel sites in the surveillance systems at initial stages logistics of sample transport from sentinel sites to national reference laboratories reporting of SARS-CoV-2 results: to whom and how to trigger response actions such as contact tracing and IHR reporting. Countries should consider implementing syndromic surveillance for SARI combined with laboratory confirmation to capture the impact of both influenza and COVID-19 on healthcare systems. Countries already collecting information on laboratory-confirmed hospitalizations might consider implementing SARI surveillance with laboratory-confirmation of both influenza and COVID-19 to understand the combined impact on hospital systems. Expansion of the of sentinel system Expansion of the sentinel system should not compromise the surveillance standards, including quality of specimens and epidemiological information. Good quality specimens and data with timely reporting, even from fewer sites, are more useful than a large volume of poor-quality specimens and failure to report data in a timely manner. It is important, before establishing more sites, to consider whether they can be effectively managed, monitored and sustained. Following an evaluation of the sentinel system, if it is decided to expand the sentinel sites, consideration should be given to increasing the geographical representativeness of the surveillance system, with the goal of improving detection and monitoring of community transmission of COVID-19 in those areas not yet covered in the sentinel surveillance system. Case detection and data collection at sentinel sites Case detection: It is recommended to continue using the existing case definitions for influenza surveillance for case detection and sampling. Data collection: Additional variables could be incorporated into the individual case reporting forms in use at sentinel sites. The benefits of adding new variables or data to collect should be balanced against the potentially increased burden on sentinel site staff when making the decision to change the sentinel site case reporting form. Data collection should be designed to meet information needs of public health decision makers, the public, and health workers. The information collected from these case reporting forms is for use at national level for analyses; not all information needs to be reported to regional and global levels. maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance 12 The fields to be reported to regional and global levels in either case-based data or aggregated data reporting is determined by the country and region. At WHO global level, only aggregated data from sentinel surveillance is reported (see “Data reporting, analysis and interpretation”). Avoid duplication of efforts (multiple case report forms, databases, etc.) wherever possible, by adding COVID-19 / ARI / ILI / SARI case definitions to the case reporting and specimen submission form so that there is one form in use to indicate which test should be performed and allow separation by case definition. Collecting information on which case definitions the patient fits would also be useful for retrospective analyses. If one case reporting form is used, ensure that all variables required for weekly aggregated reporting on COVID-19 surveillance to the global level are included. A list of potential variables to consider adding (if not already included in existing case reporting forms) is given in Annex 5. In the context of the COVID-19 pandemic, which has changed healthcare seeking behavior, influenza sentinel networks may need to adapt to ensure that adequate numbers of appropriate specimens and complete clinical and epidemiological information are available to GISRS laboratories for virologic surveillance of influenza. Furthermore, countries that have implemented robust physical distancing policies to control the spread of SARS-CoV-2 are likely to find a decrease in influenza circulation. Therefore, influenza sampling strategies will need to be adapted to ensure an appropriate supply of specimens for virologic surveillance. GISRS should continue to rely on primary care providers, emergency rooms, outpatient clinics, and hospital wards, including intensive care units that continue to serve patients with ILI/ARI and SARI as potential sources of well documented specimens for influenza and SARS-CoV-2 sentinel surveillance. To generate meaningful surveillance output, it is recommended to test at least 50 to 100 sentinel specimens, ideally 150 specimens per week per National Influenza Centre (NIC) or national reference laboratory for influenza and SARS-CoV-2. Specimens should cover all age groups and geographic regions of the country. If the minimum quota of 50-100 specimens tested per week cannot be obtained from sentinel surveillance, consider (in no particular order): Selecting a subset of SARS-CoV-2 negative specimens to test for influenza. Prioritize those samples where there is information indicating symptoms, age, presence of risk factors and geographic location. • Among those, select specimens from patients that meet ILI and SARI case definition to ensure disease severity spectrum is represented. • Among those, select specimens representing different age groups, risk factors, outcomes and geographic locations. Select the remaining specimens needed from non-sentinel surveillance. Sampling strategy and sample size considerations world health organization 13 Clinical specimens Types of clinical specimens recommended for the detection of influenza viruses include: Nasal swabs Nasopharyngeal swabs Combined nose (nasal) and throat (oropharyngeal) swabs Nasal washes Nasopharyngeal aspirates Endotracheal aspirates (for lower tract respiratory infections) Bronchoalveolar lavage (for lower tract respiratory infections). Generally, upper respiratory tract specimens have been shown to be suitable for the molecular detection of influenza and SARS-CoV-2 viruses. Indeed, nasopharyngeal and oropharyngeal swabs placed into a collection vial or directly into centrifuge tube containing 2–3 ml virus transport medium remain the specimen types of choice for influenza and SARS-CoV-2 detection (21, 22). Although current peer-reviewed literature indicates that lower respiratory specimens may be best for the molecular detection of SARS-CoV-2 (23), the sample collection procedure tends to be invasive for patients and may also generate aerosols, as is the case with bronchoalveolar lavages, and difficult for patients to produce, like sputum (24-26). Due to concerns over global paucity of supplies, reagents, and personal protective equipment for specimen collection, saliva, oral fluid, and sputum samples have also been explored as alternative samples for the detection of SARS-CoV-2 (27-30). However, the suitability of these alternative sample types for the detection of influenza (and SARS-CoV-2) remains uncertain, and further research is needed into alternative sampling strategies. At this time, WHO does not recommend the use of saliva as the sole specimen type for SARS-CoV-2 diagnostics. The clinical utility of saliva for the PCR detection of influenza is not known. SARS-CoV-2 has also been detected by reverse transcription chain reaction (PCR) in non-respiratory faecal specimens such as stools and rectal swabs. Until convincing scientific information is available, alternative respiratory and non-respiratory samples should not routinely be used for the surveillance of influenza. If nonstandard collection method is intended to be used, it needs to pass the appropriate validation procedure. Current literature suggests that collecting more than one sample type from each patient may increase the likelihood of SARS-CoV-2 detection by PCR; however, shortages in laboratory testing kits and reagents make this impractical. In the interest of preserving RNA extraction reagents and avoiding increased personnel workload, specimens for influenza testing should be the same ones for used to detect SARS-CoV-2, and vice versa (31). Storage of clinical specimens at the sentinel site If specimens cannot be transported immediately to the laboratory, they can be stored at refrigerator temperature (4oC) for up to 72 hours. If longer storage periods are necessary, specimens should be kept frozen at -70oC or below. Note: DO NOT store clinical specimens at -20oC. Where possible, specimens should not be repeatedly frozen and thawed, because this results in degradation of the virus, reducing detectability and viability for further isolation/characterization. Transport of clinical specimens to the laboratory Transportation of clinical specimens to the laboratory follows national and international transport regulations. WHO recommends (32, 33) authorities to transport patient specimens that potentially may contain human seasonal influenza viruses or SARS-CoV-2 as UN 3373, Biological substance, Category B. Laboratory considerations – sentinel surveillance specimens maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance 14 Handling of clinical specimens in the laboratory Aside from standard practices in handing influenza clinical specimens, special precautions need to be taken when handling such specimens in the laboratory (34), since respiratory specimens may also contain SARS-CoV-2 and zoonotic influenza viruses. For culture of influenza viruses, please see the section “Biosafety and Biosecurity”. Efforts must be made to confirm the absence of SARS-CoV-2 and zoonotic influenza viruses in specimens intended for influenza virus culture. Isolation and passage of samples containing SARS-CoV-2 and zoonotic influenza viruses must currently be done in a biosafety level 3 (BSL3) laboratory with BSL3 procedures or equivalent. Algorithms for surveillance testing of influenza and SARS-CoV-2 During the ongoing COVID-19 pandemic, national authorities in many countries have requested their GISRS laboratories to serve as SARS-CoV-2 testing sites, for primary clinical diagnosis, national reference laboratory service or surveillance. This has presented challenges to many laboratories on technical and programmatic fronts. These challenges include SARS-CoV-2 specific tests to be established and validated; overwhelming numbers of clinical specimens to be tested and reported; logistical problems in acquiring reagents; sourcing consumables and reagents; equipment procurement and use; hiring and training of additional staff; specimens coming from outside the sentinel network built for influenza surveillance; specimens with incomplete background information about the patient; building additional IT capacity for data registration and reporting of results. Despite the pressure from the COVID-19 pandemic, it is imperative for the GISRS to maintain meaningful surveillance of influenza worldwide and to remain vigilant of the influenza threat, both epidemic and pandemic. To address the need for both influenza and COVID-19, in a straightforward strategy is 1) to ensure optimal quantity and quality of all sentinel specimens from ILI/ARI, and SARI patients, and 2) to test these specimens for both influenza and SARS-CoV-2. Current strides are being made on the development of reliable and time-saving multiplex assays for the simultaneous detection of influenza and SARS-CoV-2 in one PCR reaction. However, for the next 3 to 6 months, single-plex assays may be the only option for molecular detection of influenza or SARS-CoV-2 in most countries. Ideally, single-plex assays for influenza and SARS-CoV-2 should be run in parallel, though this may not always be possible. Therefore, GISRS laboratories in many countries must decide the sequence of testing: either influenza viruses or SARS-CoV-2 as first line, depending on the national testing strategy. The testing algorithms below are for two situations: with influenza as the first testing preference (Figure 1A), or with SARS-CoV-2 as first preference (Figure 1B). The decision on the first preference should be made based on the epidemiological situation for COVID-19, available resources and relevant national guidance. The testing algorithms enable the monitoring of the potential co-circulation of these respiratory viruses during the influenza season 2020/2021 in the Northern Hemisphere, and the detection of co-infections with SARS-CoV-2 and influenza or other respiratory viruses. Some SARS-CoV-2 infected individuals shed virus or viral RNA over extended periods. Therefore, test results must be carefully interpreted, and clinical history combined with laboratory results may help to determine specific etiology. world health organization 15 Figure 1A. Testing algorithm for laboratories that test for influenza viruses as a first preference 1 Specimens from the sentinel surveillance site meeting specific surveillance case definition (ILI/ARI/ SARI). Nasal swabs, throat swabs, combined nasal and throat swabs, nasopharyngeal aspirates are suitable clinical specimens for the detection of both influenza viruses and SARS-CoV-2 in clinical specimens. 2 The dashed line indicates that influenza-positive specimens should, if resources allow, be shown to be SARS-CoV-2 negative prior to submitting to a WHO CC. 3 Follow the operational guidance on sharing seasonal Influenza viruses with WHO CCs under the GISRS. 4 The summary results of testing should be shared with WHO through the global database FluNet or through WHO regional databases linked with FluNet. Figure 1A shows a flow-chart for testing clinical specimens, primarily for influenza viruses and then for SARS-CoV-2. It is recommended that multiplex PCR assays for the simultaneous detection of influenza A and B viruses and SARS-CoV-2 be used if they are available (green boxes) and that influenza positive samples are passed on to WHO Collaborating Centres (CCs) for further characterization as a standard GISRS function. If resources allow, advance along dashed line under green boxes. When multiplex PCR assays are not available, then single-plex assays for influenza A and for influenza B (yellow boxes) are used and followed up with single-plex for SARS-CoV-2. Figure 1A Respiratory specimen1 Submit a subset to WHO CCs for influenza3 and/or sequence a proportion of samples Singleplex assay Influenza A/B Influenza Influenza A2 Influenza B2 Test for SARS- CoV-2 SARS-CoV-2 + SARS-CoV-2 Perform confirmatory testing (if required) Discard or test for other respiratory pathogens Subtype H1/H3 Determine lineage Vic/Yam Submit data to WHO FluNet4. Upload sequence data to GISAID or other publicly accessible database. - + + SARS-CoV-2 + SARS-CoV-2 + Influenza A/B + SARS-CoV-2 - Influenza A/B + Perform confirmatory testing (if required) Pass onto COVID-19 reference centre or culture (BSL3) or sequence as appropriate Multiplex assay Influenza A/B +/- SARS-CoV-2 +/- Submit data to WHO COVID-19 database. Upload sequence data to GISAID or other publicly accessible database SARS- CoV-2 Influenza A/B - Discard or test for other respiratory pathogens - maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance 16 Figure 1B. Testing algorithm for laboratories that test for SARS-CoV-2 as a first preference 1 Specimens from the sentinel surveillance site meeting specific surveillance case definition (ILI/ ARI/ SARI). Nasal swabs, throat swabs, combined nasal and throat swabs, nasopharyngeal aspirates are suitable clinical specimens for the detection of both influenza viruses and SARS-CoV-2 in clinical specimens. 2 Follow the operational guidance on sharing seasonal Influenza viruses with WHO CCs under the GISRS 3 The summary results of testing should be shared with WHO through the global database FluNet or through WHO regional databases linked with FluNet. Figure 1B Figure 1B shows a flow-chart for the testing of clinical specimens primarily, for SARS-CoV-2 first and then for influenza A and B viruses. It is recommended that multiplex PCR assays for the simultaneous detection of influenza A and B viruses and SARS-CoV-2 be used if available (green boxes) and that influenza positive samples are passed on to WHO CCs for further characterization as standard GISRS function; if resources allow, advance along the dashed line under green boxes. If multiplex PCR assays are not available, then single-plex assays for SARS-COV-2 (yellow boxes) are used followed up with single-plex for influenza A subtypes and B. Respiratory specimen1 Singleplex assay SARS-CoV-2 SARS-CoV-2 SARS-CoV-2 Test for influenza A/B Influenza A + Influenza B + Subtype H1/H3 Determine lineage Vic/Yam Submit a subset to WHO CCs for influenza2 and/or sequence a proportion of samples Submit data to FluNet3. Upload sequence data to GISAID or other publicly accessible database Influenza A/B - Discard or test for other respiratory pathogens + ++ + - SARS-CoV-2 + SARS-CoV-2 +Influenza A/B + SARS-CoV-2 - Influenza A/B + Perform confirmatory testing (if required) Pass onto reference centre or culture (BSL3) or sequence as appropriate Multiplex assay Influenza A/B +/- SARS-CoV-2 +/- Submit data to WHO COVID-19 database. Upload sequence data to GISAID or other publicly accessible database SARS-CoV-2 Influenza A/B - Discard or test for other respiratory pathogens world health organization 17 With the continued circulation of SARS-CoV-2, the WHO CCs of GISRS would highly prefer to receive influenza-positive clinical specimens that are negative by RT-PCR for SARS-CoV-2 from NICs and other laboratories, and influenza virus isolates derived from clinical specimens that are negative by real-time reverse transcription PCR (RT-PCR) for SARS-CoV-2. It is suggested that influenza isolates be grown only from influenza virus-positive samples that are negative for SARS-CoV-2. For SARS- CoV-2-positive specimens that require laboratory confirmation, WHO has established a network of COVID-19 reference laboratories (35) providing confirmatory testing for COVID-19. If it is not possible for a laboratory to screen influenza positive samples for SARS-CoV-2 before shipping to a WHO GISRS CC, the submission sheet should indicate that these samples have NOT been screened for SARS-CoV-2, which should also be noted in corresponding emails with the WHO CC receiving the samples. It is critical to GISRS function to share in a timely manner influenza isolates or clinical specimens that are positive for influenza. Follow the operational guidance on sharing seasonal Influenza viruses with WHO CCs under the GISRS. Select a subset of recently collected viruses or specimens representing both currently circulating subtypes of influenza A viruses and both lineages of influenza B viruses. If an influenza A virus cannot be subtyped as either H1pdm09 or H3, alert a WHO CC without delay and send the samples as soon as possible (36). GISRS laboratories need to be reminded that the selection of influenza vaccine viruses is dependent on the availability of virus isolates, and they are encouraged to continue sending influenza isolates or original clinical specimens to WHO CCs for culture and full characterization of influenza viruses. Laboratory techniques for the detection of influenza and SARS-CoV-2 Real-time reverse transcription PCR (rRT-PCR) is the gold standard for detection of influenza viruses in GISRS laboratories. PCR is a highly sensitive and specific method for the detection of pathogens in clinical specimens (37-39). Primers and probes can quickly be adapted when mutations in critical sites of the pathogens’ nucleic acid are recognized; required reagents are available in high quality from many different sources; and the procedure for extracting viral nucleic acids will inactivate viruses in clinical specimens, which allows for their safe use for other tests. For GISRS laboratories, the International Reagent Resource (IRR)(40) of the WHO CC for the Surveillance, Epidemiology and Control of Influenza at the United States Centers for Disease Control and Prevention (US CDC) has been the primary source for influenza PCR reagents and kits. Rapid sharing of sequence data following the emergence of SARS-CoV-2 allowed the design of suitable primers and probes for the specific detection of this novel virus. Suggested protocols for molecular detection of SARS-CoV-2 were published on the WHO website (23). Multiplex assays for the identification of more than one pathogen in the same PCR reaction allows for a more resourceful use of reagents, consumables and hands-on time. Multiplex PCR formats for the simultaneous detection of influenza A and B viruses have been available for several years, and for many GISRS laboratories these are the primary methods for influenza surveillance. At the time of writing this document, the US CDC has developed a multiplex rRT-PCR assay for the simultaneous detection of influenza viruses and SARS-CoV-2. However, this test will only be available to a limited number of GISRS laboratories in the next 3 to 6 months in a kit format due to limitations of production capacity. The US CDC multiplex assay’s instructions for use (41) and the sequence information for primers and probes (42) are publicly available for reference in the development of a diagnostic test based on the CDC design. Selection of influenza positive clinical specimens and virus isolates to forward to a WHO CC maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance 18 In addition to the multiplex assay developed by US CDC, other test formats, including several commercial tests, are available and have been described elsewhere (43). Whatever test format is to be used for influenza and SARS-CoV-2 surveillance, it is of utmost importance to ensure highest sensitivity and specificity for the targeted pathogens. Also, well- characterized positive and negative controls must be included in each test run. To assess their performance, laboratories should regularly participate in external quality assessment programs provided by the WHO Global Influenza Programme (GIP) and other sources (e.g. Quality Control for Molecular Diagnostics or Royal College of Pathologists of Australasia Quality Assurance Programs). Biosafety and Biosecurity The diagnosis of respiratory virus infection can rarely be established based only on clinical symptoms. Many respiratory pathogens can cause similar symptoms. Patients presenting with ILI or SARI may be infected with an influenza virus, SARS-CoV-2, one of many other respiratory viruses, bacteria or a novel virus or could be simultaneously infected with two or more pathogens. Health workers are at a high risk for contracting infections in clinical settings. Doctors, nurses and other staff who interact with suspected influenza or COVID-19 patients are at especially high risk. Health workers interacting with suspected influenza or COVID-19 patients, as well as laboratory workers handling clinical specimens from such patients, must be protected with appropriate training, and adequate personal protective equipment (PPE) based on thorough risk assessment. Every year, health care workers should be firmly encouraged to take the seasonal influenza vaccine. Health care workers and laboratory workers must be immediately tested for influenza and SARS- CoV-2 if respiratory symptoms occur. Biosafety practices recommended for seasonal or zoonotic influenza virus isolation are described in the WHO Manual for the laboratory diagnosis and virologic surveillance of influenza. Biosafety practices and guidelines for handling SARS-CoV-2 infectious material are described in several publications. For each work step, from collecting clinical specimens to transport to the laboratory to all procedures in the laboratory, a careful risk assessment must be conducted. All laboratory workers must be properly trained in the use of PPE and the required safety procedures (22, 34). If laboratories are attempting to culture influenza viruses, clinical specimens should be tested for SARS-CoV-2; and SARS-CoV-2 negative samples that are influenza A(H1)pdm09 or A(H3)/B positive can be considered for virus isolation. Although it cannot be completely excluded, it is unlikely that SARS-CoV-2 will replicate in cell lines or embryonated hens’ eggs commonly used for the isolation of influenza viruses (44). For attempts to culture SARS-CoV-2, strict biosafety level 3 (BSL3) conditions must be observed. A “sequence first” approach could be used to determine which specimens are selected for culture and would be particularly useful in the case of influenza and SARS-CoV-2 co-infections where culture at BSL3 could be restricted to specimens that warranted further investigation. All clinical specimens are regarded as potentially infectious until proven otherwise. Material potentially containing SARS-CoV-2 must be handled and stored in areas with restricted access. world health organization 19 Data reporting, analysis and interpretation Data reporting and analysis at the national level Regular analysis and reporting of national sentinel surveillance data helps to ensure that the information is available to policy makers, healthcare providers, and the public and will also improve the consistency of reporting from sentinel sites. Whenever feasible, such reports should be available to the public on the national surveillance website. Reports should include a summary interpretation with graphs, if possible, to support the interpretation. For COVID-19 data obtained using existing sentinel surveillance systems, additional reporting considerations include establishment of: procedures for routinely reporting the analysis results to authorities managing the overall COVID-19 response and determining the recipients of reports, the frequency of reporting and what data should be included in the reports procedures and actions when a SARS-CoV-2 positive result is detected in a sentinel sample, depending on the response strategy in the country; and if it would be reported (e.g., to general practitioner, COVID task force / other authorities responsible) for contract tracing or other actions Data reporting to regional and global levels Many countries are already familiar with reporting routine influenza surveillance to FLUNET (virological data) and FluID (epidemiological data) global databases, either directly or via the WHO regional platforms. FluMart (45), the global data reporting platform which houses the FLUNET and FLUID datasets, allows the uploading of any user-defined data files in their own format and transforms them into standardized data. FluMart was configured to collect COVID-19 early in the pandemic and to add this data to FLUNET and FLUID datasets. COVID-19 information should be included as additional variables in the same data file as influenza data when reporting directly to FluMart. What to report: Influenza testing data: continue reporting aggregated influenza surveillance data on a weekly basis to regional and global levels. At a minimum, this should be the number of samples from all sources processed for influenza testing, the number of samples positive for influenza and the number of samples tested and/or samples negative for influenza. Wherever possible, this data should be disaggregated by source (sentinel and non-sentinel) . COVID-19 testing data: countries are requested to report weekly-aggregated COVID-19 results in the same format and frequency as they have been reporting influenza surveillance data. Virologic data (such as the number of samples testing positive and negative for COVID-19) from cases sampled in existing sentinel and non-sentinel or syndromic surveillance systems should be reported on a weekly basis to regional and global levels. Co-infections with influenza and SARS-CoV-2: Reporting the detection of co-infections with SARS-CoV-2 and influenza or other respiratory viruses is possible. If reporting to FLUNET is done with an excel file upload, modifications to the routine reporting template would allow the reporting of the number of co-infections per week by combination of viruses detected (e.g. influenza/SARS-CoV-2 or influenza A/SARS-CoV-2). Contact flumart@who.int for further instructions on reporting co-infections. Syndromic surveillance data: continue reporting the ILI and SARI data with age breakdown and where possible by influenza type with the denominators. Where established, ARI or pneumonia data should continuously be reported. maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance 20 How to report: For countries uploading data directly to FLUMART, please contact flumart@who.int for assistance in modifying the routine reporting influenza template to include COVID-19 data and for assistance in uploading. For countries reporting influenza and COVID-19 testing data to regional platforms, this should be done through existing regional platforms and WHO regional contact persons. Please include flumart@who.int in all messages. When to report: Routine reporting of influenza and COVID-19 data should continue on a weekly basis. For direct reporting to global platforms, data should be reported by Thursday of the following week. Deadlines for reporting to regional platforms may differ. See Annex 7 for more information on how and what to report. Monitoring and evaluation Regular monitoring of the surveillance system should be done to detect and address disruptions that arise during the course of surveillance. Periodic, thorough surveillance system evaluations could be considered when time and resources allow. Actions to consider: Involve additional stakeholders in the monitoring and evaluation, such as members of incident management team (see below) or national COVID-19 task force. Document any changes in resources / governance of existing surveillance systems during -19 pandemic. Document and understand changes in information flow between sentinel sites, laboratories and national surveillance units. Document any changes in healthcare delivery in primary and hospital-based facilities during the COVID-19 pandemic. If adding SARS-CoV-2 as another respiratory pathogen under surveillance in an existing system, monitor the results of the surveillance system evaluation, especially attributes such as timeliness of sample transport and processing, completeness and representativeness of the sentinel system. More information on how, why and when to conduct monitoring and evaluation can be found in Annex 8. Translating evidence to policy National COVID-19 responses usually involve establishing an incident management team (IMT). A designated focal point for respiratory disease surveillance should be a member of this IMT and act as a liaison with routine respiratory disease surveillance programs. Information from the routine respiratory disease sentinel surveillance programs should be integrated into the overall assessment of the situation of acute respiratory infections in the country. Routine influenza sentinel surveillance should be seen as one (but not exclusive) important set of information to analyse and assess the situation. Influenza surveillance data should continue to be used in pandemic influenza severity assessments (PISA), recognizing that changes to the surveillance system may alter baselines and interpretations. Information coming from all surveillance systems should be assessed to inform clinical management, risk communication (46) and non-pharmaceutical interventions (47, 48) such as scaling up of response activities, including maintaining essential health services, increasing the number of critical care beds, restricting non-essential travel, implementing school measures, recommending social distancing measures or mandating mask use. world health organization 21 Extensive guidance on surveillance during an influenza pandemic is available, and much of the content in that guidance is relevant in the current situation. See https://apps.who.int/iris/bitstream/hand le/10665/259886/9789241513333-eng.pdf?sequence=1 for more information and background. For more information on the Pandemic Influenza Severity Assessment, see the WHO guidance: https://www.who.int/influenza/surveillance_moni- toring/pisa/en/. More information on implementing SARI surveillance is included in the WHO Global Epidemiological Surveillance Standards for Influenza: https://apps. who.int/iris/handle/10665/311268 Detailed guidance on monitoring and evaluation of sentinel surveillance systems for influenza is included in the Global Epidemiological Surveillance Standards for Influenza: https://apps.who.int/iris/handle/10665/311268, and https://www.cdc.gov/globalhealth/healthprotection/fetp/training_mod- ules/12/Eval-Surv-Sys_FieldG_Final_09262013.pdf. FURTHER READING maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance 22 References 1 Global Influenza Surveillance and Response System (GISRS). 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Geneva: World Health Organization (https://apps.who.int/iris/rest/bitstreams/1314216/retrieve, accessed 5 November 2020). 26 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance DEFINITION SOURCE CRITERIA ILI ILI ARI ARI ARI for RSV SARI Suspected COVID-191 COVID-19-like illness (CLI) COVID-19-like illness – combination-1 COVID-19- like illness – combination-2 WHO (2013) CDC WHO Regional Office for Europe / ECDC US CDC WHO WHO WHO (7 Aug 2020) US CDC (5 Aug 2020) US CSTE (Council of State and Territorial Epidemiologists) US CSTE (Council of State and Territorial Epidemiologists) Fever + cough Fever (37.80 C) + cough and/or sore throat At least ONE of the following: Cough, sore throat, shortness of breath, runny nose (note – fever not required) At least TWO of the following: Fever, cough, runny nose or nasal congestion, sore throat At least ONE of the following: Cough, sore throat, shortness of breath or runny nose Fever (measured or reported) + cough or shortness of breath + hospitalization Part A: A person who meets the clinical and epidemiological criteria: Clinical criteria: Acute onset fever and cough OR at least THREE of the following: Fever, cough, general weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnoea, anorexia/nausea/vomiting, diarrhoea, altered mental status AND Epidemiological criteria: Residing or working in an area with high risk of transmission of virus: closed residential settings, humanitarian settings such as camp and camp-like settings for displaced persons; any time within the 14 days prior to symptom onset; OR Residing or travel to an area with community transmission any time within the 14 days prior to symptom onset; OR Working in any health care setting, including within health facilities or within the community any time within the 14 days prior of symptom onset. Part B: Fever (measured or reported) + cough or shortness of breath + hospitalization At least TWO of the following: Fever (measured or reported), chills, rigours, myalgia, headache, sore throat, nausea or vomiting, diarrohea, fatigue, congestion or runny nose OR At least ONE of the following: Cough, shortness of breath, difficulty breathing, new loss of smell, new loss of taste OR At least ONE of the following: Pneumonia (clinical or x-ray), ARDS At least ONE of the following: Cough, shortness of breath or discomfort breathing OR At least TWO of the following: Fever, myalgia, headache, chills, loss of taste or smell, sore throat At least ONE of the following: Cough, shortness of breath, discomfort breathing, new olfactory disorder, new taste disorder OR at least two of the following: Fever, chills, rigors, myalgia, headache, sore throat, nausea or vomiting, diarrhoea, fatigue, congestion or runny nose Supplementary Table S1: Glossary of commonly used case definitions for influenza and COVID-19 1 For the case definition of probable and confirmed COVID-19 case please visit https://www.who.int/publications/i/item/WHO-2019-nCoV-Surveillance_Case_Definition-2020.1 27 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance CHILE1 COSTA RICA2 PARAGUAY3 SOUTH AFRICA4 TESSy5 UK6 USA7 Data source Type of surveillance Patients source Total patients Specimens Diagnostic Symptoms evaluated SARI surveillance Sentinel; (SARS-CoV-2 testing in 5 of 6 hospitals) 6 SARI hospitals SARI (2,199) RT-PCR ILI / SARI surveillance Sentinel 9 ILI centers; 18 hospitals ILI (14,528); SARI (2,577) RT-PCR ILI / SARI surveillance Sentinel 5 ILI sites; 10 SARI hospitals ILI (2,075); SARI (4,090) RT-PCR Pneumonia surveillance Sentinel 9 sentinel hospitals ARI (1,538); SARI (835) Nasopharyngeal swabs RT-PCR Any fever, cough, sore throat, difficulty of breathing ILI / ARI / SARI surveillance Comprehensive COVID-19 Primary care; Hospitals ILI (64,885); ARI (205,481); SARI (13,398) ARI (ECDC), ILI / SARI (WHO) case definition - COVID-19 tracker app; - FF100 / FluWatch Non-sentinel Community - COVID-19 tracker app (2700 positives, 14,309 negatives); - FF100 (301 cases); - FluWatch (1637 non- COVID-19 cases) Cough, fever, shortness of breath, gastrointestinal symptoms, general symptoms CDC household transmission study Non-sentinel Households with COVID-19 primary case, no hospitalizations 62 primary contacts; 195 household contacts NP swab, self-swab RT-PCR Runny nose, sore throat, cough, chest pain, shortness of breath, discomfort while breathing, wheezing, headache, new loss of smell or taste, fever/chills, fatigue, muscle ache, diarrhoea, abdominal pain, nausea/vomiting Supplementary Table S2: Source and heterogeneity of data analysed to estimate performance characteristics for ILI, ARI and SARI case definitions for COVID-19 continued ... 28 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance 0-14 years 15-39 years 40-64 years 65+y years Males Summary conclusion Limitations 5% 11% 37% 46% 55% - Specificity high in elderly - Sensitivity high in young adults - Few SARI cases in children ILI (9%, 54%, 30%, 6%), SARI (14%, 33%, 29%, 24%) ILI (51%); SARI (53%) - Sensitivity low for ILI - Sensitivity and specificity low for SARI COVID-19 case definition modified many times ILI (4%, 63%, 28%, 4%), SARI (19%, 16%; 24%, 40%) ILI (43%); SARI (55%) - Sensitivity low for ILI - acceptable performance for SARI ARI (41%, 19%, 27,13%); SARI (44%, 19%, 26%, 12%) ARI (49%) SARI (51%) - Sensitivity high for ARI - Specificity low for ARI - Acceptable performance for SARI ILI (17%, 24%, 30%, 28%), ARI (4%, 36%, 42%, 17%), SARI (26, 42%, 45%, 31%) - Sensitivity high for ARI - Sensitivity low for ILI and SARI especially for younger age- groups - Marginal increase in sensitivity by extending case definitions but at cost of marked increase in false positives - Adding delirium in older adults helps Children (<18 years) – 63 (34%) Adults (18+years) – 122 (66%) 49% - ILI was highly specific - ARI was highly sensitive - Sensitivity low in children Predictive values dependent on disease prevalence (30% secondary transmission rate in households) Supplementary Table S2: Heterogeneity of unpublished data from countries analyzed to estimate performance characteristics for ILI, ARI and SARI case definitions for COVID-19 continued ... Abbreviations: ARI, acute respiratory infection; ILI, influenza like illness; SARI, severe acute respiratory infection; USA, United States of America; UK, United Kingdom of Great Britain and Northern Ireland 1 Departamento de Epidemiología de la División de Planificací Sanitaria del Ministerio de Salud de Chile, Hospitales Centineles para la vigilancia de IRAG y el Instituto de Salud Pública, unpublished data, 23 September 2020 2 Ministerio de Salud de Costa Rica, INCIENSA, CCSS, unpublished data, 23 September 2020 3 Ministerio de Salud Pública de Paraguay, unpublished data, 23 September 2020 4 Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, South Africa, unpublished data, 23 September 2020 5 Gianfranco Spiteri, European Center for Disease Prevention and Control, personal communication, 23 September 2020. TESSy data includes 8 countries (Czechia, Germany, Estonia, Malta, Poland, Portugal, Slovakia, United Kingdom) 6 Andrew Hayward, Institute of Epidemiology and Health Care, University College London, personal communication, 23 September 2020 7 Reses HE FM et al. Performance of Existing and Novel Surveillance Case Definitions for COVID-19 in the Community. MedRxiv 2020. CHILE1 COSTA RICA2 PARAGUAY3 SOUTH AFRICA4 TESSy5 UK6 USA7 29 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Supplementary Table S3: Influenza like illness (ILI) performance characteristics for COVID-19 Abbreviations: AUC, area under the curve; CI, confidence interval; NPV, negative predictive value; PPV, positive predictive value; USA, United States of America; UK, United Kingdom of Great Britain and Northern Ireland All ages Costa Rica 28.4 (27.6 - 29.2) 71.8 (70.0 - 73.6) 82.6 (81.4 - 83.7) 17.6 (16.8 - 18.3) Paraguay 38.8 (35.3 - 42.7) 61.7 (59.0 - 64.3) 36.5 (33.2 - 39.9) 64.0 (61.3 - 66.6) USA 51 90 64 84 UK 19.7 (15.3 - 24.7) 81.6 (79.9 - 83.3) 5.3 (4.2 - 6.7) 5 95.1 (94.8 - 95.4) 5 0.507 (0.482 - 0.531) 0 - 14 years Costa Rica 27.1 (24.5 - 29.9) 63.6 (57.3 - 69.5) 76 (71.4 - 80.2) 17 (14.7 - 19.6) Paraguay 20.0 (4.3 - 48.0) 56.0 (44.0 - 67.4) 8.3 (1.7 - 22.4) 77.7 (64.4 - 87.9) Note: 0 – 18 years USA 43 96 UK 25.0 (0.6 - 80.6) 67.3 (63.1 - 71.4) 3.9 (0.7 - 18.1) 5 94.5 (90.6 - 96.8) 5 0.462 (0.216 - 0.707) 15 - 39 years Costa Rica 27.8 (26.7 - 28.9) 73.6 (71.2 - 76) 84 (82.3 - 85.5) 17 (16 - 18) Paraguay 36.7 (32.6 - 41.4) 62.7 (59.3 - 66.1) 38.6 (34.3 - 43.1) 60.8 (57.4 - 64.2) Note: 18+ years USA 86 55 UK 20.0 (12.7 - 29.2) 84 (79.8 - 87.6) 6.2 (4.0 - 9.4) 5 95.2 (94.7 - 95.7) 5 0.52 (0.476 - 0.563) 40 - 64 years Costa Rica 29.5 (28 - 31) 70.2 (66.8 - 73.4) 82.3 (80.1 - 84.3) 17.5 (16.2 - 18.9) Paraguay 45.5 (38.6 - 52.6) 59.7 (54.6 - 64.7) 37.6 (31.5 - 44.0) 67.3 (62.0 - 72.3) UK 19.1 (13.2 - 26.2) 86.3 (83.8 - 88.4) 6.8 (4.8 - 9.5) 5 95.3 (94.9 - 95.6) 5 0.527 (0.493 - 0.56) >65 years Costa Rica 30 (26.7 - 33.5) 77.3 (70.9 - 82.9) 82.6 (77.5 - 87) 23.5 (20.4 - 26.9) Paraguay 38.1 (18.1 - 61.5) 66.6 (53.9 - 77.8) 26.6 (12.2 - 45.8) 77.1 (64.1 - 87.2) UK 21.1 (9.55 -37.3) 89.8 (85.6 - 93.1) 9.8 (5.1 - 18.1) 5 95.6 (94.8 - 96.2) 5 0.554 (0.486 - 0.622) SENSITIVITY (95% CI) SPECIFICITY (95% CI) PPV (95% CI) NPV (95% CI) AUC (95% CI) COUNTRY 1 Ministerio de Salud de Costa Rica, INCIENSA, CCSS, unpublished data, 23 September 2020 2 Ministerio de Salud Pública de Paraguay, unpublished data, 23 September 2020 3 Andrew Hayward, Institute of Epidemiology and Health Care, University College London, personal communication, 23 September 2020 4 Reses HE FM et al. Performance of Existing and Novel Surveillance Case Definitions for COVID-19 in the Community. MedRxiv 2020. 5 PPV and NPV estimated at 5% prevalence 1 2 3 4 30 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Supplementary Table S4: ARI1 performance characteristics for COVID-19 Abbreviations: ARI, acute respiratory infection; AUC, area under the curve; CI, confidence interval; NPV, negative predictive value; PPV, positive predictive value. 1 ARI defined as at least ONE of the following: cough, sore throat, shortness of breath or runny nose AND symptoms ≤ 10 days; denominator is hospitalized LRTI irrespective of symptom duration 2 Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, South Africa, unpublished data, 23 September 2020 SENSITIVITY (95% CI) SPECIFICITY (95% CI) PPV (95% CI) NPV (95% CI) AUC (95% CI)COUNTRY All ages South Africa 86.5 (82.8 - 89.8) 22.7 (20.6 - 24.8) 22.2 (20.1 - 24.3) 86.9 (83.2 - 90.0) 0.5 (0.5 - 0.6) 0 - 14 years 85.2 (66.3 - 95.8) 13.3 (10.8 - 16.0) 3.6 (2.3 - 5.4) 95.9 (89.9 - 98.9) 0.5 (0.4 - 0.6) 15 - 39 years 90.7 (82.5 - 95.9) 30.1 (24.9 - 35.6) 27.4 (22.3 - 32.9) 91.8 (84.4 - 96.4) 0.6 (0.6 - 0.7) 40 - 64 years 85.1 (79.4 - 89.7) 33.3 (28.5 - 38.4) 41.2 (36.4 - 46.1) 80.3(73.0 - 86.3) 0.6(0.5 - 0.6) >65 years 86.3 (76.6 - 92.9) 26.0 (19.7 - 33.1) 34.5 (27.9 - 41.5) 80.7 (68.1 - 90.0) 0.6 (0.5 - 0.6) 2 31 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance All ages Chile 49.0 (46.2 - 51.9) 50.2 (47.0 - 53.3) 54.8 (51.8 - 57.8) 44.3 (41.4 - 47.3) Costa Rica 39.5 (37.3 - 41.6) 32.9 (29.0 - 37.0) 68.2 (65.5 - 70.9) 13.0 (11.2 - 14.8) Paraguay 55.4 (51.9 - 58.8) 60.4 (58.7 - 62.0) 25.9 (23.9 - 28.0) 84.4 (82.8 - 85.8) South Africa 51.0 (46 - 56.1) 59.0 (56.5 - 61.5) 24.1 (21.2 - 27.1) 82.8 (80.2 - 84.8) 0.6 (0.5 - 0.6) 0 - 14 years Chile 14.2 (0.36 - 57.8) 31.5 (23.0 - 41.0) 1.3 (0.03 - 7.0) 85.3 (70.8 - 94.4) Costa Rica 47.2 (38.3 - 56.3) 32.7 (26.5 - 38.6) 26.9 (21.2 - 33.2) 53.7 (45.3 - 62.1) Paraguay 44.4 (21.5 - 69.2) 54.6 (51.0 - 58.1) 2.2 (0.97 - 4.4) 97.6 (95.7 - 98.8) South Africa 51.9 (31.9 - 71.3) 50.2 (46.5 - 54.0) 3.8 (2.1 - 6.3) 96.5 (94.1 - 98.1) 0.5 (0.4 - 0.6) 15 - 39 years Chile 58.3 (48.9 - 67.2) 31.4 (23.4 - 40.4) 45.1 (37.1 - 53.3) 43.8 (33.3 - 54.7) Costa Rica 35.8 (32.4 - 39.3) 34.1 (23.8 - 45.7) 84.2 (77.9 - 88) 5.1 (3.4 - 7.3) Paraguay 66.6 (57.2 - 74.8) 51.3 (46.9 - 55.6) 24.4 (20.0 - 29.4) 86.6 (82.4 - 90.2) South Africa 54.7 (43.5 - 65.4) 62.2 (56.4 - 67.7) 29.6 (22.6 - 37.3) 82.5 (76.9 - 87.3) 0.6 (0.5 - 0.7) 40 - 64 years Chile 55.2 (50.8 - 59.5) 46.2 (40.6 - 52.0) 63.1 (58.5 - 67.6) 38.2 (33.2 - 43.3) Costa Rica 38.8 (35 - 42.7) 34 (24.7 - 44.3) 79.6 (74.7 - 83.9) 7.7 (5.3 - 10.6) Paraguay 60.3 (55.1 - 65.5) 59.5 (55.6 - 63.4) 46.1 (41.5 - 50.7) 72.4 (68.3 - 76.2) South Africa 48.8 (41.7 - 55.9) 68.6 (63.6 - 73.3) 46.0 (39.2 - 53.0) 70.9 (65.9 - 75.6) 0.6 (0.5 - 0.6) >65 years Chile 41.9 (37.8 - 46.1) 62.9 (58.2 - 67.4) 59.5 (54.5 - 64.3) 45.4 (41.4 - 49.5) Costa Rica 44.6 (40 - 49.2) 32.6 (24.8 - 41.1) 69.4 (63.8 - 74.5) 14.6 (10.9 - 19.1) Paraguay 46.0 (40.5 - 51.7) 67.7 (65.1 - 70.2) 25.2 (21.7 - 28.9) 84.1 (81.8 - 86.2) South Africa 52.5 (41.0 - 63.8) 69.5 (62.1 - 76.2) 43.8 (33.6 - 54.3) 76.4(69.1 - 82.7) 0.6 (0.5 - 0.7) Supplementary Table S5: SARI performance characteristics for COVID-19 1 Departamento de Epidemiología de la División de Planificací Sanitaria del Ministerio de Salud de Chile, Hospitales Centineles para la vigilancia de IRAG y el Instituto de Salud Pública, unpublished data, 23 September 2020 2 Ministerio de Salud de Costa Rica, INCIENSA, CCSS, unpublished data, 23 September 2020 3 Ministerio de Salud Pública de Paraguay, unpublished data, 23 September 2020 4 Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, South Africa, unpublished data, 23 September 2020 5 SARI defined as acute onset fever and cough within past 10 days and hospitalization; denominator is hospitalized LRTI rrespective of symptom SENSITIVITY (95% CI) SPECIFICITY (95% CI) PPV (95% CI) NPV (95% CI) AUC (95% CI)COUNTRY 1 2 3 4,5 Abbreviations: AUC, area under the curve; CI, confidence interval; NPV, negative predictive value; PPV, positive predictive value; SARI, severe acute respiratory infection 32 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Annex 1. Strengths and limitations of ILI / ARI / SARI surveillance to address COVID-19 objectives LIKELY POSSIBLE UNLIKELY PROS CONS/LIMITATIONSDATA SOURCE Outpatient surveillance (ARI or ILI) with laboratory confirmation of all or a subset. Sentinel syndromic and virologic approach uses a systematic case detection strategy. If sentinel virologic surveillance follows a consistent sampling strategy, the resulting percent positivity for SARS- CoV-2 may be a more accurate reflection of virus circulation than that from universal testing, where the strategy varies over time and place. Proportion of symptomatic patients among all outpatients or admissions or population- based rates can be calculated if the denominator information is often available. Trends of COVID-19 percent positivity among patients meeting the ILI case definition and presenting to outpatient sentinel sites could be one indicator for determining if community transmission is occurring and complementary to universal surveillance and reporting schemes. Captures trends in symptomatic persons seeking healthcare and meeting the specific case definition for surveillance. Depends on sustained sentinel syndromic surveillance with consistent and complete reporting. Need laboratory confirmation of all or a subset of samples from syndromic surveillance to determine trends of COVID-19. The COVID percent positivity is dependent on what else is circulating that manifests as ILI. Depends on lab algorithm, testing priorities, use of single versus multiplex assays, NPIs in place, capacities, resources, political issues, etc. Not meant to replace but complement comprehensive COVID-19 surveillance designed to allow contact tracing. Surveillance does not imply monitoring for changes in relation to intensity thresholds as there is little historical data available for threshold determination for COVID positivity among patients meeting sentinel surveillance case definitions. Data from continued sentinel syndromic surveillance could be compared to historical data if no major disruptions to surveillance occurred. Timeliness: General lag of about 2 weeks between symptom onset and reporting. Geographical representativeness: data reflects situation in population served by sentinel sites and may not be granular enough or represent the general population at the national level. Demographic representativeness: data reflects situation in population served by sentinel sites and may not reflect the general population. Validity depends on whether symptomatic COVID-19 cases seek care at sentinel outpatient sites. Monitor longer term epidemiologic trends and evolution of SARS-CoV-2 virus 33 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Annex 1. Strengths and limitations of ILI / ARI / SARI surveillance to address COVID-19 objectives LIKELY POSSIBLE UNLIKELY Inpatient surveillance (SARI or pneumonia) with laboratory confirmation If age is collected and reported by sentinel sites, trends by age group could be determined. Baselines and thresholds may be available for syndromic data. Trends of COVID-19 percent positivity among inpatients meeting the SARI case definition and presenting to sentinel sites, by age and risk groups. Further detail on COVID-19 among ICU admissions possible if this data is collected and reported consistently. The proportion of ILI among all outpatients may fluctuate with changes in out- patient health care delivery with factors affecting both the numerator and the denominator. If only influenza-negative samples are tested for SARS-CoV-2, the resulting SARS-CoV-2 percent positivity will be among influenza negative medically attended ARI or ILI population and may be difficult to interpret. Inter-country comparisons may not be possible because of different case definitions in use (ARI, ILI, or suspect COVID-19) and differing t changes in healthcare delivery and COVID-19 responses. Younger age groups may be over-represented and middle-aged groups may be under-represented in ILI surveillance. Validity and representativeness depend on whether symptomatic COVID-19 cases needing hospitalization are seen at SARI sentinel sites, as well as which health facilities and wards are involved in SARI surveillance. The COVID percent positivity is dependent on what else is circulating that manifests as SARI. The proportion of ILI among all outpatients may fluctuate with changes in outpatient health care delivery with factors affecting both the numerator and the denominator. Inter-country and intra-country comparisons may not be possible because of differential changes in healthcare delivery and COVID-19 responses, including admission criteria for suspect COVID-19 cases and hospital capacity. Younger age groups may be over-represented in SARI surveillance. PROS CONS/LIMITATIONSDATA SOURCE Outpatient surveillance (ARI or ILI) with laboratory confirmation of all or a subset. Monitor longer term epidemiologic trends and evolution of SARS-CoV-2 virus [continued ... ] 34 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Annex 1. Strengths and limitations of ILI / ARI / SARI surveillance to address COVID-19 objectives LIKELY POSSIBLE UNLIKELY PROS CONS/LIMITATIONSDATA SOURCE Monitor longer term epidemiologic trends and evolution of SARS-CoV-2 virus Contribute to the understanding of the co-circulation of SARS-CoV-2 virus, influenza and other respiratory viruses, and other pathogens. Sentinel virologic surveillance Sentinel virologic surveillance GISRS network could provide an efficient system for movement of specimens/ viruses for genetic characterization. Systematic and continued testing of samples from sentinel surveillance with reporting of denominator information and epi information (case definition) could improve understanding of transmission dynamics and inform preparedness and response measures in the short term. Competing priorities with influenza surveillance. Competing with national reference lab and network for coronavirus lab surveillance where existing. Lab capacity could quickly be overwhelmed. Not all surveillance systems test for respiratory pathogens other than influenza and not all samples are tested for all respiratory viral pathogens. Depends on testing algorithm and systematic and continued testing of samples from sentinel surveillance. Inter-country comparisons may not be possible due to differing priorities and testing algorithms. Targeted research studies may be more appropriate to reach this objective. Transmission dynamics could change over time. Transmission dynamics will vary by age, severity and risk group so unless this epi information is lined up with virologic information it may be difficult to inter- pret. Laboratory algorithms and global reporting platforms allow for the detection of co-infections with SARS-CoV-2 and influenza or other respiratory viruses and reporting of aggregated information. [continued ... ] 35 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Annex 1. Strengths and limitations of ILI / ARI / SARI surveillance to address COVID-19 objectives LIKELY POSSIBLE UNLIKELY PROS CONS/LIMITATIONSDATA SOURCE Guide the implementation and adjustment of targeted control measures, while enabling safe resumption of economic and social activities. Evaluate the impact of the pandemic on health-care systems. Outpatient surveillance (ARI or ILI) with laboratory confirmation of all or a subset. Inpatient surveillance (SARI or pneumonia) with laboratory confirmation Inpatient surveillance (SARI) with laboratory confirmation, with or without outcome information. Evaluation of COVID-19 impact on health-care system relative to short-term trends may be possible. Similar to those included in trends objective. Establishing baseline and intensity thresholds may be difficult, unless data from earlier waves of activity can be used Similar to those included in trends objective. Establishing baseline and intensity thresholds may be difficult. Same as above. Evaluation of COVID-19 impact on healthcare system relative to long- term influenza trends may be complicated due to changed or differing surveillance objectives or testing strategies and other aspects of the response. Evaluation of the overall impact on the healthcare system relative to long- term trends possible if quality historical data is available. Understanding and capturing surge capacity for ICU and hospitalization needs to be further explored in order to more accurately monitor the impact on the healthcare system by both influenza and COVID-19. Detect and contain clusters and outbreaks, especially in vulnerable populations. Enable rapid detection, isolation, testing, and contact tracing These are not primary objectives of sentinel surveillance. Sentinel surveillance can complement information from other surveillance, such as non-sentinel surveillance, event-based surveillance and surveillance in special settings, by providing baselines of usual activity for comparison and context. [continued ... ] 36 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Annex 2. Rapid situation assessment of surveillance system attributes and example questions Context and policies IT infrastructure Systems and processes Data quality Accuracy Completeness Consistency Timeliness Because of changes in healthcare delivery, are patients with respiratory symptoms: • referred to seek care at sites other than routine outpatient sites /general practitioners, and since when has this policy been in place? • admitted to designated COVID-19 hospitals as SARI patients? • referred to special screening centres (and since when has this policy been in place)? Have there been changes in healthcare-seeking behaviour? Have there been changes to sentinel sites and staff, and what proportion of sentinel sites and staff have been repurposed to COVID-19 response? Have there been improvements in the IT infrastructure for data collection and management and reporting that could be leveraged for sentinel syndromic surveillance? Have there been changes the systems and processes to collect and report data on ILI/ARI/SARI and lab results? How are the data aggregated and reported and to whom? Do the data being collected and reported reflect the true observed situation? Are numbers of ILI/SARI/ARI consultations/admissions abnormally low? Which of the systems best reflected the situation in the country? Are case reporting forms filled out completely? Are there specific data elements that are most frequently left incomplete/blank? What percentage of sentinel sites continue to report syndromic surveillance data to national level at each reporting interval? What percentage of sentinel sites continue to collect and ship samples for symptomatic patients to the laboratory? Have there been changes in the number of samples received by the labs? Have there been changes in the number of samples processed by the labs? Has the case definition for monitoring respiratory syndromes changed? Has the sampling strategy of patients meeting the case definition changed? How many of the sentinel sites have been reporting every week? Are data reported in a timely fashion? Are specific data elements barriers to timely collection and reporting? What percentage of sentinel sites report syndromic surveillance data on time each reporting interval? What percentage of sentinel sites ship samples to the laboratory by the target number of days after sample collection? What percentage of samples are processed within the target time frame? Surveillance system attribute Sample questions 37 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Annex 3. Addressing disruptions in sentinel syndromic surveillance for influenza Competing priorities and limited resources leading to decreased support of routine sentinel surveillance for influenza. Changes to sentinel sites and staff; facilities cease participating in surveillance system and / or reporting. Reassess influenza surveillance priorities. Understand which sentinel system is most useful for reaching priority influenza surveillance objectives. Try to sustain where possible the existing surveillance systems but consider alternative data sources that could aid in meeting some influenza surveillance objectives. Scale up number, diversity and geographic representation of sentinel sites, including designating COVID-19 specific consultation centers as sentinel sites for ARI / ILI /SARI syndromic surveillance. Additional data sources on hospital and ICU capacity could be useful for monitoring trends in severe cases and impact on health system. Samples from these systems could be tested for influenza. Increased awareness about and opportunity for respiratory disease surveillance, capacity building, better tools and integrated IT infrastructure (electronic reporting) may enable expansion of the primary care and hospital-based sentinel surveillance system. Additional sites and increased diversity in sites may increase representativeness of data. Inclusion of specialized COVID-19 centers may capture symptomatic patients who may be diverted from GPs to these specialized centers. Increased case detection and enrolment may increase sample yield for virologic surveillance. Increasing duration of surveillance (from seasonal to year-round) may allow for monitoring syndromic illness and respiratory viral pathogens year-round, including SARS-CoV-2. If surveillance objectives include the spectrum of influenza-associated disease or understanding the relationship of virus strains to disease severity or detecting unusual and unexpected events such as outbreaks of influenza outside the typical season, multiple surveillance systems may be needed. Financial and human resource constraints: cost/sustainability on surveillance program and sentinel sites and lab capacity; need to recruit staff at sentinel sites to collect data and samples and report. Staff at sentinel sites could be quickly overwhelmed leading to poor data quality. Knowledge constraints: training would be needed for additional sentinel site staff. Infrastructure constraints: sentinel sites participating in virologic surveillance need to be able to process, store and transport samples correctly to laboratories. Limitations on data quality and interpretation: Changing denominator (population under surveillance) may affect interpretation and introduce different biases to data. Population-based rates may not be accurate / catchment area difficult to determine. May affect historical comparison. Should not consider sentinel surveillance as an equivalent to comprehensive COVID-19 case detection/universal surveillance. ISSUE CONSIDERATION OPPORTUNITIES CONSTRAINTS/LIMITATIONS 38 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Annex 3. Addressing disruptions in sentinel syndromic surveillance for influenza Changes to primary health care delivery (e.g. referral to patient triage centers) Changes to primary healthcare delivery: increased use of primary care teleconsultations/ telemedicine/remote delivery. Changes to primary healthcare delivery: policies direct patients away fromprimary care entirely and instead to self-assessment using online tools, hotlines or directly to specialized COVID-19 consultation centres. Changes to primary healthcare delivery: changes in patient scheduling, triage and screening at outpatient sites. Include patient triage calls to primary care providers from patients meeting ARI or ILI case definition in weekly ARI / ILI count reporting. Monitor triage calls for ARI / ILI as a proxy for visits. Include teleconsultations from patients meeting ARI or ILI case definition in weekly ILI count reporting and include all teleconsultations in weekly total outpatient count reporting. Capture this information and use for syndromic surveillance. Consider how these changes affect case detection and sampling strategies. If triage calls included, will increase case counts of ARI / ILI. Might be useful to follow trends of ILI/ARI in that season. Same as above Teleconsultations more likely to be done by trained sentinel site staff (primary care physicians, nurses)? Adherence to case definition may be an issue, if patient triage is done by staff not trained in sentinel surveillance. No realistic denominator. Other biases to data are introduced. Human resource constraints (burden on primary care staff). Further delays in reporting possible. No possibility of virologic diagnosis. Same as above except perhaps better adherence to case definitions if primary care providers are conducting case detection. Same as above ISSUE CONSIDERATION OPPORTUNITIES CONSTRAINTS/LIMITATIONS [continued ... ] 39 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Annex 3. Addressing disruptions in sentinel syndromic surveillance for influenza ISSUE CONSIDERATION OPPORTUNITIES CONSTRAINTS/LIMITATIONS Change in case definition from ILI to ARI (or COVID-19 case definitions) for syndromic surveillance at outpatient sites. Additional efforts to comprehensively monitor hospitalizations/ICU admissions and healthcare capacities due to COVID-19 Primary care providers report weekly counts of both ARI and ILI (include the option to select one or both on the case reporting form) National surveillance units could collect data on ARI and ILI post-hoc if case-based data (with symptoms included) are reported. Introduce the collection symptoms in case reporting forms to facilitate post-hoc analyses by different case definitions. Capture this information and assess utility for monitoring impact of influenza as well. Would allow for restricting the analysis to patients meeting the ILI case definition for better comparability with past data. Capitalize on the development of new methods and systems for comprehensive monitoring of hospital capacity and use this for monitoring impact on the health system as part of the severity assessment for influenza. If the use of ICD-coding as a proxy for monitoring SARI admissions has been improved, this may be useful for monitoring as part of influenza surveillance. Consider benefits with added burden on primary care providers/sentinel site staff/surveillance units. For influenza surveillance, the ARI case definition is more generally more sensitive and thus will capture more cases and necessitate more laboratory testing. [continued ... ] 40 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Annex 4. Addressing disruptions in sentinel virologic surveillance for influenza ISSUE CONSIDERATION OPPORTUNITIES CONSTRAINTS/LIMITATIONS COVID testing is priority and resources are limited to test all SARS-CoV-2 samples for influenza. Testing for SARS-CoV-2 is done at labs other than NICs or labs with capacity for influenza testing. Infection prevention and control concerns / PPE availability at primary care facilities. Test a subset of samples received for SARS-COV-2 testing for influenza and other respiratory pathogens. NICs obtain a subset of samples from specialized testing centers and test SARS-CoV-2 negative samples for influenza. Implement changes to sample collection methods, such as supervised and / or unsupervised self-swabbing. Training on appropriate use of PPE at sentinel sites (droplet versus contact precautions). If any epidemiological information is linked to the sample, test those samples from cases meeting the ARI/ILI/SARI case definitions. May yield some influenza-positive samples for characterization if influenza is circulating. May be useful to monitor trends over time. Prioritize SARS-CoV-2 negative samples. As above May yield some influenza-positive samples for characterization if influenza is circulating. If no epidemiological information is linked to the samples, the influenza positivity among those fitting a case definition will not be possible. This would serve the objective of situational awareness but none of the other objectives. But this should be the minimum if nothing else can be done. If no systematic testing is done (no case definitions in use), then interpreting trends over time will be difficult. As above Additionally, there are potential data and sample transfer issues. Could contribute to testing and reporting delays. May introduce biases in case selection and sampling. As a result of possible disruptions to sample collection, there may be a need to consider alternative sample collection methods in order to ensure continued laboratory-confirmation of all or a subset of symptomatic patients seeking healthcare at a facility involved in sentinel respiratory virus surveillance. 41 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Annex 4. Addressing disruptions in sentinel virologic surveillance for influenza ISSUE CONSIDERATION OPPORTUNITIES CONSTRAINTS/LIMITATIONS Decreased enrolment in surveillance/patient compliance with swabbing/ not meeting sample quotas. Changes in swabbing case definition Increase number of sentinel primary care providers participating in virologic surveillance, if not all participate. Adapt systematic sampling strategies to increase sample yield to meet quotas. Sample all outpatient cases meeting COVID-19 case definitions and test for SARS- CoV-2 and influenza. Sample all outpatient cases meeting ARI case definition and test for COVID-19 and / or flu depending on algorithm and objectives. Potentially increased yield of samples for influenza and SARS- CoV-2 testing. Simpler protocol. Helpful for clinical management / diagnostic purposes as well. May yield some flu positive samples for characterization. Consider changing data collection form to include symptoms for retrospective analyses. Financial and human resource constraints: cost/ sustainability on surveillance program and sentinel sites and lab capacity; need to recruit staff at sentinel sites to collect data and samples and report. Staff at sentinel sites could be quickly overwhelmed leading to poor data quality. Knowledge constraints: training would be needed for additional sentinel site staff in sample collection. Infrastructure constraints: sentinel sites participating in virologic surveillance need be able to process, store and transport samples correctly to laboratories. Burden on labs / increased cost. Samples from suspect COVID-19 cases may go to a lab other than an NIC. Will not be able to determine proportion of ILI/ ARI/SARI with COVID or influenza, or compare to historical data. Even without changes, historical comparisons may be problematic anyway due to disruptions in the collection of syndromic surveillance data. Confusion around case definitions and need for clinical management for COVID-19 surveillance. If change from ILI to ARI, will lose historical context. SARS-CoV-2 positive results will need to be rapidly communicated back to the physician and patient for clinical management and public health response actions. [continued ... ] 42 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Annex 5. Changes to sentinel site case reporting form and reasons for inclusion CHANGES TO CONSIDER, IF NOT ALREADY INCLUDED COVID-19 testing data to lab results section Additional variables for SARI reporting forms, such as ICU admission / mechanical ventilation / oxygen use / outcome. Additional variables for SARI reporting forms such as risk factors and/or co-morbidities. Essential for the objective of monitoring COVID-19 trends among patients detected at sentinel site meeting existing influenza surveillance case definitions and for understanding the co-circulation of SARS-CoV-2 virus, influenza and other respiratory viruses, and other pathogens. This information informs indicators such as number of ILI or SARI patients tested for SARS- CoV-2 and number of ILI or SARI patients positive for SARS-CoV-2. If age and gender are included in case reporting forms, then trends can be stratified accordingly. This information would be reported at national level and to regional and global levels to inform regional and global responses, either in aggregated or case-based format, depending on regional and global guidance. Essential for the objective of monitoring the overall impact on the health system and monitoring trends in deaths and for guiding the implementation and adjustment of targeted control measures. If this information is included with information on laboratory testing (for influenza and SARS- CoV-2), weekly indicators such as number of SARI cases admitted to ICUs, number of SARI cases requiring mechanical ventilation or oxygen use or number of SARI deaths could be stratified for influenza and SARS-CoV-2. These indicators (either with or without associated lab testing information, and especially with denominator information), may be useful for monitoring the severity of the influenza epidemic and the COVID-19 pandemic, as described in the Pandemic Influenza Severity Assessment (PISA) guidance. Essential for the objective of monitoring COVID-19 trends among potential risk groups detected at sentinel site meeting existing influenza surveillance case definitions. This information would inform analyses at national level but would not be reported to regional and global levels. REASON FOR INCLUSION 43 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Annex 5. Changes to sentinel site case reporting form and reasons for inclusion CHANGES TO CONSIDER, IF NOT ALREADY INCLUDED REASON FOR INCLUSION Travel and / or contact history. Additional symptoms (COVID-19 related, non-respiratory symptoms) Applicable case definition(s) Consider if the case reporting form will also serve as an investigation form for suspect COVID-19 cases and to trigger associated public health responses. Consider if the case reporting form will also serve as an investigation form for suspect COVID-19 cases and to trigger associated public health responses. If syndromic surveillance case definition has changed from ILI to ARI, consider adding to the form if the case meets the ARI and ILI case definition. This would allow for analysis on cases meeting one or the other case definition. Annex 6. Influenza surveillance data and objectives and limitations to interpretation ILI cases by catchment population and/or outpatients visits by week Monitor when and where influenza-like illness activity is occurring, monitor intensity of transmission in relation to previous seasons, by age group if available. Possible complementary source of data to guide the implementation and adjustment of targeted public health and social measures Need lab-confirmation of all or a subset to understand virus-specific causes of changing trends in syndromic surveillance data. For influenza, comparison to previous years possible only if no major disruptions to system and changes in healthcare seeking behavior, as baselines and thresholds may not apply. Consider geographical representativeness of sentinel sites who are reporting. Consider timeliness and completeness of data. Consider if syndromic data from sentinel sites is capturing COVID-19 cases / activity (ideally need lab confirmation of all or a subset for SARS-CoV-2 as well). Understand laboratory testing algorithm and priorities. Understand biases in numerator and denominator. AVAILABLE DATA OBJECTIVES FOR INFLUENZA OBJECTIVES FOR COVID-19 LIMITATIONS TO INTERPRETATION [continued ... ] 44 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Annex 6. Influenza surveillance data, objectives and limitations to interpretation AVAILABLE DATA OBJECTIVES FOR INFLUENZA OBJECTIVES FOR COVID-19 LIMITATIONS TO INTERPRETATION SARI cases by catchment population and/or total hospitalizations by week. SARI cases admitted to ICU by total ICU admissions or SARI fatalities, by week. Number of SARI/ILI patients from whom samples were laboratory tested and the proportion testing positive. Monitoring and assessing the impact of influenza on high-risk populations and the healthcare system, and the severity of seasonal outbreaks in relation to previous seasons1 ; assessing burden of influenza hospitalizations; determine and monitor underlying risk conditions that are associated with severe disease; by age group if possible. Monitoring and assessing the impact of influenza on high- risk populations and the health system and the severity of seasonal outbreaks in relation to previous seasons. Same as above Possible complementary source of data to guide the implementation and adjustment of targeted public health and social measures. Possible complementary source of data to guide the implementation and adjustment of targeted public health and social measures. Monitoring long term epidemiological trends and evolution of SARS-CoV-2 virus Detecting the co-circulation of influenza and SARS-CoV-2 viruses Evaluation of the impact of COVID-19 on health systems (from SARI surveillance) Possible complementary source of data to guide the implementation and adjustment of targeted public health and social measures Understand biases in numerator and denominator. Same as above plus: Consider changes in admission criteria, if sentinel sites are admitting COVID-19 cases or not, which may make historical comparisons difficult If risk factor information is no longer collected, this objective will not be achieved. Same as above plus: Consider changes in ICU admission criteria, including whether ICU wards at sentinel sites are admitting COVID-19 cases or not, which may make historical comparisons difficult. Consider any changes to sampling strategies. Determining the percent positivity for influenza requires collecting the total samples processed or the total samples testing negative. This positivity is dependent on what else is circulating that manifests as ILI / SARI. For COVID-19 positivity, comparison to previous similar data possible but need to consider alternative threshold setting methods (short term average or levels reached during peak SARS-CoV-2 transmission). Cannot use non- disease specific ILI/SARI or influenza-positive thresholds for comparison. 1 Pandemic Influenza Severity Assessment (PISA) guidance https://www.who.int/influenza/surveillance_monitoring/pisa/en/ for comparing current activity to historical data using thresholds. [continued ... ] 45 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Annex 6. Influenza surveillance data, objectives and limitations to interpretation AVAILABLE DATA OBJECTIVES FOR INFLUENZA OBJECTIVES FOR COVID-19 LIMITATIONS TO INTERPRETATION Number of samples from sentinel sites processed; number of samples positive; percent positivity among sentinel samples. Number of samples from all sources processed; number of samples positive; percent positivity for among samples received from all sources. Monitor when and where influenza activity is occurring, monitor intensity of transmission in relation to previous seasons; by type, subtype/ lineage, if possible. Monitor when and where influenza activity is occurring, monitor intensity of transmission in relation to previous seasons. Monitor when and where COVID activity is occurring, monitor intensity of transmission in comparison with previous weeks Detecting the co-circulation of influenza and SARS-CoV-2 viruses. Possible complementary source of data to guide the implementation and adjustment of targeted public health and social measures. Monitoring when and where COVID-19 activity is occurring. Detecting the co-circulation of influenza and SARS-CoV-2 viruses. Same as above Same as above Non-sentinel samples come from a variety of sources and are not collected using a systematic testing approach. The resulting data may be biased towards reflecting influenza activity in certain populations other than the general community and may not be comparable to historical trends. [continued ... ] 46 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Annex 7. How and what to report What to report to FLUNET dataset (virological data from laboratories) Depending on the data collected in the country, the following different data can be reported on a weekly basis: Number of samples tested for influenza (from sentinel sites) Number of samples tested for influenza (from non-sentinel sites) Number of samples tested for SARS-CoV2 (from sentinel sites) Number of samples tested for SARS-CoV2 (from non-sentinel sites) Number of samples positive for influenza, SARS-CoV2, RSV and others if available (from sentinel sites) Number of samples positive for influenza, SARS-CoV2, RSV and others if available (from non-sentinel sites) Number of co-infections from sentinel sites (please contact flumart@who.int for further instructions on reporting co-infections) Number of co-infections from non-sentinel sites (please contact flumart@who.int for further instructions on reporting co-infections). What to report to FLUID dataset (epidemiological data) Depending on the data collected in the country, the following different data can be reported on a weekly basis: Data from ILI sentinel sites (outpatient facilities) Data from ARI sentinel sites (outpatient facilities) Data from SARI sentinel sites (inpatient facilities) Data from pneumonia sentinel sites (inpatient facilities) Mortality (all cause mortality or pneumonia and influenza (PNI) mortality) Number of ILI specimens tested for influenza and number of those positive Number of ARI specimens tested for influenza and number of those positive Number of SARI specimens tested for influenza and number of those positive Number of pneumonia cases tested for influenza and number of those positive Number of ICU admissions tested for influenza and number of those positive Number of deaths among people tested for influenza and number of those positive Number of ILI specimens tested for COVID-19 and number of those positive Number of ARI specimens tested for COVID-19 and number of those positive Number of SARI specimens tested for COVID-19 and number of those positive Number of pneumonia cases tested for COVID-19 and number of those positive Number of patients admitted to the ICU tested for COVID-19 and number of those positive Number of deaths among people tested for COVID-19 and number of those positive. The number of specimens with an indeterminate result can also be reported if available. Comment field: Please note which specimens are being tested for COVID-19 (e.g. all specimens received for respiratory virus testing or only influenza-negative specimens or a subset of influenza-negative specimens) as this may change over time. Any of the above can be done by age groups, and the denominator can be reported either by population or by outpatient visits or inpatients. Comments: please note any changes to your case definition, sample collection, or other changes to your routine surveillance. 47 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Already reporting weekly data to regional platforms or FLUNET (virologic data) and/or FLUID Ready to add weekly COVID testing data for sentinel and non-sentinel samples in additional to influenza data? Ready to start reporting influenza and/or COVID-19 testing detections and/or epidemiologic data on a weekly basis to FLUNET/FLUID? Issues in uploading excel files to FLUMART? Reporting to regional platform? Contact regional focal point for instructions on including COVID-19 testing data in routine reporting Contact flumart@who.int for assistance in modifying excel template to include COVID-19 fields in routine reporting files Contact flumart@who.int for immediate assistance Contact flumart@who.int for assistance in initiating reporting Uploading excel file(s) directly to FLUMART? YES YES YES NO HOW TO REPORT to FLUNET and FLUID via FLUMART 48 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance Monitoring Evaluation Ongoing review of the data entered into the system for completeness, timeliness, and aberrations or unexpected patterns should be performed at all levels of the surveillance system. All parts of the surveillance system (including each sentinel site) are thoroughly examined and checked for performance in achieving objectives. Assess the functioning of the system during the season or period under evaluation and identify disruptions that could be quickly addressed during the surveillance period. Assess the functioning of the system since the start of the COVID-19 pandemic, what disruptions may be affecting the system and where the system might benefit from adaptations. Develop monitoring plan before start of surveillance and then perform weekly to biweekly. A thorough surveillance system should be considered on a regular basis when time and resources allow and may be valuable to review changes implemented in the system. In an urgent situation, a rapid assessment may be more convenient to assess short- term opportunities and disruptions. Timeliness, completeness and aberrations in data, such as: Number of sentinel sites reporting ILI/SARI/ARI data to national level by week and timeliness Number of sentinel sites providing samples to the lab by week and timeliness Number of samples received in the lab Number of samples processed in the lab Number of samples processed in the lab in timely manner Are lab samples correctly identified as coming from sentinel vs non-sentinel sources? Are the numbers of ILI/SARI/ARI consultations/admissions abnormally low? Do the current data reflect the situation in the country? Which of the systems best reflects the situation in the country? Follow the sentinel surveillance system evaluation guidance on attributes to evaluate. For evaluation after changes are implemented, additional indicators to consider include: sentinel surveillance samples tested for SARS-CoV-2 (completeness), achieving defined COVID-19 surveillance objectives (utility), survey of sentinel site staff on changes (acceptability). WHAT HOW WHY WHEN INDICATORS Annex 8. Monitoring and evaluation of influenza sentinel surveillance systems 49 maintaining surveillance of INFLUENZA and SARS-CoV-2 – interim guidance WHO/2019-nCoV/Adapting_GISRS/2020.1 © World Health Organization 2020 influenza@who.int INTERIM GUIDANCE Maintaining surveillance of influenza and monitoring SARS-CoV-2 adapting Global Influenza surveillance and Response System (GISRS) and sentinel systems during the COVID-19 pandemic
临时指导文件 2020年11月8日 调整全球流感监测和应对系统及哨点监测系统 在COVID-19大流行期间坚持流感监测的同时 开展SARS-CoV-2监测 GISRS COVID –19流 感 监 测 世界卫生组织 全 球 流 感 规 划 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件ii WHO/2019-nCoV/Adapting_GISRS/2020.1 © 世界卫生组织，2021年 保留部分版权。本作品可根据Creative Commons Attribution-NonCommercial- ShareAlike 3.0 IGO licence（CC BY-NC-SA 3.0 IGO；https://creativecommons.org/ licenses/by-nc-sa/3.0/igo）获得。 根据本许可证的条款，如果按如下所示适当提及本作品，可以复制、重新排列和改编 本作品以用于非商业目的。在对本作品的任何使用中，都不得暗示世卫组织认可任何 特定组织、产品或服务。不允许使用世卫组织的徽标。如果对作品进行改编，就必须根 据相同或等同的知识共享许可证注册作品。如果翻译本作品，就应该添加以下免责声 明以及建议的出处说明：“该译文不是由世界卫生组织（世卫组织）翻译的。世卫组织 对此译文的内容或准确性概不负责。英文原版应作为有约束力和作准的版本”。 有关根据许可证发生的争议的任何调解都应按照世界知识产权组织的调解规则进行。 （http://www.wipo.int/amc/en/mediation/rules/） 建议的出处说明。在COVID-19大流行的背景下调整全球流感监测和应对系统： 临时指导文件。日内瓦：世界卫生组织；2020年（WHO/2019-nCoV/Adapting_ GISRS/2020.1）。许可证：CC BY-NC-SA 3.0 IGO。 在版编目（CIP）数据。CIP数据请见http://apps.who.int/iris。 销售、版权和许可证。如欲购买世卫组织出版物，请见http://apps.who.int/ bookorders。如欲提交关于商业用途的申请和询问版权和许可证事宜，请见http:// www.who.int/about/licensing。 第三方材料。如果希望使用本作品中归属于第三方的材料（如表格、图形或图像），则 有责任确定是否需要得到许可才能使用，并获得版权所有者的许可。因作品中第三方 拥有的任何内容遭到侵权而导致索赔的风险完全由使用者承担。 一般免责声明。本出版物采用的名称和陈述的材料并不代表世卫组织对任何国家、领 地、城巿或地区或其当局的合法地位，或关于边界或分界线的规定有任何意见。地图 上的虛线表示可能尚未完全达成一致的大致边界线。 凡提及某些公司或某些制造商的产品时，并不意味着它们已为世卫组织所认可或推 荐，或比其它未提及的同类公司或产品更好。除差错和疏忽外，凡专利产品名称均冠 以大写字母，以示区别。 世卫组织已采取一切合理的预防措施来核实本出版物中包含的信息。但是，已出版材 料的分发无任何明确或含蓄的保证。解释和使用材料的责任取决于读者。世卫组织对 于因使用这些材料造成的损失不承担责任。 ii 世界卫生组织 iii 鸣谢 世卫组织衷心感谢2020年10月6日至8日在线举行的世卫组织关于调整流感哨点监测 系统以涵盖COVID-19问题的协商之前、期间和之后参与制定本临时指导文件的各位 专家和国家代表，感谢他们作出的贡献。 感谢流感/SARS-CoV-2相关研究工作小组的专家们作出的贡献。病例定义小组专家 包括Luzhao Feng、Siri Hague、Jean-Michel Heraud、Gianfranco Spiteri、Sheena Sullivan和Weigong Zhou。流行病学考虑因素小组专家包括Cornelia Adlhoch、Yuzo Arima、Imad Cherkaoui、Cheryl Cohen和Sonja Olsen。实验室考虑因素小组专家包 括Ian Barr、Eeva Broberg、Rodrigo Fasce、Erik Karlsson、Rebecca Kondor、Angeliki Melidou、Catherine Thompson、Dominic NC Tsang、Sylvie van der Werf、Xiyan Xu和 Thedi Ziegler。 感谢下列专家和机构在此次协商前举行的讲习班上提供数据：智利卫生部卫生规划 司流行病学处、严重急性呼吸道感染监测哨点医院以及公共卫生研究所；哥斯达黎加 卫生部、营养与健康研究教育中心、社会保障局；巴拉圭公共卫生部；南非国家卫生实 验室国家传染病研究所呼吸道疾病和脑膜炎中心的Sibongile Walaza；英国伦敦大学 学院流行病学和卫生保健研究所的Andrew Hayward；英国爱丁堡大学亚瑟研究所的 Thulani Ashcroft、Emma Gillette、Durga Kulkarni和You Li；以及美国疾病预防控制中 心的Scott A. Nabity。 特别感谢此次咨询会的主席Rahman Mahmudur、共同主席Ian Barr和Cheryl Cohen； 会议报告员Thedi Ziegler和Shoshanna Goldin；以及所有发言人和讨论主持人。 感谢世卫组织下列工作人员和顾问为筹备此次协商提供的支持以及为编制和完 成本临时指导文件作出的贡献：Abdinasir Abubakar、Maya Allan、Tomas John Allen、Amal Barakat、Silvia Bertagnolio、Paula Couto、Vanessa Cozza、Janet Diaz、Hien Doan、Amgad A. Elkholy、Julia Fitzner、Aspen Hammond、Siddhivinayak Shriram Hirve、Belinda L. Herring、Francis Inbanathan、Jorge Jara、Kazunobu Kojima、Frank Konings、Henry Laurenson-Schafer、Sandra Jackson、Juliana Leite、Maja Lievre、Bikram Maharjan、Awandha Mamahit、Marie-jo Medina、Ann Moen、Piers Andrew Nicholas Mook、Karen Nahapetyan、Richard Pebody、Dmitriy Pereyaslov、Anne Perrocheau、Angel Rodriguez、Magdi Samaan、Soe Soe Thwin、Katelijn A.H. Vandemaele、Andrea Vicari、Karen Von Eije、Pushpa Wijesinghe和Wenqing Zhang。 本文件的技术编辑工作是由Judith Ann Mandelbaum-Schmid负责完成的。 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件iv 流感流行和大流行的 威胁仍然存在。 全球流感监测和应对 系统必须切实维持对 全球范围流感的监测， 而各国在进行相应调 整以适应COVID-19监 测目标的同时，必须保 持警惕。 世界卫生组织 1 概述 3 要点 3 引言 5 背景 5 将流感哨点监测目标扩大到COVID-19 6 COVID-19的流感监测病例定义 7 对哨点监测系统状况的快速态势评估 9 快速态势评估 9 评价就医行为的变化 10 解决流感哨点监测系统的中断问题 10 解决具体中断问题 10 将流感哨点监测扩大到COVID-19需要考虑的实际因素 11 扩大哨点系统 11 病例发现和各哨点的数据收集 11 在抽样策略和样本规模方面需要考虑的因素 12 需要考虑的实验室因素——哨点监测样本 13 临床样本 13 各哨点对临床样本的储存 13 将临床样本运输至实验室 13 实验室对临床样本的处理 14 流感和SARS-CoV-2监测的检测原则 14 选取部分流感阳性临床样本和病毒分离株送交世卫组织合作中心 17 流感和SARS-CoV-2检测的实验室技术 17 生物安全和生物保障 18 数据报告、分析和解释 19 监测和评估 20 将证据转化为政策 20 参考文献 22 目录 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件2 补充表S1： 流感和COVID-19常用病例定义词汇 26 补充表S2： 分析的数据来源和异质性，以估计流感样疾病、急性呼吸道感染以及严 重急性呼吸道感染病例定义用于COVID-19监测的表现特征 27 补充表S3： 流感样疾病用于COVID-19监测的表现特征 29 补充表S4： 急性呼吸道感染1 用于COVID-19监测的表现特征 30 补充表S5： 严重急性呼吸道感染用于COVID-19监测的表现特征 31 附件1. 流感样疾病/急性呼吸道感染/严重急性呼吸道感染监测对解决COVID-19 目标的优势和局限性 32 附件2. 对监测系统属性的快速情况评估和问题实例 36 附件3. 解决流感哨点症状监测中断的问题 37 附件4. 解决流感哨点病毒学监测中断的问题 40 附件5. 哨点病例报告表的修改以及列入理由 42 附件6. 流感监测数据和目标以及解释的局限性 43 附件7. 报告方式及报告内容 46 附件8. 流感哨点监测系统的监测和评估 48 附件 世界卫生组织 3 概述 本文件是2020年3月26日发布的临时指导文件《将全球流感监测和应对 系统用于COVID-19监测需要考虑的运行因素》以及2020年5月26日发布的 临时指导文件《在COVID-19大流行期间调整全球流感监测和应对系统以应 对即将到来的流感季——需要考虑的实际因素》的更新版。该文件包含评估 和解决流感哨点监测系统中断问题以及将流感哨点监测扩大到COVID-19 监测需要考虑的额外因素。它还包括流感和SARS-CoV-2监测检测的最新 算法，有助于在即将到来的2020/2021年流感季监测这些呼吸道病毒的潜 在共同传播，以及检测SARS-CoV-2和流感或其他呼吸道病毒的合并感染。 本版指导文件的依据是最新公布的证据以及2020年10月在线咨询会之前 和期间汇编的、各国将全球流感监测和应对系统用于COVID-19监测所得 出的经验教训。 要点 流感流行和大流行的威胁仍然存在。全球流感监测和应对系统 必须切实维持对全球范围流感的监测，而各国在进行相应调整 以适应COVID-19监测目标的同时，必须保持警惕。 建议各国在实施COVID-19哨点监测时，首先评估和解决流感哨 点监测系统中断的问题。 来自各哨点的样本应当进行流感和SARS-CoV-2病毒检测。如 有可能，应当选择多重聚合酶链反应测定法同时检测流感和 SARS-CoV-2病毒，以便提高试剂、消耗品和操作时间的利用效 率。 根据世卫组织现有指导文件，必须及时将具有代表性的流感病 毒和/或阳性样本中的临床样本送至世卫组织合作中心。 报告每周汇总的哨点监测情况是一项至关重要的监测工作。 尽管COVID-19大流行引发了种种巨大的挑战，但是它为加强核 心监测能力提供了机会，核心监测能力可以在这次突发事件期 间乃至很久之后带来公共卫生方面的益处。 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件4 尽管COVID-19大流行引发 了种种巨大的挑战，但是 它为加强核心监测能力提 供了机会，核心监测能力 可以在这次突发事件期间 乃至很久之后带来公共卫 生方面的益处。 世界卫生组织 5 引言 本文件是为参与国家级疾病和实验室监测的公共卫生专业人员编写的。它也是为参与流感和 COVID-19大流行监测和应对工作的世卫组织工作人员提供的指南。它为进行相应调整和坚持流感 哨点监测系统提供了临时指导文件，以确保在当前大流行期间继续进行流感监测，并尽可能补充 COVID-19监测。 背景 自SARS-CoV-2出现以来，全球流感监测和应对系统(1)及其在125个国家的公共卫生实验室网络 （国家流感中心、世卫组织H5参考实验室、世卫组织合作中心）在发现和遏制SARS-CoV-2传播方面 一直处于全球和国家协同应对的前沿。2020年5月，全球流感监测和应对系统开展了一项调查，结果 显示，其公共卫生实验室网络中90%以上的国家流感中心、世卫组织H5参考实验室和其他公共卫生 实验室正在进行SARS-CoV-2检测。现有的全球流感监测和应对系统的流感报告系统已成为了区域和 全球层面共享COVID-19数据的主要平台。 在全球流感监测和应对系统的流感机制基础上，建立了针对COVID-19的快速全球外部质量评估 规划，164个国家（233个实验室）参与其中。通过全球共享所有流感数据行动(2) 的一个公开数据库 GISAID），世界各地迅速开展了共享SARS-CoV-2的基因序列数据的行动。全球流感监测和应对系统 的感染性物质运输机制被用于将SARS-CoV-2病毒物质运送到世卫组织COVID-19参考实验室的过 程。此外，自2020年3月起，各国已经启动了COVID-19哨点监测，根据世卫组织关于利用流感监测系 统纳入COVID-19检测需要考虑的运行因素的指导文件(3)，通过对来自流感监测系统的哨点样本进行 SARS-CoV-2检测以监测社区传播情况。 然而，在应对COVID-19检测需求急剧增长的同时，由于就医行为和医疗卫生服务提供方面的变 化，流感监测系统已不堪重负并面临着严重的中断和资源挑战。许多国家都推迟、减少或者完全停止 了每周报告流感监测数据的工作。在那些有能力进行检测和报告的国家，2020年南半球流感季的流 感活动性比过去几年低且低于流行阈值。在目前尚在持续的COVID-19大流行期间，各国必须继续警 惕出现大流行潜在风险的非季节性流感病毒，并准备应对即将到来的2020/2021年北半球流感季。 世卫组织在主动病例发现、照护和隔离以及接触者追踪和医学观察方面提供了循证指导(4)，以此 支持国家的防范和应对工作。作为应对工作的一部分，《国际卫生条例（2005）》突发事件委员会建议， 世卫组织围绕使用严重急性呼吸道感染和流感样疾病监测系统开展疾病趋势监测、以应对预计将会 出现的流感和 SARS-CoV-2病毒共同传播的问题提供指导。它还建议，各缔约国通过全球流感监测和 应对系统以及《国际卫生条例》机制(5, 6)等数据平台，与世卫组织共享开展全球风险评估所需的一切 数据（包括严重急性呼吸道感染和流感样疾病相关数据（如有））。 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件6 监测系统应当基于若干明确的目标，以此指导其应收集何种数据以及选择哪些监测地点以提供最 适当的数据。常规流感哨点监测的目标是提供及时、高质量的流行病学数据和病毒分离株，以便描述 其季节性、示意流感季的开始和结束、提供疫苗生产的候选病毒、监测传播中的病毒的抗原和遗传进 化、监测严重疾病的高风险人群、评估严重程度、估计疾病负担、监测抗病毒药物敏感性，以及发现不 寻常和意外的事件和疫情。常规流感哨点监测系统采用的方法不是采集全部流感疑似病例，而仅仅是 系统地采集一部分流感病例。尽早发现病例以进行隔离、检测、接触者追踪、医学观察和快速控制聚集 性病例和暴发疫情，这些不是季节性流感哨点监测系统(7)的主要目标。 现有流感监测系统采用全球标准和方法，并通过全球流感监测和应对系统进行协调，它们在促进 对大流行的监视和监测方面具有独特地位，尤其是鉴于流感和SARS-CoV-2病毒可能共同传播的情 况。然而，现有哨点系统是否能够实现以下目标，则需视国内不断演变的SARS-CoV-2传播情况而定。 可能通过流感哨点系统实现的COVID-19目标： 监测SARS-CoV-2病毒的长期流行病学趋势和演变 发现流感和SARS-CoV-2病毒的共同传播。 流感哨点监测可能促进实现的COVID-19目标包括： 尽早发现SARS-CoV-2的社区传播 评估COVID-19对医疗卫生系统的影响 通报有针对性的公共卫生和社会措施的实施和调整情况。 不太可能实现的COVID-19目标包括： 早发现和遏制COVID-19疫情。 附件1介绍了基于初级保健（流感样疾病/急性呼吸道感染）和基于医院（严重急性呼吸道感染）的 哨点监测系统在实现COVID-19目标方面的优势和局限性。一些国家正在使用其他监测系统监测流感 趋势，例如，对急性呼吸道疾病的ICD-10代码的普遍监测、过高死亡率监测和参与性监测。虽然本文件 没有讨论这些系统，但在COVID监测(8)方面也应当利用这些系统。 尽管COVID-19大流行引发了种种挑战，但它为加强核心监测能力提供了机会，而核心监测能力可 以在这次突发事件期间乃至很久之后带来公共卫生方面的益处。各国在大流行期间建设的监测能力 将为能够更有效和迅速地应对未来公共卫生威胁并具有复原能力的系统奠定基础。 将流感哨点监测目标扩大到COVID-19 世界卫生组织 7 COVID-19的流感监测病例定义 确定病例定义敏感性和特异性的最佳阈值一直是基于流感、COVID-19和具有类似和无差别临床 特征的其他呼吸道感染监测需要和目标的一种平衡(9)。病例定义如果不敏感，就可能导致无法尽早 发现相关活动或错误估计疾病的严重性。相反，过度敏感的病例定义则可能由于其他原因造成的假阳 性病例数较高而对流行开始发出错误警报，导致需要更多的资源(10)。 流感样疾病、急性呼吸道感染和严重急性呼吸道感染用于流感监测 世界各国的流感监测系统通常使用世卫组织全球流感监测标准中的流感样疾病和严重急性呼吸 道感染病例定义，但有时会略作修改（专栏1)。 急性呼吸道感染病例定义也被一些国家用于 流感和其他呼吸道病毒监测，并被纳入了世 卫组织欧洲区域办事处人类流感监测指导文 件(11)。 对于初级保健就诊中的流感检测而言，流 感样疾病病例定义（表1）特异性较高（85%- 95%），而敏感性较低（45%-55%）(12)。 与此 相比，流感中更广泛的急性呼吸道感染的病 例定义则敏感性较高（94%），而特异性较低 （27%）。同样，严重急性呼吸道感染病例定义 的特异性和敏感性为45%-70%(13, 14)。 流感样疾病、急性呼吸道感染和严重 急性呼吸道感染用于COVID-19监测 世卫组织已定期更新COVID-19的病例定义，以整合不断增加的关于最常见和可预测症状、临床和 放射线征象及已知传播动力学特征（补充表S1）(15)。 COVID-19疑似病例定义的A部分规定了急性发热和咳嗽（与流感样疾病和严重急性呼吸道感染相 同），或者一系列症状（比流感的任何病例定义要求都更加广泛（胃肠、精神状态改变、肌痛、全身无力/ 疲劳、头痛））中至少三种的急性发作。COVID-19疑似病例定义的B部分规定了急性发热（测量或报告 的）、咳嗽和住院，这与流感的严重急性呼吸道感染病例定义相同。如果一个国家尚未进入社区传播阶 段，那么了解COVID-19病例的流行病学联系（例如，曾与已知的COVID-19病例接触、有过COVID-19疫 区的旅行史）就具有重要意义。 2020年9月，世卫组织委托有关机构对COVID-19临床特征进行了系统性评估，最近公布的评估结 果发现，在患者中，与COVID-19相关的最常见症状是发热（83%）和咳嗽（60%），其次是丧失嗅觉或味 流感样疾病 在过去10天内开始出现症状，并且 体温测量值等于或高于38摄氏度，并且 出现呼吸道感染（咳嗽） 急性呼吸道感染 出现咳嗽、喉咙痛、呼吸急促、流涕中至少一种症 状并伴随或不伴随发热，且临床医生诊断认为疾 病是由感染引起的 严重急性呼吸道感染 症状严重（住院），并且 急性发作（在过去10天内开始出现症状），并且 发热（报告或测量值等于或高于38摄氏度），并且 出现呼吸道感染（咳嗽） 专栏1：流感监测病例定义 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件8 觉（41%）、疲劳（31%）和食欲不振（30%）(16)。该评估主要是以住院病例的症状为依据，因此，社区或 原发性病例可能症状较轻。在已公开的文献以及对不同地域环境和严重程度的患者级数据的荟萃分 析中，关于COVID-19病例中流感样疾病、急性呼吸道感染或严重急性呼吸道感染流行情况的资料寥 寥无几。必须考察不同的症状组合，才能最好地掌握COVID-19病例。在流感样疾病/急性呼吸道感染 和严重急性呼吸道感染监测中，SARS-CoV-2阳性的比例为1.8%至25.6%——在老年群体中最高，而 在儿童群体中最低(17-19)。对七项生态学研究进行回顾后发现，过高的流感样疾病/急性呼吸道感染 与COVID-19病例或流感阴性病例之间存在正相关，这间接支持了将流感样疾病、急性呼吸道感染和 严重急性呼吸道感染病例的定义用于COVID-19监测之举(16, 20)。补充表S2-S5介绍了曾为世卫组织 关于COVID-19中流感样疾病、急性呼吸道感染和严重急性呼吸道感染病例定义的性能评估作出过贡 献的国家所提供的数据和结果的来源和异构性。 必须进一步深入分析来自不同地域和人口环境以及来自COVID-19大流行的不同阶段的广泛数据。 在此期间，流感监测系统应继续使用现行世卫组织流感样疾病和严重急性呼吸道感染病例定义 来检测流感，并在可能的情况下检测COVID-19。检测能力强的国家可以继续使用敏感性高而特 异性低的急性呼吸道感染病例定义。 流感样疾病 急性呼吸道感染 严重急性呼吸道感染 敏感性（%） 20 – 51 86 40 – 55 特异性（%） 85 – 95 27 45 – 70 特异性（%） 60 – 90 23 33 – 60 流感 COVID-19 表1：流感样疾病、急性呼吸道感染和严重急性呼吸道感染病例定义对流感和COVID-19监 测的表现特征一览 敏感性（%） 45 – 55 94 45 – 70 世界卫生组织 9 对哨点监测系统状况的快速态势评 估 完善的流感监测是根据病例定义，使用一个哨点网络来采集合适患者的临床样本。这些哨点包括 公共和私营医务室和诊所以及医院。目前的形势对常规流感监测系统产生了不同的影响。流感监测的 一些方面得益于应对COVID-19期间开展的快速能力建设和培训工作。该监测系统的其他部分则出现 中断，影响了常规流感监测活动。 在一国范围内，中断的类型和程度可能因区域和哨点而异，并随着影响国家和地方能力的SARS- CoV-2和流感传播强度的波动而不断变化。现有流感哨点监测系统的中断可能是提供医疗卫生服务方 面（包括各种资源限制和不断变化的工作重点）和就医行为发生变化所导致的，可能会影响该监测系 统在实现目标方面的效用。 中断对某个哨点系统的影响可能远远大于对其他哨点系统的影响（例如，门诊患者监测系统的中 断可能比住院患者监测系统的更加严重）。为了详细评估就医行为的变化，可以考虑采用其他调查方 法。 快速态势评估 下文所述快速态势评估是一种记录和描述流感哨点监测的潜在机会和中断、从而为COVID-19大 流行背景下可能实施的干预措施提供信息的快速方法。该评估并非用于取代建议的定期深入评分式 评价或常规监测。快速评估旨在用于因时间和资源有限而难以开展广泛评价以及需要立即考虑采取 干预措施的情形。 快速评估旨在实现以下目标： 确定监测项目执行中的优势、挑战和差距，以及确定维持流感监测和将COVID-19监测纳入哨 点系统的相关机会和威胁。 利用评估结果来评估中断程度，以及开展有针对性的适当行动以维持流感监测和将COVID-19 监测纳入哨点系统。 考虑纳入以下活动： 收集哨点属性信息，侧重于应对COVID-19大流行背景下可能出现的趋势、政策、系统流程和数 据质量变化。问题实例见附件2，但是应当根据国情进行调整。信息来源可包括对关键哨点和 实验室人员的深入访谈、直接观测以及对重要文件的案头审查。 总结调查结果并编写一份关于哨点监测系统中断程度（包括具体的中断和受影响的属性）的 简要报告。该报告还可以包括关于在必要时为维持流感哨点监测而采取的改进行动的临时建 议。 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件10 评价就医行为的变化 下列信息也许有助于更好地了解就医行为的变化以及这种变化是如何影响数据和解释的： 政策文件 出现呼吸道症状的患者是否被转至专门的筛查中心？ 严重急性呼吸道感染患者是否被转至指定医院就诊？ 对通过随机或系统抽样确定的参与者开展具有代表性的调查，由这些参与者自行完成一项用于收集包 括社会人口信息在内的数据工具 流感和流感样疾病的参与性监测系统 来自临床网络的主观传闻信息。 如果发生了严重中断，则需确定未来6至12个月应将哪些流感目标列为实际优先目标，以及可以利 用哪些资源和能力来进行调整以实现这些优先目标。 优先目标包括： 了解流感活动发生的时间、地点和相关人群（例如，不同年龄组），为国家和地方的临床管理建议和 公共卫生应对活动提供信息 提交具有代表性的样本，为作出全球疫苗组份的选择决定提供参考 促进了解国家以下、国家、区域和全球各级的趋势和影响 如果通过快速评估发现了某些中断，则解决这些具体中断问题以维持流感监测。考虑增加SARS- CoV-2，作为现有系统监测的病毒之一。如果资源允许，则对从各个哨点采集的所有样本开展流感和 SARS-CoV-2检测。 如果没有发现中断，则考虑增加SARS-CoV-2，作为现有系统监测的病毒之一。如果资源允许，则对 从各个哨点采集的所有样本开展流感和SARS-COV-2检测。 解决具体中断问题 现有流感哨点监测系统的中断可能因国家而异，其根本原因也各不相同。发生中断的原因可能是 医疗卫生服务提供方面、尤其是初级保健服务（包括电话优先政策、远程会诊、将患者转至专业的分 流/检测/治疗诊所或中心）的变化，以及哨点和工作人员（目的改为应对COVID-19）及病例定义（例如， 从流感样疾病变为急性呼吸道感染）的变化。维持流感监测的详细考虑因素见附件3 (症状监测）和附 件4 （病毒学监测），附有相关的机会和局限。哨点监测的任何改变均应予以记录并密切监测，以了解 这些改变是否解决了所发现的问题。 解决流感哨点监测系统的中断问题 世界卫生组织 11 将流感哨点监测扩大到COVID-19需要考 虑的实际因素 各国在流感监测系统中实施COVID-19哨点监测之前，应考虑以下问题： 是否存在一个由国家卫生当局管理的国家或地方监测系统 监测系统评价结果和系统中断程度评估结果 在初始阶段是否有可能（如果有能力）在监测系统中运行良好的部分哨点开展COVID-19哨点监 测试点 样本从哨点到国家参考实验室的物流运输 SARS-CoV-2结果报告：向谁报告，以及如何触发应对行动（例如，接触者追踪和《国际卫生条例》 报告）。 各国应考虑在结合实验室确认的情况下，实施严重急性呼吸道感染症状监测，以了解流感和 COVID-19两者对医疗卫生系统的影响。已经着手收集经实验室确认的住院信息的国家，可以考虑 结合对流感和COVID-19的实验室确认，实施严重急性呼吸道感染监测，以便了解医院系统受到的 综合影响。 扩大哨点系统 哨点系统的扩大不应损害监测标准，包括样本质量和流行病学信息。及时报告的优质样本和数 据，即使来自少数几个哨点，也比大量劣质样本和没有及时报告的数据更加有用。在建立更多哨点 之前，必须考虑是否能够对其实施有效管理、监测和维护。 对哨点系统进行评价之后，如果决定扩大哨点，则应考虑提高监测系统的地域代表性，其目标 是加强哨点监测系统尚未覆盖的地区对COVID-19社区传播的检测和监测。 病例发现和各哨点的数据收集 病例发现：建议在流感监测中继续使用现行病例定义进行病例发现和采样。 数据收集： 可以将更多变量纳入各哨点使用的个案病例报告表。 在决定更改哨点案例报告表时，应当参照可能给哨点工作人员增加的负担来权衡新增变量 或数据收集的好处。数据收集应旨在满足公共卫生决策者、公众和卫生工作者的信息需求。 从这些病例报告表中收集的信息旨在用于国家一级的分析；并非所有信息都需报告至地区 和全球级别。基于病例的数据或汇总数据报告中需要向区域和全球级别报告的信息部分由 国家和区域决定。需要向世卫组织全球一级报告的仅为来自哨点监测的汇总数据（见“数据 报告、分析和解释”）。 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件12 在病例报告和样本提交表中增加COVID-19/急性呼吸道感染/流感样疾病/严重急性呼吸 道感染病 例定义，以便有一种表格用于说明应开展何种检测并允许根据病例定义进行分 离，从而尽可能避免重复工作（多重病例报告表、数据库，等）。收集关于患者符合哪些病 例定义的信息也有助于进行回顾性分析。如果使用了某一份病例报告表，则确保其涵盖 了每周向全球进行的COVID-19监测情况汇总报告所需的全部变量。 可考虑增加（如果尚未纳入现有病例报告表）的潜在变量列表见附件5。 COVID-19大流行改变了就医行为，流感哨点网络可能需要调整以确保向全球流感监测和应对系统 的各实验室提供足量的合适样本和完整的临床和流行病学信息，以便开展流感的病毒学监测。此外， 为控制SARS-CoV-2传播而实施严格保持社交距离政策的国家可能会发现流感传播有所减少。因此， 流感抽样策略需要进行相应调整，以便确保病毒学监测获得适当的样本供应。全球流感监测和应对系 统应继续仰仗于初级保健提供者、急诊室、门诊部和医院病房（包括继续为流感样疾病/急性呼吸道感 染和严重急性呼吸道感染患者提供服务的重症监护室）这些有据可查的流感和SARS-CoV-2哨点监测 样本的潜在来源。 为了生成有意义的监测结果，建议每个国家流感中心或国家参考实验室每周至少对50至100份哨 点样本、最好是150份样本开展流感和SARS-CoV-2检测。样本应涵盖一国的所有年龄组和地理区域。 如果无法从哨点监测中获取供每周检测的至少50-100份样本，则考虑（没有特定顺序）： 选择某个SARS-CoV-2阴性样本子集进行流感检测。 优先选择包含表明症状、年龄、存在风险因素和地理位置信息的样本。 • 在这些样本中，选择来自符合流感样疾病和严重急性呼吸道感染病例定义的患者的样本，以 确保体现疾病严重程度的范围。 • 在这些样本中，选择代表不同年龄组、风险因素、结果和地理位置的样本。 从非哨点监测中选择所需的剩余样本。 在抽样策略和样本规模方面需要考 虑的因素 世界卫生组织 13 临床样本 推荐用于流感病毒检测的临床样本类型包括： 鼻拭子 鼻咽拭子 鼻腔（鼻）与咽喉（咽）联合拭子 鼻洗液 鼻咽抽吸物 气管内抽吸物（针对下呼吸道感染） 支气管肺泡灌洗（针对下呼吸道感染）。 一般而言，上呼吸道样本已经证明适合进行流感和SARS-CoV-2病毒的分子检测。实际上，置于采集 瓶中或直接置于装有2至3毫升病毒转运培养基的离心管中的鼻咽拭子和咽拭子仍然是流感和SARS- CoV-2检测可选择的样本类型(21, 22)。虽然目前的同行评议文献表明，下呼吸道样本可能最适合进行 SARS-CoV-2的分子检测(23)，但样本采集过程往往对患者具有侵入性且可能产生气溶胶（支气管肺泡 灌洗就是如此），以及患者难以产生痰液等分泌物(24-26)。 出于对全球样本采集中用品、试剂和个人防护装备匮乏状况的担忧，人们还探索了是否能够将唾 液、口腔液和痰液样本作为SARS-CoV-2检测的替代样本(27-30)。然而，这些替代样本类型对于流感（和 SARS-CoV-2）检测的适用性仍不确定，需要进一步研究替代采样策略。当前，世卫组织不建议将唾液作 为用于进行SARS-CoV-2诊断的唯一样本类型。唾液在流感的聚合酶链反应检测中的临床应用情况尚不 清楚。此外，通过逆转录酶链反应（聚合酶链反应）在非呼吸道排泄物样本（例如，粪便和直肠拭子）中检 测出了SARS-CoV-2。在获得令人信服的科学信息之前，不应将替代呼吸道和非呼吸道样本用于流感常 规监测。如果打算使用非标准采集方法，则需要通过适当的验证程序。 目前的文献资料表明，从每个患者身上采集一种以上的样本类型，可能会增加通过聚合酶链反应检 测出SARS-CoV-2的可能性；然而，由于实验室试剂盒和试剂短缺，这种做法并不现实。为了保存核糖核 酸提取试剂并避免增加人员工作量，用于流感检测的样本应与用于SARS-CoV-2检测的样本相同，反之 亦然(31)。 各哨点对临床样本的储存 如果无法立即将样本运输到实验室，可以在冷藏温度（4摄氏度）条件下将其储存不超过72小时。如果 必须延长储存时间，则应将样本冷冻至-70摄氏度或更低的温度。注意：切勿将临床样本储存于-20摄氏 度的环境中。应尽可能避免反复冷冻和解冻样本，因为这会导致病毒降解，从而降低进一步分离/表征的 可检测性和可行性。 将临床样本运输至实验室 将临床样本运输至实验室的过程需遵守国家和国际运输条例。世卫组织建议(32, 33)各国当局将可 能包含季节性人流感病毒或SARS-CoV-2的患者样本作为UN 3373“B类生物物质”进行运输。 需要考虑的实验室因素——哨点监测样本 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件14 实验室对临床样本的处理 除了处理流感临床样本的标准做法以外，在实验室中处理此类样本时，需要特别谨慎(34)，因为呼 吸道样本也可能包含SARS-CoV-2和人畜共患流感病毒。关于流感病毒的培养，见“生物安全和生物 保障”部分。必须努力确认用于流感病毒培养的样本中不含SARS-CoV-2和人畜共患流感病毒。包含 SARS-CoV-2和人畜共患流感病毒的样本的分离和传代，目前必须在达到生物安全三级的实验室采用 生物安全三级程序或相当于三级的程序进行。 流感和SARS-CoV-2监测的检测原则 在当前COVID-19大流行期间，许多国家当局已请求其全球流感监测和应对系统实验室作为SARS- CoV-2检测站，开展初步临床诊断、国家参考实验室服务或监测。这就在技术和规划方面给许多实验室 提出了挑战。这些挑战包括：各项SARS-CoV-2特异性检测尚待确定和验证；大量临床样本有待检测和 报告；获得试剂方面的物流问题；耗材和试剂的采购；设备采购和使用；额外雇用和培训工作人员；来 自流感监测哨点网络以外的样本；样本的相关患者背景信息不完整；为数据登记和结果报告额外开展 信息技术能力建设。 尽管面临COVID-19大流行带来的压力，但全球流感监测和应对系统必须在全球范围内维持有意义 的流感监测，并对流感流行和大流行的威胁保持警惕。为了满足流感和COVID-19两个方面的需要，可 以采用一项简单的战略，即1） 确保来自流感样疾病/急性呼吸道感染和严重急性呼吸道感染患者的所 有哨点样本的数量和质量均达到最佳水平，2）对这些样本进行流感和SARS-CoV-2检测。 目前，开发可靠而省时的多重测定法、以便在同一个聚合酶链反应中同时检测流感和SARS-CoV-2 的工作正在取得进展。然而，在未来的3至6个月，单重测定法可能是大多数国家流感或SARS-CoV-2分 子检测的唯一选择。在理想情况下，流感和SARS-CoV-2的单重测定法应同时进行，但这也许并不总是 可行。因此，许多国家的全球流感监测和应对系统实验室必须决定检测顺序：或以流感病毒为先，或以 SARS-CoV-2为先，视国家检测策略而定。 下列检测原则适用于两种情形：以流感为检测首选项（图1A），或者以SARS-CoV-2为检测首选项（ 图1B）。关于检测首选项的决定应当根据COVID-19的流行病学情况、现有资源和相关国家指导文件作 出。 这些检测原则能够有助于监测2020/2021年北半球流感季期间这些呼吸道病毒的潜在共同传播， 以及检测与SARS-CoV-2和流感或其他呼吸道病毒的共同感染。部分感染了SARS-CoV-2的个体会在 很长时期内传播病毒或病毒RNA。因此，检测结果必须仔细解读，如果将临床病史与实验室结果相结 合，可能有助于确定具体的病因。 世界卫生组织 15 图1A 可供将流感病毒检测作为首选项的实验室使用的检测原则 1 来自监测哨点且符合具 体监测病例定义（流感样 疾病/急性呼吸道感染/ 严重急性呼吸道感染）的 样本。鼻拭子、咽拭子、鼻 与咽联合拭子、鼻咽抽吸 物均为检测临床样本中 流感病毒和SARS-CoV-2 的适当临床样本。 2 虚线表示，如果资源 允许，在提交世卫组 织合作中心之前，应 将流感阳性样本标注 为SARS-CoV-2阴性。 3 遵守关于在全球流感 监测和应对系统下与 世卫组织合作中心共 享季节性流感病毒信 息的业务指导文件。 4 应当通过流感网络这 一全球数据库，或通 过与流感网络相连 的世卫组织区域数据 库，与世卫组织共享 检测结果摘要。 图1A展示了临床样本检测（首先是流感病毒、其次是 SARS-CoV-2）流程图。建议采用多重聚合酶链反应测 定法（如可用）同时检测甲型和乙型流感病毒与 SARS-CoV-2（绿框），并将流感阳性样本转交世卫组织合作 中心以进一步分析其特征（全球流感监测和应对系统的一项标准职能）。如果资源允许，可以沿绿框下方的 虚线推进。如果多重聚合酶链反应测定法不可用，则使用针对甲型和乙型流感的单重测定法（黄框），随后 使用针对 SARS-CoV-2的单重测定法。 图1A 呼吸道样本 1 向世卫组织流感合作中心3 提交一个子集和/或对 部分样本排序 �重�定法 甲/乙型流感 流感 甲型流感2 乙型流感2 SARS- CoV-2检测 SARS- CoV-2 + SARS- CoV-2 - 执行确认 性检测 （如需） 丢弃或检测 其他呼吸道 病原体 亚型 H1/H3 确定谱系 Vic/Yam 向世卫组织流感网络4 提交数据。 将序列数据上传至全球 共享所有流感数据行动或 其他公开数据库。 - + + SARS-CoV-2+ SARS-CoV-2 + 甲/乙型流感 + SARS-CoV-2 - 甲/乙型流感 + 执行确认性检测 （如需） 视情况转交COVID-19 参考中心或者培养（生物 安全三级）或排序 多重�定法 甲-乙型流感 +/- SARS-CoV-2 +/- 向世卫组织COVID-19数据库 提交数据。 将序列数据上传至全球共享所有流感 数据行动或其他公开数据库 SARS- CoV-2 甲/乙型 流感 丢弃或检测 其他呼吸道 病原体 - 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件16 图1B 可供将SARS-CoV-2检测作为首选项的实验室使用的检测原则 1 来自监测哨点且符合具体监测病例定义（ 流感样疾病/急性呼吸道感染/严重急性呼 吸道感染）的样本。鼻拭子、咽拭子、鼻与 咽联合拭子、鼻咽抽吸物均为检测临床样 本中流感病毒和SARS-CoV-2的适当临床 样本。 2 遵守关于在全球流感监测和应 对系统下与世卫组织合作中心 共享季节性流感病毒信息的业 务指导文件。 3 应当通过流感网络这一 全球数据库，或通过与流 感网络相连的世卫组织 区域数据库，与世卫组织 共享检测结果摘要。 图1B 图1B展示了临床样本检测（首先是 SARS-CoV-2、然后是甲型和乙型流感病毒）流程图。建议采用多重聚合酶 链反应测定法（如可用）同时检测甲型和乙型流感病毒与 SARS-CoV-2（绿框），并将流感阳性样本转交世卫组 织合作中心以进一步分析其特征（全球流感监测和应对系统的一项标准职能）；如果资源允许，可以沿绿框下 方的虚线推进。如果多重聚合酶链反应测定法不可用，则使用针对SARS-CoV-2的单重测定法（黄框），随后使 用针对甲型流感亚型和乙型流感的单重测定法。 呼吸道样本 1 �重�定法 SARS-CoV-2 SARS-CoV-2 SARS-CoV-2 甲-乙型 流感检测 甲型流感 + 乙型流感 + 亚型H1/H3 确定谱系 Vic/Yam 向世卫组织流感合作中心2 提交 一个子集和/或对部分样本排序 向世卫组织流感网络3提交数据。将序列数据上传至全 球共享所有流感数据行动或其他公开数据库。 甲-乙型 流感 - 丢弃或检测 其他呼吸道 病原体 + + + + - SARS-CoV-2+ SARS-CoV-2+ 甲/乙型流感+ SARS-CoV-2 - 甲/乙型流感 + 执行确认检测 （如需要） 视情况转交参考中心或者培养 （生物安全三级）或排序 多重�定法 甲-乙型流感+/- SARS-CoV-2+/- 向世卫组织COVID-19数据库 提交数据。 将序列数据上传至全球共享所有 流感数据行动或其他公开数据库 SARS- CoV-2- 甲/乙型 流感- 丢弃或检测 其他呼吸道 病原体 世界卫生组织 17 随着SARS-CoV-2继续传播，世卫组织全球流感监测和应对系统合作中心将非常愿意接收来自国 家流感中心和其他实验室通过实时逆转录聚合酶链反应确定为SARS-CoV-2阴性的流感阳性临床 样本，以及来自通过实时逆转录聚合酶链反应确定为SARS-CoV-2阴性的临床样本的流感病毒分离 株。建议仅从SARS-CoV-2阴性流感病毒阳性样本中培养流感分离株。针对需要实验室确认的SARS- CoV-2阳性样本，世卫组织已经建立了一个COVID-19参考实验室网络(35)，以提供COVID-19确认检 测。 在向世卫组织全球流感监测和应对系统合作中心运送样本之前，实验室如果无法对流感阳性样本 进行SARS-CoV-2筛查，则应在提交表中注明这些样本没有进行SARS-CoV-2筛查，同时应在发送给接 收这些样本的世卫组织合作中心的相应电子邮件中注明这一点。 及时共享流感分离株或流感阳性的临床样本，这对全球流感监测和应对系统履行职能至关重要。 应遵守关于在全球流感监测和应对系统下与世卫组织合作中心共享季节性流感病毒的业务指导文 件。应选择最近收集的能够代表目前正在传播的甲型流感病毒的两个亚型和乙型流感病毒的两个谱 系的病毒或样本的子集。如果甲型流感病毒不能区分亚型为H1pdm09或H3，则应立即向世卫组织合 作中心发出警报并尽快发送样本(36)。 需要提醒全球流感监测和应对系统实验室的是，流感疫苗病毒的选择取决于病毒分离株的可用 性，此外，鼓励它们继续将流感分离株或原始临床样本送往世卫组织合作中心进行流感病毒培养和全 面特征分析。 流感和SARS-CoV-2检测的实验室技术 实时逆转录聚合酶链反应是全球流感监测和应对系统实验室流感病毒检测的最高标准。聚合酶链 反应是一种具有高度敏感性和特异性的临床样本病原体检测方法(37-39)。当识别到病原体核酸关键 位点的突变时，引物和探针可以快速调整；优质的必要试剂可以从许多不同来源获取；提取病毒核酸 的程序将使临床样本中的病毒失去活性，以便其他检测安全使用。对全球流感监测和应对系统实验室 来说，设在美国疾控中心的世卫组织流感监测、流行病学和控制合作中心的国际试剂资源(40)已成为 流感聚合酶链反应试剂和试剂盒的主要来源。 在SARS-CoV-2病毒出现之后，序列数据的快速共享使设计出合适的引物和探针用于这种新型病 毒的特异性检测成为了可能。世卫组织网站发布了建议的SARS-CoV-2分子检测方案(23)。 在同一聚合酶链反应中，用于多病原体识别的多重测定法有助于更充分地利用试剂、耗材和操作 时间。可同时检测甲型和乙型流感病毒的多重聚合酶链反应格式已经存在若干年，对于许多全球流感 监测和应对系统实验室来说，这些是流感监测的主要方法。 在撰写本文件时，美国疾控中心已经开发了一种可同时检测流感病毒和SARS-CoV-2的多重实时 逆转录聚合酶链反应测定法。然而，由于生产能力限制，未来3至6个月只有少数的全球流感监测和应 对系统实验室会使用试剂盒进行这种检测。美国疾控中心多重测定法的使用说明(41)以及引物和探 针的序列信息(42)已公开，以供开发基于疾病控制与预防中心设计的诊断检测时参考。 除了由美国疾控中心开发的多重测定法以外，其他检测形式（包括一些商业检测）也可使用，其他 地方也已进行了相关描述(43)。 选取部分流感阳性临床样本和病毒分离株送交世卫组织合作中心 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件18 无论流感和SARS-CoV-2监测使用的检测形式是什么，最重要的是确保目标病原体的最高敏感性 和特异性。此外，每次检测运行都必须包含经充分表征的阳性和阴性对照。为了评估其表现，实验室应 定期参加世卫组织全球流感项目和其他来源（例如，分子诊断的质量控制或者澳大利亚皇家病理学学 院质量保证项目）提供的外部质量评估方案。 生物安全和生物保障 仅仅根据临床症状即可确诊呼吸道病毒感染的情况很少。许多呼吸道病原体会引起类似的症状。 出现流感样疾病或急性呼吸道感染症状的患者可能感染了一种流感病毒、SARS-CoV-2、其他多种呼 吸道病毒之一、细菌或一种新型病毒，也可能同时感染了两种或两种以上的病原体。在临床环境中，医 疗卫生工作者感染的风险很高。与疑似流感或COVID-19患者接触的医生、护士和其他工作人员的风 险尤其高。 必须在开展彻底的风险评估的基础上，向与疑似流感或COVID-19患者接触的医疗卫生工作者以及 处理来自此类患者的临床样本的实验室工作人员提供适当的培训和足够的个人防护装备，从而对其 加以保护。每年都应大力鼓励医疗卫生工作者接种季节性流感疫苗。医疗卫生工作者和实验室工作人 员一旦出现呼吸道症状，必须立即进行流感和SARS-CoV-2检测。 世卫组织《流感实验室诊断和病毒学监测手册》描述了为季节性或人畜共患流感病毒分离而建议 的生物安全做法。 一些出版物介绍了关于处理SARS-CoV-2传染性材料的生物安全做法和指南。从收集临床样本到 将其运输到实验室再到实验室的所有程序，其中每一个工作步骤都必须仔细进行风险评估。所有实验 室工作人员都必须接受有关个人防护装备使用和必要安全程序的适当培训(22, 34)。 如果实验室试图培养流感病毒，就应对临床样本进行SARS-CoV-2检测；SARS-CoV-2阴性的甲型 （H1）pdm09流感或甲型（H3）/乙型流感阳性样本可以考虑用于病毒分离。虽然不能完全排除可能 性，但是SARS-CoV-2不太可能在通常用于分离流感病毒的细胞系或鸡胚蛋中复制(44)。如果试图培 养SARS-CoV-2，就必须严格遵守生物安全三级条件。“序列第一”方法可用于确定选择哪些样本进行 培养，尤其适用于流感和SARS-CoV-2合并感染的情况，在此情况下，达到生物安全三级的培养可能仅 限于需要进一步研究的样本。 除非另有证明，所有临床样本都被认为具有潜在的传染性。可能含有SARS-CoV-2的材料必须在限 制出入的区域进行处理和储存。 世界卫生组织 19 数据报告、分析和解释 任何级别的数据报告和分析，均应优先收集和报告分母信息（病毒检测的总样本量或病毒检测为阴性 的总样本量）以及按来源收集和报告数据（哨点与非哨点）。 国家一级的数据报告和分析 定期分析和报告国家哨点监测数据，有助于确保政策制定者、医疗卫生服务提供者和公众获得这些信 息，并将提高哨点报告的一致性。只要可行，此类报告应在国家监测网站上向公众发布。如果可能，报告应 包括一份附有图表的解释摘要以支持解释。 对于使用现有哨点监测系统获得的COVID-19数据，需要考虑的其他报告因素还包括： 制定关于定期向负责COVID-19总体应对工作的国家当局报告分析结果以及确定报告接收人、报告频 率和报告应包含的数据的程序 确定从哨点样本中检测出SARS-CoV-2阳性结果时应采取的程序和行动，这需要视国家的应对战略而 定；以及是否报告（例如，给全科医生、COVID工作队/其他责任当局）以开展接触者追踪或其他行动 向区域和全球级别报告数据 许多国家已经熟知直接或通过世卫组织区域平台向FLUNET（病毒学数据）和FluID（流行病学数据）全 球数据库报告常规流感监测情况的流程。FluMart (45) 是一个包含FLUNET和FluID数据集的全球数据报 告平台，允许以自有格式上传任何用户定义的数据文件，并将其转换为标准化数据。配置FluMart的目的 是在大流行初期收集COVID-19数据，并将这些数据添加到FLUNET和FluID数据集中。在直接向FluMart 报告时，COVID-19信息应作为附加变量纳入与流感数据相同的数据文件。 报告内容： 流感检测数据：继续每周向区域和全球级别报告流感监测汇总数据。其中至少应包含经处理可供流感 检测的各来源样本数量、流感阳性样本数量以及已检测样本和/或流感阴性样本数量。只要有可能，应 按来源对（哨点和非哨点）这些数据进行分类。 COVID-19检测数据：请求各国按照其报告流感监测数据的格式和频率，报告每周汇总的COVID-19结 果。应每周向区域和全球级别报告从现有哨点和非哨点或综合征监测系统采集的病例的病毒学数据（ 如COVID-19检测阳性和阴性的样本数量）。 流感与SARS-CoV-2合并感染：可以报告对SARS-CoV-2与流感或其他呼吸道病毒合并感染的检测情 况。如果采用上传excel文件的方式向FLUNET进行报告，通过修改常规报告模板，就可以按检测到的 病毒组合报告每周的合并感染数量（例如，流感/SARS-CoV-2或甲型流感/SARS-CoV-2）。如欲了解 关于合并感染报告的进一步说明，请联系flumart@who.int。 综合征监测数据：继续报告流感样疾病和严重急性呼吸道感染数据（附年龄分类），并在可能的情况下 按流感型别（附带分母）分列。一旦确定，则应持续报告急性呼吸道感染或肺炎数据。 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件20 报告方式: 直接向FLUMART上传数据的国家，请联系flumart@who.int以获取修改常规流感报告模板并纳入 COVID-19数据方面的协助，以及上传方面的协助。 向区域平台报告流感和COVID-19检测数据的国家，则应通过现有区域平台和世卫组织区域联系人获 取相关协助。请将flumart@who.int纳入所有信息。 报告时间：应继续每周开展流感和COVID-19数据的常规报告。如果是直接向全球平台报告，应在下一 周的周四之前报告本周数据。向区域平台报告的截止日期可能各不相同。 关于报告方式和内容的更多信息，见附件7。 监测和评估 应定期对监测系统进行监测，以发现和解决监测过程中出现的中断问题。在时间和资源允许的情 况下，可以考虑定期开展全面的监测系统评估。 可以考虑采取的行动包括： 让更多利益攸关方（例如，事件管理小组（见下文）或国家COVID-19工作队成员）参与监测和评估。 记录COVID-19大流行期间现有监测系统资源/治理的所有变化。 记录和了解哨点、实验室和国家监测单位之间信息流的变化。 记录COVID-19大流行期间初级设施和医院设施在提供医疗卫生服务方面的所有变化。 如果在现有系统中增加了SARS-CoV-2作为需要监测的另一呼吸道病原体，则对监测系统评估结果、特 别是样本运输和处理的及时性、哨点系统的完整性和代表性等属性进行监测。 关于如何开展、为何开展以及何时开展监测和评估的更多信息，可查阅附件8。 将证据转化为政策 国家开展COVID-19应对工作通常需要建立一个事件管理小组。呼吸道疾病监测的指定联络员应当是 该事件管理小组的成员，负责与常规呼吸道疾病监测项目联系。来自常规呼吸道疾病哨点监测项目的信 息应纳入对国家急性呼吸道感染情况的总体评估。常规流感哨点监测应视为用于形势分析和评估的一组 （但不是唯一一组）重要信息。 流感监测数据应继续用于大流行性流感严重程度评估，同时需要认识到监测系统的变化可能会改变基 线和解释。应对所有监测系统的信息进行评估，为临床管理、风险沟通(46)以及非药物干预措施(47, 48) （例如扩大应对活动，其中包括维持基本医疗卫生服务、增加重症监护床位数量、限制非必要的旅行、实 施学校措施、建议采取增加社交距离措施或规定必须使用口罩）提供参考依据。 世界卫生组织 21 关于流感大流行期间监测的广泛指导文件业已公布，该指导文件中大部分 内容都切合当前形势。更多信息和背景情况，见https://apps.who.int/iris/ bitstream/handle/10665/259886/9789241513333-eng.pdf?sequence=1。 关于大流行性流感严重程度评估的更多信息，见世卫组织指导文件：https:// www.who.int/influenza/surveillance_monitoring/pisa/en/。 关于实施严重急性呼吸道感染监测的更多信息，可查阅世卫组织《全球流感流 行病学监测标准》：https://apps.who.int/iris/handle/10665/311268 关于监测和评估流感哨点监测系统的详细指导，可查阅《全球流感流行病学监 测标准》：https://apps.who.int/iris/handle/10665/311268和 https://www.cdc.gov/globalhealth/healthprotection/fetp/training_mod- ules/12/Eval-Surv-Sys_FieldG_Final_09262013.pdf. 延伸阅读： 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件22 参考文献 1. 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Geneva: World Health Organization （https://apps. who.int/iris/rest/bitstreams/1314216/retrieve, accessed 5 November2020）. 26 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 定义 来源 标准 流感样疾病 世卫组织（2013年） 发热+咳嗽 流感样疾病 美国疾控中心 发热（37.8°C）+咳嗽和/或咽喉痛 急性呼吸道感染 世卫组织欧洲区域办事处/欧盟疾控中心 至少出现以下一种症状： 咳嗽、咽喉痛、呼吸急促、流鼻涕（注——无需发烧） 急性呼吸道感染 美国疾控中心 至少出现以下两种症状：发热、咳嗽、流鼻涕或鼻塞、咽喉痛 呼吸道合胞病毒 引起的急性呼吸 道感染 世卫组织 至少出现以下一种症状：咳嗽、咽喉痛、呼吸急促或流鼻涕 严重急性呼吸道 感染 世卫组织 发热（已测量或已报告）+咳嗽或呼吸急促 +住院 COVID-191疑似 病例 世卫组织 （2020年8月7日） A部分: 符合临床和流行病学标准的人： 临床标准： 急性发热和咳嗽 或者 至少出现以下三种症状： 发热、咳嗽、全身虚弱/疲劳、头痛、肌痛、咽喉痛、鼻炎、呼吸困难、厌食/恶心/呕吐、腹泻、精神状态改变 以及 流行病学标准： 在病毒传播风险高的地区居住或工作；封闭的居住环境、人道主义环境（难民营和类似难民营的流离失所者的环境）；出现症状前14天内： 或者 在出现症状前14天内曾到过有社区传播的地区居住或旅行 或者 在出现症状前14天内在卫生保健机构工作，包括在卫生机构工作或在社区工作。 B部分: 发热（已测量或已报告） + 咳嗽或呼吸急促+ 住院 COVID-19样疾病 美国疾控中心（2020年8月5日） 至少出现以下两种症状： 发热（已测量或已报告）、寒颤、僵硬、肌痛、头痛、咽喉痛、恶心或呕吐、腹泻、疲劳、充血或流鼻涕 或者 至少出现以下一种症状： 咳嗽、呼吸急促、呼吸困难、新出现的嗅觉丧失、新出现的味觉丧失 或者 至少出现以下一种症状： 肺炎（临床或X射线），急性呼吸道窘迫综合征 COVID-19样疾病 合并症-1 美国地方流行病学专家 委员会 至少出现以下一种症状： 咳嗽、呼吸急促或呼吸不适 或者 至少出现以下两种症状： 发热、肌痛、头痛、寒颤、丧失味觉或嗅觉、咽喉痛 COVID-19样疾 病合并症-2 美国地方流行病学专家委 员会 至少出现以下一种症状： 咳嗽、呼吸急促、呼吸不适、新出现的嗅觉障碍、新出现的味觉障碍 或者 至少出现以下两种症状： 发热、寒颤、僵硬、头痛、咽喉痛、恶心或呕吐、腹泻、疲劳、充血或流鼻涕 1 想要了解COVID-19可能病例和确诊病例的信息，请访问 https://www.who.int/publications/i/item/WHO-2019-nCoV-Surveillance_Case_Definition-2020.1 补充表 S1: 流感和COVID-19常用病例定义词汇 27 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 智利1 哥斯达黎加2 巴拉圭3 南非4 TESSY5 英国6 美国7 数据来源 严重急性呼吸道感 染监测 流感样疾病/严重急 性呼吸道感染监测 流感样疾病/严重急 性呼吸道感染监测 肺炎监测 流感样疾病/急 性呼吸道感染 / 严重急性呼吸道 感染监测 - COVID-19追踪应用程序； - FF100/ FluWatch 美国疾控中心家庭传播研究 监测类型 哨点；（6家医院中 有5家医院进行了 SARS-CoV-2检测） 哨点 哨点 哨点 COVID-19综合 非哨点 非哨点 患者来源 6所严重急性呼吸道 感染医院 9个流感样疾病中 心；18 所医院 5个流感样疾病点；10 所严重急性呼吸道感 染医院 9所哨点医院 初级保健； 医院 社区 COVID-19原发病例家庭，未 住院 患者总数 严重急性呼吸道感染 （2199） 流感样疾病（14 528）； 严重急性呼吸道感 染 （2577） 流感样疾病（2075）； 严重急性呼吸道感染 （4090） 急性呼吸道感染（1538 ）； 严重急性呼吸道感染 （835） 流感样疾病 （64 885）； 急性呼吸道感染 （205 481）； 严重急性呼吸道 感染 （13 398） - COVID-19追踪应用程序 （2700例阳性, 14 309例 阴性）； - FF100 （301例）； - FluWatch （1637例非 COVID-19病例） 62名主要接触者； 195名家庭接触者 样本 鼻咽拭子 鼻咽拭子，自拭子 诊断 逆转录聚合酶链 反应 逆转录聚合酶链 反应 逆转录聚合酶链反应 逆转录聚合酶链反应 逆转录聚合酶链反应 评估的 症状 任何发热、咳嗽、咽喉 痛、呼吸困难 急性呼吸道感染 （欧洲疾病预防 控制中心）,流感 样疾病/严重急 性呼吸道感染（ 世卫组织）病例 定义 咳嗽、发热、呼吸急促、胃 肠道症状、一般症状 流鼻涕、咽喉痛、咳嗽、胸痛、呼 吸急促、呼吸不适、气喘、头痛、 新出现的嗅觉或味觉丧失、发 热/寒颤、疲劳、肌肉酸痛、腹 泻、腹痛、恶心/呕吐 继续 ... 补充表 S2: 分析的数据来源和异质性，以估计流感样疾病、急性呼吸道感染以及严重急性呼吸道感染病例定义用于COVID-19监测的表现特征 28 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 缩略语：ARI, 急性呼吸道感染；ILI,流感样疾病；SARI, 严重急性呼吸道感染；USA, 美利坚合众国（美国）；UK, 大不列颠及北爱尔兰联合王国（英国） 1智利卫生部卫生规划司流行病学处、严重急性呼吸道感染监测哨点医院以及公共卫生研究所，未公布的数据，2020年9月23日 2哥斯达黎加卫生部、营养与健康研究教育中心、社会保障局，未公布的数据，2020年9月23日 3 巴拉圭公共卫生部，未公布的数据，2020年9月23日 4南非国家卫生实验室国家传染病研究所呼吸道疾病和脑膜炎中心，未公布的数据，2020年9月23日 5 Gianfranco Spiteri,欧洲疾病预防控制中心，个人交流，2020年9月23日。TESSy数据包括8个国家（捷克、德国、爱沙尼亚、马耳他、波兰、葡萄牙、斯洛伐克、英国）的数据 6 Andrew Hayward,伦敦大学学院流行病学和卫生保健研究所，个人交流，2020年9月23日 7 Reses HE FM 等人。现有的和新的COVID-19监测病例定义在社区中的执行情况。MedRxiv 2020年。 智利1 哥斯达黎加2 巴拉圭3 南非4 TESSY5 英国6 美国7 0-14岁 15-39岁 40-64岁 65岁以上 5% 11% 37% 46% 流感样疾病 （9% 、54%、30%、6%）, 严重急性呼吸道感染 14%、 33%、29%、24%） 流感样疾病 （4% 、63%、28%、4% ）, 严重急性呼吸道 感染（19%、 16%、24%、 40%） 急性呼吸道感染 （41%、19%、 27、13%）；严重急性 呼吸道感染（44%、 19%、26%、12%） 流感样疾病 （17%、24%、 30%、28%）； 急性呼吸道感染 （4%、36%、 42%、17%） 严重急性呼吸道感 染 （26、42%、 45%、31%） 儿童（<18岁） — 63（34%） 成年人（18岁及以上） — 122（66%） 男性 55% 流感样疾病 （51%）； 严重急性呼吸道感染 （53%） 流感样疾病 （43%）; 严重急性呼吸道 感染 （55%） 急性呼吸道感染 （49%） 严重急性呼吸道感染 （51%） 49% 总结结论 - 在老年人中的 特异性高 - 在年轻人中敏 感性高 - 流感样疾病敏感 性低 - 严重急性呼吸道感 染的敏感性和特异 性低 - 流感样疾病敏 感性低 - 可接受的严重 急性呼吸道感染 的表现 - 急性呼吸道感染敏 感性高 - 急性呼吸道感染特 异性低 - 可接受的严重急性 呼吸道感染表现 - 急性呼吸道感染 敏感性高 - 流感样疾病和严 重急性呼吸道感染 的敏感性低，尤其 是更加年轻的群体 - 通过扩展病例定义，敏感 性略有增加，但代价是假阳 性病例会显著增加 - 致使老年人发生精神错乱 的情况增加 - 流感样疾病特异性低 - 急性呼吸道感染敏感性高 - 儿童的敏感性低 限制 - 几例严重急性 呼吸道感染儿童 病例 多次修改COVID-19 病例的定义 预测值取决于疾病的患病率 （家庭中30%继发感染率） 补充表 S2: 分析的数据来源和异质性，以估计流感样疾病、急性呼吸道感染以及严重急性呼吸道感染病例定义用于COVID-19监测的表现特征 29 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 国家 敏感性 （95% CI） 特异性（95% CI） 阳性预测值 （95% CI） 阴性预测值（95% CI） AUC （95% CI） 补充表 S3: 流感样疾病用于COVID-19监测的表现特征 所有年龄 哥斯达黎加1 28.4 (27.6 - 29.2) 71.8 (70.0 - 73.6) 82.6 (81.4 - 83.7) 17.6 (16.8 - 18.3) 巴拉圭2 38.8 (35.3 - 42.7) 61.7 (59.0 - 64.3) 36.5 (33.2 - 39.9) 64.0 (61.3 - 66.6) 美国3 51 90 64 84 英国4 19.7 (15.3 - 24.7) 81.6 (79.9 - 83.3) 5.3 (4.2 - 6.7) 5 95.1 (94.8 - 95.4) 5 0.507 (0.482 - 0.531) 0 - 14 岁 哥斯达黎加 27.1 (24.5 - 29.9) 63.6 (57.3 - 69.5) 76 (71.4 - 80.2) 17 (14.7 - 19.6) 乌拉圭 20.0 (4.3 - 48.0) 56.0 (44.0 - 67.4) 8.3 (1.7 - 22.4) 77.7 (64.4 - 87.9) 注：0 – 18 岁 美国 43 96 英国 25.0 (0.6 - 80.6) 67.3 (63.1 - 71.4) 3.9 (0.7 - 18.1) 5 94.5 (90.6 - 96.8) 5 0.462 (0.216 - 0.707) 15 - 39 岁 哥斯达黎加 27.8 (26.7 - 28.9) 73.6 (71.2 - 76) 84 (82.3 - 85.5) 17 (16 - 18) 乌拉圭 36.7 (32.6 - 41.4) 62.7 (59.3 - 66.1) 38.6 (34.3 - 43.1) 60.8 (57.4 - 64.2) 注：超过18岁 美国 86 55 英国 20.0 (12.7 - 29.2) 84 (79.8 - 87.6) 6.2 (4.0 - 9.4) 5 95.2 (94.7 - 95.7) 5 0.52 (0.476 - 0.563) 40 - 64 岁 哥斯达黎加 29.5 (28 - 31) 70.2 (66.8 - 73.4) 82.3 (80.1 - 84.3) 17.5 (16.2 - 18.9) 乌拉圭 45.5 (38.6 - 52.6) 59.7 (54.6 - 64.7) 37.6 (31.5 - 44.0) 67.3 (62.0 - 72.3) 英国 19.1 (13.2 - 26.2) 86.3 (83.8 - 88.4) 6.8 (4.8 - 9.5) 5 95.3 (94.9 - 95.6) 5 0.527 (0.493 - 0.56) 65 岁及以上 哥斯达黎加 30 (26.7 - 33.5) 77.3 (70.9 - 82.9) 82.6 (77.5 - 87) 23.5 (20.4 - 26.9) 乌拉圭 38.1 (18.1 - 61.5) 66.6 (53.9 - 77.8) 26.6 (12.2 - 45.8) 77.1 (64.1 - 87.2) 英国 21.1 (9.55 -37.3) 89.8 (85.6 - 93.1) 9.8 (5.1 - 18.1) 5 95.6 (94.8 - 96.2) 5 0.554 (0.486 - 0.622) 缩略语：AUC, 曲线下面积；CI, 置信区间；NPV, 阴性预测值；PPV, 阳性预测值；US, 美利坚合众国（美国）；UK,大不列颠及北爱尔兰联合王 国（英国） 1哥斯达黎加卫生部、营养与健康研究教育中心、社会保障局，未公布的数据，2020年9月23日 2 巴拉圭公共卫生部，未公布的数据，2020年9月23日 3 Andrew Hayward，伦敦大学学院流行病学和卫生保健研究所，个人交流，2020年9月23日 4 Reses HE FM 等人。COVID-19现有和新的监测病例定义在社区中的执行情况。MedRxiv 2020年 5 阳性预测值和阴性预测值估计患病率为5% 30 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 1 急性呼吸道感染定义为至少出现以下一种症状：咳嗽、咽喉痛、呼吸急促或流鼻涕，以及出现症状小于或等于10天；分母是与症状持续时 间无关的入院治疗的下呼吸道感染 2 南非国家卫生实验室国家传染病研究所呼吸道疾病和脑膜炎中心，未公布的数据，2020年9月23日。 补充表 S4: 急性呼吸道感染1 用于COVID-19监测的表现特征 缩略语：ARI, 急性呼吸道感染；AUC, 曲线下面积；CI, 置信区间；NPV, 阴性预测值；PPV, 阳性预测值。 国家 敏感性（95% CI） 特异性（95% CI） 阳性预测值 （95% CI）阴性预测值（95% CI）曲线下面积 5% CI） 所有年龄 南非2 86.5 （82.8 - 89.8）22.7 （20.6 - 24.8） 22.2 （20.1 - 24.3） 86.9 （83.2 - 90.0） 0.5 （0.5 - 0.6） 0 - 14 岁 85.2 （66.3 - 95.8）13.3 （10.8 - 16.0） 3.6 （2.3 - 5.4） 95.9 （89.9 - 98.9） 0.5 （0.4 - 0.6） 15 - 39 岁 90.7 （82.5 - 95.9）30.1 （24.9 - 35.6） 27.4 （22.3 - 32.9） 91.8 （84.4 - 96.4） 0.6 （0.6 - 0.7） 40 - 64 岁 85.1 （79.4 - 89.7）33.3 （28.5 - 38.4） 41.2 （36.4 - 46.1） 80.3（73.0 - 86.3） 0.6（0.5 - 0.6） 65岁及以上 86.3 （76.6 - 92.9）26.0 （19.7 - 33.1） 34.5 （27.9 - 41.5） 80.7 （68.1 - 90.0） 0.6 （0.5 - 0.6） 31 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 1智利卫生部卫生规划司流行病学处、严重急性呼吸道感染监测哨点医院以及公共卫生研究所，未公布的数据，2020年9月23日。 2哥斯达黎加卫生部、营养与健康研究教育中心、社会保障局，未公布的数据，2020年9月23日 3巴拉圭公共卫生部，未公布的数据，2020年9月23日 4南非国家卫生实验室国家传染病研究所呼吸道疾病和脑膜炎中心，未公布的数据，2020年9月23日 5严重急性呼吸道感染定义为在过去10天内急性发热和咳嗽并住院；无论症状持续时间多长，分母都是因下呼吸道感染入院。 缩略语：AUC, 曲线下面积；CI, 置信区间；NPV, 阴性预测值；PPV，阳性预测值；SARI，严重急性呼吸道感染 补充表 S5: 严重急性呼吸道感染用于COVID-19监测的表现特征 国家 敏感性（95% CI） 特异性（95% CI） 阳性预测值（95% CI） 阴性预测值（95% CI）曲线下面积（95% CI） 所有年龄 智利1 49.0 (46.2 - 51.9) 50.2 (47.0 - 53.3) 54.8 (51.8 - 57.8) 44.3 (41.4 - 47.3) 哥斯达黎加2 39.5 (37.3 - 41.6) 32.9 (29.0 - 37.0) 68.2 (65.5 - 70.9) 13.0 (11.2 - 14.8) 乌拉圭3 55.4 (51.9 - 58.8) 60.4 (58.7 - 62.0) 25.9 (23.9 - 28.0) 84.4 (82.8 - 85.8) 南非4,5 51.0 (46 - 56.1) 59.0 (56.5 - 61.5) 24.1 (21.2 - 27.1) 82.8 (80.2 - 84.8) 0.6 (0.5 - 0.6) 0 - 14岁 智利 14.2 (0.36 - 57.8) 31.5 (23.0 - 41.0) 1.3 (0.03 - 7.0) 85.3 (70.8 - 94.4) 哥斯达黎加 47.2 (38.3 - 56.3) 32.7 (26.5 - 38.6) 26.9 (21.2 - 33.2) 53.7 (45.3 - 62.1) 乌拉圭 44.4 (21.5 - 69.2) 54.6 (51.0 - 58.1) 2.2 (0.97 - 4.4) 97.6 (95.7 - 98.8) 南非 51.9 (31.9 - 71.3) 50.2 (46.5 - 54.0) 3.8 (2.1 - 6.3) 96.5 (94.1 - 98.1) 0.5 (0.4 - 0.6) 15 - 39岁 智利 58.3 (48.9 - 67.2) 31.4 (23.4 - 40.4) 45.1 (37.1 - 53.3) 43.8 (33.3 - 54.7) 哥斯达黎加 35.8 (32.4 - 39.3) 34.1 (23.8 - 45.7) 84.2 (77.9 - 88) 5.1 (3.4 - 7.3) 乌拉圭 66.6 (57.2 - 74.8) 51.3 (46.9 - 55.6) 24.4 (20.0 - 29.4) 86.6 (82.4 - 90.2) 南非 54.7 (43.5 - 65.4) 62.2 (56.4 - 67.7) 29.6 (22.6 - 37.3) 82.5 (76.9 - 87.3) 0.6 (0.5 - 0.7) 40 - 64岁 智利 55.2 (50.8 - 59.5) 46.2 (40.6 - 52.0) 63.1 (58.5 - 67.6) 38.2 (33.2 - 43.3) 哥斯达黎加 38.8 (35 - 42.7) 34 (24.7 - 44.3) 79.6 (74.7 - 83.9) 7.7 (5.3 - 10.6) 乌拉圭 60.3 (55.1 - 65.5) 59.5 (55.6 - 63.4) 46.1 (41.5 - 50.7) 72.4 (68.3 - 76.2) 南非 48.8 (41.7 - 55.9) 68.6 (63.6 - 73.3) 46.0 (39.2 - 53.0) 70.9 (65.9 - 75.6) 0.6 (0.5 - 0.6) 65岁及以上 智利 41.9 (37.8 - 46.1) 62.9 (58.2 - 67.4) 59.5 (54.5 - 64.3) 45.4 (41.4 - 49.5) 哥斯达黎加 44.6 (40 - 49.2) 32.6 (24.8 - 41.1) 69.4 (63.8 - 74.5) 14.6 (10.9 - 19.1) 乌拉圭 46.0 (40.5 - 51.7) 67.7 (65.1 - 70.2) 25.2 (21.7 - 28.9) 84.1 (81.8 - 86.2) 南非 52.5 (41.0 - 63.8) 69.5 (62.1 - 76.2) 43.8 (33.6 - 54.3) 76.4(69.1 - 82.7) 0.6 (0.5 - 0.7) 32 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 优点 缺点/局限性数据来源 有实验室确诊的全部或部分 确诊病例的门诊监测 （急性呼 吸道感染或流感样疾病）。 哨点症状和病毒学方法使用系统的 病例检测策略。如果哨点病毒学监 测遵循一致的抽样策略，那么产生 的SARS-CoV-2阳性百分比可能比 通用检测更准确地反映病毒的传播 情况，后者的策略会随着时间和地 点的不同而发生变化。 如果分母信息经常可用，则可以计 算所有门诊或住院患者中有症状患 者的比例或基于人群的比率。 在符合流感样疾病的病例定义 并向门诊哨点报告的患者中，新 COVID-19阳性百分比的趋势可能 是确定是否发生社区传播的一个指 标，并与普遍的监测和报告方案相 辅相成。 那些寻求治疗并满足监测的具体病例定义的有症状人群的趋势。 持续的哨点症状监测，并提供一致和完整的报告。 需要对症状监测的全部或部分样本进行实验室确认，以确定COVID-19的趋势。 COVID阳性百分比取决于表现为流感样病毒的其他传播情况。 依赖实验室规则、检测重点、单一检测与多重检测的使用、到位的非药物干预措施（NPI）、检测能力、资源、 政治问题等。 这不是为了取代，而是对旨在进行接触者追踪的COVID-19综合监测进行补充。 监测并不意味着监测与强度阈值有关的变化，因为在符合哨点监测病例定义的患者中，几乎没有可用于 确定COVID阳性阈值的历史数据。 如果监测没有发现重大中断，来自持续哨点症状监测的数据可以与历史数据进行比较。 及时性：一般在症状出现和报告之间有大约2周的时间间隔。 地理代表性：数据反映了哨点服务的人口情况，可能不够详细，也不能代表国家一级的总体人口情况。 人口代表性：数据反映了哨点服务的人口情况，可能不能反映总体人口情况。 有效性取决于有症状的COVID-19患者是否在哨点门诊就诊。 监测SARS-CoV-2病毒的长期流行趋势和演变 附件 1. 流感样疾病/急性呼吸道感染/严重急性呼吸道感染监测对解决COVID-19目标的优势和局限性 很可能 可能 不可能 33 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 经实验室确诊的住院患者监测 （严重急性呼吸道感染或肺炎） 如果通过哨点收集和报告年龄，就 可以按照各年龄组来确定趋势。 基线和阈值可用于症状数据。 按年龄和风险分列的符合严 重急性呼吸道感染病例定义 并在哨点就诊的入院患者的 COVID-19阳性百分比的趋势。 如果收集和报告的数据一致， 可能了解到重症监护室收治 患者中COVID-19相关的更多 详细内容。 流感样疾病在所有门诊患者中的比例可能会随着提供的门诊卫生保健服务的变化而产生 波动，影响分子和分母的因素。 如果只对流感阴性样本进行SARS-CoV-2检测，得到的SARS-CoV-2百分比阳性结果将在 接受急性呼吸道感染或流感样疾病治疗的流感阴性人群中出现，这可能很难解释。 由于使用的病例定义不同（急性呼吸道感染、流感样疾病或COVID-19疑似病例），以及提 供的卫生保健服务和COVID-19应对的不同变化，可能无法在国家之间进行比较。 在流感样疾病的监测中，年轻人群体的比例可能过高，而中年人群体的比例可能偏低。 有效性和代表性取决于需要入院治疗的有症状COVID-19病例是否在严重急 性呼吸道感染哨点就诊，以及哪些卫生机构和病房参与了严重急性呼吸道感 染监测。 COVID-19阳性百分比取决于表现为严重急性呼吸道感染的其他传播情况。流 感样疾病在所有门诊患者中的比例可能会随着提供的门诊卫生保健服务的变 化而波动，同时影响分子和分母的因素。 由于提供的卫生保健服务和COVID-19应对的不同变化，包括COVID-19疑似病 例的入院标准和医院能力方面的不同，在国家之间和国家内部进行比较可能 无法实现。 在严重急性呼吸道感染监测中，年轻群体的比例可能过高。 有实验室确诊的全部或部分确诊病 例的门诊监测 （急性呼吸道感染或 流感样疾病）。 [继续 ... ] 优点 缺点/局限性数据来源 监测SARS-CoV-2病毒的长期流行趋势和演变 附件 1. 流感样疾病/急性呼吸道感染/严重急性呼吸道感染监测对解决COVID-19目标的优势和局限性 很可能 可能 不可能 34 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 监测SARS-CoV-2病毒的长期流行趋势和演变 有助于理解SARS-CoV-2病毒、流感和其他呼吸道病毒以及其他病原体的共同传播。 哨点病毒学监测 哨点病毒学监测 “世卫组织全球流感监测和 应对系统”网络可以提供一个 有效的样本/病毒移动系统，用 于基因特征分析。 通过报告分母信息和流行病 学信息（病例定义）对哨点监 测样本进行系统和持续的检 测可以提高对传播动态的了 解，并在短期内为防范和应对 措施提供信息。 与流感监测相互竞争的重点项目。 与国家参考实验室和网络竞争的现有冠状病毒实验室监测。 实验室能力可能很快就会不堪重负。 并非所有监测系统都检测流感以外的呼吸道病原体，也不是所有样本都检测 所有呼吸道病毒病原体。 依赖检测原则以及对哨点监测样本的系统和持续检测。 由于重点事项和检测原则不同，在国家之间进行比较可能无法实现。 有针对性的研究可能更适于达成这一目标。 传播动力学特征可能会随着时间的推移而改变。 传播动力学特征将因年龄、严重程度和风险群体而异，因此，除非这些流行病 学信息与病毒学信息一致，否则可能很难解释。 实验室规则和全球报告平台允许检测与SARS-CoV-2和流感或其他呼吸道病 毒的合并感染，并报告汇总信息。 优点 缺点/局限性数据来源 附件 1. 流感样疾病/急性呼吸道感染/严重急性呼吸道感染监测对解决COVID-19目标的优势和局限性 [继续 ... ] 很可能 可能 不可能 35 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 指导实施和调整定向控制措施，同时使经济社会活动能够安全恢复。 评价大流行对医疗卫生系统产生的影响。 有实验室确诊的全部或部分确诊 病例的门诊监测 （急性呼吸道感 染或流感样疾病）。 经实验室确诊的住院患者监测 （严重急性呼吸道感染或肺炎） 经实验室确诊的，有或没有结果 信息的入院患者监测（严重急性 呼吸道感染）。 与趋势目标中包含的内容类似。 设定基线和强度阈值可能很困难，除非可以使用前几波活动的数据。 与趋势目标中包含的内容类似。 设定基线和强度阈值可能很困难。 同上。 相对于流感的长期趋势，评价COVID-19对医疗卫生系统的影响可能会因 为监测目标或检测策略以及应对的其他方面发生变化或变得不同而更加 复杂。 如果有高质量的历史数据，相对于长期的趋势，评估对医疗卫生系统的整 体影响。 为了能更准确地监测流感和COVID-19对医疗卫生系统产生的影响，需要 进一步了解和收集重症监护室和住院治疗的快速增援能力。 监测和控制聚集性病例和暴发，特别是针对易感人群。实现快速发现、隔离检测和接触者追踪。 这些都不是哨点监测的主要目标。哨点监测可以补充来自其他监测的信息，如非哨点监测、基于事件的监测和特殊情况下的监测，其手段是提供通常活动的基线 以供比较并提供背景。 相对于短期趋势，评价COVID-19对 卫生保健系统的影响是可能的。 优点 缺点/局限性数据来源 [继续 ... ]附件 1. 流感样疾病/急性呼吸道感染/严重急性呼吸道感染监测对解决COVID-19目标的优势和局限性 很可能 可能 不可能 36 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 背景和政策 信息技术基础设施 系统和程序 数据质量 准确性 完整性 连续性 及时性 由于提供医疗卫生服务的变化，有呼吸道症状的患者： • 转诊到常规门诊/全科医生以外的地点寻求治疗，这项政策是什么时候开始实施的？ • 是否作为严重急性呼吸道感染患者入住指定COVID-19医院？ • 转诊到专门的筛查中心（以及这项政策是什么时候开始实施的）？ 就医行为有变化吗？ 哨点和工作人员是否有变化，有多大比例的哨点和工作人员被指派参与COVID-19的应对工作？ 可用于哨点症状监测的数据收集、管理和报告的信息技术基础设施是否有所改进？ 收集和报告关于流感样疾病/急性呼吸道感染/严重急性呼吸道感染的数据和实验室结果的系统和流程是否有变化？ 数据是如何进行汇总和报告的？向谁报告？ 收集和报告的数据是否反映了观察到的真实情况？ 流感样疾病/急性呼吸道感染/严重急性呼吸道感染会诊/入院人数是否异常低？哪个系统最能反映该国的情况？ 病例报告表填写完整吗？ 是否有特定的数据元素最常出现填写不完整/空白的情况？ 在每个报告间隔，哨点继续向国家一级报告症状监测数据的百分比是多少？ 哨点继续收集有症状患者的样本并运送到实验室的百分比是多少？ 实验室收到的样本数量有变化吗？ 实验室处理的样本数量有变化吗？ 监测呼吸综合征的病例定义是否发生了改变？ 符合病例定义的患者抽样策略是否发生了改变？ 每周有多少个哨点已经进行了报告？ 是否及时报告数据？具体数据元素是否是及时收集和报告数据的障碍？ 在每个报告间隔，哨点及时报告症状监测数据的百分比是多少？ 在样本采集后的目标天数内，将样本运送至实验室的哨点的百分比是多少？ 在目标时间范围内，处理样本的百分比是多少? 监测系统有助于 问题实例 附件 2. 对监测系统属性的快速情况评估和问题实例 37 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 相互竞争的重点事项和有限的 资源导致对流感常规哨点监测 的支持减少。 哨点和工作人员的变化；机构 停止参与监测系统和/或报告 重新评估流感监测重点。 了解哪个哨点系统对实现流感重点监 测目标最有用。 在可能的情况下，尽量维持现有的监 测系统，但考虑其他数据来源，以帮助 实现某些流感监测目标。 扩大哨点的数量、多样性和地理 代表性，包括指定COVID-19特定 的会诊中心作为急性呼吸道感染/ 流感样疾病/严重急性呼吸道感染 症状监测的哨点。 关于医院和重症监护室能力的其他数据 来源可能有助于监测重症病例的趋势和 对卫生系统的影响。 这些系统的样本可以进行流感检测。 提高对呼吸道疾病监测、能力建设、更好的工 具和综合信息技术基础设施（电子报告）的认 识和机会，可能有助于扩大初级保健和以医院 为基础的哨点监测系统。 增加哨点数量和哨点的多样性可能会提高数 据的代表性。 纳入COVID-19专门中心可能会接收到从全科 医生转到这些专门中心的有症状患者。 增加病例检测和登记可能会增加病毒学监测 的样本量。 延长监测时间（从季节性监测增加到全年监 测）可以全年监测综合征疾病和呼吸道病毒病 原体，包括SARS-CoV-2。 如果监测目标包括流感相关疾病的范围， 或了解病毒株与疾病严重程度的关系，或 发现不寻常和意外事件，如在典型季节以 外暴发流感，可能需要多个监测系统。 财政和人力资源限制： 监测项目和哨点以及实验室能力的成本/可持续 性；需要在哨点招募工作人员来收集数据和样本 并进行报告。哨点的工作人员可能很快就会不堪 重负，导致数据质量不佳。 知识限制：需要对更多的哨点工作人员进行培 训。 基础设施限制：参与病毒学监测的哨点需要能够 正确地处理、存储样本并将其运送到实验室。 数据质量和解释方面的限制：改变分母（受监测 的人群）可能会影响解释，并使数据产生各种偏 差。基于人口的比率可能不准确/服务区很难确 定。可能会影响与历史数据进行比较。 不应将哨点监测等同于COVID-19病例全面检 测/普遍监测。 问题 需要考虑的因素 机会 限制 / 局限性 附件 3. 解决流感哨点症状监测中断的问题 38 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 提供的初级卫生保健服务的 变化（例如，转诊到患者分流 中心）。 提供的初级卫生保健服务的变化： 更多地使用初级保健远程会诊/远 程医疗/远程提供服务 提供的初级卫生保健服务的变化：政策 指导患者完全远离初级保健提供者，转 而使用在线工具、热线或直接前往专门的 COVID-19咨询中心进行自我评估。 提供的初级卫生保健服务的变 化：门诊处患者日程安排、分诊和 筛查的变化。 在每周急性呼吸道感染/流感样 疾病计数报告中纳入符合急性呼 吸道感染或流感样疾病病例定义 的患者对初级保健提供者的分诊 呼叫。 监测急性呼吸道感染/流感样疾病 的分诊呼叫，代替访问。 在每周流感样疾病计数报告中包括来 自符合急性呼吸道感染或流感样疾 病病例定义的患者的远程会诊，并在 每周门诊总计数报告中包括所有远 程会诊。 收集这些信息并用于症状监测。 考虑这些变化如何影响病例检测和 抽样策略。 如果包括分诊呼叫，将增加急性呼吸道感 染/流感样疾病的病例计数。 在该季节跟踪流感样疾病/急性呼吸道感 染的趋势可能是有用的。 同上。 远程会诊更有可能由训练有素的哨点工 作人员（初级保健医生、护士）完成？ 如果患者分诊是由没有接受过哨点监测培 训的工作人员完成的，那么遵循病例定义可 能是一个问题。 没有现实的分母。 此外，数据中还引入了其他偏差。 人力资源限制（初级保健人员的负担）。 可能会进一步推迟报告。 没有病毒学诊断的可能性。 同上，但如果初级保健提供者正在进行病例 检测，可能会更好地遵循病例定义。 同上。 附件 3. 解决流感哨点症状监测中断的问题 限制 / 局限性问题 需要考虑的因素 机会 [继续 ... ] 39 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 将门诊症状监测的病例定义从 流感样疾病改为急性呼吸道感 染（或COVID-19病例定义）。 由于COVID-19，为全面监测住 院/重症监护室收治和卫生保健 能力做出了额外努力 初级保健提供者报告急性呼吸道感染 和流感样疾病的每周计数（包括在病例 报告表上选择一个或两项）。 如果报告了基于病例的数据（包括症 状），国家监测单位可以事后收集急性 呼吸道感染和流感样疾病的数据。 在病例报告表中包括收集症状，以便按 不同的病例定义进行事后分析。 收集这些信息，并评估其对监测流 感影响的效用。 允许将分析限制在符合流感样疾病病 例定义的患者，以便更好地与过去的数 据进行比较。 利用开发的新方法和系统来全面监测 医院能力，并将其作为流感严重程度评 估的一部分，监测卫生系统的影响。 如果使用《国际疾病分类》编码作为监 测严重急性呼吸道感染入院情况的替 代指标有所改进，这对于作为流感监测 一部分的监测可能是有帮助的。 考虑增加初级保健提供者/哨点工作 人员/监测单位负担的好处。 对于流感监测，急性呼吸道感染病例 定义通常更敏感，因此将涵盖更多病 例，并需要更多实验室检测。 问题 需要考虑的因素 机会 限制 / 局限性 附件 3. 解决流感哨点症状监测中断的问题 [继续 ... ] 40 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 问题 需要考虑的因素 机会 限制/ 局限性 COVID检测是重点，资源 有限，无法对所有SARS- CoV-2样本进行流感检测。 SARS-CoV-2检测是在国 家流感中心或具有流感检 测能力的实验室以外的实 验室进行的。 初级保健机构的感染防控 问题/个人防护装备的可 得性 对收到的SARS-COV-2部分样本 进行流感和其他病原体检测。 国家流感中心从专门的检测中 心获取样本的子集，并对SARS- CoV-2阴性样本进行流感检测。 改变样本采集方法，例如有监督 和/或无监督的自拭子。 在哨点进行有关适当使用个人防 护装备的培训（飞沫与接触预防 措施）。 如果有任何流行病学信息与样本相 关联，请检测符合急性呼吸道感染/ 流感样疾病/严重急性呼吸道感染 病例定义的病例样本。 如果流感正在传播，可能会产生一 些流感阳性样本进行特征分析。 可能有助于监测一段时间内的趋 势。 优先考虑SARS-CoV-2阴性样本。 同上。 如果流感正在传播，可能会产生 一些流感阳性样本进行特征分 析。 如果没有流行病学信息与样本相关联，则 符合病例定义的人群中不可能出现流感 检测为阳性的情况。这将服务于了解情况 的目标，而不是其他目标。但如果没有其 他办法，这应该是最低限度的。 如果没有进行系统检测（没有使用病例定 义），那么解释一段时间内的趋势将会非 常困难。 同上 此外，还存在潜在的数据和样本传输 问题。 可能会导致测试和报告延迟。 可能会使病例选择和抽样中产生偏 差。 样本收集可能中断，可能需要考虑替代样本收集方法，以确保在参与哨点呼吸道病毒监测的机构中寻 求治疗的所有或部分有症状患者继续得到实验室确诊。 附件 4. 解决流感哨点病毒学监测中断的问题 41 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 监测登记人数减少/患者对 用拭子擦拭的遵从性/未达 到样本配额 对拭子病例定义进行更改 增加参与病毒学监测的哨点初 级保健提供者的数量，如果不 是所有人都参与的话。 采用系统化的抽样策略，提高 样本产量，以满足配额要求。 对所有符合COVID-19病例定 义的门诊病例进行抽样，并对 其进行SARS-CoV-2和流感检 测。 根据算法和目标，对符合急 性呼吸道感染病例定义和 COVID-19和/或流感检测的所 有门诊病例进行抽样。 潜在地增加了流感和SARS- CoV-2检测样本的产量。 更简单的协议。 对临床管理/诊断也有帮助。 可能会产生一些要进行特征分析 的流感阳性样本。 考虑修改数据收集形式，将症状 纳入回溯性分析。 财务和人力资源限制：监测项目和哨点以及实验室 能力的成本/可持续性；需要在哨点招募工作人员来 收集数据和样本并报告。哨点的工作人员可能很快 就会不堪重负，导致数据质量不佳。 知识限制：需要对更多的哨点工作人员进行样本采 集方面的培训。 基础设施限制：参与病毒学监测的哨点需要能够处 理、存储样本并将其正确传输到实验室。 实验室负担/成本增加。 COVID-19疑似病例的样本可能会被送往国家流感中心以 外的实验室。 无法确定感染COVID或流感的流感样疾病/急性呼吸道感 染/严重急性呼吸道感染的比例，也无法与历史数据进行 比较。 即使没有变化，由于症状监测数据收集的中断，不管怎样， 进行历史数据比较都可能有问题。 与病例定义以及是否需要对COVID-19监测进行临床管理 有关的混乱。 如果从流感样疾病改为急性呼吸道感染，将失去历史背景。 SARS-CoV-2阳性结果需要迅速反馈给医生和患者，以便临 床管理和公共卫生应对行动。 问题 需要考虑的因素 机会 限制/ 局限性 附件 4. 解决流感哨点病毒学监测中断的问题 [继续 ... ] 42 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 需要考虑的修改内容，如果尚未被列入 COVID-19 检测数据到实验室结果部分 严重急性呼吸道感染报告表的其他变量，例如进入重症监护 室接受治疗/使用呼吸/吸氧/结果 严重急性呼吸道感染报告表的其他变量，例如风险因素和/ 或合并症 这对于监测哨点从符合现有流感监测病例定义的患者中发现COVID-19趋势以及了解 SARS-CoV-2病毒、流感和其他呼吸道病毒以及其他病原体的共同传播至关重要。 这一信息提供了指标方面的资料，如接受SARS-CoV-2检测的流感样疾病或严重急性呼吸 道感染患者的数量，以及SARS-CoV-2检测呈阳性的流感样疾病或严重急性呼吸道感染患 者的数量。 如果病例报告表中包括年龄和性别，则可以相应地对趋势进行分层。 应在国家一级并向区域和全球各级报告这一信息，以便为区域和全球应对提供资料，可以 选择汇总格式也可以选择基于病例的格式，具体取决于区域和全球指导。 这对于监测对卫生系统的总体影响、监测死亡趋势以及指导实施和调整有针对性的控制 措施至关重要。 如果将这一信息纳入实验室检测（针对流感和SARS-CoV-2）的信息中，每周的指标，如进 入重症监护室接受治疗的严重急性呼吸道感染的病例数量、需要呼吸机或吸氧的严重 急性呼吸道感染病例数量或严重急性呼吸道感染的死亡人数，都可以被划分为流感和 SARS-CoV-2。 这些指标（无论有没有相关的实验室检测信息，尤其是分母信息）对于监测流感疫情和 COVID-19大流行的严重程度可能很有用，如《大流行流感严重程度评估指南》中所述的内 容。 在符合现有流感监测病例定义的哨点发现的潜在风险人群中监测COVID-19趋势的目标至 关重要。 这些信息将为国家一级的分析提供信息，但不会报告给区域和全球两级。 列入理由 附件 5. 哨点病例报告表的修改以及列入理由 43 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 旅行和/或接触史 其他症状（与COVID-19相关，非呼吸道症状） 适用的病例定义 考虑病例报告表是否也将作为COVID-19疑似病例的调查表，并引发相关的公共卫生响应。 考虑病例报告表是否也将作为COVID-19疑似病例的调查表，并引发相关的公共卫生响应。 如果症状监测病例定义已从流感样疾病改为急性呼吸道感染，在病例符合急性呼吸道感染和流感 样疾病病例定义的情况下，考虑将其添加到表格中。这将允许对符合一种或另一种病例定义的病例 进行分析。 按照服务区人口和/或每周 门诊量分列的流感样疾病 病例 监测流感样疾病活动发生 的事件和地点，监测与前几 个季节相关的传播强度，如 果可能，按年龄组分列。 用以指导实施和调整针对公共卫生 和社会措施的潜在补充数据来源 需要实验室确认所有样本或部分样本，才能了解导致症状 监测数据变化趋势的病毒特定原因。 对流感而言，由于基线和阈值不适用，只有在系统没有发生 重大中断以及寻求治疗行为没有发生变化的情况下，才有 可能与前几年的数据进行比较。 考虑报告哨点的地理代表性。 考虑及时性和完整性。 考虑来自哨点的症状数据是否正在收集COVID-19病例/ 活动的数据（在理想的情况下，还需要实验室确认SARS- CoV-2的全部病例或子集）。 了解实验室检测原则和重点。 了解分子和分母中出现的偏差。 可用数据 针对流感的目标 针对COVID-19的目标 解释的限制 附件 6. 流感监测数据和目标以及解释的局限性 需要考虑的修改内容，如果尚未被列入 列入理由 附件 5. 哨点病例报告表的修改以及列入理由 [继续 ... ] 44 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 按照服务区人口和/或每周 住院人数分列的严重急性 呼吸道感染 按照重症监护室总收治人数或 严重急性呼吸道感染死亡人数 分列的每周重症监护室收治的 严重急性呼吸道感染病例 样本经过实验室检测严重 急性呼吸道感染/流感样疾 病患者数量，以及检测呈阳 性的百分比 监测和评估流感对高危人群和卫生 保健系统的影响，以及与前几个季节 有关的季节性疫情的严重程度1；评 估流感住院的负担；确定和监测与严 重疾病有关的潜在风险状况；如果可 能，按年龄组分列。 监测和评估流感对高危人群和卫生 系统的影响以及与前几个季节相关 的季节性疫情的严重程度。 同上。 用以指导实施和调整针对公共卫生 和社会措施的潜在补充数据来源 用以指导实施和调整针对公共卫生 和社会措施的潜在补充数据来源 监测SARS-CoV-2病毒的长期流行 病学趋势和演变。 检测流感和SARS-CoV-2病毒的共 同传播。 评估COVID-19对卫生系统产生的 影响（来自严重急性呼吸道感染监 测） 用以指导实施和调整针对公共卫生 和社会措施的潜在补充数据来源 同上，另外： 考虑入院标准的变化，如果哨点收治了COVID-19病例， 这可能会使与历史数据进行比较变得困难。 如果不再收集风险因素信息，这一目标将无法实现。 同上，另外： 考虑重症监护室收治标准的变化，包括哨点的重症监护 室病房是否接收COVID-19病例，这可能会使与历史数据 进行比较变得困难。 考虑抽样策略的任何改变。 要确定流感阳性百分比，则需要收集经处理的总样本或 检测为阴性的总样本。 这种阳性比例取决于其他表现为流感样疾病/严重急性 呼吸道感染的传播情况。 对于COVID-19阳性数据而言，可以与之前类似的数据进 行比较，但是要考虑其他阈值设置方法（短期平均值或 SARS-CoV-2传播高峰期达到的水平）。不能使用非疾病 特定流感疾病/严重急性呼吸道感染或流感阳性阈值进 行比较。 1比较当前活动与使用阈值的历史数据见《大流行性流感严重程度评估指南》 https://www.who.int/influenza/surveillance_monitoring/pisa/en/。pisa/en/。 附件 6. 流感监测数据和目标以及解释的局限性 可用数据 针对流感的目标 针对COVID-19的目标 解释的限制 [继续 ... ] 45 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 哨点处理的样本数量；阳 性样本数量；哨点样本中 阳性样本的百分比 处理所有来源的样本数 量；阳性样本数量；从所 有来源收到的样本中阳 性样本的百分比。 监测流感活动发生的时间和地 点，监测与前几个季节相关的 传播强度；如果可能，按类型和 亚型/谱系进行监测。 监测流感活动的时间和地点， 监测与前几个季节相关的传 播强度 监测COVID活动发生的时间和地 点，监测与前几周相比的传播强度 检测流感和SARS-CoV-2病毒的共 同传播情况 用以指导实施和调整针对公共卫 生和社会措施的潜在补充数据来 源 监测COVID-19活动发生的时间和 地点。 检测流感和SARS-CoV-2病毒的共 同传播情况。 同上。 同上。 非哨点样本有各种来源，并不是使用系统检测方 法收集的。由此得出的数据可能偏向于反映除普 通社区以外的某些人群中的流感活动，可能无法 与历史趋势进行比较。 附件 6. 流感监测数据和目标以及解释的局限性 可用数据 针对流感的目标 针对COVID-19的目标 解释的限制 [继续 ... ] 46 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 向FLUNET数据集报告什么（来自实验室的病毒学数据） 根据国内收集的数据情况，可以每周报告以下不同数据： 进行流感检测的样本数量（来自哨点） 进行流感检测的样本数量（来自非哨点） 进行SARS-CoV2检测的样本数量（来自哨点） 进行SARS-CoV2检测的样本数量（来自非哨点） 流感、SARS-CoV2、呼吸道病毒综合征和其他（如有）呈阳性的样本数量（来自哨点）。 流感、SARS-CoV2、呼吸道病毒综合征和其他（如有）呈阳性的样本数量 （来自非哨点）。 来自哨点的合并感染人数（若想了解有关报告合并感染的进一步说明，请联系flumart@who.int）。 来自非哨点的合并感染人数（若想了解有关报告合并感染的进一步说明，请联系f umart@who.int）。 向FLUID数据集报告什么（流行病学数据） 根据国内收集的数据情况，可以每周报告以下不同数据： 来自流感样疾病哨点（门诊机构）的数据 来自急性呼吸道感染哨点（门诊机构）的数据 来自严重急性呼吸道感染哨点（住院机构）的数据 来自肺炎哨点（住院设施）的数 死亡率（全因死亡率或肺炎和流感死亡率） 进行流感检测的流感样疾病样本数量和其中呈阳性样本的数量 进行流感检测的急性呼吸道感染样本数量和其中呈阳性样本的数量 进行流感检测的严重急性呼吸道感染样本数量和其中呈阳性样本的数量 进行流感检测的肺炎病例数量和其中阳性病例的数量 进行流感检测的重症监护室患者人数和其中呈阳性的患者人数 进行流感检测的人中死亡人数和其中呈阳性人数 进行COVID-19检测的流感样疾病样本数量和其中呈阳性样本的数量 进行COVID-19检测的急性呼吸道感染样本数量和其中呈阳性样本的数量 进行COVID-19检测的严重急性呼吸道感染样本数量和其中呈阳性样本的数量 进行COVID-19检测的肺炎病例数量和其中阳性病例的数量 进行COVID-19的重症监护室患者人数和其中呈阳性的患者人数 进行COVID-19检测的人中死亡人数和其中呈阳性的人数。 如有结果不确定的样本数量，也可以报告。 备注：请注明哪些样本正在接受COVID-19检测（例如，所有接受呼吸道病毒检测的样本，或者只检测流感阴性的样本，或者流感阴性样本的一部 分），因为这种情况可能会随着时间的推移而改变。 上述任何一项都可以按年龄组报告，分母可以按人口也可以按照门诊或住院患者人数报告。 备注：请注明你的病例定义、样本采集或常规监测的其他变化。 附件 7. 报告方式及报告内容 47 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 已向区域平台或FLUNET（病毒学数 据）和/或FLUID报告每周数据（流行病 学数据） ? 准备好在流感数据之外添加 每周哨点和 非哨点样本的 COVID检测数据了吗？ 准备好每周向FLUNET/FLUID 报告流感和/或COVID-19检测 结果 和/或流行病学数据了吗？ 向区域平台报 告? 想要获取将 COIVD-19检测数 据纳入 常规报告的 说明，请联系区域 归口单位 想要获取修改 excel模板方面 的帮助，以便在 常规报告文件中 纳入COVID-19 的内容，请联系 flumart@who. int 如需立即帮 助，请联系 flumart@ who.int 想要获得启动 报告方面的 帮助，请联系 flumart@who. int 将excel文件直接 上传FLUMART? 是 是 是 否 如何通过FLUMART向FLUNET和FLUID报告 在将excel文件上 传至FLUMART时 出现问题？ 48 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 监测 评价 应在各级监测系统对 输入系统的数据的完 整性、及时性和异常 或意想不到的模式进 行持续审查。 对监测系统的所有部 分（包括每个哨点）在 实现目标方面的绩效 表现进行了全面审查 和检查。 评估系统在接受评估 的流行季或评估期间 的运行情况，并确定在 监测期间可以快速解 决的中断问 评估自COVID-19大流 行暴发以来系统的运 行情况，哪些干扰可能 会影响系统，系统在哪 些方面可能从适应中 受益。 在监测开始前制定监测计 划，然后每周至每两周进 行一次。 在时间和资源允许的情 况下，应定期全面审查监 测系统，这对审查系统中 实施的变化可能是有价值 的。在紧急情况下，快速评 估可能会更方便地评估短 期机会和中断情况。 数据的及时性、完整性和偏差，例如： 每周向国家以及报告流感样疾病/严重急性呼吸道感染/急 性呼吸道感染数据的哨点数量和及时性。 按周和及时性向实验室提供样本的哨点数量。 实验室收到的样本数量。 实验室处理的样本数量。 实验室及时处理的样本数量。 实验室样本是否被正确识别为来自哨点还是非哨点？ 流感样疾病/严重急性呼吸道感染/急性呼吸道感染就诊/入院 的数量是否异常低？ 目前的数据是否反映了该国的情况？ 哪种系统最能反映该国的情况？ 根据哨点监测系统评估指导文件对属性进行评估。 对于修改后的评估，需要考虑的其他指标，包括哨点监 测样本的SARS-CoV-2检测（完整性）、是否达到规定的 COVID-19监测目标（有效性）、哨点工作人员对修改的调查 （可接受性）。 内容 方式 原因 时间 指标 附件 8. 流感哨点监测系统的监测和评估 49 维持对流感和sars-cov-2的监视 – 临时指导文件 – 临时指导文件 临时指导文件 世界卫生组织 WHO/2019-nCoV/Adapting_GISRS/2020.1 © 世界卫生组织，2021年 influenza@who.int 调整全球流感监测和应对系统及哨点监测系统 在COVID-19大流行期间坚持流感监测的同时 开展SARS-CoV-2监测