key: cord-0303440-8zam01u8
authors: Egunsola, O.; Farkas, B.; Flanagan, J.; Salmon, C.; Mastikhina, L.; Clement, F.
title: Surveillance of COVID-19 in a Vaccinated Population: A Rapid Literature Review
date: 2021-11-08
journal: nan
DOI: 10.1101/2021.11.05.21265763
sha: 25e9cd3117c2492ecb5314516c513964522e59b3
doc_id: 303440
cord_uid: 8zam01u8

Objectives: With the availability of COVID-19 vaccines, public health focus is shifting to post-vaccination surveillance to identify breakthrough infections in vaccinated populations. Therefore, the objectives of these reviews are to identify scientific evidence and international guidance on surveillance and testing approaches to monitor the presence of the virus in a vaccinated population. Method: We searched Ovid MEDLINE, including Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase, EBM Reviews - Cochrane Central Register of Controlled Trials, and EBM Reviews - Cochrane Database of Systematic Reviews. We also searched the Web of Science Core Collection. A grey literature search was also conducted. This search was limited to studies conducted since December 2020 and current to June 13th, 2021. There were no language limitations. COVID-19 surveillance studies that were published after December 2020 but did not specify whether they tested a vaccinated population were also considered for inclusion. For the international guidance review, a grey literature search was conducted, including a thorough search of Google, websites of international government organizations (e.g., Center for Disease Control and Prevention [CDC], World Health Organization [WHO]), and McMaster Health Forum (CoVID-END). This search was primarily examining surveillance guidance published since December 2020 (to capture guidance specific to vaccinations) and any relevant pre-December 2020 guidance. Results: Thirty-three studies were included for data synthesis of scientific evidence on surveillance of COVID-19. All the studies were published between April and June 2021. Twenty-one studies were from peer-reviewed journals. Five approaches to monitoring post-vaccination COVID-19 cases and emerging variants of concern were identified, including screening with reverse transcriptase polymerase chain reaction (RT-PCR) and/or a rapid antigen test, genomic surveillance, wastewater surveillance, metagenomics, and testing of air filters on public buses. For population surveillance, the following considerations and limitations were observed: variability in person-to-person testing frequency; lower sensitivity of antigen tests; timing of infections relative to PCR testing can result in missed infections; large studies may fail to identify local variations; and loss of interest in testing by participants in long follow-up studies. Through comprehensive grey literature searching, 68 international guidance documents were captured for full-text review. A total of 26 documents met the inclusion criteria and were included in our synthesis. Seven overarching surveillance methods emerged in the literature. PCR-testing was the most recommended surveillance method, followed by genomic screening, serosurveillance, wastewater surveillance, antigen testing, health record screening, and syndromic surveillance. Conclusion: Evidence for post-vaccination COVID-19 surveillance was derived from studies in partially or fully vaccinated populations. Population PCR screening, supplemented by rapid antigen tests, was the most frequently used surveillance method and also the most commonly recommended across jurisdictions. Most recent guidance on COVID-19 surveillance is not specific to vaccinated individuals, or it is in effect but has not yet been updated to reflect that. Therefore, more evidence-informed guidance on testing and surveillance approaches in a vaccinated population that incorporates all testing modalities is required.

the most frequently used surveillance method and also the most commonly recommended across jurisdictions. Most recent guidance on COVID-19 surveillance is not specific to vaccinated individuals, or it is in effect but has not yet been updated to reflect that. Therefore, more evidence-informed guidance on testing and surveillance approaches in a vaccinated population that incorporates all testing modalities is required. and/or rapid antigen testing was utilized in 22 studies, mostly in healthcare settings, but also in longterm care facilities (LTCFs) and in the community. The frequency of testing varied depending on whether there was an outbreak.

For population surveillance, the following considerations and limitations were observed: studies with discretionary access to testing have highly variable person-to-person testing frequency; antigen tests have lower sensitivity, therefore some positive cases may be missed; timing of infections relative to PCR testing as well as the sensitivity of the tests can result in missed infections; large sample sizes from multicentre studies increase generalizability, but fail to identify local variations from individual centres; with electronic database surveillance, it is difficult to confirm whether patients with a breakthrough infection and a previous positive SARS-CoV-2 test result had a true reinfection or had prolonged shedding from the previous infection; and participants lose interest in studies with long follow-up, with decrease in testing rates over time.

Six wastewater surveillance and three genomic surveillance studies were identified in this review. A number of benefits such as, good correlation with clinical data, ability to predict major outbreaks, and rapid turnaround time were observed with wastewater surveillance. However, challenges such as, inconsistencies in variant representation depending on where the samples were taken within the community, differences in the capacity of wastewater to predict case numbers based on the size of the wastewater treatment plants, and cost, were noted. Emerging technologies like viral detection in public transport filters, novel sampling, and assay platforms were also identified.

Through comprehensive grey literature searching, 68 international guidance documents were captured for full-text review. A total of 26 documents met the inclusion criteria and were included in our synthesis. Most were not specific to vaccinated populations but reported on a surveillance method of COVID-19 and were therefore included in the review; it was assumed that they were still in effect but have not yet been updated. Eleven countries/regions were represented, including Australia, Brazil, France, Germany, India, New Zealand, Spain, United Kingdom, United States, Europe, and International. All of the guidance documents included surveillance methods appropriate for community settings. Other settings of interest were healthcare settings, including hospitals and primary care centres, long-term care facilities, points of entry for travel, schools, and other sentinel sites (e.g., prisons and closed settings). Seven overarching surveillance methods emerged in the literature. PCRtesting was the most recommended surveillance method, followed by genomic screening, serosurveillance, wastewater surveillance, antigen testing, health record screening, and syndromic surveillance.

Only one document (published by Public Health England) was identified that provided guidance on surveillance specific to vaccinated populations. The document outlined a plan to surveil and monitor COVID-19 in vaccinated populations through a series of targeted longitudinal studies, routine surveillance, enhanced surveillance, use of electronic health records, surveillance of vaccine failure Introduction is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of June 2021, there have been more than 179,000,000 confirmed cases of COVID-19, which have resulted in more than 3,800,000 confirmed deaths worldwide. 1 Numerous randomized controlled trials (RCTs) and real-world observational studies have found vaccines to be safe and effective at preventing COVID-19. 2 At the time of writing, more than 2,700,000 vaccine doses have been administered across the world, with several countries (e.g., Israel, the UK) approaching the 70% benchmark of having their population fully vaccinated with the goal of reaching herd immunity. 1, 3 As the number of partially and fully vaccinated people continues to grow, countries may be pivoting their population-level surveillance methods to capture the presence and resurgence of COVID-19 and its variants of concern (VOCs). RT-PCR testing of nose and throat swabs is a widely used method to identify new cases of COVID-19; however, the ability of RT-PCR testing to slow viral spread may be impacted by slow laboratory turnaround times and restricted availability of the tests. 4 As a result, there may be interest in alternative population-level testing modalities that can detect the presence and resurgence of the virus in a setting before an outbreak.

This rapid review aims to answer the following research questions:

1. What scientific evidence exists on surveillance approaches to monitor the presence of the virus in a fully vaccinated population (i.e., monitoring for resurgence and variants of concern through wastewater surveillance and metagenomics, population screening with rapid antigen testing)? How does this influence testing strategies? a. What technologies are emerging to identify infection caused by variants of concern in a vaccinated population? 2. What international guidance exists on testing and surveillance for SARS-CoV-2 and its variants of concern in a fully vaccinated population?

Recognizing that the evidence on surveillance in fully vaccinated populations may be limited, this review also includes literature assessing surveillance broadly in a partially vaccinated population to ensure that all relevant literature is captured.

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This rapid review is registered in the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42021261215. An experienced medical information specialist developed and tested the search strategies through an iterative process in consultation with the review team. Another senior information specialist peer reviewed the MEDLINE strategy prior to execution using the PRESS Checklist. 5 Using the multifile option and deduplication tool available on the OVID platform, we searched Ovid MEDLINE®, including Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase, EBM Reviews -Cochrane Central Register of Controlled Trials, and EBM Reviews -Cochrane Database of Systematic Reviews. We also searched the Web of Science Core Collection. We performed all searches on June 13, 2021.

The strategies utilized a combination of controlled vocabulary (e.g., "COVID-19", "Epidemiological Monitoring", "Population Surveillance") and keywords (e.g., "nCoV", "vaccinated", "surveillance"). Vocabulary and syntax were adjusted across the databases (full search strategies included in Appendix A). No language restrictions were applied but results were limited to the publication years 2020 to the present. Results were downloaded and deduplicated using EndNote version 9.3.3 (Clarivate Analytics) and uploaded to Microsoft Word.

A grey literature search was also conducted, including: MedRxiv, Google, McMaster Health Forum (CoVID-END), and websites of international government organizations (e.g., Center for Disease Control and Prevention [CDC] , World Health Organization [WHO] ). This search was limited to studies conducted since December 2020 and current to June 13 th , 2021. There were no language limitations.

A screening form based on the eligibility criteria was prepared. Citations identified as potentially relevant from the literature search were screened by single reviewer across a team of four reviewers and subsequently read in full text by two reviewers and assessed for eligibility based on the criteria outlined below (Table 1 ). Discrepancies were resolved by discussion or by a third reviewer. Reference lists of included studies were hand searched to ensure all relevant literature is captured. Persons who have been partially or fully vaccinated against COVID-19; populations in settings with a high vaccination rate/low prevalence rate of COVID-19 and low vaccination rate/low prevalence rate of COVID-19 were also considered . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21265763 doi: medRxiv preprint Intervention Surveillance approaches to monitor for resurgence of COVID-19 and variants of concern (e.g., wastewater surveillance and metagenomics, population screening with rapid antigen testing) Comparator No comparator required Outcome Any Study Design

Observational studies examining a surveillance approach to monitor for resurgence of COVID-19 and variants of concern; non-interventional designs like editorials, opinions, reviews were excluded Publication Year Limited to publication date or data collected December 2020-onwards A standardized data extraction sheet was used to extract the month and year of publication, country, study design, surveillance method, variant surveillance, dates of enrollment, vaccination status, population, setting, primary outcomes, and implementation considerations. All reviewers completed a calibration exercise whereby data from two sample studies were extracted by all four reviewers and areas of disagreement were discussed. Data were extracted by one reviewer.

Given the rapid nature of this request, a formal risk of bias assessment was not conducted. A high-level discussion of quality of the evidence (i.e., peer-reviewed vs. preprints) is included below.

Due to the heterogeneity in study designs and outcomes across included studies, data were synthesized narratively; a meta-analysis was not conducted. A high-level summary of the different surveillance methods, populations assessed by the methods, and outcomes is presented in the next section. A patient partner was engaged during the co-production of a plain language summary, which is presented in a separate document.

A total of 1197 articles were identified from database search. After removing duplicates, 914 unique citations were included; 90 of which were assessed in full text articles. Thirty-three studies were included for data synthesis (Figure 1 ). All the studies were published between April and June 2021. Thirteen were national studies; there were seven regional and city-wide studies each; five were single-centre studies (e.g., hospitals and long-term care facilities [LTCFs]); and one was an international study. Sixteen studies were conducted in the USA, four were from England, three each from Israel and Spain, two from Italy, and one study from each of the following: the UK, Canada, India, Indonesia, and Uruguay. The majority of the studies (n=21) were from peer-reviewed journals ( Table 2) .

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Five approaches to monitoring post-vaccination COVID-19 cases and emerging variants of concern were identified in this review. These include population screening with reverse transcriptase polymerase chain reaction (RT-PCR) and or a rapid antigen test, genomic surveillance, wastewater surveillance, metagenomics, and testing of air filters on public buses ( . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

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RT-PCR testing and or rapid antigen testing was utilized in 22 studies. The majority of these studies were in healthcare settings (10 studies), seven were in LTCFs, and two in the community. In two studies, surveillance was conducted among healthcare and essential workers, while another two studies involved LTCFs and the community ( Table 2) .

The studies involving healthcare workers (HCWs) were mostly conducted at single hospitals (7 studies); while two studies were national, 6, 7 and one was a regional study. 8 In some studies, routine post-exposure screening of symptomatic or asymptomatic HCWs using RT-PCR based testing of samples obtained from nasal or oropharyngeal swabs were implemented; 9-12 while some other studies implemented periodic (typically weekly) asymptomatic screenings. 6, [13] [14] [15] Although the majority of the surveillance involving HCWs utilized only RT-PCR testing, two studies used a combination of RT-PCR and rapid antigen testing. One was a biweekly national surveillance study of HCWs in England, 7 and the other was at a single hospital in India. 16 Seven of the hospital-based studies also implemented genetic sequencing to identify variants following a positive RT-PCR test. All the studies identified breakthrough cases among vaccinated individuals, some sequenced for VOCs, while also demonstrating the effectiveness of vaccination against infections.

There were four national LTCFs studies, 17-20 two regional studies 21, 22 and one city-wide study. 23 Five of the seven LTCF surveillance studies utilized RT-PCR and or rapid antigen testing. 18, [20] [21] [22] [23] The frequency of testing appeared to vary depending on whether there was an outbreak. In one study involving LTCFs in Catalonia, Spain, the public health guidelines required routine two-to-four weekly screening of residents and staff with RT-PCR or antigen tests, 21 another study reported two weekly screenings in the absence of an outbreak with an additional daily rapid antigen testing (with confirmatory RT-PCR for positive tests) during an outbreak. 22 Other studies reported a more frequent screening schedule varying between five-to-seven days during an outbreak. 18, 19 Of note, one national USA study reported that the Centres for Medicare and Medicaid services required all nursing homes in the same county to test all their staff and residents at the same frequency based on the county COVID-19 rate. 17 A number of the LTCF studies conducted genetic sequencing to identify variants. 19, 22 Although breakthrough cases were found among vaccinated individuals, the studies generally demonstrated the effectiveness of vaccination in the prevention of infection.

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The two community-based population surveillance studies identified in this review were national studies and were conducted in Israel and England. 24, 25 The English study utilized self-administered throat and nose swabs and questionnaire data from a random sample of the population ages 5 years and above. From this study, it was observed that 92.3% of infections in England at the time were from the B.1.1.7 lineage and 7.7% from the B.1.617.2 lineage. 24 The Israeli national study conducted surveillance in LTCFs and the community (using samples from random drive-through testing centres) 26 and showed that the B.1.1.7 variant was 45% more transmissible than the wild-type strain in Israel. These studies identified COVID-19 cases among vaccinated individuals, and also determined the prevalence and transmissibility of variants.

The following implementation considerations for and limitations to population surveillance were identified in the reviewed studies:

1. For studies allowing discretionary access to testing, the frequency of testing tends to be highly variable from person to person. 12 2. Antigen tests have lower sensitivity, therefore some positive cases may be missed during asymptomatic screening. 9 3. The timing of infections relative to PCR testing and the sensitivity of the PCR tests can result in infections being missed during follow-up. 7 4. While large sample sizes from multicentre studies increase generalizability, several studies observed that details of local variation in practices (in healthcare settings or long-term care facilities) are lost when findings from different centres are pooled and analyzed together. Therefore, the findings of such studies may not be generalizable. [19] [20] [21] For example, the Centres for Medicare and Medicaid Services in the USA required all nursing homes to test residents and staff at the same frequency dictated by the rate of COVID-19 in the community (not in the facility). 17 5. Teran et al noted that, with electronic databases, it was impossible to confirm whether patients with a breakthrough infection and a previous positive SARS-CoV-2 test result had a true reinfection or had prolonged shedding from the previous infection. 23 6 . In a study with prolonged follow up period, the authors observed a progressive decline in participants' interest. 24

Three genomic surveillance studies were identified in this review. 27, 28 Two were city-wide surveillance studies conducted in the USA, 27, 29 and one was a national scale study conducted in Uruguay. 28 All three were community-based studies. Two of the studies identified the emergence of variants in the communities. The Uruguayan national genomic surveillance study, for example, showed that variant P.1 . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21265763 doi: medRxiv preprint was introduced in Uruguay at multiple times over a period of increasing mobility. 28 

There were six wastewater surveillance studies: two were from Spain 30,31 and the USA 32,33 , respectively, and one each from Canada 34 and the UK. 35 The frequency of wastewater sampling varied between once a week 30, 32, 35 to three times a week. 34 A number of benefits of wastewater surveillance were noted across studies. In Spain, 31 wastewater surveillance predicted major outbreaks by several weeks and showed good correlation with clinical data, providing information at local level; 30 while another study in the USA reported a rapid turnaround time (average of 1.6 days). 32 The challenges observed included: inconsistencies in variant representation depending on where the samples were taken within the community 33 and differences in the capacity of wastewater to predict case numbers based on the size of the wastewater treatment plants. 35 One study reported that laboratory build-out costs approximately $100,000 USD in capital equipment and took 3 months to complete. 32

In one study, Hoffman et al. placed and retrieved filters in the existing air filtration systems on public buses in Seattle to test for the presence of trapped SARS-CoV-2 RNA using phenol-chloroform extraction and RT-PCR. The study detected SARS-CoV-2 RNA in 14% of public bus filters tested. 36

Using the nextstrain.org database, Quinonez et al. were able to predict that the rate of B.1.1.7 lineage is going to sharply decrease (near to zero) in the coming months. The authors suggested a cautious generalizability because of the lack of validation of this approach in an experimental study. 37

New surveillance technologies for COVID-19 are emerging and some of these have been validated, but not yet studied in a real-world setting. Examples include the use of wearable monitoring device to continuously monitor skin temperature, heart rate, and respiratory rate for early detection of COVID-19 symptoms 38 and the use of deep learning-based model to detect COVID-19 infection via CT scans and chest X-rays. 39 A number of new assay methods (Table 3 ) and novel sample collection methods were also identified in this review; however, not all met inclusion criteria and were therefore not included in the broader synthesis. For example, Reeves et al. described a composite autosampler that withdraws samples from wastewater outfall within surface-accessible manholes that can be used to monitor and detect SARS-CoV-2 in individual buildings and communities. 40 . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21265763 doi: medRxiv preprint . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) no findings yet. The population of fully vaccinated Arizonans at the time of publication was not reported. Outcomes and generalisability could likely be biased due to healthy worker effect. Information from participants is self-reported or self-collected, therefore possible recall bias may be present. This was a retrospective cohort analysis of 130 department of veteran affairs community living centres (CLCs). The community nursing home data are self-reported, but do not report on the testing and vaccination practices of nursing homes. There are also major differences in patient populations between VA CLCs and CMS-certified nursing homes. Staff vaccination data was lacking. The large geographic spread of the VA system allowed a nationwide sampling but limited the detail on local variation in practices. De Salazar et al 21 (Spain) Preprint Long Term Care/Regional All contacts among staff and residents were screened using molecular test (PCR or antigen test) immediately upon confirmation of an index infection in a facility; further, all staff and residents were regularly screened independently

This was a retrospective study of fully vaccinated individuals. Analysis was conducted at county level rather than facility-level. All RT-PCR positive SARS-CoV-2 specimens, from 9 COVID express laboratories serving New York City, with a cycle threshold (Ct) value <32 underwent whole genome sequencing.

Sequencing was done for samples collected during the first four months of vaccination. The number of persons with reinfection or breakthrough infection whose specimens underwent whole genome sequencing was low, limiting the statistical power to detect modest increases in immune escape that could have a substantial impact on public health. Improved capacity for genomic surveillance, establishment of automated and efficient exchange of WGS data, and integration with population-based clinical and epidemiologic data would enable the rapid characterization of emerging SARS-CoV-2 variants. Rego et al. 28 (Uruguay)

Daily sampling of four diagnostic laboratories was included in the network, that were able to process all Showed that VOC P.1 was introduced in Uruguay at multiple times over a period of increasing mobility. Variants of concern were not detected in the Territorial communities, suggesting the absence of variants of concern SARS-CoV-2 cases in those communities. Percentage of variant remained low throughout the study period in the majority of the sites tested. However, the Toronto sites showed a marked increase from ~25% to ~75% over the study period. Preprint Community/Regional RNA isolated from wastewater samples was used to quantify SARS-CoV-2 and analyze the genetic variation through high-throughput sequencing. Bioinformatics approaches were used to rapidly identify single nucleotide genetic alterations, which were compared with known variants of interest and concern.

Differences in the scale of sample pooling in the community revealed unanticipated inconsistencies in variant representation. 36 (USA) Preprint Community/Regional Individual buses were selected to be sampled via a convenience sampling approach based on which buses could be made available at the depot on a regular basis between 7:00-9:00 AM for sample retrieval. Retrieved filters in the existing HVAC system were sampled. Sample extraction for RT-PCR testing was performed within the same day of the sample collection from metro buses.

SARS-CoV-2 RNA was detected in 14% of public bus filters tested. There was an overlap between pre-and post-vaccination testing periods in this study. Mask mandates were in effect for riders during the sample period, likely reducing the number of viral particles from infected riders landing on the filters. Studies marked with an asterix (*) were included in the review of scientific evidence; more information on their findings can be found in Table 2 . § Indicates preprint. Abbreviations: RT-PCR: reverse transcriptase polymerase chain reaction; VOC: variants of concern; VOI: variants of interest . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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This review suggests that population surveillance with PCR and or rapid antigen tests were the most commonly used surveillance methods. Other approaches include: genomic surveillance, wastewater surveillance, metagenomics, and sampling of filters on public transport.

The RT-PCR detects the RNA genome of SARS-CoV-2 and has been the mainstay of COVID-19 diagnosis. 47 As observed in several studies in this review, rapid antigen testing was often used complementarily with RT-PCR and rarely alone as a surveillance tool. This test detects the presence of viral proteins, 47 is easy to perform, and can be interpreted without specialized training or equipment, thus can be widely distributed with a rapid turnaround time between sampling and results. Rapid antigen tests have generally relatively lower sensitivities compared with RT-PCR. 47-49 Consequently, the European Centres for Disease Control (ECDC) suggested a more nuanced approach to rapid antigen testing, suggesting that in a high prevalence setting, a positive result from an antigen test is likely to indicate a true infection and may not require confirmation by RT-PCR; 50 while any negative test result should be confirmed by RT-PCR immediately. 50 Conversely, the ECDC suggests that in a low prevalence setting, rapid antigen tests should be able to rule out a highly infectious case; as such, a negative test result may not require confirmation by RT-PCR, whereas a positive test will need immediate sampling for a confirmation by RT-PCR. 50 Population-level tracking of the origin, distribution, and trends of Covid-19 is challenging, especially considering the rapidly evolving profile of the virus. Wastewater surveillance may provide a non-invasive, anonymous and scalable method of tracking the virus within the population, within a geographic area, at a point in time. 51 However, challenges such as inconsistencies in variant representation, 33 differences in the capacity of wastewater to predict cases 35 and build-out cost 32 were identified in this review.

A limitation of this review is the lack of details on the methodological approaches to COVID-19 surveillance in the included studies. The majority of the studies were designed as epidemiological studies of existing surveillance programs, therefore, the authors focused on the prespecified study outcomes rather than the practicality of the surveillance programs. Although all the studies included vaccinated populations, there were variations in the reporting of vaccination rate. While some small hospital-based and LTCF studies reported institutional vaccination rates, several large studies did not.

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Due to the anticipation that the primary evidence would stem from websites of international government organizations, a database search was not conducted. A grey literature search was conducted, including a thorough search of Google, websites of international government organizations (e.g., Center for Disease Control and Prevention [CDC], World Health Organization [WHO]), and McMaster Health Forum (COVID-END). This search was primarily examining surveillance guidance published since December 2020 (to capture guidance specific to vaccinations); however, it was expanded to include guidance on surveillance programs that would have been established prior to December 2020 but were still in place. There were no language limitations.

A screening form based on the eligibility criteria was prepared. Citations identified as potentially relevant from the literature search were screened by single reviewer across a team of four reviewers and subsequently read in full text by two reviewers and assessed for eligibility based on the criteria outlined below (Table 4 ). Discrepancies were resolved by discussion or by a third reviewer. Reference lists of included studies were hand searched to ensure all relevant literature is captured. Persons who have been partially or fully vaccinated against COVID-19; populations in settings with a high vaccination rate/low prevalence rate of COVID-19 and low vaccination rate/low prevalence rate of COVID-19 were also considered Intervention Surveillance approaches to monitor for resurgence of COVID-19 and variants of concern (e.g., wastewater surveillance and metagenomics, population screening with rapid antigen testing) Outcome Any Guideline Body Guidance issued by international health organizations

Limited to publication date December 2020-onwards; ongoing surveillance programs established before December 2020 were considered for inclusion A standardized data extraction sheet was used to extract the month and year of publication, country, scope (e.g., national), surveillance method, vaccination status, population, setting, intended outcomes (e.g., variant surveillance), platform used for surveillance (e.g., any database), guidance summary, and implementation considerations. All reviewers completed a calibration exercise whereby data from two sample studies were extracted by all four reviewers and areas of disagreement were discussed. Data were extracted by one reviewer.

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The copyright holder for this preprint this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21265763 doi: medRxiv preprint A high-level summary of the guidance pertaining to surveillance across different countries is presented below, followed by a brief discussion of the evidence included in this review; given the rapid nature of this request, a formal risk of bias assessment was not conducted. A patient partner was engaged during the co-production of a plain language summary, which is presented in a separate document.

Through hand searching of grey literature, 68 guidance documents were captured and screened for eligibility. After full-text review, a total of 42 guideline documents were excluded. The most common reason for exclusion was publication date prior to December 2020, without clear indication the surveillance methods were ongoing (n=18). Other reasons for exclusion were: not a guidance document (n=15), not surveillance method(s) (n=6), or duplicate (n=3). A total of 26 guidance documents were included in the synthesis (Table 5 ); see Table 6 in Appendix B for a summary of the guidance provided across included documents. Most were not specific to vaccinated populations but reported on a surveillance method of COVID-19 and were therefore included in the review; it was assumed that they were still in effect but have not yet updated.

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The copyright holder for this preprint this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21265763 doi: medRxiv preprint Stated reason for use: To monitor coverage of the vaccine in targeted populations and identify under vaccinated groups; to rapidly detect and evaluate possible adverse events associated with vaccination; to estimate the effectiveness of the vaccine at preventing a spectrum of disease outcomes and onwards transmission in different targeted populations, and against different viral variants, as well as the duration of any protective effect; to identify risk factors for and outcomes of vaccine failure, including any impact on strain evolution; to monitor the overall impact of the vaccination programme on COVID-19 in the wider population including the indirect effect on groups not targeted by the vaccination programme; to monitor the impact of the vaccination programme on prevalence of antibodies against COVID-19 as an indicator of population level immunity, and to monitor antibody waning in the population; to monitor attitudes to vaccination and identify barriers to high vaccine uptake, and; to monitor inequalities in each of these outcome measures 56 ,61,66,73,74,76 Documents were derived from government websites (Departments/Ministries of Health, National Governments), subsidiaries of national governments (e.g., Public Health England, Centre for Disease Control), or from international organizations (e.g., World Health Organization, Pan American Health Association, and European Centre for Disease Control). The scope of the guidance documents was mostly national-focused (n=17), however there were some that were international-(n=6) and regional-focused (n=3).

All of the guidance documents included surveillance methods conducive for community settings. Other settings of interest were healthcare setting including hospitals and primary care centres, 55 55 and other sentinel sites (e.g., prisons and closed settings). 65, 70 Seven overarching surveillance methods emerged in the literature. PCR-testing was the most recommended surveillance method (n=11), followed by genomic screening (n=9), serosurveillance (n=5), wastewater surveillance (n=5), antigen testing (n=3), health record screening (n=2), and syndromic surveillance (n=2) (Figure 3 ). is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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Only one document was specific to surveillance methods to be deployed in a vaccinated population. The Public Health England COVID-19 Vaccine Surveillance Strategy 63 recommends surveillance methods including PCR-testing, health record screening, serosurveillance, and genome sequencing with the following objectives:

 To monitor coverage of the vaccine in targeted populations and identify under-vaccinated groups;  to rapidly detect and evaluate possible adverse events associated with vaccination;  to estimate the effectiveness of the vaccine at preventing a spectrum of disease outcomes and onwards transmission in different targeted populations, and against different viral variants, as well as the duration of any protective effect;  to identify risk factors for and outcomes of vaccine failure, including any impact on strain evolution;  to monitor the overall impact of the vaccination program on COVID-19 in the wider population including the indirect effect on groups not targeted by the vaccination program;  to monitor the impact of the vaccination program on prevalence of antibodies against COVID-19 as an indicator of population level immunity, and to monitor antibody waning in the population;  to monitor attitudes to vaccination and identify barriers to high vaccine uptake, and;  to monitor inequalities in each of these outcome measures.

Comprehensive hand-searching for international guidance on surveillance methods of COVID-19 yielded 26 documents. Most were not specific to vaccinated populations but reported on a surveillance method of COVID-19 and were therefore included in the review; it was assumed that they were still in effect but have not yet been updated. Seven surveillance methods emerged from the guidance documents: PCR-testing, genomic screening, serosurveillance, wastewater surveillance, antigen testing, health record screening, and syndromic surveillance. Many of the surveillance methods were recommended for use in community settings, however PCR-testing, antigen testing, genomic screening, serosurveillance, and health record screening were also recommended for targeted settings such as health care facilities, long-term care facilities, schools, and points of entry for travelers.

The objectives of the surveillance methods were consistent across countries. PCR-testing, antigentesting, syndromic surveillance, health record screening, and serosurveillance should be used to: monitor the intensity, spread, and severity of COVID-19 in order to estimate the burden of disease, . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21265763 doi: medRxiv preprint identify at-risk populations, identify outbreaks, to adjust public health measures as needed. Additionally, genomic sequencing should be used to identify variations and evolution of SARS-CoV-2 to identify variants of concern. Wastewater surveillance should be used to complement other surveillance methods, to detect if COVID-19 and its variants are present in a community setting.

Only one document (published by Public Health England) was identified that provided guidance specific to surveillance of vaccinated populations. Public Health England details their plan to surveil and monitor COVID-19 in vaccinated populations in the UK, including conducting cohort studies such as SIREN, VIVALDI, and CONSENSUS studies. 63 These will involve routine surveillance, enhanced surveillance, use of electronic health records, surveillance of vaccine failure (including follow-up with viral whole genome sequencing) and sero-surveillance (including blood donor samples, routine blood tests, and residual sera).

There are several limitations to this review. Given the rapid nature of this report and the evidence of interest (i.e., international guidance), we were unable to carry-out an exhaustive systematic search of the literature. Therefore, the international guidance captured here may not include all countries'/institutes' guidance for surveillance. Additionally, we were unable to address the quality of evidence reported in the guidance documents because of the variation in reporting and level of detail in the included documents.

Evidence for post-vaccination COVID-19 surveillance was derived from studies in partially or fully vaccinated populations. Population PCR screening, supplemented by rapid antigen tests, was the most frequently used surveillance method and also the most commonly recommended across jurisdictions. The selection of testing method and the frequency of testing was determined by the intensity of the disease and the scale of testing. Other common testing methods included wastewater surveillance and genomic surveillance. A few novel technologies are emerging, however, many of these are yet to be utilized in the real-world setting. There is limited evidence-based guidance on surveillance in a vaccinated population. Most recent guidance on COVID-19 surveillance is not specific to vaccinated individuals, or it is in effect but has not yet been updated to reflect that. Therefore, more evidenceinformed guidance on testing and surveillance approaches in a vaccinated population that incorporates all testing modalities is required.

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European Centre for Disease Prevention and Control. Options for the use of rapid antigen tests for COVID-19 in the EU/EEA and the UK, 2020. 72.

Wade M, Jones, D., Singer, A., Hart, A., Corbishley, A., Spence, C., Morvan, M., Zhang, C., Pollock, M., Hoffmann, T., Singleton, P., Grimsley, J., Bunce, J., Engeli, A., Henderson, G.,. Wastewater COVID-19 Monitoring in the UK: Summary for SAGE -19/11/20, 2020. 73.

Centers for Disease Control and Prevention. Developing a Wastewater Surveillance Sampling Strategy. November 23, 2020 2020. https://www.cdc.gov/coronavirus/2019-ncov/casesupdates/wastewater-surveillance/developing-a-wastewater-surveillance-sampling-strategy.html (accessed June 10 2021 . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The copyright holder for this preprint this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21265763 doi: medRxiv preprint 44 (epidemiolog* adj3 monitor*).tw,kf. (3222)

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The copyright holder for this preprint this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21265763 doi: medRxiv preprint . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Indexes=SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, ESCI Timespan=All years # 23 123,606 TS=(field NEAR/3 assay*) OR TS=(field NEAR/3 immunoassay*) OR TS=(field NEAR/3 "immunoassay") OR TS=(field NEAR/3 "immunoassays") OR TS=(field NEAR/3 detect*) OR TS=(field NEAR/3 diagnos*) OR TS=(field NEAR/3 screen*) OR TS=(field NEAR/3 test*)

Indexes=SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, ESCI Timespan=All years . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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Indexes=SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, ESCI Timespan=All years # 18 32,874 TOPIC: ((seroepidemiol* or "sero-epidemiology" or "sero-epidemiologic" or "seroepidemiological") NEAR/3 monitor*) OR TOPIC: ((seroepidemiol* or "sero-epidemiology" or "seroepidemiologic" or "sero-epidemiological") NEAR/3 survey*) OR TOPIC: ((seroepidemiol* or "sero-. CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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Indexes=SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, ESCI Timespan=All years # 14 229,157 TOPIC: (vaccinated or inoculated or immunised or immunized) OR TOPIC: (post NEAR/0 (vaccinat* or inoculat* or immuni*) ) OR TOPIC: ((after or already or full or fully or post or received) NEAR/3 (immunis* or immuniz* or immunity or inoculat* or vaccin*) ) OR TOPIC: (status* NEAR/3 (immunis* or immuniz* or immunity or inoculat* or vaccin*) ) Indexes=SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, ESCI Timespan=All years . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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(which was not certified by peer review) Surveillance strategies include:  Monitoring the characteristics and time trends of COVID-19 cases to support planning and evaluation of prevention activities and testing services.  Providing updates on the SARS-CoV-2 transmission potential and forecasts of epidemic activity to support planning and evaluation of prevention activities.  Characterizing clusters and secondary cases to facilitate management within and across jurisdictions and inform targeted control strategies.  Monitoring testing counts for SARS-CoV-2 and to provide denominator to track how effectively testing is being utilized and for an indication of the positivity yield.  Monitoring community trends in "fever/acute respiratory illness (ARI)" and the proportion tested and attributable to SARS-CoV-2 to assess the extent of community transmission and the effectiveness of public health measures aimed at both prevention and case detection.  Determining seroprevalence rates of SARS-CoV-2 by population group and geographic location to Stated reason for use: To monitor coverage of the vaccine in targeted populations and identify under vaccinated groups; to rapidly detect and evaluate possible adverse events associated with vaccination; to estimate the effectiveness of the vaccine at preventing a spectrum of disease outcomes and onwards transmission in different targeted populations, and against different viral variants, as well as the duration of any protective effect; to identify risk factors for and outcomes of vaccine failure, including any impact on strain evolution; to monitor the overall impact of the vaccination programme on COVID-19 in the wider population including the indirect effect on groups not targeted by the vaccination programme; to monitor the impact of the vaccination programme on prevalence of antibodies against COVID-19 as an indicator of population level immunity, and to monitor antibody waning in the population; to monitor attitudes to vaccination and identify barriers to high vaccine uptake, and; to monitor inequalities in each of these outcome measures Surveillance strategies include:  Routine COVID-19 testing through the Second-Generation Surveillance System (SGSS) linked to vaccination data from the NIMS to provide a dataset for monitoring vaccine effectiveness using a test-negative case control approach by vaccine, age group, clinical co-morbidities and different dosing schedules that may be used in the program.  Enhanced surveillance: Once a vaccination program is implemented and the earliest eligible groups have been offered a full course of vaccination, PHE will begin enhanced surveillance of a subset of cases in vaccine eligible groups identified through the routine testing. Clinical questionnaires will be completed with the case and their GP or hospital clinician on vaccination history, past medical history, symptoms and outcomes. Repeat nose and throat swabs and acute and convalescent serum and oral fluid samples will be taken, these will be used to confirm recent infection, provide evidence of immune response following vaccination and identify  Systematic sequencing of a representative or random selection of detected viruses, which should be coordinated regionally and nationally. Laboratories should consider implementing pre-screening RT-PCR approaches to detect N501Y or S-gene target failure (deletion 69-70) variant viruses.  All laboratories should be requested to report their results to the national public health institute that coordinates the collection of information. National public health authorities should notify cases of the variants of concern through the Early Warning and Response System (EWRS), and TESSy for case-based surveillance and aggregate reporting (which has been adapted for this purpose).  To be able to confirm infection with a specific variant, sequencing of the whole SARS-CoV-2 genome, or at least the S-gene for the current variants, is required.  For the VOC 202012/01, a negative S-gene result in multiplex RT-PCR assays, with positive results for the other targets, has been used as an indicator or prescreening method to identify the variant. However, it should be noted that this target failure is not exclusive to VOC 202012/01, and confirmation using sequencing is always recommended.  Increasing the numbers of sequenced samples prescreened by S-gene target failure can be considered to Country Institute/Author Scope, Setting, Evidence Surveillance Method Used Summary of Guidance assess the regional correlation between S-gene target failure and VOC 202012/01 as this varies with the regionally circulating variants. If the correlation is very high, S-gene target failure can be used to approximate the frequency of VOC 202012/01.  A minimum ability to roughly quantify the proportion of a variant present at a prevalence of 2.5% of the total circulating variants is recommended. This requires each country to sequence at least around 500 randomly selected samples each week.  Sequencing of samples from large outbreaks and samples connected to travelers (either from point of entry screening or outbreaks involving a traveler) should be prioritized.  Sequencing should be prioritized for individuals who present with a 'breakthrough infection' identified >14 days after receiving the first dose of COVID-19 vaccine (see section on Vaccination).  Viral isolation of variants of SARS-CoV-2 should be carried out in P3 (Biosafety level (BSL) laboratories to prevent the accidental dissemination of a variant through laboratory exposure.  In general, laboratory preparedness should be among the current high priorities, and laboratories should: 1) consider implementing diagnostic pre-screening for variants of concern (e.g. N501Y and deletion 69-70); 2) ensure human and material resources are available to manage an increasing number of requests for detection and characterization of SARS-  For the identification and monitoring of the circulating variants in the country, a procedure is proposed based on the principles: complete sequencing shall be carried out and done in a planned manner, including a representative number of cases from all AACs and a laboratory will be established.  In addition to the sequencing of COVID in a representative number of cases, it is important to detect early new variants of public interests and therefore sequencing of the following cases/situations will be confirmation by RT-PCR. --On the other hand, any negative test result should be confirmed by RT-PCR immediately or, in case of unavailability of RT-PCR, with another rapid antigen test a few days later (to allow the viral load to increase in previously false negative result). This is particularly true for asymptomatic cases with a known history of exposure.  In any high-risk settings with vulnerable populations only RT-PCR should be used,unless RT-PCR capacity is limited. In vulnerable populations with symptoms, multiplex RT-PCR would be best suited for confirmation to exclude symptoms caused by other respiratory pathogens.  In a low prevalence setting, rapid antigen tests will have a high NPV but a low PPV. Therefore, if used correctly, rapid antigen tests should be able to rule out a highly infectious case in such a setting. A negative test result may not require confirmation by RT-PCR, whereas a positive test will need immediate sampling for a confirmation by RT-PCR.  Recurring testing by rapid antigen test every 2-3 days with the aim to identify infectious cases in a population can partly mitigate the lower sensitivity of the test and can be used in certain settings such as in staff of health care settings.  In low prevalence settings, sufficient RT-PCR and logistics capacity will probably be in place to ensure a rapid turnaround of results. However, there could still be an added value to the use of rapid antigen tests because of the low cost and rapid turnaround time of analysis. Here, a careful cost-benefit calculation has to Stated reason for use: Wastewater testing is being used as an extra tool to help monitor for COVID-19. Wastewater testing may be able to give us an early warning of COVID-19 cases in the community. This will help to alert local communities to be more vigilant, keep up hygiene measures, and get tested and stay home if they are unwell.

 Wastewater is collected from sites that contain a mixture of the wastewater from the toilets, sinks and drains of hundreds of thousands of people in a community. Wastewater is being sampled at least once a week from many sites around the country and the Institute of Environmental Research and Science (ESR) tests these samples at their lab to determine if they can detect the virus.

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SARS-CoV-2 or SARS-CoV2 or SARSCoV-2 or SARSCoV2 or SARS2 or SARS-2 or severe acute respiratory syndrome coronavirus 2).tw,kw

-novel CoV or Sars-coronavirus2 or Sars-coronavirus-2 or SARS-like coronavirus* or ((novel or new or nouveau) adj2 (CoV or nCoV or covid or coronavirus* or corona virus or Pandemi*2)) or (coronavirus* and pneumonia)).tw,kw

coronavirus 2" or "corona virus 2").tw,kw

OC43 or NL63 or 229E or HKU1 or HCoV* or Sars-coronavirus*).tw,kw

B.1.351" or "B.1.617" or "B.1.427" or "B.1.429").tw,kw. (629) 116 ("P.1" and (Brazil* or variant?)).tw,kw

or beta or delta or gamma) adj3 variant?).tw,kw. (11631) ,kw

119853) 122 post-vaccinat*.tw,kw. (11879) 123 post-inoculat*.tw,kw. (11625) 124 post-immuni*.tw,kw

or already or full or fully or post or received) adj3 (immunis* or immuniz* or immunity or inoculat* or vaccin*)).tw,kw. (185537) 126 (status* adj3 (immunis* or immuniz* or immunity or inoculat* or vaccin*)).tw,kw

adj3 survey?).tw,kw

COVID or COVID-19 or COVID19) adj3 (monitor* or survey?)).tw,kw. (2268) 134 ((coronavirus* or corona virus*) adj3 (monitor* or survey?)).tw,kw. (283) 135 ((2019-nCoV or nCoV or n-CoV or SARS-CoV-2 or SARS-CoV2 or SARSCoV-2 or SARSCoV2 or SARS2) adj3 (monitor* or survey?)).tw,kw

BNT162 or BNT162-01 or BNT162a1 or BNT162b1 or BNT162b2 or BNT162c2) adj3 (monitor* or survey?)).tw,kw. (4) 137 ((alpha or beta or delta or gamma) adj3 variant? adj3 (monitor* or survey*)).tw,kw

* or sero-epidemiol*) adj3 (monitor* or survey* or study or studies)).tw,kw. (7224) 144 (seromonitor* or sero-monitor* or serological monitor*).tw,kw. (575) 145 (seroprevalen* or sero-prevalen* or serological prevalen*).tw,kw. (46903) 146 (serosurveillan* or sero-surveillan*).tw,kw. (1338) 147 (serosurvey? or sero-survey? or serological survey?).tw,kw

84) kw. (1017125) 153 ((community health or public health) adj3 (practice? or activit* or endeavo?r?)).tw,kw

or earlier or earliest or ongoing or regular*) adj5 (screen* or detect* or identif* or recogni*)).tw,kw. (529117) 162 (case finding? or casefinding?).tw,kw

metagenomics/ (24172) 164 (ecogenomic* or eco-genomic* or metagenomic* or meta-genomic*).tw,kw

* or ecologic* or environment* or population) adj3 genomic*).tw,kw. (11715) kw. (1062) 170 ((2019-nCoV or nCoV or n-CoV or SARS-CoV-2 or SARS-CoV2 or SARSCoV-2 or SARSCoV2 or SARS2) adj3 test*).tw

or beta or delta or gamma) adj3 variant? adj3 test*).tw,kw

POC or rapid*) adj3 (assay? or immunoassay? or immuno-assay? or detect* or diagnos* or screen* or test*)).tw,kw. (226660) 176 (field adj3 (assay? or immunoassay? or immuno-assay? or detect* or diagnos* or screen* or test*)).tw,kw. (75079) 177 POCT.tw,kw

179 (random* adj3 (assay? or immunoassay? or immuno-assay? or detect* or diagnos* or screen* or test*)).tw,kw

((coronavirus* or corona virus*) and (hubei or wuhan or beijing or shanghai)).ti,ab,kw. (9910) 204 (wuhan adj5 virus*).ti,ab,kw. (535) 205 (2019-nCoV or 19nCoV or 2019nCoV).ti,ab,kw. (3468) 206 (nCoV or n-CoV or "CoV 2" or CoV2).ti,ab,kw. (91681) 207 (SARS-CoV-2 or SARS-CoV2 or SARSCoV-2 or SARSCoV2 or SARS2 or SARS-2 or severe acute respiratory

CoV or nCoV or covid or coronavirus* or corona virus or Pandemi*2)) or (coronavirus* and pneumonia)).ti,ab,kw. (36536) 209 (novel coronavirus* or novel corona virus* or novel CoV).ti,ab,kw. (18558) 210 ((coronavirus* or corona virus*) adj2 "2019").ti,ab,kw

OC43 or NL63 or 229E or HKU1 or HCoV* or Sars-coronavirus*).ti,ab,kw

351" or "B.1.617" or "B.1.427" or "B.1.429").ti,ab,kw. (627) 216 ("P.1" and (Brazil* or variant?)).ti,ab,kw. (3403) 217 ((alpha or beta or delta or gamma) adj3 variant?).ti,ab

119795) 222 post-vaccinat*.ti,ab,kw. (11858) 223 post-inoculat*.ti,ab,kw. (11624) 224 post-immuni*.ti,ab,kw

or already or full or fully or post or received) adj3 (immunis* or immuniz* or immunity or inoculat* or vaccin*)).ti,ab,kw. (185426) 226 (status* adj3 (immunis* or immuniz* or immunity or inoculat* or vaccin*)).ti,ab,kw

((disease* or pandemic*) adj3 (monitor* or survey?)).ti,ab,kw. (56234) 232 ((COVID or COVID-19 or COVID19) adj3 (monitor* or survey?)).ti,ab,kw. (2268) 233 ((coronavirus* or corona virus*) adj3 (monitor* or survey?)).ti,ab,kw. (283) 234 ((2019-nCoV or nCoV or n-CoV or SARS-CoV-2 or SARS-CoV2 or SARSCoV-2 or SARSCoV2 or SARS2) adj3

BNT162 or BNT162-01 or BNT162a1 or BNT162b1 or BNT162b2 or BNT162c2) adj3 (monitor* or survey?)).ti,ab,kw

236 ((alpha or beta or delta or gamma) adj3 variant? adj3 (monitor* or survey*)).ti,ab,kw

Epidemiological Monitoring/ (10263) 239 (epidemiolog* adj3 monitor*).ti,ab,kw

Seroepidemiologic Studies/ (26333)

* or sero-epidemiol*) adj3 (monitor* or survey* or study or studies)).ti,ab,kw. (7220) 242 (seromonitor* or sero-monitor* or serological monitor*).ti,ab,kw. (574) 243 (seroprevalen* or sero-prevalen* or serological prevalen*).ti,ab,kw. (46880) 244 (serosurveillan* or sero-surveillan*).ti,ab,kw. (1338) 245 (serosurvey? or sero-survey? or serological survey?).ti,ab,kw

Data Collection/ (305772)

* or monitor*) adj3 data).ti,ab,kw

or public health) adj3 (practice? or activit* or endeavo?r?)).ti,ab,kw. (15865) ,ab,kw. (477093) 256 (biosurveillance* or bio-surveillance*).ti,ab,kw

or earlier or earliest or ongoing or regular*) adj5 (screen* or detect* or identif* or recogni*)).ti,ab,kw. (526276) 262 (case finding? or casefinding?).ti,ab,kw

32988) 265 ((communit* or ecologic* or environment* or population) adj3 genomic*).ti,ab,kw. (11715) ab,kw. (7783) 268 ((coronavirus* or corona virus*) adj3 test*).ti,ab,kw. (1061) 269 ((2019-nCoV or nCoV or n-CoV or SARS-CoV-2 or SARS-CoV2 or SARSCoV-2 or SARSCoV2 or SARS2) adj3 test*).ti,ab,kw. (7733) 270 ((BNT162 or BNT162-01 or BNT162a1 or BNT162b1 or BNT162b2 or BNT162c2) adj3 test*).ti,ab,kw. (8) 271 ((alpha or beta or delta or gamma) adj3 variant? adj3 test*).ti,ab,kw

Point-of-Care Testing/ (18292)

point-of-care or bedside? or bed side? or POC or rapid*) adj3 (assay? or immunoassay? or immuno-assay? or detect* or diagnos* or screen* or test*)).ti,ab,kw

immunoassay? or immuno-assay? or detect* or diagnos* or screen* or test*)).ti,ab,kw. (74971) 276 POCT.ti,ab,kw. (5130) 277 (rapid adj3 (antigen* adj3 (assay? or immunoassay? or immuno-assay? or test*))).ti,ab,kw. (3261) 278 (random* adj3 (assay? or immunoassay? or immuno-assay?

279 (random* adj3 sampl*).ti,ab,kw. (178562) 280 (pool* adj3 sampl*).ti,ab,kw

p oint-ofcare" or bedside* or "bed side" or "bed sides" or POC or rapid*) NEAR/3 immunoassay*) OR TS=(("point-ofcare" or bedside* or "bed side" or "bed sides" or POC or rapid*) NEAR/3 "immunoassay") OR TS=(("point-ofcare" or bedside* or "bed side" or "bed sides" or POC or rapid*) NEAR/3 "immunoassays") OR TS=(("point-ofcare" or bedside* or "bed side" or "bed sides" or POC or rapid*) NEAR/3 detect*) OR TS=(("p oint-ofcare" or bedside* or "bed side" or "bed sides" or POC or rapid*) NEAR/3 diagnos*) OR TS=((" point-ofcare" or bedside* or "bed side" or "bed sides" or POC or rapid*) NEAR/3 screen*) OR TS=(("p oint-of-care

2019-nCoV" or nCoV or "n-CoV" or "SARS-CoV-2" or "SARS-CoV2" or "SARSCoV-2" or SARSCoV2 or SARS2) NEAR/3 test*) OR TS=((BNT162 or BNT162-01 or BNT162a1 or BNT162b1 or BNT162b2 or BNT162c2) NEAR/3 test*) OR TS=(("alpha vari ant" or "alpha variants" or "beta variant" or "beta variants" or "delta variant" or "delta variants" or "gamma variant" or

TOPIC: (screening) OR TOPIC: ((mass or population*) NEAR/3 screen*) OR TITLE: (screen* or detect* or identif* or recogni*) OR TOPIC: ((early or earlier or earliest or ongoing or regular*) NEAR/5 (screen* or detect* or identif* or recogni*) ) OR TOPIC: ("case finding" or "case findings

OR TOPIC: ((communit* or ecologic* or environment* or population) NEAR/3 genomic*) epidemiology" or "sero-epidemiologic" or "seroepidemiological") NEAR/3 study) OR TOPIC: ((seroepidemiol* or "sero-epidemiology" or "seroepidemiologic" or "sero-epidemiological") NEAR/3 studies) OR TOPIC: (seromonitor* or (sero NEAR/0 monitor*) or (serological NEAR/0 monitor*)

prevalen*) or (serological NEAR/0 prevalen*) ) OR TOPIC: (serosurveillan* or

OR TOPIC: (serosurvey* or (sero NEAR/0 survey*) or (serological NEAR/0 survey*) )

SARS-CoV-2" or "SARS-CoV2" or "SARSCoV-2" or SARSCoV2 or SARS2) NEAR/3 monitor*) OR TOPIC: (("2019-nCoV" or nCoV or "n-CoV" or "SARS-CoV-2" or "SARS-CoV2" or "SARSCoV-2" or SARSCoV2 or SARS2) NEAR/3 survey*) OR TOPIC: ((BNT162 or BNT162-01 or BNT162a1 or BNT162b1 or BNT162b2 or BNT162c2) NEAR/3 monitor*) OR TOPIC: ((BNT162 or BNT162-01 or BNT162a1 or BNT162b1 or BNT162b2 or BNT162c2) NEAR/3 survey*) OR TOPIC: (("alpha variant" or "alpha variants" or "beta variant" or "beta variants" or "delta variant" or "delta variants" or "gamma variant" or "gamma variants") NEAR/3 monitor*) OR TOPIC: (("alpha variant" or "alpha variants" or "beta variant" or "beta variants" or "delta variant" or

TOPIC: ((health or population*) NEAR/3 survey*) OR TOPIC: ((disease* or pandemic*) NEAR/3 monitor*) OR TOPIC: ((disease* or pandemic*) NEAR/3 survey*) OR TOPIC: ((COVID or "COVID-19" or COVID19) NEAR/3 monitor*) OR TOPIC: ((COVID or "COVID-19" or COVID19) NEAR/3 survey*) OR TOPIC: ((coronavirus* or "corona virus" or "corona viruses") NEAR/3 monitor*) OR TOPIC: ((coronavirus* or

Stated reason for use: Monitor the intensity, geographic spread and severity of COVID-19 in the population in order to estimate the burden of disease, assess the direction of recent time trends, and inform appropriate mitigation measures; monitor viral changes to inform drug and vaccine development, and to identify markers of severe infection; monitor changes in which risk groups are most affected in order to better target prevention efforts; monitor the epidemic's impact on the healthcare system to predict the trajectory of the epidemic curve and inform resource allocation and mobilization of surge capacity as well as external emergency support; monitor the impact of any mitigation measures to inform authorities so they can adjust the choice of measures, as well as their timing and intensity; detect and contain nosocomial outbreaks to protect healthcare workers and patients, and; detect and contain outbreaks in long-term care facilities and other closed communities to protect those most at risk of severe disease and poor outcomes.will be the absolute number of newly confirmed cases and their notification rate per 100 000 population.  Sentinel syndromic surveillance: should integrate COVID-19 surveillance with sentinel surveillance of influenza-like illness (ILI) or acute respiratory infection (ARI), which is in place in most EU/EEA Member States. The naso-pharyngeal swabs obtained by sentinel physicians from a systematic sample of patients presenting with ILI/ARI should also be tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in addition to influenza virus and other respiratory viruses. In countries where sentinel physicians are not able to swab their patients, other approaches can be considered, such as self-swabbing and shipping of specimens using dedicated channels.  Helplines, surveys, participatory surveillance. Countries not systematically testing most suspected cases while limiting physical access to primary healthcare (for example by encouraging people to call specific COVID-19 helplines, or when people are placed in in lockdown) should consider analysing data from alternative sources. These could include phone consultations of sentinel physicians, calls to regional/national healthcare telephone helplines, consultations of online healthcare apps or self-assessment tools for advice on COVID-19 testing, or population-based participatory syndromic surveillance schemes for influenza that exist in a number of Member States. Resources permitting, countries can also conduct their own regular telephone surveys.