Surveillance of COVID-19 in a Vaccinated Population: A Rapid Literature Review
Authors: Egunsola Oluwaseun , Farkas Brenlea , Flanagan Jordyn , Salmon Charleen , Mastikhina Liza , Clement Fiona 
Published: November 2021

ABSTRACTObjectivesWith 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.MethodWe 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.ResultsThirty-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.ConclusionEvidence 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.EXECUTIVE SUMMARYObjectivesWith 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: 1) identify scientific evidence on surveillance and testing approaches to monitor the presence of the virus in a vaccinated population and determine how these influence testing strategies; 2) identify international guidance on testing and surveillance for COVID-19 and its variants of concern in a vaccinated population; and 3) identify emerging technologies for surveillance.DesignA rapid review was conducted to identify scientific evidence on COVID-19 surveillance and testing approaches, and a targeted literature review was conducted on international guidance.MethodWe 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. 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 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. Although the primary focus was on surveillance guidance in a vaccinated population, guidance that was published after December 2020 but was not vaccine-specific was also considered for inclusion; it was assumed that this guidance was still in effect and was not yet updated. There were no language limitations. A patient partner was engaged during the co-production of a plain language summary for both the rapid review of primary literature and the review of international guidance.ResultsThirty-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. Population surveillance with RT-PCR testing and/or rapid antigen testing was utilized in 22 studies, mostly in healthcare settings, but also in long-term 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. PCR-testing 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 (including follow-up with viral whole genome sequencing), and sero-surveillance (including blood donor samples, routine blood tests, and residual sera).ConclusionEvidence 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 evidence-informed guidance on testing and surveillance approaches in a vaccinated population that incorporates all testing modalities is required.Protocol/Topic RegistrationPROSPERO-CRD42021261215.Key DefinitionsAntigen:a foreign protein which induces an immune response in the body, especially the production of antibodiesFully vaccinated: refers to individuals who have received complete dosage of a given vaccinePartially vaccinated:refers to individuals who have received an incomplete dosage of a given vaccineSero-surveillance:estimation of antibody levels against infectious diseasesSurveillance:ongoing systematic collection, analysis, and interpretation of health data that are essential to the planning, implementation, and evaluation of public health practiceVariants of Concern:a variant for which there is evidence of an increase in transmissibility and/or more severe diseaseVariants:virus with a permanent change in its genetic sequence