Abstract Influenza surveillance has typically been carried out using influenza-like illness (ILI) rates and proportions of laboratory tests positive for influenza as metrics to monitor, with sample sizes for the number of tests to carry out based on the precision of the resulting estimate of proportions positive. The transition out of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic period has encouraged the establishment of integrated surveillance of respiratory pathogens, in the context of multiple surveillance objectives, as set out by WHO in its revised integrated surveillance guidance and Mosaic Respiratory Surveillance Framework. These objectives include outbreak detection, situational awareness and intensity evaluation, among others. We illustrate how to design respiratory surveillance in primary care, by considering multiple surveillance objectives for different metrics of different types of respiratory pathogen circulation seasons in England, the USA and Hong Kong. We focus on a proxy of influenza activity as a metric to compare between these countries/regions. Taking advantage of England’s integrated sentinel primary care surveillance system, we propose further metrics to monitor: a proxy of respiratory activity, novelly defined as the product of an acute respiratory infection (ARI) consultation rate and the proportion of tests positive for at least one pathogen ; pathogen-specific ARI-based activity proxies for more detailed monitoring of influenza and SARS-CoV-2; and integrated monitoring of proportions positive for all pathogens tested. We use a simulation approach to determine sample sizes by optimising either the probability of, or time to, detection of different events in monitored metrics, according to the different surveillance objectives. We find that sample sizes to maximise detection probabilities or minimise detection times vary by metric, objective, event and country/region. At a national level, the current sample sizes used are sufficient to detect most events in most weeks for both the USA and Hong Kong, but for England the numbers of swabs taken for ILI consultations may not be sufficient in all weeks, particularly at the start of the season when outbreak detection is important. However, broadening the criteria for swabbing to acute respiratory symptoms does allow for sufficient sample sizes.

We analysed weekly influenza A intensive care unit (ICU) or high dependency unit (HDU) admissions reported by age group and subtype by NHS trusts in England through mandatory surveillance during the 2023-2024 influenza season. We investigated whether subtype reporting varied with patient age group, NHS trust type and region. We estimated the subtype ratio and explored whether this estimate varied among subsets of trusts grouped by the regularity of subtype reporting. Our aim was to explore factors relating to subtype reporting and investigate how these affect subtype ratio estimates. 112 NHS trusts reported data, with 86 trusts reporting influenza A cases and 28 trusts reporting subtyped influenza A cases. The proportion of subtype reporting trusts varied with region and trust type, but not patient age group. The estimated ratio of influenza A(H1N1)pdm09 to influenza A(H3N2) was 3.13 (95% CI: 2.17, 4.51), indicating that influenza A(H1N1)pdm09 was dominant; this was approximately similar across levels of regularity of trust subtype reporting. The accuracy of subtype ratio estimates depends on the availability of influenza A subtype information and data representativeness. We identified low levels of subtype reporting, which likely limits early recognition of new influenza strains and informing of the prescription of antivirals in influenza outbreaks.

Fluctuations in disease severity occurred throughout the COVID-19 pandemic in England due to emerging variants and changing population immunity. Deaths caused by COVID-19 reduced from 2022; however, a smaller reduction was observed in deaths following a COVID-19 test. This study examines whether mortality risk within 28 days of a positive SARS-CoV-2 test remained elevated during a period of reduced disease severity. National-level routinely collected health data containing SARS-CoV-2 test results, vaccination, hospital, and death records were linked to create a population-level cohort. Individuals testing positive and negative were matched on demographic and disease characteristics. Mortality risk was compared using univariable and multivariable conditional logistic regression models for the overall time-period (March 2020-April 2022) and the focus time-period (January-April 2022). Individuals testing positive in the overall time-period had a 228% increased risk of death than those testing negative. In the focused time-period, test positive individuals had 63% higher odds of death, accounting for vaccination and previous hospitalisation. The increased risk of death associated with testing positive was greater among unvaccinated individuals (238%) than vaccinated individuals (155%). Mortality risk following COVID-19 remained elevated at the end of the pandemic, especially among unvaccinated individuals, supporting continued COVID-19 booster vaccination campaigns.

FluSurvey is a participatory surveillance system used to monitor trends in influenza and other respiratory viruses through weekly symptom surveys among the UK population. We aimed to characterise the wider impact of influenza-like illnesses (ILI) among FluSurvey participants and assess correlations of ILI with other established influenza surveillance systems. We included data reported by FluSurvey participants over the 2023-24 and 2024-25 winter seasons. Using weekly symptoms surveys, we derived ILI episodes and estimated the proportion reporting healthcare service use, medication use, impact on daily life, absenteeism and use of tests. We applied existing data methods (omitting first report and weighting to the age-sex structure of England) and assessed cross-correlations of weekly FluSurvey ILI rates with the national surveillance of GP ILI consultations, influenza hospital admissions, and influenza PCR test positivity at time lags of up to +/-2 weeks. There were 3057 participants over two winter seasons (N2023-24=2540, 63% female, mean age 60 years; N2024-25=2273, 64% female, mean age 61 years). Of 1868 ILI episodes, only a minority contacted healthcare services (14%, most frequently visiting the GP). A large proportion of episodes reported medication use (89%), impact on daily life (75%) and missing school or work (47%). Notable differences in testing behaviour were apparent by season, with fewer reporting use of tests in 2024-25. FluSurvey ILI rates were strongly correlated with other influenza surveillance, predominantly leading GP ILI consultations (max r=0.73), coinciding with influenza hospital admissions (max r=0.88) and lagging influenza test positivity (max r=0.88). The majority of ILI reported to FluSurvey do not contact healthcare due to symptoms but experienced wider impacts on daily life. FluSurvey ILI corresponds well with other national influenza surveillance and provides broader context on community illness, supplementing the monitoring of influenza activity for public health response. ### Competing Interest Statement The Immunisations and Vaccine Preventable Diseases division at UKHSA has undertaken post-marketing surveillance and regulatory analyses requested by vaccine manufacturers for which cost-recovery charges have been made. No other conflicts of interest have been declared. ### Funding Statement This work was funded by the UK Health Security Agency. No external funding was received. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Data are processed under the UK General Data Protection Regulation (UK GDPR) lawful bases that relate to public interest and public health: Article 6(1)(e) and Article 9(2)(i). Separately, common law consent is obtained to meet the legal and ethical requirements for processing confidential patient information, in line with the common law duty of confidentiality. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Summary data used for cross-correlation analysis are publicly available https://www.gov.uk/government/statistics/national-flu-and-covid-19-surveillance-reports-2024-to-2025-season. Authors cannot make the underlying dataset publicly available for ethical and legal reasons.

OBJECTIVES:Gathering real-time surveillance data on infectious diseases in prisons can be challenging, and can contribute to health inequalities, including poorer health outcomes and increased risk of transmission. This study assessed the reliability of the address-matching method developed by the UK Security Health Agency (UKHSA) in detecting COVID-19 cases in prisons across England. STUDY DESIGN:Retrospective descriptive study. METHODS:The retrospective descriptive study compared data from the UKHSA prison line list generated using the enhanced address-matching enrichment procedure with pseudonymized line list data from the Ministry of Justice (MOJ) in selected English prisons between March 2020 and January 2023. Cases were compared at the regional and prison levels to examine the consistency of positive episode counts over time, and by prison. The study included 104 prisons and excluded young offenders' institutions. RESULTS:Overall, the comparison showed both MOJ and UKHSA COVID-19 prison episodes were very closely aligned in 2020 and 2021 with generally over ninety percent agreement in most prisons, the close alignment remained consistent overall and at regional levels until January 2022, coinciding with the arrival of the Omicron variant and shortly thereafter the relaxation in testing aligning with the governments living with COVID-19 plan when differences in case counts became more noticeable. CONCLUSION:The enhanced address matching method is reliable in identifying COVID-19 prison episodes and could be adapted for active and timely surveillance of other infectious diseases, and in other settings beyond prisons. This can facilitate better and evidence-based policies for planning and intervention during public health outbreaks.

IntroductionThe emergence of SARS-CoV-2 variants necessitated identification of travel-associated COVID-19 cases in England.MethodsWe implemented a novel integrated COVID-19-episode-level travel surveillance system, Surveillance of International COVID-19 Cases (SuITCases), to assign imported, sporadic or unknown travel status to COVID-19 cases, using data linkage between two enhanced and two routine data sources.ResultsSuITCases identified 517,988 travel-associated SARS-CoV-2 episodes (3.0% of total), where the two enhanced systems assigned most travel statuses.ConclusionsOur unique system facilitated rapid identification of travel-associated COVID-19 cases, reducing transmission and informing public health actions. Enhanced surveillance data sources should be considered as potential tools for future outbreak investigations and pandemic preparedness.

IntroductionElectronic health records can be used to understand the diverse presentation of post-acute and long-term health outcomes following COVID-19 infection. In England, the UK Health Security Agency, in collaboration with the University of Oxford, has created the Evaluation of post-acute COVID-19 Health Outcomes (ECHOES) dataset to monitor how an initial SARS-CoV-2 infection episode is associated with changes in the risk of health outcomes that are recorded in routinely collected health data.MethodsThe ECHOES dataset is a national-level dataset combining national-level surveillance, administrative, and healthcare data. Entity resolution and data linkage methods are used to create a cohort of individuals who have tested positive and negative for SARS-CoV-2 in England throughout the COVID-19 pandemic, alongside information on a range of health outcomes, including diagnosed clinical conditions, mortality, and risk factor information.ResultsThe dataset contains comprehensive COVID-19 testing data and demographic, socio-economic, and health-related information for 44 million individuals who tested for SARS-CoV-2 between March 2020 and April 2022, representing 15,720,286 individuals who tested positive and 42,351,016 individuals who tested negative.DiscussionWith the application of epidemiological and statistical methods, this dataset allows a range of clinical outcomes to be investigated, including pre-specified health conditions and mortality. Furthermore, understanding potential determinants of health outcomes can be gained, including pre-existing health conditions, acute disease characteristics, SARS-CoV-2 vaccination status, and genomic variants.

Background Growing numbers of people have been potentially exposed to avian influenza (AI), as the United Kingdom has managed the largest and most sustained series outbreaks in recent years. Antiviral medication is recommended for exposed individuals for chemoprophylaxis to reduce the severity of illness and the likelihood of secondary transmission. However, some individuals have been hesitant or declined antivirals. In this study, we aimed to identify the factors affecting the uptake of and adherence to antiviral medication. Methods We interviewed 14 individuals occupationally exposed to avian influenza and conducted focus groups with 15 public health professionals involved in advising and arranging antivirals. The data were analysed thematically based on COM-B factors (capability, opportunity, motivation). Results Although participants saw avian influenza as a severe disease, most did not consider themselves susceptible to it because they felt safe in personal protective equipment and knew that bird-to-human transmission was rare. The biggest barrier to uptake and adherence was experiencing side effects, especially if these disrupted day-to-day life or work. Participants who took antivirals followed medical advice in a novel situation, had health conditions or vulnerable family members they wanted to protect. As responding to an outbreak was exhausting, easy access to antivirals for those at most risk was considered important for improving uptake. Conclusions The factors affecting antiviral uptake were multifaceted. Public health interventions should prioritise those at most risk and address multiple components of behaviour, such as advising how to manage side effects, addressing concerns about long-term usage and providing convenient access to antivirals for those at most risk.

BACKGROUND:Early in the COVID-19 pandemic, due to limited testing, a potential gap in capturing SARS-CoV-2-positive community deaths was identified. Post-mortem testing for respiratory viruses had never been implemented in the United Kingdom. AIM:Through implementing and evaluating a pilot, we aimed to establish feasibility and acceptability of post-mortem SARS-CoV-2 surveillance using funeral directors (FDs) to capture 'missed' COVID-19 community deaths. METHODS:Between January 2021 and February 2022, four FDs took upper respiratory tract samples from eligible people who died outside hospital. We tested for SARS-CoV-2 and other respiratory viruses using reverse transcription-polymerase chain reaction and matched results to the national COVID-19 mortality dataset. We evaluated the pilot for acceptability, data completeness and timeliness, and simplicity, using semi-structured interviews, a questionnaire, and data audit. RESULTS:Two thousand eight hundred sixty-five deaths were handled by FDs: 998 were assessed for eligibility, 342 were eligible 81 were tested. Eight were SARS-CoV-2-positive, of which three were not identified by ante-mortem clinical testing. The programme was acceptable in principle to FDs and families, but FDs' participation was limited by the burden of legal requirements and existing workloads. Families' willingness to consent fluctuated (monthly consent rate 4-83%, overall 30%); fewer consented when overall cases were low. Completeness and timeliness of data was good. FDs judged the programme simple. CONCLUSION:The pilot established feasibility and demonstrated, even with small numbers, the ability to detect 'missed' deaths. There were significant obstacles to implementation. Alternative settings for taking specimens are being explored instead to address this gap in national surveillance.

Introduction COVID-19 disease has been associated with severe illness, hospitalisation and death, however, widespread vaccination coverage in England has resulted in reduced disease severity. From 2022, the national vaccination programme has been run twice per year, prioritising older age groups or those classified as clinically vulnerable. Here we assess the trends in COVID-19 outcomes between September 2023 and April 2024, using national-level data held by the UK Health Security Agency (UKHSA). Methods Data linkage of national-level COVID-19 episode data, NHS emergency and hospital attendance data, and death registrations were used to analyse COVID-19 outcomes. Outcomes were defined as COVID-19 associated A&E attendances, hospital admissions, severe hospitalisations, and deaths The number and rate of each COVID-19 outcome category between September 2023 and April 2024 was calculated, stratified by clinical risk status and age and sex. Results The most common COVID-19 outcomes during this time-period were A&E attendance and hospital admission, with the rates highest among those aged 75 and over. Among this age group, all outcomes disproportionately affect those who have been identified as at clinical risk and those who were immunosuppressed. High rates of A&E attendance and hospital admission were also observed among infants (under 6 months old) but were lower for more severe outcomes. Discussion Groups that were most affected by COVID-19 outcomes were currently prioritised for COVID-19 vaccination in England, which will help protect against more severe outcomes including admission to intensive care and death. Routine national levels surveillance of COVID-19 outcomes is essential to monitor populations most of severe disease and informing vaccination policy. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was performed as part of UKHSA routine work to monitor COVID-19. No external funding received. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: UKHSA has legal permission, provided by Regulation 3 of The Health Service (Control of Patient Information) Regulations 2002 to process confidential patient information under Section 3(i) (a)–(c), 3(i)(d) (i) and (ii) and 3(iii) as part of its outbreak response activities. This study falls within the research activities approved by the UKHSA Research Ethics and Governance Group. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data produced in the present study are available through formal collaboration with UKHSA. Proposals for collaboration will be considered by the UKHSA Immunisation and Vaccine Preventable Diseases team to evaluate the scientific quality and feasibility of the proposal.

BACKGROUND:By March, 2023, 54 countries, areas, and territories (hereafter CAT) in the WHO European Region had reported more than 2·2 million COVID-19-related deaths to the WHO Regional Office for Europe. Here, we estimated how many lives were directly saved by vaccinating adults in the WHO European Region from December, 2020, to March, 2023. METHODS:In this retrospective surveillance study, we estimated the number of lives directly saved by age group, vaccine dose, and circulating variant-of-concern (VOC) period, regionally and nationally, using weekly data on COVID-19 mortality and infection, COVID-19 vaccination uptake, and SARS-CoV-2 virus characterisations by lineage downloaded from The European Surveillance System on June 11, 2023, as well as vaccine effectiveness data from the literature. We included data for six age groups (25-49 years, 50-59 years, ≥60 years, 60-69 years, 70-79 years, and ≥80 years). To be included in the analysis, CAT needed to have reported both COVID-19 vaccination and mortality data for at least one of the four older age groups. Only CAT that reported weekly data for both COVID-19 vaccination and mortality by age group for 90% of study weeks or more in the full study period were included. We calculated the percentage reduction in the number of expected and reported deaths. FINDINGS:Between December, 2020, and March, 2023, in 34 of 54 CAT included in the analysis, COVID-19 vaccines reduced deaths by 59% overall (CAT range 17-82%), representing approximately 1·6 million lives saved (range 1·5-1·7 million) in those aged 25 years or older: 96% of lives saved were aged 60 years or older and 52% were aged 80 years or older; first boosters saved 51% of lives, and 60% were saved during the Omicron period. INTERPRETATION:Over nearly 2·5 years, most lives saved by COVID-19 vaccination were in older adults by first booster dose and during the Omicron period, reinforcing the importance of up-to-date vaccination among the most at-risk individuals. Further modelling work should evaluate indirect effects of vaccination and public health and social measures. FUNDING:US Centers for Disease Control and Prevention.

Background The Sanofi/GSK AS03-adjuvanted (VidPrevtyn Beta) vaccine and the Pfizer-BioNTech mRNA (Comirnaty Original/Omicron BA.4-5) bivalent vaccine were offered to adults aged 75 years and over in England from 3rd April 2023. This is the first time an adjuvanted COVID-19 vaccine has been administered as part of a UK COVID-19 vaccination programme. In clinical trials, antibody levels generated were comparable with mRNA vaccines but there are no real-world data on the effectiveness or duration of protection. Methods We used a test-negative case–control study design to estimate the incremental vaccine effectiveness of the Sanofi/GSK and Pfizer bivalent BA.4-5 boosters against hospitalisation amongst those aged 75 years and older in England. Cases (those testing positive) and controls (those testing negative) were identified from the national COVID-19 PCR testing data undertaken in hospital settings. The study period included tests from 3rd April 2023 to 27th August 2023. Tests were linked to the COVID-19 vaccination register and to the national hospital admission database, restricting to those with an acute respiratory infection coded in the primary diagnosis field. Vaccine effectiveness was estimated using multivariable logistic regression amongst those who had last received an autumn 2022 booster given at least 3 months prior. The test result was the outcome and vaccination status the exposure. Analyses were adjusted for week of test, gender, age, clinical risk group status, care home resident status, region, index of multiple deprivation, ethnicity, influenza vaccination status and recent COVID-19 positivity. Findings There were 14,169 eligible tests from hospitalised individuals aged 75 years and older; 3005 cases (positive tests) and 11,164 controls (negative tests). Effectiveness was highest in the period 9–13 days post vaccination for both manufacturers at about 50%; 43.7% (95% CI, 20.1–60.3%) and 56.1% (95% CI, 25.2–74.2%) for Sanofi/GSK and Pfizer BA.4-5, respectively. There was evidence of waning with a reduction to about 30% for both manufacturers after 5–9 weeks. The longest time interval post vaccination for which we were able to estimate effectiveness was 10+ weeks post vaccination, at which point vaccine effectiveness was 17.6% (95% CI, −3.6 to 34.5%) and 37.9% (95% CI, 13.2–55.5%) for the Sanofi/GSK and Pfizer BA.4-5 boosters, respectively. Interpretation Both boosters provided good protection against hospitalisation amongst older adults. The finding that the adjuvanted vaccine targeting the distant Beta strain had similar effectiveness to the bivalent mRNA vaccine targeting more closely matched Omicron sub-lineages is notable and highlights the need for further real-world studies into the effectiveness of vaccines from different vaccine platforms and formulations in the presence of matched and unmatched strains. Funding No external funding.

Background The Sano fi /GSK AS03-adjuvanted (VidPrevtyn Beta) vaccine and the P fi zer-BioNTech mRNA (Comirnaty Original/Omicron BA.4-5) bivalent vaccine were offered to adults aged 75 years and over in England from 3rd April 2023. This is the fi rst time an adjuvanted COVID-19 vaccine has been administered as part of a UK COVID-19 vaccination programme. In clinical trials, antibody levels generated were comparable with mRNA vaccines but there are no real-world data on the effectiveness or duration of protection. Methods We used a test -negative case - control study design to estimate the incremental vaccine effectiveness of the Sano fi /GSK and P fi zer bivalent BA.4-5 boosters against hospitalisation amongst those aged 75 years and older in England. Cases (those testing positive) and controls (those testing negative) were identi fi ed from the national COVID-19 PCR testing data undertaken in hospital settings. The study period included tests from 3rd April 2023 to 27th August 2023. Tests were linked to the COVID-19 vaccination register and to the national hospital admission database, restricting to those with an acute respiratory infection coded in the primary diagnosis fi eld. Vaccine effectiveness was estimated using multivariable logistic regression amongst those who had last received an autumn 2022 booster given at least 3 months prior. The test result was the outcome and vaccination status the exposure. Analyses were adjusted for week of test, gender, age, clinical risk group status, care home resident status, region, index of multiple deprivation, ethnicity, in fl uenza vaccination status and recent COVID19 positivity. Findings There were 14,169 eligible tests from hospitalised individuals aged 75 years and older; 3005 cases (positive tests) and 11,164 controls (negative tests). Effectiveness was highest in the period 9 - 13 days post vaccination for both manufacturers at about 50%; 43.7% (95% CI, 20.1 - 60.3%) and 56.1% (95% CI, 25.2 - 74.2%) for Sano fi /GSK and P fi zer BA.4-5, respectively. There was evidence of waning with a reduction to about 30% for both manufacturers after 5 - 9 weeks. The longest time interval post vaccination for which we were able to estimate effectiveness was 10+ weeks post vaccination, at which point vaccine effectiveness was 17.6% (95% CI, - 3.6 to 34.5%) and 37.9% (95% CI, 13.2 - 55.5%) for the Sano fi /GSK and P fi zer BA.4-5 boosters, respectively. Interpretation Both boosters provided good protection against hospitalisation amongst older adults. The fi nding that the adjuvanted vaccine targeting the distant Beta strain had similar effectiveness to the bivalent mRNA vaccine targeting more closely matched Omicron sub-lineages is notable and highlights the need for further real-world studies into the effectiveness of vaccines from different vaccine platforms and formulations in the presence of matched and unmatched strains.

We developed a new activity level setting threshold method, the mean standard deviation (MSD) method to quantify COVID-19 activity levels. This has been validated against the moving epidemic method (MEM), which has been used for influenza for many years, and we observed very similar results. The MSD method can prove to be a tool to use for respiratory viruses with limited historical data or seasonality to quantify activity levels when other respiratory viruses are also circulating.

Background: The Emergency Care Data Set (ECDS) provides insight into emergency care activity in England, and combined with COVID-19 surveillance data, can provide new insights into acute COVID-19 infection. Methods: This study identified individuals <18 years old who tested positive for SARS-CoV-2 between February 2020 and March 2023 and attended emergency care 1-14 days after a positive test. The main objective of the study was to explore emergency department (ED) attendance outcomes by demographic characteristics. Results: There were significant differences (p < 0.05) across most of the characteristics of <18s admitted to hospital from emergency departments, and those who were discharged from ED. <18s in IMD decile 1 (14.9%) made up the highest proportion of admissions, with those in less deprived areas having a greater proportion of individuals discharged from ED. February to August 2020 (1.5%) and September 2022 to March 2023 (2.8%) saw the highest proportion of <18 cases attending ED, though the highest number of cases were seen between September 2021 and February 2022. Conclusions: There is great value in the use of ECDS. It facilitates quick, regular insights into the health outcomes of key demographics, and provides a window into the health-seeking behaviours of individuals. Furthermore, outcomes of emergency care attendance can potentially inform assessments of infection severity across multiple demographics during outbreaks and pandemics. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study did not receive any specific grant from funding agencies. The study was supported by the UK Health Security Agency. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: UKHSA has legal permission, provided by Regulation 3 of The Health Service (Control of Patient Information) Regulations 2002 to process confidential patient information under Sections 3(i) (a) to (c), 3(i)(d) (i) and (ii) and 3(iii) as part of its outbreak response activities. This study falls within the research activities approved by the UKHSA Research Ethics and Governance Group. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The individual-level nature of the data used risks individuals being identified, or being able to self-identify, if the data are released publicly. Requests for access to these non-publicly available data should be directed to UKHSA.

The Gamma (P.1/501Y.V3) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected through whole-genome sequencing (WGS) in Japan in early January 2021 among a group of travellers arriving from Brazil [1]. This was later reported in more than 50 countries, including England. Early evidence from Brazil suggested that Gamma was associated with higher transmissibility and propensity for re-infection [2] as well as a possible increased likelihood of hospitalisation [3]. Considering the potential increased risks, further investigation into the epidemiology of the variant in other settings was necessary. Herein, we describe the epidemiology of the Gamma variant in England to 31 August 2021. Individuals infected with the Gamma variant were identified through genotyping by polymerase chain reaction (PCR) and WGS from the national COVID-19 Genomics UK Consortium (COG-UK) sequencing initiative. These data were linked to demographic information held in UK Health Security Agency's Second Generation Surveillance System (SGSS) [4]. Travel exposure was derived from Passenger Location Forms (PLFs), required for entry to the United Kingdom, and routine NHS Test and Trace (T&T) surveys. For cases with no known travel from these sources, information came from additional follow up by UKHSA's Health Protection Teams (HPTs). Imported cases were defined as confirmed Gamma cases with international travel into England within 14 days before the earlier of symptom onset or specimen date. Secondary cases were those who had contact with a PCR-confirmed SARS-CoV-2 case who had travelled within 14 days of symptom onset or specimen date. Sporadic Gamma cases had no history of travel nor contact with a SARS-CoV-2 infected traveller. Only T&T and HPT surveys could confirm secondary and sporadic cases. Cases without confirmation of travel status were excluded from the analysis. Descriptive analysis was stratified by travel exposure, with imported and secondary cases grouped as travel-related, and examined by demographic factors including, age, sex, region and place of residence. Residence at the time of testing was identified by test location information or unique property registration number (UPRN); the latter was also used to derive data on residential clustering to assess potential onwards transmission based on initial travel status [5]. Between May and October 2021, the United Kingdom assigned Red, Amber and Green (RAG) categories to countries with perceived risk for importation of SARS-CoV-2 variants. Returning travellers from Red-listed countries required hotel quarantine in Managed Quarantine Facilities (MQF) and those returning from Amber-listed countries had at-home quarantine. In this analysis, travel-related cases were assigned a RAG category based on the highest rating of the countries involved in their journey at the time of travel [6]. Where RAG assignments were unavailable, an assignment of Red was given to those who travelled from a country on the initial travel ban list of countries associated with the Gamma variant [7]. Between 12 February and 31 August 2021, there were 251 confirmed Gamma cases detected in England. Excluding cases with no confirmation of travel status (n = 75, 29.9%), 88 (35.1%) were imported, 14 (5.6%) were secondary travel cases, and 74 (29.5%) were sporadic. Early Gamma cases were mostly imported or secondary cases (Figure 1). There were no reported deaths among confirmed Gamma cases in England during the study period. Those aged between 20 and 29 years had the highest number of travel-related (n = 33, 32.4%) and sporadic cases (n = 19, 25.7%). Approximately half of both travel-related and sporadic cases were from the London region (Table S1). Contrary to the expected areas of highest risk for importation, the majority of travel-related cases were associated with Amber countries as the highest RAG rating for their journeys (n = 52, 51.0%) (Table S1). However, 40.2% (n = 41) of travellers had visited Red countries, including the most frequently reported country of travel, Brazil (n = 27, 21.4%), which had been on the Red list since May 2021. Mexico, an Amber country upgraded to Red on 8 August 2021, had 15 returning travellers (11.9%), followed by Amber countries USA (n = 14, 11.9%) and France (n = 12, 11.1%). These travel-related cases include those detected within MQFs as part of the travel restrictions. A larger proportion of sporadic cases were part of a residential cluster (n = 31, 41.9%) compared to travel-related cases (n = 28, 27.5%). Cluster size that included sporadic cases ranged from 2 to 6. This analysis shows that earlier cases of the Gamma variant in England were predominantly travel-associated, transitioning to a larger proportion of cases likely obtained through community transmission. However, Gamma did not have widespread expansion, despite initial concerns of increased virulence and transmissibility. This may be due to the rapid dominance of Delta, which was observed to have surpassed Gamma in other parts of the world where the two variants co-occurred in greater numbers, such as Brazil and Mexico [8, 9]. At its peak, Gamma comprised of 2.8% of all cases in England with a variant designation, whereas in the same time period Delta was at 80.4% (Figure S1). However, the proportion of travel-associated compared with sporadic cases may have been biased by targeted sequencing of new arrivals and their contacts as well as routine testing of travellers at the time of study [10]. Community-transmitted cases have potentially lower ascertainment, as they are subject to randomised population-level sample-picking processes. However, during the peak of Gamma incidence between March and June, the proportion of positive tests that were sequenced was above 50%, which should mitigate some of the risk for lower detection. In October 2021, the RAG policy removed Amber and Green categories and only required quarantine for travellers from Red-list countries [6]. The analysis indicates the policy requiring quarantine in MQFs for Red-list travellers and at-home quarantine for Amber-list travellers, implemented from 7 May 2021, may have contributed to preventing onward transmission as suggested by the small numbers of secondary cases from the time of the policy being introduced. However, within the limitations of the available data, we are unable to definitively conclude which factors most contributed to the decline of Gamma detections in England. Further research is needed to explore the association between quarantine policies and secondary transmission of SARS-CoV-2 in other settings. While larger scale surveillance of travellers has ceased, a similar approach could also be considered when new variants emerge, including using existing surveillance systems such as surveys to monitor the travel status of variant cases. Nurin Abdul Aziz: conceptualization, formal analysis, methodology, writing–original draft, writing–review and editing. Katherine Twohig: data curation, methodology, writing–original draft, writing–review and editing. Mary Sinnathamby: methodology, writing–original draft, writing–review and editing. Asad Zaidi: data curation, methodology, writing–original draft, writing–review and editing. Shirin Aliabadi: data curation, methodology, writing–review and editing. Natalie Groves: data curation, formal analysis, methodology, resources, software, writing–review and editing. Sophie Nash: methodology, writing–original draft, writing–review and editing. Simon Thelwall: methodology, supervision, writing–original draft, writing–review and editing. Gavin Dabrera: conceptualization, methodology, supervision, writing–review and editing. The author declares no conflicts of interest. The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/irv.13308. Table S1 Demographic description of SARS-CoV-2 Gamma (P.1) cases in England. Data up to 31 August 2021. Figure S1. Proportions and counts of SARS-CoV-2 cases by variant designation over time in England from 12 February 2021 to 30 August 2021. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.