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.

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.

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.

On 31 December 2019, the Municipal Health Commission of Wuhan, China, reported a cluster of atypical pneumonia cases. On 5 January 2020, the WHO publicly released a Disease Outbreak News (DON) report, providing information about the pneumonia cases, implemented response interventions, and WHO’s risk assessment and advice on public health and social measures. Following 9 additional DON reports and 209 daily situation reports, on 17 August 2020, WHO published the first edition of the COVID-19 Weekly Epidemiological Update (WEU). On 1 September 2023, the 158th edition of the WEU was published on WHO’s website, marking its final issue. Since then, the WEU has been replaced by comprehensive global epidemiological updates on COVID-19 released every 4 weeks. During the span of its publication, the webpage that hosts the WEU and the COVID-19 Operational Updates was accessed annually over 1.4 million times on average, with visits originating from more than 100 countries. This article provides an in-depth analysis of the WEU process, from data collection to publication, focusing on the scope, technical details, main features, underlying methods, impact and limitations. We also discuss WHO’s experience in disseminating epidemiological information on the COVID-19 pandemic at the global level and provide recommendations for enhancing collaboration and information sharing to support future health emergency responses.

Background Influenza is known to predispose to secondary bacterial infections including invasive group A streptococcal (iGAS) disease. The universal pediatric live attenuated influenza vaccine (LAIV) program introduced in England from the 2013/2014 influenza season was implemented incrementally, introducing cohorts of children annually to 2-16 years of coverage. Additionally, from the beginning of the program, discrete pilot areas offered LAIV vaccination to all primary school-age children, allowing for a unique comparison of infection rates between pilot and nonpilot areas during the program rollout. Methods Cumulative incidence rate ratios (IRRs) of GAS infections (all), scarlet fever (SF), and iGAS infection within each season by age group were compared for pilot and nonpilot areas using Poisson regression. The overall effect of the pilot program in the pre- (2010/2011-2012/2013 seasons) and postintroduction (2013/2014-2016/2017 seasons) periods was assessed using negative binomial regression by comparing changes in incidence between pilot/nonpilot areas (ratio of IRR [rIRR]). Results Reductions in IRRs of GAS and SF were observed within most post-LAIV program seasons, among the age groups 2-4 and 5-10 years. Significant reductions were seen among 5-10 years (rIRR, 0.57; 95% CI, 0.45-0.71; P < .001), 2-4 years (rIRR, 0.62; 95% CI, 0.43-0.90; P = .011), and 11-16 years (rIRR, 0.63; 95% CI, 0.43-0.90; P = .018) for GAS infections when assessing the overall effect of the program. Conclusions Our findings suggest that vaccination with LAIV may be associated with a reduced risk of GAS infection and support attaining high uptake of childhood influenza vaccination.

The emergence of the SARS-CoV-2 Beta (B.1.351) variant in November 2020 raised concerns of increased transmissibility and severity. We describe the epidemiology of 949 confirmed SARS-CoV-2 Beta variant cases in England, identified between December 2020 and June 2022. Most cases were detected in the first 3 months. A total of 10 deaths (1.1%; 10/949) were identified among all cases and of those with travel information, 38 (4.9%; 38/781) cases with hospital admissions within 14 days of a positive test being detected. 52.9% (413/781) cases were imported. This study reinforces the importance of monitoring of travel-associated cases to inform public health response and reduce transmissibility of new variants.

OBJECTIVES:We determined the age and sociodemographic distribution of COVID-19 cases between January and September 2020 to identify the group with the highest incidence rates at the beginning of the second wave in England. STUDY DESIGN:We undertook a retrospective cohort study design. METHODS:SARS-CoV-2 cases in England were linked with area-level socio-economic status indicators using quintiles of the Index of Multiple Deprivation (IMD). Age-specific incidence rates were stratified by IMD quintile to further assess rates by area-level socio-economic status. RESULTS:Between July and September 2020, SARS-CoV-2 incidence rates were highest amongst those aged 18-21 years, reaching rates of 213.9 (18-19 years) and 143.2 (20-21 years) per 100,000 population by week ending 21 September 2022. Stratification of incidence rates by IMD quintile evidenced that despite high rates observed in the most deprived areas of England amongst the very young and older age groups, the highest rates were observed in the most affluent areas of England amongst the 18- to 21-year-olds. CONCLUSIONS:The reversal of sociodemographic trend in COVID-19 cases in England for those aged 18-21 years at the end of the summer of 2020 and beginning of the second wave showed a novel pattern of COVID-19 risk. For other age groups, the rates remained highest for those from more deprived areas, which highlighted persisting inequalities. Combined, this demonstrates the need to reinforce awareness of COVID-19 risk for young people, particularly given the late inclusion of the 16-17 years age group for vaccination administration, as well as continued efforts to reduce the impact of COVID-19 on vulnerable populations.

BackgroundThe emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in early 2020 and subsequent implementation of public health and social measures (PHSM) disrupted the epidemiology of respiratory viruses. This work describes the epidemiology of respiratory syncytial virus (RSV) observed during two winter seasons (weeks 40-20) and inter-seasonal periods (weeks 21-39) during the pandemic between October 2020 and September 2022.MethodsUsing data submitted to The European Surveillance System (TESSy) by countries or territories in the World Health Organization (WHO) European Region between weeks 40/2020 and 39/2022, we aggregated country-specific weekly RSV counts of sentinel, non-sentinel and Severe Acute Respiratory Infection (SARI) surveillance specimens and calculated percentage positivity. Results for both 2020/21 and 2021/22 seasons and inter-seasons were compared with pre-pandemic 2016/17 to 2019/20 seasons and inter-seasons.ResultsAlthough more specimens were tested than in pre-COVID-19 pandemic seasons, very few RSV detections were reported during the 2020/21 season in all surveillance systems. During the 2021 inter-season, a gradual increase in detections was observed in all systems. In 2021/22, all systems saw early peaks of RSV infection, and during the 2022 inter-seasonal period, patterns of detections were closer to those seen before the COVID-19 pandemic.ConclusionRSV surveillance continued throughout the COVID-19 pandemic, with an initial reduction in transmission, followed by very high and out-of-season RSV circulation (summer 2021) and then an early start of the 2021/22 season. As of the 2022/23 season, RSV circulation had not yet normalised.

Background: COVID-19 vaccines have been shown to be highly effective against hospitalisation and death following COVID-19 infection. COVID-19 vaccine effectiveness estimates against severe endpoints among individuals with clinical conditions that place them at increased risk of critical disease are limited. Methods: We used English primary care medical record data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre sentinel network (N > 18 million). Data were linked to the National Immunisation Management Service database, Second Generation Surveillance System for virology test data, Hospital Episode Statistics, and death registry data. We estimated adjusted vaccine effectiveness (aVE) against COVID-19 infection followed by hospitalisation and death among individuals in specific clinical risk groups using a cohort design during the delta-dominant period. We also report mortality statistics and results from our antibody surveillance in this population. Findings: aVE against severe endpoints was high, 14-69d following a third dose aVE was 96.4% (95.1%-97.4%) and 97.9% (97.2%-98.4%) for clinically vulnerable people given a Vaxzevria and Comirnaty primary course respectively. Lower aVE was observed in the immunosuppressed group: 88.6% (79.1%-93.8%) and 91.9% (85.9%-95.4%) for Vaxzevria and Comirnaty respectively. Antibody levels were significantly lower among the immunosuppressed group than those not in this risk group across all vaccination types and doses. The standardised case fatality rate within 28 days of a positive test was 3.9/1000 in people not in risk groups, compared to 12.8/1000 in clinical risk groups. Waning aVE with time since 2nd dose was also demonstrated, for example, Comirnaty aVE against hospitalisation reduced from 96.0% (95.1-96.7%) 14-69days post-dose 2-82.9% (81.4-84.2%) 182days+ post-dose 2. Interpretation: In all clinical risk groups high levels of vaccine effectiveness against severe endpoints were seen. Reduced vaccine effectiveness was noted among the immunosuppressed group. (c) 2023 Published by Elsevier Ltd on behalf of The British Infection Association.

Whole-genome sequencing (WGS) information has played a crucial role in the SARS-CoV-2 (COVID-19) pandemic by providing evidence about variants to inform public health policy. The purpose of this study was to assess the representativeness of sequenced cases compared with all COVID-19 cases in England, between March 2020 and August 2021, by demographic and socio-economic characteristics, to evaluate the representativeness and utility of these data in epidemiological analyses. To achieve this, polymerase chain reaction (PCR)-confirmed COVID-19 cases were extracted from the national laboratory system and linked with WGS data. During the study period, over 10% of COVID-19 cases in England had WGS data available for epidemiological analysis. With sequencing capacity increasing throughout the period, sequencing representativeness compared to all reported COVID-19 cases increased over time, allowing for valuable epidemiological analyses using demographic and socio-economic characteristics, particularly during periods with emerging novel SARS-CoV-2 variants. This study demonstrates the comprehensiveness of England's sequencing throughout the COVID-19 pandemic, rapidly detecting variants of concern, and enabling representative epidemiological analyses to inform policy.

BackgroundThe universal paediatric live attenuated influenza vaccine (LAIV) programme commenced in the United Kingdom (UK) in 2013/2014. Since 2014/2015, all pre-school and primary school children in Scotland and Northern Ireland have been offered the vaccine. England and Wales incrementally introduced the programme with additional school age cohorts being vaccinated each season. The Republic of Ireland (ROI) had no universal paediatric programme before 2017. We evaluated the potential population impact of vaccinating primary school-aged children across the five countries up to the 2016/2017 influenza season. MethodsWe compared rates of primary care influenza-like illness (ILI) consultations, confirmed influenza intensive care unit (ICU) admissions, and all-cause excess mortality using standardised methods. To further quantify the impact, a scoring system was developed where each weekly rate/z-score was scored and summed across each influenza season according to the weekly respective threshold experienced in each country. ResultsResults highlight ILI consultation rates in the four seasons' post-programme, breached baseline thresholds once or not at all in Scotland and Northern Ireland; in three out of the four seasons in England and Wales; and in all four seasons in ROI. No differences were observed in the seasons' post-programme introduction between countries in rates of ICU and excess mortality, although reductions in influenza-related mortality were seen. The scoring system also reflected similar results overall. ConclusionsFindings of this study suggest that LAIV vaccination of primary school age children is associated with population-level benefits, particularly in reducing infection incidence in primary care.

Background COVID-19 vaccines approved in the UK are highly effective in general population cohorts, however, data on effectiveness amongst individuals with clinical conditions that place them at increased risk of severe disease are limited. Methods We used GP electronic health record data, sentinel virology swabbing and antibody testing within a cohort of 712 general practices across England to estimate vaccine antibody response and vaccine effectiveness against medically attended COVID-19 amongst individuals in clinical risk groups using cohort and test-negative case control designs. Findings There was no reduction in S-antibody positivity in most clinical risk groups, however reduced S-antibody positivity and response was significant in the immunosuppressed group. Reduced vaccine effectiveness against clinical disease was also noted in the immunosuppressed group; after a second dose, effectiveness was moderate (Pfizer: 59.6%, 95%CI 18.0-80.1%; AstraZeneca 60.0%, 95%CI -63.6-90.2%). Interpretation In most clinical risk groups, immune response to primary vaccination was maintained and high levels of vaccine effectiveness were seen. Reduced antibody response and vaccine effectiveness were seen after 1 dose of vaccine amongst a broad immunosuppressed group, and second dose vaccine effectiveness was moderate. These findings support maximising coverage in immunosuppressed individuals and the policy of prioritisation of this group for third doses.

BackgroundThe emergence of the SARS-CoV-2 Alpha variant in England coincided with a rapid increase in the number of PCR-confirmed COVID-19 cases in areas where the variant was concentrated.AimOur aim was to assess whether infection with Alpha was associated with more severe clinical outcomes than the wild type.MethodsLaboratory-confirmed infections with genomically sequenced SARS-CoV-2 Alpha and wild type between October and December 2020 were linked to routine healthcare and surveillance datasets. We conducted two statistical analyses to compare the risk of hospital admission and death within 28 days of testing between Alpha and wild-type infections: a matched cohort study and an adjusted Cox proportional hazards model. We assessed differences in disease severity by comparing hospital admission and mortality, including length of hospitalisation and time to death.ResultsOf 63,609 COVID-19 cases sequenced in England between October and December 2020, 6,038 had the Alpha variant. In the matched cohort analysis, we matched 2,821 cases with Alpha to 2,821 to cases with wild type. In the time-to-event analysis, we observed a 34% increased risk in hospitalisation associated with Alpha compared with wild type, but no significant difference in the risk of mortality.ConclusionWe found evidence of increased risk of hospitalisation after adjusting for key confounders, suggesting increased infection severity associated with the Alpha variant. Rapid assessments of the relative morbidity in terms of clinical outcomes and mortality associated with emerging SARS-CoV-2 variants compared with dominant variants are required to assess overall impact of SARS-CoV-2 mutations.

BackgroundHouseholds appear to be the highest risk setting for COVID-19 transmission. Large household transmission studies in the early stages of the pandemic in Asia reported secondary attack rates ranging from 5 to 30%.AimWe aimed to investigate the transmission dynamics of COVID-19 in household and community settings in the UK.MethodsA prospective case-ascertained study design based on the World Health Organization FFX protocol was undertaken in the UK following the detection of the first case in late January 2020. Household contacts of cases were followed using enhanced surveillance forms to establish whether they developed symptoms of COVID-19, became confirmed cases and their outcomes. We estimated household secondary attack rates (SAR), serial intervals and individual and household basic reproduction numbers. The incubation period was estimated using known point source exposures that resulted in secondary cases.ResultsWe included 233 households with two or more people with 472 contacts. The overall household SAR was 37% (95% CI: 31-43%) with a mean serial interval of 4.67 days, an R0 of 1.85 and a household reproduction number of 2.33. SAR were lower in larger households and highest when the primary case was younger than 18 years. We estimated a mean incubation period of around 4.5 days.ConclusionsRates of COVID-19 household transmission were high in the UK for ages above and under 18 years, emphasising the need for preventative measures in this setting. This study highlights the importance of the FFX protocol in providing early insights on transmission dynamics.

Background Coronavirus Disease 2019 (COVID-19) deaths are rare in children and young people (CYP). The high rates of asymptomatic and mild infections complicate assessment of cause of death in CYP. We assessed the cause of death in all CYP with a positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test since the start of the pandemic in England. Methods and findings CYP aged <20 years who died within 100 days of laboratory-confirmed SARS-CoV-2 infection between 01 March 2020 and 31 December 2021 in England were followed up in detail, using national databases, surveillance questionnaires, post-mortem reports, and clinician interviews. There were 185 deaths during the 22-month follow-up and 81 (43.8%) were due to COVID-19. Compared to non-COVID-19 deaths in CYP with a positive SARS-CoV-2 test, death due to COVID-19 was independently associated with older age (aOR 1.06 95% confidence interval (CI) 1.01 to 1.11, p = 0.02) and underlying comorbidities (aOR 2.52 95% CI 1.27 to 5.01, p = 0.008), after adjusting for age, sex, ethnicity group, and underlying conditions, with a shorter interval between SARS-CoV-2 testing and death. Half the COVID-19 deaths (41/81, 50.6%) occurred within 7 days of confirmation of SARS-CoV-2 infection and 91% (74/81) within 30 days. Of the COVID-19 deaths, 61 (75.3%) had an underlying condition, especially severe neurodisability (n = 27) and immunocompromising conditions (n = 12). Over the 22-month surveillance period, SARS-CoV-2 was responsible for 1.2% (81/6,790) of all deaths in CYP aged <20 years, with an infection fatality rate of 0.70/100,000 SARS-CoV-2 infections in this age group estimated through real-time, nowcasting modelling, and a mortality rate of 0.61/100,000. Limitations include possible under-ascertainment of deaths in CYP who were not tested for SARS-CoV-2 and lack of direct access to clinical data for hospitalised CYP. Conclusions COVID-19 deaths remain extremely rare in CYP, with most fatalities occurring within 30 days of infection and in children with specific underlying conditions.

The Omicron variant of SARS-CoV-2 became the globally dominant variant in early 2022. A sub-lineage of the Omicron variant (BA.2) was identified in England in January 2022. Here, we investigated hospitalisation and mortality risks of COVID-19 cases with the Omicron sub-lineage BA.2 ( n = 258,875) compared to BA.1 ( n = 984,337) in a large cohort study in England. We estimated the risk of hospital attendance, hospital admission or death using multivariable stratified proportional hazards regression models. After adjustment for confounders, BA.2 cases had lower or similar risks of death (HR = 0.80, 95% CI 0.71–0.90), hospital admission (HR = 0.88, 95% CI 0.83–0.94) and any hospital attendance (HR = 0.98, 95% CI 0.95–1.01). These findings that the risk of severe outcomes following infection with BA.2 SARS-CoV-2 was slightly lower or equivalent to the BA.1 sub-lineage can inform public health strategies in countries where BA.2 is spreading.

Abstract Background In England, the emergence the more transmissible SARS-CoV-2 variant Alpha (B.1.1.7) led to a third national lockdown from December 2020, including restricted attendance at schools. Nurseries, however, remained fully open. COVID-19 outbreaks (≥ 2 laboratory-confirmed cases within 14 days) in nurseries were investigated to assess the risk of SARS-CoV-2 infection and cumulative incidence in staff and children over a three-month period when community SARS-CoV-2 infections rates were high and the Alpha variant was spreading rapidly across England. Methods This was a cross-sectional national investigation of COVID-19 outbreaks in nurseries across England. Nurseries reporting a COVID-19 outbreak to PHE between November 2020 and January 2021 were requested to complete a questionnaire about their outbreak. Results Three hundred and twenty-four nurseries, comprising 1% (324/32,852) of nurseries in England, reported a COVID-19 outbreak. Of the 315 (97%) nurseries contacted, 173 (55%) reported 1,657 SARS-CoV-2 cases, including 510 (31%) children and 1,147 (69%) staff. A child was the index case in 45 outbreaks (26%) and staff in 125 (72%) outbreaks. Overall, children had an incidence rate of 3.50% (95%CI, 3.21–3.81%) and was similar irrespective of whether the index case was a child (3.55%; 95%CI, 3.01–4.19%) or staff (3.44%; 95%CI, 3.10–3.82%). Among staff, cumulative incidence was lower if the index case was a child (26.28%; 95%CI, 23.54–29.21%%) compared to a staff member (32.98%; 95%CI, 31.19–34.82%), with the highest cumulative incidence when the index case was also a staff member (37.52%; 95%CI, 35.39–39.70%). Compared to November 2020, outbreak sizes and cumulative incidence was higher in January 2021, when the Alpha variant predominated. Nationally, SARS-CoV-2 infection rates in < 5 year-olds remained low and followed trends in older age-groups, increasing during December 2020 and declining thereafter. Conclusions In this cross-sectional study of COVID-19 outbreaks in nurseries, one in three staff were affected compared to one in thirty children. There was some evidence of increased transmissibility and higher cumulative incidence associated with the Alpha variant, highlighting the importance of maintaining a low level of community infections.

Purpose The Gamma variant of SARS-CoV-2, first detected in travellers from Brazil, was found to have high transmissibility and virulence; following this finding, this paper aims to describe the epidemiology of Gamma cases in England from its first detection on 12 February 2021 to 31 August 2021. Methods The demographic analysis of Gamma cases was stratified by travel exposure. Travel-associated cases were further analysed by countries travelled from, stratified by categories set in place by the Red (highest risk countries), Amber, Green (lowest risk countries) travel policy, which was implemented from May to October 2021. Results There were 251 confirmed Gamma cases detected in England in the study period. 35.1% were imported, 5.6% were secondary, and 29.5% were not travel associated. Early cases were predominantly travel-associated, with later cases likely obtained through community transmission. 51.0% of travel-related cases were travellers from Amber countries, and 40.2% had at least one Red country in their journey. Conclusion The Gamma variant has not seen the same expansion as other variants such as Delta, most likely due to Delta out-competing community transmission of Gamma. Findings indicate the travel policy requiring quarantine for Red and Amber list travellers may have also contributed to preventing onward transmission of Gamma.

BACKGROUND:The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. METHODS:This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. FINDINGS:Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17-43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32-3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08-1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47-8·05] and for hospital admission or emergency care attendance 1·58 [0·69-3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29-4·16] and 1·43 [1·04-1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. INTERPRETATION:This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. FUNDING:Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

Vaccines are a key part of the global strategy to tackle antimicrobial resistance (AMR) since prevention of infection should reduce antibiotic use. England commenced national rollout of a live attenuated influenza vaccine (LAIV) programme for children aged 2-3 years together with a series of geographically discrete pilot areas for primary school age children in 2013 extending to older children in subsequent seasons. We investigated vaccine programme impact on community antibiotic prescribing rates. Antibiotic prescribing incidence rates for respiratory (RTI) and urinary tract infections (UTI; controls) were calculated at general practice (GP) level by age category (children<=10 years/adults) and season for LAIV pilot and non-pilot areas between 2013/14 and 2015/16. To estimate the LAIV (primary school age children only) intervention effect, a random effects model was fitted. A multivariable random-effects Poisson regression investigated the association of antibiotic prescribing rates in children with LAIV uptake (2-3-year-olds only) at GP practice level. RTI antibiotic prescribing rates for children <=10 years and adults showed clear seasonal trends and were lower in LAIV-pilot and non-pilot areas after the introduction of the LAIV programme in 2013. The reductions for RTI prescriptions (children) were similar (within 3%) in all areas, which coincided with the start the UK AMR strategy. Antibiotic prescribing was significantly (p < 0.0001) related to LAIV uptake in 2-3-year-olds with antibiotic prescribing reduced by 2.7% (95% CI: 2.1% to 3.4%) for every 10% increase in uptake. We found no evidence the LAIV programme for primary school age children resulted in reductions in RTI antibiotic prescribing, however we detected a significant inverse association between increased vaccine uptake in pre-school age children and antibiotic prescribing at GP level. The temporal association of reduced RTI and UTI antibiotic prescribing with the launch of the UK's AMR Strategy in 2013 highlights the importance of a multifaceted approach to tackle AMR. Crown Copyright (c) 2021 Published by Elsevier Ltd. All rights reserved.