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Background Between October 2022 and January 2023, influenza A(H1N1)pdm09, A(H3N2) and B/Victoria viruses circulated in Europe with different influenza (sub)types dominating in different areas. Aim To provide interim 2022/23 influenza vaccine effectiveness (VE) estimates from six European studies, covering 16 countries in primary care, emergency care and hospital inpatient settings. Methods All studies used the test- negative design, but with differences in other study characteristics, such as data sources, patient selection, case definitions and included age groups. Overall and influenza (sub)type- specific VE was estimated for each study using logistic regression adjusted for potential confounders. Results There were 20, 477 influenza cases recruited across the six studies, of which 16, 589 (81%) were influenza A. Among all ages and settings, VE against influenza A ranged from 27 to 44%. Against A(H1N1)pdm09 (all ages and settings), VE point estimates ranged from 28% to 46%, higher among children (< 18 years) at 49–77%. Against A(H3N2), overall VE ranged from 2% to 44%, also higher among children (62–70%). Against influenza B/Victoria, overall and age-specific VE were ≥ 50% (87–95% among children < 18 years). Conclusions Interim results from six European studies during the 2022/23 influenza season indicate a ≥ 27% and ≥ 50% reduction in disease occurrence among all- age influenza vaccine recipients for influenza A and B, respectively, with higher reductions among children. Genetic virus characterisation results and end-of-season VE estimates will contribute to greater understanding of differences in influenza (sub)type-specific results across studies.

Background: Since its emergence in November, 2021, in southern Africa, the SARS-CoV-2 omicron variant of concern (VOC) has rapidly spread across the world. We aimed to investigate the severity of omicron and the extent to which booster vaccines are effective in preventing symptomatic infection. Methods: In this study, using the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, we did a cohort analysis with a nested test-negative design incident case-control study covering the period Nov 1–Dec 19, 2021, to provide initial estimates of omicron severity and the effectiveness of vaccine boosters against symptomatic disease relative to 25 weeks or more after the second vaccine dose. Primary care data derived from 940 general practices across Scotland were linked to laboratory data and hospital admission data. We compared outcomes between infection with the delta VOC (defined as S-gene positive) and the omicron VOC (defined as S-gene negative). We assessed effectiveness against symptomatic SARS-CoV-2 infection, with infection confirmed through a positive RT-PCR. Findings: By Dec 19, 2021, there were 23 840 S-gene-negative cases in Scotland, which were predominantly among those aged 20–39 years (11 732 [49·2%]). The proportion of S-gene-negative cases that were possible reinfections was more than ten times that of S-gene-positive cases (7·6% vs 0·7%; p

Funding: EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health [MC_PC_19004], which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through Public Health Scotland and Scottish Government DG Health and Social Care and the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation. SVK is funded by a NHS Research Scotland Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17).

To describe the clinical presentation, course of disease and health-care seeking behaviour of the first few hundred cases of coronavirus disease 2019 (COVID-19) in the United Kingdom of Great Britain and Northern Ireland.We implemented the World Health Organization's First Few X cases and contacts investigation protocol for COVID-19. Trained public health professionals collected information on 381 virologically confirmed COVID-19 cases from 31 January 2020 to 9 April 2020. We actively followed up cases to identify exposure to infection, symptoms and outcomes. We also collected limited data on 752 symptomatic people testing negative for COVID-19, as a control group for analyses of the sensitivity, specificity and predictive value of symptoms.Approximately half of the COVID-19 cases were imported (196 cases; 51.4%), of whom the majority had recent travel to Italy (140 cases; 71.4%). Of the 94 (24.7%) secondary cases, almost all reported close contact with a confirmed case (93 cases; 98.9%), many through household contact (37 cases; 39.8%). By age, a lower proportion of children had COVID-19. Most cases presented with cough, fever and fatigue. The sensitivity and specificity of symptoms varied by age, with nonlinear relationships with age. Although the proportion of COVID-19 cases with fever increased with age, for those with other respiratory infections the occurrence of fever decreased with age. The occurrence of shortness of breath also increased with age in a greater proportion of COVID-19 cases.The study has provided useful evidence for generating case definitions and has informed modelling studies of the likely burden of COVID-19.Décrire la manifestation clinique, l'évolution de la maladie et la propension à recourir aux services de santé des premières centaines de cas de maladie à coronavirus 2019 (COVID-19) au Royaume-Uni de Grande-Bretagne et d'Irlande du Nord.Nous avons appliqué leEnviron la moitié des cas de COVID-19 ont été importés (196 cas; 51,4%), la majorité s'étant récemment rendue en Italie (140 cas; 71,4%). Sur les 94 (24,7%) cas secondaires, presque tous ont signalé un contact rapproché avec un cas confirmé (93 cas; 98,9%), généralement au sein de leur foyer (37 cas; 39,8%). Au niveau de l'âge, la proportion d'enfants ayant contracté la COVID-19 était moindre. La plupart des cas avaient de la toux, de la fièvre et de la fatigue. La sensibilité et la spécificité des symptômes variaient en fonction de l'âge, présentant une relation non linéaire avec cet élément. Plus l'âge des cas de COVID-19 avançait, plus ils étaient susceptibles de développer de la fièvre, à l'exception de ceux touchés par d'autres infections respiratoires. Le risque d'essoufflement augmentait lui aussi avec l'âge chez une grande partie des cas de COVID-19.Cette étude a apporté un éclairage utile dans l'établissement d'une définition des cas. Elle a également fourni, pour diverses modélisations, des indications sur la charge que pourrait faire peser la COVID-19.Describir la presentación clínica, el curso de la enfermedad y el comportamiento de búsqueda de atención sanitaria de los primeros cientos de casos de la enfermedad del coronavirus de 2019 (COVID-19) en Reino Unido e Irlanda del Norte.Implementamos el protocolo de investigación de los primeros casos y contactos de la Organización Mundial de la Salud para la COVID-19. Profesionales expertos en el área de la salud pública recopilaron información sobre 381 casos virológicamente confirmados de COVID-19 entre el 31 de enero de 2020 y el 9 de abril de 2020. Realizamos un seguimiento activo de los casos para identificar la exposición a la infección, los síntomas y los resultados. También recogimos datos limitados sobre 752 personas sintomáticas que dieron negativo en los resultados de la COVID-19, como grupo de control para el análisis de la sensibilidad, la especificidad y el valor predictivo de los síntomas.Casi la mitad de los casos de COVID-19 fueron importados (196 casos; 51,4%), de los cuales la mayoría había hecho un viaje reciente a Italia (140 casos; 71,4%). De los 94 (24,7%) casos secundarios, casi todos informaron de un contacto cercano con un caso confirmado (93 casos; 98,9%), muchos de ellos a través del contacto con el hogar (37 casos; 39,8%). Por edad, una proporción menor de niños tenía COVID-19. La mayoría de los casos se presentaban con tos, fiebre y fatiga. La sensibilidad y especificidad de los síntomas variaba según la edad, con relaciones no lineales con la edad. Aunque la proporción de casos de COVID-19 con fiebre aumentaba con la edad, en el caso de los que tenían otras infecciones respiratorias la aparición de fiebre disminuía con la edad. La incidencia de la falta de aliento también aumentó con la edad en una mayor proporción de casos de COVID-19.El estudio ha aportado pruebas útiles para generar definiciones de casos y también ha servido de base a los estudios de modelización del probable coste de la COVID-19.الغرض وصف العرض السريري، ومسار المرض وسلوك البحث عن الرعاية الصحية لأول بضع مئات من حالات الإصابة بمرض فيروس كورونا 2019 (كوفيد 19) في المملكة المتحدة لبريطانيا العظمى وأيرلندا الشمالية. الطريقة قمنا بتنفيذ بروتوكول منظمة الصحة العالمية للتحقيق بخصوص الحالات الـ X القليلة الأولى للإصابة بكوفيد 19، والمخالطين لهم. وقام أخصائيو الصحة العامة المدربون بتجميع معلومات عن 381 حالة إصابة فيروسية مؤكدة بكوفيد 19 في الفترة من 31 يناير/كانون ثاني 2020 إلى 9 أبريل (نيسان) 2020. وتابعنا بدأب الحالات لتحديد التعرض للعدوى والأعراض والنتائج. كما قمنا بجمع بيانات محدودة عن 752 شخصاً يعانون من أعراض كوفيد 19، ولكن كانت نتيجة الاختبار سلبية، كمجموعة تحكم لتحليلات الحساسية، والنوعية، والقيمة التنبؤية للأعراض. النتائج تم استيراد نصف حالات الإصابة بكوفيد 19 تقريباً (196 حالة؛ 51.4%)، سافر معظمهم مؤخراً إلى إيطاليا (140 حالة؛ 71.4%). من بين 94 حالة ثانوية (24.7%)، أبلغت كل الحالات تقريباً عن مخالطة وثيقة مع حالة مؤكدة (93 حالة؛ 98.9%)، والعديد منها عن طريق الاتصال المنزلي (37 حالة؛ 39.8%). وبالنسبة للعمر، فقد أُصيبت نسبة أقل من الأطفال بكوفيد 19. وكانت معظم الحالات مصحوبة بسعال وحمى وإرهاق. تختلف حساسية ونوعية الأعراض تبعاً للعمر، مع علاقات غير خطية مع العمر. على الرغم من أن نسبة حالات الإصابة بكوفيد 19 المصحوبة بالحمى قد زادت مع تقدم العمر، إلا أنه بالنسبة للمصابين بأمراض الجهاز التنفسي، فإن الإصابة بالحمى انخفضت مع التقدم في العمر. كما زاد كذلك حدوث ضيق التنفس مع التقدم في العمر في نسبة أكبر من حالات الإصابة بكوفيد 19. الاستنتاج قدمت الدراسة أدلة مفيدة لوضع تعريفات الحالة، وأوضحت لدراسات النماذج العبء المحتمل لمرض كوفيد 19.旨在描述大不列颠及北爱尔兰联合王国最初数百个新型冠状病毒肺炎（新冠肺炎）病例的临床表现、病程及就医行为。.我们实施了世界卫生组织制定的少数最初新冠肺炎病例和接触者调查方案。经过培训的公共卫生专业人员收集了 2020 年 1 月 31 日至 2020 年 4 月 9 日期间通过病毒学方法确诊的 381 例新冠肺炎病例的相关信息。我们积极跟踪病例，以确定接触感染情况、症状和结果。我们还针对 752 名具有新冠肺炎症状但其检测结果为阴性的病例收集了有限的数据，并将其作为对照组，以分析症状的敏感性、特异性和预测价值。.约有一半的新冠肺炎病例属于境外输入病例（196 例；51.4%），且其中大多数病例近期曾前往意大利旅行（140 例；71.4%）。在 94 例 (24.7%) 二代病例中，几乎所有病例都报告称曾与确诊病例密切接触（93 例；98.9%），且许多病例是因家庭内部接触而导致感染（37 例；39.8%）。按年龄统计，患有新冠肺炎的儿童比例较低。大多数病例表现为咳嗽、发热和疲乏。症状的敏感性和特异性因年龄而异，并与年龄呈非线性关系。虽然其他呼吸道疾病感染病例的发热症状发生率随着年龄增长而降低，但新冠肺炎病例的发热症状发生比例却随年龄增长而增加。而且，大部分新冠肺炎病例的呼吸短促发生率也随年龄的增长而增加。.本研究为制定诊断标准提供了有用的证据，并为针对新冠肺炎潜在负担的模拟研究提供了素材。.Описать клинические признаки, течение болезни и обращение за медицинской помощью первых нескольких сотен случаев коронавирусного заболевания 2019 г. (COVID-19) в Соединенном Королевстве Великобритании и Северной Ирландии.Авторы внедрили протокол исследования первых случаев заболевания новой коронавирусной инфекцией 2019 г. (COVID-19) и контактов, разработанный Всемирной организацией здравоохранения. Квалифицированные специалисты в области общественного здравоохранения собрали информацию о 381 подтвержденном вирусологическим тестированием случае заболевания COVID-19 в период с 31 января по 9 апреля 2020 года. Авторы активно отслеживали данные случаи для определения контакта с инфекцией, изучения симптомов и исхода болезни. Были собраны ограниченные данные по 752 пациентам, имеющим клинические симптомы заболевания, но отрицательный результат теста на COVID-19, в качестве контрольной группы для анализа чувствительности, специфичности и прогностической ценности симптомов.Примерно половина случаев COVID-19 была завезена из-за границы (196 случаев; 51,4%), большинство из которых недавно путешествовали в Италию (140 случаев; 71,4%). Из 94 (24,7%) вторичных случаев заражения почти все сообщали о тесном контакте с лицами с подтвержденным случаями заболевания (93 случая; 98,9%), многие из которых проживали совместно с инфицированными (37 случаев; 39,8%). Вирус COVID-19 редко заражает детей. В большинстве случаев отмечались кашель, высокая температура и утомляемость. Чувствительность и специфичность симптомов варьировались в зависимости от возраста и находились в нелинейной зависимости от возраста. Несмотря на то что доля случаев COVID-19 с высокой температурой увеличивалась с возрастом, у людей с другими респираторными инфекциями частота наличия лихорадки с возрастом снижалась. Возникновение одышки также увеличивалось с возрастом для большинства случаев COVID-19.Исследование предоставило полезную информацию для определения случаев возникновения и послужило основой для модельных исследований вероятного бремени COVID-19.

Public health preparedness for coronavirus (CoV) disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal CoVs (sCoVs) and other cocirculating viruses in the West of Scotland, United Kingdom. We analyzed routine diagnostic data for >70 000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43, and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently, and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.

Background Inappropriate antibiotic prescribing, such as for viral illness, remains common in primary care. The objective of this study was to estimate the proportion of community-prescribed antibiotics to children aged less than 5 years attributable to common respiratory viruses. Methods We fitted time-series negative binomial models to predict weekly antibiotic prescribing rates from positive viral pathogen tests for the period 1 April 2009 through 27 December 2017 using comprehensive, population-based administrative data for all children ( Results We included data on 6 066 492 antibiotic prescriptions among 452 877 children. The antibiotic-prescribing rate among all Scottish children ( Conclusions Nearly 14% of antibiotics prescribed to children in this study were estimated to be attributable to common viruses for which antibiotics are not recommended. A future RSV vaccine could substantially reduce unnecessary antibiotic prescribing among children.

Background Households 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%. Aim We aimed to investigate the transmission dynamics of COVID-19 in household and community settings in the UK. Methods A 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. Results We 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. Conclusions Rates 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.

Legionella pneumophila is the main cause of a severe pneumonic illness known as Legionnaires' disease and is a global public health threat. Whole-genome sequencing (WGS) can be applied to trace environmental origins of L pneumophila infections, providing information to guide appropriate interventions. We aim to explore the evolutionary and epidemiological relationships in a 36-year Scottish L pneumophila reference isolate collection.We investigated the genomic epidemiology of Legionnaires' disease over 36 years in Scotland, comparing genome sequences for all clinical L pneumophila isolates (1984-2020) with a sequence dataset of 3211 local and globally representative isolates. We used a stratified clustering approach to capture epidemiological relationships by core genome Multi-locus Sequence Typing, followed by high-resolution phylogenetic analysis of clusters to measure diversity and evolutionary relatedness in context with epidemiological metadata.Clustering analysis showed that 111 (57·5 %) of 193 of L pneumophila infections in Scotland were caused by ten endemic lineages with a wide temporal and geographical distribution. Phylogenetic analysis of L pneumophila identified hospital-associated sublineages that had been detected in the hospital environment up to 19 years. Furthermore, 12 (30·0%) of 40 community-associated infections (excluding a single, large outbreak) that occurred over a 13 year period (from 2000 to 2013) were caused by a single widely distributed endemic clone (ST37), consistent with enhanced human pathogenicity. Finally, our analysis revealed clusters linked by national or international travel to distinct geographical regions, indicating several previously unrecognised travel links between closely related isolates (fewer than five single nucleotide polymorphisms) connected by geography.Our analysis reveals the existence of previously undetected endemic clones of L pneumophila that existed for many years in hospital, community, and travel-associated environments. In light of these findings, we propose that cluster and outbreak definitions should be reconsidered, and propose WGS-based surveillance as a critical public health tool for real-time identification and mitigation of clinically important endemic clones.Chief Scientist Office, Biotechnology and Biological Sciences Research Council (UK), Medical Research Council Precision Medicine Doctoral Training Programme, Wellcome Trust, and Medical Research Council (UK).

Background: \ud Reports suggest that COVID-19 vaccine effectiveness is decreasing, but whether this reflects waning or new SARS-CoV-2 variants—especially delta (B.1.617.2)—is unclear. We investigated the association between time since two doses of ChAdOx1 nCoV-19 vaccine and risk of severe COVID-19 outcomes in Scotland (where delta was dominant), with comparative analyses in Brazil (where delta was uncommon).\ud \ud Methods: \ud In this retrospective, population-based cohort study in Brazil and Scotland, we linked national databases from the EAVE II study in Scotland; and the COVID-19 Vaccination Campaign, Acute Respiratory Infection Suspected Cases, and Severe Acute Respiratory Infection/Illness datasets in Brazil) for vaccination, laboratory testing, clinical, and mortality data. We defined cohorts of adults (aged ≥18 years) who received two doses of ChAdOx1 nCoV-19 and compared rates of severe COVID-19 outcomes (ie, COVID-19 hospital admission or death) across fortnightly periods, relative to 2–3 weeks after the second dose. Entry to the Scotland cohort started from May 19, 2021, and entry to the Brazil cohort started from Jan 18, 2021. Follow-up in both cohorts was until Oct 25, 2021. Poisson regression was used to estimate rate ratios (RRs) and vaccine effectiveness, with 95% CIs.\ud \ud Findings: \ud 1 972 454 adults received two doses of ChAdOx1 nCoV-19 in Scotland and 42 558 839 in Brazil, with longer follow-up in Scotland because two-dose vaccination began earlier in Scotland than in Brazil. In Scotland, RRs for severe COVID-19 increased to 2·01 (95% CI 1·54–2·62) at 10–11 weeks, 3·01 (2·26–3·99) at 14–15 weeks, and 5·43 (4·00–7·38) at 18–19 weeks after the second dose. The pattern of results was similar in Brazil, with RRs of 2·29 (2·01–2·61) at 10–11 weeks, 3·10 (2·63–3·64) at 14–15 weeks, and 4·71 (3·83–5·78) at 18–19 weeks after the second dose. In Scotland, vaccine effectiveness decreased from 83·7% (95% CI 79·7–87·0) at 2–3 weeks, to 75·9% (72·9–78·6) at 14–15 weeks, and 63·7% (59·6–67·4) at 18–19 weeks after the second dose. In Brazil, vaccine effectiveness decreased from 86·4% (85·4–87·3) at 2–3 weeks, to 59·7% (54·6–64·2) at 14–15 weeks, and 42·2% (32·4–50·6) at 18–19 weeks.\ud \ud Interpretation: \ud We found waning vaccine protection of ChAdOx1 nCoV-19 against COVID-19 hospital admissions and deaths in both Scotland and Brazil, this becoming evident within three months of the second vaccine dose. Consideration needs to be given to providing booster vaccine doses for people who have received ChAdOx1 nCoV-19.\ud \ud Funding: \ud UK Research and Innovation (Medical Research Council), Scottish Government, Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, Fiocruz, Fazer o Bem Faz Bem Programme; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro.\ud \ud Translation: \ud For the Portuguese translation of the abstract see Supplementary Materials section.

BackgroundThere have been no population-based studies of SARS-CoV-2 testing, PCR-confirmed infections and COVID-19-related hospital admissions across the full paediatric age range. We examine the epidemiology of SARS-CoV-2 in children and young people (CYP) aged MethodsWe used a birth cohort of all children born in Scotland since 1997, constructed via linkage between vital statistics, hospital records and SARS-CoV-2 surveillance data. We calculated risks of tests and PCR-confirmed infections per 1000 CYP-years between August and December 2020, and COVID-19-related hospital admissions per 100,000 CYP-years between February and December 2020. We used Poisson and Cox proportional hazards regression models to determine risk factors.ResultsAmong the 1226855 CYP in the cohort, there were 378402 tests, 19005 PCR confirmed infections and 346 admissions, corresponding to rates of 770.8/1000 (95% confidence interval 768.4-773.3), 179.4 (176.9-182.0) and 29.4/100,000 (26.3-32.8) CYP-years respectively. Infants had the highest COVID-19-related admission rates. Chronic conditions, particularly multiple types of conditions, was strongly associated with COVID-19-related admissions across all ages. The hazard ratio for >1 chronic condition type was 12.2 (7.9-18.82) compared to children with no chronic conditions. 89% of admitted children had no chronic conditions recorded.ConclusionsInfants, and CYP with chronic conditions are at highest risk of admission with COVID-19, however the majority of admitted CYP have no chronic conditions. These results provide evidence to support risk/benefit analyses for paediatric COVID-19 vaccination programmes. Studies examining whether maternal vaccine during pregnancy prevents COVID-19 admissions in infants are urgently needed.FundingUK Research and Innovation-Medical Research Council

Funding Medical Research Council (MR/R008345/1), National Institute for Health Research Health Technology Assessment Programme, funded through the UK Research and Innovation Industrial Strategy Challenge Fund Health Data Research UK. Background : The QCovid algorithm is a risk prediction tool that can be used to stratify individuals by risk of COVID-19 hospitalisation and mortality. Version 1 of the algorithm was trained using data covering 10.5 million patients in England in the period 24 January 2020 to 30 April 2020. We carried out an external validation of version 1 of the QCovid algorithm in Scotland. Methods : We established a national COVID-19 data platform using individual level data for the population of Scotland (5.4 million residents). Primary care data were linked to reverse-transcription PCR (RT-PCR) virology testing, hospitalisation and mortality data. We assessed the performance of the QCovid algorithm in predicting COVID-19 hospitalisations and deaths in our dataset for two time periods matching the original study: 1 March 2020 to 30 April 2020, and 1 May 2020 to 30 June 2020. Results : Our dataset comprised 5 384 819 individuals, representing 99% of the estimated population (5 463 300) resident in Scotland in 2020. The algorithm showed good calibration in the first period, but systematic overestimation of risk in the second period, prior to temporal recalibration. Harrell’s C for deaths in females and males in the first period was 0.95 (95% CI 0.94 to 0.95) and 0.93 (95% CI 0.92 to 0.93), respectively. Harrell’s C for hospitalisations in females and males in the first period was 0.81 (95% CI 0.80 to 0.82) and 0.82 (95% CI 0.81 to 0.82), respectively. Conclusions : Version 1 of the QCovid algorithm showed high levels of discrimination in predicting the risk of COVID-19 hospitalisations and deaths in adults resident in Scotland for the original two time periods studied, but is likely to need ongoing recalibration prospectively. Publisher PDF

Effect of Vaccination on Transmission of SARS-CoV-2 In this report from Scotland, vaccination of health care workers for SARS-CoV-2 was associated with a decrease in household transmission.

This work was supported by the Scottish Government. Objectives : Studies that measure the prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (‘seroprevalence’) are essential to understand population exposure to SARS-CoV-2 among symptomatic and asymptomatic individuals. We aimed to measure seroprevalence in the Scottish population over the course of the COVID-19 pandemic – from before the first recorded case in Scotland through to the second pandemic wave. Study design : The study design of this study is serial cross sectional. Methods : We tested 41,477 residual samples retrieved from primary and antenatal care settings across Scotland for SARS-CoV-2 antibodies over a 12-month period from December 2019-December 2020 (before rollout of COVID-19 vaccination). Five-weekly rolling seroprevalence estimates were adjusted for the sensitivity and specificity of the assays and weighted to reference populations. Temporal trends in seroprevalence estimates and weekly SARS-CoV-2 notifications were compared. Results : Five-weekly rolling seroprevalence rates were 0% until the end of March, when they increased contemporaneously with the first pandemic wave. Seroprevalence rates remained stable through the summer (range: 3%–5%) during a period of social restrictions, after which they increased concurrently with the second wave, reaching 9.6% (95% confidence interval [CI]: 8.4%–10.8%) in the week beginning 28th December in 2020. Seroprevalence rates were lower in rural vs. urban areas (adjusted odds ratio [AOR]: 0.70, 95% CI: 0.61–0.79) and among individuals aged 20–39 years and 60 years and older (AOR: 0.74, 95% CI: 0.64–0.86; AOR: 0.80, 95% CI: 0.69–0.91, respectively) relative to those aged 0–19 years. Conclusions : After two waves of the COVID-19 pandemic, less than one in ten individuals in the Scottish population had antibodies to SARS-CoV-2. Seroprevalence may underestimate the true population exposure as a result of waning antibodies among individuals who were infected early in the first wave. Postprint

EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE—The Health Data Research Hub for Respiratory Health [MC_PC_19004], which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. UA, CM, AA-L, and AFF acknowledge funding from Chief Scientist Office Rapid Research in COVID-19 programme (COV/SAN/20/06) and Health Data Research UK (measuring and understanding multimorbidity using routine data in the UK—HDR-9006; CFC0110). SVK acknowledges funding from a NHS Research Scotland Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2), and the Scottish Government's Chief Scientist Office (SPHSU17). SJS is funded by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z). Background The UK COVID-19 vaccination programme has prioritised vaccination of those at the highest risk of COVID-19 mortality and hospitalisation. The programme was rolled out in Scotland during winter 2020–21, when SARS-CoV-2 infection rates were at their highest since the pandemic started, despite social distancing measures being in place. We aimed to estimate the frequency of COVID-19 hospitalisation or death in people who received at least one vaccine dose and characterise these individuals. Methods We conducted a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) national surveillance platform, which contained linked vaccination, primary care, RT-PCR testing, hospitalisation, and mortality records for 5·4 million people (around 99% of the population) in Scotland. Individuals were followed up from receiving their first dose of the BNT162b2 (Pfizer–BioNTech) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) COVID-19 vaccines until admission to hospital for COVID-19, death, or the end of the study period on April 18, 2021. We used a time-dependent Poisson regression model to estimate rate ratios (RRs) for demographic and clinical factors associated with COVID-19 hospitalisation or death 14 days or more after the first vaccine dose, stratified by vaccine type. Findings Between Dec 8, 2020, and April 18, 2021, 2 572 008 individuals received their first dose of vaccine—841 090 (32·7%) received BNT162b2 and 1 730 918 (67·3%) received ChAdOx1. 1196 (

BackgroundInfluenza infection is a trigger of asthma attacks. Influenza vaccination can potentially reduce the incidence of influenza in people with asthma, but uptake remains persistently low, partially reflecting concerns about vaccine effectiveness (VE).MethodsWe conducted a test-negative designed case-control study to estimate the effectiveness of influenza vaccine in people with asthma in Scotland over 6 seasons (2010/2011 to 2015/2016). We used individual patient–level data from 223 practices, which yielded 1 830 772 patient-years of data that were linked with virological (n = 5910 swabs) data.ResultsVaccination was associated with an overall 55.0% (95% confidence interval [CI], 45.8–62.7) risk reduction of laboratory-confirmed influenza infections in people with asthma over 6 seasons. There were substantial variations in VE between seasons, influenza strains, and age groups. The highest VE (76.1%; 95% CI, 55.6–87.1) was found in the 2010/2011 season, when the A(H1N1) strain dominated and there was a good antigenic vaccine match. High protection was observed against the A(H1N1) (eg, 2010/2011; 70.7%; 95% CI, 32.5–87.3) and B strains (eg, 2010/2011; 83.2%; 95% CI, 44.3–94.9), but there was lower protection for the A(H3N2) strain (eg, 2014/2015; 26.4%; 95% CI, −12.0 to 51.6). The highest VE against all viral strains was observed in adults aged 18–54 years (57.0%; 95% CI, 42.3–68.0).ConclusionsInfluenza vaccination gave meaningful protection against laboratory-confirmed influenza in people with asthma across all seasons. Strategies to boost influenza vaccine uptake have the potential to substantially reduce influenza-triggered asthma attacks.

Background: For the last 17 years, the UK has employed a routine influenza vaccination programme with the aim of reducing the spread of seasonal influenza. In mid-2000, the programme moved from a purely risk-based approach to a risk and age group targeted approach with all those aged 65+ years being included. To date, there has been no assessment of the population effectiveness of this age targeted policy in Scotland. Objectives: Statistical modelling techniques were used to determine what impact the routine vaccination of those aged 65+ years has had on influenza related morbidity and mortality in Scotland. Methods: Two Poisson regression models were developed using weekly counts of all-cause mortality, cause specific mortality and emergency hospitalisations for the period 1981 – 2012, one using week-in-year and the other using temperature to capture the seasonal variability in mortality/hospitalisations. These models were used to determine the number of excess deaths/hospitalisations associated with the introduction of the local risk and age-based vaccination programme in 2000. Results: Routinely vaccinating those aged 65+ years is associated with a reduction in excess allcause mortality, cardiovascular and COPD related mortality and COPD related hospitalisations. Our analysis suggests that using the week-in-year model, on average, 732 (95%CI 66 – 1,398) deaths from all-causes, 248 (95%CI 10 – 486) cardiovascular related deaths, 123 (95%CI 28 – 218) COPD related deaths, and 425 (95%CI 258 – 592) COPD related hospitalisations have been prevented each flu season among the those aged 65+. Similar results were found using the temperature model. There was no evidence to suggest that the change in policy was associated with reductions in influenza/pneumonia related mortality or influenza/cardiovascular related hospitalisations. Conclusions: Routinely vaccinating those aged 65+ years appears to have reduced influenza related morbidity and mortality in Scotland. With the childhood vaccination programme well underway, these data provide an importance benchmark which can be used to accurately assess the impact of this new seasonal influenza vaccination programme.

Objectives This study aimed to determine SARS-CoV-2 seroprevalence among pregnant women in the Scottish population during the second wave of the COVID-19 pandemic. Study design Prospective national serosurvey. Methods We tested 13,428 residual samples retrieved from pregnant women participating in the first trimester combined ultrasound and biochemical screening for fetal trisomy across Scotland for SARS-CoV-2 antibodies over a 6-month period from November 2020 to April 2021. Seroprevalence estimates were adjusted for the sensitivity and specificity of the assays and weighted to reference populations. Results Seroprevalence rates in the antenatal samples significantly increased from 5.5% (95% confidence interval [CI] 4.7%–6.5%) in the 5-week period up to and including International Organization for Standardization (ISO) Week 51 (w/b Monday 14 December 2020) to 11.3% (95% CI 10.1%–12.6%) in the 5-week period up to and including ISO Week 14 (w/b Monday 5 April 2021). Increasing seroprevalence trends across the second wave were observed among all age groups. Conclusions By the end of the second wave of the COVID-19 pandemic, approximately one in 10 women tested around the end of the first trimester of pregnancy had antibodies to SARS-CoV-2, suggesting that the vast majority were still susceptible to COVID-19 as they progressed to the later stages of pregnancy, when risks from infection are elevated for both mother and baby.

This study is part of the EAVE II project. EAVE II is funded by the MRC (MR/R008345/1) with the support of BREATHE—The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through Public Health Scotland and Scottish Government Director General Health and Social Care. The original EAVE project was funded by the NIHR Health Technology Assessment programme (11/46/23). Background As the COVID-19 pandemic continues, national-level surveillance platforms with real-time individual person-level data are required to monitor and predict the epidemiological and clinical profile of COVID-19 and inform public health policy. We aimed to create a national dataset of patient-level data in Scotland to identify temporal trends and COVID-19 risk factors, and to develop a novel statistical prediction model to forecast COVID-19-related deaths and hospitalisations during the second wave. Methods We established a surveillance platform to monitor COVID-19 temporal trends using person-level primary care data (including age, sex, socioeconomic status, urban or rural residence, care home residence, and clinical risk factors) linked to data on SARS-CoV-2 RT-PCR tests, hospitalisations, and deaths for all individuals resident in Scotland who were registered with a general practice on Feb 23, 2020. A Cox proportional hazards model was used to estimate the association between clinical risk groups and time to hospitalisation and death. A survival prediction model derived from data from March 1 to June 23, 2020, was created to forecast hospital admissions and deaths from October to December, 2020. We fitted a generalised additive spline model to daily SARS-CoV-2 cases over the previous 10 weeks and used this to create a 28-day forecast of the number of daily cases. The age and risk group pattern of cases in the previous 3 weeks was then used to select a stratified sample of individuals from our cohort who had not previously tested positive, with future cases in each group sampled from a multinomial distribution. We then used their patient characteristics (including age, sex, comorbidities, and socioeconomic status) to predict their probability of hospitalisation or death. Findings Our cohort included 5 384 819 people, representing 98·6% of the entire estimated population residing in Scotland during 2020. Hospitalisation and death among those testing positive for SARS-CoV-2 between March 1 and June 23, 2020, were associated with several patient characteristics, including male sex (hospitalisation hazard ratio [HR] 1·47, 95% CI 1·38–1·57; death HR 1·62, 1·49–1·76) and various comorbidities, with the highest hospitalisation HR found for transplantation (4·53, 1·87–10·98) and the highest death HR for myoneural disease (2·33, 1·46–3·71). For those testing positive, there were decreasing temporal trends in hospitalisation and death rates. The proportion of positive tests among older age groups (>40 years) and those with at-risk comorbidities increased during October, 2020. On Nov 10, 2020, the projected number of hospitalisations for Dec 8, 2020 (28 days later) was 90 per day (95% prediction interval 55–125) and the projected number of deaths was 21 per day (12–29). Interpretation The estimated incidence of SARS-CoV-2 infection based on positive tests recorded in this unique data resource has provided forecasts of hospitalisation and death rates for the whole of Scotland. These findings were used by the Scottish Government to inform their response to reduce COVID-19-related morbidity and mortality. Publisher PDF

Objective To estimate the real world effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S vaccines against confirmed covid-19 symptoms (including the UK variant of concern B.1.1.7), admissions to hospital, and deaths. Design Test negative case-control study. Setting Community testing for covid-19 in England. Participants 156 930 adults aged 70 years and older who reported symptoms of covid-19 between 8 December 2020 and 19 February 2021 and were successfully linked to vaccination data in the National Immunisation Management System. Interventions Vaccination with BNT162b2 or ChAdOx1-S. Main outcome measures Primary outcomes were polymerase chain reaction confirmed symptomatic SARS-CoV-2 infections, admissions to hospital for covid-19, and deaths with covid-19. Results Participants aged 80 years and older vaccinated with BNT162b2 before 4 January 2021 had a higher odds of testing positive for covid-19 in the first nine days after vaccination (odds ratio up to 1.48, 95% confidence interval 1.23 to 1.77), indicating that those initially targeted had a higher underlying risk of infection. Vaccine effectiveness was therefore compared with the baseline post-vaccination period. Vaccine effects were noted 10 to 13 days after vaccination, reaching a vaccine effectiveness of 70% (95% confidence interval 59% to 78%), then plateauing. From 14 days after the second dose a vaccination effectiveness of 89% (85% to 93%) was found compared with the increased baseline risk. Participants aged 70 years and older vaccinated from 4 January (when ChAdOx1-S delivery commenced) had a similar underlying risk of covid-19 to unvaccinated individuals. With BNT162b2, vaccine effectiveness reached 61% (51% to 69%) from 28 to 34 days after vaccination, then plateaued. With ChAdOx1-S, effects were seen from 14 to 20 days after vaccination, reaching an effectiveness of 60% (41% to 73%) from 28 to 34 days, increasing to 73% (27% to 90%) from day 35 onwards. On top of the protection against symptomatic disease, a further 43% (33% to 52%) reduced risk of emergency hospital admission and 51% (37% to 62%) reduced risk of death was observed in those who had received one dose of BNT162b2. Participants who had received one dose of ChAdOx1-S had a further 37% (3% to 59%) reduced risk of emergency hospital admission. Follow-up was insufficient to assess the effect of ChAdOx1-S on mortality. Combined with the effect against symptomatic disease, a single dose of either vaccine was about 80% effective at preventing admission to hospital with covid-19 and a single dose of BNT162b2 was 85% effective at preventing death with covid-19. Conclusion Vaccination with either one dose of BNT162b2 or ChAdOx1-S was associated with a significant reduction in symptomatic covid-19 in older adults, and with further protection against severe disease. Both vaccines showed similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 was associated with further protection against symptomatic disease. A clear effect of the vaccines against the B.1.1.7 variant was found.

Reports of ChAdOx1 vaccine–associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0–27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41–13.83), with an estimated incidence of 1.13 (0.62–1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29–3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12–1.34) 0–27 d after vaccination, with an SCCS RR of 0.97 (0.93–1.02). For hemorrhagic events 0–27 d after vaccination, the aRR was 1.48 (1.12–1.96), with an SCCS RR of 0.95 (0.82–1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events., New data from the EAVE II cohort in Scotland suggests that a first dose of the ChAdOx1 nCoV-19 vaccine might be associated with a small increase in the risk of idiopathic thrombocytopenic purpura between 0 and 27 d after vaccination.

BackgroundThe effect of vaccination for COVID-19 on onward transmission is unknown.MethodsA national record linkage study determined documented COVID-19 cases and hospitalisations in unvaccinated household members of vaccinated and unvaccinated healthcare workers from 8th December 2020 to 3rd March 2021. The primary endpoint was COVID-19 14 days following the first dose.ResultsThe cohort comprised of 194,362 household members (mean age 31·1 ± 20·9 years) and 144,525 healthcare workers (mean age 44·4 ± 11·4 years). 113,253 (78·3%) of healthcare workers received at least one dose of the BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccine and 36,227 (25·1%) received a second dose. There were 3,123 and 4,343 documented COVID-19 cases and 175 and 177 COVID-19 hospitalisations in household members of healthcare workers and healthcare workers respectively. Household members of vaccinated healthcare workers had a lower risk of COVID-19 case compared to household members of unvaccinated healthcare worker (rate per 100 person-years 9·40 versus 5·93; HR 0·70, 95% confidence interval [CI] 0·63 to 0·78). The effect size for COVID-19 hospitalisation was similar, with the confidence interval crossing the null (HR 0·77 [95% CI 0·53 to 1·10]). The rate per 100 person years was lower in vaccinated compared to unvaccinated healthcare workers for documented (20·13 versus 8·51; HR 0·45 [95% CI 0·42 to 0·49]) and hospitalized COVID-19 (0·97 versus 0·14; HR 0·16 [95% CI 0·09 to 0·27]). Compared to the period before the first dose, the risk of documented COVID-19 case was lower at ≥ 14 days after the second dose for household members (HR 0·46 [95% CI 0·30to 0·70]) and healthcare workers (HR 0·08 [95% CI 0·04 to 0·17]).InterpretationVaccination of health care workers was associated with a substantial reduction in COVID-19 cases in household contacts consistent with an effect of vaccination on transmission.

ObjectivesTo estimate the real-world effectiveness of the Pfizer/BioNTech BNT162b2 vaccine and Astrazeneca ChAdOx1 vaccine against Confirmed COVID-19, hospitalisations and deaths. To estimate effectiveness on the UK variant of concern.DesignTest negative case control designSettingCommunity COVID-19 PCR testing in EnglandParticipantsAll adults in England aged 70 years and older (over 7.5 million). All COVID-19 testing in the community among eligible individuals who reported symptoms between 8thDecember 2020 and 19thFebruary 2021 was included in the analysis.InterventionsOne and two doses of BNT162b2 vaccine. One dose of ChAdOx1 vaccine.Main outcome measuresSymptomatic PCR confirmed SARS-CoV-2 infection, hospitalisations and deaths with COVID-19.ResultsIndividuals aged >=80 years vaccinated with BNT162b2 prior to 4thJanuary, had a higher odds of testing positive in the first 9 days after vaccination (odds ratio up to 1.48, 95%CI 1.23-1.77), indicating that those initially targeted had a higher underlying risk of infection. Vaccine effectiveness was therefore estimated relative to the baseline post-vaccination period. Vaccine effects were noted from 10-13 days after vaccination, reaching an effectiveness of 70% (95% CI 59-78%) from 28-34 days, then plateauing. From 14 days after the second dose a vaccine effectiveness of 89% (95%CI: 85-93%) was seen.Individuals aged >=70 years vaccinated from 4thJanuary had a similar underlying risk of COVID-19 to unvaccinated individuals. With BNT162b2, vaccine effectiveness reached 61% (95%CI 51-69%) from 28-34 days after vaccination then plateaued. With the ChAdOx1 vaccine, vaccine effects were seen from 14-20 days after vaccination reaching an effectiveness of 60% (95%CI 41-73%) from 28-34 days and further increasing to 73% (95%CI 27-90%) from day 35 onwards.On top of the protection against symptomatic disease, cases who had been vaccinated with one dose of BNT162b2 had an additional 43% (95%CI 33-52%) lower risk of emergency hospitalisation and an additional 51% (95%CI 37-62%) lower risk of death. Cases who had been vaccinated with one dose of ChAdOx1 had an additional 37% (95% CI 3-59%) lower risk of emergency hospitalisation. There was insufficient follow-up to assess the effect of ChAdOx1 on mortality due to the later rollout of this vaccine. Combined with the effect against symptomatic disease, this indicates that a single dose of either vaccine is approximately 80% effective at preventing hospitalisation and a single dose of BNT162b2 is 85% effective at preventing death with COVID-19.ConclusionVaccination with either a single dose of BNT162b2 or ChAdOx1 COVID-19 vaccination was associated with a significant reduction in symptomatic SARS-CoV2 positive cases in older adults with even greater protection against severe disease. Both vaccines show similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 provides further protection against symptomatic disease but second doses of ChAdOx1 have not yet been rolled out in England. There is a clear effect of the vaccines against the UK variant of concern.

SHu reports grants from Health Protection Scotland during the conduct of the study. TMC reports grants from Diabetes UK (18/0005786). CR reports grants from Public Health Scotland and UK Research and Innovation. Background We aimed to ascertain the cumulative risk of fatal or critical care unit-treated COVID-19 in people with diabetes and compare it with that of people without diabetes, and to investigate risk factors for and build a cross-validated predictive model of fatal or critical care unit-treated COVID-19 among people with diabetes. Methods In this cohort study, we captured the data encompassing the first wave of the pandemic in Scotland, from March 1, 2020, when the first case was identified, to July 31, 2020, when infection rates had dropped sufficiently that shielding measures were officially terminated. The participants were the total population of Scotland, including all people with diabetes who were alive 3 weeks before the start of the pandemic in Scotland (estimated Feb 7, 2020). We ascertained how many people developed fatal or critical care unit-treated COVID-19 in this period from the Electronic Communication of Surveillance in Scotland database (on virology), the RAPID database of daily hospitalisations, the Scottish Morbidity Records-01 of hospital discharges, the National Records of Scotland death registrations data, and the Scottish Intensive Care Society and Audit Group database (on critical care). Among people with fatal or critical care unit-treated COVID-19, diabetes status was ascertained by linkage to the national diabetes register, Scottish Care Information Diabetes. We compared the cumulative incidence of fatal or critical care unit-treated COVID-19 in people with and without diabetes using logistic regression. For people with diabetes, we obtained data on potential risk factors for fatal or critical care unit-treated COVID-19 from the national diabetes register and other linked health administrative databases. We tested the association of these factors with fatal or critical care unit-treated COVID-19 in people with diabetes, and constructed a prediction model using stepwise regression and 20-fold cross-validation. Findings Of the total Scottish population on March 1, 2020 (n=5 463 300), the population with diabetes was 319 349 (5·8%), 1082 (0·3%) of whom developed fatal or critical care unit-treated COVID-19 by July 31, 2020, of whom 972 (89·8%) were aged 60 years or older. In the population without diabetes, 4081 (0·1%) of 5 143 951 people developed fatal or critical care unit-treated COVID-19. As of July 31, the overall odds ratio (OR) for diabetes, adjusted for age and sex, was 1·395 (95% CI 1·304–1·494; p

The coronavirus disease (COVID-19) global pandemic is ongoing, with Europe and the Americas the current epicentres of transmission. As at 1 January, 2021, over 82 million cases and 1.8 million deaths have been reported globally [1,2]. In Europe alone, the number of cases reported has now passed 26 million, with over 580,000 laboratory-confirmed COVID-19 deaths [3,4]. As many COVID-19 cases and deaths may not be confirmed by virological testing, and as the pandemic causes a range of indirect and collateral harms, the officially reported figures of laboratory-confirmed COVID-19 cases and deaths represent only a part of the total disease, mortality and overall public health burden associated with the pandemic. Here we report some noteworthy estimates of a marked increase in excess all-cause mortality in Europe coinciding with a steep second wave of COVID-19 in many countries since September 2020.

EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE—The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through Public Health Scotland and the Scottish Government's director-general of Health and Social Care. FDRH acknowledges part support from the National Institutes of Health Research (NIHR) School for Primary Care Research, the NIHR Collaboration for Leadership in Applied Health Research and Care Oxford, and the NIHR Oxford Biomedical Research Centre. SVK acknowledges funding from an NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2), and Scottish Government Chief Scientist Office (SPHSU13). Background The BNT162b2 mRNA (Pfizer–BioNTech) and ChAdOx1 nCoV-19 (Oxford–AstraZeneca) COVID-19 vaccines have shown high efficacy against disease in phase 3 clinical trials and are now being used in national vaccination programmes in the UK and several other countries. Studying the real-world effects of these vaccines is an urgent requirement. The aim of our study was to investigate the association between the mass roll-out of the first doses of these COVID-19 vaccines and hospital admissions for COVID-19. Methods We did a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19—EAVE II—database comprising linked vaccination, primary care, real-time reverse transcription-PCR testing, and hospital admission patient records for 5·4 million people in Scotland (about 99% of the population) registered at 940 general practices. Individuals who had previously tested positive were excluded from the analysis. A time-dependent Cox model and Poisson regression models with inverse propensity weights were fitted to estimate effectiveness against COVID-19 hospital admission (defined as 1–adjusted rate ratio) following the first dose of vaccine. Findings Between Dec 8, 2020, and Feb 22, 2021, a total of 1 331 993 people were vaccinated over the study period. The mean age of those vaccinated was 65·0 years (SD 16·2). The first dose of the BNT162b2 mRNA vaccine was associated with a vaccine effect of 91% (95% CI 85–94) for reduced COVID-19 hospital admission at 28–34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 88% (95% CI 75–94). Results of combined vaccine effects against hospital admission due to COVID-19 were similar when restricting the analysis to those aged 80 years and older (83%, 95% CI 72–89 at 28–34 days post-vaccination). Interpretation Mass roll-out of the first doses of the BNT162b2 mRNA and ChAdOx1 vaccines was associated with substantial reductions in the risk of hospital admission due to COVID-19 in Scotland. There remains the possibility that some of the observed effects might have been due to residual confounding. Funding UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK. Publisher PDF

Since December 2019, over 1.5 million SARS-CoV-2-related fatalities have been recorded in the World Health Organization European Region - 90.2% in people ≥ 60 years. We calculated lives saved in this age group by COVID-19 vaccination in 33 countries from December 2020 to November 2021, using weekly reported deaths and vaccination coverage. We estimated that vaccination averted 469,186 deaths (51% of 911,302 expected deaths; sensitivity range: 129,851–733,744; 23–62%). Impact by country ranged 6–93%, largest when implementation was early.

Background: The QCovid algorithm is a risk prediction tool for COVID-19 hospitalisation and mortality that can be used to stratify patients by risk into vulnerability groups . We carried out an external validation of the QCovid algorithm in Scotland. Methods: We established a national COVID-19 data platform using individual level data for the population of Scotland (5.4 million residents). Primary care data were linked to reverse-transcription polymerase chain reaction (RT-PCR) virology testing, hospitalisation and mortality data. We assessed the performance of the QCovid algorithm in predicting COVID-19 hospitalisation and deaths in our dataset for two time periods: 1 March, 2020 to 30 April, 2020, and 1 May, 2020 to 30 June, 2020. Findings: Our dataset comprised 5,384,819 individuals, representing 99% of the estimated population (5,463,300) resident in Scotland in 2020. The algorithm showed excellent calibration in both time periods with close correspondence between observed and predicted risks. Harrell ’s C for deaths in males and females in the first period was 0.946 (95% CI: 0.941 - 0.951) and 0.925 (95% CI: 0.919 - 0.931) respectively. Harrell’s C for hospitalisations in males and females in the first period was 0.809 (95% CI: 0.801 - 0.817) and 0.816 (95% CI: 0.808 - 0.823) respectively. Interpretation: The QCovid algorithm shows high levels of external validity in predicting the risk of COVID- 19 hospitalisation and death in the population of Scotland. Funding: Medical Research Council, National Institute for Health Research Health Technology Assessment Programme, funded through the UK Research and Innovation Industrial Strategy Challenge Fund Health Data Research UK. Declaration of Interests: Dr. Hippisley-Cox reports grants from MRC, grants from Wellcome Trrust, grants from NIHR, during the conduct of the study; other from ClinRisk Ltd, outside the submitted work. Dr. Sheikh reports grants from NIHR, grants from MRC, grants from HRR UK, during the conduct of the study. All other authors report no conflict of interest. Ethics Approval Statement: Ethical permission for this study was granted from South East Scotland Research Ethics Committee 02 [12/SS/0201]. The Public Benefit and Privacy Panel Committee of Public Health Scotland, approved the linkage and analysis of the de-identified datasets for this project [1920-0279].

Public Health Scotland used Scottish national contact tracing data to estimate the European football championship (EURO 2020) contributions to a third wave of SARS-CoV-2 infections. From 11 June to 7 July 2021, 2,632 (4%) of 63,874 SARS-CoV-2 cases self-reported attending a EURO 2020 event; 90% were male, of whom 73% were 20–39-year-olds. Most cases attended unofficial gatherings and averaged more contacts than the general population. Targeted guidance on celebrating safely in closed spaces is key.