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Background We aimed to quantify the unknown losses in health-related quality of life of coronavirus disease 2019 (COVID-19) cases using quality-adjusted lifedays (QALDs) and the recommended EQ-5D instrument in England. Methods Prospective cohort study of nonhospitalized, polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2–positive (SARS-CoV-2–positive) cases aged 12–85 years and followed up for 6 months from 1 December 2020, with cross-sectional comparison to SARS-CoV-2–negative controls. Main outcomes were QALD losses; physical symptoms; and COVID-19-related private expenditures. We analyzed results using multivariable regressions with post hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls. Results Of 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on nonprescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 13.7 (95% confidence interval [CI]: 9.7, 17.7) QALDs, whereas those reporting symptoms at month 6 lost 32.9 (95% CI: 24.5, 37.6) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 18% of the total COVID-19-related disease burden in the England. Conclusions One in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms.

Syndromic surveillance was originally developed to provide early warning compared to laboratory surveillance, but it is increasing used for real-time situational awareness. When a potential threat to public health is identified, a rapid assessment of its impact is required for public health management. When threats are localised, analysis is more complex as local trends need to be separated from national trends and differences compared to unaffected areas may be due to confounding factors such as deprivation or age distributions. Accounting for confounding factors usually requires an in-depth study, which takes time. Therefore, a tool is required which can provide a rapid estimate of local incidents using syndromic surveillance data. Here, we present ‘DiD IT?’, a new investigation tool designed to measure the impact of local threats to public health. ‘DiD IT?’ uses a difference-in-differences statistical approach to account for temporal and spatial confounding and provide a direct estimate of impact due to incidents. Temporal confounding differences are estimated by comparing unaffected locations during and outside of exposure periods. Whilst spatial confounding differences are estimated by comparing unaffected and exposed locations outside of the exposure period. Any remaining differences can be considered to be the direct effect of the local incident. We illustrate the potential utility of the tool through four examples of localised health protection incidents in England. The examples cover a range of data sources including general practitioner (GP) consultations, emergency department (ED) attendances and a telehealth call and online health symptom checker; and different types of incidents including, infectious disease outbreak, mass-gathering, extreme weather and an industrial fire. The examples use the UK Health Security Agency's ongoing real-time syndromic surveillance systems to show how results can be obtained in near real-time. The tool identified 700 additional online difficulty breathing assessments associated with a severe thunderstorm, 53 additional GP consultations during a mumps outbreak, 2–3 telehealth line calls following an industrial fire and that there was no significant increase in ED attendances during the G7 summit in 2021. DiD IT? can provide estimates for the direct impact of localised events in real-time as part of a syndromic surveillance system. Thus, it has the potential for enhancing surveillance and can be used to evaluate the effectiveness of extending national surveillance to a more granular local surveillance.

The monkeypox epidemic in the UK began in May 2022, and subsequently and rather quickly, rates of new cases have declined during August 2022. Identifying the causes of this decline requires accurate estimates of the time-varying epidemic growth rate r(t), which in turn depend upon the reporting delays (defined as the time from onset of symptoms to presenting to healthcare). Using a custom nowcasting method which allows for time-varying delays (EpiLine), we show that the reporting delay for Monkeypox in the UK decreased from an average of 22 days in early May 2022 to 10 days by early June and 7 days in August 2022. Accounting for these dynamic delays shows that the time-varying r(t) declined gradually in the UK over this period. Not accounting for varying time delays would have incorrectly characterised r(t) by a sharp increase followed by a rapid drop. We discuss the importance of this gradual decline, which helps identify the potential mechanisms responsible for the decline in the rate of spread of Monkeypox, which was gradual and started well before vaccines were widely used.

Excess mortality is an important measure of the scale of the coronavirus-2019 pandemic. It includes both deaths caused directly by the pandemic, and deaths caused by the unintended consequences of containment such as delays to accessing care or postponements of healthcare provision in the population. In 2020 and 2021, in England, multiple groups have produced measures of excess mortality during the pandemic. This paper describes the data and methods used in five different approaches to estimating excess mortality and compares their estimates. The fundamental principles of estimating excess mortality are described, as well as the key commonalities and differences between five approaches. Two of these are based on the date of registration: a quasi-Poisson model with offset and a 5-year average; and three are based on date of occurrence: a Poisson model without offset, the European monitoring of excess mortality model and a synthetic controls model. Comparisons between estimates of excess mortality are made for the period March 2020 through March 2021 and for the two waves of the pandemic that occur within that time-period. Model estimates are strikingly similar during the first wave of the pandemic though larger differences are observed during the second wave. Models that adjusted for reduced circulation of winter infection produced higher estimates of excess compared with those that did not. Models that do not adjust for reduced circulation of winter infection captured the effect of reduced winter illness as a result of mobility restrictions during the period. None of the estimates captured mortality displacement and therefore may underestimate excess at the current time, though the extent to which this has occurred is not yet identified. Models use different approaches to address variation in data availability and stakeholder requirements of the measure. Variation between estimates reflects differences in the date of interest, population denominators and parameters in the model relating to seasonality and trend.

Respiratory Syncytial Virus (RSV) is a common seasonal respiratory virus and an important cause of illness among infants, but the burden of RSV disease is not well described among the older population. The objective of this study was to estimate the age-specific incidence of hospital admission among over 65s due to respiratory illnesses attributable to RSV in England to inform optimal vaccine and therapeutic interventions. We used linear multiple regression to examine the effect of changes in weekly counts of respiratory pathogens on the weekly counts of respiratory hospital admissions. The study population was all patients aged 65 years or over admitted to English hospitals between 2nd August 2010 and 30th July 2017. RSV was estimated to account for a seasonal annual average of 71 (95% CI 52-90) respiratory admissions per 100,000 in adults age 65-74 and 251 (95% CI 186-316) admissions per 100,000 adults age 75+. Pneumococcus was the pathogen responsible for highest annual average respiratory admission with 448 (95% CI 310-587) admissions per 100,000 adults age 65-74 and 1010 (95%CI 527-1493) admissions per 100,000 adults aged 75+. This study shows that RSV continues to exert a significant burden of disease among older adults in England. These findings will support development of policy for the use of RSV therapeutics and vaccines in this age group.

Aims Hip fracture commonly affects the frailest patients, of whom many are care-dependent, with a disproportionate risk of contracting COVID-19. We examined the impact of COVID-19 infection on hip fracture mortality in England. Methods We conducted a cohort study of patients with hip fracture recorded in the National Hip Fracture Database between 1 February 2019 and 31 October 2020 in England. Data were linked to Hospital Episode Statistics to quantify patient characteristics and comorbidities, Office for National Statistics mortality data, and Public Health England’s SARS-CoV-2 testing results. Multivariable Cox regression examined determinants of 90-day mortality. Excess mortality attributable to COVID-19 was quantified using Quasi-Poisson models. Results Analysis of 102,900 hip fractures (42,630 occurring during the pandemic) revealed that among those with COVID-19 infection at presentation (n = 1,120) there was a doubling of 90-day mortality; hazard ratio (HR) 2.09 (95% confidence interval (CI) 1.89 to 2.31), while the HR for infections arising between eight and 30 days after presentation (n = 1,644) the figure was greater at 2.51 (95% CI 2.31 to 2.73). Malnutrition (1.45 (95% CI 1.19 to 1.77)) and nonoperative treatment (2.94 (95% CI 2.18 to 3.95)) were the only modifiable risk factors for death in COVID-19-positive patients. Patients who had tested positive for COVID-19 more than two weeks prior to hip fracture initially had better survival compared to those who contracted COVID-19 around the time of their hip fracture; however, survival rapidly declined and by 365 days the combination of hip fracture and COVID-19 infection was associated with a 50% mortality rate. Between 1 January and 30 June 2020, 1,273 (99.7% CI 1,077 to 1,465) excess deaths occurred within 90 days of hip fracture, representing an excess mortality of 23% (99.7% CI 20% to 26%), with most deaths occurring within 30 days. Conclusion COVID-19 infection more than doubles the rate of early hip fracture mortality. Those contracting infection between 8 and 30 days after initial presentation are at even higher mortality risk, signalling the potential for targeted interventions during this period to improve survival. Cite this article: Bone Joint J 2022;104-B(10):1156–1167.

Introduction Understanding the effectiveness and durability of protection against SARS-CoV-2 infection conferred by previous infection and COVID-19 is essential to inform ongoing management of the pandemic. This study aims to determine whether prior SARS-CoV-2 infection or COVID-19 vaccination in healthcare workers protects against future infection. Methods and analysis This is a prospective cohort study design in staff members working in hospitals in the UK. At enrolment, participants are allocated into cohorts, positive or naïve, dependent on their prior SARS-CoV-2 infection status, as measured by standardised SARS-CoV-2 antibody testing on all baseline serum samples and previous SARS-CoV-2 test results. Participants undergo monthly antibody testing and fortnightly viral RNA testing during follow-up and based on these results may move between cohorts. Any results from testing undertaken for other reasons (eg, symptoms, contact tracing) or prior to study entry will also be captured. Individuals complete enrolment and fortnightly questionnaires on exposures, symptoms and vaccination. Follow-up is 12 months from study entry, with an option to extend follow-up to 24 months. The primary outcome of interest is infection with SARS-CoV-2 after previous SARS-CoV-2 infection or COVID-19 vaccination during the study period. Secondary outcomes include incidence and prevalence (both RNA and antibody) of SARS-CoV-2, viral genomics, viral culture, symptom history and antibody/neutralising antibody titres. Ethics and dissemination The study was approved by the Berkshire Research Ethics Committee, Health Research Authority (IRAS ID 284460, REC reference 20/SC/0230) on 22 May 2020; the vaccine amendment was approved on 12 January 2021. Participants gave informed consent before taking part in the study. Regular reports to national and international expert advisory groups and peer-reviewed publications ensure timely dissemination of findings to inform decision making. Trial registration number NCT11041050.

ObjectiveIn September 2020, records of 15,861 SARS-CoV-2 cases failed to upload from the Second Generation Laboratory Surveillance System (SGSS) to the Contact Tracing Advisory Service (CTAS) tool, resulting in a delay in the contact tracing of these cases. This study used CTAS data to determine the impact of this delay on health outcomes: transmission events, hospitalisations, and mortality. Previously, a modelling study had suggested a substantial impact.DesignObservational studySettingEngland.PopulationIndividuals testing positive for SARS-CoV-2 and their reported contacts.Main outcome measuresSecondary attack rates (SARs), hospitalisations, and deaths amongst primary and secondary contacts were calculated, compared to all other concurrent, unaffected cases. SGSS records affected by the event were matched to CTAS records and successive contacts and cases were identified.ResultsThe initiation of contact tracing was delayed by 3 days on average in the primary cases in the delay group (6 days) compared to the control group (3 days). This was associated with lower completion of contact tracing of primary cases in the delay group: 80% (95%CI: 79-81%) in the delay group and 83% (95%CI: 83-84%) in the control group. There was some evidence to suggest an increase in transmission to non-household contacts amongst those affected by the delay. The SAR for non-household contacts was higher amongst secondary contacts in the delay group than the control group (delay group: 7.9%, 95%CI:6.4% to 9.2%; control group: 5.9%, 95%CI: 5.3% to 6.6%). There was no evidence of a difference between the delay and control groups in the odds of hospitalisation (crude odds ratio: 1.1 (95%CI: 0.9 to 1.2) or death (crude odds ratio: 0.7 (0.1 to 4.0)) amongst secondary contacts.ConclusionsThe delay in contact tracing had a limited impact on population health outcomes.Strengths and limitations of the studyShows empirical data on the health impact of an event leading to a delay in contact tracing so can test hypotheses generated by models of the potential impact of a delay in contact tracingEstimates the extent of further transmission and odds of increased mortality or hospitalisation in up to the third generation of cases affected by the eventThe event acts as a natural experiment to describe the possible impact of contact tracing, comparing a group affected by chance by delayed contact tracing to a control group who experienced no delayContact tracing was not completed for all individuals, so the study might not capture all affected contacts or transmissions

Background Increased understanding of whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection is an urgent requirement. We aimed to investigate whether antibodies against SARS-CoV-2 were associated with a decreased risk of symptomatic and asymptomatic reinfection. Methods A large, multicentre, prospective cohort study was done, with participants recruited from publicly funded hospitals in all regions of England. All health-care workers, support staff, and administrative staff working at hospitals who could remain engaged in follow-up for 12 months were eligible to join The SARS-CoV-2 Immunity and Reinfection Evaluation study. Participants were excluded if they had no PCR tests after enrolment, enrolled after Dec 31, 2020, or had insufficient PCR and antibody data for cohort assignment. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2–4 weeks) and completed questionnaires every 2 weeks on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive, or previous positive PCR or antibody test) or negative cohort (antibody negative, no previous positive PCR or antibody test). The primary outcome was a reinfection in the positive cohort or a primary infection in the negative cohort, determined by PCR tests. Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, or possible) and symptom-status, depending on the hierarchy of evidence. Primary infections in the negative cohort were defined as a first positive PCR test and seroconversions were excluded when not associated with a positive PCR test. A proportional hazards frailty model using a Poisson distribution was used to estimate incidence rate ratios (IRR) to compare infection rates in the two cohorts. Findings From June 18, 2020, to Dec 31, 2020, 30 625 participants were enrolled into the study. 51 participants withdrew from the study, 4913 were excluded, and 25 661 participants (with linked data on antibody and PCR testing) were included in the analysis. Data were extracted from all sources on Feb 5, 2021, and include data up to and including Jan 11, 2021. 155 infections were detected in the baseline positive cohort of 8278 participants, collectively contributing 2 047 113 person-days of follow-up. This compares with 1704 new PCR positive infections in the negative cohort of 17 383 participants, contributing 2 971 436 person-days of follow-up. The incidence density was 7·6 reinfections per 100 000 person-days in the positive cohort, compared with 57·3 primary infections per 100 000 person-days in the negative cohort, between June, 2020, and January, 2021. The adjusted IRR was 0·159 for all reinfections (95% CI 0·13–0·19) compared with PCR-confirmed primary infections. The median interval between primary infection and reinfection was more than 200 days. Interpretation A previous history of SARS-CoV-2 infection was associated with an 84% lower risk of infection, with median protective effect observed 7 months following primary infection. This time period is the minimum probable effect because seroconversions were not included. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals. Funding Department of Health and Social Care of the UK Government, Public Health England, The National Institute for Health Research, with contributions from the Scottish, Welsh and Northern Irish governments.

Background UK asymptomatic contacts of confirmed COVID-19 cases are not routinely tested for SARS-CoV-2. Testing contacts may improve case ascertainment and reduce onward transmission. This study investigated the acceptability of SARS-CoV-2 testing among contacts of confirmed cases as an integral part of the contact-tracing process. Methods A cross-sectional descriptive survey of case contacts was conducted in the UK. All contacts who completed a telephone call with the NHS Test and Trace Agile Lighthouse team were eligible for inclusion and were offered a molecular test. Consenting participants were sent a self-swab kit. Results Of the 1523 individuals contacted, 602 (39.5%) accepted the test offer. Of the 240 (39.9%) samples returned for testing, 16.3% tested polymerase chain reaction-positive for SARS-CoV-2. Most individuals who declined with a reason (638/905; 70.5%) reported they had already taken or booked a SARS-CoV-2 test, or were part of a testing programme. Matched laboratory records confirmed 73.1% of those who declined were tested by another route. Conclusions Most case contacts were tested, either through arranging a test by themselves or by accepting the study offer. Results demonstrate high acceptability, with substantial test positivity, indicating that there is public health benefit in offering tests to contacts as a routine part of the contact-tracing process.

Background Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks. Methods An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid (‘intervention’) or a daily combination of rifampicin/isoniazid (‘standard’), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded. Results Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7–91.4), compared with 19 of 25 (76.0%, CI 54.9–90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms. Conclusion In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment. Trial registration The trial was funded by the NIHR, UK and registered with ISRCTN (26/02/2013-No.04379941).

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.

Results from monitoring of the microbiological quality of 2,721 samples of ready-to-eat cooked chicken collected between 2013 to 2017 in England were reviewed: 70% of samples were from retail, catering or manufacture and 30% were imported and collected at English ports. Samples were tested for a range of bacterial pathogens and indicator organisms. Six samples (

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.

Background Public health surveillance requires historical baselines to identify unusual activity. However, these baselines require adjustment after public health interventions. We describe an example of such an adjustment after the introduction of rotavirus vaccine in England in July 2013. Methods We retrospectively measured the magnitude of differences between baselines and observed counts (residuals) before and after the introduction of a public health intervention, the introduction of a rotavirus vaccine in July 2013. We considered gastroenteritis, diarrhea, and vomiting to be indicators for national syndromic surveillance, including telephone calls to a telehealth system, emergency department visits, and unscheduled consultations with general practitioners. The start of the preintervention period varied depending on the availability of surveillance data: June 2005 for telehealth, November 2009 for emergency departments, and July 2010 for general practitioner data. The postintervention period was July 2013 to the second quarter of 2016. We then determined whether baselines incorporating a step-change reduction or a change in seasonality resulted in more accurate models of activity. Results Residuals in the unadjusted baseline models increased by 42%-198% from preintervention to postintervention. Increases in residuals for vomiting indicators were 19%-44% higher than for diarrhea. Both step-change and seasonality adjustments improved the surveillance models; we found the greatest reduction in residuals in seasonally adjusted models (4%-75%). Conclusion Our results demonstrated the importance of adjusting surveillance baselines after public health interventions, particularly accounting for changes in seasonality. Adjusted baselines produced more representative expected values than did unadjusted baselines, resulting in fewer false alarms and a greater likelihood of detecting public health threats.

Background: \ud 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.\ud \ud Methods: \ud 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.\ud \ud Findings: \ud 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.\ud \ud Interpretation: \ud 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.\ud \ud Funding: \ud Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

We investigated risk factors associated with COVID-19 by conducting a retrospective, frequency-matched case-control study, with three sampling periods (August–October 2020). We compared cases completing routine contact tracing to asymptomatic population controls. Multivariable analyses estimated adjusted odds ratios (aORs) for non-household community settings. Meta-analyses using random effects provided pooled odds ratios (pORs). Working in healthcare (pOR 2.87; aORs 2.72, 2.81, 3.08, for study periods 1–3 respectively), social care (pOR 4.15; aORs 2.46, 5.06, 5.41, for study periods 1–3 respectively) or hospitality (pOR 2.36; aORs 2.01, 2.54, 2.63, for study periods 1–3 respectively) were associated with increased odds of being a COVID-19 case. Additionally, working in bars, pubs and restaurants, warehouse settings, construction, educational settings were significantly associated. While definitively determining where transmission occurs is impossible, we provide evidence that in certain sectors, the impact of mitigation measures may only be partial and reinforcement of measures should be considered in these settings.

On 26th November 2021, a novel SARS-CoV-2 variant B.1.1.529 (Omicron variant) was designated as a variant of concern by the World Health Organisation. Using data from the Virology laboratory at the Manchester Medical Microbiology Partnership (MMMP, a partnership between UKHSA and the Manchester Foundation Trust), we have extracted a real-time feed of Omicron samples from hospitals across Greater Manchester, an area of the United Kingdom with a population size of approximately three million individuals. Omicron hospital samples are growing exponentially across Greater Manchester (doubling time 2.7 days (95% CI: 2.1, 3.7)). The proportion of Omicron in hospital samples follows a similar trajectory to the SGTF proportion in cases, but with a two-day offset. This is consistent with the delay from testing positive to hospital admission, implying a similar proportion of Omicron cases are converting to hospital admissions as for Delta cases. Comparing the Greater Manchester data to national hospitalisation data, similar tends are observed. Therefore, there is no signal of a substantial reduction in hospital admission risk with Omicron, and Omicron epidemics are likely to place a substantial burden on public health infrastructure.

Summary Background BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been rapidly rolled out in the UK from December, 2020. We aimed to determine the factors associated with vaccine coverage for both vaccines and documented the vaccine effectiveness of the BNT162b2 mRNA vaccine in a cohort of health-care workers undergoing regular asymptomatic testing. Methods The SIREN study is a prospective cohort study among staff (aged ≥18 years) working in publicly-funded hospitals in the UK. Participants were assigned into either the positive cohort (antibody positive or history of infection [indicated by previous positivity of antibody or PCR tests]) or the negative cohort (antibody negative with no previous positive test) at the beginning of the follow-up period. Baseline risk factors were collected at enrolment, symptom status was collected every 2 weeks, and vaccination status was collected through linkage to the National Immunisations Management System and questionnaires. Participants had fortnightly asymptomatic SARS-CoV-2 PCR testing and monthly antibody testing, and all tests (including symptomatic testing) outside SIREN were captured. Data cutoff for this analysis was Feb 5, 2021. The follow-up period was Dec 7, 2020, to Feb 5, 2021. The primary outcomes were vaccinated participants (binary ever vacinated variable; indicated by at least one vaccine dose recorded by at least one of the two vaccination data sources) for the vaccine coverage analysis and SARS-CoV-2 infection confirmed by a PCR test for the vaccine effectiveness analysis. We did a mixed-effect logistic regression analysis to identify factors associated with vaccine coverage. We used a piecewise exponential hazard mixed-effects model (shared frailty-type model) using a Poisson distribution to calculate hazard ratios to compare time-to-infection in unvaccinated and vaccinated participants and estimate the impact of the BNT162b2 vaccine on all PCR-positive infections (asymptomatic and symptomatic). This study is registered with ISRCTN, number ISRCTN11041050, and is ongoing. Findings 23 324 participants from 104 sites (all in England) met the inclusion criteria for this analysis and were enrolled. Included participants had a median age of 46·1 years (IQR 36·0–54·1) and 19 692 (84%) were female; 8203 (35%) were assigned to the positive cohort at the start of the analysis period, and 15 121 (65%) assigned to the negative cohort. Total follow-up time was 2 calendar months and 1 106 905 person-days (396 318 vaccinated and 710 587 unvaccinated). Vaccine coverage was 89% on Feb 5, 2021, 94% of whom had BNT162b2 vaccine. Significantly lower coverage was associated with previous infection, gender, age, ethnicity, job role, and Index of Multiple Deprivation score. During follow-up, there were 977 new infections in the unvaccinated cohort, an incidence density of 14 infections per 10 000 person-days; the vaccinated cohort had 71 new infections 21 days or more after their first dose (incidence density of eight infections per 10 000 person-days) and nine infections 7 days after the second dose (incidence density four infections per 10 000 person-days). In the unvaccinated cohort, 543 (56%) participants had typical COVID-19 symptoms and 140 (14%) were asymptomatic on or 14 days before their PCR positive test date, compared with 29 (36%) with typical COVID-19 symptoms and 15 (19%) asymptomatic in the vaccinated cohort. A single dose of BNT162b2 vaccine showed vaccine effectiveness of 70% (95% CI 55–85) 21 days after first dose and 85% (74–96) 7 days after two doses in the study population. Interpretation Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort was vaccinated when the dominant variant in circulation was B1.1.7 and shows effectiveness against this variant. Funding Public Health England, UK Department of Health and Social Care, and the National Institute for Health Research.

BackgroundThis study measured the long-term health-related quality of life of non-hospitalised COVID-19 cases with PCR-confirmed SARS-CoV-2(+) infection using the recommended instrument in England (the EQ-5D).MethodsProspective cohort study of SARS-CoV-2(+) cases aged 12-85 years and followed up for six months from 01 December 2020, with cross-sectional comparison to SARS-CoV-2(-) controls. Main outcomes were loss of quality-adjusted life days (QALDs); physical symptoms; and COVID-19-related private expenditures. We analysed results using multivariable regressions with post-hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls.ResultsOf 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on non-prescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 15.9 (95%-CI: 12.1, 19.7) QALDs, while those reporting symptoms at month 6 lost 34.1 (29.0, 39.2) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 21% of the total COVID-19-related disease burden in England.ConclusionsOne in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms.summaryLosses of health-related quality of life in non-hospitalised COVID-19 cases increase by age and for cases with symptoms after 6 months. At a population level, at least 21% of the total COVID-19-related disease burden in England is attributable to morbidity.

Background The SARS-CoV-2 delta (B.1.617.2) variant is highly transmissible and spreading globally, including in populations with high vaccination rates. We aimed to investigate transmission and viral load kinetics in vaccinated and unvaccinated individuals with mild delta variant infection in the community. Methods Between Sept 13, 2020, and Sept 15, 2021, 602 community contacts (identified via the UK contract-tracing system) of 471 UK COVID-19 index cases were recruited to the Assessment of Transmission and Contagiousness of COVID-19 in Contacts cohort study and contributed 8145 upper respiratory tract samples from daily sampling for up to 20 days. Household and non-household exposed contacts aged 5 years or older were eligible for recruitment if they could provide informed consent and agree to self-swabbing of the upper respiratory tract. We analysed transmission risk by vaccination status for 231 contacts exposed to 162 epidemiologically linked delta variant-infected index cases. We compared viral load trajectories from fully vaccinated individuals with delta infection (n=29) with unvaccinated individuals with delta (n=16), alpha (B.1.1.7; n=39), and pre-alpha (n=49) infections. Primary outcomes for the epidemiological analysis were to assess the secondary attack rate (SAR) in household contacts stratified by contact vaccination status and the index cases’ vaccination status. Primary outcomes for the viral load kinetics analysis were to detect differences in the peak viral load, viral growth rate, and viral decline rate between participants according to SARS-CoV-2 variant and vaccination status. Findings The SAR in household contacts exposed to the delta variant was 25% (95% CI 18–33) for fully vaccinated individuals compared with 38% (24–53) in unvaccinated individuals. The median time between second vaccine dose and study recruitment in fully vaccinated contacts was longer for infected individuals (median 101 days [IQR 74–120]) than for uninfected individuals (64 days [32–97], p=0·001). SAR among household contacts exposed to fully vaccinated index cases was similar to household contacts exposed to unvaccinated index cases (25% [95% CI 15–35] for vaccinated vs 23% [15–31] for unvaccinated). 12 (39%) of 31 infections in fully vaccinated household contacts arose from fully vaccinated epidemiologically linked index cases, further confirmed by genomic and virological analysis in three index case–contact pairs. Although peak viral load did not differ by vaccination status or variant type, it increased modestly with age (difference of 0·39 [95% credible interval –0·03 to 0·79] in peak log10 viral load per mL between those aged 10 years and 50 years). Fully vaccinated individuals with delta variant infection had a faster (posterior probability >0·84) mean rate of viral load decline (0·95 log10 copies per mL per day) than did unvaccinated individuals with pre-alpha (0·69), alpha (0·82), or delta (0·79) variant infections. Within individuals, faster viral load growth was correlated with higher peak viral load (correlation 0·42 [95% credible interval 0·13 to 0·65]) and slower decline (–0·44 [–0·67 to –0·18]). Interpretation Vaccination reduces the risk of delta variant infection and accelerates viral clearance. Nonetheless, fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts. Host–virus interactions early in infection may shape the entire viral trajectory. Funding National Institute for Health Research.