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1.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21267408

RESUMO

Adolescents in the UK were recommended to have their first dose of mRNA vaccine during a period of high community transmission due to the highly transmissible Delta variant, followed by a second dose at an extended interval of 8-12 weeks. We used national SARS-CoV-2 testing, vaccination and hospitalisation data to estimate vaccine effectiveness (VE) using a test-negative case-control design, against PCR-confirmed symptomatic COVID-19 in England. BNT162b2 vaccination in 12-15-year-olds and 16-17-year-olds was associated with lower VE against symptomatic COVID-19 caused by Omicron compared to Delta. Data shows a rapid increase in VE against symptomatic COVID-19 after the second dose for both Delta and Omicron, although this declines to 23% against Omicron after 70+ days. Very high protection was achieved for Delta against hospitalisation after one dose. Our data highlight the importance of the second vaccine dose for protection against symptomatic COVID-19 and raise important questions about the objectives of an adolescent immunisation programme. If prevention of infection is the primary aim, then regular COVID-19 vaccine boosters will be required.

2.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21255275

RESUMO

SARS-CoV-2 infection is generally mild or asymptomatic in children but the biological basis for this is unclear. We studied the profile of antibody and cellular immunity in children aged 3-11 years in comparison with adults. Antibody responses against spike and receptor binding domain (RBD) were high in children and seroconversion boosted antibody responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Seroneutralisation assays against alpha, beta and delta SARS-CoV-2 variants demonstrated comparable neutralising activity between children and adults. T cell responses against spike were >2-fold higher in children compared to adults and displayed a TH1 cytokine profile. SARS-CoV-2 spike-specific T cells were also detected in many seronegative children, revealing pre-existing responses that were cross-reactive with seasonal Alpha and Beta-coronaviruses. Importantly, all children retained high antibody titres and cellular responses at 6 months after infection whilst relative antibody waning was seen in adults. Spike-specific responses in children also remained broadly stable beyond 12 months. Children thus distinctly generate robust, cross-reactive and sustained immune responses after SARS-CoV-2 infection with focussed specificity against spike protein. These observations demonstrate novel features of SARS-CoV-2-specific immune responses in children and may provide insight into their relative clinical protection. Furthermore, this information will help to guide the introduction of vaccination regimens in the paediatric population.

3.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20178574

RESUMO

BackgroundThere are limited data on SARS-CoV-2 infection and transmission in educational settings. This information is critical for policy makers and practitioners to ensure the safety of staff, students and the wider community during the COVID-19 pandemic. MethodsPublic Health England initiated enhanced national surveillance following the reopening of educational settings during the summer mini-term on 01 June 2020. COVID-19 related situations in educational settings across England were reviewed daily and followed-up until 31 July 2020. SARS-CoV-2 infection and outbreak rates were calculated for staff and students attending early year settings, primary and secondary schools during June 2020. FindingsThere were 67 single confirmed cases, 4 co-primary cases and 30 COVID-19 outbreaks during June 2020, with a strong correlation between number of outbreaks and regional COVID-19 incidence (0.51 outbreaks for each SARS-CoV-2 infection per 100,000 in the community; p=0.001). Overall, SARS-CoV-2 infections and outbreaks were uncommon across all educational settings. Staff members had an increased risk of SARS-CoV-2 infections compared to students in any educational setting, and the majority of cases linked to outbreaks were in staff. The probable transmission direction for the 30 confirmed outbreaks was: staff-to-staff (n=15), staff-to-student (n=7), student-to-staff (n=6) and student-to-student (n=2). InterpretationSARS-CoV-2 infections and outbreaks were uncommon in educational settings during the first month after the easing of national lockdown in England. The strong correlation with regional SARS-CoV-2 incidence emphasises the importance of controlling community transmission to protect educational settings. Additional interventions should focus on reducing transmission in and among staff members. Fundingnone

4.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20177188

RESUMO

BackgroundHouseholds appear to be the highest risk setting for transmission of COVID-19. Large household transmission studies were reported in the early stages of the pandemic in Asia with secondary attack rates ranging from 5-30% but few large scale household transmission studies have been conducted outside of Asia. MethodsA prospective case ascertained study design based on the World Health Organization FFX protocol was undertaken in the UK following the detection of the first case in late January 2020. Household contacts of cases were followed using enhanced surveillance forms to establish whether they developed symptoms of COVID-19, became confirmed cases and their outcomes. Household secondary attack rates and serial intervals were estimated. Individual and household basic reproduction numbers were also estimated. The incubation period was estimated using known point source exposures that resulted in secondary cases. ResultsA total of 233 households with two or more people were included with a total of 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. We find lower secondary attack rates in larger households. SARs were highest when the primary case was a child. We estimate a mean incubation period of around 4.5 days. ConclusionsHigh rates of household transmission of COVID-19 were found in the UK emphasising the need for preventative measures in this setting. Careful monitoring of schools reopening is needed to monitor transmission from children.

5.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20086157

RESUMO

ObjectivesFollowing detection of the first virologically-confirmed cases of COVID-19 in Great Britain, an enhanced surveillance study was initiated by Public Health England to describe the clinical presentation, course of disease and underlying health conditions associated with infection of the first few hundred cases. MethodsInformation was collected on the first COVID-19 cases according to the First Few X WHO protocol. Case-control analyses of the sensitivity, specificity and predictive value of symptoms and underlying health conditions associated with infection were conducted. Point prevalences of underlying health conditions among the UK general population were presented. FindingsThe majority of FF100 cases were imported (51.4%), of which the majority had recent travel to Italy (71.4%). 24.7% were secondary cases acquired mainly through household contact (40.4%). Children had lower odds of COVID-19 infection compared with the general population. The clinical presentation of cases was dominated by cough, fever and fatigue. Non-linear relationships with age were observed for fever, and sensitivity and specificity of symptoms varied by age. Conditions associated with higher odds of COVID-19 infection (after adjusting for age and sex) were chronic heart disease, immunosuppression and multimorbidity. ConclusionThis study presents the first epidemiological and clinical summary of COVID-19 cases in Great Britain. The FFX study design enabled systematic data collection. The study characterized underlying health conditions associated with infection and set relative risks in context with population prevalence estimates. It also provides important evidence for generating case definitions to support public health risk assessment, clinical triage and diagnostic algorithms.

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