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 histo...

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. MethodsThe 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 infecti...

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 and TSC2 genes on chromosomes 9 and 16 respectively. Diagnosis is based on clinical features but can be difficult as a result of variable phenotypic expression. With the advantage of mutation analysis in making a diagnosis of TSC, and improved identification of the associated clinical features, there have been few new data on its prevalence and on the proportion of cases due to new mutations. We have performed a retrospective epidemiological study on the prevalence of TSC, the clinical features attributed to it, and the availability of mutational analysis. We identified 73 known patients with TSC (5 deceased): 39 were female and 34 male. Ages ranged from 10 months to 69 years, with a mean age of 27 years 11 months (SD 16y 10mo). The point prevalence of TSC in our study was estimated at 1 out of 24 956 on the prevalence day (30 April 2004). The majority of patients (42.5%) were diagnosed at less than 15 months of age; 25% were not given a diagnosis on first developing symptoms. In all, 93.2% had epilepsy and 71.2% had a learning disability.* A mutation was identified in 95.8% of those tested (26% TSC1 and 74% TSC2). TSC2 mutations were correlated with a more severe phenotype. The new mutation rate was calculated at 64%. We conclude that the prevalence of TSC is higher than previously calculated. We recommend that all children with epilepsy be assessed for features of TSC. Larger studies will be required to assess the prevalence of mutations in each gene, and genotype-phenotype correlation.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 and TSC2 genes on chromosomes 9 and 16 respectively. Diagnosis is based on clinical features but can be difficult as a result of variable phenotypic expression. With the advantage of mutation analysis in making a diagnosis of TSC, and improved identification of the associated clinical features, there have been few new data on its prevalence and on the proportion of cases due to new mutations. We have performed a retrospective epidemiological study on the prevalence of TSC, the clinical features attributed to it, and the availability of mutational analysis. We identified 73 known patients with TSC (5 deceased): 39 were female and 34 male. Ages ranged from 10 months to 69 years, with a mean age of 27 years 11 months (SD 16y 10mo). The point prevalence of TSC in our study was estimated at 1 out of 24 956 on the prevalence day (30 April 2004). The majority of patients (42.5%) were diagnosed at less than 15 months of age; 25% were not given a diagnosis on first developing symptoms. In all, 93.2% had epilepsy and 71.2% had a learning disability. A mutation was identified in 95.8% of those tested (26% TSC1 and 74% TSC2). TSC2 mutations were correlated with a more severe phenotype. The new mutation rate was calculated at 64%. We conclude that the prevalence of TSC is higher than previously calculated. We recommend that all children with epilepsy be assessed for features of TSC. Larger studies will be required to assess the prevalence of mutations in each gene, and genotype-phenotype correlation.

Operation CROSSROADS, conducted at Bikini Atoll in 1946, was the first post World War II test of nuclear weapons. Mortality experience of 40,000 military veteran participants in CROSSROADS was compared to that of a similar cohort of nonparticipating veterans. All-cause mortality of the participants was slightly increased over nonparticipants by 5% (p < .001). Smaller increases in participant mortality for all malignancies (1.4%, p = 0.26) or leukemia (2.0%, p = 0.9) were not statistically significant. These results do not support a hypothesis that radiation had increased participant cancer mortality over that of nonparticipants.