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...

IntroductionThe United Kingdom is in the fourth season of introducing a universal childhood influenza vaccine programme. The 2016/17 season saw early influenza A(H3N2) virus circulation with care home outbreaks and increased excess mortality particularly in those 65 years or older. Virus characterisation data indicated emergence of genetic clusters within the A(H3N2) 3C.2a group which the 2016/17 vaccine strain belonged to. Methods: The test-negative case–control (TNCC) design was used to estimate vaccine effectiveness (VE) against laboratory confirmed influenza in primary care. Results: Adjusted end-of-season vaccine effectiveness (aVE) estimates were 39.8% (95% confidence interval (CI): 23.1 to 52.8) against all influenza and 40.6% (95% CI: 19.0 to 56.3) in 18–64-year-olds, but no significant aVE in ≥ 65-year-olds. aVE was 65.8% (95% CI: 30.3 to 83.2) for 2–17-year-olds receiving quadrivalent live attenuated influenza vaccine. Discussion: The findings continue to provide support for the ongoing roll-out of the paediatric vaccine programme, with a need for ongoing evaluation. The importance of effective interventions to protect the ≥ 65-year-olds remains.

Background In the United Kingdom (UK), in recent influenza seasons, children are offered a quadrivalent live attenuated influenza vaccine (LAIV4), and eligible adults mainly trivalent inactivated vaccine (TIV). Aim To estimate the UK end-of-season 2017/18 adjusted vaccine effectiveness (aVE) and the seroprevalence in England of antibodies against influenza viruses cultured in eggs or tissue. Methods This observational study employed the test-negative case–control approach to estimate aVE in primary care. The population-based seroprevalence survey used residual age-stratified samples. Results Influenza viruses A(H3N2) (particularly subgroup 3C.2a2) and B (mainly B/Yamagata/16/88-lineage, similar to the quadrivalent vaccine B-virus component but mismatched to TIV) dominated. All-age aVE was 15% (95% confidence interval (CI): −6.3 to 32) against all influenza; −16.4% (95% CI: −59.3 to 14.9) against A(H3N2); 24.7% (95% CI: 1.1 to 42.7) against B and 66.3% (95% CI: 33.4 to 82.9) against A(H1N1)pdm09. For 2–17 year olds, LAIV4 aVE was 26.9% (95% CI: −32.6 to 59.7) against all influenza; −75.5% (95% CI: −289.6 to 21) against A(H3N2); 60.8% (95% CI: 8.2 to 83.3) against B and 90.3% (95% CI: 16.4 to 98.9) against A(H1N1)pdm09. For ≥ 18 year olds, TIV aVE against influenza B was 1.9% (95% CI: −63.6 to 41.2). The 2017 seroprevalence of antibody recognising tissue-grown A(H3N2) virus was significantly lower than that recognising egg-grown virus in all groups except 15–24 year olds. Conclusions Overall aVE was low driven by no effectiveness against A(H3N2) possibly related to vaccine virus egg-adaption and a new A(H3N2) subgroup emergence. The TIV was not effective against influenza B. LAIV4 against influenza B and A(H1N1)pdm09 was effective.

BackgroundIn 2016/17, seasonal influenza vaccine was less effective in those aged 65 years and older in the United Kingdom. We describe the uptake, influenza-associated mortality and adjusted vaccine effectiveness (aVE) in this age group over influenza seasons 2010/11–2016/17. Methods: Vaccine uptake in 2016/17 and five previous seasons were measured using a sentinel general practitioners cohort in England; the test-negative case-control design was used to estimate pooled aVE by subtype and age group against laboratory-confirmed influenza in primary care from 2010–2017. Results: Vaccine uptake was 64% in 65–69-year-olds, 74% in 70–74-year-olds and 80% in those aged 75 and older. Overall aVE was 32.5% (95% CI: 11.6 to 48.5); aVE by sub-type was 60.8% (95% CI: 33.9 to 76.7) and 50.0% (95% CI: 21.6 to 68.1) against influenza A(H1N1)pdm09 and influenza B, respectively, but only 5.6% (95% CI: - 39.2 to 35.9) against A(H3N2). Against all laboratory-confirmed influenza aVE was 45.2% (95% CI: 25.1 to 60.0) in 65–74 year olds; - 26.2% (95% CI: - 149.3 to 36.0) in 75–84 year olds and - 3.2% (95% CI: - 237.8 to 68.5) in those aged 85 years and older. Influenza-attributable mortality was highest in seasons dominated by A(H3N2). Conclusions: Vaccine uptake with non-adjuvanted, normal-dose vaccines remained high, with evidence of effectiveness against influenza A(H1N1)pdm09 and B, though poor against A(H3N2), particularly in those aged 75 years and older. Forthcoming availability of newly licensed vaccines with wider use of antivirals can potentially further improve prevention and control of influenza in this group.