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...

Pioneering studies have revealed the presence of endogenous microRNAs (miRNAs) in the circulation that are not cell-associated. 1 The cellular origin and the biological function of circulating miRNAs, however, are less clear. Editorial, see p 576We have previously quantified circulating miRNAs in a large population-based cohort, the Bruneck study.3,4 Using concepts of network topology, 5 we identified altered miRNA signatures in patients with type 2 diabetes mellitus 3 and with future myocardial infarction. 4 In addition, we subjected healthy volunteers to limb ischemia-reperfusion generated by thigh cuff inflation. 4 Computational analysis identified 6 distinct miRNA clusters. 4 One cluster included all miRNAs associated with risk of myocardial infarction and consisted of miRNAs predominantly expressed in platelets. Microarray screening revealed that miR-126, miR-197, miR-223, miR-24, and miR-21 are among the most highly expressed miRNAs in platelets and platelet microparticles (PMPs), and their circulating levels correlated with PMPs as quantified by flow cytometry.Original received November 14, 2012; revision received December 21, 2012; accepted December 28, 2012. In November 2012, the average time from submission to first decision for all original research papers submitted to Circulation Research was 15.8 days.Brief UltraRapid Communications are designed to be a format for manuscripts that are of outstanding interest to the readership, report definitive observations, but have a relatively narrow scope.

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PurposeTo assess the caregiver burden and factors determining the burden in patients receiving ranibizumab therapy for neovascular AMD (nAMD).MethodsThis is a cross-sectional questionnaire survey of 250 matched patient caregiver dyads across three large ophthalmic treatment centres in United Kingdom. The primary outcome was the subjective caregiver burden measured using caregiver reaction assessment scale (CRA). Objective caregiver burden was determined by the caregiver tasks and level of care provided. The factors that may predict the caregiver burden such as the patient’s visual acuity of the better eye and vision related quality of life, demographics, satisfaction and support provided by the healthcare and the health status of the dyads were also collected and assessed in a hierarchical regression model.ResultsThe mean CRA score was 3.2±0.5, similar to the score reported by caregivers for atrial fibrillation who require regular hospital appointments for monitoring their thromboprophylaxis. Caregiver tasks including accompanying for hospital appointments for eye treatment and patient’s visual acuity in the better eye were the biggest contributors to the caregiver burden hierarchical model explaining 18% and 11% of the variance respectively.ConclusionRanibizumab therapy for nAMD is associated with significant caregiver burden. Both disease impact and treatment frequency contributed to the overall burden.

OBJECTIVERecent studies have shown an increased risk for cognitive impairment and dementia in patients with diabetes. An association between diabetic retinopathy (DR) and retinal microvasculature disease and cognitive impairment has been reported as potential evidence for a microvascular component to the cognitive impairment. It was hypothesized that severity of DR would be associated with cognitive impairment in individuals with type 2 diabetes.RESEARCH DESIGN AND METHODSThree hundred eighty patients with type 2 diabetes were recruited from a population-based eye screening program and grouped by severity of DR as follows: no/mild DR (n = 252) and proliferative diabetic retinopathy (PDR) (n = 128). Each participant underwent psychosocial assessment; depression screening; ophthalmic and physical examination, including blood assays; and cognitive assessment with the Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini-Mental State Examination (MMSE), and the Mini-Cog. General linear modeling was used to examine severity of DR and cognitive impairment, adjusting for confounders.RESULTSSeverity of DR demonstrated an inverse relationship with cognitive impairment (fully adjusted R2 = 0.415, P < 0.001). Ethnicity contributed most to the variance observed (16%) followed by education (7.3%) and retinopathy status (6.8%). The no/mild DR group had lower cognitive impairment scores on ACE-R (adjusted mean ± SE 77.0 ± 1.9) compared with the PDR group (82.5 ± 2.2, P < 0.001). The MMSE cutoff scores showed that 12% of the no/mild DR group (n = 31) had positive screening results for dementia or significant cognitive impairment compared with 5% in the PDR group (n = 6).CONCLUSIONSPatients with minimal DR demonstrated more cognitive impairment than those with advanced DR. Therefore, the increased prevalence of cognitive impairment in diabetes may be associated with factors other than evident retinal microvascular disease.

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Purpose: To determine whether changes in retinal vascular calibre and geometry are associated with progression of diabetic retinopathy in type 2 diabetes (T2D). Procedures: The retinal vascular calibre and geometry of 30 subjects with more than 20 years of diagnosed T2D with no retinopathy (NR) were compared to 30 subjects that progressed to proliferative diabetic retinopathy (PDR). The images of PDR subjects included in this study were those obtained before the onset of retinopathy. The diameter of retinal arterioles (CRAE), retinal venules (CRVE), tortuosity of retinal vessels, junctional exponent deviation (JE_a) and fractal dimension (D_f) were measured using Singapore I Vessel Assessment (SIVA 3.0) software and compared using Mann-Whitney U test. Results: The median CRAE and the median CRVE were significantly wider in PDR subjects compared to NR subjects (p = 0.014 and 0.016), respectively. Curvature tortuosity of the retinal arteries and veins and D_f were significantly decreased in the PDR subjects compared to NR subjects (p = 0.015, 0.016 and 0.03, respectively). The JE_a was significantly increased in PDR subjects (p = 0.01). Conclusions: Retinal vessel calibre and geometry of the retinal vasculature may be important risk factors for the progression to PDR. More longitudinal prospective studies will be needed to further explore the findings of this study.