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.
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.
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.
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.
Public Health England, UK Department of Health and Social Care, and the National Institute for Health Research.
Objective
Molecular subtyping of non‐small cell lung cancer (NSCLC) is critical in the diagnostic evaluation of patients with advanced disease. This study aimed to examine whether samples from ...endobronchial ultrasound transbronchial needle aspiration (EBUS‐TBNA) of intrathoracic lymph nodes and/or lung lesions are adequate for molecular analysis across various institutions.
Methods
We retrospectively reviewed all cases of linear EBUS‐TBNA with a final bronchoscopic diagnosis of NSCLC entered in the Stather Canadian Outcomes registry for chest ProcEdures database. The primary outcome was specimen inadequacy rate for each molecular target, as defined by the local laboratory or pathologist.
Results
A total of 866 EBUS‐TBNA procedures for NSCLC were identified. Specimen inadequacy rates were 3.8% for EGFR, 2.5% for ALK‐1 and 3.5% for PD‐L1. Largest target size was not different between adequate and inadequate specimens, and rapid onsite evaluation did not increase specimen adequacy rates. One centre using next‐generation sequencing for EGFR had lower adequacy rates than 2 others using matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrophotometry.
Conclusion
EBUS‐TBNA specimens have a very low‐specimen inadequacy rate for molecular subtyping of non‐small cell lung cancer.
EBUS‐TBNA is often the first test to diagnose non‐small cell lung cancer. Molecular subtyping is needed to optimize treatment for advanced stage disease. Our large multicentre registry demonstrates that real‐world EBUS‐TBNA specimens have a very low‐specimen inadequacy rate for molecular subtyping.
A 61‐year‐old male with a history of coeliac disease was diagnosed with organizing pneumonia (OP) on transbronchial and transthoracic lung biopsies. He then developed refractory coeliac disease type ...II and haemophagocytic lymphohistiocytosis. Nine months after his initial diagnosis of OP and after multiple biopsies of the lung, duodenum, and bone marrow, he was diagnosed with enteropathy‐associated T‐cell lymphoma (EATL). Although OP in patients with lymphoma is most commonly attributed to chemotherapeutic agents or bone marrow transplant, it may be seen in the absence of prior anticancer treatment. The mechanism linking OP and lymphoma is unclear but OP could represent a syndrome of T‐cell dysfunction or develop as a direct reaction to malignant infiltration of the lung. In patients with atypical presentations, exclusion of an alternate diagnosis must be pursued using surgical lung biopsy, wherever possible. This is the first reported case of OP associated with EATL.
We report a rare case of organizing pneumonia (OP) associated with T‐cell lymphoma without prior anticancer therapy. OP could represent a syndrome of T‐cell dysfunction or develop as a direct reaction to malignant infiltration of the lung. In patients with atypical presentations, exclusion of an alternate diagnosis must be pursued using surgical lung biopsy, wherever possible.
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.
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.
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.
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.
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.
The idea of alternate stable states (ASS) has been used to explain the juxtaposition of distinct vegetation types within the same climate regime. ASS may explain the co‐existence of relatively ...inflammable closed‐canopy Afrotemperate forest patches (‘Forest’) within fire‐prone open‐canopy Fynbos in the Cape Floristic Region (CFR) on sandstone‐derived soils. We evaluated the hypothesis that although fire and local topography and hydrology likely determined the paleogeographic boundaries of Forest, present‐day boundaries are additionally imposed by emergent edaphic properties and disturbance histories. We studied vegetation and edaphic properties of Forest‐Transition‐Fynbos vegetation at two sites within the CFR on sandstone‐derived soils and tracked historical change using aerial photography. Whereas Forest and Fynbos have changed little in extent or density since 1945, transition vegetation increased into areas formerly occupied by Fynbos. Forest soils were ubiquitously more nutrient‐rich than Fynbos soils, with transition soils being intermediate. These edaphic differences are not due to geological differences, but instead appear to have emerged as a consequence of different nutrient cycling within the different ecosystems. Soil nutrients are now so different that a switch from Fynbos to Forest is unlikely, in the short term (i.e. decades). Floristically and nutritionally, transitional vegetation is more similar to Fynbos than Forest and may be less resilient to changes in exogenous drivers (e.g. fire). Our findings are consistent with the idea that geologically Forest and Fynbos are largely fire‐derived long‐term ASS, with the stability of each state reinforced by marked soil nutrient differences. In contrast, the intermediate transitional vegetation that might switch states is unlikely to be stable.
Abstract
For effective fishery management, estimated stock sizes, along with their uncertainties, should be accurate, precise, and unbiased. Atlantic salmon Salmo salar stock assessment in England ...and Wales (and elsewhere across the Atlantic) estimate returning salmon stocks by applying a measure of rod exploitation rate (RER), derived from less abundant fishery-independent stock estimates, to abundant fishery-dependent data. Currently, RER estimates are generated for individual principal salmon rivers based on available local data and assumptions. We propose a single, consistent, transparent, and statistically robust method to estimate salmon stocks that transfers strength of information from “data-rich” rivers, i.e. those with fisheries-independent data, to “data-poor” rivers without such data. We proposed, fitted, simplified, and then validated a Beta–Binomial model of RER, including covariates representing angler and fish behaviours, river flow, and random effects to control for nuisance effects. Our “best” model revealed covariate effects in line with our hypotheses and generalized to data not used to train it. We used this model to extrapolate stock estimates from 12 data-rich to 52 data-poor rivers, together with their uncertainties. The resulting river-specific salmon stock estimates were judged to be useful and can be used as key inputs to river-specific, national, and international salmon stock assessments.
Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were ...lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6–14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.
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•BNT162b2 vaccine with an extended interval between doses is highly protective•Antibody levels were higher after the extended regimen compared with the short regimen•The extended regimen enriches for virus-specific CD4+ T cells expressing IL-2•Antibody levels wane after each dose, but B and T cell pools are maintained
After giving a primary dose, delaying administration of a second dose of BNT162b2 COVID-19 vaccine up to 6–14 weeks continues to provide strong protection and contributes to favorable antibody, B cell, and T cell responses.
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