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Background: In July 2021, a new variant of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in the Delta lineage was detected in the United Kingdom (UK), named AY.4.2 or "Delta plus". By October 2021, the AY.4.2 variant accounted for approximately 10-11% of cases in the UK. AY.4.2 was designated as a variant under investigation by the UK Health and Security Agency on 20 October 2021. This study aimed to investigate vaccine effectiveness (VE) against symptomatic COVID-19 (Coronavirus disease 2019) infection and COVID-19 hospitalisation/death for the AY.4.2 variant.Methods: We used the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance (EAVE-II) platform to estimate the VE of the ChAdOx1, BNT162b2, and mRNA-1273 vaccines against symptomatic infection and severe COVID-19 outcomes in adults. The study was conducted from June 8 to October 25, 2021. We used a test-negative design (TND) to estimate VE against reverse transcriptase polymerase chain reaction (RT-PCR) confirmed symptomatic SARS-CoV-2 infection while adjusting for sex, socioeconomic status, number of coexisting conditions, and splines in time and age. We also performed a cohort study using a Cox proportional hazards model to estimate VE against a composite outcome of COVID-19 hospital admission or death, with the same adjustments.Results: We found an overall VE against symptomatic SARS-CoV-2 infection due to AY.4.2 of 73% (95% confidence interval (CI) = 62-81) for >14 days post-second vaccine dose. Good protection against AY.4.2 symptomatic infection was observed for BNT162b2, ChAdOx1, and mRNA-1273. In unvaccinated individuals, the hazard ratio (HR) for COVID-19 hospital admission or death from AY.4.2 among community detected cases was 1.77 (95% CI = 1.02-3.07) relative to unvaccinated individuals who were infected with Delta, after adjusting for multiple potential confounders. VE against AY.4.2 COVID-19 admissions or deaths was 87% (95% CI = 74-93) >28 days post-second vaccination relative to unvaccinated.Conclusions: We found that AY.4.2 was associated with an increased risk of COVID-19 hospitalisations or deaths in unvaccinated individuals compared with Delta and that vaccination provided substantial protection against symptomatic SARS-CoV-2 and severe COVID-19 outcomes following Delta AY.4.2 infection. High levels of vaccine uptake and protection offered by existing vaccines, as well as the rapid emergence of the Omicron variant may have contributed to the AY.4.2 variant never progressing to a variant of concern.

In this, second of the two editorials on children and young people (CYP) in the COVID-19 pandemic, we focus on the complex discussion on vaccination of minors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccination of children and young people (CYP) against COVID-19 remains highly debated, with considerable policy divergence internationally. Vaccinating younger age groups was not an initial plan when the original variant of the SARS-CoV-2 virus emerged, because CYP seemed mildly affected by COVID-19 when compared to adults, as discussed in the first editorial. However, new mutations led to increased transmission of SARS-CoV-2. This led to an increase in the population threshold of vaccination coverage required for prevention of viral spread, possibly to levels above 80% vaccine uptake in the whole population. Also, due to the successful roll-out of vaccination to older and at-risk populations, the virus began to circulate in greater numbers amongst younger populations, which became a new concern. An important element was also the issue of broader harms, such as educational disruption, which can also become a determinant of long-term health. A broader perspective weighted the long-term impact across multiple dimensions of human life and shorter-term health concerns. In addition, increasing awareness of the possible rare complications of COVID-19 in CYP, such as Multisystem Inflammatory Syndrome in Children (MIS-C), and the "long COVID" syndrome prompted the scientific study and comparison of the risks of disease vs the safety of vaccination, even among the very young

With the emergence of the Omicron variant, it has become critical to identify risk factors associated with COVID-19 death in individuals who have completed primary vaccination and received a messenger RNA (mRNA) booster dose. Existing evidence is based on people who have received 1 or 2 doses of a COVID-19 vaccine and were infected by the Alpha or Delta variant.1-3 Understanding which groups are at increased risk of COVID-19 death after receiving a booster is crucial for the prioritization of further booster doses and access to COVID-19 therapeutics.

Background The COVID-19 pandemic and ensuing national lockdowns have dramatically changed the healthcare landscape. The pandemic’s impact on people with chronic obstructive pulmonary disease (COPD) remains poorly understood. We hypothesised that the UK-wide lockdown restrictions were associated with reductions in severe COPD exacerbations. We provide the first national level analyses of the impact of the COVID-19 pandemic and first lockdown on severe COPD exacerbations resulting in emergency hospital admissions and/or leading to death as well as those recorded in primary care or emergency departments. Methods Using data from Public Health Scotland and the Secure Anonymised Information Linkage Databank in Wales, we accessed weekly counts of emergency hospital admissions and deaths due to COPD over the first 30 weeks of 2020 and compared these to the national averages over the preceding 5 years. For both Scotland and Wales, we undertook interrupted time-series analyses to model the impact of instigating lockdown on these outcomes. Using fixed-effect meta-analysis, we derived pooled estimates of the overall changes in trends across the two nations. Results Lockdown was associated with 48% pooled reduction in emergency admissions for COPD in both countries (incidence rate ratio, IRR 0.52, 95% CI 0.46 to 0.58), relative to the 5-year averages. There was no statistically significant change in deaths due to COPD (pooled IRR 1.08, 95% CI 0.87 to 1.33). In Wales, lockdown was associated with 39% reduction in primary care consultations for acute exacerbation of COPD (IRR 0.61, 95% CI 0.52 to 0.71) and 46% reduction in COPD-related emergency department attendances (IRR 0.54, 95% CI 0.36 to 0.81). Conclusions The UK-wide lockdown was associated with the most substantial reductions in COPD exacerbations ever seen across Scotland and Wales, with no corresponding increase in COPD deaths. This may have resulted from reduced transmission of respiratory infections, reduced exposure to outdoor air pollution and/or improved COPD self-management.

Additional file 1 Supplementary Figure and Tables.

Additional file 1: Figure S1. Flow diagram for case ascertainment from scan reports.

Additional file 1. Includes Read codes for COPD diagnosis, acute exacerbation of COPD, and smoking status used for sensitivity analysis, model diagnostics (Table A), the results of the sensitivity analysis (Tables B, C, D, and E), and the reporting checklists (FERITS, STROBE, RECORD).

Additional file 1 Supplementary information.

Supplemental material, sj-pdf-1-jrs-10.1177_0141076820962447 for Impact of COVID-19 on accident and emergency attendances and emergency and planned hospital admissions in Scotland: an interrupted time-series analysis by Rachel H Mulholland, Rachael Wood, Helen R Stagg, Colin Fischbacher, Jaime Villacampa, Colin R Simpson, Eleftheria Vasileiou, Colin McCowan, Sarah J Stock, Annemarie B Docherty, Lewis D Ritchie, Utkarsh Agrawal, Chris Robertson, Josephine LK Murray, Fiona MacKenzie and Aziz Sheikh in Journal of the Royal Society of Medicine

Supplemental material, sj-pdf-1-jrs-10.1177_0141076820962447 for Impact of COVID-19 on accident and emergency attendances and emergency and planned hospital admissions in Scotland: an interrupted time-series analysis by Rachel H Mulholland, Rachael Wood, Helen R Stagg, Colin Fischbacher, Jaime Villacampa, Colin R Simpson, Eleftheria Vasileiou, Colin McCowan, Sarah J Stock, Annemarie B Docherty, Lewis D Ritchie, Utkarsh Agrawal, Chris Robertson, Josephine LK Murray, Fiona MacKenzie and Aziz Sheikh in Journal of the Royal Society of Medicine

Faced with the 2020 SARS-CoV2 epidemic, public health officials have been seeking models that could be used to predict not only the number of new cases but also the levels of hospitalisation, critical care and deaths. In this paper we present a stochastic compartmental model capable of real-time monitoring and forecasting of the pandemic incorporating multiple streams of real-world data, reported cases, testing intensity, deaths, hospitalisations and critical care occupancy. Model parameters are estimated via a Bayesian particle filtering technique. The model successfully tracks the key variables (reported cases, critical care and deaths) throughout the two waves (March-June and September-November 2020) of the COVID-19 outbreak in Scotland. The model hospitalisation predictions in Summer 2020 are consistently lower than the recorded data, but consistent with the change to the reporting criteria by the Health Protection Scotland on 15th September. Most parameter estimates were constant over the two waves, but the infection rate and consequently the reproductive number decrease in the later stages of the first wave and increase again from July 2020. The death rates are initially high but decrease over Summer 2020 before rising again in November. The model can also be used to provide short-term predictions. We show that the 2-week predictability is very good for the period from March to June 2020, even at early stages of the pandemic. The model has been slower to pick up the increase in the case numbers in September 2020 but forecasting improves again in the later stages of the epidemic., Comment: 30 pages, 9 figures, 1 table

Figure schedule of enrolment, interventions, and assessments. (DOC 53Â kb)

Summary table of hospital characteristics based on one measure of hospital size, Occupied Bed Days (OBD). OBD is divided into 4 categories based on 1st quartile (5550), median (12168) and 3rd quartile (34135). Unless specified the values represent the range within a given OBD category (min â max). (DOCX 14Â kb)

List of all variables considered in the risk factor analysis (Model 1: Logistic regressionâ +â Model 2: Poisson regression. (DOCX 17Â kb)

List of all 46 hospital specialities that were obtained from Information Services Division (ISD). Results of univariate screening using Chi-square or Fisher’s exact where appropriate and Odds Ratios (for specialities that with statistically significant chisquare tests and no cells where n = 0). Specialities in bold print (n = 36) were used in the Nonmetric Multidimensional Scaling (NMS) carried out (Fig. 3). (DOCX 18 kb)