Immunogenicity and reactogenicity of COVID-19 Pfizer-BioNTech (Bnt162b2) mRNA vaccination in immunocompromised adolescents and young adults: a systematic review and meta-analyses

This study aimed to evaluate the safety and effectiveness of the BNT162b2 vaccine in immunocompromised adolescents and young adults. The study conducted a meta-analysis of post-marketing studies examining BNT162b2 vaccination efficacy and safety among immunocompromised adolescents and young adults worldwide. The review included nine studies and 513 individuals aged between 12 and 24.3 years. The study used a random effect model to estimate pooled proportions, log relative risk, and mean difference, and assessed heterogeneity using the I2 test. The study also examined publication bias using Egger’s regression and Begg’s rank correlation and assessed bias risk using ROBINS-I. The pooled proportions of combined local and systemic reactions after the first and second doses were 30% and 32%, respectively. Adverse events following immunization (AEFI) were most frequent in rheumatic diseases (40%) and least frequent in cystic fibrosis (27%), although hospitalizations for AEFIs were rare. The pooled estimations did not show a statistically significant difference between immunocompromised individuals and healthy controls for neutralizing antibodies, measured IgG, or vaccine effectiveness after the primary dose. However, the evidence quality is low to moderate due to a high risk of bias, and no study could rule out the risk of selection bias, ascertainment bias, or selective outcome reporting. This study provides preliminary evidence that the BNT162b2 vaccine is safe and effective in immunocompromised adolescents and young adults, but with low to moderate evidence quality due to bias risk. The study calls for improved methodological quality in studies involving specific populations.</p

Mycobacterial-specific secretion of cytokines and chemokines in healthcare workers with apparent resistance to infection with Mycobacterium tuberculosis

Background: Currently, diagnosis of latent TB infection (LTBI) is based on the secretion of IFN-γ in response to Mycobacterium tuberculosis (Mtb) antigens, the absence of which is regarded as no infection. Some individuals appear to resist Mtb infection despite sustained exposure (resisters). In this study, we aimed to assess cytokines, chemokines and antibodies that may be associated with resistance to Mtb infection. We hypothesized that there may be an alternative immune response to Mtb exposure in the absence of IFN-γ in resisters. Methods: We enrolled HIV-uninfected healthcare workers who had worked in high TB-exposure environments for 5 years or longer. We screened them for LTBI using the tuberculin skin test and the QuantiFERON-TB Gold Plus assay. We performed multiplex Luminex to measure concentrations of T cell-associated cytokines and chemokines as well as total antibodies in plasma collected from unstimulated fresh whole blood and supernatants from QuantiFERON-TB Gold Plus tubes following incubation of whole blood for 16-24 hours with ESAT6/CFP10 peptides. Results: Samples from 78 individuals were analyzed: 33 resisters (TST<10mm; IGRA<0.35 IU/mL), 33 with LTBI (TST≥10mm and IGRA≥0.35 IU/mL) and 12 discordant (TST=0mm; IGRA≥1.0 IU/mL). There were no differences in concentrations of cytokines and chemokines in plasma between the different groups. Resisters had significantly lower concentrations of IFN-γ, IL-2, TNF-α, MIP-1α, MIP-1β, ITAC, IL-13 and GM-CSF in supernatants compared with LTBI group. There were no significant differences in the concentrations in supernatants of IL-10, IL-1β, IL-17A, IL-21, IL-23, MIP-3α, IL-4, IL-5, IL-6, IL-7, IL-8, Fractalkine and IL-12p70 between the groups. We observed that resisters had similar concentrations of total antibodies (IgG1, IgG2, IgG3, IgG4, IgA, and IgM) in plasma and supernatants compared to the LTBI and discordant groups. Conclusion: Resistance to Mtb infection despite sustained exposure is associated with lower Mtb-specific secretion of Th1-associated cytokines and chemokines. However, resisters showed secreted concentrations after Mtb stimulation of total antibodies and cytokines/chemokines associated with innate and Th17 immune responses similar to those with Mtb infection. This suggests an ability to mount non-IFN-γ immune responses to Mtb in apparent resisters

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

BackgroundRegularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels.MethodsWe applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level.FindingsIn 2019, there were 12·2 million (95% UI 11·0-13·6) incident cases of stroke, 101 million (93·2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6·55 million (6·00-7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8-12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1-6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0-73·0), prevalent strokes increased by 85·0% (83·0-88·0), deaths from stroke increased by 43·0% (31·0-55·0), and DALYs due to stroke increased by 32·0% (22·0-42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0-18·0), mortality decreased by 36·0% (31·0-42·0), prevalence decreased by 6·0% (5·0-7·0), and DALYs decreased by 36·0% (31·0-42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0-24·0) and incidence rates increased by 15·0% (12·0-18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5-3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5-3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57-8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97-3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01-1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7-90·8] DALYs or 55·5% [48·2-62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3-48·6] DALYs or 24·3% [15·7-33·2]), high fasting plasma glucose (28·9 million [19·8-41·5] DALYs or 20·2% [13·8-29·1]), ambient particulate matter pollution (28·7 million [23·4-33·4] DALYs or 20·1% [16·6-23·0]), and smoking (25·3 million [22·6-28·2] DALYs or 17·6% [16·4-19·0]).InterpretationThe annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.FundingBill & Melinda Gates Foundation

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

BackgroundRegularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels.MethodsWe applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level.FindingsIn 2019, there were 12·2 million (95% UI 11·0-13·6) incident cases of stroke, 101 million (93·2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6·55 million (6·00-7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8-12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1-6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0-73·0), prevalent strokes increased by 85·0% (83·0-88·0), deaths from stroke increased by 43·0% (31·0-55·0), and DALYs due to stroke increased by 32·0% (22·0-42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0-18·0), mortality decreased by 36·0% (31·0-42·0), prevalence decreased by 6·0% (5·0-7·0), and DALYs decreased by 36·0% (31·0-42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0-24·0) and incidence rates increased by 15·0% (12·0-18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5-3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5-3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57-8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97-3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01-1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7-90·8] DALYs or 55·5% [48·2-62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3-48·6] DALYs or 24·3% [15·7-33·2]), high fasting plasma glucose (28·9 million [19·8-41·5] DALYs or 20·2% [13·8-29·1]), ambient particulate matter pollution (28·7 million [23·4-33·4] DALYs or 20·1% [16·6-23·0]), and smoking (25·3 million [22·6-28·2] DALYs or 17·6% [16·4-19·0]).InterpretationThe annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.FundingBill & Melinda Gates Foundation

Global Burden of Cardiovascular Diseases and Risks, 1990-2022

No description supplied</p