Understanding the time-driven shifts of vaccine effectiveness against any and severe COVID-19 before and after the surge of Omicron variants within 2.5 years of vaccination: A meta-regression.

OBJECTIVES: The COVID-19 pandemic required rapid development of vaccines within a short period of time which did not allow to assess vaccine effectiveness (VE) in the long-term. METHODS: A computerized literature search was undertaken to identify eligible studies, with no language restrictions, published between 1 December 2020 and 30 June 2023. RESULTS: Out of a total of 27,597 publications, 761 studies were included. Early VE of 87.2% decreased to 55.1% after 9 months among populations fully immunized not only with mRNA (proxy mRNA) vaccines, and 66.3% decreased to 23.5% in populations immunized exclusively with non-mRNA vaccines. Protection against severe COVID-19 declined to 80.9% for proxy mRNA vaccines and 67.2% for non-mRNA vaccines. Omicron variants significantly diminished VE. Within 6-8 months of receiving a single booster of an mRNA vaccine, VE declined to 14.0% and 67.7% for any and severe COVID-19, respectively. Multiple mRNA booster doses restored protection that declined to 29.5% and 70.6% for any and severe COVID-19, respectively, within 5-7 months. CONCLUSION: Outcomes of this meta-regression underscore the evolving nature of COVID-19 in response to vaccination, dosing schedules, and emerging variants, and provide crucial insights for public health interventions and vaccination strategies.

Timing of HPV vaccination as adjuvant treatment of CIN2+ recurrence in women undergoing surgical excision: a meta-analysis and meta-regression.

OBJECTIVE: The main aim was to determine the overall vaccine effectiveness (VE) against recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+) including specific VE associated with timing of human papillomavirus (HPV) vaccination using data from published studies. DESIGN: Meta-analysis and meta-regression. DATA SOURCES: A computerised literature search was undertaken using the MEDLINE, EMBASE, International Pharmaceutical Abstracts, Derwent Drug File, ProQuest Science and Technology, Cochrane and MedRxiv databases. To be eligible, the studies, with no language restrictions, had to be published between 1 January 2001 and 25 May 2023. REVIEW METHODS: Included were studies with an unvaccinated reference group that assessed CIN2+ recurrence irrespective of the HPV genotype in women undergoing conisation provided. The present study was carried out in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analyses and Meta-analysis Of Observational Studies in Epidemiology guidelines. The risk of study bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. The Grading of Recommendations Assessment, Development, and Evaluation guidelines were used to assess the strength of evidence for the primary outcome. Data synthesis was conducted using meta-analysis and meta-regression. RESULTS: Out of a total of 14 322 publications, 20 studies with a total of 21 estimates were included. The overall VE against recurrent CIN2+ irrespective of the HPV genotype achieved 69.5% (95% CI: 54.7% to 79.5%). While the HPV vaccine valency, follow-up duration, type of study including its risk of bias had no effect on VE, the highest VE of 78.1% (95% CI: 68.7% to 84.7%) was reported for women receiving their first dose not earlier than the day of excision. This outcome was supported by additional analyses and a VE prediction interval ranging from 67.1% to 85.4%. CONCLUSIONS: The outcome of this meta-analysis and meta-regression convincingly showed the beneficial effect of post-excisional HPV vaccination against CIN2+ recurrence. Studies published to date have been unable to determine whether or not vaccination, completed or initiated before conisation, would be associated with more favourable results. PROSPERO REGISTRATION NUMBER: CRD42022353530.

BMI-Associated Anti-Apolipoprotein A-1 Positivity in Healthy Adults after mRNA-Vaccination against COVID-19.

Elevated anti-apolipoprotein A-1 (AAA1) antibody levels associated with cardiovascular risk have been observed in previously SARS-CoV-2-infected or COVID-19-vaccinated individuals. Since patient safety is generally a priority in vaccination, we sought to investigate AAA1 antibody levels in healthy adults after mRNA vaccination. We conducted a prospective cohort study in healthy adult volunteers recruited from military workers of the Transport Air Base in Prague who had received two doses of mRNA vaccines. Anti-apolipoprotein A-1 antibody levels were determined using ELISA from serum samples obtained at three and four time points after the first and second vaccine doses, respectively, within almost 17 weeks of follow-up. The transient AAA1 positivity rate achieved 24.1% (95% confidence interval CI: 15.4-34.7%), i.e., 20 out of 83 participants had at least one positive post-vaccination sample, with a repeat positivity confirmed in only 5 of them. This rate was associated with a BMI > 26 kg/m2, as documented by an adjusted odds ratio of 6.79 (95% CI: 1.53-30.01). In addition, the highest positivity rate of 46.7% (21.3-73.4%) was observed in obese subjects with >30 kg/m2. Since the incidence rate of AAA1 positivity remained unchanged after the first and second vaccine doses, any relationship between AAA1 positivity and mRNA vaccination was inconclusive. The present study showed a transient AAA1 positivity rate associated with overweight or obesity without a proven association with mRNA vaccination.

Risk factors affecting COVID-19 vaccine effectiveness identified from 290 cross-country observational studies until February 2022: a meta-analysis and meta-regression.

BACKGROUND: Observational studies made it possible to assess the impact of risk factors on the long-term effectiveness of mRNA and adenoviral vector (AdV) vaccines against COVID-19. METHODS: A computerized literature search was undertaken using the MEDLINE, EMBASE, and MedRxiv databases to identify eligible studies, with no language restrictions, published up to 28 February 2022. Eligible were observational studies assessing vaccine effectiveness (VE) by disease severity with reference groups of unvaccinated participants or participants immunized with one, two, or three vaccine doses. Our study was carried out in compliance with the PRISMA and MOOSE guidelines. The risk of study bias was identified using the Newcastle-Ottawa Quality Assessment Scale. The GRADE guidelines were applied to assess the strength of evidence for the primary outcome. The synthesis was conducted using a meta-analysis and meta-regression. RESULTS: Out of a total of 14,155 publications, 290 studies were included. Early VE of full vaccination against COVID-19 of any symptomatology and severity decreased from 96% (95% CI, 95-96%) for mRNA and from 86% (95% CI, 83-89%) for AdV vaccines to 67% for both vaccine types in the last 2 months of 2021. A similar 1-year decline from 98 to 86% was found for severe COVID-19 after full immunization with mRNA, but not with AdV vaccines providing persistent 82-87% effectiveness. Variant-reduced VE was only associated with Omicron regardless of disease severity, vaccine type, or vaccination completeness. The level of protection was reduced in participants aged >65 years, with a comorbidity or those in long-term care or residential homes independently of the number of doses received. The booster effect of the third mRNA dose was unclear because incompletely restored effectiveness, regardless of disease severity, declined within a short-term interval of 4 months. CONCLUSIONS: Full vaccination provided an early high, yet waning level of protection against COVID-19 of any severity with a strong impact on the high-risk population. Moreover, the potential risk of new antigenically distinct variants should not be underestimated, and any future immunization strategy should include variant-updated vaccines.

Can Vaccination Trigger Autoimmune Disorders? A Meta-Analysis.

Vaccination as an important tool in the fight against infections has been suggested as a possible trigger of autoimmunity over the last decades. To confirm or refute this assumption, a Meta-analysis of Autoimmune Disorders Association With Immunization (MADAWI) was conducted. Included in the meta-analysis were a total of 144 studies published in 1968-2019 that were available in six databases and identified by an extensive literature search conducted on 30 November 2019. The risk of bias classification of the studies was performed using the Newcastle-Ottawa Quality Assessment Scale. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation. While our primary analysis was conducted in terms of measures of association employed in studies with a low risk of bias, the robustness of the MADAWI outcome was tested using measures independent of each study risk of bias. Additionally, subgroup analyses were performed to determine the stability of the outcome. The pooled association of 0.99 (95% confidence interval, 0.97-1.02), based on a total of 364 published estimates, confirmed an equivalent occurrence of autoimmune disorders in vaccinated and unvaccinated persons. The same level of association reported by studies independently of the risk of bias was supported by a sufficient number of studies, and no serious limitation, inconsistency, indirectness, imprecision, and publication bias. A sensitivity analysis did not reveal any discrepancy in the primary result. Current common vaccination is not the cause of any of the examined autoimmune disorders in the medium and long terms.

The Effectiveness of Post-Vaccination and Post-Infection Protection in the Hospital Staff of Three Prague Hospitals: A Cohort Study of 8-Month Follow-Up from the Start of the COVID-19 Vaccination Campaign (COVANESS).

Continuous assessment of the effectiveness of approved COVID-19 vaccines is crucial to gain an insight into the longer-term impact on health outcomes, and eventually boosting public confidence. For this reason, we conducted a multicenter, retrospective cohort study using data on infection and vaccination rates among employees of three Prague hospitals in the period between 27 December 2020 and 31 August 2021. The post-vaccination and post-infection protectiveness were assessed in a total of 11,443 hospital workers who were followed up for more than 14 days either after their Comirnaty vaccination or study enrolment, depending on their previous SARS-CoV-2 infection. The effectiveness of full vaccination against any SARS-CoV-2 infection achieved 88.3% (83.2-91.8%) over the eight months of follow-up, a figure not much different from the 92.5% (76.5-97.6%) level of protection built by a previous infection. Despite this, the post-vaccination level of protection declined to about 65% between June and August. No case of breakthrough infection was registered among hospital workers having received one or two vaccine doses more than three months after previous infection. The eight-month effectiveness of the Comirnaty vaccine exhibited a declining trend requiring a new booster dose. The need for vaccination in the previously infected employees was not demonstrated conclusively in this study.

Is an Increased Risk of Developing Guillain-Barré Syndrome Associated with Seasonal Influenza Vaccination? A Systematic Review and Meta-Analysis.

While the weight of epidemiological evidence does not support a causal link with influenza vaccination evaluated over the last 30 years, Guillain-Barré syndrome (GBS) has been considered a vaccine-associated adverse event of interest since 1976. To investigate the existence of GBS risk after vaccination against seasonal influenza, a systematic review and meta-analysis have been conducted based on 22 eligible epidemiological studies from 1981 to 2019 reporting 26 effect sizes (ESs) in different influenza seasons. The primary result of our meta-analysis pointed to no risk of vaccine-associated GBS, as documented by a pooled ES of 1.15 (95% CI: 0.97-1.35). Conversely, an obvious high risk of GBS was observed in patients with previous influenza-like illness (ILI), as demonstrated by a pooled ES of 9.6 (95% CI: 4.0-23.0) resulting from a supplementary analysis. While the meta-analysis did not confirm the putative risk of vaccine-associated GBS suggested by many epidemiological studies, vaccination against seasonal influenza reduced the risk of developing ILI-associated GBS by about 88%. However, to obtain strong evidence, more epidemiological studies are warranted to establish a possible coincidence between vaccination and ILI prior to GBS onset.

Polarization of Macrophages in Human Adipose Tissue is Related to the Fatty Acid Spectrum in Membrane Phospholipids.

Residential macrophages in adipose tissue play a pivotal role in the development of inflammation not only within this tissue, but also affect the proinflammatory status of the whole body. Data on human adipose tissue inflammation and the role of macrophages are rather scarce. We previously documented that the proportion of proinflammatory macrophages in human adipose tissue correlates closely with non-HDL cholesterol concentrations. We hypothesized that this is due to the identical influence of diet on both parameters and decided to analyze the fatty acid spectrum in cell membrane phospholipids of the same individuals as a parameter of the diet consumed. Proinflammatory and anti-inflammatory macrophages were isolated from human adipose tissue (n = 43) and determined by flow cytometry as CD14+CD16+CD36high and CD14+CD16-CD163+, respectively. The spectrum of fatty acids in phospholipids in the cell membranes of specimens of the same adipose tissue was analyzed, and the proportion of proinflammatory macrophage increased with the proportions of palmitic and palmitoleic acids. Contrariwise, these macrophages decreased with increasing alpha-linolenic acid, total n-3 fatty acids, n-3/n-6 ratio, and eicosatetraenoic acid. A mirror picture was documented for the proportion of anti-inflammatory macrophages. The dietary score, obtained using a food frequency questionnaire, documented a positive relation to proinflammatory macrophages in individuals who consumed predominantly vegetable fat and fish, and individuals who consumed diets based on animal fat without fish and nut consumption. he present data support our hypothesis that macrophage polarization in human visceral adipose tissue is related to fatty acid metabolism, cell membrane composition, and diet consumed. It is suggested that fatty acid metabolism might participate also in inflammation and the risk of developing cardiovascular disease.

Factors Influencing Persistence of Diphtheria Immunity and Immune Response to a Booster Dose in Healthy Slovak Adults.

We assessed the long-term persistence of humoral immunity against diphtheria in adults with childhood vaccination and the immunogenicity of a booster dose considering demographic, behavioural and vaccinating factors. We conducted a trial in 200 healthy Slovak adults aged 24-65 years, immunised against diphtheria in childhood and against tetanus at regular 10-15 year intervals, and receiving a dose of a tetanus-diphtheria toxoid vaccine. The response was determined by ELISA antibody concentrations of paired sera before and at 4 weeks post-vaccination. A seroprotection rate of 21% (95% confidence interval, CI 15.6-27.3%) was found in adults up to 59 years since the last vaccination with seroprotective levels of antibodies against diphtheria ≥0.1 IU/mL and a geometric mean concentration of 0.05 IU/mL. Conversely, seropositive levels ≥0.01 IU/mL were observed in 98% of adults (95% CI 95-99.5%). Booster-induced seroprotection was achieved in 78% of adults (95% CI 71.6-83.5%) clearly depending on pre-booster antibody levels correlating with age and time since the last vaccination. Moreover, only 54.2% of smokers and 53.3% of patients on statins exhibited seroprotection. Booster vaccination against diphtheria was unable to confer seroprotection in all recipients of only childhood vaccination.

Inflammation and atherosclerosis.

Although current treatment of hypertension and hypercholesterolemia is most effective, cardiovascular mortality still remains at 50 % in industrialized countries. This could be explained by the rather high contribution of the inflammatory process to atherogenesis development. Use of high-sensitivity C-reactive protein (hsCRP) determination in several large epidemiological studies has made it possible to document increased risk of myocardial infarction in individuals with slightly increased hsCRP concentrations, which could thus serve as a discriminatory factor in cardiovascular disease risk assessment. However, the situation is not that simple since hsCRP concentrations correlate significantly with BMI, age and smoking as major cardiovascular risk factors. Increased proportion of pro-inflammatory macrophages in visceral adipose tissue has also been shown to rise with BMI, age (differently in men and women) and non-HDL-cholesterol levels. It has been suggested that the pro-inflammatory status induced by a higher proportion of pro-inflammatory macrophages in visceral adipose tissue acts synergistically in atherogenesis development. Key words: atherosclerosis - cardiovascular disease - inflammation.

[Effect of pulsatility on markers of vascular damage in patients with implanted continuous flow mechanical circulatory support]. / Vliv pulzatility na markery poskození vaskulatury u pacientu s implantovanou mechanickou srdecní podporou s kontinuálním prutokem.

Ventricular assist devices are an important therapeutic modality in advanced surgical therapy of end-stage heart failure. Previously most frequently used devices generated mainly non-pulsatile blood flow. Despite indisputable clinical success of this therapy, we encounter complications specific to the devices generating continuous flow. Complications are mainly attributed to changes in shear stress and subsequent changes of the blood vessel characteristics, mainly of endothelium. Effect of continuous flow on the vasculature and blood elements, therefore, became a subject of intense recent research. Effect of continuous flow on the vascular bed is subject of intensive research. Widespread methods used in angiology measuring the state of vasculature are based mainly on imaging modalities and on the presence of pulsatile flow; therefore, under circumstances of non-pulsatile flow their use is limited and the attention is shifted also to laboratory methods, namely to detection of circulating indicators of vascular damage. Therefore, in our recent studies of the effect of mechanical ventricular assist devices on the blood flow we exploit combination of imaging and laboratory methods, including measurements of circulating microparticles and endothelial progenitor cells. Based on these studies interesting data were obtained studying the effect of implantation of mechanical cardiac support on the dynamics of vascular changes taking into account also response to changes of blood flow characteristics. In this paper we summarize our observations.Key words: continuous flow - endothelial progenitor cells - mechanical circulatory support - microparticles - vascular damage.

Both sublingual and supralingual routes of administration are effective in long-term allergen-specific immunotherapy.

The aim of this study was to confirm or refute the difference between efficacy of long-term specific immunotherapy (SIT) with standardized allergen vaccine consisting of six grass pollens (oat grass, orchard grass, fescue, rye grass, timothy grass, and rye) administered either by sublingual or by supralingual route. To investigate clinical and immunologic changes, 51 patients of a previous 1-year double-blind, placebo-controlled, randomized study were enrolled in an open randomized study that continued over the next 3 years. Sublingual or supralingual immunotherapy (SLIT) was performed in the same way, keeping the drops under or on the tongue, respectively, for 1-2 minutes before swallowing them. Data about symptoms scores and rescue medication intake during grass pollen seasons, as well as skin-prick test results, levels of specific IgG, and IgE antibodies were collected after each pollen season. It was clearly shown that both routes of administration were effective, leading to a significant decrease of clinical symptoms of grass pollen allergy after SIT lasting 3-4 years. No statistically significant difference between sublingually and supralingually treated patients was observed at the end of the study. Adverse effects were limited to a small number of generally mild local and/or systemic reactions with no significant difference between both administration ways of SIT. The significant therapeutic effect of both SLIT and supralingual immunotherapy lasting 3-4 years was clearly achieved. Despite no significant difference between efficacy of both administration ways of SIT, the onset of sublingual SIT effect seems to be slightly faster than that of supralingual SIT.