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.

Active surveillance study of adverse events following immunisation of children in the Czech Republic.

BACKGROUND: Despite the undisputed public health benefits of routine vaccination, adverse events following immunisation (AEFI) remain a concern. As most adverse events are mild, they may be under-reported; this may underlie the wide range of AEFI rates reported in the literature. We investigated the rates of AEFI related to routine vaccination of children 0-10 years old in the Czech Republic. METHODS: The study reviewed patients' records in a sample of 49 paediatric GP practices covering all 12 administrative regions of the Czech Republic between 2011 and 2013. Adverse events following routine immunisation of children aged 0-10 years were identified and recorded. RESULTS: The overall rate of AEFI was 209/100,000 doses; this was 6 times higher than the rate reported to the Czech State Institute for Drug Control (34/100,000 doses). Over two fifths (44%) of all AEFI occurred after the booster dose of the combined diphteria, tetanus and pertussis vaccine in 5-year old children. The vast majority of AEFI were non-serious local events (e.g. redness) and fever. Most AEFI occurred the second day after the immunisation, lasted 4 days on average, and were treated by cold therapy, antipyretics and analgesics. CONCLUSIONS: The rate of AEFI identified in this study was considerably higher than the officially reported rate. Although the vast majority of AEFI were non-serious, health care providers and the public should be educated and encouraged to report AEFI to address the issue of underreporting, to increase the safety profile of vaccines, and to improve public confidence in immunisation programmes.

Factors Associated with Parental Refusal of Routine Vaccination in the Czech Republic.

AIM: Routine vaccination is one of the most important preventive methods which is responsible for the decreasing trend of morbidity and mortality of vaccine preventable infectious diseases, their complications and sequelae. The impact of vaccination on declining trend of these diseases is well known and confirmed by a large number of epidemiological studies. In the Czech Republic, there is high vaccination coverage in regards to most vaccine preventable diseases. However, during the last decade proportion of parents refusing routine vaccination of their children due to different factors is increasing. The presented study evaluates current situation in the Czech Republic and describes the most significant factors in parents decision making. METHODS: The study was conducted between 1 July 2013 and 31 March 2014 as a questionnaire based survey (cross-sectional study). The questionnaire was created with multiple choice answers. Questions were addressed to parents or legal representatives of children aged 0-18 years. Types of questions were divided into several subgroups. The study was performed in the Czech Republic in two different districts of Prague and Zlín. RESULTS: In the sample size (n=480) we detected 11 parents who refused vaccination of 11 children (2.29%). The most often refused vaccines in the prevalence study were hexavaccine (1st dose) and measles, mumps and rubella vaccine (1st dose). The hexavaccine includes tetanic anatoxin, diphtheric anatoxin, acellular pertussis vaccine, conjugate vaccine against Haemophilus influenzae b, inactivated polio vaccine, and recombinant vaccine against viral hepatitis B. The measles, mumps, rubella vaccine contains live attenuated viruses of measles, mumps, rubella. CONCLUSION: We observed increasing trend of routine vaccination refusal in children during the last ten years (compared to situation in the year 2004, p<0.001). The most important factors associated with this progression were distrust to vaccination, fear of some vaccine components and fear of adverse reactions.

Risk factors for malignant melanoma and preventive methods.

UV radiation is an important environmental risk factor for cutaneous melanoma; however, information concerning UV exposure in many populations is lacking. The aim of our study was to investigate risk factors for malignant melanoma (MM), particularly those related to UV exposure behavior in the Czech Republic and Germany. This case-control study included 207 patients who were consecutively diagnosed with MM in 2 dermatology clinics in Prague, Czech Republic, and Munich, Germany. Controls were 235 patients with other dermatologic conditions. All 442 participants completed a questionnaire on sociodemographic data and factors related to UV exposure. The association between risk factors and MM was assessed using multivariate logistic regression. Patients with Fitzpatrick skin types I and II had a higher likelihood of developing melanoma than those with Fitzpatrick skin type III. Frequent sunburns during childhood and adolescence were strongly related to developing melanoma. A higher level of education also was associated with a higher melanoma incidence. Variables related to UV exposure were strongly associated with melanoma in our study population. Prevention campaigns should be implemented to improve awareness of melanoma to reduce exposure to UV radiation among high-risk patient populations.

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.

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.

Vaccination Perception and Attitude among Undergraduate Medical and Teacher Education Students at Charles University, Prague, Czech Republic.

This cross-sectional comparative study was designed to evaluate different opinions and their impact on vaccine confidence, as perceived by students of two different university programs (medicine and teacher education), as both of them play important roles in patient education, with the latter major shaping the skills of critical thinking. Multi-item, opinion-based, paper-and-pencil anonymous questionnaires were distributed among students of medicine and teacher education. Data were sorted and divided into two sets to be analyzed using logistic regression. Out of a total of 722 respondents, 386 were medical students and 336 were teacher education students. While most respondents said they were not in favor of alternative medicine, a significantly higher number of alternative medicine followers were teacher education students. The positive vaccination perception rate (PVPR) is not dependent on the behavioral factors of student respondents (irrespective of their major) but is largely affected by their attitude to alternative medicine. Fear of infection dramatically increased the PVPR (up to 6.7 times) in those who were versus were not afraid of getting infected or were not quite sure whether to fear it. Fear of side effects of vaccination clearly decreased the PVPR, by at least 84%.

A Serosurvey Identifying Vulnerability to Measles in Health Care Workers. A Hospital-Based Prospective Seroprevalence Study.

The aim of this serological survey was to assess the persistence of measles antibodies among health care workers (HCWs) at risk of incidental measles. A prospective study of measles-specific antibodies in serum samples obtained from a total of 2782 participants aged 19-89 years was conducted between May 2018 and December 2019. The seropositivity rate of 93.7% (95% CI: 92.4-94.9%) in fully vaccinated participants aged 19-48 years was significantly lower than that of 98.0% (95% CI: 96.5-99.0%) in participants naturally immunised before 54 years. A cohort of those born in 1971-1975, vaccinated predominantly with one dose, showed lower seropositivity persistence (86.6%) than those fully vaccinated with two doses or naturally immunised. Otherwise, seropositivity was not markedly influenced by sex, age, smoking status, overweight, obesity or concomitant disease. The presence of sufficient antibody levels in a high proportion of HCWs irrespective of the way they acquired immunity is a favourable finding for managing incidental measles; hence, in the presence of a risk of a measles outbreak, it would be possible to perform targeted vaccination of only at-risk HCWs with a history of incomplete vaccination or missing information about the way in which immunity is acquired.

Risk of Breast Cancer Revealed by Mammographic Screening in Czech Women Aged 40-45 Years, a Monocentric Cohort Study.

The aim of the present study was to evaluate breast cancer risk in women aged 40-45 years not included in the routine mammographic screening programme in the Czech Republic and to assess the suitability of the screening interval. Our cohort study was conducted using registry data of one mammography centre (Bulovka Hospital in Prague) between 1 January 2008 and 31 December 2017. The risk of breast cancer was evaluated using a positive predictive finding (PPF) corresponding to the Breast Imaging-Reporting and Data System (BI-RADS) scores of 4 and 5. The annual PPF incidence rate achieved 2.25 per 1000 women aged 40-45 years and was not significantly different from that (3.31) of women of 45-50 years of age as demonstrated by an adjusted hazard ratio of 0.75 (95% confidence interval: 0.42-1.33). It was found that a screening interval longer than 3 years increased the chance of PPF occurrence 1.7 times independently of the women's age, signalling a risk of failure of early detection of breast cancer. The same PPF incidence rates both in women aged 40-45 years and in older ones indicates that even younger women should be eligible for enrolment in the routine mammographic screening programme in the Czech Republic.

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.

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.

Preventive administration of GS Imunostim as a protection against acute respiratory infections.

With respect to the fact that acute respiratory infections (hereafter ARI) are a world-wide serious social and economic problem, more and more attention is being paid to the development and application of oral bacterial immunomodulators. The preventive effect of GS Imunostim has been evaluated during the respiratory season 2005. The study took place at 10 outpatient sites of general practitioners and lung specialists in Prague, Pilsen and Brno in the respiratory season from January to April 2005. The comparison with the ARI morbidity reports in the studied period revealed statistically significant morbidity reduction in the study participants compared to the ARI morbidity in the Czech population in the studied period from January to April 2005. The morbidity rate in the studied group was 7%, whereas ARI morbidity 15.1% was reported in the general population. The morbidity in the study group was significantly lower that in the general population.