Reactogenicity and Peak Anti-RBD-S1 IgG Concentrations in Individuals with No Prior COVID-19 Infection Vaccinated with Different SARS-CoV-2 Vaccines.

OBJECTIVE: To investigate the association of immune response with vaccination adverse effects at peak anti-receptor-binding domain spike subunit 1 (anti-RBDS1) IgG after full vaccination with Comirnaty, Spikevax, or Vaxzevria. METHODS: Anti-RBDS1 IgG concentrations after vaccination were determined in healthy adults vaccinated with the Comirnaty, Spikevax, and Vaxzevria vaccines. The association of reactogenicity and peak antibody response after vaccination was tested. RESULTS: Anti-RBDS1 IgG values were significantly higher in the Comirnaty and Spikevax group, compared with the Vaxzevria group (P < .001). Fever and muscle pain were found to be significant independent predictors of peak anti-RBDS1 IgG in the Comirnaty and Spikevax groups (P = .03 and P = .02, respectively). The multivariate model, adjusted for covariates, showed that no association between reactogenicity and peak antibody concentrations was found in the Comirnaty, Spikevax, and Vaxzevria groups. CONCLUSIONS: No association between reactogenicity and peak anti-RBDS1 IgG after vaccination with the Comirnaty, Spikevax, and Vaxzevria vaccine was found.

mRNA Vaccines against SARS-CoV-2: Advantages and Caveats.

The application of BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2 infection has constituted a determinant resource to control the COVID-19 pandemic. Since the beginning of 2021, millions of doses have been administered in several countries of North and South America and Europe. Many studies have confirmed the efficacy of these vaccines in a wide range of ages and in vulnerable groups of people against COVID-19. Nevertheless, the emergence and selection of new variants have led to a progressive decay in vaccine efficacy. Pfizer-BioNTech and Moderna developed updated bivalent vaccines-Comirnaty and Spikevax-to improve responses against the SARS-CoV-2 Omicron variants. Frequent booster doses with monovalent or bivalent mRNA vaccines, the emergence of some rare but serious adverse events and the activation of T-helper 17 responses suggest the need for improved mRNA vaccine formulations or the use of other types of vaccines. In this review, we discuss the advantages and limitations of mRNA vaccines targeting SARS-CoV-2 focusing on the most recent, related publications.

Immune response to mRNA-based COVID-19 booster vaccination in people living with HIV.

OBJECTIVES: Our objective was to assess immune responses and their influencing factors in people living with HIV after messenger RNA (mRNA)-based COVID-19 booster vaccination (third dose). METHODS: This was a retrospective cohort study of people living with HIV who received booster vaccination with BNT-162b2 or mRNA-1273 between October 2021 and January 2022. We assessed anti-spike receptor-binding domain (RBD) immunoglobulin G (IgG), virus neutralizing activity (VNA) titres reported as 100% inhibitory dilution (ID100 ), and T-cell response (using interferon-gamma-release-assay [IGRA]) at baseline and quarterly follow-up visits. Patients with reported COVID-19 during follow-up were excluded. Predictors of serological immune response were analyzed using multivariate regression models. RESULTS: Of 84 people living with HIV who received an mRNA-based booster vaccination, 76 were eligible for analysis. Participants were on effective antiretroviral therapy (ART) and had a median of 670 CD4+ cells/µL (interquartile range [IQR] 540-850). Following booster vaccination, median anti-spike RBD IgG increased by 705.2 binding antibody units per millilitre (BAU/mL) and median VNA titres increased by 1000 ID100 at the follow-up assessment (median 13 weeks later). Multivariate regression revealed that time since second vaccination was a predictor of stronger serological responses (p < 0.0001). No association was found for other factors, including CD4+ status, choice of mRNA vaccine, or concomitant influenza vaccination. In total, 45 patients (59%) had a reactive baseline IGRA, of whom two lost reactivity during follow-up. Of 31 patients (41%) with non-reactive baseline IGRA, 17 (55%) converted to reactive and seven (23%) remained unchanged following booster vaccination. CONCLUSIONS: People living with HIV with ≥500 CD4+ cells/µL showed favourable immune responses to mRNA-based COVID-19 booster vaccination. A longer time (up to 29 weeks) since second vaccination was associated with higher serological responses, whereas choice of mRNA vaccine or concomitant influenza vaccination had no impact.

Atypical Hemolytic Uremic Syndrome Occurring After Receipt of mRNA-1273 COVID-19 Vaccine Booster: A Case Report.

Atypical hemolytic uremic syndrome (aHUS) is a subtype of thrombotic microangiopathy (TMA) characterized by a dysregulation of the alternative complement pathway. Here, we report a previously healthy 38-year-old woman in whom aHUS developed after a COVID-19 vaccine booster. One day after receipt of a booster dose of mRNA-1273 vaccine, she felt ill. Because of persistent headache, nausea, and general malaise, she went to her general practitioner, who referred her to the hospital after detecting hypertension and acute kidney injury. A diagnosis of TMA was made. Her treatment consisted of blood pressure control, hemodialysis, plasma exchange, and respiratory support. Kidney biopsy confirmed the diagnosis of acute TMA. The patient was referred for treatment with eculizumab, and kidney function improved after initiation of this therapy. Genetic analysis revealed a pathogenic C3 variant. SARS-CoV-2 infection as a trigger for complement activation and development of aHUS has been described previously. In addition, there is one reported case of aHUS occurring after receipt of the adenovirus-based COVID-19 vaccine ChAdOx1 nCoV-19, but, to our knowledge, this is the first case of aHUS occurring after a booster dose of an mRNA COVID-19 vaccine in a patient with an underlying pathogenic variant in complement C3. Given the time frame, we hypothesize that the vaccine probably was the trigger for development of aHUS in this patient.

Analysis of spontaneous reports of suspected adverse reactions after vaccination against COVID-19 in Slovakia.

Introduction: The COVID-19 pandemic has resulted in more than 6.5 million deaths worldwide yet. Vaccination against the SARS-CoV-2 virus is a reliable way out of the pandemic, however, vaccination rate reaches only 58% in the Slovak Republic. Concerns about the adverse reactions of vaccines are one of the reasons for the low vaccination rate. Objective: The aim of our analysis was to review reported suspicions of adverse reactions (ARs) of registered COVID-19 vaccines (Comirnaty, Vaxzevria, Spikevax), which State Institute for Drug Control received from healthcare professionals and patients in the period from 1 January 2021 to 31 May 2021. Methods: Data were collected from the State Institute for Drug Control database, a retrospective analysis was carried out focusing on trends in the number of all reports of suspicions of adverse reactions sent to the State Institute for Drug Control during the previously mentioned period. We analysed the Retrieved data were analysed with the usage of descriptive statistics and comparison to historical data on drug adverse reactions in Slovakia was performed. Results: During the evaluation period, 5,763 reported suspicions of adverse reactions were analysed, overall, there was a significant (p < 0.0001) increase in the number of reported adverse reactions fivefold. 93% of ARs (n = 5,346) were reported for COVID-19 vaccines. In comparison of the extentof all adverse reactions, there is clearly a statistically significant difference between all types of vaccines administered at that time (p ≤ 0.0001). No statistically significant difference (p ≤ 0.238) was identified between Spikevax and Comirnaty in the proportion of serious adverse reactions. However, a significantly higher (p ≤ 0.00001) proportion of reported suspicions of serious adverse reactions was observed after the administration of Vaxzevria. Conclusion: This is the first analysis conducted in Slovakia aimed to reported adverse reactions in relation to the administration of COVID-19 vaccines. The rate of spontaneously reported suspected adverse reactions has been insufficient in the past for a long time; during the period from January to May 2021 the reporting rate increased due active calls for adverse reactions reporting. In concordance with European data, Vaxzevria had a significantly higher ratio of reported suspicions of serious adverse reactions.

The epidemiological situation in Ukraine in terms of the implementation of preventive vaccinations according to the Protective Vaccination Program

The level of immunization of children and adolescents under the Protective Vaccination Program in Ukraine is lower than in Poland, and, due to the outbreak of the war in Ukraine, many people now live in conditions that are often unsanitary. Centers for refugees are also places of increased risk of outbreaks of infectious diseases. This risk is increased by the low percentage of the vaccinated, limited access to healthcare (including diagnostics) and overcrowding. The paper presents the state of vaccination in Ukraine against poliomyelitis, measles, diphtheria, tetanus and pertussis, the most important problems in the field of infectious diseases, as well as the resulting risks and the need to prevent them.

A multinational, phase 2, randomised, adaptive protocol to evaluate immunogenicity and reactogenicity of different COVID-19 vaccines in adults ≥75 already vaccinated against SARS-CoV-2 (EU-COVAT-1-AGED): a trial conducted within the VACCELERATE network.

BACKGROUND: In the ongoing COVID-19 pandemic, advanced age is a risk factor for a severe clinical course of SARS-CoV-2 infection. Thus, older people may benefit in particular from booster doses with potent vaccines and research should focus on optimal vaccination schedules. In addition to each individual's medical history, immunosenescence warrants further research in this population. This study investigates vaccine-induced immune response over 1 year. METHODS/DESIGN: EU-COVAT-1-AGED is a randomised controlled, adaptive, multicentre phase II protocol evaluating different booster strategies in individuals aged ≥75 years (n=600) already vaccinated against SARS-CoV-2. The initial protocol foresaw a 3rd vaccination (1st booster) as study intervention. The present modified Part B of this trial foresees testing of mRNA-1273 (Spikevax®) vs. BNT162b2 (Comirnaty®) as 4th vaccination dose (2nd booster) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 wild-type and variants. The primary endpoint of the trial is to assess the rate of 2-fold antibody titre increase 14 days after vaccination measured by quantitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wild-type virus. Secondary endpoints include the changes in neutralising antibody titres (Virus Neutralisation Assay) against wild-type as well as against Variants of Concern (VOC) at 14 days and up to 12 months. T cell response measured by qPCR will be performed in subgroups at 14 days as exploratory endpoint. Biobanking samples are being collected for neutralising antibody titres against potential future VOC. Furthermore, potential correlates between humoral immune response, T cell response and neutralising capacity will be assessed. The primary endpoint analysis will be triggered as soon as for all patients the primary endpoint (14 days after the 4th vaccination dose) has been observed. DISCUSSION: The EU-COVAT-1-AGED trial Part B compares immunogenicity and safety of mRNA-1273 (Spikevax®) and BNT162b2 (Comirnaty®) as 4th SARS-CoV-2 vaccine dose in adults ≥75 years of age. The findings of this trial have the potential to optimise the COVID-19 vaccination strategy for this at-risk population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05160766 . Registered on 16 December 2021. PROTOCOL VERSION: V06_0: 27 July 2022.

Immunogenicity, effectiveness, safety and psychological impact of COVID-19 mRNA vaccines.

In December 2019, a new single-stranded RNA coronavirus, SARS-CoV-2, appeared in China and quickly spread around the world leading to a pandemic. Infection with SARS-CoV-2 generates symptoms ranging from asymptomatic to severe, occasionally requiring hospitalization in intensive care units, and, in more severe cases, leading to death. Scientists and researchers around the world have made a real race against time to develop various vaccines to slow down and stop the spread of the virus. In addition to conventional viral vector vaccines, new generation mRNA vaccines, BNT152b2 (Comirnaty) and mRNA-1273 (Spikevax), have been developed respectively by Pfizer/BioNTech and Moderna. These vaccines act on immune cells to induce an immune response with the production of specific antibodies against Spike protein of SARS-CoV-2, and to stimulate the differentiation of T and B memory cells. The objective of this review is to provide a detailed picture of the validity of these new vaccines and the safety of vaccination. Not only was the immunogenic effect of mRNA vaccines evaluated, but also the psychosocial impact they had on the population. The data collected show that this type of vaccine can also be an excellent candidate for future treatment and eradication of possible new pathologies with viral and non-viral etiology.

Immunogenicity and Safety of the Spikevax® (Moderna) mRNA SARS-CoV-2 Vaccine in Patients with Primary Humoral Immunodeficiency.

INTRODUCTION: Reports on the immunogenicity and efficacy of the Spikevax® vaccine against SARS-CoV-2 in immunodeficient patients are still scarce. We aimed to evaluate the safety and immunogenicity of the vaccine in patients with primary humoral immunodeficiency. METHODS: We enrolled 46 patients, including 34 patients with common variable immunodeficiency (CVID), 10 patients with unclassified hypogammaglobulinemia (HypoIg), and 2 patients with X-linked agammaglobulinemia. We collected the blood samples before vaccination (D 0), and 10 days (D +38) and 90 days (D +118) after the second vaccination. Further, we quantified SARS-CoV-2-specific T-cell response (QuantiFERON ELISA test), serum anti-RBD IgG, and anti-RBD IgA-specific antibodies (enzyme immunoassay). RESULTS: We found that the vaccination elicited predominantly mild adverse events, comparable to healthy population. Vaccination response negatively correlated with a value of Immune Deficiency and Dysregulation Activity in all measured parameters. D +38, seroconversion for anti-RBD IgG and anti-RBD IgA was observed in 65% and 21% CVID patients, respectively. SARS-CoV-2-specific T-cell response was detected in less than 50% of CVID patients. Meanwhile, HypoIg patients had 100%, 90%, and 60% positivity rates for anti-RBD IgG, anti-RBD IgA, and T-cell response, respectively. Three months after the second vaccination, 82% of the responders remained positive for anti-RBD IgG, but only less than 50% remained positive for T-cell activity in CVIDs. Low immunogenicity was observed in patients with lung involvement and/or rituximab treatment history. No SARS-CoV-2 infection was reported within 6 months after the second vaccination. CONCLUSION: Spikevax® seems to be safe with satisfactory immunogenicity in patients with primary humoral immunodeficiency.

Adolescent vaccination: The important role of GPs

GPs have an important role in supporting adolescent vaccination, including ensuring vaccinations are up to date and in promoting health literacy among parents and adolescents. With the recently approved COIVD-19 vaccines and boosters for adolescents, it is timely for GPs to consider missed doses and catch-up vaccination as part of standard preventive health activity for the adolescent patient in general practice.

Risk Perception of Treatment and Prevention of Covid-19 Disease in Slovakia

The COVID-19 pandemic has resulted in more than 6.2 million deaths worldwide. Despite advances in the treatment of this disease over the last 2 years, the only way out of the pandemic is vaccination against the SARS-CoV-2 virus, which is constantly confronted with considerable mistrust and fears of adverse reactions (ADRs) in Slovakia. The aim of this study is to analyse reported suspicions of ADRs of registered COVID-19 vaccines (Comirnaty, Vaxzevria, Spikevax), which the State Institute for Drug Control received from health care professionals and patients between 1 January and 31 May 2021. The program R (version 3.6.3), a language and environment for statistical calculations, GNU GPL license was used for data analysis. During the evaluation period, 5,763 reported suspicions of ADRs were analysed. Overall, there was a significant (p < .0001) fivefold increase in the number of reported ADRs. Ninety-three percent of ADRs (n = 5,346) were reported for COVID-19 vaccines. No statistically significant difference (p = .238) was identified between Spikevax and Comirnaty in the proportion of serious ADRs. However, a significantly higher (p = .00001) proportion of reported suspicions of severe ADRs was observed with Vaxzevria. There is a significant difference in the ratio of serious ADRs between the sexes for all COVID-19 vaccines (p < .00001);in women this ratio is in all cases significantly higher than in men (p < .0001). ADRs were most often reported by patients (p < .0001). In Slovakia, the rate of spontaneous reporting of suspected ADRs has been low for a long time;in the period between January and May 2021, however, the rate increased as a result of active calls for ADR reporting, most often from patients. According to European data, Vaxzevria has a significantly higher ratio of reported suspicions of serious ADRs. For all vaccines, the incidence of severe ADRs is significantly higher in women. [ FROM AUTHOR] Copyright of Acta Facultatis Pharmaceuticae Universitatis Comenianae is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Updated principles of prevention, diagnosis and treatment of COVID-19 in children in Poland - recommendations for paediatricians and family medicine doctors

Since late 2021, we have observed a significant increase in the proportion of children infected with SARS-CoV-2. The course of the disease in children is usually sparsely symptomatic or asymptomatic. However, the predominance of new virus variants makes children more likely to become symptomatically ill and require hospitalisation. This paper aims to update recommendations for managing a child with COVID-19 in out- and inpatient settings. Current options for prevention and antiviral treatment are discussed, noting the limited availability of therapy for children. In most children with COVID-19, the basis for treatment remains symptomatic and supportive therapy and measures to reduce SARS-CoV-2 infection spread.