Safety profile of recombinant adjuvanted anti-herpes zoster vaccine (RZV) in high-risk groups: Data from active surveillance program. Puglia (Italy), 2021-23.

BACKGROUND: Since 2021 a recombinant adjuvanted anti-Herpes Zoster vaccine(Recombinant Zoster Vaccine, RZV) is offered in Italy to high-risk patients. Few real-life data about RZV safety are available in target populations. OBJECTIVES: This study investigates Adverse Events Following Immunization(AEFIs), baseline disease flare-ups, and Herpes Zoster (HZ) episodes occurring after RZV administration in a heterogeneous population of fragile patients to design its safety profile. METHODS: This is a retrospective population-based study. RZV-vaccinated patients at Bari Policlinico General Hospital vaccination clinic from October 1st, 2021, to March 31st, 2023, were enrolled. Subjects were screened for reason of RZV eligibility and baseline chronic pathologies. AEFIs occurred in the first 7-days post-vaccination period were collected, and baseline disease flare-ups and post-vaccination HZ episodes were assessed via a 3-month follow-up. RESULTS: Five-hundred-thirty-eight patients were included and total of 1,031 doses were administered. Most patients were vaccinated due to ongoing immunosuppressive therapy(54.65 %); onco-hematological and cardiovascular conditions were the most common chronic baseline pathologies. Out of 1,031 follow-ups, 441 AEFI cases were reported(42.7/100). The most common symptoms were injection site pain/itching(35.60/100), asthenia/malaise(11.44/100), and fever (10.09/100). Four serious AEFIs occurred(0.38/100). Older age, male sex, and history of cardiovascular diseases(OR:0.71; 95CI:0.52-0.98; p-value <0.05) were found to decrease AEFIs risk, while endocrine-metabolic illnesses(OR:1.61; 95CI:1.15-2.26; p-value <0.05) increased it. Twelve patients(2.23 %) reported a flare-up/worsening of their baseline chronic condition within the first three months after vaccination(mean interval 31.75 days, range 0-68 days). Patients with rheumatological illnesses had a higher risk of relapse(OR:16.56; 95CI:3.58-76.56; p-value <0.001), while male sex behaved as a protective factor. Twelve patients who completed the vaccination cycle(2.43%) had at least one HZ episode by the long-term follow-up. CONCLUSIONS: The study demonstrates RZV safety in a significant number of high-risk patients. Hence, RZV should be actively offered as part of tailored vaccination programs to decrease the burden of HZ in fragile populations.

Management of vaccinations in patients with non-Hodgkin lymphoma.

Vaccinations are fundamental tools in preventing infectious diseases, especially in immunocompromised patients like those affected by non-Hodgkin lymphomas (NHLs). The COVID-19 pandemic made clinicians increasingly aware of the importance of vaccinations in preventing potential life-threatening SARS-CoV-2-related complications in NHL patients. However, several studies have confirmed a significant reduction in vaccine-induced immune responses after anti-CD20 monoclonal antibody treatment, thus underscoring the need for refined immunization strategies in NHL patients. In this review, we summarize the existing data about COVID-19 and other vaccine's efficacy in patients with NHL and propose multidisciplinary team-based recommendations for the management of vaccines in this specific group of patients.

Infectious risk profile and strategies for prevention and control of outbreaks in refugee, asylum seekers and migrant populations in EU/EEA countries: a systematic narrative review of evidences.

Introduction: The recent surge in migration to and within the European Union and European Economic Area has brought the development of migration policy, including health policy, to the forefront of regional priorities. While migrants, in general, do not pose a health threat to the host population, specific subgroups of migrants, including refugees, asylum seekers, and irregular migrants, are particularly vulnerable to infectious diseases. To support public health policies in this area, the Emergency Preparedness and Management' working group of the Italian Society of Hygiene, Preventive Medicine and Public Health has conducted a systematic narrative review with the aim to comprehensively analyze the infectious disease risk within the refugee and asylum seeker populations in EU, EEA, and EU-applicant countries. Methods: Forty-two studies were systematically selected from scientific articles in the MEDLINE/PubMed database from January 1, 2008, to June 1, 2023. The infectious risk associated with each infectious disease among refugees and asylum seekers, as well as the strategies to prevent and control outbreaks, was collected from all available studies. Results: The congregate living conditions in refugee camps, transit centers, and temporary housing facilities make this population particularly vulnerable to infectious diseases. As such, implementing stringent hygiene and preventive measures is critical to safeguarding the health of refugees and reducing the risk of outbreaks that may affect both the refugee population and the host communities. Conclusion: Effective vaccination and preventive strategies for migrants, refugees, and asylum seekers are vital for public health and the well-being of these populations. They should be delivered as part of universal health care. By addressing barriers and implementing tailored programs, we can ensure equitable access to vaccines and protect the health of these vulnerable individuals.

Low-intensity rehabilitation in persistent post COVID-19 dyspnoea: the value of Spa health resort as appropriate setting.

Background: Post COVID-19 syndrome is a frequent disabling outcome, leading to a delay in social reintegration and return to working life. Study design: This was a prospective observational cohort study. The main objective was to explore the effectiveness of a Spa rehabilitation treatment on the improvement of post COVID-19 dyspnoea and fatigue, also analyzing the relationship between such symptoms. Additionally, it was assessed if different clinical characteristics could predispose patients in experiencing post COVID-19 symptoms or could influence the effectiveness of a Spa intervention. Methods: From July to November 2021, 187 post COVID-19 patients were enrolled in the study. All the patients complained persisting dyspnoea, whose impact on daily activities was assessed using the modified Medical Research Council dyspnoea scale. 144 patients (77.0%) reported also fatigue. The Spa treatment was started at least 3 months after COVID-19 acute phase. At the end of the treatment, patients were asked to rate the improvement in the dyspnoea and fatigue sensation. 118 patients also underwent the modified Borg Dyspnoea Scale for severity estimation of Exertion Dyspnoea and the Barthel index for severity estimation of Physical Limitation. Results: 165 out of 187 patients (88.2%) reported an improvement in dyspnoea, while 116 out 144 patients (80.6%) reported an improvement in both dyspnoea and fatigue. On a total of 118 subjects, a clinically significant improvement in the modified Borg Dyspnoea Scale (i.e. Delta Borg equal or more than -2.0 points) was reached by the 50.8% of patients, while a clinically significant improvement in the Barthel index (i.e. Delta Barthel equal or more than +10.0 points) was reached by the 51.7% of them. The 31.4% of patients reached a minimal clinically important improvement in both the modified Borg Dyspnoea Scale and the Barthel index. No risk factors were associated to a clinically impacting dyspnoea at entry, while a BMI>30 Kg/m2 was the main risk factor for chronic fatigue. Presence of respiratory comorbidities, obesity and severe acute COVID-19 (phenotype 4) configured risk factors for the lack of improvement of dyspnoea after the treatment, while no risk factors were associated to a lack of improvement for fatigue. Older age, obesity and comorbidities seemed to make more difficult to reach a clinically meaningful improvement in the modified Borg Dyspnoea Scale and the Barthel index after treatment. Female gender may imply more physical limitation at entry, while male patients seem to show less improvement in the Barthel index after treatment. Conclusions: Dyspnoea and fatigue were confirmed to be important post COVID-19 symptoms even in younger subjects of working age and subjects with absent or modest pulmonary alterations at distance from acute COVID-19. A Spa health resort seems to be an effective "low-intensity" setting for a rehabilitation program of such patients. There is a strong relationship in terms of improvement between dyspnoea and fatigue, even if risk factors for their occurrence appear to be different. The improvement in exertion dyspnoea and physical limitation seemed to be less mutually related, probably due to a greater complexity in the assessment questionnaires. Some risk factors may predict a lack of improvement in symptoms after treatment.

Exploring future perspectives and pipeline progression in vaccine research and development.

Introduction: The COVID-19 pandemic had a profound impact on vaccines' Research and Development, on vaccines' market, and on immunization programmes and policies. The need to promptly respond to the health emergency boostered resources' allocation and innovation, while new technologies were made available. Regulatory procedures were revised and expedited, and global production and distribution capacities significantly increased. Aim of this review is to outline the trajectory of research in vaccinology and vaccines' pipeline, highlighting major challenges and opportunities, and projecting future perspectives in vaccine preventables diseases' prevention and control. Study Design: Narrative review. Methods: We comprehensively consulted key biomedical databases including "Medline" and "Embase", preprint platforms, including"MedRxiv" and "BioRxiv", clinical trial registries, selected grey literature sources and scientific reports. Further data and insights were collected from experts in the field. We first reflect on the impact that the COVID-19 had on vaccines' Research and Development, regulatory frameworks, and market, we then present updated figures of vaccines pipeline, by different technologies, comparatively highlighting advantages and disadvantages. We conclude summarizing future perspectives in vaccines' development and immunizations strategies, outlining key challenges, knowledge gaps and opportunities for prevention strategies. Results: COVID-19 vaccines' development has been largely supported by public funding. New technologies and expetited authorization and distribution processes allowed to control the pandemic, leading vaccines' market to grow exponentially. In the postpandemic era investments in prevention are projected to decrease but advancements in technology offer great potential to future immunization strategies. As of 2023, the vaccine pipeline include almost 1,000 candidates, at different Research and Development phase, including innovative recombinant protein vaccines, nucleic acid vaccines and viral vector vaccines. Vaccines' technology platforms development varies by disease. Overall, vaccinology is progressing towards increasingly safe and effective products that are easily manufacturable and swiftly convertible. Conclusions: Vaccine research is rapidly evolving, emerging technologies and new immunization models offer public health new tools and large potential to fight vaccines preventables diseases, with promising new platforms and broadened target populations. Real-life data analysis and operational research is needed to evaluate how such potential is exploited in public health practice to improve population health.

Assessing the temporal and cause-effect relationship between myocarditis and mRNA COVID-19 vaccines. A retrospective observational study.

OBJECTIVE: In 2021, the US Centers for Disease Control and Prevention reported increased cases of myocarditis and pericarditis in the United States after mRNA COVID-19 vaccines. Our study aims to estimate the incidence of myocarditis in Apulia (Southern Italy) and the cause-effect relationship between COVID-19 mRNA vaccines and the risk of myocarditis. METHODS: The Apulian regional archive of hospital discharge forms was used to define the cases of myocarditis in Apulia, considering data from 2017 to 2022. The overall vaccination status of patients was assessed via data collected from the Regional Immunization Database. The history of SARS-CoV-2 infection was extracted from the Italian Institute of Health platform. RESULTS: Since 2017, 5687 cases of myocarditis have been recorded in Apulian subjects; the overall incidence described a decreasing trend, with a slight increase in 0-40 years-old subjects. From 2021 to 2022, 2,930,276 doses of COVID-19 mRNA vaccines were administered; a diagnosis of myocarditis after the second dose of the mRNA vaccine was reported for 894 (0.03%) of Apulian inhabitants, with an incidence rate of 17.9 × 1,000,000 persons-month. The multivariate analysis, adjusted for age, sex, underlying medical conditions, and diagnosis of COVID-19, showed that mRNA vaccination is a protective factor for myocarditis even in younger subjects (aOR = 0.4; 95% CI = 0.3-0.5). CONCLUSION: A temporal association between an exposure and an outcome is not equivalent to a causal association. Our study underlines how an approach that considers the other potential causes of myocarditis (primarily COVID-19) and a causality assessment must be prioritized in the study of the topic.

The community nurse's role on the promotion of papillomavirus vaccination among young students: A study protocol.

Vaccination is the principal strategy for primary prevention of infection by Human Papilloma Virus (HPV), which causes different pathological conditions, up to cancer, in both males and females. However, to date, knowledge among adolescents and their parents about the HPV vaccine is still low. The aim of this quasi-experimental, multicenter study is to assess the effectiveness of a digital educational intervention, conducted by a multidisciplinary health-care team including a Community Nurse, to increase adolescents' HPV vaccination uptake, their knowledge, self-efficacy, feelings and involvement in HPV vaccine decision-making, and parents' vaccination hesitancy. The study will be carried out among a population of students (and their parents), aged between 11 and 13, at secondary schools in Italy. Validated questionnaires will be administered to both students and parents at baseline (T0) and 3 months after a digital educational intervention (T1). The findings may be useful in evaluating and deepening a methodology for designing and implementing educational interventions, embedded in the school setting, that could promote the achievement of outcomes within the broader process of youth's health promotion.

Impact of COVID-19 pandemic on emergency and elective surgery. A retrospective observational analysis in Apulia, southern Italy.

Introduction: In Italy, at the beginning of the COVID19 pandemic, only emergency and life-saving elective surgical procedures were allowed with obvious limitations in terms of numbers of operable cases. The aim of our study is to evaluate the performance of surgical activities by Apulian healthcare facilities (Southern Italy) under the pandemic emergency pressure. Methods: The surgical procedures in study were identified via the Apulian regional archive of hospital discharge forms. We used the ICD9 codes in order to define the elective and urgency surgeries in analysis, and we extended our search to all procedures performed from 2019 to 2021. Results: The number of all procedures decreased from 2019 to 2020; the reduction was higher for elective surgery (-43.7%) than urgency surgery (-15.5%). In 2021, an increase compared to 2020 was recorded for all procedures; nevertheless, elective surgeries registered a further slightly decrease compared to 2019 (-12.4%), while a slightly increase was observed for urgency surgeries (+3.5%). No particular variation was observed considering sex and age at surgery of the patients, and days of hospitalization from 2019 to 2021. Conclusions: The impact of COVID19 on Apulian regional health system has been extremely shocked and has required the implementation of strategies aimed at containing the infection and guaranteeing health services as far as possible. A new paradigm of hospital care for SARS-COV-2 patients in the post-emergency phase in Italy is needed, in order to optimize the resources available and to guarantee high standards of quality and efficiency for citizens.

SARS-CoV-2 Infections, Re-Infections and Clinical Characteristics: A Two-Year Retrospective Study in a Large University Hospital Cohort of Vaccinated Healthcare Workers.

At the University Hospital of Bari, during the first year after the start of the mandatory vaccination campaign with BNT162b2 mRNA COVID-19 vaccine, the preliminary results of an observational study showed a significant prevalence of SARS-CoV-2 breakthrough infections (BIs) among healthcare workers (HCWs), but no hospitalization or deaths. In the present study, we extended the observation period (January 2021-January 2023) with the aim of determining the incidence, characteristics and clinical course of SARS-CoV-2 BIs among 6213 HCWs. All HCWs were regularly monitored and screened. To allow return to work after BI, the protocol required one negative nasopharyngeal swab test followed by a medical examination certifying complete clinical recovery. We observed an overall incidence rate of SARS-CoV-2 BIs of 20.2%. Females were most affected, especially in the nurse group compared with doctors and other HCWs (p < 0.0001). Cardiovascular diseases were the most frequent comorbidity (n = 140; 11.4%). The source of infection was non-occupational in 52.4% of cases. Most cases (96.9%) showed minor symptoms and only two cases of hospitalization (one in intensive care unit), 13 cases of re-infection and no deaths were recorded. Our results confirm that SARS-CoV-2 infection can break vaccination protection but the clinical course is favorable.

Attitudes toward influenza vaccination in healthcare workers in Italy: A systematic review and meta-analysis.

Healthcare workers (HCWs) are among the at-risk groups for whom influenza vaccination is strongly recommended. To assess the proportion of Italian HCWs with positive attitudes toward influenza vaccination, we conducted a systematic review of relevant literature and a meta-analysis. Our focus was on the influenza seasons from 2017/18 to 2021/22. The prevalence of favorable attitudes toward vaccination varied, ranging from 12% during the 2017/18 influenza season to 59% in the 2020/21 season. The significant increase in the 2020/21 season can be attributed to adaptations necessitated by the COVID-19 pandemic. During the 2021/22 influenza season, there was a decline in vaccination coverage (37%), likely due to the absence of a robust preventive culture. Various strategies have been employed to enhance HCWs' attitudes to achieve higher vaccination rates, but none of them have demonstrated satisfactory results. Policymakers should consider implementing a policy of mandatory vaccination to ensure elevated vaccination coverage among HCWs.

Adverse events following immunization (AEFIs) with anti-meningococcus type B vaccine (4CMenB): Data of post-marketing active surveillance program. Apulia Region (Italy), 2019-2023.

The four-component recombinant-DNA anti-meningococcus B vaccine (4CMenB) has been approved by the European Medicines Agency in 2013. In Italy, 4CMenB is recommended since 2017 for use in infants under one year of age. Due to the strong evidence of increased risk of fever after administration, surveillance of adverse events following immunization (AEFIs) is a priority for 4CMenB. This cross-sectional prospective study aims at investigating 4CMenB's safety profile. The study population is represented by infants under twelve months of age vaccinated with 4CMenB in selected ambulatories in Apulia, a region in South-Eastern Italy, from October 1st, 2020, to March 31st, 2023. Parents were provided with a post-vaccination diary covering up to seven days after immunization and were contacted one week after the vaccination day. Information about AEFIs was collected, and reactions were classified following World Health Organization guidelines. For serious AEFIs, causality assessment was carried out. AEFI risk determinants were investigated via logistic regression. A total of 4,773 diaries were completed, with 78.13 % of them (3,729/4,773) containing one or more AEFI reports. Systemic reactions such as malaise, drowsiness/insomnia and fatigue were the most common ones, followed by fever and local pain, tenderness, redness and swelling. Twenty-three cases of serious AEFIs were reported. Following causality assessment, 78.26 % of serious adverse events (18/23) were deemed to have a consistent causal association with the administration of 4CMenB (reporting rate: 0.38 %). Three infants were hospitalized following vaccination, but no cases of death or permanent/severe impairment were reported. Prophylactic paracetamol administration showed a significant protective effect against the risk of manifesting fever within the first 24 h after administration (OR: 0.75; p < 0.005). Our data confirms existing evidence regarding the safety of 4CMenB vaccination in babies under 2 years of age, but also highlight a significant risk of fever after vaccination. Prophylactic paracetamol administration could represent a protective factor against fever, especially during the first 24 h after vaccination.

Spreading of misinformation on mass media and digital platforms regarding vaccines. A systematic scoping review on stakeholders, policymakers, and sentiments/behavior of Italian consumers.

Studies on traditional and social media have found that misinformation about vaccines has been widely spread over the last decade, negatively impacting public opinion and people's willingness to get vaccinated. We reviewed the sentiments of Italian users to define the characteristic of anti-vax and pro-vax contents and defined the strategies to deal with the misinformation. Scopus, MEDLINE/PubMed, Google Scholar (up to page 10), and ISI Web of Knowledge databases were systematically searched. Research articles, brief reports, commentaries, and letters published between January 1, 2010 and March 30, 2022 were included in the search. No-vax or ambiguous contents in Italian mass media are not prevalent compared to neutral and pro-vax content; the communication of no-vax groups is significantly simplified, favoring the understanding of the topics by users. Events related to vaccinations are associated with news coverage by media, search engine consultations, and user reactions on social networks. In this context, the activity of no-vax groups is triggered, and misinformation and fake news spread even further. A multifactorial approach is necessary to manage online user sentiment and use mass and social media as health promotion tools.

Determinants of compliance to influenza and COVID-19 vaccination in a cohort of solid organ transplant patients in Puglia, Southern Italy (2017-2022).

Influenza and Coronavirus Disease 2019 (COVID-19) vaccination are recommended in both solid organ transplant (SOT) candidates and recipients. In Puglia, Southern Italy, an active vaccination offer program has been activated targeting these patients. This study aims at investigating vaccination coverage (VC) for both vaccines in a SOT patients' cohort, as well as at identifying the vaccination compliance determinant. This is a retrospective, population-based study. The study population consists of the SOT patients who accessed Bari's "Policlinico" General Hospital during 2017-2022. Patients were contacted and, after providing their consent, asked their immunization status regarding influenza and COVID-19 and whether they had already undergone transplant or were waiting to do so. Regression models were fitted to investigate the determinants of VCs for influenza vaccination (2021/22 and 2022/23 seasons) and for COVID-19 vaccination (three-dose base cycle, first and second booster doses). Three-hundred and ten SOT patients were identified; 85.2% (264/310) had already undergone SOT. VCs were suboptimal, especially for constant yearly influenza vaccination (17.7%) and COVID-19 vaccination's second booster (1.94%). Logistic regression highlighted that influenza VCs are higher for SOT recipients than SOT candidates, as well as for older patients, although when considering both vaccination seasons only age significantly impact the vaccination uptake. Older age was the only influential variable for COVID-19 VC. VCs for SOT patients seem to be unsatisfying. Stronger interventions are required.

Impact of COVID-19 pandemic on flu vaccine uptake in healthcare workers in Europe: a systematic review and meta-analysis.

INTRODUCTION: Influenza immunization policies in Europe primarily target at-risk and vulnerable subjects. Healthcare workers (HCWs) are a key focus of vaccination campaigns. Our systematic review and meta-analysis aim to evaluate the role of the COVID-19 pandemic on influenza vaccine uptake among HCWs since the 2020/21 influenza season. AREAS COVERED: Fourteen studies were included in the meta-analysis and systematic review, selected from scientific articles available in MEDLINE/PubMed, ISI Web of Knowledge, and Scopus databases between 1 January 2021 and 15 January 2023 The analysis revealed a significant relationship between influenza vaccine uptake and COVID-19 related determinants, such as willingness to receive COVID-19 vaccination, fear of COVID-19, and differentiating between influenza and COVID-19 symptoms (OR = 5.70; 95%CI = 2.08-15.60). Several studies reported higher vaccination coverages in the 2020/21 season compared to previous seasons, with VC values ranging from + 17% to + 38% compared to the 2019/20 season. The included studies identified a shift in HCWs' attitudes toward influenza vaccination, attributed to increased awareness due to the COVID-19 pandemic. EXPERT OPINION: Vaccine hesitancy is common among HCWs in Europe, necessitating mutual strategies across all European countries. So far, mandatory vaccination policies have shown the most potential in achieving high and sustainable influenza vaccination rates among HCWs.

Policy of vaccination of "fragile children": Results of a survey of 14 Italian children's hospitals.

Children with chronic disease are at higher risk of invasive infectious disease, including several vaccine-preventable infections. The Italian Association of Pediatric Hospitals (AOPI) carried out a survey of immunization practices: 14/16 AOPI hospitals completed the survey; 50% of them include 100-199 beds, while 21% have <100 beds. In 12/14 hospitals (86%) all vaccinations included in the National Immunization Plan (plus influenza e COVID-19 vaccines) are available for inpatients, in selected wards (n = 4), on single pediatrician initiative (n = 3), by a centralized in-hospital immunization service (n = 2), and the remaining 3 in a "protected vaccination area" or in a COVID-19 pathway. The wards in which vaccination is more frequently offered to in-patients are: General Pediatrics, Neonatology, Pediatric Hematology & Oncology, Pediatric Diabetology, Pediatric Cardiology, and Pediatric Infectious Diseases (range, 58% to 83%). In 58% of vaccinating hospitals, <500 vaccinations/year are reported, while in 17% this number is >2,000/year. A COVID-19 vaccination team is in place for any inpatient child older than 12 years in 42% of hospitals, in 42% only for "fragile" children. A centralized in-hospital immunization service is an emerging model that may contribute to increase compliance to vaccination of fragile patients and to fight against vaccination hesitancy.

Elevated levels of IL-6 in IgA nephropathy patients are induced by an epigenetically driven mechanism modulated by viral and bacterial RNA.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulonephritis and the role of IL-6 in pathogenesis is becoming increasingly important. A recent whole genome DNA methylation screening in IgAN patients identified a hypermethylated region comprising the non-coding RNA Vault RNA 2-1 (VTRNA2-1) that could explain the high IL-6 levels. METHODS: The pathway leading to IL-6 secretion controlled by VTRNA2-1, PKR, and CREB was analyzed in peripheral blood mononuclear cells (PBMCs) isolated from healthy subjects (HS), IgAN patients, transplanted patients with or without IgAN. The role of double and single-strand RNA in controlling the pathway was investigated. RESULTS: VTRNA2-1 was downregulated in IgAN compared to HS and in transplanted IgAN patients (TP-IgAN) compared to non-IgAN transplanted (TP). The loss of the VTRNA2-1 natural restrain in IgAN patients caused PKR hyperphosphorylation, and consequently the activation of CREB by PKR, which, in turn, led to high IL-6 production, both in IgAN and in TP-IgAN patients. IL-6 levels could be decreased by the PKR inhibitor imoxin. In addition, PKR is normally activated by bacterial and viral RNA, and we found that both the RNA poly(I:C), and the COVID-19 RNA-vaccine stimulation significantly increased the IL-6 levels in PBMCs from HS but had an opposite effect in those from IgAN patients. CONCLUSION: The discovery of the upregulated VTRNA2-1/PKR/CREB/IL-6 pathway in IgAN patients may provide a novel approach to treating the disease and may be useful for the development of precision nephrology and personalized therapy by checking the VTRNA2-1 methylation level in IgAN patients.

Kinetics of humoral immune response and severity of infection after three doses of SARS-CoV-2 mRNA vaccine in a large cohort of kidney transplant recipients.

BACKGROUND: COVID-19 in kidney transplant recipients is associated with high morbidity and mortality. In this study we aimed to evaluate: (i) the seroconversion rate after BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine, (ii) factors associated with humoral response, (iii) clinical outcome of COVID-19 in kidney transplanted patients. METHODS: We enrolled a cohort of 743 kidney transplant recipients followed up from March 2020 until April 2022. A subset of 336 patients, who received three-doses of SARS-CoV-2 vaccine, was analyzed in terms of kinetics of humoral immune response and compared to a control group of 94 healthcare workers. Antibody response was tested before vaccination (T0), 15 and 90 days after the second dose (T1 and T2), on the day of the third dose (T3) and one month after the third dose (T4). RESULTS: We observed that 66 out of 743 subjects had COVID-19 infection pre-vaccination: 65.2% had severe symptoms, 27.3% were hospitalized (9 deaths), none were asymptomatic. After three doses, 51 patients had COVID-19 infection, 60.8% were asymptomatic, 27.5% reported mild symptoms, 3.9% showed severe symptoms, 7.8% were hospitalized (2 deaths). In the subset of 336 vaccinated patients, an antibody level > 0.8 U/ml was detected at T1, that increased at T2 and T3, peaking at T4. Independent factors associated with a negative antibody titer at T4 were decreasing estimated glomerular filtration rate, time from transplantation, and antimetabolites (all p < 0.001) and age (p = 0.007). CONCLUSIONS: The kinetics of humoral response after three doses of vaccine in kidney transplant patients is characterized by a late but effective immune response against SARS-CoV-2, reducing morbidity and mortality.

The Effects of the COVID-19 Pandemic on Vaccination Hesitancy: A Viewpoint.

Vaccination hesitancy is considered by the World Health Organization as a danger to global health. In recent years, vaccine hesitancy rates to COVID-19 have been studied worldwide. In our study, we aim to provide an overview of the concept of vaccine hesitancy, with regard to the post-COVID era, and to provide prevention and management strategies. A search of the international literature until March 2023 was conducted in the PubMed database. The 5723 papers found were divided into two groups: prior to the COVID-19 era and from 2021 onward. Papers about the vaccine hesitation phenomenon are becoming more common during the SARS-CoV-2 pandemic and following the marketing that the vaccine companies have carried out on the different types of COVID-19 vaccines. It is advisable that healthcare authorities, at the national and international level, as well as healthcare professionals, at the local level, should promote a series of activities to reduce the vaccine hesitancy rate.

Incidence and Determinants of Symptomatic and Asymptomatic SARS-CoV-2 Breakthrough Infections After Booster Dose in a Large European Multicentric Cohort of Health Workers-ORCHESTRA Project.

BACKGROUND: SARS-CoV-2 breakthrough infections (BI) after vaccine booster dose are a relevant public health issue. METHODS: Multicentric longitudinal cohort study within the ORCHESTRA project, involving 63,516 health workers (HW) from 14 European settings. The study investigated the cumulative incidence of SARS-CoV-2 BI after booster dose and its correlation with age, sex, job title, previous infection, and time since third dose. RESULTS: 13,093 (20.6%) BI were observed. The cumulative incidence of BI was higher in women and in HW aged < 50 years, but nearly halved after 60 years. Nurses experienced the highest BI incidence, and administrative staff experienced the lowest. The BI incidence was higher in immunosuppressed HW (28.6%) vs others (24.9%). When controlling for gender, age, job title and infection before booster, heterologous vaccination reduced BI incidence with respect to the BNT162b2 mRNA vaccine [Odds Ratio (OR) 0.69, 95% CI 0.63-0.76]. Previous infection protected against asymptomatic infection [Relative Risk Ratio (RRR) of recent infection vs no infection 0.53, 95% CI 0.23-1.20] and even more against symptomatic infections [RRR 0.11, 95% CI 0.05-0.25]. Symptomatic infections increased from 70.5% in HW receiving the booster dose since < 64 days to 86.2% when time elapsed was > 130 days. CONCLUSIONS: The risk of BI after booster is significantly reduced by previous infection, heterologous vaccination, and older ages. Immunosuppression is relevant for increased BI incidence. Time elapsed from booster affects BI severity, confirming the public health usefulness of booster. Further research should focus on BI trend after 4th dose and its relationship with time variables across the epidemics.