Search Results (48)

Background: Neisseria meningitidis B is one of the main causative pathogens of meningitis and other forms of severe meningococcal disease. In the past decade, meningococcal B vaccines have been developed to address this infection and its sequelae. Objective: This article aims to present an example of how the EU regulatory framework allowed the early authorisation of two life-saving vaccines initially based on immunogenicity surrogates of clinical evidence. This was subsequently followed by post-marketing surveillance providing real-world evidence to support their safety profile and impact on the paediatric population in the EU. Methods: We review the evidence supporting the initial regulatory approval of the vaccines, the confirmatory data demonstrating vaccine effectiveness post-authorisation, and the real-world impact of these vaccines on the paediatric population. Results: Two vaccines were approved in the EU for active immunisation to prevent IMD caused by MenB (4CMenB in 2013 and MenB-fHBP in 2017). Both marketing authorisations were based on immunogenicity data (efficacy studies were not feasible due to the rarity of the disease) and safety data generated from pre-authorisation studies. Additional pharmacovigilance activities to further investigate the safety profile and effectiveness studies were requested to be conducted after approval. Both the effectiveness and safety profile of the vaccines were confirmed by these data. Conclusions: This paper illustrates that the EU medicines regulatory framework and safety monitoring system are robust. By supplementing the initial evidence with post-authorisation studies, further effectiveness and safety data enabled regulators to confirm the positive benefit–risk of the vaccines without delaying their access to the people who need them. Full article

Background: Respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract infections and hospitalizations in infants and young children globally. Recently, RSV prevention has advanced with the introduction of nirsevimab, a long-acting monoclonal antibody, and the RSV preF vaccine for maternal immunization. While these interventions have improved early protection, several limitations hinder their broader impact and long-term effectiveness. Methods: This narrative review synthesizes evidence from clinical trials, observational studies, and regulatory reports to evaluate the main limitations of nirsevimab and maternal RSV vaccination. Literature searches were conducted in major databases, focusing on efficacy, safety, immunogenicity, implementation, and population-specific challenges. Results: Both nirsevimab and maternal vaccination provide strong protection during the first six months of life, but their effectiveness wanes thereafter. This is concerning as nearly half of RSV-related deaths occur in children over six months old. Maternal vaccine efficacy is uncertain in very-preterm infants, and safety concerns persist, including potential associations with preterm birth, Guillain–Barré syndrome, and hypertensive disorders. Real-world data from low-income countries are lacking, limiting generalizability. Additionally, the risk of vaccine-associated enhanced disease (VAED), although unconfirmed, has delayed pediatric vaccine development. Emerging monoclonal antibodies and live-attenuated vaccines are under investigation to extend protection beyond infancy. Conclusions: Despite substantial progress, current RSV prevention strategies leave critical gaps, particularly for older infants and underserved populations. There is a pressing need for next-generation vaccines, enhanced pharmacovigilance, and equitable global implementation to ensure sustained and inclusive RSV protection. Full article

We conducted a real-life case–control study among outpatients with Omicron SARS-CoV-2 infection to assess the effectiveness of molnupiravir (MNP) in reducing hospital admission, admission to the intensive care unit, and death at day 28. Cases were SARS-CoV-2-positive patients seeking medical care within five days of symptom onset from 1 January to 31 December 2022, who received MNP. Controls were selected from a regional database among positive subjects who did not receive antiviral treatment for SARS-CoV-2. A total of 1382 patients were included (146 cases, 1236 controls). Vaccinated patients had a lower risk of mortality and of the composite outcome (hospital admission, ICU admission, or all-cause death) than unvaccinated ones (0.6% vs. 7.8%, p < 0.001 and 2% vs. 7.8%, p = 0.001, respectively). After full-matching propensity score analysis, MNP-treated subjects had a lower incidence of the composite outcome, although no effect was observed on individual outcomes. In subgroup analyses by vaccination status, MNP was effective in preventing all outcomes among unvaccinated patients and reduced the risk of ICU admission in both vaccinated and unvaccinated patients. Molnupiravir treatment effectively reduced the composite outcome risk in outpatients with SARS-CoV-2 infection, with a more pronounced benefit in unvaccinated patients. These findings highlight MNP’s potential to help prevent disease progression in high-risk patients, thereby supporting its role as an outpatient therapeutic option for COVID-19. Full article

Background: Several influenza vaccine formulations are available, including adjuvanted, high-dose, trivalent, and quadrivalent vaccines, and direct, comparative evidence on the relative effectiveness is limited. Real-life data on the potential impact of the co-administration of pneumococcal and/or SARS-CoV-2 vaccinations are also very scarce. During the 2023–2024 influenza season, we carried out a retrospective cohort study on the entire elderly population of the Pescara province, Italy, in order to evaluate the effectiveness of the quadrivalent influenza vaccine, offered alone or in combination with other recommended vaccinations. Methods: All the immunization, demographic, co-payment, and hospitalization data were extracted from the official National Healthcare System, and the follow-up lasted from October 2023 to September 2024. The outcomes were all-cause mortality and hospital admissions for influenza and/or pneumonia. All the Cox models were adjusted (or stratified) for gender, age, hypertension, diabetes, COPD, CVD, renal disorders, cancer, and previous SARS-CoV-2 infection. Results: Overall, 43.9% of the population aged ≥60 years received an influenza vaccine (n = 46,355/105,527). A total of 3188 (3.0%) and 1047 (1.0%) individuals died of any cause or were hospitalized for influenza and/or pneumonia, respectively. During the follow-up, compared with the unvaccinated, those who received an influenza vaccine showed almost half the likelihood of death (adjusted HR: 0.52; 95%CI: 0.49–0.56) and hospitalization (aHR: 0.55; 95%CI: 0.48–0.62), regardless of the gender and age group. As compared with sole influenza immunization, the co-administration of a pneumococcal or COVID-19 vaccine was associated with a significantly lower risk of both outcomes. No substantial differences were observed by influenza vaccine formulation (MF59 adjuvanted; non-adjuvanted, standard dose; non-adjuvanted, high dose), with the exception of a greater mortality reduction for the MF59-adjuvanted vaccine as compared with the high-dose formulation. Conclusions: During the influenza season 2023–2024, all the influenza vaccines were largely effective among the elderly, with no substantial differences by formulation, age, or gender. However, the co-administration of a pneumococcal and/or SARS-CoV-2 vaccine further reduced the risk of both death and hospitalization. Specific, head-to-head randomized trials are required to confirm both findings. Full article

Background/Objectives: Vaccination against SARS-CoV-2 remains a key measure to control COVID-19. Nuvaxovid, a recombinant Matrix-M–adjuvanted protein-based vaccine, showed similar efficacy to mRNA vaccines in clinical trials and real-world studies, with lower rates of reactogenicity. Methods: To support decision making on UK vaccine selection, a population-based compartmental dynamic transmission model with a cost-utility component was developed to evaluate the cost-effectiveness of Nuvaxovid compared with mRNA vaccines from a UK National Health Service perspective. The model was calibrated to official epidemiology statistics for mortality, incidence, and hospitalisation. Scenario and sensitivity analyses were conducted. Results: In the probabilistic base case, a Nuvaxovid-only strategy provided total incremental cost savings of GBP 1,338,323 and 1558 additional quality-adjusted life years (QALYs) compared with an mRNA-only vaccination strategy. Cost savings were driven by reduced cold chain-related operational costs and vaccine wastage, while QALY gains were driven by potential differences in vaccine tolerability. Probabilistic sensitivity analysis indicated an approximately 70% probability of cost-effectiveness with Nuvaxovid-only versus mRNA-only vaccination across most cost-effectiveness thresholds (up to GBP 300,000/QALY gained). Conclusions: Nuvaxovid remained dominant over mRNA vaccines in scenario analyses assessing vaccine efficacy waning, Nuvaxovid market shares, and the vaccinated population. Full article

Background/Objectives: Urinary tract infections (UTI) represent a highly frequent and debilitating disease. Immunoactive prophylaxis, such as the polyvalent bacterial whole-cell-based sublingual vaccine MV140, have been developed to avoid antibiotic use. However, the effectiveness of this tool in the Portuguese population is still unknown. This study aims at assessing the effectiveness of treatment with MV140 in a cohort of Portuguese patients presenting with recurrent UTIs. Methods: Prospective observational real-life study of 125 patients with complicated and uncomplicated recurrent UTIs treated with MV140. The primary outcome was a reduction in frequency and severity of UTIs after a follow-up of 12 months. Overall satisfaction, adverse events, and assessment of the effectiveness of MV140 in subgroups of patients with specific risk factors for UTIs were secondary outcomes. Results: In the 12 months after treatment outset, 38% of patients were UTI-free, 34% reported 1 or 2 UTI episodes, and the remaining 28% presented 3 or more UTIs, corresponding to a mean reduction of 3.20 (2.87–3.53, 95% C.I.; p < 0.001) UTI episodes per year per patient. The effectiveness of MV140 was the same regardless of sex, BMI, regular sexual activity, hypertension, diabetes mellitus, depression, paraplegia, performance of intermittent self-catheterization, indwelling bladder catheter, or previous use of other UTI-preventing vaccines. We observed a higher effectiveness in post-menopausal women compared to pre-menopausal (74.7% vs. 59.4%, respectively, p = 0.029). A total of 73% of patients reported a reduction in symptom severity or days of disease, and the mean global satisfaction was 7.52/10. Conclusions: MV140 demonstrated to be effective in the reduction rate of recurrent UTIs in a cohort of adult Portuguese patients. Full article

Background/Objectives: The effectiveness of COVID-19 vaccine in patients with immune-mediated inflammatory diseases (IMID) depends on the underlying disease, immunosuppression degree and the vaccine regimens. We evaluate the safety and immunogenicity of different COVID-19 vaccine schedules. Methods: The SAFER study: “Safety and effectiveness of the COVID-19 Vaccine in Rheumatic Disease”, is a Brazilian multicentric prospective observational phase IV study in the real-life. Data were analyzed after 2 or 3 doses of COVID-19 vaccines: adenoviral vectored vaccine (ChAdOx1 nCoV-19, Astrazeneca), mRNA vaccine (BNT162b2, Pfizer–BioNTech) or inactivated SARS-COV-2 vaccine (CoronaVac, Sinovac Biotech). IgG antibody against SARS-CoV-2 spike (IgG-S) receptor-binding domain level were quantified at baseline (T1) and 28 days after the first (T2), 2nd (T3) and 3rd (T4) doses by chemiluminescence (SARS-CoV-2-IgG-II Quant-assay, Abbott-Laboratories). Results: 721 patients with IMID were included in the analysis. The median titers of IgG-S (BAU/mL) increased progressively over the times: at baseline was 6.26 (5.41–7.24), T2: 73.01 (61.53–86.62), T3: 200.0 (174.36–229.41) and T4: 904.92 (800.49–1022.97). The multivariate linear regression showed that greater IgG-S titers were associated with pre-exposure to COVID-19 (p < 0.001) and BNT162b2 booster vaccine (p < 0.001). Rituximab and immunosuppressant drugs were independent factors for low titers (p = 0.002, p < 0.001, respectively). No serious adverse event was reported. Conclusions: All platforms were safe and induced an increase in IgG-S antibodies. COVID-19 pre-exposure and BNT162b2 booster regimens were predictors of higher humoral immune responses, which is relevant in immunosuppressed populations. Immunosuppressants (mainly rituximab) predicted the lowest antibodies. Full article

Background: Vaccination is the most effective strategy for preventing infectious diseases and related complications, and proving its efficacy is crucial for its success and adherence, especially for newly introduced vaccines, such as adjuvanted recombinant herpes zoster virus vaccination (RZV). In this observational real-life study, we recorded adverse effects following immunization (AEFIs) after RZV administration in frail populations. Methods: A total of 271 subjects underwent RZV at Vaccination Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, Italy. Most subjects were solid organ transplant recipients (kidney, 77.1%; liver, 4.8%). Demographics, clinical data, and AEFIs (type, duration, and medications used) were recorded. Results: Overall, 37% of participants reported at least one AEFI following the first dose, predominantly pain at the injection site (60%), while 41% did so after the second dose (pain at the injection site in 62% of cases). Medications were more frequently used for AEFI treatment after the second dose (28%) rather than after the first dose (13%) (p = 0.01). After stratification by sex, females experienced AEFIs more frequently than males, particularly local skin reactions. Conclusions: Our study added evidence of safety and tolerability of the adjuvanted recombinant RZV in frail adults. Full article

This is a multicentric investigation involving two Italian centers that examined the clinical course of COVID-19 in patients receiving biological therapy targeting type 2 inflammation and those not receiving biologicals. Since the beginning of the COVID-19 pandemic, the management of respiratory and allergic disorders and the potential impact of biological therapy in the most severe forms has been a point of uncertainty. Our multicentric investigation aimed to compare the clinical course of COVID-19 and the impact of vaccination in an Italian cohort of patients with atopic disorders caused by a type 2 inflammation, such as eosinophilic asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). A questionnaire was given to patients coming to our outpatient clinic for the first evaluation or follow-up visit, asking for the clinical characteristics of the infection, the ongoing therapy during the infection, any relevant change, and the patient’s vaccination status. We enrolled 132 atopic patients from two Italian centers; 62 patients were on biological therapy at the time of infection (omalizumab 31%, mepolizumab 26%, benralizumab 19%, and dupilumab 24%). The median age was 56 (IQR 22.8) for patients on biologicals and 48 (IQR 26.5) for those not on biologicals (p = 0.028). The two groups were comparable in terms of sex, body mass index (BMI), smoking history, and systemic oral corticosteroid use (OCS). There were no significant differences in non-biological therapy and comorbidity between the two groups. The patients not on biological therapy had a prevalence of 87% for asthma, 52% for CRSwNP, 10% for CSU, and 6% for AD. The patients on biologicals had a prevalence of 93% for asthma, 17% for CRSwNP, and 10% for CSU. In our work, we observed that mAbs targeting type 2 inflammation in patients with COVID-19 appeared to be safe, with no worsening of symptoms, prolongation of infection, or increase in hospitalizations. Between the two groups, there were no significant differences in the duration of swab positivity (p = 0.45) and duration of symptoms (p = 0.38). During COVID-19, patients on biologicals experienced a significant increase in common cold-like symptoms (p = 0.038), dyspnea (p = 0.016), and more, but not significant, asthma exacerbations, with no significant differences between the different biologicals. Regarding the vaccination status, we observed that there was an increased number of hospitalizations among unvaccinated patients in both groups, although the difference did not reach statistical significance. No patients on biologicals reported safety issues or adverse effects associated with the use of biological treatments during COVID-19. Our investigation showed that mAbs against type 2 inflammation given during Coronavirus Disease 2019 are safe and do not impact the clinical course or main outcomes. Therefore, we found no signals suggesting that anti-Th2 biological therapy should be discontinued during SARS-CoV-2 infection. Controlled studies and analysis, including data from registries and real-life studies, are required to draw firm conclusions regarding the safety or possible advantages that anti-type 2 mAbs could offer in particular clinical contexts, such as infections. Full article

Background: Kidney transplant recipients (KTRs) are likely to develop severe COVID-19 and are less well-protected by vaccines than immunocompetent subjects. Thus, the use of neutralizing anti–SARS-CoV-2 monoclonal antibodies (mAbs) to confer a passive immunity appears attractive in KTRs. Methods: This retrospective monocentric cohort study was conducted between 1 January 2022 and 30 September 2022. All KTRs with a weak antibody response one month after three doses of mRNA vaccine (anti spike IgG < 264 (BAU/mL)) have received tixagevimab-cilgavimab in pre-exposure (group 1), post-exposure (group 2) or no specific treatment (group 3). We compared COVID-19 symptomatic hospitalizations, including intensive care unit hospitalizations, oxygen therapy, and death, between the three groups. Results: A total of 418 KTRs had SARS-CoV-2 infection in 2022. During the study period, we included 112 KTRs in group 1, 40 KTRs in group 2, and 27 KTRs in group 3. The occurrence of intensive care unit hospitalization, oxygen therapy, and COVID-19 death was significantly increased in group 3 compared to group 1 or 2. In group 3, 5 KTRs (18.5%) were admitted to the intensive care unit, 7 KTRs (25.9%) needed oxygen therapy, and 3 KTRs (11.1%) died. Patients who received tixagevimab-cilgavimab pre- or post-exposure had similar outcomes. Conclusions: This retrospective real-life study supports the relative effectiveness of tixagevimab-cilgavimab on COVID-19 infection caused by Omicron, used as a pre- or post-exposure therapy. The continued evolution of Omicron variants has made tixagevimab-cilgavimab ineffective and reinforces the need for new therapeutic monoclonal antibodies for COVID-19 active on new variants. Full article

Background: Phase III clinical trials have documented the efficacy of the SARS-CoV-2 vaccines in preventing symptomatic COVID-19. Nonetheless, it is imperative to continue analyzing the clinical response to different vaccines in real-life studies. Our objective was to evaluate the effectiveness of five different vaccines in hospitalized patients with COVID-19 during the third COVID-19 outbreak in Mexico dominated by the Delta variant. Methods: A test-negative case–control study was performed in nine tertiary-care hospitals for COVID-19. We estimated odds ratios (OR) adjusted by variables related a priori with the likelihood of SARS-CoV-2 infection and its severity. Results: We studied 761 subjects, 371 cases, and 390 controls with a mean age of 53 years (SD, 17 years). Overall, 51% had a complete vaccination scheme, and an incomplete scheme (one dose from a scheme of two), 14%. After adjustment for age, gender, obesity, and diabetes mellitus, we found that the effectiveness of avoiding a SARS-CoV-2 infection when hospitalized with at least one vaccination dose was 71% (OR 0.29, 95% CI 0.19–0.45), that of an incomplete vaccination scheme, 67% (OR 0.33, 95% CI 0.18–0.62), and that of any complete vaccination scheme, 73% (OR 0.27, 95% CI 0.17–0.43). Conclusions: The SARS-CoV-2 vaccination program showed effectiveness in preventing SARS-CoV-2 infection in hospitalized patients during a Delta variant outbreak. Full article

Pembrolizumab has been shown to increase survival in patients with metastatic melanoma. Considering the numerous oncoming studies, we decided to conduct a narrative review of the latest efficacy evidence regarding the use of pembrolizumab, alone or in combination, in patients with metastatic melanoma. A search was conducted in PubMed using “pembrolizumab,” and “metastatic melanoma” as keywords, considering studies from 2022 onward. We reviewed pembrolizumab and associations, cost-effectiveness, virus, advanced acral melanoma, long-term outcomes, real-life data, biomarkers, obesity, and vaccines. In conclusion, pembrolizumab is a fundamental option in the therapy of metastatic melanoma. However, a certain group of patients do not respond and, therefore, new combination options need to be evaluated. In particular, the use of vaccines tailored to tumor epitopes could represent a breakthrough in the treatment of resistant forms. Further studies with larger sample numbers are needed to confirm the preliminary results. Full article

In Italy, a sequential pneumococcal vaccination with conjugate vaccine (PCV) and polysaccharide vaccine (PPSV23) is recommended for individuals aged ≥ 65 years and those at risk for pneumococcal disease (PD) aged ≥ 6 years. The aim of this study was to assess the cost-effectiveness of the new vaccines, i.e., approved 15-valent and 20-valent PCVs. A published Markov model was adapted to evaluate the lifetime cost-effectiveness of vaccination with PCV15 + PPSV23 versus PCV13 + PPSV23, PCV20 alone, PCV20 + PPSV23, and No Vaccination. Simulated cohorts representing the Italian population, including individuals aged ≥ 65 years, those at risk aged 50–100 years, and those deemed high risk aged 18–100 years were assessed. Outcomes were accrued in terms of incremental PD cases, costs, quality-adjusted life years, life years, and the cost–utility ratio relative to PCV13 + PPSV23. The conservative base case analysis, including vaccine efficacy based on PCV13 data, showed that sequential vaccination with PCV15 or PCV20 in combination with PPSV23 is preferred over sequential vaccination with PCV13 + PPSV23. Especially in the high-risk group, PCV15 + PPSV23 sequential vaccination was dominant over No Vaccination and resulted in an ICUR of €3605 per QALY gained. Including PCV20 + PPSV23 into the comparison resulted in the domination of the PCV15 + PPSV23 and No Vaccination strategies. Additionally, explorative analysis, including the geometric mean titer (GMT) informed vaccine effectiveness (VE) was performed. In the low-risk and high-risk groups, the results of the GMT scenarios showed PCV15 + PPSV23 to be dominant over the other sequential vaccines. These findings suggest that if real-world studies would confirm a difference in vaccine effectiveness of PCV15 and PCV20 versus PCV13 based on GMT ratios, PCV15 + PPSV23 could prove a highly immunogenic and effective vaccination regime for the Italian adult population. Full article

Background: Nirmatrelvir/ritonavir (NMV/r) and three-day course remdesivir (3RDV) have been approved as early treatments for COVID-19 outpatients not requiring supplemental oxygen. Real-life data on the efficacy of antivirals among immunocompromised patients or directly comparing their effectiveness in preventing hospitalization and/or death are scarce. Methods: Prospective, observational study conducted in a tertiary care hospital, from 1 January 2022 until 15 March 2023, during the prevalence of the Omicron variant. Inverse probability of treatment weighting (IPTW) was used to account for differences between treatment groups. Results: We included 521, mainly immunocompromised (56%), patients in our analysis; 356 (68.3%) received 3RDV and 165 (31.7%) NMV/r. Overall, 15/521 (2.9%) patients met the primary end-point of hospitalization at 30 days (3RDV arm: 10/356, 2.8% vs. NMV/r arm: 5/165, 3%, p = 1). On IPTW-adjusted univariable analysis, the choice of treatment did not affect outcomes. In multivariable logistic regression analysis, we found that one (OR 0.26, 95%CI 0.07–0.99, p = 0.049) or two (OR 0.06, 95%CI 0.01–0.55, p = 0.014) vaccine booster shots reduced the risk for adverse outcomes. Conclusion: In our patient population of high-risk, mainly immunocompromised, vaccinated patients during the prevalence of the Omicron variant, NMV/r and 3RDV were equally effective early treatments for the prevention of hospitalization and/or death. Full article

Introduction: In Italy, on December 2020, workers in the education sector were identified as a priority population to be vaccinated against COVID-19. The first authorised vaccines were the Pfizer-BioNTech mRNA (BNT162b2) and the Oxford-AstraZeneca adenovirus vectored (ChAdOx1 nCoV-19) vaccines. Aim: To investigate the adverse effects of two SARS-CoV-2 vaccines in a real-life preventive setting at the University of Padova. Methods: Vaccination was offered to 10116 people. Vaccinated workers were asked to voluntarily report symptoms via online questionnaires sent to them 3 weeks after the first and the second shot. Results: 7482 subjects adhered to the vaccination campaign and 6681 subjects were vaccinated with ChAdOx1 nCoV-19 vaccine and 137 (fragile subjects) with the BNT162b2 vaccine. The response rate for both questionnaires was high (i.e., >75%). After the first shot, the ChAdOx1 nCoV-19 vaccine caused more fatigue (p < 0.001), headache (p < 0.001), myalgia (p < 0.001), tingles (p = 0.046), fever (p < 0.001), chills (p < 0.001), and insomnia (p = 0.016) than the BNT162b2 vaccine. After the second dose of the BNT162b2 vaccine, more myalgia (p = 0.033), tingles (p = 0.022), and shivers (p < 0.001) than the ChAdOx1 nCoV-19 vaccine were elicited. The side effects were nearly always transient. Severe adverse effects were rare and mostly reported after the first dose of the ChAdOx1 nCoV-19 vaccine. They were dyspnoea (2.3%), blurred vision (2.1%), urticaria (1.3%), and angioedema (0.4%). Conclusions: The adverse effects of both vaccines were transient and, overall, mild in severity. Full article