Search Results (832)

Background/Objectives: This retrospective multicenter study, conducted within the ORCHESTRA Project, investigated SARS-CoV-2 reinfections among 5777 healthcare workers (HCWs) from four University Hospitals (Modena, Verona, Padova and Trieste) in northern Italy, aiming to assess the risk of reinfection and its determinants, comparing the clinical characteristics of reinfections with those of first infections, and examining the impact of preventive measures and vaccination strategies. Methods: HCWs completed an online questionnaire between June and August 2022. The survey collected demographic, occupational, and clinical data, including information on first infections and reinfections. Statistical analyses were performed using SPSS 28.0, through bivariate and multivariate approaches. Results: Response rates were 41.8% for Modena, 39.5% for Verona, 17.9% for Padova, and 17.4% for Trieste. Among the respondents, 4.8% (n = 276) experienced 2 infections and 0.5% (n = 27) reported 3 infections, out of a total of 330 reinfection cases. Additionally, 43.0% (n = 2787) reported only one infection, while 51.5% were never infected. Reinfection rates increased across five study phases (based on the epidemiological context), likely due to the emergence of new SARS-CoV-2 variants. A booster vaccine dose significantly reduced reinfection risk. Higher reinfection risk was found among HCWs aged ≤30 years, those with chronic respiratory diseases, and those working in COVID-19 wards, particularly nurses and allied health professionals. Reinfections were associated with a lower frequency of symptoms both during the period of swab positivity and after a negative swab, as well as with a shorter duration of swab positivity. No significant differences in symptom duration were found between first infections and reinfections. Conclusions: Despite its limitations, the online questionnaire proved a useful tool. Natural infection and vaccination reduced both reinfection risk and symptom severity. Prior infections should be considered in planning vaccination schedules and prioritizing HCWs. Full article

Background/Objectives: mRNA vaccines introduced during the COVID-19 pandemic were a significant step forward in the rapid development and deployment of vaccines in a global pandemic context. These vaccines showed good protective efficacy, but—due to limited breadth of the immune response—they required frequent boosters with manufactured spike sequences that often lagged behind the circulating strains. In order to enhance the breadth, durability, and magnitude of immune responses, we studied the effect of combining priming with an RNA vaccine technology with boosting with protein/adjuvant using a TLR4-agonist based adjuvant. Methods: Specifically, four proprietary adjuvants (EmT4^TM, LiT4Q^TM, MiT4^TM, and AlT4^TM) were investigated in combination with multiple modes of SARS-CoV-2 vaccination (protein, peptide, RNA) for their effectiveness in boosting antibody responses to SARS-CoV-2 spike protein in murine models. Results: Results showed significant improvement in immune response strength and breadth—especially against more distant SARS-CoV-2 variants such as Omicron—when adjuvants were used in combination with boosters following an RNA vaccine prime. Conclusions: The use of novel TLR4 adjuvants in combination with protein or RNA vaccinations presents a promising strategy for improving the efficacy of vaccines in the event of future pandemics, by leveraging rapid response using an RNA vaccine prime and following up with protein/adjuvant-based vaccines to enhance the breadth of immunity. Full article

The COVID-19 pandemic accelerated the rapid development and distribution of various vaccine platforms, resulting in a significant reduction in disease severity, hospitalizations, and mortality. However, persistent challenges remain concerning the durability and breadth of vaccine-induced protection, especially in the face of emerging SARS-CoV-2 variants. This review aimed to evaluate the factors influencing the immunogenicity and effectiveness of COVID-19 vaccines to inform future vaccine advancement strategies. A narrative review with systematic approach was conducted following PRISMA guidelines for narrative review. Literature was sourced from databases including PubMed, Embase, and Web of Science for studies published between December 2019 and May 2025. Encompassed studies assessed vaccine efficacy, immunogenicity, and safety across various populations and vaccine platforms. Data were collected qualitatively, with quantitative data from reviews highlighted where available. We have uncovered a decline in vaccine efficacy over time and weakened protection against novel variants such as Delta and Omicron. Booster doses, specifically heterologous regimens, improved immunogenicity and increased protection. Vaccine-induced neutralizing antibody titers have been found to correlate with clinical protection, although the long-term correlates of immunity remain poorly defined. The induction of IgG4 antibodies after repeated mRNA vaccinations raised concerns about potential modulation of the immune response. COVID-19 vaccines have contributed significantly to pandemic control; however, their efficacy is limited by the evolution of the virus and declining immunity. Forthcoming vaccine strategies should focus on broad-spectrum, variant-adapted formulations and defining robust comparisons of protection. Recognizing the immunological basis of vaccine response, including the role of specific antibody subclasses, is fundamental for optimizing long-term protection. Full article

Background: The long-term immune implications of administering more than four doses of COVID-19 vaccine and the impact of breakthrough infections are not fully understood. Research Design and Methods: We conducted a follow-up cohort study on Japanese healthcare workers who received more than three doses of the BNT162b2 vaccine. We assessed both the anti-SARS-CoV-2 antibody titer and cellular immunity in 429 participants and investigated the numbers, types, and brands of COVID-19 vaccines administered, as well as the episodes of COVID-19 infections after the third dose. Results: Individuals who received three total doses of vaccines with BTI episodes demonstrated higher antibody titers than those who received four total doses of vaccines with no BTIs. The cellular immune responses between these two groups were comparable. Conclusions: These findings suggest that BTIs occurring after the primary series of COVID-19 vaccinations (first to third dose) induced humoral immunity to the spike protein that is greater than that induced by booster doses (fourth or fifth dose) and elicit cellular immunity to the spike protein comparable to that of booster doses. Full article

Background: Starting in early 2022, SARS-CoV-2 Omicron has driven large outbreaks in China, a predominantly infection-naive population with high inactivated vaccine coverage. This unique context provided a substantially less-confounded opportunity to evaluate how vaccination, public health, and social measures influenced severity. Methods: We systematically reviewed 86 studies (224 severity estimates) published from 2022 to 2024, reporting symptom and clinical severity outcomes (fever, cough, and sore throat; symptomatic, severe/critical, and fatal illness) of Omicron infections in China. Using meta-regression, we evaluated the associations of study setting, age group, vaccination status, predominant subvariants, and Oxford COVID-19 Government Response Tracker (OxCGRT) indices, including the Government Response Index (GRI), Containment and Health Index (CHI), and the Stringency Index (SI), with infection outcomes, adjusting for key confounders. Results: We found the primary or booster series of inactivated vaccines conferred strong protection against severe/critical illness (pooled relative risk (RR) 0.17 [95% CI: 0.09–0.33]) but did not reduce symptom frequency (RR 0.99 [95% CI: 0.95–1.02]). Each 10-unit increase in GRI or CHI was associated with 7% (95% CI: 1–12%) and 6% (95% CI: 1–10%) lower odds of symptomatic infection and 3% (95% CI: 1–4%) lower odds of severe/critical illness. Later subvariants (BA.5, BF.7, and XBB) showed 24–38% higher odds of upper respiratory symptoms versus BA.1. Conclusions: The data collection context significantly impacted severity estimates, with higher estimates from emergency hospitals. Overall, inactivated vaccines provided strong protection against severe/critical outcomes while stringent public health measures were associated with lower severity. Our findings underscore the importance of consistent and standardized protocols to produce reliable estimates of SARS-CoV-2 severity in evolving epidemiological contexts. Full article

Background/Objectives: Adult vaccination remains suboptimal, particularly among older adults and individuals with chronic conditions. Hospitals represent a strategic setting for improving vaccination coverage among these high-risk populations. This systematic review and meta-analysis evaluated hospital-based interventions aimed at enhancing vaccine uptake in adults aged ≥60 years or 18–64 years with at-risk medical conditions. Methods: We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. Searches in PubMed, EMBASE, and Scopus identified studies published in the last 10 years evaluating hospital-based interventions reporting vaccination uptake. The risk of bias was assessed using validated tools (NOS, RoB 2, ROBINS-I, QI-MQCS). A meta-analysis was conducted for categories with ≥3 eligible studies reporting pre- and post-intervention vaccination coverage in the same population. Results: We included 44 studies. Multi-component strategies (n = 21) showed the most consistent results (e.g., pneumococcal uptake from 2.2% to 43.4%, p < 0.001). Reminder-based interventions (n = 4) achieved influenza coverage increases from 31.0% to 68.0% and a COVID-19 booster uptake boost of +38% after SMS reminders. Educational strategies (n = 11) varied in effectiveness, with one study reporting influenza coverage rising from 1.6% to 12.2% (+662.5%, OR 8.86, p < 0.01). Standing order protocols increased pneumococcal vaccination from 10% to 60% in high-risk adults. Hospital-based catch-up programs improved DTaP-IPV uptake from 56.2% to 80.8% (p < 0.001). For patient education, the pooled OR was 2.11 (95% CI: 1.96–2.27; p < 0.001, I² = 97.2%) under a fixed-effects model, and 2.47 (95% CI: 1.53–3.98; p < 0.001) under a random-effects model. For multi-component strategies, the OR was 2.39 (95% CI: 2.33–2.44; p < 0.001, I² = 98.0%) with fixed effects, and 3.12 (95% CI: 2.49–3.92; p < 0.001) with random effects. No publication bias was detected. Conclusions: Hospital-based interventions, particularly those using multi-component approaches, effectively improve vaccine coverage in older and high-risk adults. Embedding vaccination into routine hospital care offers a scalable opportunity to reduce disparities and enhance population-level protection. Future policies should prioritize the institutional integration of such strategies to support healthy aging and vaccine equity. Full article

Background: SARS-CoV-2 booster vaccination remains essential to prevent severe COVID-19, particularly in vulnerable populations such as older adults. This study evaluated the durability and dynamics of immune responses following booster vaccination(s) in >65-year-old individuals and examined their association with protection against new infections. Methods: Immune responses were evaluated at 3, 9, and 15 months post-booster, measuring SARS-CoV-2-specific IgG antibodies against spike [IgG(S)] and nucleocapsid [IgG(N)] proteins, neutralizing activity against the Omicron BA.2 variant, and cellular immunity. A subset of participants was tested before booster administration. Regression analyses examined the influence of clinical and immunological factors—including a bivalent fourth dose—on infection risk over time. Results: Booster vaccination significantly enhanced IgG(S) and neutralizing capacity, peaking at 3 months. Although a decline was observed by 9 months, responses remained above baseline. Individuals with prior SARS-CoV-2 infection exhibited higher IgG(S) levels and neutralizing titers, and significantly lower reinfection rates (15%), compared to uninfected individuals. A fourth vaccine dose further increased IgG(S) levels. While neutralizing capacity was not consistently enhanced by the fourth dose, recipients experienced a lower rate of new infections. Immune trajectory analyses revealed that breakthrough infections elicited strong humoral responses comparable to those seen in previously infected individuals, highlighting the role of hybrid immunity. Conclusions: In older adults, booster vaccination induces durable immune responses, with hybrid immunity offering enhanced protection. A fourth dose boosts antibody levels and reduces infection risk, supporting its use in this high-risk group. Continued monitoring is needed to determine the long-term effectiveness of boosters, particularly against emerging variants. Full article

Background: Breakthrough infections (BTIs) continue to occur among healthcare workers (HCWs) despite full COVID-19 vaccination, raising concerns about ongoing vulnerability in this high-risk group. In addition to initial BTIs, breakthrough reinfections (BTRs) have emerged as a challenge, with some HCWs experiencing multiple episodes of infection after vaccination. This study investigated the factors influencing breakthrough infection and reinfection rates among HCWs between January 2021 and December 2022 in Davao City, Philippines. Methods: This retrospective cohort study was conducted using secondary data from the Davao City Epidemiological Surveillance Unit, approved by the Department of Health. This study included 1011 fully vaccinated HCWs from various congressional districts. Results: BTI was observed in all HCWs included in the study. However, BTRs varied across occupational groups: medical technologists showed the highest reinfection rate (22.37%), followed by physicians (13.48%), and nurses/nurse aides (10.14%). Booster vaccination significantly reduced BTRs (5.83% vs. 11.18%, p = 0.0267). Occupation and institutional type were significant factors, with higher rates reported by physicians and in public hospitals (p = 0.0002 and p = 0.0041, respectively). The vaccine manufacturer, sex, age, and booster type showed no significant differences. Conclusion: These findings highlight the importance of targeted interventions for high-risk HCWs and emphasize the effectiveness of the booster vaccination. Full article

Patients undergoing peritoneal dialysis (PD) represent a uniquely vulnerable population due to intrinsic immunological dysfunction and a high prevalence of comorbid conditions. This review examines the complex interplay between natural and vaccine-induced immune responses to SARS-CoV-2 in this group, focusing on viral entry, immune activation, and immune evasion mechanisms. Particular attention is given to the impaired cellular and humoral responses seen in PD patients, including reduced T-cell function, diminished antibody production, and abnormal cytokine signaling, all of which contribute to an elevated risk of severe COVID-19 outcomes. The immunogenicity and clinical efficacy of various vaccine platforms, including inactivated, vector-based, and mRNA formulations, are critically assessed, with an emphasis on the role of booster doses in enhancing protection amid waning immunity and evolving viral variants. Furthermore, the review highlights the advantages of PD as a home-based modality that is compatible with telemedicine and may reduce the risk of viral exposure. These insights underscore the importance of developing individualized vaccination strategies, maintaining close immunological surveillance, and implementing innovative dialysis care approaches to improve clinical outcomes during the ongoing pandemic and future public health crises. Tailored booster strategies and telemedicine-integrated care models are essential for improving outcomes in this high-risk population. Full article

Background/Objectives: This prospective study investigated the impact of high-dose chemotherapy and autologous stem cell transplantation (ASCT) on anti-COVID-19 antibody levels in previously vaccinated multiple myeloma (MM) patients with confirmed antibody response (AR). Methods: All patients underwent at least a two-dose regimen mRNA vaccination and later received a high-dose melphalan conditioning regimen and ASCT. Results: Fourteen MM patients with confirmed AR underwent a total of nineteen ASCT reinfusions; their median age was 55 (34–67). The study found a significant and progressive decrease in antibody levels after ASCT, from 311 BAU/mL at baseline to 276 BAU/mL and 188 BAU/mL after one and three months, respectively, with a median anti-COVID-19 antibody level reduction of 39% (range 16–66%) that was statistically significant (p = 0.014) using the Friedman test. However, the third “booster” vaccination post-ASCT improved the humoral response at six months in nine patients (50% response rate) and corrected, at least in part, the negative impact of high-dose chemotherapy (p = 0.597). Despite the antibody decline, three patients who contracted COVID-19 after ASCT experienced mild, outpatient-managed infections, suggesting sufficient immune response. Furthermore, booster doses increased the proportion of high-responders (AR > 500 BAU/mL) post-ASCT from 22% to 55% (5/9 patients) at three and six months, respectively. Conclusions: The study concludes that ASCT negatively affects the humoral response, but booster vaccination can improve it, and residual antibodies may prevent severe COVID-19 in these vulnerable patients. Full article

Background/Objectives: The COVID-19 pandemic significantly threatened cancer patients and oncologic care. The rollout of vaccines emerged as a critical milestone, despite the initial lack of evidence regarding their safety and efficacy in this population. This systematic review and meta-analysis evaluate the current evidence on COVID-19 vaccination in patients undergoing radiotherapy (RT). Methods: PubMed, Livivo, Scopus, and Cochrane Library were systematically reviewed for relevant publications on COVID-19 vaccination in the context of radiation oncology, published by 19 April 2024. The treatment effects were calculated as the proportion of seroconverted individuals. Results: A total of 22 studies published between 2021 and 2024 were included, covering various aspects of vaccination, including safety, tolerability, qualitative and quantitative humoral responses, cellular responses, vaccination efficacy, and booster vaccinations. Notably, patients undergoing RT exhibited a high willingness to receive vaccination. Vaccination was overall well tolerated and safe, with a low incidence of side effects, which were primarily mild. The primary meta-analysis showed a seroconversion proportion of 91% [95% CI: 84–96%] overall, with a somewhat higher proportion of 93% in patients receiving RT alone, compared to 90% in patients receiving either RT or RT combined with chemotherapy. Furthermore, immunization during RT led to a sustained increase in antibody titers, with a notable long-term persistence of IgG. Conclusions: COVID-19 vaccines demonstrate excellent safety, immunogenicity, and efficacy in patients receiving RT, who also exhibit a high willingness to be vaccinated. The outcomes observed are comparable to those in healthy controls and superior to those seen in patients receiving other cancer treatments, such as chemotherapy. The vaccination of radiation oncology patients in future pandemics or epidemics is strongly advocated even during active treatment. Full article

Background and objective: The approval of mRNA-based vaccines for children and adolescents has contributed to global efforts to control the SARS-CoV-2 pandemic. While hybrid immunity—combining prior SARS-CoV-2 infection and vaccination—may offer enhanced protection, data on its effectiveness versus vaccine-induced immunity in the pediatric population are limited. Methods: This retrospective matched cohort study used linked health data from Norwegian nationwide health registries and the Italian Pedianet network. The study included children and adolescents aged 5–14 years eligible for COVID-19 vaccination at the time of approval (May/September 2021 and November 2021/January 2022, respectively). Mono- and two-dose vaccination schedules were assessed, and hybrid immunity was defined as prior SARS-CoV-2 infection followed by vaccination within 12 months. Conditional Cox regression models were used to estimate hazard ratios (HRs) for SARS-CoV-2 infection risk, adjusting for sociodemographics, comorbidities, and healthcare utilization. Results: The study included 626,537 children and adolescents in Norway and 38,938 in Italy. A single dose of the vaccine did not reduce the risk of infection among SARS-CoV-2–naive individuals in Norway (HR: 1.05; 95% CI: 1.04–1.07), whereas it was associated with an 8% risk reduction in Italy (HR: 0.92; 95% CI: 0.88–0.96). Among individuals with a recent prior infection (within 12 months), vaccination was associated with a reduced risk of reinfection in Norway (HR: 0.10; 95% CI: 0.05–0.13), but not in Italy (HR: 1.22; 95% CI: 0.83–1.80), compared to no vaccination. Among those with prior infection, vaccination was associated with a significantly reduced risk of reinfection in Norway (HR = 0.10; 95% CI: 0.05–0.20), but not in Italy (HR = 0.55; 95% CI: 0.27–1.11). Hybrid immunity provided greater protection against (re-)infection compared to vaccine-induced immunity alone, with a 26% risk reduction observed in Norway (HR = 0.74; 95% CI = 0.47–0.1.16) and an 86% reduction in Italy (HR = 0.14; 95% CI = 0.09–0.21). Conclusions: This analysis supports the effectiveness of SARS-CoV-2 vaccines in children, with hybrid immunity offering enhanced protection against reinfection. Given the waning effectiveness of vaccines over time, continued research and booster strategies are essential to sustain protection and mitigate transmission. Full article

Background/Objectives: Despite significant advancements in vaccine development and distribution, the optimal timing and integration of COVID-19 vaccination in Canada remain crucial to public health. As the SARS-CoV-2 virus continues to evolve, determining effective timing strategies for booster doses is necessary to sustain immunity, especially in high-risk populations. This systematic review aims to critically evaluate the timing and co-administration strategies of COVID-19 vaccines in Canada, comparing them with approaches in other G7 nations. Methods: The review seeks to identify best practices to inform national vaccination policies, with a particular focus on synchronizing COVID-19 and seasonal influenza vaccinations. We systematically searched Scopus, PubMed, Medline, and Web of Science (17 August 2021 to 7 July 2024) using the PECOS framework. Two independent reviewers screened titles/abstracts, extracted key data on immunogenicity, efficacy, and safety, and performed a narrative synthesis on timing and co-administration outcomes. Results: Evidence summarized across G7 countries reveals that most nations are converging on annual or flexible booster schedules tailored to high-risk groups, often aligning COVID-19 vaccination with influenza campaigns. Countries like Canada, the UK, and the US have integrated these efforts, while others maintain more independent or heterogeneous approaches. In addition, timely booster doses, whether administered annually or more frequently in high-risk settings, consistently reduce infection rates and hospitalizations. Conclusions: These findings collectively support the continued evolution of COVID-19 vaccination programs toward integrated, seasonally aligned strategies. Future public health efforts can build on these lessons not only to sustain protection against SARS-CoV-2 but also to strengthen preparedness for other respiratory infections. Full article

Previous studies have shown that 5-aminolevulinic acid phosphate together with sodium ferrous citrate, which is marketed as a food supplement, appears to be an important metabolic regulator in depleted T cell metabolism. Therefore, it was hypothesized that its administration in subjects vaccinated against COVID-19 could enhance their immune system. Therefore, the aim of our proof-of-concept study was to determine the safety (by adverse events monitoring) and the tolerability (by subject questionnaires) and to investigate immune-boosting properties (by Immunoglobulins) in which 200 subjects were randomized in a ratio of 1:1 within 2 arms. In the intervention arm, the study product was administered together with the vaccines Covishield or Covaxin, and up to 21 days thereafter with a 150 mg daily dose, whereas in the control arm, the subjects were vaccinated only. No safety issues were detected, and the evaluation of the subject questionnaires showed no limitation of the well-being, which confirms the excellent tolerability of 5-aminolevulinic acid phosphate with sodium ferrous citrate. Moreover, the ‘Change in Immunoglobulin G levels’, although statistically insignificant, showed strong signals of its immune supportive potential. However, further studies are recommended to verify the results. Full article

Background: Increasing evidence suggests that the immunogenicity of COVID-19 mRNA vaccines might influence the efficacy of immune checkpoint inhibitors (ICIs). Current studies have not considered the impact of additional vaccinations, which are now recommended as a preventive strategy against SARS-CoV-2 infection for cancer patients receiving active treatments. Consequently, we leveraged the prospective monitoring from the Vax-On-Third study to explore whether periodic mRNA vaccine boosters administered around the start of ICIs could influence the rates of immune-related adverse events (irAEs) and survival outcomes in patients with advanced non-small cell lung cancer (NSCLC). Methods: Our study included patients with a histological diagnosis of metastatic NSCLC and available PD-L1 tumor proportion score (TPS), who had undergone at least two cycles of upfront treatment with pembrolizumab, cemiplimab, or their combination with platinum-based chemotherapy. Patients who received any additional mRNA-based vaccine doses within 60 days before to 30 days after starting ICIs accounted for the exposed cohort. Those who declined further boosters formed the reference cohort. We analyzed differences in irAE frequencies, progression-free survival (PFS), and overall survival (OS) using univariate and multivariate analyses. Results: Between 27 November 2021 and 31 March 2024, we enrolled 226 eligible patients. The exposed cohort consisted of 112 patients who had received either a third or fourth dose of tozinameran or a bivalent booster. Based on PD-L1 expression levels, 93 (41%) and 133 (59%) patients received single-agent ICIs (PD-L1 TPS ≥ 50%) or combination regimens (PD-L1 TPS < 50%), respectively. Propensity-score matching using comprehensive criteria resulted in two cohorts of 102 patients each, with an optimal balance of prognostic factors. A thorough analysis of any grade irAEs showed no significant differences between the cohorts. A longitudinal survival assessment with a median follow-up of 22.8 (95% CI 19.2–26.0) months showed no difference between the cohorts. The median PFS for the reference and exposed cohorts was 7.5 (95% CI 5.9–9.1) and 8.2 (95% CI 6.2–10.2) months, respectively (p = 0.408; HR 0.88 [95% CI 0.66–1.18]). The median OS for the reference and exposed cohorts was 10.5 (95% CI 7.9–13.0) and 13.8 (95% CI 12.0–15.5) months, respectively (p = 0.170; HR 0.81 [95% CI 0.59–1.09]). Multivariate analysis confirmed that receiving additional mRNA vaccine boosters did not significantly affect the risk of disease progression or mortality. Univariate analysis within the subgroup of patients with high PD-L1 TPS who received single-agent ICIs showed a significant OS advantage for patients in the exposed cohort (9.7 [95% CI 8.1–11.2] vs. 18.6 [95% CI 13.5–23.6] months; p = 0.034; HR 0.59 [95% CI 0.36–0.96]). Conclusion: After optimally balancing prognostic factors, regular mRNA vaccine boosters at the onset of ICIs did not impact the safety and survival of patients with advanced NSCLC. The improved outcome observed in patients with high PD-L1 expression levels aligns with previous findings and warrants further investigation. Full article