High-dose versus standard-dose influenza vaccine for immunocompromised patients: A systematic review and meta-analysis of randomised clinical trials Rivera Izquierdo, Mario Verddejo-Iañez, Alejandro Morales-Portillo, Arturo Gómez-Alcaide, Manuel Láinez-Ramos-Bossini, Antonio Jesús Martínez Ruiz, Virginia Ana Fernández-Martínez, Nicolás Francisco Martín de los Reyes, Luis Miguel Jiménez Mejías, Eladio Guerrero Fernández de Alba, Inmaculada Valero Ubierna, María del Carmen Lardelli Claret, Pablo Schoenenberger-Arnaiz, Joan Antoni Jiménez Moleón, José Juan Immunosuppression Vaccination Influenza This paper was funded by the Instituto de Investigación Biomédica de Lleida, Fundación Dr Pifarré (IRBLleida).This paper was funded by the Instituto de Investigación Biomédica de Lleida, Fundación Dr Pifarré (IRBLleida). Background: Immunocompromised patients present a higher risk of severe influenza disease and respond worse to vaccination. Objective: We aimed to assess immunogenicity and safety of high-dose vs. standard-dose influenza vaccine in immunocompromised patients. Data source: A search was conducted in Medline, Web of Science, Scopus and ClinicalTrials.gov from inception to March 2024 with no other restrictions. Study eligibility: Randomised clinical trials reporting immunogenicity or safety of high-dose versus standard-dose influenza vaccine in immunocompromised patients were included. Methods: The protocol was prospectively registered (PROSPERO ID: CRD42023466202). A meta-analysis was conducted using random-effects models. Heterogeneity was assessed through I2 statistic. Subgroup analyses were conducted, and publication bias was assessed through funnel plots and Egger’s tests. Results: A total of 21 analyses from 16 randomised clinical trials were included. Regarding immunogenicity (including 1862 patients), high-dose influenza vaccine showed higher geometric mean titre of hemagglutination inhibition and higher seroconversion rates for all strains (RR=1.30, 95%CI:1.04–1.57, I2=45.0% for H1N1; RR=1.22, 95%CI:1.03–1.41, I2=39.5% for H3N2; RR=1.39, 95%CI:1.15–1.63, I2=18.1% for B). These findings were reinforced in studies with higher methodological quality and higher sample sizes. Regarding safety (including 1403 patients), there were no differences in reported adverse events except for pain, higher in the high-dose influenza vaccine group (RR=1.29, 95%CI:1.04–1.54). Although high-dose influenza vaccine showed less frequency of clinical outcomes, data were not conclusive as few studies analysed clinical effectiveness. Conclusions: High-dose influenza vaccine showed higher immunogenicity and similar safety than standarddose vaccine and should be recommended for immunocompromised patients. Future larger randomised clinical trials analysing clinical effectiveness are required to provide recommendations for specific immunocompromised populations. 2026-01-19T12:20:48Z 2026-01-19T12:20:48Z 2025-06-23 journal article Rivera-Izquierdo M, Verdejo-Iáñez A, Morales-Portillo A, González-Alcaide M, Láinez-Ramos-Bossini AJ, Martínez-Ruiz V, Fernández-Martínez NF, Martín-delosReyes LM, Jiménez-Mejías E, Guerrero-Fernández de Alba I, Valero-Ubierna MDC, Lardelli-Claret P, Schoenenberger-Arnaiz JA, Jiménez-Moleón JJ. High-dose versus standard-dose influenza vaccine for immunocompromised patients: A systematic review and meta-analysis of randomised clinical trials. J Infect. 2025 Aug;91(2):106538. doi: 10.1016/j.jinf.2025.106538 1532-2742 0163-4453 https://hdl.handle.net/10481/109892 10.1016/j.jinf.2025.106538 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Elsevier