The Infectious Diseases Society of America (IDSA) convened an expert panel to develop a rapid, evidence-based guideline on the use of influenza vaccination for immunocompromised adults and children for the 2025–2026 respiratory virus season. The guideline aims to inform clinical decision-making for patients with underlying immunocompromising conditions or who are receiving immunosuppressive therapies, recognizing that these individuals are at heightened risk for severe influenza-related complications while often exhibiting attenuated vaccine responses.
The panel conducted a systematic review of the literature published between August 2023 and July 2025 and supplemented findings with analyses from the Vaccine Integrity Project. The review included only comparative effectiveness and harm data. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of evidence and to determine the strength of recommendations.
Based on the review, direct evidence in immunocompromised populations was limited but indicated a meaningful clinical benefit: influenza vaccination reduced influenza-associated hospitalization by 32%. Indirect evidence from studies in older adult populations demonstrated consistent reductions in hospitalization, intensive care unit admission, and all-cause mortality, supporting the applicability of benefit to immunocompromised groups.
Given a moderate certainty of benefit and a low likelihood of serious harm, IDSA issues a strong recommendation that all immunocompromised individuals aged 6 months and older receive an age-appropriate 2025–2026 influenza vaccine. The guideline emphasizes individualized decisions that account for the patient’s underlying condition, the timing of immunosuppressive therapies, and prevailing community influenza activity.
The panel notes that some vaccine formulations may elicit stronger immune responses in populations with reduced immunogenicity. Specifically, high-dose or adjuvanted vaccines may offer enhanced immunogenicity in immunocompromised patients. The guideline indicates these formulations as potential options but emphasizes tailoring vaccine choice to age, availability, and individual clinical circumstances.
Safety data reviewed by the panel did not demonstrate an increased risk of Guillain-Barré syndrome or other serious adverse events associated with influenza vaccination in the populations studied. Studies that specifically evaluated autoimmune disease activity or exacerbation of immunocompromising conditions did not reveal significant safety concerns. Overall, the available evidence supports a favorable safety profile in immunocompromised individuals.
The guideline stresses that vaccination should be individualized. Key considerations include the patient’s specific immunocompromising condition, the timing of planned or recent immunosuppressive therapy, and local community influenza transmission. Clinicians are advised to weigh these factors when scheduling vaccination to optimize potential immune response while minimizing disruption to disease-specific care.
To reduce the risk of transmission to immunocompromised patients, the panel strongly recommends vaccination of household contacts. Vaccinating close contacts is presented as an adjunct strategy to directly vaccinating the patient, recognizing that indirect protection may be particularly important for individuals with blunted vaccine responses.
The guideline identifies several areas where evidence is insufficient and further research is needed. Priorities include:
These knowledge gaps shaped the panel’s recommendations and were highlighted as targets for future investigation.
A conflict of interest statement accompanies the guideline; the source notes that evaluation of disclosed relationships for potential conflicts was determined through a review process considering the weight and relevance of financial relationships. The guideline was published as a practice guideline and systematic review in Clinical Infectious Diseases (2026 Aug 24;82[Supplement_3]:i117–i122) with DOI 10.1093/cid/ciag116 and is available as a free article. The guideline authors include members of academic infectious diseases divisions and IDSA Clinical Affairs and Practice Guidelines staff.