IDSA 2025 Guidelines on the use of vaccines for the prevention of seasonal Influenza infections in immunocompromised patients

Immunocompromised individuals are at heightened risk for severe influenza-related complications, yet vaccine responses may be attenuated due to underlying disease or immunosuppressive therapies. To inform clinical decision-making for the 2025-2026 respiratory virus season, the Infectious Diseases Society of America (IDSA) convened an expert panel to develop rapid evidence-based guidelines on influenza vaccination for immunocompromised adults and children. The panel conducted a systematic review of literature published between August 2023 and July 2025, supplemented by analyses from the Vaccine Integrity Project. Only comparative effectiveness and harm data were included. Certainty of evidence and strength of recommendations were assessed using the GRADE approach. Direct evidence in immunocompromised populations was limited but demonstrated that influenza vaccination reduced influenza-associated hospitalization by 32%. Indirect evidence from older adult populations showed consistent reductions in hospitalization, intensive care admission, and all-cause mortality, supporting applicability to immunocompromised groups. No increased risk of Guillain-Barré syndrome or serious adverse events was detected, and studies evaluating autoimmune or immunocompromising disease exacerbation showed no significant safety concerns. Given moderate certainty of benefit and low likelihood of serious harm, IDSA strongly recommends that all immunocompromised individuals aged ≥6 months receive an age-appropriate 2025-2026 influenza vaccine. Vaccination should be individualized based on underlying conditions, timing of immunosuppressive therapy, and community influenza activity. High-dose or adjuvanted vaccines may offer enhanced immunogenicity. Household contacts should also be vaccinated to reduce transmission risk. Ongoing research is needed to define correlates of protection, optimize vaccine timing, improve real-world effectiveness data, and enhance strategies for patients with blunted immune responses.