IDSA 2025 Guidelines on the Use of Vaccines for the Prevention of Seasonal COVID-19 Infections in Immunocompromised Patients

Immunocompromised individuals face elevated risks of severe COVID-19, yet vaccination guidance for these populations continues to evolve. To support evidence-based decision-making for the 2025-2026 respiratory virus season, the Infectious Diseases Society of America (IDSA) convened a multidisciplinary panel to develop rapid guidelines on the use of US-licensed COVID-19 vaccines in adults and children with hematologic malignancies, primary immunodeficiency, autoimmune disease on immunosuppressive therapy, HIV with severe immunosuppression, solid organ transplantation, hematopoietic cell transplantation (HCT), chimeric antigen receptor T-cell therapy (CAR-T), or solid tumor chemotherapy. A systematic evidence review of studies published from June 2024 to July 2025 identified comparative data on vaccine effectiveness and safety. Using the GRADE framework, the panel evaluated 7 observational effectiveness studies and 4 safety-focused studies. Across studies, COVID-19 vaccination was associated with reduced hospitalization (33%-56% effectiveness), critical illness, mortality, and COVID-19-related outpatient or emergency care visits. Serious adverse events were rare, and available evidence did not show consistent increases in exacerbations of underlying immunocompromising conditions. Most studies had short follow-up durations, likely reflecting higher-end estimates of vaccine effectiveness. Given moderate certainty of benefit and low certainty of harm, the panel strongly recommends the 2025-2026 COVID-19 vaccine for all immunocompromised individuals aged ≥6 months, with timing tailored to immunosuppressive therapy, clinical stability, and community transmission levels. Adjunct strategies-including vaccination of household contacts and early antiviral access-remain essential. Research priorities include defining immunologic correlates of protection, evaluating durability, optimizing vaccine timing, and improving real-world effectiveness and safety data.