IDSA 2025 Guidelines on the use of vaccines for the prevention of seasonal COVID-19 infections in immunocompromised patients

Abstract 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 U.S.-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 seven observational effectiveness studies and four 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.