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

Introduction

To support evidence-based clinical & shared decision-making during the 2025-2026 respiratory tract infection season, IDSA developed rapid guidelines for the use of U.S-licensed vaccine against COVID-19, Influenza, and RSV in adult and pediatric patients who are immunocompromised.  

Immunocompromised patients are defined as individuals who have impaired immune systems either due to their underlying disease (e.g. HIV, malignancy) or due to the medications they must take (e.g. solid organ transplant). Patients with chronic organ dysfunction (e.g. end stage renal disease: requiring dialysis, cirrhosis, or end-stage heart disease) are not considered in this guideline. 

These recommendations address patients who have a hematologic malignancy, primary immunodeficiency, autoimmune disease treated with immunosuppressants or biologics, or HIV with severe immunosuppression (CD4 <15% or <200/mm³), as well as patients who are  recipients of solid organ transplants (SOT), hematopoietic cell transplantation (HCT), chimeric antigen receptor T-cell therapy (CAR-T), or solid-tumor chemotherapy. 

Methods

The IDSA panel included clinicians with expertise in infectious diseases, hematology/oncology, solid organ transplantation, immunology, virology/vaccinology, immunosuppressive medications and monoclonal antibodies, pediatrics, and HIV. The panel established one clinical question for the use of each vaccine (“should [virus] vaccine vs no vaccine be used in immunocompromised patients?”) and identified patient-importance outcomes for both vaccine effectiveness and adverse events (e.g., hospitalization, mortality, progression to severe disease; and serious adverse events, or exacerbation of immunocompromising or autoimmune conditions, respectively). 

To establish the basis for recommendations, the panel reviewed the best available evidence published in the 18–24 months since the evidence base for the last CDC recommendations for each vaccine (search start dates were June 2024 for COVID-19; August 2024 for RSV; and August 2023 for influenza and search end date was July 31, 2025). Using the results of a systematic literature review conducted by the Vaccine Integrity Project, and supplementary searches for additional patient-important outcomes, the IDSA panel used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the certainty of evidence and determine the strength of each recommendation (Figure 1). A summary of the systematic review and guideline development processes is available in the supplemental materials.   

Pooled vaccine effectiveness rates and corresponding relative effect measures (RR, HR, OR) were summarized in the GRADE evidence profile. To better illustrate population effects, absolute risk differences were calculated by using baseline risk estimates from cohort studies as well as additional estimates from published cumulative incidence rates [1] adjusted for immunocompromised status. Risk of bias of included studies were evaluated using the ROBINS-I tool. The overall certainty of evidence was rated for each outcome and across studies using established GRADE criteria. 

Figure 1. Approach and implications to rating the quality of evidence and strength of recommendations using GRADE methodology (unrestricted use of figure granted by the U.S. GRADE Network)

Recommendation

In adults and children with compromised immunity*, the IDSA guideline panel recommends administering age-appropriate 2025-2026 COVID-19 vaccinations (strong recommendation, moderate certainty of evidence). 
*see Table 1 for risk group and timing. 

Remarks

• An FDA-approved 2025-2026 COVID-19 vaccine dose should be given as soon as possible.
• A second dose of COVID-19 vaccination is likely to extend protection.
• For never vaccinated and incompletely vaccinated patients refer to published guidelines [2].
• Household members and close contacts of immunocompromised patients should be up to date with COVID-19 vaccination.
• It is appropriate for patients to receive COVID-19, influenza, and RSV vaccines together.

Table 1. COVID-19 Vaccination Guidance by Immunocompromised Population^[2-8]

*Defer during acute transplant rejection treatment or severe/acute illness
**Use shared-decision making for early windows based on levels of community virus circulation 

Evidence Summaries

Results

The search identified two cohort studies [9, 10] and five test-negative case control studies [11-15] that reported on vaccine effectiveness outcomes. The search identified a self-controlled case series [16] that reported serious adverse events and 3 observational studies [17-19] that reported exacerbations of immunocompromising or autoimmune conditions.

Table 2. GRADE Evidence Profile: Should COVID-19 vaccination vs. no vaccination be used in immunocompromised patients (adults and children)? 

*Note: Interval since last dose, days median (IQR): Caffrey 2024: 52 (33-73); Link Gelles 2024: 56 (32-81); Link Gelles 2025 MMWR: 53 (31-78); Nguyen 2025: 58 (41-71)

CI: confidence interval; HR: hazard ratio; OR: odds ratio 

Explanations 

a. Applying ROBINS-I tool, residual, unknown confounders could not be ruled out 
b. Some identified confounders were unlikely to have materially inflated the vaccine effectiveness; rather point in the opposite direction to potentially strengthen our inference of vaccine effectiveness. Not rated down further.  
c. To further illustrate population impact by providing absolute risk differences, an additional baseline risk for hospitalization of 1% was set; estimated using COVID-net (Taylor CA, Patel K, Pham H, et al. COVID-19-Associated Hospitalizations Among U.S. Adults Aged ≥18 Years - COVID-NET, 12 States, October 2023-April 2024. MMWR Morb Mortal Wkly Rep 2024; 73(39): 869-75) cumulative incidence rate (88% of hospitalized patients were not vaccinated), multiplied by RR of 2.75 to account for immunocompromised conditions (Chapman A, Berenbaum F, Curigliano G, Pliakas T, Sheikh A, Abduljawad S. Risk of Severe Outcomes From COVID-19 in Immunocompromised People During the Omicron Era: A Systematic Review and Meta-Analysis. Clin Ther 2025; 47(9): 770-87). 
d. Due to low number of events, fragility in the estimate may be present 
e. Applying ROBINS-I tool, bias was present for confounding and measurement of outcomes 
f. Applying ROBINS-I tool, bias was present in several domains including confounding, selection of participants, and measurement of outcomes 
g. Increase in imaging detected brain lesions of uncertain clinical relevance 
h. Due to low number of events 

Vaccine Effectiveness

COVID-19 vaccination in the immunocompromised population is associated with a reduction in COVID-19 associated hospitalization. Vaccine effectiveness estimates ranged from 33% to 56% in studies and included one cohort study [9] (VE 46%, 95% CI 39-52%) and four test-negative case-control studies [11-13, 15] (VE 37%, 95% CI 29-44; moderate certainty evidence). Vaccination is associated with reductions in critical illness [14] (VE 40%, 95% CI 26-51; moderate certainty evidence) and COVID-19-related mortality [10] (VE 61%, 95% CI 36-77; low certainty evidence) as well as COVID-19 associated emergency department/urgent care visits [11] (VE 34%, 95% CI 22-45) and COVID-19 associated outpatient vists [11] (VE 40%, 95% CI 19-55; moderate certainty evidence). For most studies, follow-up time or time since last vaccine dose was relatively short, with a median of less than two months. Given that vaccine protection decreases over time, these estimates are likely to represent higher-end values.

Adverse Events

An increased risk of a small number of adverse events was observed in a self-controlled case series [16] conducted from 2020-2022 following a third vaccine dose of mRNA-based vaccine; however, due to a large number of evaluated conditions (52), multiple testing, and low event rates, a spurious association cannot be ruled out (Bonferroni-corrected p value was not significant at the 1% level (corrected p=0.22). Several adverse outcomes of interest, such as thrombotic events (e.g., myocardial infarction and stroke) were less frequent in the vaccinated population. Although cases of myocarditis were observed in the vaccinated cohort, the observed risk was lower in the vaccinated group compared to the unvaccinated group likely due to increased risk of myocarditis during COVID infections. However, this estimate was imprecise due to the rarity of this outcome (<1:48,000) after 1^st and 2^nd vaccine dose). In summary, little or no serious adverse events were associated with currently available COVID-19 vaccines (low certainty evidence). 

Overall, exacerbations of immunocompromising or autoimmune conditions do not increase due to vaccination; however, an increase in lesions on imaging in multiple sclerosis patients was reported in one study [19] (very low certainty evidence) although the clinical implication remains uncertain. 

Rationale for Recommendation

The panel agreed that the overall certainty of evidence is moderate due to evidence on COVID-19 vaccine effectiveness in immunocompromised patients driven by the prevention of hospitalization. The moderate size of beneficial effects combined with little or no serious adverse effects justifies a strong recommendation for the administration of the 2025-2026 COVID-19 vaccine.

Implementation Considerations

Immunocompromised patients remain at increased risk for severe COVID-19 and may have attenuated vaccine responses, necessitating tailored vaccination strategies and ongoing risk mitigation. Implementation of COVID-19 vaccine recommendations in this population should address the following core considerations:

General Principles:

• All immunocompromised individuals aged ≥6 months should receive at least one dose of the current season’s COVID-19 vaccine, with additional doses based on prior vaccination history and clinical judgment.
• Majority of evidence came from mRNA vaccines.
• Shared clinical decision-making is essential, allowing flexibility in timing and dosing to accommodate immunosuppressive therapy schedules, travel, and individual risk factors.
• Household members and close contacts should be up to date with COVID-19 vaccination to reduce transmission risk. 

Subgroup-Specific Considerations:

• Solid Organ Transplant (SOT): Vaccination is optimally timed ≥2 weeks pre-transplant or ≥3 months post-transplant, avoiding periods of pulse immunosuppression and active rejection. Consider earlier administration during high community transmission or patient risk factors.
• Hematopoietic Cell Transplant (HCT)/CAR-T: Vaccination is recommended ≥3 months post-HCT/CAR-T, or ≥3-6 months after B-cell depleting therapy, with earlier vaccination considered during high community transmission.
• Hematologic Malignancy: Align vaccination with treatment cycles, ideally ≥2 weeks before new immunosuppression; defer during febrile neutropenia or severe illness. Consider during high community transmission.
• Solid Tumor Chemotherapy: Prefer vaccination ≥2 weeks before therapy, but vaccination during or after therapy is acceptable if needed; defer during severe illness. Consider during high community transmission.
• Primary Immunodeficiency: Vaccinate when clinically stable, aligning with IVIG/SCIG schedules or clinic access; defer during acute illness. Consider during high community transmission.
• Autoimmune Immunosuppression: Vaccinate ≥2 weeks prior to biologics or ≥3 months after therapy; ≥3-6 months after B-cell depletion; defer during severe flare or infection. Consider during high community transmission.
• HIV: Vaccinate regardless of CD4 count or viral load, ideally when stable and aligned with preventive routine care; defer during acute illness. Consider during high community transmission.

Additional Implementation Issues:

• Vaccine effectiveness is lower than in the immunocompetent population supporting the need for ongoing risk assessment based on levels of community transmission.
• Rapid access to antivirals targeting SARS-CoV2 and nonpharmaceutical interventions remain important adjuncts, especially for those with poor vaccine responses or contraindications.  
• Patients may self-attest to immunocompromised status for vaccine eligibility. 

Staying up to date with COVID-19 vaccination is critical for immunocompromised populations, with individualized schedules, and close coordination with clinical care. Ongoing communication, equitable access, and integration of preventive strategies are essential for optimal protection.

Research Priorities

The evidence highlights persistent gaps in immunogenicity, clinical effectiveness, and optimal vaccine strategies for diverse immunocompromised subgroups, as well as the need for tailored approaches and robust outcome data. 

Research priorities for COVID-19 vaccination in immunocompromised patients should address critical gaps in immunogenicity, clinical effectiveness, and implementation strategies across heterogeneous populations. Immunocompromised individuals—including those with solid organ transplants, hematologic malignancies, autoimmune diseases, and HIV—exhibit variable and often attenuated immune responses to COVID-19 vaccines, with organ transplant recipients and those receiving B-cell depleting therapies at highest risk for poor seroconversion and breakthrough infection.

Key Priorities Include:

• Defining correlates of protection and immunogenicity thresholds for diverse immunocompromised subgroups, including the role of cellular and humoral immunity, and the impact of specific immunosuppressive regimens.
• Longitudinal studies of vaccine durability and waning immunity, especially in the context of emerging SARS-CoV-2 variants and evolving immunosuppressive therapies.
• Comparative effectiveness studies of vaccine platforms and dosing strategies, including mRNA versus protein subunit vaccines, and the impact of additional (booster) doses on seroconversion and clinical outcomes.
• Evaluation of modified vaccine schedules and timing relative to immunosuppressive therapy, including optimal intervals for vaccination before or after transplantation, chemotherapy, or biologic therapy.
• Real-world effectiveness data, including breakthrough infection rates, hospitalization, and mortality, with subgroup analyses by age, comorbidity, and immunosuppressive regimen.
• Enhanced safety data for rare vaccine adverse events (e.g. myocarditis) and concerns specific to this patient population (i.e. risk of organ transplant rejection or autoimmune flare) with subgroup analyses by comorbidity and immunosuppressive regimen.
• Strategies to enhance vaccine response, such as temporary modification of immunosuppression, use of adjuvanted or higher-dose vaccines, and integration of nonpharmaceutical interventions and early therapeutics.
• Equity in vaccine access and uptake, with research on barriers to vaccination, disparities in coverage, and interventions to improve outreach in high-risk populations. 

Addressing these priorities will require multicenter, prospective studies with harmonized outcome measures, robust subgroup analyses, and integration of immunologic and clinical endpoints. Enhanced vaccine regimens and tailored preventive strategies remain essential for protecting immunocompromised patients as COVID-19 transitions to endemicity. 

References

1. Taylor CA, Patel K, Pham H, et al. COVID-19-Associated Hospitalizations Among U.S. Adults Aged ≥18 Years - COVID-NET, 12 States, October 2023-April 2024. MMWR Morb Mortal Wkly Rep 2024; 73(39): 869-75.
2. Panagiotakopoulos L, Moulia DL, Godfrey M, et al. Use of COVID-19 Vaccines for Persons Aged ≥6 Months: Recommendations of the Advisory Committee on Immunization Practices - United States, 2024-2025. MMWR Morb Mortal Wkly Rep 2024; 73(37): 819-24.
3. Viganò M, Beretta M, Lepore M, et al. Vaccination Recommendations in Solid Organ Transplant Adult Candidates and Recipients. Vaccines (Basel) 2023; 11(10).
4. American Society of Transplant Surgeons ASoT, The International Society for Health & Lung Transplantation (ISHLT). Joint Statement about COVID-19 Vaccination in Organ Transplant Candidates and Recipients, 2022.
5. ASH-ASTCT COVID-19 Vaccination for HCT and CAR T Cell Recipients: Frequently Asked Questions Available at: https://www.hematology.org/covid-19/ash-astct-covid-19-vaccination-for-hct-and-car-t-cell-recipients. Accessed October, 15 2025.
6. Silva-Pinto A, Abreu I, Martins A, Bastos J, Araújo J, Pinto R. Vaccination After Haematopoietic Stem Cell Transplant: A Review of the Literature and Proposed Vaccination Protocol. Vaccines (Basel) 2024; 12(12).
7. Dioverti V, Boghdadly ZE, Shahid Z, et al. Revised Guidelines for Coronavirus Disease 19 Management in Hematopoietic Cell Transplantation and Cellular Therapy Recipients (August 2022). Transplant Cell Ther 2022; 28(12): 810-21.
8. Bass AR, Chakravarty E, Akl EA, et al. 2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases. Arthritis Care Res (Hoboken) 2023; 75(3): 449-64.
9. Wilson A, Rahai N, Beck E, et al. Evaluating the Effectiveness of mRNA-1273.815 Against COVID-19 Hospitalization Among Adults Aged ≥ 18 Years in the United States. Infect Dis Ther 2025; 14(1): 199-216.
10. Payne AB, Novosad S, Sung HM, et al. Effectiveness of 2023-2024 COVID-19 vaccines against COVID-19-associated hospitalizations among adults aged ≥18 years with end stage kidney disease - United States, September 2023-April 2024. Vaccine 2025; 55: 127010.
11. Caffrey AR, Appaneal HJ, Lopes VV, et al. Effectiveness of BNT162b2 XBB vaccine in the US Veterans Affairs Healthcare System. Nat Commun 2024; 15(1): 9490.
12. Link-Gelles R, Rowley EAK, DeSilva MB, et al. Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Hospitalization Among Adults Aged ≥18 Years with Immunocompromising Conditions - VISION Network, September 2023-February 2024. MMWR Morb Mortal Wkly Rep 2024; 73(12): 271-6.
13.  Link-Gelles R, Chickery S, Webber A, et al. Interim Estimates of 2024-2025 COVID-19 Vaccine Effectiveness Among Adults Aged ≥18 Years - VISION and IVY Networks, September 2024-January 2025. MMWR Morb Mortal Wkly Rep 2025; 74(6): 73-82.
14. Link-Gelles R, Rowley EAK, Irving SA, et al. Estimated 2023-2024 COVID-19 Vaccine Effectiveness in Adults. JAMA Netw Open 2025; 8(6): e2517402.
15. Nguyen JL, Mitratza M, Volkman HR, et al. Effectiveness of the BNT162b2 XBB.1.5-adapted vaccine against COVID-19 hospitalization related to the JN.1 variant in Europe: a test-negative case-control study using the id.DRIVE platform. EClinicalMedicine 2025; 79: 102995.
16. Chen DT, Copland E, Hirst JA, et al. Uptake, effectiveness and safety of COVID-19 vaccines in individuals at clinical risk due to immunosuppressive drug therapy or transplantation procedures: a population-based cohort study in England. BMC Med 2024; 22(1): 237.
17. Rossier LN, Décosterd NP, Matter CB, et al. SARS-CoV-2 vaccination in inflammatory bowel disease patients is not associated with flares: a retrospective single-centre Swiss study. Ann Med 2024; 56(1): 2295979.
18. Li M, Liao L, Huang W, et al. Patients with advanced cancer were treated with immune checkpoint inhibitors and injected with COVID-19 vaccine to improve their prognosis without increasing pancreatic related adverse events. Hum Vaccin Immunother 2024; 20(1): 2358575.
19. Ganelin-Cohen E, Buxbaum C, Bosak N, et al. The effect of COVID-19 vaccination on multiple sclerosis activity as reflected by MRI. Brain Behav 2024; 14(7): e3587.

Notes

Acknowledgments

We thank Lindsey Fraser-Green for medical librarian support (creation and execution of literature searches) and Genet Demisashi, Loretta Dzanya, Jonathan Heald, and Dana Wollins for project coordination. 

Lindsey Baden served as Chair and oversaw cross-subgroup integration. Anoma Nellore (COVID-19), Paul Goepfert (Influenza), and Chen Sabrina Tan (RSV) served as subgroup leads. Members of the COVID-19 subgroup included Kristina Bajema, Katherine Belden, and Dean Blumberg; the Influenza subgroup included Morgan J. Katz, Daniel Kaul, and Tanvi Sharma; and the RSV subgroup included Shweta Anjan, Ella J. Ariza-Heredia, Francisco Magana, and Timothy Minniear. 

For COVID-19, Yngve Falck-Ytter and Elizabeth York served as lead methodologists; Dipleen Kaur and Jennifer Loveless provided methodological support. For Influenza and RSV, Yngve Falck-Ytter and Dipleen Kaur served as lead methodologists; Jennifer Loveless and Elizabeth York provided methodological support. All authors contributed to drafting and revising the guideline and approved the final version and recommendations.

Conflicts of Interest

Possible conflicts of interest. Evaluation of relationships as potential conflicts of interest is determined by a review process. The assessment of disclosed relationships for possible COIs is based on the relative weight of the financial relationship (i.e., monetary amount) and the relevance of the relationship (i.e., the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration).

The following panelists disclosed relationships with companies that own products unrelated to the topic of COVID-19, Influenza, and RSV: A.N receives research funding from National Institutes of Health (NIH); C.T receives research funding from NIH; D.K received research funding from Nobelpharma and National Institute of Allergy and Infectious Diseases (NIAID); served as a non-promotional (CME) speaker for CME Outfitters; E.J.A.H received research funding from ASCO and receives research funding from SoftDev Incorporated; K.B receives research funding from VA Cooperative Studies Program; L.B receives research funding from the NIH and the NIAID, serves as Editor for New England Journal of Medicine, and serves as an advisor for the Biomedical Advanced Research and Development Authority (BARDA)/NIH and FDA;  M.J.K serves as an advisor for Skinclique, receives research funding from the Agency for Healthcare Research and Quality (AHRQ), and provides expert testimony for law firms on infectious disease related issues; P.G receives research funding from NIAID; and T.M receives research funding from NIAID; C.S.T. receives research funding from NINDS and Eurofin-Viracor.
 
The following panelists have relationships with companies that own products related to the topic of COVID-19 and RSV:
P.G received research funding from Pfizer (concluded prior to joining the panel); and D.K receives research funding from Pfizer.