About
- CDC vaccine recommendations are developed using an explicit evidence-based method based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.
Background
The number of solid organ transplants (SOTs) performed each year in the United States has increased steadily over the last two decades, from 25,475 in 2003 to 46,630 in 2023. The most commonly transplanted organs are kidney (59% in 2023), followed by liver (23%), heart (10%), lung (6%), and dual kidney/pancreas (2%).1 The majority of transplants are performed among adults ages 18 through 64 years (72% in 2023), with a lesser proportion in adults aged ≥65 years (24%) and children aged <18 years (4%).1 SOT recipients generally require lifelong immunosuppressive medications to maintain viability of the grafted organ. This population has been shown in some studies to be at potentially increased risk of severe and complicated influenza illness.23
SOT recipients aged ≥6 months are recommended to receive routine annual influenza vaccination with an age-appropriate inactivated or recombinant vaccine.4 Given their potential increased susceptibility to severe influenza, higher antigen dose vaccination strategies and adjuvanted influenza vaccines have been studied in this population. Moreover, the American Society for Transplantation (AST) has stated that either high-dose or booster influenza vaccination strategies might be preferable for this population.5 However, high-dose influenza vaccine and adjuvanted influenza vaccine are approved in the United States only for persons aged ≥65 years; administration to persons aged <65 years might not be covered by insurance.
The purpose of this review was to determine whether there is adequate evidence to support a recommendation that higher dose and adjuvanted influenza vaccines are acceptable options for influenza vaccination of solid organ transplant recipients who are younger than the approved age for these vaccines.
Methods
A systematic literature search was conducted to identify and review published literature relevant to the efficacy, effectiveness and safety of HD-IIV, aIIV, and RIV, and other increased antigen dose strategies (e.g., double doses of standard -dose vaccine administered simultaneously) compared with unadjuvanted SD-IIVs and with one another among immunocompromised persons. Literature search strategies are summarized in Appendix 2. Following screening of literature for eligibility, papers describing data for solid organ transplant populations were identified. Randomized and observational studies (traditional and test-negative case-control, retrospective and prospective cohort designs) were included. Case reports and case series were excluded. Risk of bias was assessed with the Cochrane Risk of Bias version 2 tool for randomized studies6 and the tool proposed by Murad et al. for nonrandomized studies without comparison groups.7 Meta-analyses were performed using R8. Given the small number of available studies for each comparison, meta-analyses were performed using a fixed-effects (or common effects) model. Risk ratios were calculated using the Mantel-Haenzel exact method; if both arms had zero events, the study was excluded from the meta-analysis model. GRADE tables were compiled using GRADEPro.9
Tables
Table 1: Policy Question and PICO
| Population | Solid organ transplant recipients aged ≥6 months |
|---|---|
| Intervention | High-dose (HD-IIV), adjuvanted (aIIV), or recombinant (RIV) trivalent or quadrivalent influenza vaccines |
| Comparison | Single intramuscular dose of standard dose unadjuvanted influenza vaccines (trivalent or quadrivalent) |
| Outcomes | Primary outcomes (included in GRADE)
Benefits:
Harms:
|
Table 2: Outcomes and Rankings
| Outcome | Importance | Included in Evidence Profile |
|---|---|---|
| Benefits | ||
| Influenza-associated hospitalization | Critical | Yes |
| Medically-attended influenza | Critical | No |
| Laboratory-confirmed influenza—immunogenicity data acceptable | Important | Yes |
| Harms | ||
| Transplant rejection or graft failure | Critical | Yes |
| Neuroinflammatory conditions , e.g. Guillain-Barré syndrome (GBS), acute disseminated encephalomyelitis (ADEM) | Critical | No |
| Other immune-related adverse events, including new onset or exacerbation of an autoimmune condition | Critical | No |
Table 3: Summary of Studies Reporting Outcomes of Interest
Table 3a: Summary of Studies Reporting Influenza-Associated Hospitalizations (Critical)
| Author/Year | Age Transplant population | N intervention | N comparison | Risk ratio (95% CI) | Risk of Bias |
|---|---|---|---|---|---|
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
1/205 aIIV3 | 0/198 SD-IIV4 | 2.90 (0.12, 70.71) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
1/195 HD-IIV3 | 0/198 SD-IIV4 | 3.05 (0.12, 74.32) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
1/205 aIIV3 | 1/195 HD-IIV3 | 0.95 (0.06, 15.10) | Some concerns |
References in this table: 10
Table 3b: Summary of Studies Reporting Medically-Attended Influenza Illness (Critical)
No studies reported this outcome.
Table 3c: Summary of Studies Reporting Laboratory-confirmed Influenza (Important)
| Author/Year | Age Transplant population |
N intervention | N comparison | Risk ratio (95% CI) | Risk of Bias |
|---|---|---|---|---|---|
| Microbiologically-confirmed influenza | |||||
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
11/205 aIIV3 | 11/198 SD-IIV4 | 0.97 (0.43, 2.18) | Some concerns |
| Mombelli 2018 (11) | ≥18 yrs; median 58-59 yrs Renal/liver (80% renal) |
1/40 double-dose SD-IIV3 | 0/39 SD-IIV3 | 2.93 (0.12, 69.69) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
13/195 HD-IIV3 | 11/198 SD-IIV4 | 1.20 (0.55, 2.61) | Some concerns |
| Natori 2018 (12) | ≥18 yrs; median 57 yrs Mixed (39% renal) |
1/87 HD-IIV3 | 2/85 SD-IIV3 | 1.49 (0.05, 5.29) | Some concerns |
| Immunogenicity: Seroconversion to A(H1N1) (surrogate outcome) | |||||
| Kumar 2016 (13) | ≥18 yrs; mean 50 yrs Renal |
14/31 aIIV3 | 14/29 SD-IIV3 | 0.94 (0.54,1.61) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
55/205 aIIV3 | 34/198 SD-IIV4 | 1.56 (1.07, 2.29) | Some concerns |
| Pollok 2004 (14) | 18 through 64 years Renal |
34/45 aIIV3 | 28/50 SD-IIV3 | 1.35 (1.00, 1.82) | High |
| Mombelli 2018 (11) | ≥18 yrs; median 58-59 yrs Renal/liver (80% renal) |
10/40 double dose SD-IIV3 | 8/39 SD-IIV3 | 1.22 (0.54, 2.76) | Some concerns |
| Odongo 2022 (15) (seronegative baseline) | 18-60 yrs; median 44 yrs Renal |
10/18 double dose SD-IIV3 | 2/20 double dose SD-IIV3 | 5.56 (1.40, 22.04) | Some concerns |
| Odongo 2022 (15) (seropositive baseline) | 18-60 yrs; median 44 yrs Renal |
2/34 double dose SD-IIV3 | 3/31 double dose SD-IIV3 | 0.61 (0.11, 3.40) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
91/195 HD-IIV3 | 34/198 SD-IIV4 | 2.72 (1.93, 3.82) | Some concerns |
| Natori 2018 (12) | ≥18 yrs; median 57 yrs Renal/Liver (80% renal) |
34/84 HD-IIV3 | 16/77 SD-IIV3 | 1.95 (1.17, 3.24) | Some concerns |
| Immunogenicity: Seroconversion to A(H3N2) (surrogate outcome) | |||||
| Kumar 2016 (13) | ≥18 yrs; mean 50 yrs Renal |
15/31 aIIV3 | 10/29 SD-IIV3 | 1.40 (0.76, 2.61) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
106/205 aIIV3 | 69/198 SD-IIV4 | 1.48 (1.18, 1.87) | Some concerns |
| Pollok 2004 (14) | 18 through 64 years Renal |
34/45 aIIV3 | 23/50 SD-IIV3 | 1.64 (1.17, 2.32) | High |
| Mombelli 2018 (11) | ≥18 yrs; median 58-59 yrs Renal/liver (80% renal) |
10/40 double dose SD-IIV3 | 9/39 SD-IIV3 | 1.08 (0.49, 2.38) | Some concerns |
| Odongo 2022 (15) (seronegative baseline) | 18-60 yrs; median 44 yrs Renal |
11/25 double dose SD-IIV3 | 7/24 double dose SD-IIV3 | 1.51 (0.70, 3.24) | Some concerns |
| Odongo 2022 (15) (seropositive baseline) | 18-60 yrs; median 44 yrs Renal |
2/27 double dose SD-IIV3 | 4/27 double dose SD-IIV3 | 0.50 (0.10, 2.50) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
111/195 HD-IIV3 | 69/198 SD-IIV4 | 1.63 (1.30, 2.05) | Some concerns |
| Natori 2018 (12) | ≥18 yrs; median 57 yrs Renal/Liver (80% renal) |
48/84 HD-IIV3 | 25/77 SD-IIV3 | 1.76 (1.21, 2.55) | Some concerns |
| Immunogenicity: Seroconversion to B (surrogate outcome) | |||||
| Kumar 2016 (13) | ≥18 yrs; mean 50 yrs Renal |
10/31 aIIV3 | 7/29 SD-IIV3 | 0.34 (0.59,3.04) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
52/205 aIIV3 | 25/198 SD-IIV4 | 2.01 (1.30, 3.10) | Some concerns |
| Pollok 2004 (14) | 18 through 64 years Renal |
36/45 aIIV3 | 29/50 SD-IIV3 | 1.38 (1.05, 1.82) | High |
| Mombelli 2018 (11) | ≥18 yrs; median 58-59 yrs Renal/liver (80% renal) |
5/40 double dose SD-IIV3 | 4/39 SD-IIV3 | 1.22 (035, 1.21) | Some concerns |
| Odongo 2022 (15) (seronegative baseline) | 18-60 yrs; median 44 yrs Renal |
7/14 double dose SD-IIV3 | 8/19 double dose SD-IIV3 | 1.19 (0.56, 2.50) | Some concerns |
| Odongo 2022 (15) (seropositive baseline) | 18-60 yrs; median 44 yrs Renal |
4/38 double dose SD-IIV3 | 6/32 double dose SD-IIV3 | 0.56 (0.17, 1.82) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
63/195 HD-IIV3 | 25/198 SD-IIV4 | 2.56 (1.68, 3.89) | Some concerns |
| Natori 2018 (12) | ≥18 yrs; median 57 yrs Renal/Liver (80% renal) |
49/84 HD-IIV3 | 32/77 SD-IIV3 | 1.95 (1.40, 1.93) | Some concerns |
| Immunogenicity: Seroprotection A(H1N1) (surrogate outcome) | |||||
| Kumar 2016 (13) | ≥18 yrs; mean 50 yrs Renal |
26/31 aIIV3 | 25/29 SD-IIV3 | 0.97 (0.79,1.20) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
174/205 aIIV3 | 159/198 SD-IIV4 | 1.06 (0.97, 1.16) | Some concerns |
| Pollok 2004 (14) | 18 through 64 years Renal |
40/45 aIIV3 | 39/50 SD-IIV3 | 1.14 (0.95, 1.36) | High |
| Mombelli 2018 (11) | ≥18 yrs; median 58-59 yrs Renal/liver (80% renal) |
37/40 double dose SD-IIV3 | 30/39 SD-IIV3 | 1.20 (0.99, 1.46) | Some concerns |
| Odongo 2022 (15) (seronegative baseline) | 18-60 yrs; median 44 yrs Renal |
14/18 double dose SD-IIV3 | 5/20 double dose SD-IIV3 | 3.11 (1.40, 6.91) | Some concerns |
| Odongo 2022 (15) (seropositive baseline) | 18-60 yrs; median 44 yrs Renal |
34/34 double dose SD-IIV3 | 31/31 double dose SD-IIV3 | 1.00 (0.94, 1.06) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
162/195 HD-IIV3 | 159/198 SD-IIV4 | 1.03 (0.94, 1.14) | Some concerns |
| Natori 2018 (12) | ≥18 yrs; median 57 yrs Renal/Liver (80% renal) |
70/84 HD-IIV3 | 64/77 SD-IIV3 | 1.00 (0.87, 1.15) | Some concerns |
| Immunogenicity: Seroprotection A(H3N2) (surrogate outcome) | |||||
| Kumar 2016 (13) | ≥18 yrs; mean 50 yrs Renal |
31/31 aIIV3 | 27/29 SD-IIV3 | 1.07 (0.97,1.18) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
146/205 aIIV3 | 122/198 SD-IIV4 | 1.16 (1.00, 1.33) | Some concerns |
| Pollok 2004 (14) | 18 through 64 years Renal |
38/45 aIIV3 | 28/50 SD-IIV3 | 1.51 (1.14, 1.99) | High |
| Mombelli 2018 (11) | ≥18 yrs; median 58-59 yrs Renal/liver (80% renal) |
39/40 double dose SD-IIV3 | 35/39 SD-IIV3 | 1.49 (0.80, 2.78) | Some concerns |
| Odongo 2022 (15) (seronegative baseline) | 18-60 yrs; median 44 yrs Renal |
14/25 double dose SD-IIV3 | 9/24 double dose SD-IIV3 | 1.49 (0.80, 2.78) | Some concerns |
| Odongo 2022 (15) (seropositive baseline) | 18-60 yrs; median 44 yrs Renal |
27/27 double dose SD-IIV3 | 27/27 double dose SD-IIV3 | 1.00 (0.93, 1.07) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
139/195 HD-IIV3 | 122/198 SD-IIV4 | 1.16 (1.00, 1.33) | Some concerns |
| Natori 2018 (12) | ≥18 yrs; median 57 yrs Renal/Liver (80% renal) |
67/84 HD-IIV3 | 57/77 SD-IIV3 | 1.08 (0.91, 1.28) | Some concerns |
| Immunogenicity: Seroprotection B (surrogate outcome) | |||||
| Kumar 2016 (13) | ≥18 yrs; mean 50 yrs Renal |
19/31 aIIV3 | 19/29 SD-IIV3 | 0.94 (0.64,1.37) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
109/205 aIIV3 | 80/198 SD-IIV4 | 1.32 (1.06, 1.63) | Some concerns |
| Pollok 2004 (14) | 18 through 64 years Renal |
40/45 aIIV3 | 45/50 SD-IIV3 | 0.99 (0.86, 1.13) | High |
| Mombelli 2018 (11) | ≥18 yrs; median 58-59 yrs Renal/liver (80% renal) |
38/40 double dose SD-IIV3 | 35/39 SD-IIV3 | 1.06 (0.93, 1.20) | Some concerns |
| Odongo 2022 (15) (seronegative baseline) | 18-60 yrs; median 44 yrs Renal |
9/14 double dose SD-IIV3 | 10/19 double dose SD-IIV3 | 1.22 (0.69, 2.18) | Some concerns |
| Odongo 2022 (15) (seropositive baseline) | 18-60 yrs; median 44 yrs Renal |
38/38 double dose SD-IIV3 | 32/32 double dose SD-IIV3 | 1.00 (0.95, 1.06) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
110/195 HD-IIV3 | 80/198 SD-IIV4 | 1.40 (1.13, 1.72) | Some concerns |
| Natori 2018 (12) | ≥18 yrs; median 57 yrs Renal/Liver (80% renal) |
79/84 HD-IIV3 | 70/77 SD-IIV3 | 1.03 (0.95, 1.13) | Some concerns |
References in this table: 8101112131415
Table 3d: Summary of Studies Reporting Graft Rejection (Critical)R
| Author/Year | Age Transplant population | N intervention | N comparison | Risk ratio (95% CI) | Risk of Bias |
|---|---|---|---|---|---|
| Kumar 2016 (13) | ≥18 yrs; mean 50 yrs Renal |
0/31 aIIV3 | 1/31 SD-IIV3 | 0.33 (0.01, 7.87) | Low |
| Magnani 2005 (16) | adult; mean 55 yrs Heart |
1/21 aIIV3 | 1/21 SD-IIV3 | 1.00 (0.07, 14.95) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
1/209 aIIV3 | 5204 SD-IIV4 | 0.20 (0.02, 1.66) | High |
| Mombelli 2018 (11) | ≥18 yrs; median 58-59 yrs Renal/liver (80% renal) |
0/40 Double dose SD-IIV3 | 0/39 SD-IIV3 | Not estimable | Some concerns |
| Odongo 2022 (15) | 18-60 yrs; median 44 yrs Renal |
2/58 Double dose SD-IIV3 | 5/57 SD-IIV3 | 0.39 (0.08, 1.94) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
3/203 HD-IIV3 | 5/204 SD-IIV4 | 0.60 (0.15, 2.49) | High |
| Natori 2018 (12) | ≥18 yrs; median 57 yrs Renal/Liver (80% renal) |
3/87 HD-IIV3 | 5/85 SD-IIV3 | 2.93 (0.31, 27.62) | Some concerns |
| Mombelli 2024 (10) | ≥18 yrs; median 58 yrs Mixed (68% renal) |
1/209 aIIV3 | 3/203 HD-IIV3 | 0.32 (0.03, 3.09) | High |
References in this table: 101112131516
Table 3e: Summary of Studies Reporting Neuroinflammatory Adverse Events (Critical)
No studies reported this outcome.
Table 3f: Summary of Studies Reporting Other Immune-Mediated Adverse Events (Critical)
No studies reported this outcome.
Table 4 GRADE Summary of Findings Tables
Table 4a: GRADE Summary of Findings Table—aIIV3 vs. SD-IIV
| Certainty assessment | № of patients | Effect | Certainty | Importance | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| № of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | aIIV3 | SD-IIV | Relative (95% CI) |
Absolute (95% CI) |
||
| Influenza-associated hospitalization | ||||||||||||
| 1 | randomized trials | not serious | not serious | not serious | very seriousa | none | 1/205 (0.5%) | 0/198 (0.0%) | RR 2.90 (0.12 to 70.71) |
0 fewer per 10,000 (from 0 fewer to 0 fewer) |
Low | CRITICAL |
| Graft rejection | ||||||||||||
| 3 | randomized trials | not serious | not serious | not serious | seriousb | none | 2/261 (0.8%) | 7/256 (2.7%) | RR 0.28 (0.06 to 1.34) |
197 fewer per 10,000 (from 257 fewer to 93 more) |
Moderate | CRITICAL |
| Laboratory-confirmed influenza | ||||||||||||
| 1 | randomized trials | not serious | not serious | not serious | seriousc | none | 11/205 (5.4%) | 11/198 (5.6%) | RR 0.97 (0.43 to 2.18) |
17 fewer per 10,000 (from 317 fewer to 656 more) |
Moderate | IMPORTANT |
| Seroconversion to influenza A(H1N1) | ||||||||||||
| 3 | randomized trials | seriousd | not serious | seriouse | not serious | none | 103/281 (36.7%) | 76/277 (27.4%) | RR 1.37 (1.09 to 1.72) |
1,015 more per 10,000 (from 247 more to 1,975 more) |
Low | IMPORTANT |
| Seroconversion to influenza A(H3N2) | ||||||||||||
| 3 | randomized trials | seriousd | not serious | seriouse | not serious | none | 155/281 (55.2%) | 102/277 (36.8%) | RR 1.51 (1.25 to 1.82) |
1,878 more per 10,000 (from 921 more to 3,019 more) |
Low | IMPORTANT |
| Seroconversion to influenza B | ||||||||||||
| 3 | randomized trials | seriousd | not serious | seriouse | not serious | none | 98/281 (34.9%) | 61/277 (22.0%) | RR 1.64 (1.28 to 2.11) |
1,409 more per 10,000 (from 617 more to 2,444 more) |
Low | IMPORTANT |
| Seroprotection to influenza A(H1N1) | ||||||||||||
| 3 | randomized trials | seriousd | not serious | seriouse | seriousc | none | 240/281 (85.4%) | 223/277 (80.5%) | RR 1.06 (0.98 to 1.14) |
483 more per 10,000 (from 161 fewer to 1,127 more) |
Very low | IMPORTANT |
| Seroprotection to influenza A(H3N2) | ||||||||||||
| 3 | randomized trials | seriousd | not serious | seriouse | not serious | none | 215/281 (76.5%) | 177/277 (63.9%) | RR 1.20 (1.07 to 1.33) |
1,278 more per 10,000 (from 447 more to 2,109 more) |
Low | IMPORTANT |
| Seroprotection to influenza B | ||||||||||||
| 3 | randomized trials | seriousd | not serious | seriouse | not serious | none | 168/281 (59.8%) | 144/277 (52.0%) | RR 1.17 (1.01 to 1.34) |
884 more per 10,000 (from 52 more to 1,768 more) |
Low | IMPORTANT |
CI: confidence interval; RR: risk ratio
Explanations
a. Only one hospitalization detected; risk estimate is fragile and would be easily altered by misclassification of a single event. Likely inadequate power to detect difference in risk for this outcome.
b. Wide confidence interval in relative effect; likely inadequate power for an uncommon outcome. Choice of intervention includes approximately 1.5% rate of rejection.
c. Wide confidence interval for absolute effect; small sample size for adequate power to estimate relative and absolute benefits of interventions.
d. Two papers rated for "Some concerns" for risk of bias, including the one with the largest sample size.
e. Surrogate outcome (immunogenicity) rather than lab confirmed influenza.
Table 4b: GRADE Summary of Findings Table —Double-dose SD-IIV3 vs. SD-IIV3
| Certainty assessment | № of patients | Effect | Certainty | Importance | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| № of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | double SD-IIV3 | SD-IIV3 | Relative (95% CI) | Absolute (95% CI) | ||
| Graft rejection | ||||||||||||
| 2 | randomized trials | seriousa | not serious | seriousb | seriousc | none | 2/98 (2.0%) | 5/96 (5.2%) | RR 0.39 (0.08 to 1.94) |
318 fewer per 10,000 (from 479 fewer to 490 more) |
Very low | CRITICAL |
| Laboratory-confirmed influenza | ||||||||||||
| 1 | randomized trials | not serious | not serious | seriousb | very seriousd | none | 1/40 (2.5%) | 0/39 (0.0%) | RR 2.93 (0.12 to 69.69) |
0 fewer per 10,000 (from 0 fewer to 0 fewer) |
Very low | IMPORTANT |
| Seroconversion to influenza A(H1N1) | ||||||||||||
| 2 | randomized trials | seriousa | not seriouse | seriousb,f | seriousg | none | 22/92 (23.9%) | 13/90 (14.4%) | RR 1.70 (0.92 to 3.13) |
1,011 more per 10,000 (from 116 fewer to 3,077 more) |
Very low | IMPORTANT |
| Seroconversion to influenza A(H3N2) | ||||||||||||
| 2 | randomized trials | seriousa | not seriouse | seriousb,f | seriousg | none | 23/92 (25.0%) | 20/90 (22.2%) | RR 1.12 (0.67 to 1.87) |
267 more per 10,000 (from 733 fewer to 1,933 more) |
Very low | IMPORTANT |
| Seroconversion to influenza B | ||||||||||||
| 2 | randomized trials | seriousa | not seriouse | seriousb,f | seriousg | none | 16/92 (17.4%) | 18/90 (20.0%) | RR 0.96 (0.54 to 1.70) |
80 fewer per 10,000 (from 920 fewer to 1,400 more) |
Very low | IMPORTANT |
| Seroprotection to influenza A(H1N1) | ||||||||||||
| 2 | randomized trials | seriousa | not seriouse | seriousb,f | not serious | none | 85/92 (92.4%) | 66/90 (73.3%) | RR 1.24 (1.10 to 1.40) |
1,760 more per 10,000 (from 733 more to 2,933 more) |
Low | IMPORTANT |
| Seroprotection to influenza A(H3N2) | ||||||||||||
| 2 | randomized trials | seriousa | not seriouse | seriousb,f | not serious | none | 80/92 (87.0%) | 71/90 (78.9%) | RR 1.11 (0.99 to 1.23) |
868 more per 10,000 (from 79 fewer to 1,814 more) |
Low | IMPORTANT |
| Seroprotection to influenza B | ||||||||||||
| 2 | randomized trials | seriousa | not serious | seriousb,f | seriousg | none | 85/92 (92.4%) | 77/90 (85.6%) | RR 1.05 (0.96 to 1.15) |
428 more per 10,000 (from 342 fewer to 1,283 more) |
Very low | IMPORTANT |
CI: confidence interval; RR: risk ratio
Explanations
a. Open-label studies; both with "Some concerns" for risk of bias.
b. While the intervention represents a higher antigen dose strategy, the dose is lower than that contained in the approved high-dose inactivated influenza vaccine (twice the antigen dose per virus as compared with four times the dose per virus, as compared with standard-dose inactivated influenza vaccines..
c. Wide confidence interval in relative effect; likely inadequate power for an uncommon outcome. While point estimate favors intervention, confidence interval includes approximately 4.9% rate of rejection.
d. Sample size very small and only one event detected. Risk estimate is fragile and would be easily altered by misclassification of a single event. Likely inadequate power to detect difference in risk for this outcome.
e. Though point estimates are different, this is explainable by stratification of the Odongo 2022 results by baseline seropositivity.
f. Surrogate outcome (immunogenicity) rather than lab confirmed influenza.
g. Wide confidence interval for absolute effect; small sample size for adequate power to estimate relative and absolute benefits of interventions
Table 4c: GRADE Summary of Findings Table —HD-IIV3 vs. SD-IIV
| Certainty assessment | № of patients | Effect | Certainty | Importance | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| № of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | HD-IIV3 | SD-IIV adults only (sans GiaQunta) | Relative (95% CI) |
Absolute (95% CI) |
||
| Influenza-associated hospitalization | ||||||||||||
| 1 | randomized trials | not serious | not serious | not serious | very seriousa | none | 1/195 (0.5%) | 0/198 (0.0%) | RR 3.05 (0.12 to 74.32) |
0 fewer per 10,000 (from 0 fewer to 0 fewer) |
Low | CRITICAL |
| Graft rejection | ||||||||||||
| 2 | randomized trials | not serious | not serious | not serious | seriousb | none | 6/290 (2.1%) | 6/289 (2.1%) | RR 1.00 (0.32 to 3.06) |
0 fewer per 10,000 (from 141 fewer to 428 more) |
Moderate | CRITICAL |
| Laboratory-confirmed influenza | ||||||||||||
| 2 | randomized trials | not serious | not serious | not serious | seriousc | none | 14/282 (5.0%) | 13/283 (4.6%) | RR 1.09 (0.52 to 2.27) |
41 more per 10,000 (from 220 fewer to 583 more) |
Moderate | IMPORTANT |
| Seroconversion to influenza A(H1N1) | ||||||||||||
| 2 | randomized trials | not serious | not serious | seriousd | not serious | none | 125/279 (44.8%) | 50/275 (18.2%) | RR 2.46 (1.86 to 3.27) |
2,655 more per 10,000 (from 1,564 more to 4,127 more) |
Moderate | IMPORTANT |
| Seroconversion to influenza A(H3N2) | ||||||||||||
| 2 | randomized trials | not serious | not serious | seriousd | not serious | none | 159/279 (57.0%) | 94/275 (34.2%) | RR 1.67 (1.38 to 2.02) |
2,290 more per 10,000 (from 1,299 more to 3,487 more) |
Moderate | IMPORTANT |
| Seroconversion to influenza B | ||||||||||||
| 2 | randomized trials | not serious | not serious | seriousd | not serious | none | 112/279 (40.1%) | 57/275 (20.7%) | RR 1.90 (1.46 to 2.46) |
1,865 more per 10,000 (from 953 more to 3,026 more) |
Moderate | IMPORTANT |
| Seroprotection to influenza A(H1N1) | ||||||||||||
| 2 | randomized trials | not serious | not serious | seriousd | seriousc | none | 232/279 (83.2%) | 223/275 (81.1%) | RR 1.03 (0.95 to 1.11) |
243 more per 10,000 (from 405 fewer to 892 more) |
Low | IMPORTANT |
| Seroprotection to influenza A(H3N2) | ||||||||||||
| 2 | randomized trials | not serious | not serious | seriousd | not serious | none | 206/279 (73.8%) | 179/275 (65.1%) | RR 1.13 (1.01 to 1.26) |
846 more per 10,000 (from 65 more to 1,692 more) |
Moderate | IMPORTANT |
| Seroprotection to influenza B | ||||||||||||
| 2 | randomized trials | not serious | not serious | seriousd | not serious | none | 189/279 (67.7%) | 150/275 (54.5%) | RR 1.22 (1.08 to 1.38) |
1,200 more per 10,000 (from 436 more to 2,073 more) |
Moderate | IMPORTANT |
CI: confidence interval; RR: risk ratio
Explanations
a. Only one hospitalization detected; risk estimate is fragile and would be easily altered by misclassification of a single event. Likely inadequate power to detect difference in risk for this outcome.
b. Wide confidence interval in relative effect; likely inadequate power for an uncommon outcome. Choice of intervention includes approximately 4.2% rate of rejection.
c. Wide confidence interval in absolute effect; small sample size for adequate power to estimate relative and absolute benefits of interventions.
d. Surrogate outcome (immunogenicity) rather than lab confirmed influenza.
Table 4d: GRADE Summary of Findings Table —aIIV3 vs. HD-IIV3
| Certainty assessment | № of patients | Effect | Certainty | Importance | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| № of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | aIIV3 | HD-IIV | Relative (95% CI) |
Absolute (95% CI) |
||
| Influenza-associated hospitalization | ||||||||||||
| 1 | randomized trials | not serious | not serious | not serious | very seriousa | none | 1/205 (0.5%) | 1/195 (0.5%) | RR 0.95 (0.06 to 15.10) |
0 fewer per 100 (from 0 fewer to 7 more) |
Low | CRITICAL |
| Graft rejection | ||||||||||||
| 1 | randomized trials | not serious | not serious | not serious | seriousb | none | 1/209 (0.5%) | 3/203 (1.5%) | RR 0.32 (0.03 to 3.09) |
1 fewer per 100 (from 1 fewer to 3 more) |
Moderate | CRITICAL |
| Laboratory-confirmed influenza | ||||||||||||
| 1 | randomized trials | not serious | not serious | not serious | seriousb | none | 11/205 (5.4%) | 13/195 (6.7%) | RR 0.80 (0.37 to 1.75) |
1 fewer per 100 (from 4 fewer to 5 more) |
Moderate | IMPORTANT |
| Seroconversion to influenza A(H1N1) | ||||||||||||
| 1 | randomized trials | not serious | not serious | seriousc | not serious | none | 55/205 (26.8%) | 91/195 (46.7%) | RR 0.57 (0.44 to 0.75) |
20 fewer per 100 (from 26 fewer to 12 fewer) |
Moderate | IMPORTANT |
| Seroconversion to influenza A(H3N2) | ||||||||||||
| 1 | randomized trials | not serious | not serious | seriousc | seriousb | none | 106/205 (51.7%) | 111/195 (56.9%) | RR 0.91 (0.76 to 1.09) |
5 fewer per 100 (from 14 fewer to 5 more) |
Low | IMPORTANT |
| Seroconversion to influenza B | ||||||||||||
| 1 | randomized trials | not serious | not serious | seriousc | seriousb | none | 52/205 (25.4%) | 63/195 (32.3%) | RR 0.79 (0.58 to 1.07) |
7 fewer per 100 (from 14 fewer to 2 more) |
Low | IMPORTANT |
| Seroprotection to influenza A(H1N1) | ||||||||||||
| 1 | randomized trials | not serious | not serious | seriousc | seriousb | none | 174/205 (84.9%) | 162/195 (83.1%) | RR 1.02 (0.94 to 1.11) |
2 more per 100 (from 5 fewer to 9 more) |
Low | IMPORTANT |
| Seroprotection to influenza A(H3N2) | ||||||||||||
| 1 | randomized trials | not serious | not serious | seriousc | seriousb | none | 146/205 (71.2%) | 139/195 (71.3%) | RR 1.00 (0.88 to 1.13) |
0 fewer per 100 (from 9 fewer to 9 more) |
Low | IMPORTANT |
| Seroprotection to influenza B | ||||||||||||
| 1 | randomized trials | not serious | not serious | seriousc | seriousb | none | 109/205 (53.2%) | 110/195 (56.4%) | RR 0.94 (0.79 to 1.13) |
3 fewer per 100 (from 12 fewer to 7 more) |
Low | IMPORTANT |
CI: confidence interval; RR: risk ratio
Explanations
a. Only two hospitalizations detected; risk estimate is fragile and would be easily altered by misclassification of a single event. Likely inadequate power to detect difference in risk for this outcome.
b. Wide confidence interval in absolute effect; small sample size for adequate power to estimate relative and absolute benefits of interventions.
c. Surrogate outcome (immunogenicity) rather than lab confirmed influenza.
Table 5: Summary of Evidence for Outcomes of Interest
aIIV3 vs SD-IIV
| Outcome | Importance | No. studies | Included in profile | Favored vaccine | Certainty |
|---|---|---|---|---|---|
| Benefits | |||||
| Medically-attended influenza | Critical | 0 | - | - | - |
| Influenza-associated hospitalization | Critical | 1 | Yes | Neither | Low |
| Laboratory-confirmed influenza | Important | 1 | Yes | Neither | Moderate |
| Immunogenicity (surrogate outcome) | |||||
| Seroconversion to A(H1N1) | Important | 3 | Yes | aIIV3 | Low |
| Seroconversion to A(H3N2) | Important | 3 | Yes | aIIV3 | Low |
| Seroconversion to B | Important | 3 | Yes | aIIV3 | Low |
| Seroprotection to A(H1N1) | Important | 3 | Yes | Neither | Very Low |
| Seroprotection to A(H3N2) | Important | 3 | Yes | aIIV3 | Low |
| Seroprotection to B | Important | 3 | Yes | aIIV3 | Low |
| Harms | |||||
| Transplant rejection/graft failure | Critical | 3 | Yes | Neither | Moderate |
| Neuroinflammatory conditions | Critical | 0 | - | - | - |
| Other immune-mediated adverse events | Critical | 0 | - | - | - |
Double-dose SD-IIV3 vs SD-IIV3
| Outcome | Importance | No. studies | Included in profile | Favored vaccine | Certainty |
|---|---|---|---|---|---|
| Benefits | |||||
| Medically-attended influenza | Critical | 0 | - | - | - |
| Influenza-associated hospitalization | Critical | 0 | - | - | - |
| Laboratory-confirmed influenza | Important | 1 | Yes | Neither | Very low |
| Immunogenicity (surrogate outcome) | |||||
| Seroconversion to A(H1N1) | Important | 2 | Yes | Neither | Very low |
| Seroconversion to A(H3N2) | Important | 2 | Yes | Neither | Very low |
| Seroconversion to B | Important | 2 | Yes | Neither | Very low |
| Seroprotection to A(H1N1) | Important | 2 | Yes | Double-dose SD-IIV3 | Low |
| Seroprotection to A(H3N2) | Important | 2 | Yes | Neither | Low |
| Seroprotection to B | Important | 2 | Yes | Neither | Very low |
| Harms | |||||
| Transplant rejection/graft failure | Critical | 2 | Yes | Neither | Very low |
| Neuroinflammatory conditions | Critical | 0 | - | - | - |
| Other immune-mediated adverse events | Critical | 0 | - | - | - |
HD-IIV3 vs SD-IIV
| Outcome | Importance | No. studies | Included in profile | Favored vaccine | Certainty |
|---|---|---|---|---|---|
| Benefits | |||||
| Medically-attended influenza | Critical | 0 | - | - | - |
| Influenza-associated hospitalization | Critical | 1 | Yes | Neither | Low |
| Laboratory-confirmed influenza | Important | 2 | Yes | Neither | Moderate |
| Immunogenicity (surrogate outcome) | |||||
| Seroconversion to A(H1N1) | Important | 3 | Yes | HD-IIV3 | Moderate |
| Seroconversion to A(H3N2) | Important | 3 | Yes | HD-IIV3 | Moderate |
| Seroconversion to B | Important | 3 | Yes | HD-IIV3 | Moderate |
| Seroprotection to A(H1N1) | Important | 3 | Yes | Neither | Low |
| Seroprotection to A(H3N2) | Important | 3 | Yes | HD-IIV3 | Moderate |
| Seroprotection to B | Important | 3 | Yes | HD-IIV3 | Moderate |
| Harms | |||||
| Transplant rejection/graft failure | Critical | 3 | Yes | Neither | Moderate |
| Neuroinflammatory conditions | Critical | 0 | - | - | - |
| Other immune-mediated adverse events | Critical | 0 | - | - | - |
aIIV3 vs HD-IIV3
| Outcome | Importance | No. studies | Included in profile | Favored vaccine | Certainty |
|---|---|---|---|---|---|
| Benefits | |||||
| Medically-attended influenza | Critical | 0 | - | - | - |
| Influenza-associated hospitalization | Critical | 1 | Yes | Neither | Low |
| Laboratory-confirmed influenza | Important | 1 | Yes | Neither | Moderate |
| Immunogenicity (surrogate outcome) | |||||
| Seroconversion to A(H1N1) | Important | 1 | Yes | Neither | Moderate |
| Seroconversion to A(H3N2) | Important | 1 | Yes | Neither | Low |
| Seroconversion to B | Important | 1 | Yes | Neither | Low |
| Seroprotection to A(H1N1) | Important | 1 | Yes | Neither | Low |
| Seroprotection to A(H3N2) | Important | 1 | Yes | Neither | Low |
| Seroprotection to B | Important | 1 | Yes | Neither | Low |
| Harms | |||||
| Transplant rejection/graft failure | Critical | 1 | Yes | Neither | Moderate |
| Neuroinflammatory conditions | Critical | 0 | - | - | - |
| Other immune-mediated adverse events | Critical | 0 | - | - | - |
Appendix 1. Studies Included in the Review of Evidence
| Author/Year | Study Design | Country | Season(s) | Age | Sample Size (Total) | Vaccine Groups | Funding Source |
|---|---|---|---|---|---|---|---|
| Kumar 2016 (13) | Randomized | Canada | 2012-13 | Median 49.7 yrs; range 22-79 |
60 | aIIV3 SD-IIV3 |
Unclear |
| Magnani 2005 (16) | Randomized | Italy | 1999-00 | 55 +/- 14 yrs | 58 | aIIV3 SD-IIV3 |
Unclear |
| Mombelli 2018 (11) | Randomized | Switzerland | 2014-15 | 2 doses SD-IIV3: Median 58 yrs; range 31-73 1 dose SD-IIV3: Median 59 yrs; range 23-74 |
79 | 2 doses of SD-IIV3 1 dose of SD-IIV3 |
Leenaards Foundation |
| Mombelli 2024 (10) | Randomized | Spain Switzerland |
2018-19 2019-20 |
aIIV3: Median 57 yrs; range 45-64 HD-IIV3: Median 56 yrs; range 47-66 SD-IIV4: Median 58 yrs; range 49-65 |
616 | aIIV3 HD-IIV3 SD-IIV4 |
Swiss National Science Foundation |
| Natori 2018 (12) | Randomized | Canada | 2016-17 | Median 57 yrs. Range 18-86 yrs. |
161 | HD-IIV3 vs. SD-IIV3 |
Multi-Organ Transplant Program |
| Odongo 2022 (15) | Randomized | Brazil | 2014 | 2 doses SD-IIV3: Median 4 yrs; range 24-61 1 dose SD-IIV3: Median 45 yrs; range 19-59 |
115 | 2 doses of SD-IIV3 1 dose of SD-IIV3 |
Butantan Institute |
| Pollok 2004 (14) | Randomized | Germany | 2000-01 | 18-64 yrs. | 95 | aIIV3 SD-IIV3 |
Unclear |
Appendix 2. Databases and strategies used for systematic review
Appendix 2: Literature Search Strategy
Literature through June 23, 2023
| Database | Strategy |
|---|---|
| Medline (OVID) 1946- |
( exp Immunocompromised Host/ OR exp Immune System Diseases/ OR exp Immunosuppressive Agents/ OR exp immunosuppression therapy/ OR Autoimmunity/ OR exp organ transplantation/ OR exp tissue transplantation/ OR exp Bone Marrow Transplantation/ OR exp Stem Cell Transplantation/ OR exp Leukemia/ OR exp Lymphoma/ OR exp neoplasms/ OR exp HIV infections/ OR exp Anemia, Sickle Cell/ OR (sickle-cell anemia OR immunocompromised OR immunosuppress* OR immunodeficien* OR immuno-compromised OR immuno-suppress* OR immuno-deficien* OR immunopathology OR (immun* ADJ2 incompeten*) OR (immun* ADJ2 suppress*) OR (immun* ADJ2 deficien*) OR (immun* ADJ2 syndrome*) OR autoimmun* OR auto-immun* OR transplant* OR Leukemia* OR Lymphoma* OR neoplasm* OR cancer* OR malignan* OR HIV* OR asplenia OR Agammaglobulinemia* OR hypogammaglobulinemia* OR Specific polysaccharide antibody deficiency OR Interferon alpha deficiency OR Interferon gamma deficiency OR Chronic granulomatous disease OR Chediak-Higashi syndrome OR Leukocyte adhesion deficiency OR DiGeorge syndrome OR Complement deficiency OR Wiskott-Adlrich syndrome OR X-linked lymphoproliferative disease OR arthritis OR Multiple Sclerosis OR Psoriasis OR lupus OR Sjogren syndrome OR Sicca Syndrome OR Systemic sclerosis OR Scleroderma OR Dermatomyositis OR Polymyositis OR Mixed connective tissue disease OR Inflammatory bowel disease OR Crohn's disease OR Ulcerative colitis OR Polyarteritis nodosa OR Granulomatosis OR arteritis OR Polymyalgia rheumatica OR Celiac disease OR Primary sclerosing cholangitis).ti,ab,kf. OR (Corticosteroid* OR Prednisone OR Prednisolone OR Dexamethasone OR Budesonide OR tumor necrosis factor alpha OR TNF-alpha OR Janus kinase inhibitor* OR Tofacitinib OR Rituximab OR Methotrexate OR 6-mercaptopurine OR IMDH inhibitor* OR Azathioprine OR Leflunomide OR Mycophenolate OR Biologics OR Abatacept OR Adalimumab OR Anakinra OR Certolizumab OR Etanercept OR Infliximab OR Ixekizumab OR Natalizumab OR Secukinumab OR Tocilizumab OR Ustekinumab OR Vedolizumab OR Basilixumab OR Daclizumab OR Calcineurin inhibitor* OR Cyclosporine OR Tacrolimus OR mTOR inhibitor* OR Sirolimus OR Everolimus OR Checkpoint inhibitor* OR Pembrolizumab OR Nivolumab OR Ipilimumab OR Atezolibumab OR Avelumab OR Durvalumab OR Cyclophosphomide OR Vincristine OR Vinblastine OR Busulfan OR Doxorubucin OR Daunorubicin OR Gemcitabine OR Mercaptopurine OR Cladribine OR Hydroxyurea OR Capecitabine OR Plaratrexate OR Fludarabine OR Fluorouracil OR Pemetrexed OR Thioguanine OR Floxuridine OR Citarabine OR Clofarabine OR Decitabine OR Nelarabine).ti,ab,kf,hw. ) AND Exp Influenza Vaccines/ OR (exp vaccination/ and exp influenza, human/) OR (((influenza OR flu) ADJ5 (vaccin* OR immunization*)) OR Fluzone OR Fluad OR Flublok).ti,ab,kf. NOT Exp animals/ NOT exp humans/ |
| Embase (OVID) 1974- |
( exp Immunocompromised patient/ OR exp immunopathology/ OR exp Immunosuppressive Agent/ OR exp immunosuppressive treatment/ OR Autoimmunity/ OR exp organ transplantation/ OR exp tissue transplantation/ OR exp Bone Marrow Transplantation/ OR exp Stem Cell Transplantation/ OR exp Leukemia/ OR exp Lymphoma/ OR exp neoplasm/ OR exp Human immunodeficiency virus infection/ OR exp sickle cell anemia/ OR (sickle-cell anemia OR immunocompromised OR immunosuppress* OR immunodeficien* OR immuno-compromised OR immuno-suppress* OR immuno-deficien* OR immunopathology OR (immun* ADJ2 incompeten*) OR (immun* ADJ2 suppress*) OR (immun* ADJ2 deficien*) OR (immun* ADJ2 syndrome*) OR autoimmun* OR auto-immun* OR transplant* OR Leukemia* OR Lymphoma* OR neoplasm* OR cancer* OR malignan* OR HIV* OR asplenia OR Agammaglobulinemia* OR hypogammaglobulinemia* OR Specific polysaccharide antibody deficiency OR Interferon alpha deficiency OR Interferon gamma deficiency OR Chronic granulomatous disease OR Chediak-Higashi syndrome OR Leukocyte adhesion deficiency OR DiGeorge syndrome OR Complement deficiency OR Wiskott-Adlrich syndrome OR X-linked lymphoproliferative disease OR arthritis OR Multiple Sclerosis OR Psoriasis OR lupus OR Sjogren syndrome OR Sicca Syndrome OR Systemic sclerosis OR Scleroderma OR Dermatomyositis OR Polymyositis OR Mixed connective tissue disease OR Inflammatory bowel disease OR Crohn's disease OR Ulcerative colitis OR Polyarteritis nodosa OR Granulomatosis OR arteritis OR Polymyalgia rheumatica OR Celiac disease OR Primary sclerosing cholangitis).ti,ab,kf. OR (Corticosteroid* OR Prednisone OR Prednisolone OR Dexamethasone OR Budesonide OR tumor necrosis factor alpha OR TNF-alpha OR Janus kinase inhibitor* OR Tofacitinib OR Rituximab OR Methotrexate OR 6-mercaptopurine OR IMDH inhibitor* OR Azathioprine OR Leflunomide OR Mycophenolate OR Biologics OR Abatacept OR Adalimumab OR Anakinra OR Certolizumab OR Etanercept OR Infliximab OR Ixekizumab OR Natalizumab OR Secukinumab OR Tocilizumab OR Ustekinumab OR Vedolizumab OR Basilixumab OR Daclizumab OR Calcineurin inhibitor* OR Cyclosporine OR Tacrolimus OR mTOR inhibitor* OR Sirolimus OR Everolimus OR Checkpoint inhibitor* OR Pembrolizumab OR Nivolumab OR Ipilimumab OR Atezolibumab OR Avelumab OR Durvalumab OR Cyclophosphomide OR Vincristine OR Vinblastine OR Busulfan OR Doxorubucin OR Daunorubicin OR Gemcitabine OR Mercaptopurine OR Cladribine OR Hydroxyurea OR Capecitabine OR Plaratrexate OR Fludarabine OR Fluorouracil OR Pemetrexed OR Thioguanine OR Floxuridine OR Citarabine OR Clofarabine OR Decitabine OR Nelarabine).ti,ab,kf,hw. ) AND Exp Influenza Vaccine/ OR (exp vaccination/ and exp influenza/) OR (((influenza OR flu) ADJ5 (vaccin* OR immunization*)) OR Fluzone OR Fluad OR Flublok).ti,ab,kf. NOT Exp animal/ NOT exp human/ |
| Cochrane Library | ( [mh "Immunocompromised Host"] OR [mh "Immune System Diseases"] OR [mh "Immunosuppressive Agents"] OR [mh "immunosuppression therapy"] OR [mh "Autoimmunity"] OR [mh "organ transplantation"] OR [mh "tissue transplantation"] OR [mh "Bone Marrow Transplantation"] OR [mh "Stem Cell Transplantation"] OR [mh Leukemia] OR [mh Lymphoma] OR [mh neoplasms] OR [mh "HIV infections"] OR [mh "Anemia, Sickle Cell"] OR ("sickle-cell anemia" OR immunocompromised OR immunosuppress* OR immunodeficien* OR immuno-compromised OR immuno-suppress* OR immuno-deficien* OR immunopathology OR (immun* NEAR/2 incompeten*) OR (immun* NEAR/2 suppress*) OR (immun* NEAR/2 deficien*) OR (immun* NEAR/2 syndrome*) OR autoimmun* OR auto-immun* OR transplant* OR Leukemia* OR Lymphoma* OR neoplasm* OR cancer* OR malignan* OR HIV* OR asplenia OR Agammaglobulinemia* OR hypogammaglobulinemia* OR "Specific polysaccharide antibody deficiency" OR "Interferon alpha deficiency" OR "Interferon gamma deficiency" OR "Chronic granulomatous disease" OR "Chediak-Higashi syndrome" OR "Leukocyte adhesion deficiency" OR "DiGeorge syndrome" OR "Complement deficiency" OR "Wiskott-Adlrich syndrome" OR "X-linked lymphoproliferative disease" OR arthritis OR "Multiple Sclerosis" OR Psoriasis OR lupus OR "Sjogren syndrome" OR "Sicca Syndrome" OR "Systemic sclerosis" OR Scleroderma OR Dermatomyositis OR Polymyositis OR "Mixed connective tissue disease" OR "Inflammatory bowel disease" OR "Crohn's disease" OR "Ulcerative colitis" OR "Polyarteritis nodosa" OR Granulomatosis OR arteritis OR "Polymyalgia rheumatica" OR "Celiac disease" OR "Primary sclerosing cholangitis"):ti,ab OR (Corticosteroid* OR Prednisone OR Prednisolone OR Dexamethasone OR Budesonide OR "tumor necrosis factor alpha" OR "TNF-alpha" OR "Janus kinase inhibitor*" OR Tofacitinib OR Rituximab OR Methotrexate OR "6-mercaptopurine" OR "IMDH inhibitor*" OR Azathioprine OR Leflunomide OR Mycophenolate OR Biologics OR Abatacept OR Adalimumab OR Anakinra OR Certolizumab OR Etanercept OR Infliximab OR Ixekizumab OR Natalizumab OR Secukinumab OR Tocilizumab OR Ustekinumab OR Vedolizumab OR Basilixumab OR Daclizumab OR "Calcineurin inhibitor*" OR Cyclosporine OR Tacrolimus OR "mTOR inhibitor*" OR Sirolimus OR Everolimus OR "Checkpoint inhibitor*" OR Pembrolizumab OR Nivolumab OR Ipilimumab OR Atezolibumab OR Avelumab OR Durvalumab OR Cyclophosphomide OR Vincristine OR Vinblastine OR Busulfan OR Doxorubucin OR Daunorubicin OR Gemcitabine OR Mercaptopurine OR Cladribine OR Hydroxyurea OR Capecitabine OR Plaratrexate OR Fludarabine OR Fluorouracil OR Pemetrexed OR Thioguanine OR Floxuridine OR Citarabine OR Clofarabine OR Decitabine OR Nelarabine):ti,ab ) AND [mh "Influenza Vaccines"] OR ([mh "vaccination"] and [mh "influenza, human"]) OR (((influenza OR flu) NEAR/5 (vaccin* OR immunization*)) OR Fluzone OR Fluad OR Flublok):ti,ab |
| CINAHL (EbscoHost) |
( (MH "Immunocompromised Host") OR (MH "Immune System Diseases") OR (MH "Immunosuppressive Agents") OR (MH "immunosuppression therapy") OR (MH "Autoimmunity") OR (MH "organ transplantation") OR (MH "tissue transplantation") OR (MH "Bone Marrow Transplantation") OR (MH "Stem Cell Transplantation") OR (MH Leukemia) OR (MH Lymphoma) OR (MH neoplasms) OR (MH "HIV infections") OR (MH "Anemia, Sickle Cell") OR ("sickle-cell anemia" OR immunocompromised OR immunosuppress* OR immunodeficien* OR immuno-compromised OR immuno-suppress* OR immuno-deficien* OR immunopathology OR (immun* N2 incompeten*) OR (immun* N2 suppress*) OR (immun* N2 deficien*) OR (immun* N2 syndrome*) OR autoimmun* OR auto-immun* OR transplant* OR Leukemia* OR Lymphoma* OR neoplasm* OR cancer* OR malignan* OR HIV* OR asplenia OR Agammaglobulinemia* OR hypogammaglobulinemia* OR "Specific polysaccharide antibody deficiency" OR "Interferon alpha deficiency" OR "Interferon gamma deficiency" OR "Chronic granulomatous disease" OR "Chediak-Higashi syndrome" OR "Leukocyte adhesion deficiency" OR "DiGeorge syndrome" OR "Complement deficiency" OR "Wiskott-Adlrich syndrome" OR "X-linked lymphoproliferative disease" OR arthritis OR "Multiple Sclerosis" OR Psoriasis OR lupus OR "Sjogren syndrome" OR "Sicca Syndrome" OR "Systemic sclerosis" OR Scleroderma OR Dermatomyositis OR Polymyositis OR "Mixed connective tissue disease" OR "Inflammatory bowel disease" OR "Crohn's disease" OR "Ulcerative colitis" OR "Polyarteritis nodosa" OR Granulomatosis OR arteritis OR "Polymyalgia rheumatica" OR "Celiac disease" OR "Primary sclerosing cholangitis") OR (Corticosteroid* OR Prednisone OR Prednisolone OR Dexamethasone OR Budesonide OR "tumor necrosis factor alpha" OR "TNF-alpha" OR "Janus kinase inhibitor*" OR Tofacitinib OR Rituximab OR Methotrexate OR "6-mercaptopurine" OR "IMDH inhibitor*" OR Azathioprine OR Leflunomide OR Mycophenolate OR Biologics OR Abatacept OR Adalimumab OR Anakinra OR Certolizumab OR Etanercept OR Infliximab OR Ixekizumab OR Natalizumab OR Secukinumab OR Tocilizumab OR Ustekinumab OR Vedolizumab OR Basilixumab OR Daclizumab OR "Calcineurin inhibitor*" OR Cyclosporine OR Tacrolimus OR "mTOR inhibitor*" OR Sirolimus OR Everolimus OR "Checkpoint inhibitor*" OR Pembrolizumab OR Nivolumab OR Ipilimumab OR Atezolibumab OR Avelumab OR Durvalumab OR Cyclophosphomide OR Vincristine OR Vinblastine OR Busulfan OR Doxorubucin OR Daunorubicin OR Gemcitabine OR Mercaptopurine OR Cladribine OR Hydroxyurea OR Capecitabine OR Plaratrexate OR Fludarabine OR Fluorouracil OR Pemetrexed OR Thioguanine OR Floxuridine OR Citarabine OR Clofarabine OR Decitabine OR Nelarabine) ) AND (MH "Influenza Vaccines") OR ((MH "vaccination") and (MH "influenza, human")) OR (((influenza OR flu) N5 (vaccin* OR immunization*)) OR Fluzone OR Fluad OR Flublok) Exclude Medline records ; Abstract Available |
| Scopus | (TITLE-ABS-KEY("sickle-cell anemia" OR immunocompromised OR immunosuppress* OR immunodeficien* OR immuno-compromised OR immuno-suppress* OR immuno-deficien* OR immunopathology OR (immun* W/2 incompeten*) OR (immun* W/2 suppress*) OR (immun* W/2 deficien*) OR (immun* W/2 syndrome*) OR autoimmun* OR auto-immun* OR transplant* OR Leukemia* OR Lymphoma* OR neoplasm* OR cancer* OR malignan* OR HIV* OR asplenia OR Agammaglobulinemia* OR hypogammaglobulinemia* OR "Specific polysaccharide antibody deficiency" OR "Interferon alpha deficiency" OR "Interferon gamma deficiency" OR "Chronic granulomatous disease" OR "Chediak-Higashi syndrome" OR "Leukocyte adhesion deficiency" OR "DiGeorge syndrome" OR "Complement deficiency" OR "Wiskott-Adlrich syndrome" OR "X-linked lymphoproliferative disease" OR arthritis OR "Multiple Sclerosis" OR Psoriasis OR lupus OR "Sjogren syndrome" OR "Sicca Syndrome" OR "Systemic sclerosis" OR Scleroderma OR Dermatomyositis OR Polymyositis OR "Mixed connective tissue disease" OR "Inflammatory bowel disease" OR "Crohn's disease" OR "Ulcerative colitis" OR "Polyarteritis nodosa" OR Granulomatosis OR arteritis OR "Polymyalgia rheumatica" OR "Celiac disease" OR "Primary sclerosing cholangitis") OR TITLE-ABS-KEY(Corticosteroid* OR Prednisone OR Prednisolone OR Dexamethasone OR Budesonide OR "tumor necrosis factor alpha" OR "TNF-alpha" OR "Janus kinase inhibitor*" OR Tofacitinib OR Rituximab OR Methotrexate OR "6-mercaptopurine" OR "IMDH inhibitor*" OR Azathioprine OR Leflunomide OR Mycophenolate OR Biologics OR Abatacept OR Adalimumab OR Anakinra OR Certolizumab OR Etanercept OR Infliximab OR Ixekizumab OR Natalizumab OR Secukinumab OR Tocilizumab OR Ustekinumab OR Vedolizumab OR Basilixumab OR Daclizumab OR "Calcineurin inhibitor*" OR Cyclosporine OR Tacrolimus OR "mTOR inhibitor*" OR Sirolimus OR Everolimus OR "Checkpoint inhibitor*" OR Pembrolizumab OR Nivolumab OR Ipilimumab OR Atezolibumab OR Avelumab OR Durvalumab OR Cyclophosphomide OR Vincristine OR Vinblastine OR Busulfan OR Doxorubucin OR Daunorubicin OR Gemcitabine OR Mercaptopurine OR Cladribine OR Hydroxyurea OR Capecitabine OR Plaratrexate OR Fludarabine OR Fluorouracil OR Pemetrexed OR Thioguanine OR Floxuridine OR Citarabine OR Clofarabine OR Decitabine OR Nelarabine)) AND TITLE-ABS-KEY(((influenza OR flu) W/5 (vaccin* OR immunization*)) OR Fluzone OR Fluad OR Flublok) AND NOT INDEX(medline) AND NOT INDEX(embase) |
View the complete list of GRADE evidence tables
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