Grading of Recommendations, Assessment, Development, and Evaluation (GRADE): Higher-Dose and Adjuvanted Influenza Vaccines for Solid Organ Transplant Recipients

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:

  • Influenza-associated hospitalization
  • Medically-attended influenza
  • Laboratory-confirmed influenza—immunogenicity data acceptable

Harms:

  • Transplant rejection or graft failure
  • Neuroinflammatory conditions , e.g. Guillain-Barré syndrome (GBS), acute disseminated encephalomyelitis (ADEM)
  • Other immune-related adverse events, including new onset or exacerbation of an autoimmune condition

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/
Limit to Abstracts Available

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/
Remove Medline records; NOT conference abstract
Limit to Abstracts Available

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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