TY - JOUR
T1 - Relative effectiveness of high-dose versus standard-dose influenza vaccine against hospitalizations and mortality according to Charlson Comorbidity Index
T2 - A post-hoc analysis of the DANFLU-1 randomized trial
AU - Bernholm, Katrine Feldballe
AU - Johansen, Niklas Dyrby
AU - Espersen, Caroline
AU - Modin, Daniel
AU - Hyldekær, Kira Janstrup
AU - Nealon, Joshua
AU - Samson, Sandrine
AU - Loiacono, Matthew M
AU - Harris, Rebecca C
AU - Larsen, Carsten Schade
AU - Jensen, Anne Marie Reimer
AU - Landler, Nino Emanuel
AU - Nielsen, Signe Tellerup
AU - Russell, Lene
AU - Itenov, Theis Skovsgaard
AU - Claggett, Brian L
AU - Solomon, Scott D
AU - Landray, Martin J
AU - Gislason, Gunnar H
AU - Køber, Lars
AU - Sivapalan, Pradeesh
AU - Jensen, Jens Ulrik Stæhr
AU - Biering-Sørensen, Tor
N1 - © 2026. The Author(s).
PY - 2026/1/29
Y1 - 2026/1/29
N2 - PURPOSE: The DANFLU-1 trial suggested lower incidence of hospitalizations for pneumonia and influenza, respiratory disease and all-cause mortality among older adults receiving high-dose (HD-IV) versus standard-dose (SD-IV) influenza vaccine. This study assessed the relative effectiveness of HD-IV versus SD-IV according to comorbidity in elderly individuals.METHODS: This was a post-hoc analysis of the DANFLU-1 randomized controlled feasibility trial of HD-IV versus SD-IV conducted during the 2021-2022 influenza season in adults aged 65-79 years. Outcomes assessed included influenza-related, respiratory, and cardiovascular hospitalizations, and mortality. We tested for effect modification by level of the Charlson Comorbidity Index (CCI) using ICD-10 codes up to 10 years prior to randomization.RESULTS: Of the 12,477 randomly assigned participants (mean age 71.7 ± 3.9 years, 47.1% female), 8,020 (64.3%) had CCI = 0, 3,560 (28.5%) had CCI = 1-2 and 893 (7.2%) had CCI ≥ 3. When comparing HD-IV with SD-IV, hazard ratios of hospitalizations for pneumonia and influenza were similar across CCI groups (HR [95%CI]: 0.15 [0.03-0.68] for CCI = 0, 0.36 [0.11-1.15] for CCI = 1-2, 1.00 [0.25-4.00] for CCI ≥ 3). Comparable patterns were found for hospitalizations for respiratory disease (0.46 [0.17-1.20] for CCI = 0, 0.67 [0.32-1.39] for CCI = 1-2, 0.66 [0.24-1.87] for CCI ≥ 3) and all-cause mortality (0.28 [0.09-0.86] for CCI = 0, 0.70 [0.30-1.63] for CCI = 1-2, 0.57 [0.24-1.36] for CCI ≥ 3). There was no statistical evidence of effect modification by CCI for any outcome.CONCLUSIONS: The lower incidences of clinical outcomes for HD-IV compared to SD-IV were not significantly modified by CCI. The potential benefit of HD-IV versus SD-IV may therefore be applicable regardless of comorbidity burden. Further research is required to confirm these findings.
AB - PURPOSE: The DANFLU-1 trial suggested lower incidence of hospitalizations for pneumonia and influenza, respiratory disease and all-cause mortality among older adults receiving high-dose (HD-IV) versus standard-dose (SD-IV) influenza vaccine. This study assessed the relative effectiveness of HD-IV versus SD-IV according to comorbidity in elderly individuals.METHODS: This was a post-hoc analysis of the DANFLU-1 randomized controlled feasibility trial of HD-IV versus SD-IV conducted during the 2021-2022 influenza season in adults aged 65-79 years. Outcomes assessed included influenza-related, respiratory, and cardiovascular hospitalizations, and mortality. We tested for effect modification by level of the Charlson Comorbidity Index (CCI) using ICD-10 codes up to 10 years prior to randomization.RESULTS: Of the 12,477 randomly assigned participants (mean age 71.7 ± 3.9 years, 47.1% female), 8,020 (64.3%) had CCI = 0, 3,560 (28.5%) had CCI = 1-2 and 893 (7.2%) had CCI ≥ 3. When comparing HD-IV with SD-IV, hazard ratios of hospitalizations for pneumonia and influenza were similar across CCI groups (HR [95%CI]: 0.15 [0.03-0.68] for CCI = 0, 0.36 [0.11-1.15] for CCI = 1-2, 1.00 [0.25-4.00] for CCI ≥ 3). Comparable patterns were found for hospitalizations for respiratory disease (0.46 [0.17-1.20] for CCI = 0, 0.67 [0.32-1.39] for CCI = 1-2, 0.66 [0.24-1.87] for CCI ≥ 3) and all-cause mortality (0.28 [0.09-0.86] for CCI = 0, 0.70 [0.30-1.63] for CCI = 1-2, 0.57 [0.24-1.36] for CCI ≥ 3). There was no statistical evidence of effect modification by CCI for any outcome.CONCLUSIONS: The lower incidences of clinical outcomes for HD-IV compared to SD-IV were not significantly modified by CCI. The potential benefit of HD-IV versus SD-IV may therefore be applicable regardless of comorbidity burden. Further research is required to confirm these findings.
U2 - 10.1007/s10096-026-05408-5
DO - 10.1007/s10096-026-05408-5
M3 - Journal article
C2 - 41609947
SN - 0934-9723
JO - European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
JF - European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
ER -