High-Dose Influenza Vaccine (QIV-HD) Shows Promise Results in Reducing Hospitalizations


A recent study reveals the QIV-HD vaccine significantly lowers hospitalization rates compared to the standard-dose vaccine (QIV-SD).

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A randomized DANFLU-1 clinical vaccine trial, as documented in Clinical Microbiology and Infection compared the QIV-HD with the QIV-SD. The vaccine was associated with lower incidence rates of hospitalizations for pneumonia or influenza and all-cause hospitalizations compared with QIV-SD with trends evident independent of influenza circulation levels. The exploratory results suggest a number needed to treat of 65 (95% CI 35-840) persons with QIV-HD compared to QIV-SD to prevent 1 additional all-cause hospitalization per season.

In a study involving 12,477 participants, those who received QIV-HD had only 10 events of hospitalizations for pneumonia or influenza compared to those who received QIV-SD with 33 events. The risk of such hospitalizations was 70% lower with QIV-HD. The total number of hospitalizations for any reason was also lower in the QIV-HD group, with 647 events compared to 742 events in the QIV-SD group, indicating a 13% reduction.

“Effectiveness estimates for all significantly reduced outcomes (hospitalizations for pneumonia or influenza, all-cause hospitalizations, and all-cause death) consistently favored QIV-HD in our temporal analysis,” according to the investigators. “The observed effectiveness even prior to active influenza transmission during the study season may point to beneficial immunomodulatory effects of vaccination independent of the prevention of overt influenza infection.”

3 Key Takeaways

  1. The DANFLU-1 trial found that QIV-HD was more effective than QIV-SD in reducing the incidence of hospitalizations for pneumonia or influenza and all-cause hospitalizations.
  2. The study observed that QIV-HD's effectiveness was noticeable even before the peak of influenza transmission, suggesting that the vaccine may have immunomodulatory effects that go beyond the prevention of overt influenza infection.
  3. The finding supports the hypothesis that influenza vaccination could have broader health benefits, potentially even in seasons where there is a mismatch between the vaccine strains and the circulating influenza strains.

QIV-HD consistently showed better results even in the period before active influenza transmission. Although widespread flu was not observed until the 10th week of 2022, a noticeable decrease in hospitalizations for pneumonia or influenza among those who received QIV-HD was already evident by the 3rd week of 2022. At the time, there were only 5 cases of such hospitalizations in the QIV-HD group, compared to 15 cases in the group that received the standard-dose vaccine.

“While our results should surely be considered hypothesis-generating, the observed effectiveness against less specific outcomes with trends evident outside of influenza circulation support previous literature on non-specific effects of influenza vaccination,” explains investigators. “Several prior reports have indicated the effectiveness of influenza vaccination in seasons with substantial vaccine mismatch.”

The study had several limitations. First, the size of the sample group wasn't initially planned for this specific analysis, which could affect the results' reliability. Additionally, no adjustments were made for multiple comparisons, raising the possibility that some findings might be coincidental. While using registry data for clinical outcomes is practical, it might lead to some inaccuracies, although these are expected to be uniform across all groups. Another issue was distinguishing whether hospital readmissions were for new health problems or related to ongoing ones. Moreover, the trial did not systematically test for influenza and was conducted during a single flu season with a significant mismatch between the vaccine strains and circulating viruses, limiting the ability to apply these findings to other seasons with different strain matches.

In summary, the DANFLU-1 clinical trial suggests that QIV-HD is more effective than QIV-SD. The study's limitations, including its design and the fact that it was conducted over a single flu season, indicate that while the findings are promising, they require further research due to the limitations.


Johansen N, Modin D, Skaarup K, Valentiner-Branth P, Krause T, et. al. Effectiveness of high-dose vs. standard-dose quadrivalent influenza vaccine against recurrent hospitalisations and mortality in relation to influenza circulation: a post-hoc analysis of the DANFLU-1 randomised clinical trial. Clinical Microbiology and Infection. Published January 27, 2024. Accessed January 30, 2024. doi: https://doi.org/10.1016/j.cmi.2024.01.017

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