Question explored with the scientific record
Conversation so far
- 1 does the flu vaccine work
- 2 show me only rct TRIALS
- 3 so any evidence it works on hard endpoints
- 4 Any RCTs using hard endpoints beyond deaths, like ICU admission or excess flu deaths?
Answered on this page ↓
Any RCTs using hard endpoints beyond deaths, like ICU admission or excess flu deaths?
The short version: a few observational studies report flu vaccine reduces ICU admission in specific high-risk groups, but no randomized trial has tested this in the general population.
The evidence here is all observational and limited to narrow populations. One Taiwanese study of lupus patients found vaccination was associated with a 45% lower risk of ICU admission (adjusted hazard ratio 0.55, 95% CI 0.39-0.79) [3]. Another Taiwanese study of dialysis patients reported an even larger association: an 81% reduction in ICU admission (adjusted HR 0.19, 95% CI 0.14-0.27) [4]. A Spanish study of hospitalized flu patients found lack of vaccination was associated with severe illness (pneumonia, ICU, or death) with an odds ratio of 0.59 (95% CI 0.36-0.97) [10]. But these are all retrospective, not randomized, and the healthy-vaccinee bias is well documented [20].
| Population | Outcome | Adjusted effect | Study design | Source |
|---|---|---|---|---|
| Lupus patients | ICU admission | HR 0.55 (0.39-0.79) | Retrospective cohort | [3] |
| Dialysis patients | ICU admission | HR 0.19 (0.14-0.27) | Retrospective cohort | [4] |
| Hospitalized flu patients | Severe illness (ICU/pneumonia/death) | OR 0.59 (0.36-0.97) | Retrospective cohort | [10] |
| General population | ICU admission | No RCT found | - | - |
The Nordic comparison study [1] and the Spanish ICU report [13] describe flu severity by season and vaccination coverage, but neither is a controlled trial. The Michigan chart review found vaccination did not significantly reduce ICU admission or death among hospitalized flu patients [5]. The Casado study found repeated vaccination reduced ICU admission risk by 74% in older hospitalized patients, but also found current-season vaccination was associated with increased mortality (OR 3.35, 95% CI 1.06-10.58) [6] — a signal that deserves attention, not dismissal.
My call: the evidence for flu vaccine reducing ICU admission comes only from observational studies in specific high-risk groups, not from randomized trials in the general population. The healthy-vaccinee bias is large and unaddressed. Confidence: low that the effect generalizes to healthy adults.
Sources examined 32
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Pandemic vaccination strategies and influenza severe outcomes during the influenza A(H1N1)pdm09 pandemic and the post-pandemic influenza season: the Nordic experience
Nordic countries with higher pandemic vaccination coverage experienced fewer A(H1N1)pdm09-related ICU admissions and deaths in the post-pandemic season, suggesting vaccination strategy and timing can influence subsequent influenza severity.
DOI: 10.2807/1560-7917.es.2016.21.16.30208 -
Clinical impact of influenza – lessons learnt from the pandemic influenza A (H1N1) 2009
A global systematic review with Australian PAEDS data shows the 2009 H1N1 pandemic imposed a heavier burden on children, younger adults, pregnant women, and the obese than seasonal influenza, with more gastrointestinal symptoms and ICU admissions, though overall mortality was no…
DOI: 10.1071/ma11029 -
Effects of annual influenza vaccination on morbidity and mortality in patients with Systemic Lupus Erythematosus: A Nationwide Cohort Study
A nationwide retrospective cohort study in Taiwan found that annual influenza vaccination in adults with systemic lupus erythematosus was associated with lower risks of total hospitalization, ICU admission, septicemia/bacteremia/viremia, in-hospital dialysis, and death over one …
DOI: 10.1038/srep37817 -
Effectiveness of Influenza Vaccination in Patients with End-Stage Renal Disease Receiving Hemodialysis: A Population-Based Study
A population-based Taiwanese study shows that influenza vaccination in end-stage renal disease patients on hemodialysis is associated with reduced morbidity and mortality, especially among the elderly, based on nationwide insurance data and time-dependent Cox analyses.
DOI: 10.1371/journal.pone.0058317 -
Impact of Vaccination on Hospitalized Adults With Influenza A, 2012–2013
A retrospective chart review at the University of Michigan Health System during the 2012-2013 influenza season evaluated whether prior influenza vaccination influences clinical outcomes among adults hospitalized with influenza A, finding vaccination was associated with lower lik…
DOI: 10.1097/ipc.0000000000000214 -
Healthy-vaccinated effect
The study by Casado et al. demonstrates that repeated influenza vaccination significantly reduces the risk of severe influenza in older hospitalized patients, although it raises concerns about increased mortality in those vaccinated in the current season.
DOI: 10.1503/cmaj.69406 -
2635. Outbreak of Enterovirus D68 Among Children in Japan and Simultaneous Circulation of Clade B3 in Europe
Human metapneumovirus admissions in a pediatric hospital over six winter seasons (2014–2019) were more frequent than RSV or influenza, while ICU/HAI rates and mortality were similar across viruses, with many ICU patients having chronic lung disease or requiring tracheostomy.
DOI: 10.1093/ofid/ofz360.2313 -
Paediatric Active Enhanced Disease Surveillance (PAEDS) annual report 2015: Prospective hospital-based surveillance for serious paediatric conditions
Hospital-based prospective surveillance across five Australian paediatric centres in 2015 identified 674 cases across six serious paediatric conditions, highlighting influenza impact, rotavirus-vaccine–related intussusception signals, and varicella vaccination uptake trends to i…
DOI: 10.33321/cdi.2017.41.37 -
Critical care services and the H1N1 (2009) influenza epidemic in Australia and New Zealand in 2010: the impact of the second winter epidemic
Second winter wave of H1N1 2009 in Australia and New Zealand caused substantial ICU demand, but was markedly lower than 2009, with vaccination present but not fully protective against critical illness.
DOI: 10.1186/cc10266 -
Influenza vaccination coverage and factors associated with severe laboratory-confirmed influenza-related illness in patients receiving care at a tertiary hospital in Catalonia (Spain) during the 2018–2019 epidemic season
In a retrospective analysis of 682 laboratory-confirmed influenza cases during the 2018-2019 season in a Spanish tertiary hospital, influenza vaccination coverage was suboptimal (42.4% in high-risk patients) and lack of vaccination, older age, and smoking were associated with se…
DOI: 10.1371/journal.pone.0260397 -
Public Health and Economic Effects of Influenza Vaccination
Raising influenza vaccination coverage lowers infections, hospitalizations, antiviral use, and costs, with uptake shaped by policy design, affordability, and communication across regions.
DOI: 10.61173/ke3h8d53 -
Summer 2023 ACIP Update: RSV Prevention and Updated Recommendations on Other Vaccines
ACIP's Summer 2023 update outlines RSV prevention advances, notably nirsevimab for infants, and revised pediatric vaccine recommendations across influenza, pneumococcal, meningococcal, mpox, and COVID-19, with emphasis on implementation, safety monitoring, and cost consideration…
DOI: 10.1542/peds.2023-063955 -
First influenza season after the 2009 pandemic influenza: report of the first 300 ICU admissions in Spain
This study reports on the clinical profiles and outcomes of the first 300 critically ill patients admitted to intensive care units in Spain during the 2010-11 influenza season caused by the An/H1N1 virus, highlighting a higher severity of illness and mortality compared to the pr…
DOI: 10.1016/j.medin.2011.03.001 -
The importance of Haemophilus influenzae in community-acquired pneumonia: an emerging pathogen in the elderly regardless of comorbidities compared to Streptococcus pneumoniae
In a Swedish ECAPS cohort sub-study, Haemophilus influenzae emerged as a notable cause of community-acquired pneumonia in older adults, with similar short-term mortality to Streptococcus pneumoniae despite greater age, while detection patterns differed between pathogens.
DOI: 10.1186/s41479-024-00136-w -
The impact of targeting all elderly persons in England and Wales for yearly influenza vaccination: excess mortality due to pneumonia or influenza and time trend study
The switch from risk-based to age group-based targeting of yearly influenza vaccination in England and Wales was associated with weakly supportive evidence of lower pneumonia/influenza mortality in the elderly, but the effect was small and possibly confounded.
DOI: 10.1136/bmjopen-2013-002743 -
Influenza-related excess mortality necessitates an urgent call for action
The study highlights the significant underreporting of influenza-related excess mortality in Austria from 2001 to 2009, emphasizing the need for improved vaccination rates among vulnerable populations to prevent avoidable deaths.
DOI: 10.1007/s00508-011-0081-1 -
Emerging Infections: Pandemic Influenza
This study reviews the historical impact of pandemic influenza, emphasizing the need for effective control strategies in light of the virus's mutability and the challenges posed by modern society.
DOI: 10.1093/oxfordjournals.epirev.a017917 -
The Japanese Experience with Vaccinating Schoolchildren against Influenza
A long-term ecological time-series analysis comparing Japan and the United States shows that mass vaccination of Japanese schoolchildren against influenza markedly reduced winter excess mortality—particularly among the elderly—and that substantial deaths were averted in associat…
DOI: 10.1056/NEJM200103223441204 -
Estimating mortality associated with seasonal influenza among adults aged 65 years and above in China from 2011 to 2016: A systematic review and model analysis
A systematic review and model-based analysis estimated seasonal influenza–associated mortality among Chinese adults aged 65+ from 2011–2016, revealing substantial excess mortality in respiratory, circulatory, and all-cause outcomes with large provincial variation and policy impl…
DOI: 10.1111/irv.13067 -
Influenza Vaccination of Pregnant Women and Serious Adverse Events in the Offspring
This perspective argues that influenza vaccination of pregnant women lacks sufficient evidence of benefit and shows safety signals from RCTs, calling for further trials before universal vaccination.
DOI: 10.3390/ijerph16224347 -
Changes in influenza-associated excess mortality in China between 2012–2019 and 2020–2021: a population-based statistical modelling study
This study evaluates influenza-associated excess mortality in China from 2012 to 2021, revealing a significant reduction in mortality during the COVID-19 pandemic due to decreased influenza activity.
DOI: 10.1186/s40249-025-01323-7 -
Cost-effectiveness and budget impact analysis for high dose quadrivalent influenza vaccine in the Italian elderly population
High-dose quadrivalent influenza vaccine in Italians aged 65+ is cost-effective and cost-saving versus standard-dose, mainly due to reduced influenza-related hospitalizations, with about €5.39 million in three-year savings and a dominant cost-effectiveness profile.
DOI: 10.33393/grhta.2021.2247 -
Influenza Vaccination in the Face of Immune Exhaustion: Is Herd Immunity Effective for Protecting the Elderly?
This narrative review examines why trivalent inactivated influenza vaccines (TIVs) are suboptimal in elderly and immunosenescent populations, describes mechanisms of immune aging and alternative immunization strategies, and evaluates herd immunity—particularly through childhood …
DOI: 10.1155/2011/419216 -
Early Indication of Long-Term Impact of COVID Injections
Analysis of Australian mortality data through June 2023 suggests COVID injections caused successive waves of excess deaths at a 21-week lag, with a fulfilled prediction and progressively larger dose-response, indicating possible long-term harm.
DOI: 10.33140/mcr.07.048 -
Novel vaccine safety issues and areas that would benefit from further research
This BMJ Global Health paper reviews five vaccine safety case studies (dengue, pandemic influenza, rotavirus, HPV, and RTS,S malaria vaccine), summarizes the safety signals, mechanisms, and epidemiological evidence, and outlines lessons and research gaps to improve future vaccin…
DOI: 10.1136/bmjgh-2020-003814 -
Guillain-Barré Syndrome and Vaccination: Usually Unrelated
A narrative review of epidemiological data on Guillain-Barré syndrome (GBS) and vaccines concludes that GBS is usually triggered by antecedent infections rather than vaccination; clear causal associations were limited to the obsolete neural-tissue rabies vaccine and the 1976 swi…
DOI: 10.1177/001857870003500214 -
Antibiotic Resistance in Community-Acquired Pneumonia Pathogens
A comprehensive narrative review of antibiotic resistance among community-acquired pneumonia (CAP) pathogens, detailing mechanisms, prevalence, and clinical implications across pathogens (S. pneumoniae, S. aureus, H. influenzae, M. pneumoniae, C. pneumoniae, L. pneumophila, Ente…
DOI: 10.1055/s-0036-1593753 -
The role of vaccines in combating antimicrobial resistance
The chapter/lecture argues that vaccination can reduce antimicrobial resistance by preventing infections, lowering resistant subtypes, and reducing bystander and hospital transmission, with evidence for certain vaccines and a call for expanded economic evaluations and a global g…
DOI: 10.1093/eurpub/ckaa165.1204 -
Bird Flu as Next Health Risk for Human Being
An opinionated analysis arguing avian influenza could pose a future health risk and discussing immunological mechanisms, vaccine history, and cross-viral considerations, supported by largely non-empirical claims.
DOI: 10.14738/bjhmr.1201.18337 -
Preventing Myocardial Infarction With Vaccination
Commentary on whether pneumococcal vaccination reduces the risk of acute myocardial infarction or stroke in adults, summarizing Tseng et al.'s retrospective cohort study (n≈360,000 men aged 45–69) that found no association, and discussing methodological limitations of observatio…
DOI: 10.1001/jama.2010.571 -
Biological activity of monoclonal antibodies to operationally defined antigenic regions on the hemagglutinin molecule of A/Seal/Massachusetts/1 /80 (H7N7) influenza virus
Monoclonal antibodies targeting four operational antigenic regions on the HA of A/Seal/Massachusetts/1/80 (H7N7) reveal that some antibodies neutralize infection without inhibiting hemagglutination, suggesting distinct mechanisms and implications for influenza vaccine evaluation…
DOI: 10.1016/0042-6822(82)90375-0 -
Potential effects of vaccinations on the prevention of COVID-19: rationale, clinical evidence, risks, and public health considerations
A narrative review evaluating whether existing vaccines (influenza, pneumococcal, and BCG) may influence COVID-19 risk or outcomes, summarizing immunologic mechanisms, available clinical evidence, regulatory aspects, and public health implications.
DOI: 10.1080/14760584.2020.1825951