Influenza (seasonal) vaccines — Vaccine Data Navigator

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Seasonal influenza (including the 2009 A(H1N1)pdm09 pandemic) Influenza A and B viruses

Disease risks

Acute risks of the infection itself: complications, hospitalisation, ICU, death.

Outcome (O)	Population (P)	Estimate	Design (S)	Source
Death among laboratory-confirmed 2009 A(H1N1)pdm09 cases (confirmed CFR) severity: death strain: A(H1N1)pdm09 case definition: Fatal cases among laboratory-confirmed pandemic influenza cases in 12 of 42 included studies	all ages (weighted mean age of confirmed cases 18.1 years) vaccination status: unvaccinated country: multiple setting: mixed, mostly hospital-ascertained confirmed cases period: April 2009 to January 2010 n: 937 fatal cases among 31,980 confirmed cases All ages	2.9 (0.0–6.7) confirmed-case CFR (%) per laboratory-confirmed case	systematic review	Khandaker et al. 2011 Influenza Other Respir Viruses quote The confirmed case fatality ratio was 2·9% (95% CI 0·0-6·7%), an extracted average from 12 of 42 studies reporting fatal cases (937 fatal cases among 31,980 confirmed cases), which gives an overall estimated infected case fatality ratio of 0·02%. abstract Confirmed cases over-represent severe illness, which inflates the ratio: the same sentence gives an estimated infected-case fatality ratio of 0.02%. Do not present the 2.9% figure without that denominator caveat.
Death per infection with 2009 A(H1N1)pdm09 (infected-case fatality ratio) severity: death strain: A(H1N1)pdm09 case definition: Estimated fatality ratio per infection, derived by the review from confirmed-case data	all ages vaccination status: unvaccinated country: multiple setting: community period: April 2009 to January 2010 All ages	0.02 infected-case fatality ratio (%) per infection	systematic review	Khandaker et al. 2011 Influenza Other Respir Viruses quote The confirmed case fatality ratio was 2·9% (95% CI 0·0-6·7%), an extracted average from 12 of 42 studies reporting fatal cases (937 fatal cases among 31,980 confirmed cases), which gives an overall estimated infected case fatality ratio of 0·02%. abstract An estimate derived by the review, not a direct observation, and the abstract gives no confidence interval. Same sentence as the confirmed-case CFR of 2.9%; the two differ by two orders of magnitude because of the denominator.
Death among confirmed 2009 A(H1N1)pdm09 cases in early pandemic studies (confirmed CFR) severity: death strain: A(H1N1)pdm09 case definition: Deaths among confirmed cases, as estimated in the earliest pandemic studies	all ages vaccination status: unvaccinated country: multiple setting: mixed period: 2009 All ages	0.5 confirmed-case CFR (%) per confirmed case	systematic review	Nishiura 2010 Expert Rev Respir Med quote Epidemiological studies in the very early stages of the pandemic estimated the confirmed CFR (cCFR), using confirmed cases as the denominator, to be approximately 0.5%. abstract A narrative review summary of early estimates; the next sentence of the abstract puts the symptomatic CFR an order of magnitude lower. Both varied greatly by age and risk group.
Deaths in the 1918-1919 influenza pandemic severity: death case definition: Historical estimate of pandemic deaths	all ages vaccination status: unvaccinated country: worldwide setting: community period: 1918-1919 (pre-vaccine era: inactivated vaccines were first developed in the late 1930s and 1940s) All ages	21 million estimated number of deaths worldwide per world population	expert body	cdc.gov quote The pandemic of "Spanish" influenza in 1918–1919 caused an estimated 21 million deaths worldwide. Pink Book chapter 12, Introduction A historical pandemic figure quoted by the Pink Book; other published estimates for 1918-1919 are considerably higher, and no uncertainty range is given. It describes a pandemic strain, not seasonal influenza, and predates any vaccine.
Influenza-associated death in children severity: death case definition: Laboratory-confirmed influenza-associated paediatric deaths reported to national surveillance	children younger than 18 years vaccination status: mixed country: United States setting: community and hospital period: 2010-2016 n: 675 reported deaths Infant <1y1-4y5-11y12-17y	0.15 (0.14–0.16) average annual incidence per 100,000 children per 100,000 children per year	surveillance	Shang et al. 2018 Pediatrics quote The average annual incidence was 0.15 per 100 000 children (95% confidence interval: 0.14-0.16) and was highest among children aged <6 months (incidence: 0.66; 95% confidence interval: 0.53-0.82), followed by children aged 6-23 months (incidence: 0.33; 95% confidence interval: 0.27-0.39). abstract, RESULTS Counts only reported, laboratory-confirmed deaths, so this is a lower bound. Half of the children who died had no pre-existing medical condition.
Influenza-associated death in infants under 6 months severity: death case definition: Laboratory-confirmed influenza-associated paediatric deaths reported to national surveillance	children aged under 6 months vaccination status: unvaccinated country: United States setting: community and hospital period: 2010-2016 NeonateInfant <1y	0.66 (0.53–0.82) average annual incidence per 100,000 children per 100,000 infants under 6 months per year	surveillance	Shang et al. 2018 Pediatrics quote The average annual incidence was 0.15 per 100 000 children (95% confidence interval: 0.14-0.16) and was highest among children aged <6 months (incidence: 0.66; 95% confidence interval: 0.53-0.82), followed by children aged 6-23 months (incidence: 0.33; 95% confidence interval: 0.27-0.39). abstract, RESULTS The highest paediatric death rate is in infants too young to be vaccinated. The same sentence gives 0.33 for children aged 6-23 months (next record).
Influenza-associated death in children aged 6-23 months severity: death case definition: Laboratory-confirmed influenza-associated paediatric deaths reported to national surveillance	children aged 6-23 months vaccination status: mixed country: United States setting: community and hospital period: 2010-2016 Infant <1y1-4y	0.33 (0.27–0.39) average annual incidence per 100,000 children per 100,000 children aged 6-23 months per year	surveillance	Shang et al. 2018 Pediatrics quote The average annual incidence was 0.15 per 100 000 children (95% confidence interval: 0.14-0.16) and was highest among children aged <6 months (incidence: 0.66; 95% confidence interval: 0.53-0.82), followed by children aged 6-23 months (incidence: 0.33; 95% confidence interval: 0.27-0.39). abstract, RESULTS Children in this age band are eligible for vaccination (two doses in the first season). Compare with the all-children rate of 0.15 in the same sentence.
Influenza vaccination among children who died of influenza severity: death case definition: Any influenza vaccination recorded among decedents aged 6 months and older	children aged 6 months to 17 years who died of influenza vaccination status: mixed country: United States setting: community and hospital period: 2010-2016 n: 477 decedents with vaccination information Infant <1y1-4y5-11y12-17y	31 proportion of decedents with any influenza vaccination (%) per influenza-associated paediatric death with vaccination information	surveillance	Shang et al. 2018 Pediatrics quote Only 31% (n = 149 of 477) of children aged ≥6 months had received any influenza vaccination. abstract, RESULTS A descriptive proportion among deaths, not a vaccine effectiveness estimate; it cannot be read as a risk without the vaccination coverage of the population the deaths came from. See influenza-eff records for the case-control estimate of VE against paediatric death.
Influenza-associated death in infants under 6 months severity: death case definition: Influenza-associated deaths among children reported by state health departments	children younger than six months vaccination status: unvaccinated country: United States setting: community and hospital period: 2003-2004 season n: 153 deaths reported among children NeonateInfant <1y	0.88 (0.52–1.39) mortality rate per 100,000 children per 100,000 infants under 6 months	surveillance	Bhat et al. 2005 N Engl J Med quote The mortality rate was highest among children younger than six months of age (0.88 per 100,000 children; 95 percent confidence interval, 0.52 to 1.39 per 100,000). abstract, RESULTS A single severe A(H3N2) season, the first with mandatory national reporting. Forty-seven percent of the children who died had previously been healthy.
Laboratory-confirmed influenza-associated hospitalisation severity: hospitalisation case definition: Laboratory-confirmed influenza in residents of the FluSurv-NET catchment area admitted to hospital	all ages vaccination status: mixed country: United States (FluSurv-NET catchment, about 9% of the population) setting: hospital period: 2010-11 to 2019-20 (pre-COVID seasons) All ages	8.7 to 102.9 hospitalisation rate per 100,000 population (lowest and highest season) per 100,000 population per season	surveillance	Naquin et al. 2024 MMWR Surveill Summ quote Before the COVID-19 pandemic, hospitalization rates per 100,000 population ranged from 8.7 (2011-12) to 102.9 (2017-18) and had consistent seasonality. abstract, RESULTS Season range, not a confidence interval: 8.7 in 2011-12 and 102.9 in 2017-18. Rates depend on clinician testing practices and are not adjusted for under-testing; the CDC burden model adjusts for this and gives higher totals.
ICU admission among patients hospitalised with laboratory-confirmed influenza severity: ICU admission case definition: ICU admission during hospitalisation with laboratory-confirmed influenza	all ages vaccination status: mixed country: United States (FluSurv-NET) setting: hospital period: 2010-11 to 2022-23 seasons All ages	14.1% to 22.3% proportion of hospitalised influenza patients admitted to ICU (%) (range across seasons) per laboratory-confirmed influenza hospitalisation	surveillance	Naquin et al. 2024 MMWR Surveill Summ quote Admission to the intensive care unit, need for invasive mechanical ventilation, and in-hospital death ranged from 14.1% to 22.3%, 4.9% to 11.1%, and 2.2% to 3.5% of patients hospitalized with influenza, respectively, during the reported surveillance period. abstract, RESULTS Denominator is hospitalised patients, not all infections; do not multiply by the hospitalisation rate to obtain a population risk. The same sentence gives invasive mechanical ventilation and in-hospital death (next records).
Invasive mechanical ventilation among patients hospitalised with laboratory-confirmed influenza severity: mechanical ventilation case definition: Invasive mechanical ventilation during hospitalisation with laboratory-confirmed influenza	all ages vaccination status: mixed country: United States (FluSurv-NET) setting: hospital period: 2010-11 to 2022-23 seasons All ages	4.9% to 11.1% proportion of hospitalised influenza patients receiving invasive mechanical ventilation (%) (range across seasons) per laboratory-confirmed influenza hospitalisation	surveillance	Naquin et al. 2024 MMWR Surveill Summ quote Admission to the intensive care unit, need for invasive mechanical ventilation, and in-hospital death ranged from 14.1% to 22.3%, 4.9% to 11.1%, and 2.2% to 3.5% of patients hospitalized with influenza, respectively, during the reported surveillance period. abstract, RESULTS Denominator is hospitalised patients. Range across seasons, not a confidence interval.
In-hospital death among patients hospitalised with laboratory-confirmed influenza severity: death case definition: Death during hospitalisation with laboratory-confirmed influenza	all ages vaccination status: mixed country: United States (FluSurv-NET) setting: hospital period: 2010-11 to 2022-23 seasons All ages	2.2% to 3.5% proportion of hospitalised influenza patients dying in hospital (%) (range across seasons) per laboratory-confirmed influenza hospitalisation	surveillance	Naquin et al. 2024 MMWR Surveill Summ quote Admission to the intensive care unit, need for invasive mechanical ventilation, and in-hospital death ranged from 14.1% to 22.3%, 4.9% to 11.1%, and 2.2% to 3.5% of patients hospitalized with influenza, respectively, during the reported surveillance period. abstract, RESULTS An in-hospital case-fatality proportion among the hospitalised, not a case-fatality ratio per infection. Older adults had the highest hospitalisation rate in every season.
Influenza-associated death in children, 2024-25 season severity: death case definition: Influenza-associated paediatric deaths reported to national surveillance (nationally notifiable since 2004)	children aged under 18 years vaccination status: mixed country: United States setting: community and hospital period: 2024-25 season (highest non-pandemic season on record) n: 280 reported deaths Infant <1y1-4y5-11y12-17y	3.8 deaths per 1 million children (season) per 1 million children aged under 18 per season	surveillance	Reinhart et al. 2025 MMWR Morb Mortal Wkly Rep quote Through September 13, 2025, a total of 280 influenza-associated pediatric deaths were reported, representing a national rate of 3.8 deaths per 1 million children. abstract The highest paediatric death count since reporting began, excluding the pandemic season. More than half of the children had at least one underlying medical condition, so nearly half did not.
Vaccination status of children who died of influenza, 2024-25 severity: death case definition: Not fully vaccinated against influenza among vaccine-eligible paediatric decedents with available data	vaccine-eligible children aged 6 months to 17 years who died of influenza vaccination status: mixed country: United States setting: community and hospital period: 2024-25 season n: 208 decedents with available data Infant <1y1-4y5-11y12-17y	89 proportion of decedents not fully vaccinated (%) per vaccine-eligible influenza-associated paediatric death with data	surveillance	Reinhart et al. 2025 MMWR Morb Mortal Wkly Rep quote Among the 208 pediatric decedents with available data who were eligible for influenza vaccine, 89% were not fully vaccinated. abstract Descriptive, not a vaccine effectiveness estimate: it must be read against population coverage, which the abstract does not give. The case-control VE against paediatric death is a separate efficacy record.
Symptomatic influenza illnesses per year (modelled) severity: any symptomatic illness case definition: Modelled from FluSurv-NET hospitalisation surveillance with multipliers for testing and care-seeking	all ages vaccination status: mixed country: United States setting: community period: 2010-2025 (current era, annual vaccination recommended for everyone aged 6 months and older) All ages	9.4 million - 51 million annual number of influenza illnesses (range across seasons) per United States population per season	modelling	cdc.gov quote View Larger Download Estimated Range of Annual-Burden of Flu in the US from 2010-2025 CDC estimates that flu has resulted in 9.4 million – 51 million illnesses, 120,000 – 710,000 hospitalizations and 6,300 – 52,000 deaths annually between 2010 and 2025. About Estimated Flu Burden, Estimated Range of Annual Burden 2010-2025 Season-to-season range, not a confidence interval. No estimate exists for the first coronavirus pandemic season because influenza activity was minimal. Hospitalisations and deaths from the same sentence are separate records.
Influenza-associated hospitalisations per year (modelled) severity: hospitalisation case definition: Modelled from laboratory-confirmed hospitalisations in FluSurv-NET, adjusted for under-testing	all ages vaccination status: mixed country: United States setting: hospital period: 2010-2025 (current era) All ages	120,000 - 710,000 annual number of influenza-associated hospitalisations (range across seasons) per United States population per season	modelling	cdc.gov quote View Larger Download Estimated Range of Annual-Burden of Flu in the US from 2010-2025 CDC estimates that flu has resulted in 9.4 million – 51 million illnesses, 120,000 – 710,000 hospitalizations and 6,300 – 52,000 deaths annually between 2010 and 2025. About Estimated Flu Burden, Estimated Range of Annual Burden 2010-2025 Season-to-season range, not a confidence interval. The lower bound is the mildest season of the period and the upper bound the most severe; the Pink Book record names them.
Influenza-associated deaths per year (modelled) severity: death case definition: Modelled influenza-associated deaths from hospitalisation surveillance and death-certificate data	all ages vaccination status: mixed country: United States setting: community and hospital period: 2010-2025 (current era) All ages	6,300 - 52,000 annual number of influenza-associated deaths (range across seasons) per United States population per season	modelling	cdc.gov quote View Larger Download Estimated Range of Annual-Burden of Flu in the US from 2010-2025 CDC estimates that flu has resulted in 9.4 million – 51 million illnesses, 120,000 – 710,000 hospitalizations and 6,300 – 52,000 deaths annually between 2010 and 2025. About Estimated Flu Burden, Estimated Range of Annual Burden 2010-2025 Season-to-season range, not a confidence interval. Influenza-associated deaths are modelled, not counted from death certificates alone, because influenza is often not recorded as the cause of death.
Influenza-associated deaths per season (modelled) severity: death case definition: CDC modelled estimates of influenza-associated deaths	all ages vaccination status: mixed country: United States setting: community and hospital period: 2010-11 to 2019-20 seasons (current era) All ages	12,447 to 61,099 annual number of influenza-associated deaths (lowest and highest season) per United States population per season	modelling	cdc.gov quote Since 2010, CDC estimates the number of annual influenza-associated deaths has ranged from a low of 12,447 (2011–2012 season) to a high of 61,099 (2017–2018 season), with an average of 37,463 influenza-associated deaths annually. Pink Book chapter 12, Secular Trends in the United States The same sentence gives the mean across seasons (next record). The Pink Book edition quoted predates the coronavirus pandemic seasons, so those are excluded.
Influenza-associated deaths per season, mean (modelled) severity: death case definition: CDC modelled estimates of influenza-associated deaths	all ages vaccination status: mixed country: United States setting: community and hospital period: 2010-11 to 2019-20 seasons (current era) All ages	37,463 mean annual number of influenza-associated deaths per United States population per season	modelling	cdc.gov quote Since 2010, CDC estimates the number of annual influenza-associated deaths has ranged from a low of 12,447 (2011–2012 season) to a high of 61,099 (2017–2018 season), with an average of 37,463 influenza-associated deaths annually. Pink Book chapter 12, Secular Trends in the United States A mean across seasons with very different severity; see the range record. Most of these deaths are in older adults (next record).
Share of influenza-attributed deaths occurring in people aged 65 years and older severity: death case definition: CDC modelled influenza-associated deaths by age group	65 years and older as a share of all ages vaccination status: mixed country: United States setting: community and hospital period: since 2010 (current era) 65+	80 proportion of influenza-attributed deaths (%) per influenza-attributed death, all ages	modelling	cdc.gov quote Persons age 65 years and older account for approximately 80% of deaths attributed to influenza. Pink Book chapter 12, Secular Trends in the United States A share of deaths, not a risk per infection. The pandemic year was the exception, with most deaths in younger people (see the pandemic records).
Hospitalisations and deaths in the 2009 A(H1N1)pdm09 pandemic (modelled) severity: death strain: A(H1N1)pdm09 case definition: CDC modelled estimates of pandemic illnesses, hospitalisations and deaths	all ages vaccination status: mixed country: United States setting: community and hospital period: 2009-2010 pandemic All ages	12,500 estimated number of deaths per United States population over the pandemic	modelling	cdc.gov quote In January 2011, CDC estimated that the 2009 H1N1 caused illness in more than 60 million Americans, leading to more than 270,000 hospitalizations and 12,500 deaths. Pink Book chapter 12, Pandemics The same sentence gives more than 60 million illnesses and more than 270,000 hospitalisations. The next Pink Book sentence states that, unlike typical seasons, the large majority of hospitalisations and deaths were in people below retirement age.
Influenza-associated death rate, respiratory and circulatory causes (modelled) severity: death case definition: Regression models of death-certificate data for pneumonia and influenza and for respiratory and circulatory underlying causes	all ages vaccination status: mixed country: United States setting: community and hospital period: 1976-2007 (31 seasons spanning low to moderate vaccine coverage) All ages	1.4 to 16.7 annual influenza-associated deaths per 100,000 persons (lowest to highest season) per 100,000 population per season	modelling	Centers 2010 MMWR Morb Mortal Wkly Rep quote The annual rate of influenza-associated death in the United States overall during this period ranged from 1.4 to 16.7 deaths per 100,000 persons. abstract Range across seasons, not a confidence interval. The report ties the season-to-season variation to the virus type and subtype in circulation, with A(H3N2) seasons the most deadly.
Influenza-associated deaths per season, respiratory and circulatory causes (modelled) severity: death case definition: Regression models of death-certificate data for respiratory and circulatory underlying causes including pneumonia and influenza	all ages vaccination status: mixed country: United States setting: community and hospital period: 1976-2007 All ages	3,349 to 48,614 annual number of influenza-associated deaths (lowest and highest season) per United States population per season	modelling	Centers 2010 MMWR Morb Mortal Wkly Rep quote This report summarizes the results of these analyses, which found that, during 1976-2007, estimates of annual influenza-associated deaths from respiratory and circulatory causes (including pneumonia and influenza causes) ranged from 3,349 in 1986-87 to 48,614 in 2003-04. abstract The majority of seasonal influenza deaths in this period were in older adults. The denominator population grew over the period, so the rate record is the better comparison across seasons.
Global seasonal influenza-associated respiratory deaths per year (modelled) severity: death case definition: Excess respiratory mortality attributable to influenza from time-series regression in 33 countries, extrapolated to all countries	all ages vaccination status: mixed country: global setting: community and hospital period: 1999-2015 All ages	291 243-645 832 annual influenza-associated respiratory deaths (range) per world population per year	modelling	Iuliano et al. 2018 Lancet quote We estimated that 291 243-645 832 seasonal influenza-associated respiratory deaths (4·0-8·8 per 100 000 individuals) occur annually. abstract, FINDINGS Respiratory deaths only; the authors say non-respiratory (for example cardiovascular) influenza deaths are not included. The same sentence gives the equivalent rate per population.
Influenza-associated respiratory mortality rate, people aged 75 years and older (modelled) severity: death case definition: Excess respiratory mortality attributable to influenza	75 years or older vaccination status: mixed country: global setting: community and hospital period: 1999-2015 65+	51.3-99.4 annual influenza-associated respiratory deaths per 100,000 (range) per 100,000 people aged 75 and older per year	modelling	Iuliano et al. 2018 Lancet quote The highest mortality rates were estimated in sub-Saharan Africa (2·8-16·5 per 100 000 individuals), southeast Asia (3·5-9·2 per 100 000 individuals), and among people aged 75 years or older (51·3-99·4 per 100 000 individuals). abstract, FINDINGS Compare with the all-ages global rate in the previous record: mortality is concentrated at the oldest ages. The same sentence gives the highest regional rates for sub-Saharan Africa and southeast Asia.
Influenza-associated respiratory mortality rate, people younger than 65 years (modelled, range across countries) severity: death case definition: Country-specific excess respiratory mortality attributable to influenza	younger than 65 years vaccination status: mixed country: 33 countries with vital registration and influenza surveillance setting: community and hospital period: 1999-2015 Infant <1y1-4y5-11y12-17y18-49y50-64y	0.1 to 6.4 mean annual influenza-associated respiratory deaths per 100,000 (range across countries) per 100,000 people under 65 per year	modelling	Iuliano et al. 2018 Lancet quote The estimated mean annual influenza-associated respiratory EMR ranged from 0·1 to 6·4 per 100 000 individuals for people younger than 65 years, 2·9 to 44·0 per 100 000 individuals for people aged between 65 and 74 years, and 17·9 to 223·5 per 100 000 for people older than 75 years. abstract, FINDINGS The range is across countries, not a confidence interval. The same sentence gives 2.9 to 44.0 for ages 65 to 74 and 17.9 to 223.5 for over 75, a steep age gradient.
Influenza-associated respiratory deaths in children under 5 years (modelled) severity: death case definition: Excess respiratory mortality attributable to influenza in 92 countries with high respiratory-infection mortality	children younger than 5 years vaccination status: mixed country: 92 countries with high rates of respiratory-infection mortality setting: LMIC period: 1999-2015 Infant <1y1-4y	9243-105 690 annual influenza-associated respiratory deaths in children under 5 (range) per under-5 population of the 92 countries per year	modelling	Iuliano et al. 2018 Lancet quote For 92 countries, we estimated that among children younger than 5 years, 9243-105 690 influenza-associated respiratory deaths occur annually. abstract, FINDINGS Wide range reflects uncertainty in extrapolation to countries without data. The burden in young children is concentrated in low-income settings; see the under-5 hospitalisation records from the later global analysis.
Influenza-associated acute lower respiratory infection hospital admissions in children under 5 (modelled) severity: hospitalisation case definition: Influenza-virus-associated ALRI from a systematic review of population-based studies	children under 5 years vaccination status: mixed country: global setting: hospital period: 2018 Infant <1y1-4y	870 000 (543 000–1 415 000) annual number of hospital admissions (uncertainty range) per global under-5 population per year	modelling	Wang et al. 2020 Lancet Glob Health quote FINDINGS: In 2018, among children under 5 years globally, there were an estimated 109·5 million influenza virus episodes (uncertainty range [UR] 63·1-190·6), 10·1 million influenza-virus-associated ALRI cases (6·8-15·1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000-1 415 000), 15 300 in-hospital deaths (5800-43 800), and up to 34 800 (13 200-97 200) overall influenza-virus-associated ALRI deaths. abstract, FINDINGS The uncertainty range is as reported by the authors, not a confidence interval. The same sentence gives 109.5 million influenza episodes and 10.1 million ALRI cases.
In-hospital deaths from influenza-associated ALRI in children under 5 (modelled) severity: death case definition: Influenza-virus-associated ALRI deaths among hospitalised children	children under 5 years vaccination status: mixed country: global setting: hospital period: 2018 Infant <1y1-4y	15 300 (5800–43 800) annual number of in-hospital deaths (uncertainty range) per global under-5 population per year	modelling	Wang et al. 2020 Lancet Glob Health quote FINDINGS: In 2018, among children under 5 years globally, there were an estimated 109·5 million influenza virus episodes (uncertainty range [UR] 63·1-190·6), 10·1 million influenza-virus-associated ALRI cases (6·8-15·1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000-1 415 000), 15 300 in-hospital deaths (5800-43 800), and up to 34 800 (13 200-97 200) overall influenza-virus-associated ALRI deaths. abstract, FINDINGS In-hospital deaths only; the same sentence gives up to 34 800 overall influenza-associated ALRI deaths once deaths outside hospital are included.
Share of under-5 influenza ALRI in-hospital deaths occurring in low-income and lower-middle-income countries severity: death case definition: Influenza-virus-associated ALRI in-hospital deaths by World Bank income group	children under 5 years vaccination status: mixed country: low-income and lower-middle-income countries versus the rest of the world setting: LMIC, hospital period: 2018 Infant <1y1-4y	82 proportion of in-hospital deaths (%) per in-hospital influenza ALRI death in children under 5 worldwide	modelling	Wang et al. 2020 Lancet Glob Health quote About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries. abstract, FINDINGS A share of deaths, not a risk. The preceding sentence places over a third of in-hospital deaths in young infants too young for influenza vaccination.
Share of under-5 influenza ALRI in-hospital deaths occurring in infants under 6 months severity: death case definition: Influenza-virus-associated ALRI in-hospital deaths by age	infants under 6 months as a share of children under 5 vaccination status: unvaccinated country: global setting: hospital period: 2018 NeonateInfant <1y	36 proportion of in-hospital deaths (%) per in-hospital influenza ALRI death in children under 5	modelling	Wang et al. 2020 Lancet Glob Health quote About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. abstract, FINDINGS Infants under 6 months cannot be vaccinated, which is the rationale for maternal vaccination; see the pregnancy efficacy records.
Influenza-associated critical illness hospitalisation in adults (modelled) severity: ICU admission or critical illness case definition: Critical illness hospitalisations attributable to influenza by negative binomial regression of discharge data against virus surveillance	adults vaccination status: mixed country: United States (three states) setting: hospital period: study seasons before 2010 18-49y50-64y65+	12.0 (6.6–21.6) incidence per 100,000 person-years per 100,000 adult person-years	modelling	Ortiz et al. 2014 Crit Care Med quote The population-based incidence estimate for influenza-associated critical illness was 12.0 per 100,000 person-years (95% CI, 6.6, 21.6) or 1.3% of all critical illness hospitalizations (95% CI, 0.7%, 2.3%). abstract, RESULTS Modelled attribution, not laboratory-confirmed cases; the authors found only a small fraction carried an ICD-coded influenza diagnosis, suggesting severe influenza is under-recognised in ICUs.
Death among symptomatic 2009 A(H1N1)pdm09 cases (symptomatic CFR) severity: death strain: A(H1N1)pdm09 case definition: Bayesian evidence synthesis of medically attended cases in Milwaukee and hospitalisations, ICU admissions and deaths in New York City	all ages vaccination status: unvaccinated country: United States (Milwaukee and New York City) setting: community period: April to July 2009 All ages	0.048 (0.026–0.096) symptomatic case-fatality ratio (%) per symptomatic case	modelling	Presanis et al. 2009 PLoS Med quote Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI] 0.026%-0.096%), sCIR of 0.239% (0.134%-0.458%), and sCHR of 1.44% (0.83%-2.64%). abstract, FINDINGS Credible interval, not a frequentist CI. The same sentence gives a symptomatic case-hospitalisation ratio of 1.44% and a symptomatic case-ICU ratio of 0.239% (next record). Estimates using self-reported ILI as the denominator were about 7-9 times lower.
Hospitalisation among symptomatic 2009 A(H1N1)pdm09 cases (symptomatic case-hospitalisation ratio) severity: hospitalisation strain: A(H1N1)pdm09 case definition: Bayesian evidence synthesis of medically attended cases and hospitalisations	all ages vaccination status: unvaccinated country: United States (Milwaukee and New York City) setting: community period: April to July 2009 All ages	1.44 (0.83–2.64) symptomatic case-hospitalisation ratio (%) per symptomatic case	modelling	Presanis et al. 2009 PLoS Med quote Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI] 0.026%-0.096%), sCIR of 0.239% (0.134%-0.458%), and sCHR of 1.44% (0.83%-2.64%). abstract, FINDINGS Credible interval. The symptomatic case-ICU ratio in the same sentence is 0.239% (0.134-0.458). The abstract notes the sCFR and sCIR were highest in adults and lowest in school-age children.
Global respiratory deaths in the first 12 months of 2009 A(H1N1)pdm09 circulation (modelled) severity: death strain: A(H1N1)pdm09 case definition: Respiratory deaths modelled from symptomatic attack rates and symptomatic case-fatality ratios, with regional mortality multipliers	all ages vaccination status: mixed country: global setting: community and hospital period: first 12 months of pandemic virus circulation in each country (2009-2010) All ages	201,200 (105,700–395,600) estimated number of respiratory deaths (range) per world population over 12 months	modelling	Dawood et al. 2012 Lancet Infect Dis quote FINDINGS: We estimate that globally there were 201,200 respiratory deaths (range 105,700-395,600) with an additional 83,300 cardiovascular deaths (46,000-179,900) associated with 2009 pandemic influenza A H1N1. abstract, FINDINGS The same sentence adds 83,300 cardiovascular deaths. The estimate was many times the laboratory-confirmed deaths reported to WHO, which is why confirmed-death counts understate pandemic burden.
Share of 2009 pandemic deaths in people younger than 65 years severity: death strain: A(H1N1)pdm09 case definition: Modelled respiratory and cardiovascular deaths associated with A(H1N1)pdm09 by age	younger than 65 years as a share of all ages vaccination status: mixed country: global setting: community and hospital period: 2009-2010 Infant <1y1-4y5-11y12-17y18-49y50-64y	80 proportion of pandemic-associated deaths (%) per modelled pandemic-associated death	modelling	Dawood et al. 2012 Lancet Infect Dis quote 80% of the respiratory and cardiovascular deaths were in people younger than 65 years and 51% occurred in southeast Asia and Africa. abstract, FINDINGS The reverse of the seasonal pattern, where about 80% of deaths are in people aged 65 and older (Pink Book record). Older adults had partial immunity from exposure to related H1N1 viruses decades earlier.

Vaccine efficacy and effectiveness

Every estimate compiled, annotated by population (P), intervention (I), comparator (C), outcome (O) and study design (S).

Outcome (O)	Population (P)	Intervention / comparator	Estimate	Design (S)	Source
Laboratory-confirmed influenza severity: any confirmed influenza case definition: Confirmed influenza as defined in the included trials	healthy adults aged 16 to 65 years risk group: healthy adults country: North America, South America and Europe period: trials conducted 1969-2009 n: 71,221 participants 12-17y18-49y50-64y	inactivated parenteral influenza vaccine platform: inactivated doses: 1 per season vs placebo or no intervention	0.41 (0.36–0.47) risk ratio (RR), vaccinated vs placebo or no vaccination	meta-analysis GRADE: moderate 25 RCTs of inactivated parenteral vaccine vs placebo or do-nothing	Demicheli et al. 2018 Cochrane Database Syst Rev quote We did not consider studies at high risk of bias to influence the results of our outcomes except for hospitalisation.Inactivated influenza vaccines probably reduce influenza in healthy adults from 2.3% without vaccination to 0.9% (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.36 to 0.47; 71,221 participants; moderate-certainty evidence), and they probably reduce ILI from 21.5% to 18.1% (RR 0.84, 95% CI 0.75 to 0.95; 25,795 participants; moderate-certainty evidence; 71 healthy adults need to be vaccinated to prevent one of them experiencing influenza, and 29 healthy adults need to be vaccinated to prevent one of them experiencing an ILI). abstract, MAIN RESULTS Absolute risk fell from 2.3% to 0.9% over a single season, giving a number needed to vaccinate of 71. Pooled across seasons of different match.
Influenza-like illness severity: any ILI case definition: ILI as defined in the included trials, not laboratory-confirmed	healthy adults aged 16 to 65 years risk group: healthy adults country: North America, South America and Europe period: trials conducted 1969-2009 n: 25,795 participants 12-17y18-49y50-64y	inactivated parenteral influenza vaccine platform: inactivated doses: 1 per season vs placebo or no intervention	0.84 (0.75–0.95) risk ratio (RR), vaccinated vs placebo or no vaccination	meta-analysis GRADE: moderate	Demicheli et al. 2018 Cochrane Database Syst Rev quote We did not consider studies at high risk of bias to influence the results of our outcomes except for hospitalisation.Inactivated influenza vaccines probably reduce influenza in healthy adults from 2.3% without vaccination to 0.9% (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.36 to 0.47; 71,221 participants; moderate-certainty evidence), and they probably reduce ILI from 21.5% to 18.1% (RR 0.84, 95% CI 0.75 to 0.95; 25,795 participants; moderate-certainty evidence; 71 healthy adults need to be vaccinated to prevent one of them experiencing influenza, and 29 healthy adults need to be vaccinated to prevent one of them experiencing an ILI). abstract, MAIN RESULTS Much smaller effect than against confirmed influenza because most ILI is caused by other pathogens; NNV 29 reflects the higher ILI incidence, not stronger protection.
Hospitalisation (as reported by trials) severity: hospitalisation case definition: Hospitalisation as reported in the included trials	healthy adults aged 16 to 65 years risk group: healthy adults country: North America, South America and Europe n: 11,924 participants 12-17y18-49y50-64y	inactivated parenteral influenza vaccine platform: inactivated doses: 1 per season vs placebo or no intervention	0.96 (0.85–1.08) risk ratio (RR), vaccinated vs placebo or no vaccination	meta-analysis GRADE: low	Demicheli et al. 2018 Cochrane Database Syst Rev quote Vaccination may lead to a small reduction in the risk of hospitalisation in healthy adults, from 14.7% to 14.1%, but the CI is wide and does not rule out a large benefit (RR 0.96, 95% CI 0.85 to 1.08; 11,924 participants; low-certainty evidence). abstract, MAIN RESULTS A null result in healthy working-age adults, from 14.7% to 14.1% with a CI that includes no effect; the review notes that studies at high risk of bias influenced this outcome. Hospitalisation is rare in this group, so RCTs are underpowered for it.
Laboratory-confirmed influenza in vaccinated pregnant women severity: any confirmed influenza strain: A(H1N1)pdm09-containing vaccine case definition: Confirmed influenza in mothers in one RCT and one controlled clinical trial	pregnant women pregnancy: vaccinated during pregnancy 18-49y	inactivated influenza vaccine containing pH1N1 platform: inactivated doses: 1 vs placebo or no vaccination	50 (14–71) VE (%)	meta-analysis 1 RCT and 1 controlled clinical trial	Demicheli et al. 2018 Cochrane Database Syst Rev quote The efficacy of inactivated vaccine containing pH1N1 against influenza was 50% (95% CI 14% to 71%) in mothers (NNV 55), and 49% (95% CI 12% to 70%) in infants up to 24 weeks (NNV 56). abstract, MAIN RESULTS NNV 55. The review found no RCT data on efficacy against seasonal influenza during pregnancy and describes protection in mothers and newborns as smaller than in other groups.
Laboratory-confirmed influenza in infants of vaccinated mothers severity: any confirmed influenza case definition: Confirmed influenza in infants up to 24 weeks of age born to women vaccinated in pregnancy	infants up to 24 weeks pregnancy: mother vaccinated during pregnancy; infant unvaccinated NeonateInfant <1y	inactivated influenza vaccine containing pH1N1 given to the mother platform: inactivated doses: 1 maternal dose vs infants of placebo or unvaccinated mothers	49 (12–70) VE (%) in infants via maternal vaccination	meta-analysis	Demicheli et al. 2018 Cochrane Database Syst Rev quote The efficacy of inactivated vaccine containing pH1N1 against influenza was 50% (95% CI 14% to 71%) in mothers (NNV 55), and 49% (95% CI 12% to 70%) in infants up to 24 weeks (NNV 56). abstract, MAIN RESULTS NNV 56. Protection is passive (transplacental antibody) and wanes over the first months; see the South African trial records for the time course.
Influenza-like illness in pregnant women (observational) severity: any ILI case definition: ILI in pregnant women in observational studies	pregnant women pregnancy: vaccinated during pregnancy 18-49y	influenza vaccines (as used in the observational studies) platform: inactivated doses: 1 vs unvaccinated pregnant women	24 (11–36) VE (%)	meta-analysis observational studies retained from earlier review versions	Demicheli et al. 2018 Cochrane Database Syst Rev quote Evidence from observational studies showed effectiveness of influenza vaccines against ILI in pregnant women to be 24% (95% CI 11% to 36%, NNV 94), and against influenza in newborns from vaccinated women to be 41% (95% CI 6% to 63%, NNV 27).Live aerosol vaccines have an overall effectiveness corresponding to an NNV of 46. abstract, MAIN RESULTS Observational, not randomised, and against ILI rather than confirmed influenza; the review stopped updating observational searches because of their uncertain quality. NNV 94.
Influenza in newborns of vaccinated women (observational) severity: any influenza case definition: Influenza in newborns in observational studies	newborns pregnancy: mother vaccinated during pregnancy NeonateInfant <1y	influenza vaccines given to the mother platform: inactivated doses: 1 maternal dose vs newborns of unvaccinated women	41 (6–63) VE (%) in newborns via maternal vaccination	meta-analysis observational studies	Demicheli et al. 2018 Cochrane Database Syst Rev quote Evidence from observational studies showed effectiveness of influenza vaccines against ILI in pregnant women to be 24% (95% CI 11% to 36%, NNV 94), and against influenza in newborns from vaccinated women to be 41% (95% CI 6% to 63%, NNV 27).Live aerosol vaccines have an overall effectiveness corresponding to an NNV of 46. abstract, MAIN RESULTS Observational; confounding by health-seeking behaviour of vaccinated mothers is the main concern. NNV 27.
Laboratory-confirmed influenza severity: any confirmed influenza case definition: Confirmed influenza in the included RCTs	children aged 3 to 16 years risk group: healthy children country: USA, Western Europe, Russia and Bangladesh period: trials conducted 1984-2013 n: 7718 children 1-4y5-11y12-17y	live attenuated influenza vaccine platform: live attenuated doses: as given in the included trials vs placebo or do nothing	0.22 (0.11–0.41) risk ratio (RR), vaccinated vs placebo or do nothing	meta-analysis GRADE: moderate	Jefferson et al. 2018 Cochrane Database Syst Rev quote Variability in study design and reporting impeded meta-analysis of harms outcomes.Live attenuated vaccinesCompared with placebo or do nothing, live attenuated influenza vaccines probably reduce the risk of influenza infection in children aged 3 to 16 years from 18% to 4% (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.11 to 0.41; 7718 children; moderate-certainty evidence), and they may reduce ILI by a smaller degree, from 17% to 12% (RR 0.69, 95% CI 0.60 to 0.80; 124,606 children; low-certainty evidence). abstract, MAIN RESULTS Absolute risk 18% to 4% over a single season, a small number needed to vaccinate. The review found very few RCTs in children under two years. Contrast with the null US LAIV estimate against pandemic H1N1 in the test-negative records.
Influenza-like illness severity: any ILI case definition: ILI as defined in the included RCTs	children aged 3 to 16 years risk group: healthy children n: 124,606 children 1-4y5-11y12-17y	live attenuated influenza vaccine platform: live attenuated doses: as given in the included trials vs placebo or do nothing	0.69 (0.60–0.80) risk ratio (RR), vaccinated vs placebo or do nothing	meta-analysis GRADE: low	Jefferson et al. 2018 Cochrane Database Syst Rev quote Variability in study design and reporting impeded meta-analysis of harms outcomes.Live attenuated vaccinesCompared with placebo or do nothing, live attenuated influenza vaccines probably reduce the risk of influenza infection in children aged 3 to 16 years from 18% to 4% (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.11 to 0.41; 7718 children; moderate-certainty evidence), and they may reduce ILI by a smaller degree, from 17% to 12% (RR 0.69, 95% CI 0.60 to 0.80; 124,606 children; low-certainty evidence). abstract, MAIN RESULTS ILI is mostly caused by other viruses, so the RR is closer to no effect than for confirmed influenza.
Laboratory-confirmed influenza severity: any confirmed influenza case definition: Confirmed influenza in the included RCTs	children aged 2 to 16 years risk group: healthy children n: 1628 children 1-4y5-11y12-17y	inactivated influenza vaccine platform: inactivated doses: as given in the included trials vs placebo or no vaccination	0.36 (0.28–0.48) risk ratio (RR), vaccinated vs placebo or no vaccination	meta-analysis GRADE: high	Jefferson et al. 2018 Cochrane Database Syst Rev quote Data on nausea were not reported.Inactivated vaccinesCompared with placebo or no vaccination, inactivated vaccines reduce the risk of influenza in children aged 2 to 16 years from 30% to 11% (RR 0.36, 95% CI 0.28 to 0.48; 1628 children; high-certainty evidence), and they probably reduce ILI from 28% to 20% (RR 0.72, 95% CI 0.65 to 0.79; 19,044 children; moderate-certainty evidence). abstract, MAIN RESULTS High-certainty evidence but from only 1628 children; absolute risk 30% to 11%, NNV 5, in trial populations with unusually high attack rates. No RCT data on hospitalisation were available.
Influenza-like illness severity: any ILI case definition: ILI as defined in the included RCTs	children aged 2 to 16 years risk group: healthy children n: 19,044 children 1-4y5-11y12-17y	inactivated influenza vaccine platform: inactivated doses: as given in the included trials vs placebo or no vaccination	0.72 (0.65–0.79) risk ratio (RR), vaccinated vs placebo or no vaccination	meta-analysis GRADE: moderate	Jefferson et al. 2018 Cochrane Database Syst Rev quote Data on nausea were not reported.Inactivated vaccinesCompared with placebo or no vaccination, inactivated vaccines reduce the risk of influenza in children aged 2 to 16 years from 30% to 11% (RR 0.36, 95% CI 0.28 to 0.48; 1628 children; high-certainty evidence), and they probably reduce ILI from 28% to 20% (RR 0.72, 95% CI 0.65 to 0.79; 19,044 children; moderate-certainty evidence). abstract, MAIN RESULTS The same review found otitis media probably similar between vaccinated and unvaccinated children, with a CI not excluding an increase.
Influenza (as diagnosed by the trials) severity: any influenza case definition: Influenza as diagnosed in the included RCTs; the review rated certainty down for uncertainty over how influenza was diagnosed	65 years or older country: Europe and the USA setting: community and residential care period: trials conducted 1965-2000 n: over 5000 participants in 8 RCTs 65+	influenza vaccine (any preparation in the included trials) platform: inactivated doses: 1 per season vs placebo or no intervention	0.42 (0.27–0.66) risk ratio (RR), vaccinated vs placebo	meta-analysis GRADE: low	Demicheli et al. 2018 Cochrane Database Syst Rev quote Risk of bias reduced our certainty in the findings for influenza and ILI, but not for other outcomes.Older adults receiving the influenza vaccine may experience less influenza over a single season compared with placebo, from 6% to 2.4% (risk ratio (RR) 0.42, 95% confidence interval (CI) 0.27 to 0.66; low-certainty evidence). abstract, MAIN RESULTS Low certainty. The RCT evidence base in older adults is old and small, and the review found no hospitalisation data and only one underpowered study for mortality (next records).
Influenza-like illness severity: any ILI case definition: ILI as defined in the included RCTs	65 years or older country: Europe and the USA setting: community and residential care period: trials conducted 1965-2000 65+	influenza vaccine (any preparation in the included trials) platform: inactivated doses: 1 per season vs placebo or no intervention	0.59 (0.47–0.73) risk ratio (RR), vaccinated vs no vaccination	meta-analysis GRADE: moderate	Demicheli et al. 2018 Cochrane Database Syst Rev quote Older adults probably experience less ILI compared with those who do not receive a vaccination over the course of a single influenza season (3.5% versus 6%; RR 0.59, 95% CI 0.47 to 0.73; moderate-certainty evidence). abstract, MAIN RESULTS The review states it is uncertain how big a difference the vaccines make across different seasons.
Death (as reported by the single trial) severity: death case definition: Deaths in the single RCT reporting mortality	65 years or older n: 522 vaccinated and 177 placebo participants in one trial 65+	influenza vaccine platform: inactivated doses: 1 per season vs placebo	1.02 (0.11–9.72) risk ratio (RR), vaccinated vs placebo	meta-analysis GRADE: very low 1 RCT (3 deaths vs 1 death)	Demicheli et al. 2018 Cochrane Database Syst Rev quote There were 3 deaths from 522 participants in the vaccination arm and 1 death from 177 participants in the placebo arm, providing very low-certainty evidence for the effect on mortality (RR 1.02, 95% CI 0.11 to 9.72). abstract, MAIN RESULTS Uninformative: four deaths in total. This is the only randomised mortality evidence in older adults the review found; the RCT literature cannot answer whether vaccination reduces death in this group, which is why that question rests on observational studies and comparative high-dose trials.
Medically attended laboratory-confirmed influenza A(H3N2) severity: medically attended illness strain: A(H3N2) case definition: Laboratory-confirmed influenza in test-negative design studies	all ages country: multiple period: studies published to 2015 All ages	seasonal influenza vaccines (mostly inactivated) platform: mixed doses: 1 per season vs test-negative controls	33 (26–39) VE (%)	meta-analysis 56 test-negative studies	Belongia et al. 2016 Lancet Infect Dis quote Pooled VE was 33% (95% CI 26-39; I(2)=44·4) for H3N2, 54% (46-61; I(2)=61·3) for type B, 61% (57-65; I(2)=0·0) for H1N1pdm09, and 67% (29-85; I(2)=57·6) for H1N1; VE was 73% (61-81; I(2)=31·4) for monovalent vaccine against H1N1pdm09. abstract, FINDINGS The same sentence gives 54% for type B and 61% for H1N1pdm09 (next records): protection against H3N2 is consistently the weakest, which drives low-VE seasons.
Medically attended laboratory-confirmed influenza B severity: medically attended illness strain: influenza B (lineage not separated) case definition: Laboratory-confirmed influenza in test-negative design studies	all ages country: multiple All ages	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	54 (46–61) VE (%)	meta-analysis 56 test-negative studies	Belongia et al. 2016 Lancet Infect Dis quote Pooled VE was 33% (95% CI 26-39; I(2)=44·4) for H3N2, 54% (46-61; I(2)=61·3) for type B, 61% (57-65; I(2)=0·0) for H1N1pdm09, and 67% (29-85; I(2)=57·6) for H1N1; VE was 73% (61-81; I(2)=31·4) for monovalent vaccine against H1N1pdm09. abstract, FINDINGS Pooled across seasons with and without B lineage match; lineage-specific estimates are in the later pooled meta-analysis records.
Medically attended laboratory-confirmed influenza A(H1N1)pdm09 severity: medically attended illness strain: A(H1N1)pdm09 case definition: Laboratory-confirmed influenza in test-negative design studies	all ages country: multiple All ages	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	61 (57–65) VE (%)	meta-analysis 56 test-negative studies	Belongia et al. 2016 Lancet Infect Dis quote Pooled VE was 33% (95% CI 26-39; I(2)=44·4) for H3N2, 54% (46-61; I(2)=61·3) for type B, 61% (57-65; I(2)=0·0) for H1N1pdm09, and 67% (29-85; I(2)=57·6) for H1N1; VE was 73% (61-81; I(2)=31·4) for monovalent vaccine against H1N1pdm09. abstract, FINDINGS Heterogeneity was zero across studies for this subtype. Monovalent pandemic vaccine against H1N1pdm09 reached 73% in the same sentence.
Medically attended laboratory-confirmed influenza A(H3N2) in older adults severity: medically attended illness strain: A(H3N2) case definition: Laboratory-confirmed influenza in test-negative design studies	older than 60 years country: multiple 50-64y65+	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	24 (-6–45) VE (%)	meta-analysis	Belongia et al. 2016 Lancet Infect Dis quote Among older adults (aged >60 years), pooled VE was 24% (-6 to 45; I(2)=17·6) for H3N2, 63% (33-79; I(2)=0·0) for type B, and 62% (36-78; I(2)=0·0) for H1N1pdm09. abstract, FINDINGS The interval includes zero: in older adults the pooled H3N2 estimate is not distinguishable from no effect, whereas the same sentence gives 63% for type B and 62% for H1N1pdm09 in this age group.
Medically attended laboratory-confirmed influenza A(H3N2), antigenically variant (drifted) viruses severity: medically attended illness strain: A(H3N2) variant viruses case definition: Laboratory-confirmed influenza in test-negative studies, stratified by antigenic match	all ages country: multiple All ages	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	23 (2–40) VE (%)	meta-analysis	Belongia et al. 2016 Lancet Infect Dis quote VE against H3N2 for antigenically matched viruses was 33% (22-43; I(2)=56·1) and for variant viruses was 23% (2-40; I(2)=55·6). abstract, FINDINGS Same sentence gives 33% (22-43) for antigenically matched H3N2 viruses; the matched-versus-drifted gap for H3N2 is smaller than often assumed.
Laboratory-confirmed influenza (any type) severity: medically attended illness (outpatient and inpatient) case definition: Laboratory-confirmed influenza in test-negative design studies	all ages country: multiple period: studies to 2023 All ages	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	41.4 (39.2–43.5) VE (%)	meta-analysis 191 test-negative publications	Guo et al. 2024 Vaccine quote The pooled IVE was 41.4 % (95 % CI: 39.2-43.5 %) against any influenza. abstract, RESULTS Pooled over many seasons and products; the strain- and age-specific records from the same review show the spread behind this average.
Laboratory-confirmed influenza B/Yamagata severity: medically attended illness strain: B/Yamagata lineage case definition: Laboratory-confirmed influenza in test-negative design studies	all ages country: multiple All ages	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	47.2 (38.1–54.9) VE (%)	meta-analysis	Guo et al. 2024 Vaccine quote For specific strains, the IVE was 55.4 % (95 % CI: 52.7-58.1 %) against A/H1N1, 26.8 % (95 % CI: 23.5-29.9 %) against A/H3N2, 47.2 % (95 % CI: 38.1-54.9 %) against B/Yamagata, and 40.6 % (95 % CI: 23.7-53.7 %) against B/Victoria, and the effectiveness against A/H3N2 was significantly lower than A/H1N1 (p < 0.0001) and B/Yamagata (p < 0.0001). abstract, RESULTS B/Yamagata has not been detected globally since the coronavirus pandemic and was subsequently removed from vaccines; this estimate is historical.
Laboratory-confirmed influenza B/Victoria severity: medically attended illness strain: B/Victoria lineage case definition: Laboratory-confirmed influenza in test-negative design studies	all ages country: multiple All ages	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	40.6 (23.7–53.7) VE (%)	meta-analysis	Guo et al. 2024 Vaccine quote For specific strains, the IVE was 55.4 % (95 % CI: 52.7-58.1 %) against A/H1N1, 26.8 % (95 % CI: 23.5-29.9 %) against A/H3N2, 47.2 % (95 % CI: 38.1-54.9 %) against B/Yamagata, and 40.6 % (95 % CI: 23.7-53.7 %) against B/Victoria, and the effectiveness against A/H3N2 was significantly lower than A/H1N1 (p < 0.0001) and B/Yamagata (p < 0.0001). abstract, RESULTS Wider interval than B/Yamagata because fewer B/Victoria-dominant seasons contributed.
Laboratory-confirmed influenza A(H3N2) severity: medically attended illness strain: A(H3N2) case definition: Laboratory-confirmed influenza in test-negative design studies	all ages country: multiple All ages	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	26.8 (23.5–29.9) VE (%)	meta-analysis	Guo et al. 2024 Vaccine quote For specific strains, the IVE was 55.4 % (95 % CI: 52.7-58.1 %) against A/H1N1, 26.8 % (95 % CI: 23.5-29.9 %) against A/H3N2, 47.2 % (95 % CI: 38.1-54.9 %) against B/Yamagata, and 40.6 % (95 % CI: 23.7-53.7 %) against B/Victoria, and the effectiveness against A/H3N2 was significantly lower than A/H1N1 (p < 0.0001) and B/Yamagata (p < 0.0001). abstract, RESULTS Significantly lower than A/H1N1 (55.4%, same sentence) and B/Yamagata (p < 0.0001). Egg-adaptation of H3N2 vaccine viruses is one proposed reason.
Laboratory-confirmed influenza A(H1N1) severity: medically attended illness strain: A(H1N1) including pdm09 case definition: Laboratory-confirmed influenza in test-negative design studies	all ages country: multiple All ages	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	55.4 (52.7–58.1) VE (%)	meta-analysis	Guo et al. 2024 Vaccine quote For specific strains, the IVE was 55.4 % (95 % CI: 52.7-58.1 %) against A/H1N1, 26.8 % (95 % CI: 23.5-29.9 %) against A/H3N2, 47.2 % (95 % CI: 38.1-54.9 %) against B/Yamagata, and 40.6 % (95 % CI: 23.7-53.7 %) against B/Victoria, and the effectiveness against A/H3N2 was significantly lower than A/H1N1 (p < 0.0001) and B/Yamagata (p < 0.0001). abstract, RESULTS The best-protected subtype in both this and the earlier Belongia pooled analysis.
Laboratory-confirmed influenza (any type) in children severity: medically attended illness case definition: Laboratory-confirmed influenza in test-negative design studies	children aged under 18 years country: multiple Infant <1y1-4y5-11y12-17y	seasonal influenza vaccines platform: mixed doses: as given vs test-negative controls	48.6 (44.7–52.2) VE (%)	meta-analysis	Guo et al. 2024 Vaccine quote The IVE against any influenza was 48.6 % (95 % CI: 44.7-52.2 %) for children aged < 18 years, 36.7 % (95 % CI: 31.9-41.1 %) for adults aged 18-64 years, and 30.6 % (95 % CI: 26.2-34.8 %) for elderly aged ≥65 years. abstract, RESULTS The same sentence gives 36.7% for adults 18-64 and 30.6% for those 65 and older (next records); meta-regression confirmed lower VE with older age.
Laboratory-confirmed influenza (any type) in adults aged 18-64 severity: medically attended illness case definition: Laboratory-confirmed influenza in test-negative design studies	adults aged 18-64 years country: multiple 18-49y50-64y	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	36.7 (31.9–41.1) VE (%)	meta-analysis	Guo et al. 2024 Vaccine quote The IVE against any influenza was 48.6 % (95 % CI: 44.7-52.2 %) for children aged < 18 years, 36.7 % (95 % CI: 31.9-41.1 %) for adults aged 18-64 years, and 30.6 % (95 % CI: 26.2-34.8 %) for elderly aged ≥65 years. abstract, RESULTS Lower than in children; the review's meta-regression found significantly lower effectiveness in young adults than in children.
Laboratory-confirmed influenza (any type) in adults aged 65 and older severity: medically attended illness case definition: Laboratory-confirmed influenza in test-negative design studies	65 years and older country: multiple 65+	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	30.6 (26.2–34.8) VE (%)	meta-analysis	Guo et al. 2024 Vaccine quote The IVE against any influenza was 48.6 % (95 % CI: 44.7-52.2 %) for children aged < 18 years, 36.7 % (95 % CI: 31.9-41.1 %) for adults aged 18-64 years, and 30.6 % (95 % CI: 26.2-34.8 %) for elderly aged ≥65 years. abstract, RESULTS The lowest of the three age bands, in the group with the highest death rate. Standard-dose and enhanced products are pooled here; see the high-dose and adjuvanted records.
Hospitalisation with laboratory-confirmed influenza (any type) severity: hospitalisation case definition: Laboratory-confirmed influenza among hospitalised adults in test-negative case-control studies	adults 18 years and older country: multiple period: 2010-11 to 2014-15 18-49y50-64y65+	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative hospitalised controls	41 (34–48) VE (%)	meta-analysis 30 test-negative studies	Rondy et al. 2017 J Infect quote Between 2010-11 and 2014-15, the pooled seasonal IVE was 41% (95%CI:34;48) for any influenza (51% (95%CI:44;58) among people aged 18-64y and 37% (95%CI:30;44) among ≥65 years). abstract, RESULTS Same sentence: 51% among people aged 18-64 and 37% among those 65 and older. Subtype-specific hospitalisation VE from the same review follows.
Hospitalisation with laboratory-confirmed influenza A(H3N2) in older adults, seasons with antigenically variant viruses severity: hospitalisation strain: A(H3N2), variant (drifted) viruses predominating case definition: Laboratory-confirmed A(H3N2) among hospitalised adults in test-negative studies	65 years and older country: multiple period: 2010-11 to 2014-15 65+	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative hospitalised controls	14 (-3–30) VE (%)	meta-analysis	Rondy et al. 2017 J Infect quote Among persons aged ≥65 year, IVE against A(H3N2) was 43% (95%CI:33;53) in seasons when circulating and vaccine strains were antigenically similar and 14% (95%CI:-3;30) when A(H3N2) variant viruses predominated. abstract, RESULTS A null-to-low estimate against hospitalisation in older adults in drifted H3N2 seasons; the same sentence gives 43% (33-53) in antigenically similar seasons.
Influenza-associated hospitalisation severity: hospitalisation case definition: Laboratory-confirmed influenza hospitalisation in test-negative design studies	all ages country: multiple period: studies to 2023 All ages	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	42 (39–44) VE (%)	meta-analysis GRADE: very low 165 test-negative publications	Yegorov et al. 2026 Clin Microbiol Infect quote Pooled IVE was 42% (95% CI: 39-44) against influenza-associated hospitalisation (very low certainty), 36% (95% CI: 24-46) against death (no certainty), 51% (95% CI: 36-63) against pneumonia (low certainty), 52% (95% CI: 38-63) against intensive care unit admission (very low certainty), and 55% (95% CI: 44-64) against ventilatory support (low certainty). abstract, RESULTS GRADE very low certainty as stated by the authors because all evidence is observational. Same sentence gives VE against death, pneumonia, ICU admission and ventilatory support (next records).
Influenza-associated death severity: death case definition: Death among laboratory-confirmed influenza cases in test-negative design studies	all ages country: multiple All ages	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	36 (24–46) VE (%)	meta-analysis	Yegorov et al. 2026 Clin Microbiol Infect quote Pooled IVE was 42% (95% CI: 39-44) against influenza-associated hospitalisation (very low certainty), 36% (95% CI: 24-46) against death (no certainty), 51% (95% CI: 36-63) against pneumonia (low certainty), 52% (95% CI: 38-63) against intensive care unit admission (very low certainty), and 55% (95% CI: 44-64) against ventilatory support (low certainty). abstract, RESULTS The authors assign no certainty rating to the death estimate. Few deaths per study, so this is driven by a handful of large studies.
Influenza-associated intensive care unit admission severity: ICU admission case definition: ICU admission with laboratory-confirmed influenza in test-negative design studies	all ages country: multiple All ages	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	52 (38–63) VE (%)	meta-analysis GRADE: very low	Yegorov et al. 2026 Clin Microbiol Infect quote Pooled IVE was 42% (95% CI: 39-44) against influenza-associated hospitalisation (very low certainty), 36% (95% CI: 24-46) against death (no certainty), 51% (95% CI: 36-63) against pneumonia (low certainty), 52% (95% CI: 38-63) against intensive care unit admission (very low certainty), and 55% (95% CI: 44-64) against ventilatory support (low certainty). abstract, RESULTS Same sentence gives 55% (44-64) against ventilatory support and 51% (36-63) against pneumonia. VE was up to 2-fold higher in children than adults.
Hospitalisation for influenza severity: hospitalisation case definition: Hospitalisation for influenza as reported in the included RCTs	65 years and older country: multiple 65+	high-dose inactivated influenza vaccine platform: inactivated doses: 1 vs standard-dose inactivated influenza vaccine	0.61 (0.50–0.74) risk ratio (RR), high-dose vs standard-dose	meta-analysis GRADE: high 14 RCTs, 581 845 participants	Zhao et al. 2026 Lancet Healthy Longev quote Compared with SD-IIV, HD-IIV reduced hospitalisation for influenza (RR 0·61 [95% CI 0·50-0·74]; I2=0%; absolute risk difference -4 events per 10 000 vaccinated individuals [95% CI -5 to -3]; high certainty), hospitalisation for laboratory-confirmed influenza (RR 0·68 [0·58-0·80]; I2=0%; absolute risk difference -4 events per 10 000 vaccinated individuals [-5 to -3]; high certainty), hospitalisation for cardiorespiratory disease (RR 0·92 [0·86-0·98]; I2=5·9%; absolute risk difference -15 events per 10 000 vaccinated individuals [-26 to -4]; high certainty), and all-cause hospitalisation (RR 0·97 [0·95-0·99]; I2=8·7%; absolute risk difference -29 events per 10 000 vaccinated individuals [-48 to -10]; high certainty). abstract, FINDINGS Absolute risk difference -4 events per 10 000 vaccinated; the authors stress absolute benefits are modest on average. The all-cause mortality result follows.
All-cause mortality severity: death case definition: Deaths from any cause in the included RCTs	65 years and older country: multiple 65+	high-dose inactivated influenza vaccine platform: inactivated doses: 1 vs standard-dose inactivated influenza vaccine	0.98 (0.92–1.05) risk ratio (RR), high-dose vs standard-dose	meta-analysis GRADE: moderate 14 RCTs	Zhao et al. 2026 Lancet Healthy Longev quote There was probably little or no difference between the effects of HD-IIV and SD-IIV on all-cause mortality (RR 0·98 [0·92-1·05]; I2=0·0%; absolute risk difference -1 event per 10 000 vaccinated individuals [-4 to 3]; moderate certainty). abstract, FINDINGS Probably little or no difference in all-cause death; absolute risk difference -1 per 10 000. The review concludes the evidence does not support routine preferential use irrespective of context.
Influenza-associated hospitalisation severity: hospitalisation case definition: Influenza-associated hospitalisation as reported in randomised studies	65 years and older country: multiple period: studies 1990-2023 65+	MF59-adjuvanted inactivated influenza vaccine platform: inactivated, adjuvanted doses: 1 vs standard-dose unadjuvanted inactivated vaccine	20 (-54–59) relative VE (%) of adjuvanted vs standard-dose	meta-analysis randomised studies in a network meta-analysis	Ferdinands et al. 2024 J Am Geriatr Soc quote Pooled rVE from randomized studies was 20% (95% CI -54 to 59) and 25% (95% CI -19 to 53) for ADJ and HD compared with SD, respectively; rVE was 6% (95% CI -109 to 58) for HD compared with ADJ; these differences were not statistically significant. abstract, RESULTS Not statistically significant; same sentence gives 25% (-19 to 53) for high-dose vs standard-dose and 6% (-109 to 58) for high-dose vs adjuvanted. The combined enhanced-vaccine estimate is a separate record.
Influenza-associated hospitalisation severity: hospitalisation case definition: Influenza-associated hospitalisation, randomised studies, all enhanced vaccines combined	65 years and older country: multiple 65+	high-dose, MF59-adjuvanted or recombinant influenza vaccines combined platform: mixed enhanced doses: 1 vs standard-dose unadjuvanted inactivated vaccine	18 (3–32) relative VE (%) of enhanced (HD, adjuvanted or recombinant) vs standard-dose	meta-analysis 5 randomised studies	Ferdinands et al. 2024 J Am Geriatr Soc quote With enhanced vaccines combined, rVE versus SD was 18% (95% CI 3 to 32) from randomized and 11% (95% CI 8 to 14) from observational evidence. abstract, RESULTS Observational evidence in the same sentence gives 11% (8-14). No differences were found between the three enhanced products.
Hospitalisation with laboratory-confirmed influenza severity: hospitalisation case definition: Laboratory-confirmed influenza among hospitalised patients, test-negative studies	65 years and older country: multiple period: 2006/07 to 2019/20 seasons 65+	MF59-adjuvanted trivalent inactivated vaccine (aTIV) platform: inactivated, adjuvanted doses: 1 vs test-negative controls	58.5 (40.7–70.9) VE (%), absolute, adjuvanted vaccine vs unvaccinated	meta-analysis test-negative studies (16 studies in meta-analyses)	Coleman et al. 2021 Influenza Other Respir Viruses quote Meta-analysis of test-negative studies found that aTIV reduced medical encounters due to lab-confirmed influenza with pooled estimates of 40.7% (95% CI: 21.9, 54.9; I2 = 0%) for non-emergency outpatient visits and 58.5% (40.7, 70.9; I2 = 52.9%) for hospitalized patients. abstract, RESULTS Absolute VE; the same sentence gives 40.7% (21.9, 54.9) for outpatient visits. Relative VE versus standard trivalent and versus high-dose vaccine is a separate record.
Influenza-related medical encounters severity: medically attended illness case definition: Influenza-related medical encounters in comparative observational studies	65 years and older country: multiple 65+	MF59-adjuvanted trivalent inactivated vaccine platform: inactivated, adjuvanted doses: 1 vs non-adjuvanted standard-dose trivalent inactivated vaccine	13.9 (4.2–23.5) relative VE (%) of adjuvanted vs standard-dose trivalent	meta-analysis	Coleman et al. 2021 Influenza Other Respir Viruses quote The pooled estimates for the relative VE of aTIV for the prevention of influenza-related medical encounters were 13.9% (4.2, 23.5; I2 = 95.9%) compared with TIV, 13.7% (3.1, 24.2; I2 = 98.8%) compared with QIV, and 2.8% (-2.9, 8.5; I2 = 94.5%) compared with HD-TIV. abstract, RESULTS Very high heterogeneity (I2 = 95.9%). Relative VE vs high-dose TIV in the same sentence was 2.8% (-2.9, 8.5), that is no measurable difference between the two enhanced products.
Laboratory-confirmed influenza A(H3N2), change in VE from 15-90 to 91-180 days after vaccination severity: medically attended illness strain: A(H3N2) case definition: Laboratory-confirmed influenza in test-negative studies reporting VE by time since vaccination	all ages country: multiple All ages	seasonal influenza vaccines platform: mixed doses: 1 per season time since vaccination: 91-180 days vs 15-90 days vs test-negative controls (VE in the early window as reference)	-33 (-57–-12) change in VE (percentage points) between 15-90 days and 91-180 days after vaccination	meta-analysis 14 test-negative studies	Young et al. 2018 J Infect Dis quote A significant decline in VE was observed for influenza virus subtype A/H3 (change in VE, -33; 95% confidence interval [CI], -57 to -12) and type B (change in VE, -19; 95% CI, -33 to -6). abstract, RESULTS Same sentence block: -19 (-33 to -6) for type B; the A/H1 change was not significant (next record). Meta-regression linked the apparent decline to case and control proportions, which could reflect within-season mismatch, herd immunity or reduced late-season power rather than waning alone.
Laboratory-confirmed influenza A(H1N1), change in VE from 15-90 to 91-180 days after vaccination severity: medically attended illness strain: A(H1N1) case definition: Laboratory-confirmed influenza in test-negative studies reporting VE by time since vaccination	all ages country: multiple All ages	seasonal influenza vaccines platform: mixed doses: 1 per season time since vaccination: 91-180 days vs 15-90 days vs test-negative controls (VE in the early window as reference)	-8 (-27–21) change in VE (percentage points) between 15-90 days and 91-180 days after vaccination	meta-analysis	Young et al. 2018 J Infect Dis quote VE declined for influenza virus subtype A/H1, but this difference was not statistically significant (change in VE -8; 95% CI, -27 to 21). abstract, RESULTS Not statistically significant; waning appears subtype-dependent and is clearest for A(H3N2).
Influenza-like illness in immunocompromised patients severity: any ILI case definition: ILI as defined in the included studies	all ages immune status: immunocompromised (HIV, cancer, transplant and other) country: multiple All ages	influenza vaccines platform: inactivated doses: as given vs placebo or unvaccinated immunocompromised controls	0.23 (0.16–0.34) odds ratio (OR), vaccinated vs placebo or unvaccinated	meta-analysis 209 eligible studies in the review; meta-analyses where feasible	Beck et al. 2011 PLoS One quote Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR]=0.23; 95% confidence interval [CI]=0.16-0.34; p<0.001) and laboratory confirmed influenza infection (OR=0.15; 95% CI=0.03-0.63; p=0.01) through vaccinating immunocompromised patie nts compared to placebo or unvaccinated controls. abstract, FINDINGS The authors rate the evidence as generally weak with potential for bias and confounding. Same sentence: OR 0.15 (0.03-0.63) for laboratory-confirmed influenza (next record). Seroconversion odds were lower than in immunocompetent controls.
Laboratory-confirmed influenza in immunocompromised patients severity: any confirmed infection case definition: Laboratory-confirmed influenza as defined in the included studies	all ages immune status: immunocompromised country: multiple All ages	influenza vaccines platform: inactivated doses: as given vs placebo or unvaccinated immunocompromised controls	0.15 (0.03–0.63) odds ratio (OR), vaccinated vs placebo or unvaccinated	meta-analysis	Beck et al. 2011 PLoS One quote Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR]=0.23; 95% confidence interval [CI]=0.16-0.34; p<0.001) and laboratory confirmed influenza infection (OR=0.15; 95% CI=0.03-0.63; p=0.01) through vaccinating immunocompromised patie nts compared to placebo or unvaccinated controls. abstract, FINDINGS Wide interval from few studies with confirmed outcomes. Contrast with the negative point estimate against hospitalised pandemic H1N1 in immunosuppressed older adults in the I-MOVE/VEBIS record.
Laboratory-confirmed influenza with protocol-defined influenza-like illness severity: any confirmed illness case definition: Laboratory-confirmed influenza of any type or subtype with protocol-defined ILI, intention-to-treat	65 years or older country: United States and Canada period: 2011-12 and 2012-13 seasons n: 31,989 participants 65+	high-dose trivalent inactivated vaccine (IIV3-HD, 60 microgram HA per strain) platform: inactivated doses: 1 vs standard-dose trivalent inactivated vaccine (IIV3-SD)	24.2 (9.7–36.5) relative efficacy (%) of high-dose vs standard-dose	RCT	DiazGranados et al. 2014 N Engl J Med quote In the intention-to-treat analysis, 228 participants in the IIV3-HD group (1.4%) and 301 participants in the IIV3-SD group (1.9%) had laboratory-confirmed influenza caused by any viral type or subtype associated with a protocol-defined influenza-like illness (relative efficacy, 24.2%; 95% confidence interval [CI], 9.7 to 36.5). abstract, RESULTS A relative comparison: attack rates were 1.4% vs 1.9%, so the absolute difference is well under one percentage point. Funded by the manufacturer.
Hospitalisation for influenza or pneumonia severity: hospitalisation case definition: ICD-coded hospitalisation for influenza or pneumonia in registry data, primary endpoint	mean 73.3 years (65 and older) risk group: 48.9% had at least one chronic condition country: Denmark, Finland and other pragmatic trial countries period: 2021-22 to 2023-24 seasons n: 466 320 individually randomised participants 65+	high-dose inactivated influenza vaccine (HD-IIV) platform: inactivated doses: 1 vs standard-dose inactivated influenza vaccine (SD-IIV)	8.8 (1.7–15.5) relative VE (%) of high-dose vs standard-dose	RCT individual-level pooled analysis of pragmatic RCTs	Johansen et al. 2025 Lancet quote The primary endpoint of hospitalisation for influenza or pneumonia occurred in 1312 (0·56%) of 233 311 participants in the HD-IIV group compared with 1437 (0·62%) of 233 009 participants in the SD-IIV group (rVE 8·8%, 95% CI 1·7 to 15·5; one-sided p=0·0082). abstract, FINDINGS Absolute rates 0.56% vs 0.62%. Relative VE against laboratory-confirmed influenza hospitalisation and all-cause mortality from the same abstract are separate records. Funded by Sanofi.
Laboratory-confirmed influenza hospitalisation severity: hospitalisation case definition: Registry-recorded hospitalisation with laboratory-confirmed influenza	65 years and older country: multiple (pragmatic RCT countries) period: 2021-22 to 2023-24 seasons n: 466 320 participants 65+	high-dose inactivated influenza vaccine platform: inactivated doses: 1 vs standard-dose inactivated influenza vaccine	31.9 (19.7–42.2) relative VE (%) of high-dose vs standard-dose	RCT	Johansen et al. 2025 Lancet quote HD-IIV also reduced the incidence of cardiorespiratory hospitalisation (4720 [2·02%] participants in the HD-IIV group vs 5033 [2·16%] participants in the SD-IIV group; rVE 6·3%, 2·5 to 10·0; p=0·0006), laboratory-confirmed influenza hospitalisation (249 [0·11%] participants vs 365 [0·16%] participants; rVE 31·9%, 19·7 to 42·2; p<0·0001), and all-cause hospitalisation (19 921 [8·54%] vs 20 348 [8·73%]; rVE 2·2%, 0·3 to 4·1; p=0·012). abstract, FINDINGS Absolute rates 0.11% vs 0.16%. The relative benefit is larger for laboratory-confirmed than for coded influenza-or-pneumonia outcomes, consistent with outcome specificity.
All-cause mortality severity: death case definition: Deaths from any cause in registry data	65 years and older country: multiple (pragmatic RCT countries) period: 2021-22 to 2023-24 seasons n: 466 320 participants 65+	high-dose inactivated influenza vaccine platform: inactivated doses: 1 vs standard-dose inactivated influenza vaccine	1.2 (-6.3–8.3) relative VE (%) of high-dose vs standard-dose	RCT	Johansen et al. 2025 Lancet quote All-cause mortality occurred with similar frequency in both groups (1421 [0·61%] vs 1437 [0·62%]; rVE 1·2%, -6·3 to 8·3; p=0·38). abstract, FINDINGS No difference in all-cause death (0.61% vs 0.62%) in nearly half a million randomised older adults; influenza-attributable deaths are a small share of all deaths, so this does not rule out an effect on influenza death.
RT-PCR-confirmed influenza-like illness severity: any confirmed illness strain: A(H3N2) predominant (181 of 234 cases) case definition: RT-PCR-confirmed influenza with protocol-defined ILI	50 years of age or older country: United States period: 2014-15 season n: 9003 participants randomised 50-64y65+	quadrivalent recombinant influenza vaccine (RIV4) platform: recombinant doses: 1 vs standard-dose quadrivalent inactivated vaccine (IIV4)	30 (10–47) relative reduction in probability of confirmed ILI (%), RIV4 vs IIV4	RCT	Dunkle et al. 2017 N Engl J Med quote The probability of influenza-like illness was 30% lower with RIV4 than with IIV4 (95% confidence interval, 10 to 47; P=0.006) and satisfied prespecified criteria for the primary noninferiority analysis and an exploratory superiority analysis of RIV4 over IIV4. abstract, RESULTS Attack rates were about a third lower with RIV4. Met prespecified non-inferiority and an exploratory superiority analysis in a drifted H3N2 season. Funded by Protein Sciences.
Culture-confirmed influenza severity: any confirmed illness case definition: Culture-confirmed influenza in a randomised head-to-head trial	6 to 59 months country: multiple period: 2004-05 season n: 8352 children with safety data, 7852 per protocol Infant <1y1-4y	live attenuated influenza vaccine (cold-adapted, trivalent) platform: live attenuated doses: 2 in vaccine-naive children vs trivalent inactivated influenza vaccine	54.9 relative reduction in cases (%), live attenuated vs inactivated	RCT	Belshe et al. 2007 N Engl J Med quote There were 54.9% fewer cases of cultured-confirmed influenza in the group that received live attenuated vaccine than in the group that received inactivated vaccine (153 vs. abstract, RESULTS Fewer cases with LAIV; no CI in the abstract. Superiority held for matched and drifted viruses. Medically significant wheezing and all-cause hospitalisation were higher with LAIV in the youngest infants, which is why LAIV is licensed only from two years of age.
RT-PCR-confirmed influenza in HIV-uninfected pregnant women severity: any confirmed illness case definition: RT-PCR-confirmed influenza illness in mothers through 24 weeks post partum	pregnant women, HIV-uninfected immune status: HIV-uninfected pregnancy: vaccinated in pregnancy country: South Africa period: 2011 and 2012 seasons n: 2116 HIV-uninfected pregnant women 18-49y	trivalent inactivated influenza vaccine (IIV3) platform: inactivated doses: 1 vs placebo	50.4 (14.5–71.2) VE (%)	RCT	Madhi et al. 2014 N Engl J Med quote The attack rates among HIV-uninfected IIV3 recipients and their infants were 1.8% and 1.9%, respectively, and the respective vaccine-efficacy rates were 50.4% (95% confidence interval [CI], 14.5 to 71.2) and 48.8% (95% CI, 11.6 to 70.4). abstract, RESULTS Attack rates were halved; infant efficacy from the same sentence follows.
RT-PCR-confirmed influenza in infants of vaccinated HIV-uninfected mothers severity: any confirmed illness case definition: RT-PCR-confirmed influenza illness in infants up to 24 weeks of age	infants up to 24 weeks pregnancy: mother vaccinated in pregnancy; infant unvaccinated country: South Africa period: 2011 and 2012 seasons NeonateInfant <1y	trivalent inactivated influenza vaccine given to the mother platform: inactivated doses: 1 maternal dose vs infants of placebo recipients	48.8 (11.6–70.4) VE (%) in infants via maternal vaccination	RCT	Madhi et al. 2014 N Engl J Med quote The attack rates among HIV-uninfected IIV3 recipients and their infants were 1.8% and 1.9%, respectively, and the respective vaccine-efficacy rates were 50.4% (95% confidence interval [CI], 14.5 to 71.2) and 48.8% (95% CI, 11.6 to 70.4). abstract, RESULTS Attack rates were halved. Protection is concentrated in the first weeks of life (see the duration record).
RT-PCR-confirmed influenza in HIV-infected pregnant women severity: any confirmed illness case definition: RT-PCR-confirmed influenza illness in HIV-infected mothers	pregnant women, HIV-infected immune status: HIV-infected pregnancy: vaccinated in pregnancy country: South Africa period: 2011 and 2012 seasons n: 194 HIV-infected pregnant women 18-49y	trivalent inactivated influenza vaccine platform: inactivated doses: 1 vs placebo	57.7 (0.2–82.1) VE (%)	RCT	Madhi et al. 2014 N Engl J Med quote Among HIV-infected women, the attack rate for placebo recipients was 17.0% and the rate for IIV3 recipients was 7.0%; the vaccine-efficacy rate for these IIV3 recipients was 57.7% (95% CI, 0.2 to 82.1). abstract, RESULTS Attack rate 17.0% in placebo vs 7.0% in vaccinees, much higher than in HIV-uninfected women; the CI barely excludes zero because of the small cohort.
PCR-confirmed influenza illness in infants aged 8 weeks or younger severity: any confirmed illness case definition: PCR-confirmed influenza illness in infants born to IIV3 or placebo recipients, by infant age	infants 8 weeks of age or younger pregnancy: mother vaccinated in pregnancy country: South Africa period: 2011 and 2012 seasons n: 1026 infants of IIV3 recipients and 1023 of placebo recipients NeonateInfant <1y	trivalent inactivated influenza vaccine given to the mother platform: inactivated doses: 1 maternal dose time since vaccination: infant age as time since maternal vaccination vs infants of placebo recipients	85.6 (38.3–98.4) VE (%) in infants via maternal vaccination	RCT	Nunes et al. 2016 JAMA Pediatr quote The vaccine's efficacy against PCR-confirmed influenza illness was highest among infants 8 weeks of age or younger at 85.6% (95% CI, 38.3%-98.4%) and decreased with increasing age to 25.5% (95% CI, -67.9% to 67.8%) among infants 8 to 16 weeks of age and to 30.3% (95% CI, -154.9% to 82.6%) among infants 16 to 24 weeks of age. abstract, RESULTS Secondary analysis. Same sentence: 25.5% (-67.9 to 67.8) at 8-16 weeks and 30.3% (-154.9 to 82.6) at 16-24 weeks, tracking the fall in maternally derived antibody.
PCR-confirmed influenza illness in infants aged 8 to 16 weeks severity: any confirmed illness case definition: PCR-confirmed influenza illness in infants born to IIV3 or placebo recipients, by infant age	infants 8 to 16 weeks pregnancy: mother vaccinated in pregnancy country: South Africa period: 2011 and 2012 seasons Infant <1y	trivalent inactivated influenza vaccine given to the mother platform: inactivated doses: 1 maternal dose time since vaccination: 8 to 16 weeks of infant age vs infants of placebo recipients	25.5 (-67.9–67.8) VE (%) in infants via maternal vaccination	RCT	Nunes et al. 2016 JAMA Pediatr quote The vaccine's efficacy against PCR-confirmed influenza illness was highest among infants 8 weeks of age or younger at 85.6% (95% CI, 38.3%-98.4%) and decreased with increasing age to 25.5% (95% CI, -67.9% to 67.8%) among infants 8 to 16 weeks of age and to 30.3% (95% CI, -154.9% to 82.6%) among infants 16 to 24 weeks of age. abstract, RESULTS No protection beyond the first two months of life can be demonstrated; the authors link this to the decline in maternally derived antibody.
Severe clinical pneumonia in young infants (all-cause) severity: severe pneumonia case definition: WHO-defined severe pneumonia in infants, pooled from three maternal immunisation RCTs	young infants (first 6 months) pregnancy: mother vaccinated in pregnancy country: Nepal, Mali and South Africa setting: LMIC n: 10,002 mothers and 9801 live-born infants NeonateInfant <1y	inactivated influenza vaccine given to the mother platform: inactivated doses: 1 maternal dose vs infants of control-vaccine or placebo mothers	0.80 (0.66–0.99) incidence rate ratio, infants of vaccinated vs control mothers	RCT 3 RCTs	Omer et al. 2018 Pediatr Infect Dis J quote Overall, incidence rate of severe pneumonia was 20% lower in the IIV group compared with the control group (IRR: 0.80; 95% CI: 0.66-0.99; P = 0.04). abstract, RESULTS All-cause pneumonia, not influenza-confirmed, so a vaccine-probe of influenza's contribution. Heterogeneous across sites: a significant reduction in Nepal, a borderline one in South Africa and no difference in Mali; protection was highest during high influenza circulation.
All-cause acute lower respiratory tract infection hospitalisation in the first 90 days of life severity: hospitalisation case definition: ALRI hospitalisation in infants born to IIV or placebo recipients	infants in the first 90 days of life pregnancy: mother vaccinated in pregnancy country: South Africa period: 2011 and 2012 seasons n: 1026 infants of IIV recipients and 1023 of placebo recipients; 30 ALRI hospitalisations in the first 90 days NeonateInfant <1y	trivalent inactivated influenza vaccine given to the mother platform: inactivated doses: 1 maternal dose vs infants of placebo recipients	0.43 (.19–.93) incidence rate ratio, infants of vaccinated vs placebo mothers	RCT	Nunes et al. 2017 Clin Infect Dis quote Thirty of the ALRI hospitalizations occurred during the first 90 days of life, 9 in the IIV group (3.0 [95% CI, 1.6-5.9]) and 21 in the placebo group (7.2 [95% CI, 4.7-11.0]) (incidence rate ratio, 0.43 [95% CI, .19-.93]) for a vaccine efficacy of 57.5% (P = .032). abstract, RESULTS A vaccine-probe outcome: almost none of the tested hospitalised infants were influenza-positive, so the effect, if real, runs through infections that influenza predisposes to. Over the full follow-up the reduction was borderline significant. Small numbers.
Medically attended acute respiratory illness with laboratory-confirmed influenza A or B severity: medically attended outpatient illness strain: A(H3N2) and B co-circulating, 2012-13 case definition: RT-PCR-confirmed influenza among outpatients with acute respiratory illness	6 months and older country: United States period: December 2012 to January 2013 (2012-13 season) n: 2,697 children and adults All ages	2012-13 seasonal influenza vaccine platform: mixed doses: 1 per season vs test-negative controls	56 VE (%), adjusted	test-negative	Centers 2013 MMWR Morb Mortal Wkly Rep quote During this period, overall vaccine effectiveness (VE) (adjusted for age, site, race/ethnicity, self-rated health, and days from illness onset to enrollment) against influenza A and B virus infections associated with medically attended acute respiratory illness was 56%, similar to the earlier interim estimate (62%). abstract Interim estimate; no CI is given in the abstract. The report gives lower VE against A(H3N2) than against B, and VE was lower and not statistically significant among older adults.
Medically attended acute respiratory illness with laboratory-confirmed influenza severity: medically attended outpatient illness strain: A(H3N2) predominant, more than two-thirds antigenically drifted from the vaccine component case definition: Laboratory-confirmed influenza among outpatients with acute respiratory illness	6 months and older country: United States period: November 2014 to January 2015 (2014-15 season) n: 2,321 children and adults All ages	2014-15 Northern Hemisphere seasonal influenza vaccine platform: mixed doses: 1 per season vs test-negative controls	23 (8–36) VE (%), adjusted	test-negative	Flannery et al. 2015 MMWR Morb Mortal Wkly Rep quote During this period, overall vaccine effectiveness (VE) (adjusted for study site, age, sex, race/ethnicity, self-rated health, and days from illness onset to enrollment) against laboratory-confirmed influenza associated with medically attended ARI was 23% (95% confidence interval [CI] = 8%-36%). abstract A low-VE season attributed to antigenic drift of A(H3N2) away from the vaccine strain. Interim estimate.
Medically attended laboratory-confirmed influenza (any) severity: medically attended outpatient illness strain: A(H1N1)pdm09 and B predominant, 2015-16 case definition: RT-PCR-confirmed influenza among outpatients with acute respiratory illness	6 months and older country: United States period: 2015-16 season n: 6879 participants All ages	2015-16 seasonal influenza vaccines (inactivated and live attenuated) platform: mixed doses: 1 per season vs test-negative controls	48 (41–55) VE (%)	test-negative	Jackson et al. 2017 N Engl J Med quote The effectiveness of the influenza vaccine against any influenza illness was 48% (95% confidence interval [CI], 41 to 55; P<0.001). abstract, RESULTS Pooled across products; the inactivated and live attenuated estimates in children differed sharply (next records).
Medically attended laboratory-confirmed influenza in children, inactivated vaccine severity: medically attended outpatient illness case definition: RT-PCR-confirmed influenza among outpatients	children 2 to 17 years country: United States period: 2015-16 season 1-4y5-11y12-17y	inactivated influenza vaccine platform: inactivated doses: as given vs test-negative controls	60 (47–70) VE (%)	test-negative	Jackson et al. 2017 N Engl J Med quote Among children 2 to 17 years of age, the inactivated influenza vaccine was 60% effective (95% CI, 47 to 70; P<0.001), and the live attenuated vaccine was not observed to be effective (vaccine effectiveness, 5%; 95% CI, -47 to 39; P=0.80). abstract, RESULTS The same sentence reports the live attenuated vaccine as not effective (5%, -47 to 39) in the same children and season.
Medically attended laboratory-confirmed influenza in children, live attenuated vaccine severity: medically attended outpatient illness case definition: RT-PCR-confirmed influenza among outpatients	children 2 to 17 years country: United States period: 2015-16 season 1-4y5-11y12-17y	live attenuated influenza vaccine (LAIV4) platform: live attenuated doses: as given vs test-negative controls	5 (-47–39) VE (%)	test-negative	Jackson et al. 2017 N Engl J Med quote Among children 2 to 17 years of age, the inactivated influenza vaccine was 60% effective (95% CI, 47 to 70; P<0.001), and the live attenuated vaccine was not observed to be effective (vaccine effectiveness, 5%; 95% CI, -47 to 39; P=0.80). abstract, RESULTS A null result in a season where the inactivated vaccine was 60% effective in the same children; it led ACIP to recommend against LAIV for the following season. Contrast with the Cochrane RCT pooled estimate for LAIV.
Medically attended laboratory-confirmed influenza A(H1N1)pdm09 in children, live attenuated vaccine severity: medically attended outpatient illness strain: A(H1N1)pdm09 case definition: RT-PCR-confirmed A(H1N1)pdm09 among outpatients	children 2 to 17 years country: United States period: 2015-16 season 1-4y5-11y12-17y	live attenuated influenza vaccine (LAIV4) platform: live attenuated doses: as given vs test-negative controls	-19 (-113–33) VE (%)	test-negative	Jackson et al. 2017 N Engl J Med quote Vaccine effectiveness against A(H1N1)pdm09 among children was 63% (95% CI, 45 to 75; P<0.001) for the inactivated vaccine, as compared with -19% (95% CI, -113 to 33; P=0.55) for the live attenuated vaccine. abstract, RESULTS Negative point estimate with a CI spanning zero (P = 0.55); the inactivated vaccine was 63% (45-75) against the same subtype in the same sentence. The LAIV A(H1N1)pdm09 component was subsequently replaced.
Outpatient medically attended laboratory-confirmed influenza (any) severity: medically attended outpatient illness strain: A(H3N2) predominant, 2017-18 case definition: Laboratory-confirmed influenza among outpatients with acute respiratory illness	6 months and older country: United States period: 2017-18 season (the most severe season of the decade) All ages	2017-18 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	38 (31–43) VE (%)	test-negative	Rolfes et al. 2019 Clin Infect Dis quote RESULTS: The VE against outpatient, medically attended, laboratory-confirmed influenza was 38% (95% confidence interval [CI], 31%-43%), including 22% (95% CI, 12%-31%) against influenza A(H3N2), 62% (95% CI, 50%-71%) against influenza A(H1N1)pdm09, and 50% (95% CI, 41%-57%) against influenza B. abstract, RESULTS Same sentence: 22% against A(H3N2), 62% against A(H1N1)pdm09, 50% against B (next records). Despite modest VE the authors estimate large numbers of hospitalisations and deaths were prevented because of high disease burden.
Outpatient medically attended laboratory-confirmed influenza A(H3N2) severity: medically attended outpatient illness strain: A(H3N2) case definition: Laboratory-confirmed A(H3N2) among outpatients	6 months and older country: United States period: 2017-18 season All ages	2017-18 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	22 (12–31) VE (%)	test-negative	Rolfes et al. 2019 Clin Infect Dis quote RESULTS: The VE against outpatient, medically attended, laboratory-confirmed influenza was 38% (95% confidence interval [CI], 31%-43%), including 22% (95% CI, 12%-31%) against influenza A(H3N2), 62% (95% CI, 50%-71%) against influenza A(H1N1)pdm09, and 50% (95% CI, 41%-57%) against influenza B. abstract, RESULTS Low H3N2 VE in a severe H3N2 season; egg-adapted changes in the vaccine virus were implicated (see the cell-based vaccine record for the same season).
Outpatient medically attended laboratory-confirmed influenza A(H1N1)pdm09 severity: medically attended outpatient illness strain: A(H1N1)pdm09 case definition: Laboratory-confirmed A(H1N1)pdm09 among outpatients	6 months and older country: United States period: 2017-18 season All ages	2017-18 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	62 (50–71) VE (%)	test-negative	Rolfes et al. 2019 Clin Infect Dis quote RESULTS: The VE against outpatient, medically attended, laboratory-confirmed influenza was 38% (95% confidence interval [CI], 31%-43%), including 22% (95% CI, 12%-31%) against influenza A(H3N2), 62% (95% CI, 50%-71%) against influenza A(H1N1)pdm09, and 50% (95% CI, 41%-57%) against influenza B. abstract, RESULTS Same season and network as the 22% H3N2 estimate: subtype, not season, explains most of the difference.
Outpatient medically attended laboratory-confirmed influenza B severity: medically attended outpatient illness strain: influenza B (B/Yamagata predominant in 2017-18) case definition: Laboratory-confirmed influenza B among outpatients	6 months and older country: United States period: 2017-18 season All ages	2017-18 seasonal influenza vaccines (trivalent vaccines lacked the B/Yamagata lineage) platform: mixed doses: 1 per season vs test-negative controls	50 (41–57) VE (%)	test-negative	Rolfes et al. 2019 Clin Infect Dis quote RESULTS: The VE against outpatient, medically attended, laboratory-confirmed influenza was 38% (95% confidence interval [CI], 31%-43%), including 22% (95% CI, 12%-31%) against influenza A(H3N2), 62% (95% CI, 50%-71%) against influenza A(H1N1)pdm09, and 50% (95% CI, 41%-57%) against influenza B. abstract, RESULTS Trivalent and quadrivalent products pooled; the Kaiser cell-based record shows trivalent egg-based vaccines were far less effective against B that season.
Medically attended laboratory-confirmed influenza (any) severity: medically attended outpatient illness strain: B/Victoria and A(H1N1)pdm09 co-dominant, 2019-20 case definition: Laboratory-confirmed influenza among outpatients with acute respiratory illness	6 months and older country: United States period: 2019-20 season n: 8845 enrollees All ages	2019-20 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	39 (32–44) VE (%)	test-negative	Tenforde et al. 2021 Clin Infect Dis quote Effectiveness against any influenza illness was 39% (95% confidence interval [CI]: 32-44), 45% (95% CI: 37-52) against B/Victoria and 30% (95% CI: 21-39) against A(H1N1)pdm09-associated illness. abstract, RESULTS Same sentence: 45% against B/Victoria and 30% against A(H1N1)pdm09; the drifted H1N1 clade record follows.
Medically attended laboratory-confirmed influenza A(H1N1)pdm09, antigenically drifted clade 6B.1A 183P-5A+156K severity: medically attended outpatient illness strain: A(H1N1)pdm09 clade 6B.1A 183P-5A+156K case definition: Laboratory-confirmed A(H1N1)pdm09 of the drifted clade among outpatients	6 months and older country: United States period: 2019-20 season, predominantly after January 2020 All ages	2019-20 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	7 (-14–23) VE (%)	test-negative	Tenforde et al. 2021 Clin Infect Dis quote Vaccination offered no protection against A(H1N1)pdm09 viruses with antigenically drifted clade 6B.1A 183P-5A+156K HA genes (VE 7%; 95% CI: -14 to 23%) which predominated after January. abstract, RESULTS A null estimate against a late-season drifted clade, in a subtype that usually has the highest VE: antigenic drift within season can abolish protection.
Hospitalisation with laboratory-confirmed influenza severity: hospitalisation case definition: Laboratory-confirmed influenza among adults hospitalised with acute respiratory illness	adults, median 63 years country: United States period: 2019-20 season n: 3116 participants 18-49y50-64y65+	2019-20 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative hospitalised controls	41 (27–52) VE (%)	test-negative	Tenforde et al. 2021 J Infect Dis quote Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI], 27%-52%). abstract, RESULTS VE differed sharply between the two major pandemic H1N1 genetic subgroups, with no VE against the drifted group that also gave a null estimate in the outpatient network.
Severe influenza-associated illness (hospitalised, 45% ICU) in adults severity: hospitalisation or ICU admission case definition: Laboratory-confirmed influenza among adults admitted with acute respiratory illness, nearly half treated in ICU	adults, median 57 years country: United States period: 2019-20 season n: 638 patients 18-49y50-64y65+	2019-20 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	32 (2–53) VE (%)	test-negative	Grijalva et al. 2021 Clin Infect Dis quote Forty-five percent of cases and 61% of controls were vaccinated, which resulted in an overall VE of 32% (95% CI: 2-53%), including 28% (-9% to 52%) against influenza A and 52% (13-74%) against influenza B. abstract, RESULTS Same sentence: 28% (-9 to 52) against influenza A and 52% (13-74) against influenza B. Age-stratified estimates follow.
Severe influenza-associated illness in adults aged 65 and older severity: hospitalisation or ICU admission case definition: Laboratory-confirmed influenza among adults admitted with acute respiratory illness	65 years and older country: United States period: 2019-20 season 65+	2019-20 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	-3 (-97–46) VE (%)	test-negative	Grijalva et al. 2021 Clin Infect Dis quote VE was higher in adults 18-49 years old (62%; 95% CI: 27-81%) than those aged 50-64 years (20%; -48% to 57%) and ≥65 years old (-3%; 95% CI: -97% to 46%) (P = .0789 for interaction). abstract, RESULTS Null in older adults versus 62% (27-81) in adults 18-49 and 20% (-48 to 57) at 50-64 in the same sentence; the interaction test did not reach significance. Small sample.
Influenza-associated in-hospital death in adults severity: death case definition: Death during hospitalisation among laboratory-confirmed influenza cases	adults, median 57 years country: United States period: 2019-20 season n: 42 in-hospital deaths 18-49y50-64y65+	2019-20 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	80 (4–96) VE (%)	test-negative	Grijalva et al. 2021 Clin Infect Dis quote VE was significantly higher against influenza-associated death (80%; 95% CI: 4-96%) than nonfatal influenza illness. abstract, RESULTS Based on few deaths, hence the very wide interval. Higher than the VE against non-fatal hospitalised illness in the same study.
Medically attended outpatient acute respiratory infection with influenza A(H3N2) severity: medically attended outpatient illness strain: A(H3N2) case definition: Laboratory-confirmed A(H3N2) among outpatients with acute respiratory infection	6 months and older country: United States period: October 2021 to February 2022 (2021-22 season) n: 3,636 children and adults All ages	2021-22 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	16 (-16–39) VE (%), interim	test-negative	Chung et al. 2022 MMWR Morb Mortal Wkly Rep quote Overall, vaccine effectiveness (VE) against medically attended outpatient ARI associated with influenza A(H3N2) virus was 16% (95% CI = -16% to 39%), which is considered not statistically significant. abstract Not statistically significant: the report states vaccination did not reduce the risk of outpatient A(H3N2) illness that season. Enrolment was too small for age- or product-specific estimates.
Influenza A-associated hospitalisation in adults severity: hospitalisation strain: influenza A (H3N2 and H1N1pdm09) case definition: Laboratory-confirmed influenza A among adults hospitalised with acute respiratory illness, SARS-CoV-2-negative controls	adults 18 years and older country: United States (IVY Network) period: 2022-23 season (early, well-matched) n: 3707 patients 18-49y50-64y65+	2022-23 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	37 (27–46) VE (%)	test-negative	Lewis et al. 2024 Clin Infect Dis quote VE against influenza-associated hospitalization was 37% (95% confidence interval [CI]: 27%-46%) and varied by age (18-64 years: 47% [30%-60%]; ≥65 years: 28% [10%-43%]), and virus (A[H3N2]: 29% [6%-46%], A[H1N1]: 47% [23%-64%]). abstract, RESULTS Same sentence: 47% (30-60) at 18-64 and 28% (10-43) at 65 and older; 29% (6-46) against A(H3N2) and 47% (23-64) against A(H1N1). Severe-outcome estimates follow.
Influenza A-associated hospitalisation in adults aged 65 and older severity: hospitalisation strain: influenza A case definition: Laboratory-confirmed influenza A among hospitalised adults	65 years and older country: United States (IVY Network) period: 2022-23 season 65+	2022-23 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	28 (10–43) VE (%)	test-negative	Lewis et al. 2024 Clin Infect Dis quote VE against influenza-associated hospitalization was 37% (95% confidence interval [CI]: 27%-46%) and varied by age (18-64 years: 47% [30%-60%]; ≥65 years: 28% [10%-43%]), and virus (A[H3N2]: 29% [6%-46%], A[H1N1]: 47% [23%-64%]). abstract, RESULTS Lower than the 47% in adults 18-64 from the same sentence, the usual age gradient.
Influenza A with organ failure treated with organ support severity: ICU-level organ support strain: influenza A case definition: Laboratory-confirmed influenza A with respiratory, cardiovascular or renal failure requiring organ support	adults 18 years and older country: United States (IVY Network) period: 2022-23 season 18-49y50-64y65+	2022-23 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	65 (56–72) VE (%)	test-negative	Lewis et al. 2024 Clin Infect Dis quote VE against more severe influenza-associated outcomes included: 41% (29%-50%) against influenza with hypoxemia treated with supplemental oxygen; 65% (56%-72%) against influenza with respiratory, cardiovascular, or renal failure treated with organ support; and 66% (40%-81%) against influenza with respiratory failure treated with invasive mechanical ventilation. abstract, RESULTS VE rises with outcome severity in this study: lower against any hospitalisation, higher with organ failure and 66% (40-81) with invasive mechanical ventilation.
Medically attended outpatient laboratory-confirmed influenza, late season severity: medically attended outpatient illness strain: A(H1N1)pdm09 and A(H3N2) late-season case definition: Laboratory-confirmed influenza among outpatients enrolled after the season peak	6 months and older country: United States period: December 2022 to April 2023 (late 2022-23 season) n: 2561 participants, 91 influenza cases All ages	2022-23 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	30 (-9–54) VE (%)	test-negative	Chung et al. 2024 Influenza Other Respir Viruses quote Overall, VE was 30% (95% confidence interval -9%, 54%); low late-season activity precluded estimation for most subgroups. abstract, RESULTS Not statistically significant; low late-season activity gave few cases. Late-season estimates also carry any within-season waning.
Influenza-associated outpatient visits in children and adolescents severity: medically attended outpatient illness case definition: Laboratory-confirmed influenza among outpatients with acute respiratory illness, four VE networks	6 months to 17 years country: United States period: 2023-24 season (interim) Infant <1y1-4y5-11y12-17y	2023-24 seasonal influenza vaccines platform: mixed doses: as given vs test-negative controls	59% to 67% VE (%), range across networks	test-negative	Frutos et al. 2024 MMWR Morb Mortal Wkly Rep quote Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. abstract A range of point estimates across four networks, not a confidence interval. Same sentence: 52% to 61% against paediatric hospitalisation. Adult estimates follow.
Influenza-associated hospitalisation in adults severity: hospitalisation case definition: Laboratory-confirmed influenza among hospitalised adults, VE networks	adults 18 years and older country: United States period: 2023-24 season (interim) 18-49y50-64y65+	2023-24 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	41% to 44% VE (%), range across networks	test-negative	Frutos et al. 2024 MMWR Morb Mortal Wkly Rep quote Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. abstract Range of network point estimates, not a CI; same sentence gives 33% to 49% against adult outpatient visits.
Outpatient acute respiratory illness with laboratory-confirmed influenza (any) severity: medically attended outpatient illness strain: A(H3N2), A(H1N1)pdm09 and B/Victoria co-circulating case definition: Laboratory-confirmed influenza among outpatients with acute respiratory illness	6 months and older country: United States period: 2024-25 season n: 6,793 enrolled patients, 2,016 influenza-positive All ages	2024-25 seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative controls	33 (24–41) VE (%)	test-negative	Chung et al. 2026 Clin Infect Dis quote Overall vaccine effectiveness against any influenza illness was 33% (95% Confidence Interval [CI]: 24 to 41): 27% (95% CI: 14 to 39) against influenza A(H3N2), 37% (95% CI: 24 to 48) against A(H1N1)pdm09, and 40% (95% CI: 12 to 59) against B/Victoria. abstract, RESULTS Same sentence: 27% (14-39) against A(H3N2), 37% (24-48) against A(H1N1)pdm09 and 40% (12-59) against B/Victoria. No significant interaction between current and prior season vaccination.
Outpatient laboratory-confirmed influenza B/Victoria severity: medically attended outpatient illness strain: B/Victoria case definition: Laboratory-confirmed B/Victoria among outpatients	6 months and older country: United States period: 2024-25 season n: 183 B/Victoria cases All ages	2024-25 seasonal influenza vaccines (trivalent, B/Yamagata removed) platform: mixed doses: 1 per season vs test-negative controls	40 (12–59) VE (%)	test-negative	Chung et al. 2026 Clin Infect Dis quote Overall vaccine effectiveness against any influenza illness was 33% (95% Confidence Interval [CI]: 24 to 41): 27% (95% CI: 14 to 39) against influenza A(H3N2), 37% (95% CI: 24 to 48) against A(H1N1)pdm09, and 40% (95% CI: 12 to 59) against B/Victoria. abstract, RESULTS The first season with trivalent vaccines after removal of B/Yamagata. Same sentence gives 27% against A(H3N2).
Influenza-associated hospitalisation in children and adolescents severity: hospitalisation case definition: Laboratory-confirmed influenza among hospitalised children in two VE networks	under 18 years country: United States period: October 2024 to February 2025 (interim 2024-25) Infant <1y1-4y5-11y12-17y	2024-25 seasonal influenza vaccines platform: mixed doses: as given vs test-negative controls	63% and 78% VE (%), two network point estimates	test-negative	Frutos et al. 2025 MMWR Morb Mortal Wkly Rep quote Among children and adolescents aged <18 years, VE against any influenza was 32%, 59%, and 60% in the outpatient setting in three networks, and against influenza-associated hospitalization was 63% and 78% in two networks. abstract Two separate network estimates, no pooled CI in the abstract. Outpatient VE in children was 32%, 59% and 60% across three networks in the same sentence.
Medically attended laboratory-confirmed influenza A(H1N1)pdm09 in primary care severity: medically attended outpatient illness strain: A(H1N1)pdm09 case definition: Laboratory-confirmed influenza among ILI patients in primary care, multicentre test-negative	all ages country: multiple (Europe, I-MOVE sites) period: 2013-14 season n: 531 cases and 1712 controls All ages	2013-14 seasonal influenza vaccines platform: inactivated doses: 1 per season vs test-negative controls	47.5 (16.4–67.0) VE (%), adjusted	test-negative	Valenciano et al. 2015 Vaccine quote Using a one-stage model, the overall pooled adjusted VE against influenza A(H1N1)pdm2009 was 47.5% (95% CI: 16.4-67.0). abstract, RESULTS No heterogeneity across sites for this subtype (I2 = 0%). The A(H3N2) estimate from the same season follows and was heterogeneous.
Medically attended laboratory-confirmed influenza A(H3N2) in primary care severity: medically attended outpatient illness strain: A(H3N2) case definition: Laboratory-confirmed influenza among ILI patients in primary care, two-stage pooled	all ages country: multiple (Europe, I-MOVE sites) period: 2013-14 season n: 623 cases and 1920 controls All ages	2013-14 seasonal influenza vaccines platform: inactivated doses: 1 per season vs test-negative controls	29.7 (-34.4–63.2) VE (%), adjusted	test-negative	Valenciano et al. 2015 Vaccine quote Using a two-stage model for the pooled analysis, the adjusted VE against A(H3N2) was 29.7 (95% CI: -34.4-63.2). abstract, RESULTS Interval includes zero and estimates were heterogeneous across countries.
Medically attended laboratory-confirmed influenza A(H1N1)pdm09 in primary care severity: medically attended outpatient illness strain: A(H1N1)pdm09 case definition: Laboratory-confirmed influenza among ILI patients, multicentre test-negative	all ages country: multiple (Europe) period: 2015/16 season n: 11 430 ILI patients, 2272 A(H1N1)pdm09 cases All ages	2015/16 seasonal influenza vaccines platform: inactivated doses: 1 per season vs test-negative controls	32.9 (15.5–46.7) VE (%)	test-negative	Kissling et al. 2018 Influenza Other Respir Viruses quote Overall VE against influenza A(H1N1)pdm09 was 32.9% (95% CI: 15.5-46.7). abstract, RESULTS Age-stratified estimates in the next sentence were moderate in children and working-age adults and low in older adults (next record).
Medically attended laboratory-confirmed influenza A(H1N1)pdm09 in adults aged 65 and older severity: medically attended outpatient illness strain: A(H1N1)pdm09 case definition: Laboratory-confirmed influenza among ILI patients in primary care	65 years and older country: multiple (Europe) period: 2015/16 season 65+	2015/16 seasonal influenza vaccines platform: inactivated doses: 1 per season vs test-negative controls	13.2 (-38.0–45.3) VE (%)	test-negative	Kissling et al. 2018 Influenza Other Respir Viruses quote Among those aged 0-14, 15-64 and ≥65 years, VE against A(H1N1)pdm09 was 31.9% (95% CI: -32.3 to 65.0), 41.4% (95% CI: 20.5-56.7) and 13.2% (95% CI: -38.0 to 45.3), respectively. abstract, RESULTS Low and non-significant in older adults versus 41.4% (20.5-56.7) at 15-64 in the same sentence.
Medically attended laboratory-confirmed influenza B in children, lineage-mismatched vaccine severity: medically attended outpatient illness strain: influenza B (B/Victoria circulating; vaccine contained B/Yamagata lineage) case definition: Laboratory-confirmed influenza B among ILI patients in primary care	0-14 years country: multiple (Europe) period: 2015/16 season n: 2901 influenza B cases overall Infant <1y1-4y5-11y12-17y	2015/16 trivalent seasonal influenza vaccine (B lineage mismatched) platform: inactivated doses: as given vs test-negative controls	-47.6 (-124.9–3.1) VE (%)	test-negative	Kissling et al. 2018 Influenza Other Respir Viruses quote Among those aged 0-14, 15-64 and ≥65 years, VE against influenza B was -47.6% (95% CI: -124.9 to 3.1), 27.3% (95% CI: -4.6 to 49.4) and 9.3% (95% CI: -44.1 to 42.9), respectively. abstract, RESULTS A negative point estimate in children against a lineage-mismatched B virus; the CI just reaches zero. The same sentence gives 27.3% at 15-64 and 9.3% at 65 and older. The authors call for data on prior vaccination and infection to interpret it.
Hospitalisation with laboratory-confirmed influenza A(H1N1)pdm09 in older adults severity: hospitalisation strain: A(H1N1)pdm09 case definition: Laboratory-confirmed influenza among patients aged 65 and older admitted with severe acute respiratory infection, 27 hospitals	65 years and older country: multiple (11 European countries) period: 2015/16 season n: 355 A(H1N1)pdm09 cases and 1,274 controls 65+	2015/16 seasonal influenza vaccines platform: inactivated doses: 1 per season vs test-negative hospitalised controls	42 (22–57) VE (%), adjusted	test-negative	Rondy et al. 2017 Euro Surveill quote Adjusted IVE against influenza A(H1N1)pdm09 was 42% (95% confidence interval (CI): 22 to 57). abstract Estimates in patients with diabetes, cancer, lung and heart disease were similar in the same abstract. VE against hospitalised influenza B follows.
Hospitalisation with laboratory-confirmed influenza B in older adults severity: hospitalisation strain: influenza B case definition: Laboratory-confirmed influenza B among patients aged 65 and older admitted with severe acute respiratory infection	65 years and older country: multiple (11 European countries) period: 2015/16 season n: 110 influenza B cases 65+	2015/16 seasonal influenza vaccines platform: inactivated doses: 1 per season vs test-negative hospitalised controls	52 (24–70) VE (%), adjusted	test-negative	Rondy et al. 2017 Euro Surveill quote Adjusted IVE against influenza B was 52% (95% CI: 24 to 70). abstract Moderate protection against hospitalised B in the same season that gave a negative outpatient B estimate in children (lineage mismatch); outcomes and age groups differ.
Medically attended laboratory-confirmed influenza A(H1N1)pdm09 in primary care severity: medically attended outpatient illness strain: A(H1N1)pdm09 (new vaccine component) case definition: Laboratory-confirmed influenza among ILI patients, I-MOVE multicentre	all ages country: multiple (Europe) period: 2017-18 season All ages	2017-18 seasonal influenza vaccines platform: inactivated doses: 1 per season vs test-negative controls	59 (47–69) VE (%)	test-negative	Kissling et al. 2019 Vaccine X quote RESULTS: During the 2017-18 season, the overall VE against influenza A(H1N1)pdm09 was 59% (95% CI: 47-69). abstract, RESULTS Age-stratified estimates in the following sentence show good protection in older adults when the H1N1 component was updated.
Medically attended laboratory-confirmed influenza A(H3N2) in primary care severity: medically attended outpatient illness strain: A(H3N2) case definition: Laboratory-confirmed influenza among ILI patients, I-MOVE multicentre	all ages country: multiple (Europe) period: 2017-18 season (second season with the same A(H3N2) vaccine component) All ages	2017-18 seasonal influenza vaccines platform: inactivated doses: 1 per season vs test-negative controls	13 (-15–34) VE (%)	test-negative	Kissling et al. 2019 Vaccine X quote Overall VE against influenza A(H3N2) was 28% (95% CI: 17-38) in 2016-17 and 13% (95% CI: -15 to 34) in 2017-18. abstract, RESULTS The same sentence gives 28% (17-38) in 2016-17 with the same H3N2 component. Egg-adaptation mismatch of the vaccine seed virus is the authors' explanation.
Medically attended laboratory-confirmed influenza A(H3N2) in adults aged 65 and older severity: medically attended outpatient illness strain: A(H3N2) case definition: Laboratory-confirmed influenza among ILI patients, I-MOVE multicentre	65 years and older country: multiple (Europe) period: 2017-18 season 65+	2017-18 seasonal influenza vaccines platform: inactivated doses: 1 per season vs test-negative controls	-9 (-74–32) VE (%)	test-negative	Kissling et al. 2019 Vaccine X quote Among 0-14-year-olds VE against A(H3N2) was 28% (95%CI: -10 to 53) and 29% (95% CI: -87 to 73), among 15-64-year-olds 34% (95% CI: 18-46) and 33% (95% CI: -3 to 56) and among those aged ≥65 years 15% (95% CI: -10 to 34) and -9% (95% CI: -74 to 32) in 2016-17 and 2017-18, respectively. abstract, RESULTS Negative point estimate in older adults, 15% (-10 to 34) the season before. Same sentence gives 29% (-87 to 73) at 0-14 and 33% (-3 to 56) at 15-64 for 2017-18.
Medically attended laboratory-confirmed influenza A(H3N2) in primary care severity: medically attended outpatient illness strain: A(H3N2) clades 3C.2a and 3C.3a co-circulating case definition: Laboratory-confirmed influenza among ILI patients, I-MOVE multicentre	all ages country: multiple (Europe) period: 2018/19 season All ages	2018/19 seasonal influenza vaccines platform: inactivated doses: 1 per season vs test-negative controls	-1 (-24–18) VE (%)	test-negative	Kissling et al. 2019 Euro Surveill quote To assess the imprint-regulated effect of vaccine (I-REV) hypothesis, we further stratified the middle-aged group, notably including 32-54-year-olds (1964-86) sharing potential childhood imprinting to serine at haemagglutinin position 159.ResultsInfluenza A(H3N2) VE among all ages was -1% (95% confidence interval (CI): -24 to 18) and 46% (95% CI: 8-68), -26% (95% CI: -66 to 4) and 20% (95% CI: -20 to 46) among 0-14, 15-64 and ≥ 65-year-olds, respectively. abstract, Results A null season against H3N2 overall: 46% (8-68) at 0-14, -26% (-66 to 4) at 15-64 and 20% (-20 to 46) at 65 and older in the same sentence.
Medically attended laboratory-confirmed influenza A(H3N2) clade 3C.3a in 15-64-year-olds severity: medically attended outpatient illness strain: A(H3N2) clade 3C.3a case definition: Laboratory-confirmed A(H3N2) of clade 3C.3a among ILI patients	15-64 years country: multiple (Europe) period: 2018/19 season 12-17y18-49y50-64y	2018/19 seasonal influenza vaccines platform: inactivated doses: 1 per season vs test-negative controls	-74 (-259–16) VE (%)	test-negative	Kissling et al. 2019 Euro Surveill quote Among 15-64-year-olds, VE against clades 3C.2a1b and 3C.3a was 15% (95% CI: -34 to 50) and -74% (95% CI: -259 to 16), respectively. abstract, Results The lowest clade-specific estimate in the study, with a very wide interval. The same sentence gives 15% (-34 to 50) against clade 3C.2a1b.
Medically attended laboratory-confirmed influenza A(H3N2) in adults born 1964-86 severity: medically attended outpatient illness strain: A(H3N2) case definition: Laboratory-confirmed A(H3N2) among ILI patients, birth-cohort stratified	32-54 years (born 1964-86) country: multiple (Europe) period: 2018/19 season 18-49y50-64y	2018/19 seasonal influenza vaccines platform: inactivated doses: 1 per season vs test-negative controls	-53 (-131–-2) VE (%)	test-negative	Kissling et al. 2019 Euro Surveill quote VE was -18% (95% CI: -140 to 41), -53% (95% CI: -131 to -2) and -12% (95% CI: -74 to 28) among 15-31-year-olds (1987-2003), 32-54-year-olds (1964-86) and 55-64-year-olds (1954-63), respectively.DiscussionThe lowest 2018/19 influenza A(H3N2) VE was against clade 3C.3a and among those born 1964-86, corresponding to the I-REV hypothesis. abstract, Results A statistically significant negative VE in one birth cohort, which the authors interpret under the imprint-regulated effect of vaccine (I-REV) hypothesis; it could also reflect bias in test-negative designs. Flagged for review.
Hospitalisation with laboratory-confirmed influenza A(H1N1)pdm09 in older adults severity: hospitalisation strain: A(H1N1)pdm09 case definition: Laboratory-confirmed influenza among patients aged 65 and older admitted with severe acute respiratory infection, 13 sites	65 years and older risk group: 63-67% of cases had two or more chronic conditions country: multiple (12 European countries) period: 2015/16 to 2023/24 pooled n: 1805 cases with 16,329 controls 65+	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative hospitalised controls	37 (29–44) VE (%), pooled seasons	test-negative	Rose et al. 2025 BMC Med quote Against A(H1N1)pdm09, pooled-season IVE was 37% (95%CI: 29-44) overall; 49% (95%CI: 9-72), 30% (95%CI: 12-44) and 38% (95%CI: 29-46) in those with 0, 1, ≥ 2 chronic conditions. abstract, RESULTS Point estimates were similar in most chronic-condition groups but negative in immunosuppression and low in kidney disease, with significant interaction for both (next record).
Hospitalisation with laboratory-confirmed influenza A(H1N1)pdm09 in immunosuppressed older adults severity: hospitalisation strain: A(H1N1)pdm09 case definition: Laboratory-confirmed influenza among hospitalised SARI patients aged 65 and older with immunosuppression	65 years and older immune status: immunosuppressed country: multiple (Europe) period: 2015/16 to 2023/24 pooled 65+	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative hospitalised controls	-7 VE (%), point estimate	test-negative	Rose et al. 2025 BMC Med quote Most IVE point estimates were 34-45%, apart from immunosuppression (-7%), kidney disease (17%) and liver disease (54%), but 95% CIs overlapped. abstract, RESULTS No CI is given in the abstract for this subgroup, but the interaction test for immunosuppression was significant. Against A(H3N2) the immunosuppressed estimate was also near zero.
Hospitalisation with laboratory-confirmed influenza A(H3N2) in older adults severity: hospitalisation strain: A(H3N2) case definition: Laboratory-confirmed influenza among hospitalised SARI patients aged 65 and older	65 years and older country: multiple (12 European countries) period: 2015/16 to 2023/24 pooled n: 2590 cases with 14,920 controls 65+	seasonal influenza vaccines platform: mixed doses: 1 per season vs test-negative hospitalised controls	17 (8–25) VE (%), pooled seasons	test-negative	Rose et al. 2025 BMC Med quote Against A(H3N2), pooled-season IVE was 17% (95%CI: 8-25) overall; 15% (95%CI: -26-42), 11% (95%CI: -8-27) and 18% (95%CI: 7-28) in those with 0, 1, ≥ 2 chronic conditions. abstract, RESULTS Low but significant across nine pooled seasons; 15% (-26 to 42), 11% (-8 to 27) and 18% (7-28) with 0, 1 and 2 or more chronic conditions.
PCR-confirmed influenza A severity: any confirmed illness strain: A(H3N2) predominant case definition: PCR-confirmed influenza A among Kaiser Permanente Northern California members	4-64 years country: United States period: 2017-18 season n: 3,053,248 members, 84,420 cell-culture vaccinees 1-4y5-11y12-17y18-49y50-64y	quadrivalent cell-culture inactivated vaccine platform: inactivated, cell-based doses: 1 vs egg-based inactivated vaccines (mostly trivalent)	8.0 (-10–23) relative VE (%), cell-culture vs egg-based vaccine	cohort	Klein et al. 2020 PLoS One quote The rVE against influenza A was 8.0% (95% CI: -10, 23); aVE was 31.7% (CI: 18.7, 42.6) for cell-culture and 20.1% (CI: 14.5, 25.4) for egg-based vaccines. abstract No significant advantage against influenza A in a season when egg adaptation of H3N2 was suspected; absolute VE was 31.7% (18.7, 42.6) for cell-culture and 20.1% (14.5, 25.4) for egg-based vaccines.
PCR-confirmed influenza B severity: any confirmed illness strain: B/Yamagata predominant (absent from trivalent vaccines) case definition: PCR-confirmed influenza B among Kaiser Permanente Northern California members	4-64 years country: United States period: 2017-18 season 1-4y5-11y12-17y18-49y50-64y	quadrivalent cell-culture inactivated vaccine platform: inactivated, cell-based doses: 1 vs egg-based inactivated vaccines (mostly trivalent, lacking B/Yamagata)	39.6 (27.9–49.3) relative VE (%), quadrivalent cell-culture vs mostly trivalent egg-based vaccine	cohort	Klein et al. 2020 PLoS One quote The rVE against influenza B was 39.6% (CI: 27.9, 49.3); aVE was 40.9% (CI: 30, 50.1) for cell-culture and 9.7% (CI 3.5, 15.6) for egg-based trivalent vaccines. abstract The B advantage reflects the quadrivalent formulation containing B/Yamagata rather than the cell-culture platform: absolute VE was 40.9% (30, 50.1) for cell-culture and 9.7% (3.5, 15.6) for egg-based trivalent vaccines.
Influenza-related medical encounters (any setting) severity: medically attended illness case definition: Influenza-related medical encounters in electronic health records	adults 18 years and older country: United States period: 2019-20 season n: 1 499 215 cell-based and 4 126 263 egg-based recipients 18-49y50-64y65+	cell-based quadrivalent inactivated vaccine (IIV4c) platform: inactivated, cell-based doses: 1 vs egg-based quadrivalent inactivated vaccine (IIV4e)	9.5 (7.9–11.1) relative VE (%), cell-based vs egg-based quadrivalent	cohort	Imran et al. 2022 Open Forum Infect Dis quote The rVE for IIV4c versus IIIV4e for any IRME was 9.5% (95% confidence interval [CI], 7.9%-11.1%). abstract, RESULTS Retrospective cohort without laboratory confirmation; rVE favoured the cell-based vaccine except in the oldest adults. Inpatient and outpatient rVEs are given separately in the abstract.
Medically attended laboratory-confirmed influenza A(H3N2) and B, change in VE per month since vaccination severity: medically attended outpatient illness strain: A(H3N2) and influenza B case definition: Laboratory-confirmed influenza among outpatients, US Flu VE Network, VE modelled against days since vaccination	6 months and older country: United States period: 2011-12 through 2014-15 seasons All ages	seasonal inactivated and live attenuated vaccines platform: mixed doses: 1 per season time since vaccination: modelled from 14 days to 6 months after vaccination vs test-negative controls	7 absolute decline in VE per month since vaccination (percentage points)	test-negative	Ferdinands et al. 2017 Clin Infect Dis quote Maximum VE was observed shortly after vaccination, followed by a decline in VE of about 7% (absolute) per month for influenza A(H3N2) and influenza B and 6% - 11% per month for influenza A(H1N1)pdm09 viruses. abstract, RESULTS Same sentence: 6%-11% per month for A(H1N1)pdm09. VE stayed above zero for at least 5 months (H3N2) and 6 months (H1N1pdm09, B). The authors say bias or residual confounding could explain the pattern; decline was steeper in people vaccinated the prior season.
Laboratory-confirmed influenza-associated death in children severity: death case definition: Laboratory-confirmed influenza-associated paediatric deaths reported to national surveillance, vaccination compared with survey-cohort coverage	6 months to 17 years country: United States period: August 2016 through July 2025 n: 1086 deaths with vaccination information Infant <1y1-4y5-11y12-17y	seasonal influenza vaccines platform: mixed doses: fully vaccinated per age-appropriate schedule vs vaccination coverage in survey cohorts (49% average)	80 (75–84) VE (%) against death, full vaccination	case-control	Leonard et al. 2026 Pediatrics quote VE was 80% (95% CI 75-84) overall, 77% (95% CI 71-82) among children with underlying medical conditions and 87% (95% CI 84-89) among children without known conditions. abstract, RESULTS Case-cohort style design using population survey coverage as the comparator, so unmeasured differences between decedents and the surveyed population (for example access to care) are a confounding risk. Same sentence: 77% (71-82) with underlying conditions, 87% (84-89) without.
Laboratory-confirmed influenza-associated death in children with underlying medical conditions severity: death case definition: Influenza-associated paediatric deaths among children with underlying conditions	6 months to 17 years risk group: underlying medical conditions country: United States period: 2016-2025 n: 530 deaths with underlying conditions Infant <1y1-4y5-11y12-17y	seasonal influenza vaccines platform: mixed doses: fully vaccinated vs vaccination coverage in survey cohorts	77 (71–82) VE (%) against death, full vaccination	case-control	Leonard et al. 2026 Pediatrics quote VE was 80% (95% CI 75-84) overall, 77% (95% CI 71-82) among children with underlying medical conditions and 87% (95% CI 84-89) among children without known conditions. abstract, RESULTS Lower than the 87% (84-89) in children without known conditions in the same sentence. Fewer than a quarter of these children had been fully vaccinated.
Admission to a paediatric intensive care unit with RT-PCR-confirmed influenza severity: ICU admission case definition: RT-PCR-confirmed influenza among children admitted to PICU, compared with PICU controls	children country: United States period: 2010-11 and 2011-12 seasons n: 44 cases, 172 PICU controls, 93 community controls Infant <1y1-4y5-11y12-17y	seasonal influenza vaccines platform: mixed doses: fully vaccinated per age-appropriate schedule vs unvaccinated children (PICU controls)	74 (19–91) VE (%) against PICU admission, full vaccination vs unvaccinated	case-control	Ferdinands et al. 2014 J Infect Dis quote Compared to unvaccinated children, children who were fully vaccinated were 74% (95% CI, 19% to 91%) or 82% (95% CI, 23% to 96%) less likely to be admitted to a PICU for influenza compared to PICU controls or community controls, respectively. abstract, RESULTS 82% (23-96) against community controls in the same sentence. Receipt of 1 dose when 2 were recommended was not protective. Small case numbers.
Influenza-coded ambulatory visits severity: medically attended outpatient illness case definition: Influenza-coded ambulatory visits in administrative data, not laboratory-confirmed	6-23 months country: United States period: multiple seasons Infant <1y1-4y	trivalent inactivated influenza vaccine platform: inactivated doses: 2 (full vaccination) vs unvaccinated children	0.81 (0.68–0.97) hazard ratio, fully vaccinated vs unvaccinated	cohort	Shen et al. 2013 Vaccine quote RESULTS: Full vaccination was associated with a 19% reduction in influenza-coded ambulatory visits (HR=0.81; 95% CI, 0.68-0.97) in all children, and an 18% reduction in full-term children (HR=0.82; 95% CI, 0.68-0.99). abstract, RESULTS Modest effect against a non-specific coded outcome; no significant effectiveness was found for preterm children, and no benefit for partial (one-dose) vaccination.

Post-influenza cardiovascular events (myocardial infarction, stroke) Influenza A and B viruses

Post-acute and long-term sequelae

What can follow the acute illness: chronic disease, disability, cancers, congenital syndromes, post-infectious conditions.

Outcome (O)	Population (P)	Comparator	Estimate	Design (S)	Source
Hospitalisation for acute myocardial infarction in the 7 days after laboratory-confirmed influenza severity: hospitalised acute myocardial infarction case definition: Admission for acute myocardial infarction within 7 days after a positive influenza test (risk interval) versus the year before and after (control interval)	adults with laboratory-confirmed influenza and an MI admission within a year prior infection: laboratory-confirmed influenza infection vaccination status: mixed country: Canada (Ontario) setting: hospital, linked laboratory and administrative data period: 2009-2014 n: 364 MI admissions within 1 year before or after a positive influenza test 18-49y50-64y65+	vs the same individuals during control intervals (1 year before and after infection, excluding the 7-day risk interval)	6.05 (3.86–9.50) incidence ratio, risk interval vs control interval follow-up: 7 days after specimen collection	SCCS	Kwong et al. 2018 N Engl J Med quote The incidence ratio of an admission for acute myocardial infarction during the risk interval as compared with the control interval was 6.05 (95% confidence interval [CI], 3.86 to 9.50). abstract, RESULTS Self-controlled design removes fixed between-person confounding; residual confounding from time-varying factors (for example the acute illness prompting both testing and admission) remains. No increased incidence was observed after day 7.
Acute myocardial infarction within 7 days after influenza B detection severity: hospitalised acute myocardial infarction strain: influenza B case definition: Admission for acute myocardial infarction within 7 days after a positive influenza B test	adults with laboratory-confirmed influenza prior infection: laboratory-confirmed influenza B infection vaccination status: mixed country: Canada (Ontario) setting: hospital, linked data period: 2009-2014 18-49y50-64y65+	vs the same individuals during control intervals	10.11 (4.37–23.38) incidence ratio, risk interval vs control interval follow-up: 7 days	SCCS	Kwong et al. 2018 N Engl J Med quote Incidence ratios for acute myocardial infarction within 7 days after detection of influenza B, influenza A, respiratory syncytial virus, and other viruses were 10.11 (95% CI, 4.37 to 23.38), 5.17 (95% CI, 3.02 to 8.84), 3.51 (95% CI, 1.11 to 11.12), and 2.77 (95% CI, 1.23 to 6.24), respectively. abstract, RESULTS Based on few events, hence the wide interval. The same sentence gives 5.17 for influenza A (next record) and smaller ratios for RSV and other viruses, so the triggering effect is not unique to influenza.
Acute myocardial infarction within 7 days after influenza A detection severity: hospitalised acute myocardial infarction strain: influenza A case definition: Admission for acute myocardial infarction within 7 days after a positive influenza A test	adults with laboratory-confirmed influenza prior infection: laboratory-confirmed influenza A infection vaccination status: mixed country: Canada (Ontario) setting: hospital, linked data period: 2009-2014 18-49y50-64y65+	vs the same individuals during control intervals	5.17 (3.02–8.84) incidence ratio, risk interval vs control interval follow-up: 7 days	SCCS	Kwong et al. 2018 N Engl J Med quote Incidence ratios for acute myocardial infarction within 7 days after detection of influenza B, influenza A, respiratory syncytial virus, and other viruses were 10.11 (95% CI, 4.37 to 23.38), 5.17 (95% CI, 3.02 to 8.84), 3.51 (95% CI, 1.11 to 11.12), and 2.77 (95% CI, 1.23 to 6.24), respectively. abstract, RESULTS Self-controlled design; the main residual confounding is the acute illness itself, which can prompt both testing and admission.
First myocardial infarction in days 1-3 after laboratory-confirmed influenza severity: first myocardial infarction case definition: First MI in the Scottish Morbidity Record within days 1-3 after a laboratory-confirmed influenza virus record	adults with a first MI and a laboratory-confirmed respiratory infection prior infection: laboratory-confirmed influenza virus infection vaccination status: mixed country: Scotland setting: national linked surveillance and hospital data period: 2004-2014 n: 1227 myocardial infarctions after any laboratory-confirmed respiratory infection 18-49y50-64y65+	vs baseline time in the same individuals	9.80 (2.37–40.5) incidence ratio vs baseline time, age- and season-adjusted follow-up: days 1-3 after infection	SCCS	Warren-Gash et al. 2018 Eur Respir J quote Using self-controlled case series analysis, we generated age- and season-adjusted incidence ratios (IRs) for myocardial infarction (n=1227) or stroke (n=762) after infections compared with baseline time.We found substantially increased myocardial infarction rates in the week after Streptococcus pneumoniae and influenza virus infection: adjusted IRs for days 1-3 were 5.98 (95% CI 2.47-14.4) and 9.80 (95% CI 2.37-40.5), respectively. abstract Very wide interval from few influenza-linked events. The same sentence gives 5.98 for Streptococcus pneumoniae. Confounding by the acute illness prompting testing is the main concern.
First stroke in days 1-3 after laboratory-confirmed influenza severity: first stroke case definition: First stroke in the Scottish Morbidity Record within days 1-3 after a laboratory-confirmed influenza virus record	adults with a first stroke and a laboratory-confirmed respiratory infection prior infection: laboratory-confirmed influenza virus infection vaccination status: mixed country: Scotland setting: national linked data period: 2004-2014 n: 762 strokes after any laboratory-confirmed respiratory infection 18-49y50-64y65+	vs baseline time in the same individuals	7.82 (1.07–56.9) incidence ratio vs baseline time, age- and season-adjusted follow-up: days 1-3 after infection; stroke rates remained elevated to 28 days	SCCS	Warren-Gash et al. 2018 Eur Respir J quote Rates of stroke after infection were similarly high and remained elevated to 28 days: day 1-3 adjusted IRs 12.3 (95% CI 5.48-27.7) and 7.82 (95% CI 1.07-56.9) for S. pneumoniae and influenza virus, respectively. abstract Interval barely excludes 1 because of few events. The same sentence gives 12.3 for S. pneumoniae. Laboratory-confirmed infections over-represent severe illness.
First-ever acute myocardial infarction or stroke after influenza infection severity: first-ever AMI or stroke case definition: First-ever AMI or stroke in national registers after a laboratory-confirmed influenza infection, risk period versus baseline	median 75 years (IQR 66-82) prior infection: laboratory-confirmed influenza infection vaccination status: mixed country: Denmark setting: national registers period: 2014-2025 n: 1,221 individuals with first-ever AMI or stroke 50-64y65+	vs baseline periods in the same individuals	3.5 (2.6–4.7) incidence rate ratio, risk period vs baseline, calendar-month adjusted	SCCS	Croci et al. 2026 Euro Surveill quote After calendar-month adjustment, the IRR for cardiovascular events during the risk period was 3.5 (95% CI: 2.6-4.7), higher for AMI (IRR = 4.7; 95% CI: 3.1-7.4) than stroke (IRR = 2.9; 95% CI: 2.0-4.2). abstract, RESULTS Prior same-season influenza vaccination was recorded in about half of episodes and reduced the excess risk (significant interaction), so this pooled ratio mixes vaccinated and unvaccinated episodes. Separate AMI and stroke ratios follow.
First-ever acute myocardial infarction after influenza infection severity: first-ever acute myocardial infarction case definition: First-ever AMI in national registers after laboratory-confirmed influenza	median 75 years prior infection: laboratory-confirmed influenza infection vaccination status: mixed country: Denmark setting: national registers period: 2014-2025 n: 429 AMI cases 50-64y65+	vs baseline periods in the same individuals	4.7 (3.1–7.4) incidence rate ratio, risk period vs baseline	SCCS	Croci et al. 2026 Euro Surveill quote After calendar-month adjustment, the IRR for cardiovascular events during the risk period was 3.5 (95% CI: 2.6-4.7), higher for AMI (IRR = 4.7; 95% CI: 3.1-7.4) than stroke (IRR = 2.9; 95% CI: 2.0-4.2). abstract, RESULTS Consistent in direction with the Ontario and Scottish SCCS estimates. Residual confounding by the acute illness prompting both testing and admission is the main caveat.
First-ever stroke after influenza infection severity: first-ever stroke case definition: First-ever stroke in national registers after laboratory-confirmed influenza	median 75 years prior infection: laboratory-confirmed influenza infection vaccination status: mixed country: Denmark setting: national registers period: 2014-2025 n: 792 stroke cases 50-64y65+	vs baseline periods in the same individuals	2.9 (2.0–4.2) incidence rate ratio, risk period vs baseline	SCCS	Croci et al. 2026 Euro Surveill quote After calendar-month adjustment, the IRR for cardiovascular events during the risk period was 3.5 (95% CI: 2.6-4.7), higher for AMI (IRR = 4.7; 95% CI: 3.1-7.4) than stroke (IRR = 2.9; 95% CI: 2.0-4.2). abstract, RESULTS Lower than the AMI ratio in the same study. Vaccination in the same season attenuated the excess risk (significant interaction).
Atherothrombotic events (acute MI or ischaemic stroke) in the 14 days after influenza severity: acute myocardial infarction or ischaemic stroke case definition: AMI and ischaemic stroke in electronic registries after clinically diagnosed (primary care) or laboratory-confirmed (hospital) influenza	50 years and older prior infection: influenza diagnosed in primary care or confirmed in hospital vaccination status: mixed country: Spain setting: population-based electronic registries period: 2011-2018 n: 2 230 015 individuals in the registries 50-64y65+	vs baseline periods in the same individuals	more than 2-fold fold increase in risk during the 14 days after influenza vs baseline (gradient from mildest to most severe cases) follow-up: 14 days; remained more than 2-fold for 2 months after severe cases in the most vulnerable	SCCS	Muñoz-Quiles et al. 2024 J Infect Dis quote The risk of atherothrombotic events in subjects ≥50 years old increased more than 2-fold during the 14 days after the mildest influenza cases in patients with fewer risk factors and more than 4-fold after severe cases in the most vulnerable patients, remaining in them more than 2-fold for 2 months. abstract The abstract gives no numeric interval; the same sentence reports more than 4-fold after severe cases in the most vulnerable patients. Four sensitivity analyses supported the association, but clinically diagnosed influenza in primary care is not laboratory-confirmed.

Gaps

No pre-vaccine-era seasonal (non-pandemic) burden record: the only pre-1940s figure found is the Pink Book 1918-1919 pandemic death estimate. Seasonal influenza mortality before the 1940s was not separately searched for.
No pooled, interval-bearing waning estimate expressed as VE at fixed months since vaccination; the two waning records give per-month decline (Ferdinands 2017) and change in VE between 15-90 and 91-180 days (Young 2018).
No record of post-influenza sequelae other than cardiovascular events (for example post-viral fatigue, encephalopathy sequelae, or Guillain-Barre after infection) was compiled.
No separate B/Yamagata versus B/Victoria season-specific estimate from a single season was compiled; lineage-specific VE comes only from the Zhang 2024 pooled meta-analysis, the 2015/16 I-MOVE lineage-mismatched B estimate, and the 2024-25 B/Victoria estimate.
The CDC per-season burden pages (for example 2023-24) could not be snapshotted (HTTP 404), so season-by-season burden tables are represented only by the 2010-2025 range on the About page and the Pink Book.

Flags for review

Burden records influenza-bur-025, -026 and -027 (ICU, ventilation, in-hospital death) use hospitalised patients as the denominator, and influenza-bur-031 uses laboratory-confirmed cases. None is a population risk; do not multiply them by the hospitalisation rate or present them beside the symptomatic CFR (bur-033) without labelling the denominator.
The 2009 pandemic case-fatality figures differ by two orders of magnitude depending on denominator: confirmed-case CFR 2.9% (bur-031) and approximately 0.5% in early studies (bur-037), symptomatic CFR 0.048% (bur-033), infected-case CFR 0.02% (bur-032). They must be shown together with their denominators, never as one number.
Most burden ranges (bur-001 to -004, -009, -010, -011, -013, -024 to -027) are season-to-season or country-to-country ranges written into value=, not confidence intervals; bur-015, -016 and -035 carry author-defined uncertainty ranges in lo=/hi=. Check that the renderer does not label these as 95% CIs.
Cochrane records eff-001 to -003 and eff-008 to -014 are reported as risk ratios (value and CI on the same RR scale), so no ci_scale is set; the Cochrane pregnancy records eff-004 to -007 are on the VE % scale. Do not mix them in one chart without converting, which the brief forbids the compiler from doing.
Negative or null VE point estimates are compiled as found: eff-003 (hospitalisation RR 0.96 in healthy adults), eff-014 (mortality RR 1.02, 4 deaths), eff-018, -029, -034, -037, -038, -044, -045 text, -047, -049, -053, -060, -062, -063, -067, -068, -069, -070, -071, -073, -078, -080, -081, -086, -092, -100. eff-071 (-53%, CI -131 to -2, adults born 1964-86, 2018/19 A(H3N2)) is the only statistically significant negative estimate; the authors offer an immunological imprinting hypothesis, and test-negative bias is an alternative. A reviewer should decide how it is presented.
Several efficacy records from MMWR interim reports carry ranges of network point estimates in value= with no CI (eff-054, -055, -058) or a point estimate with no CI (eff-033, -073, -089, -090). Check whether the site may display interval-free records next to interval-bearing ones.
eff-093 and -094 (VE against paediatric death) use survey vaccination coverage as the comparator rather than individually matched controls; eff-105 uses influenza-coded visits, not laboratory confirmation; eff-088 uses coded medical encounters. These are weaker designs than the test-negative and RCT records they sit beside.
The post-acute records are all cardiovascular (MI and stroke) SCCS estimates. Vaccination status is mixed in every one, and the Danish study (pa-006 to -008) shows same-season vaccination attenuated the excess risk, so these ratios are not the risk an unvaccinated person faces; they mix vaccinated and unvaccinated infections.
The brief asked for pre- and post-vaccine-era burden. For seasonal influenza no true pre-vaccine era figure was found; bur-007 (1918 pandemic, Pink Book, 21 million deaths) is the only pre-1940s number and other published estimates are far higher. bur-009/-010 (1976-2007) span rising vaccine coverage and are labelled as such.
High-dose vaccine evidence is internally consistent on relative benefit (eff-075 to -082) but eff-078 and eff-080 show no all-cause mortality benefit in about 580,000 randomised older adults; present the hospitalisation and mortality results together.
tools/websource.py --grep and plain python printing crash with a cp1252 UnicodeDecodeError on Windows unless PYTHONUTF8=1 is set; the tool was not edited. compile.py --show expects a slug, not a spec path (the brief's example invocation fails).

Search log (38 searches)

Cochrane vaccines for preventing influenza in healthy adults · PubMed → Found PMID 29388196 (Demicheli 2018 Cochrane, healthy adults incl. pregnancy); compiled as efficacy records.
Cochrane vaccines for preventing influenza in healthy children · PubMed → Found PMID 29388195 (Jefferson 2018 Cochrane, children); compiled as efficacy records.
Cochrane vaccines for preventing influenza in the elderly · PubMed → Found PMID 29388197 (Demicheli 2018 Cochrane, elderly) and PMID 39230284 (Ferdinands 2024 network meta-analysis of enhanced vaccines); compiled as efficacy records.
estimates of global seasonal influenza-associated respiratory mortality modelling study · PubMed → Found PMID 29248255 (Iuliano 2018 Lancet) and PMID 32087815 (Wang 2020 under-5 burden); compiled as burden records.
2009 pandemic H1N1 case fatality ratio estimate · PubMed → Found PMID 21477133 (Khandaker 2011 systematic review), 19997612 (Presanis 2009 Bayesian severity), 22738893 (Dawood 2012 global mortality), 20524916 (Wong 2010 CFR perspective); compiled as burden records.
influenza-associated pediatric deaths United States surveillance · PubMed → Found PMID 29440502 (Shang 2018), 16354892 (Bhat 2005), 40996933 (MMWR 2024-25 deaths), 42402353 (VE against pediatric death 2016-2025), 38051664 (IVY 2022-23 severe outcomes); compiled.
influenza hospitalization rates by age FluSurv-NET · PubMed → Found PMID 39471107 (MMWR Surveillance Summary 2010-2023); compiled as burden records.
estimates of deaths associated with seasonal influenza United States 1976-2007 · PubMed → Found PMID 20798667 (MMWR 2010); compiled as burden records.
acute myocardial infarction after laboratory-confirmed influenza infection self-controlled case series · PubMed → Found PMID 29365305 (Kwong 2018 NEJM), 29563170 (Warren-Gash 2018 Scotland), 38330324 (Spain SCCS), 42141868 (Denmark SCCS 2026); compiled as post_acute records.
stroke after influenza infection self-controlled case series · PubMed → Same Scottish and Danish SCCS studies as above; no additional stroke-specific source compiled.
influenza vaccine effectiveness United States Flu VE Network 2014-15 H3N2 · PubMed → Found PMID 25590680 (interim 2014-15 VE) and 28039340 (Ferdinands 2017 intraseason waning); compiled.
influenza vaccine effectiveness United States 2017-18 season test-negative network · PubMed → Nothing usable in the first page; the 2017-18 estimate was found via the Rolfes search below.
influenza vaccine effectiveness United States 2019-20 season test-negative · PubMed → No hits; found via the Tenforde search below.
influenza vaccine effectiveness 2022-23 season United States outpatient test-negative · PubMed → Found PMID 38923314 (late-season 2022-23 outpatient VE); compiled.
influenza vaccine effectiveness 2023-24 season United States interim · PubMed → Found PMID 38421935 (interim 2023-24 MMWR); compiled.
influenza vaccine effectiveness 2024-25 season United States · PubMed → Found PMID 40014791 (interim 2024-25 MMWR) and 42442752 (full-season outpatient 2024-25); compiled.
I-MOVE influenza vaccine effectiveness Europe multicentre test-negative season · PubMed → Found PMID 41185010, 29125681, 28797322, 31796152, 25936723, 31660536 (I-MOVE / I-MOVE+ / VEBIS); compiled.
high-dose versus standard-dose influenza vaccine older adults randomized trial efficacy · PubMed → Found PMID 25119609 (DiazGranados 2014 RCT), 41115437 (FLUNITY-HD pooled RCTs), 42476160 (2026 meta-analysis of HD RCTs); compiled.
recombinant influenza vaccine versus standard-dose efficacy randomized adults 50 years · PubMed → Found PMID 28636855 (Dunkle 2017 RIV4 RCT); compiled.
live attenuated versus inactivated influenza vaccine infants young children randomized · PubMed → Found PMID 17301299 (Belshe 2007 LAIV vs IIV RCT); compiled.
live attenuated influenza vaccine effectiveness children 2013-14 2015-16 H1N1pdm09 United States · PubMed → Only the 2017-18 ACIP recommendations returned; the LAIV null estimate was found via the Jackson 2015-16 search below.
maternal influenza immunization infant randomized trial South Africa · PubMed → Found PMID 25184864 (Madhi 2014 RCT), 27380464 (Nunes 2016 duration), 28575286 (Nunes 2017 ALRI hospitalisation), 29443825 (Omer 2018 pooled trials); compiled.
influenza vaccine effectiveness immunocompromised meta-analysis · PubMed → Found PMID 22216224 (Beck 2011 meta-analysis) and 22904335 (Beck 2012 by aetiology, no pooled numbers in abstract); compiled 22216224.
influenza vaccine effectiveness hospitalization older adults 65 pooled test-negative · PubMed → Found PMID 27061888 (Belongia 2016 subtype meta-analysis), 38423813 (Zhang 2024 meta-analysis), 34081398 (adjuvanted meta-analysis), 28935236 (Rondy 2017 severe illness meta-analysis); compiled.
influenza vaccine effectiveness intensive care unit admission children · PubMed → Found PMID 24676207 (Ferdinands 2014 PICU case-control), 35271561 (interim 2021-22 VE), 41093140 (2026 severe-outcome meta-analysis); compiled.
influenza vaccine effectiveness waning time since vaccination meta-analysis · PubMed → Nothing usable on first query; the Young 2018 meta-analysis was found with the reworded search below.
live attenuated influenza vaccine effectiveness children United States 2013-2016 meta-analysis · PubMed → No hits.
cell-based versus egg-based influenza vaccine relative effectiveness · PubMed → Found PMID 32101582 (Klein 2020 Kaiser 2017-18) and 36320195 (2019-20 retrospective cohort); compiled.
duration of influenza vaccine effectiveness systematic review meta-analysis waning · PubMed → No relevant hit (COVID review returned).
influenza vaccine effectiveness children 6-23 months · PubMed → Found PMID 23688524 (6-23 month cohort, pre- and full-term); compiled.
Rolfes effects of influenza vaccination United States 2017-2018 season · PubMed → Found PMID 30715278 (Rolfes 2019); compiled.
Tenforde influenza vaccine effectiveness 2019-2020 season United States · PubMed → Found PMID 33367650 (outpatient, drift), 33378531 (hospitalisation), 34014274 (severe illness); compiled.
influenza vaccine effectiveness 2012-13 season United States Flu VE Network · PubMed → Found PMID 23425960 (interim 2012-13 MMWR); compiled.
Madhi influenza vaccination of pregnant women and protection of their infants · PubMed → Found PMID 25184864; compiled.
Jackson influenza vaccine effectiveness United States 2015-2016 season live attenuated inactivated · PubMed → Found PMID 28792867 (Jackson 2017 NEJM, LAIV null); compiled.
influenza vaccine effectiveness decline time since vaccination systematic review pooled · PubMed → No relevant hit.
Young duration of influenza vaccine effectiveness meta-analysis test-negative · PubMed → Found PMID 29220496 (Young 2018); compiled.
Pink Book chapter 12 influenza and CDC About Estimated Flu Burden page · websource.py → Snapshotted as cdc-gov-7fdb77ce99 and cdc-gov-c0fa169878; compiled as burden records. The CDC 2023-24 season burden page URL returned HTTP 404.