Influenza vaccine effectiveness against hospitalization in the United States, 2019-2020

Abstract Background Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019-2020 influenza vaccine against influenza-associated hospitalizations in the United States. Methods We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases versus test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups. Results 3116 participants were included, including 18% (553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI]: 27-52). VE against A(H1N1)pdm09 viruses was 40% (95% CI: 24-53) and 33% against B viruses (95% CI: 0-56). Of the two major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A+187A,189E) was 59% (95% CI: 34-75) whereas no significant VE was observed against the other group (5A+156K) [-1%, 95% CI: -61-37]. Conclusions In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness.

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Effects of Influenza Vaccination in the United States During the 2018–2019 Influenza Season

Clinical Infectious Diseases ◽

10.1093/cid/ciz1244 ◽

2020 ◽

Vol 71 (8) ◽

pp. e368-e376 ◽

Cited By ~ 7

Author(s):

Jessie R Chung ◽

Melissa A Rolfes ◽

Brendan Flannery ◽

Pragati Prasad ◽

Alissa O’Halloran ◽

...

Keyword(s):

United States ◽

Influenza Vaccine ◽

Influenza Vaccination ◽

Influenza Season ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza Viruses ◽

Monte Carlo Algorithm ◽

Medical Visits ◽

The Us

Abstract Background Multivalent influenza vaccine products provide protection against influenza A(H1N1)pdm09, A(H3N2), and B lineage viruses. The 2018–2019 influenza season in the United States included prolonged circulation of A(H1N1)pdm09 viruses well-matched to the vaccine strain and A(H3N2) viruses, the majority of which were mismatched to the vaccine. We estimated the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the season. Methods We used a mathematical model and Monte Carlo algorithm to estimate numbers and 95% uncertainty intervals (UIs) of influenza-associated outcomes prevented by vaccination in the United States. The model incorporated age-specific estimates of national 2018–2019 influenza vaccine coverage, influenza virus–specific vaccine effectiveness from the US Influenza Vaccine Effectiveness Network, and disease burden estimated from population-based rates of influenza-associated hospitalizations through the Influenza Hospitalization Surveillance Network. Results Influenza vaccination prevented an estimated 4.4 million (95%UI, 3.4 million–7.1 million) illnesses, 2.3 million (95%UI, 1.8 million–3.8 million) medical visits, 58 000 (95%UI, 30 000–156 000) hospitalizations, and 3500 (95%UI, 1000–13 000) deaths due to influenza viruses during the US 2018–2019 influenza season. Vaccination prevented 14% of projected hospitalizations associated with A(H1N1)pdm09 overall and 43% among children aged 6 months–4 years. Conclusions Influenza vaccination averted substantial influenza-associated disease including hospitalizations and deaths in the United States, primarily due to effectiveness against A(H1N1)pdm09. Our findings underscore the value of influenza vaccination, highlighting that vaccines measurably decrease illness and associated healthcare utilization even in a season in which a vaccine component does not match to a circulating virus.

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Vaccine effectiveness against influenza-associated hospitalization among children aged < 13 years using a hospital-based surveillance system in Minnesota, 2013 – 2016

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx162.142 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S60-S60

Author(s):

Ashley Fowlkes ◽

Hannah Friedlander ◽

Andrea Steffens ◽

Kathryn Como-Sabetti ◽

Dave Boxrud ◽

...

Keyword(s):

Influenza Vaccine ◽

Influenza Vaccination ◽

Influenza A ◽

Respiratory Illness ◽

Vaccine Effectiveness ◽

Influenza Viruses ◽

Point Estimate ◽

Influenza B ◽

Current Season ◽

Immunization Registry

Abstract Background Due to marked variability in circulating influenza viruses each year, annual evaluation of the vaccine’s effectiveness against severe outcomes is essential. We used the Minnesota Department of Health’s (MDH) Severe Acute Respiratory Illness (SARI) surveillance to evaluate vaccine effectiveness (VE) against influenza-associated hospitalization over three influenza seasons. Methods Residual respiratory specimens from patients admitted with SARI were sent to the MDH laboratory for influenza RT-PCR testing. Medical records were reviewed to collect patient data. Vaccination history was verified using the state immunization registry. We included patients aged ≥6 months to < 13 years, after which immunization reporting is not required, hospitalized from the earliest influenza detection after July through April each year. We defined vaccinated patients as those ≥1 dose of influenza vaccine in the current season. Children aged < 9 years with no history of vaccination were considered vaccinated if 2 were doses given a month apart. Partially vaccinated children were excluded. We estimated VE as 1 minus the adjusted odds ratio (x100%) of influenza vaccination among influenza cases vs. negative controls, controlling for age, race, days from onset to admission, comorbidities, and admission month. Results Among 2198 SARI patients, 763 (35%) were vaccinated for influenza, 180 (8.2%) were partially vaccinated, and 1255 (57%) were unvaccinated. Influenza was detected among 202 (9.2%) children, and significantly more frequently among children aged ≥5 years (17%) compared with younger children (7.4%). The adjusted VE in 2013–14 was 68% (95% Confidence Interval: 34, 85), but was non-significant during the 2014–15 and 2015–16 seasons (Figure). Estimates of VE by influenza A subtypes varied substantially by year; VE against influenza B viruses was significant, but could not be stratified by year. VE was impacted when live attenuated influenza vaccine recipients were excluded. Conclusion We report moderately high influenza VE in 2013–14 and a point estimate higher than other published estimates from outpatient data in 2014–15. These results, underscore the importance of influenza vaccination to prevent severe outcomes such as hospitalization. Disclosures All authors: No reported disclosures.

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Influenza Vaccine Effectiveness in Inpatient and Outpatient Settings in the United States, 2015–2018

Clinical Infectious Diseases ◽

10.1093/cid/ciaa407 ◽

2020 ◽

Author(s):

Mark W Tenforde ◽

Jessie Chung ◽

Emily R Smith ◽

H Keipp Talbot ◽

Christopher H Trabue ◽

...

Keyword(s):

United States ◽

High Risk ◽

Influenza Vaccine ◽

Patient Characteristics ◽

Respiratory Illness ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza Activity ◽

Outpatient Settings ◽

Negative Controls

Abstract Background Demonstration of influenza vaccine effectiveness (VE) against hospitalized illness in addition to milder outpatient illness may strengthen vaccination messaging. Our objective was to compare patient characteristics and VE between United States (US) inpatient and outpatient VE networks. Methods We tested adults with acute respiratory illness (ARI) for influenza within 1 outpatient-based and 1 hospital-based VE network from 2015 through 2018. We compared age, sex, and high-risk conditions. The test-negative design was used to compare vaccination odds in influenza-positive cases vs influenza-negative controls. We estimated VE using logistic regression adjusting for site, age, sex, race/ethnicity, peak influenza activity, time to testing from, season (overall VE), and underlying conditions. VE differences (ΔVE) were assessed with 95% confidence intervals (CIs) determined through bootstrapping with significance defined as excluding the null. Results The networks enrolled 14 573 (4144 influenza-positive) outpatients and 6769 (1452 influenza-positive) inpatients. Inpatients were older (median, 62 years vs 49 years) and had more high-risk conditions (median, 4 vs 1). Overall VE across seasons was 31% (95% CI, 26%–37%) among outpatients and 36% (95% CI, 27%–44%) among inpatients. Strain-specific VE (95% CI) among outpatients vs inpatients was 37% (25%–47%) vs 53% (37%–64%) against H1N1pdm09; 19% (9%–27%) vs 23% (8%–35%) against H3N2; and 46% (38%–53%) vs 46% (31%–58%) against B viruses. ΔVE was not significant for any comparison across all sites. Conclusions Inpatients and outpatients with ARI represent distinct populations. Despite comparatively poor health among inpatients, influenza vaccination was effective in preventing influenza-associated hospitalizations.

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Relative and Absolute Effectiveness of High-Dose and Standard-Dose Influenza Vaccine Against Influenza-Related Hospitalization Among Older Adults—United States, 2015–2017

Clinical Infectious Diseases ◽

10.1093/cid/ciaa160 ◽

2020 ◽

Cited By ~ 3

Author(s):

Joshua D Doyle ◽

Lauren Beacham ◽

Emily T Martin ◽

H Keipp Talbot ◽

Arnold Monto ◽

...

Keyword(s):

United States ◽

Older Adults ◽

Influenza Vaccine ◽

Standard Dose ◽

Relative Effectiveness ◽

Respiratory Illness ◽

The United States ◽

Vaccine Effectiveness ◽

High Dose ◽

Confounding Variables

Abstract Background Seasonal influenza causes substantial morbidity and mortality in older adults. High-dose inactivated influenza vaccine (HD-IIV), with increased antigen content compared to standard-dose influenza vaccines (SD-IIV), is licensed for use in people aged ≥65 years. We sought to evaluate the effectiveness of HD-IIV and SD-IIV for prevention of influenza-associated hospitalizations. Methods Hospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at 8 hospitals in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015–2016 and 2016–2017 influenza seasons. Enrolled patients were tested for influenza, and receipt of influenza vaccine by type was recorded. Effectiveness of SD-IIV and HD-IIV was estimated using a test-negative design (comparing odds of influenza among vaccinated and unvaccinated patients). Relative effectiveness of SD-IIV and HD-IIV was estimated using logistic regression. Results Among 1487 enrolled patients aged ≥65 years, 1107 (74%) were vaccinated; 622 (56%) received HD-IIV, and 485 (44%) received SD-IIV. Overall, 277 (19%) tested positive for influenza, including 98 (16%) who received HD-IIV, 87 (18%) who received SD-IIV, and 92 (24%) who were unvaccinated. After adjusting for confounding variables, effectiveness of SD-IIV was 6% (95% confidence interval [CI] −42%, 38%) and that of HD-IIV was 32% (95% CI −3%, 54%), for a relative effectiveness of HD-IIV versus SD-IIV of 27% (95% CI −1%, 48%). Conclusions During 2 US influenza seasons, vaccine effectiveness was low to moderate for prevention of influenza hospitalization among adults aged ≥65 years. High-dose vaccine offered greater effectiveness. None of these findings were statistically significant.

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988. Effectiveness of Seasonal Influenza Vaccines Against Influenza A(H3N2) Illness Among Children Aged <18 Years, US Flu VE Network, 2010–2018

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.825 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S292-S292

Author(s):

Brendan L Flannery ◽

Jessie Chung ◽

Michael L Jackson ◽

Lisa A Jackson ◽

Arnold S Monto ◽

...

Keyword(s):

Influenza Vaccine ◽

Influenza A ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza Viruses ◽

Older Children ◽

Research Support ◽

Illness Onset ◽

Negative Controls ◽

Research Grant

Abstract Background Interim estimates of 2017–2018 influenza vaccine effectiveness (VE) against influenza A(H3N2)-related illness in the United States indicated better protection among young children than among older children and adolescents. We examined VE against influenza A(H3N2) illness during five A(H3N2)-predominant seasons from 2010–2011 through 2016–2017 to investigate differences between VE among younger vs. older children. Methods We analyzed data from 11,736 outpatients aged <18 years with medically attended acute respiratory illnesses enrolled at US Flu VE Network study sites during five influenza A(H3N2)-predominant seasons. Respiratory specimens from all enrollees were tested for influenza viruses using reverse transcription PCR. Children with documented receipt of the recommended number of doses of current season inactivated influenza vaccine at least 14 days before illness onset were considered fully vaccinated; partially vaccinated children and those who received live attenuated influenza vaccine were excluded. Vaccine effectiveness was estimated as 100 × (1 – adjusted odds ratio) from multivariable logistic regression adjusting for study site, age, sex, presence of high-risk medical conditions, and days from illness onset to enrollment comparing odds of vaccination among A(H3N2)-positive cases vs. influenza-negative controls. Results A total of 1,854 influenza A(H3N2) cases and 9,882 influenza-negative controls were included; 494 (28%) influenza A(H3N2) cases and 3,637 (41%) controls were fully vaccinated before illness onset. VE ranged from 26% (95% confidence interval [CI], −17% to 53%) to 60% (38%–75%) among children aged 6 months–4 years and from 9% (−16% to 29%) to 66% (37%–82%) among 5–17 year olds (figure). During 2012–2013 and 2014–2015, A(H3N2) VE estimates were significantly higher among younger compared with older children (P < 0.05); in other seasons before 2017–2018, A(H3N2) VE estimates were similar among younger and older children. Conclusion Higher VE against A(H3N2) viruses in younger vs. older children in some seasons suggests immunologic differences in response to vaccine components. Overall, inactivated influenza vaccine provided moderate protection against A(H3N2)-related illness among children. Disclosures M. L. Jackson, sanofi pasteur: Grant Investigator, Research support. L. A. Jackson, Novartis: Grant Investigator, Research support. R. K. Zimmerman, sanofi pasteur: Grant Investigator, Research support. Pfizer: Grant Investigator, Research support. Merck: Grant Investigator, Research support. M. P. Nowalk, Merck: Grant Investigator, Research support. Pfizer: Grant Investigator, Research support. M. R. Griffin, MedImmune: Grant Investigator, Research support. H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none. J. J. Treanor, Novartis: Board Member and Consultant, Consulting fee.

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Vaccine Effectiveness Against Influenza Hospitalization Among Children in the United States, 2015–2016

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piaa017 ◽

2020 ◽

Cited By ~ 1

Author(s):

Leora R Feldstein ◽

Constance Ogokeh ◽

Brian Rha ◽

Geoffrey A Weinberg ◽

Mary A Staat ◽

...

Keyword(s):

United States ◽

Influenza Vaccination ◽

Respiratory Illness ◽

The United States ◽

Vaccine Effectiveness ◽

Limited Data ◽

Surveillance Network ◽

Number Of Children ◽

Influenza Illness ◽

Us Children

Abstract Background Annual United States (US) estimates of influenza vaccine effectiveness (VE) in children typically measure protection against outpatient medically attended influenza illness, with limited data evaluating VE against influenza hospitalizations. We estimated VE for preventing laboratory-confirmed influenza hospitalization among US children. Methods We included children aged 6 months–17 years with acute respiratory illness enrolled in the New Vaccine Surveillance Network during the 2015–2016 influenza season. Documented influenza vaccination status was obtained from state immunization information systems, the electronic medical record, and/or provider records. Midturbinate nasal and throat swabs were tested for influenza using molecular assays. We estimated VE as 100% × (1 – odds ratio), comparing the odds of vaccination among subjects testing influenza positive with subjects testing negative, using multivariable logistic regression. Results Of 1653 participants, 36 of 707 (5%) of those fully vaccinated, 18 of 226 (8%) of those partially vaccinated, and 85 of 720 (12%) of unvaccinated children tested positive for influenza. Of those vaccinated, almost 90% were documented to have received inactivated vaccine. The majority (81%) of influenza cases were in children ≤ 8 years of age. Of the 139 influenza-positive cases, 42% were A(H1N1)pdm09, 42% were B viruses, and 14% were A(H3N2). Overall, adjusted VE for fully vaccinated children was 56% (95% confidence interval [CI], 34%–71%) against any influenza-associated hospitalization, 68% (95% CI, 36%–84%) for A(H1N1)pdm09, and 44% (95% CI, –1% to 69%) for B viruses. Conclusions These findings demonstrate the importance of annual influenza vaccination in prevention of severe influenza disease and of reducing the number of children who remain unvaccinated or partially vaccinated against influenza.

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Effect of antigenic drift on influenza vaccine effectiveness in the United States – 2019-2020

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1884 ◽

2020 ◽

Author(s):

Mark W Tenforde ◽

Rebecca J Garten Kondor ◽

Jessie R Chung ◽

Richard K Zimmerman ◽

Mary Patricia Nowalk ◽

...

Keyword(s):

United States ◽

Respiratory Illness ◽

The United States ◽

Vaccine Effectiveness ◽

Antigenic Drift ◽

Emerging Viruses ◽

Vaccine Protection ◽

Polymerase Chain ◽

Influenza Illness ◽

Negative Controls

Abstract Background At the start of the 2019-2020 influenza season, concern arose that circulating B/Victoria viruses of the globally emerging clade V1A.3 were antigenically drifted from the strain included in the vaccine. Intense B/Victoria activity was followed by circulation of genetically diverse A(H1N1)pdm09 viruses, that were also antigenically drifted. We measured vaccine effectiveness (VE) in the United States against illness from these emerging viruses. Methods We enrolled outpatients aged ≥6 months with acute respiratory illness at five sites. Respiratory specimens were tested for influenza by reverse-transcriptase polymerase chain reaction (RT-PCR). Using the test-negative design, we determined influenza VE by virus sub-type/lineage and genetic subclades by comparing odds of vaccination in influenza cases versus test-negative controls. Results Among 8,845 enrollees, 2,722 (31%) tested positive for influenza, including 1,209 (44%) for B/Victoria and 1,405 (51%) for A(H1N1)pdm09. 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. 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. Conclusions Vaccination provided protection against influenza illness, mainly due to infections from B/Victoria viruses. Vaccine protection against illness from A(H1N1)pdm09 was lower than historically observed effectiveness of 40-60%, due to late-season vaccine mismatch following emergence of antigenically drifted viruses. The effect of drift on vaccine protection is not easy to predict and, even in drifted years, significant protection can be observed.

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Influenza Vaccine Effectiveness in the United States During the 2016–2017 Season

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.1151 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S451-S452

Author(s):

Brendan Flannery ◽

Jessie Chung ◽

Arnold S Monto ◽

Emily T Martin ◽

Edward Belongia ◽

...

Keyword(s):

United States ◽

Influenza Vaccine ◽

The United States ◽

Vaccine Effectiveness

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Influenza vaccine effectiveness among patients with high-risk medical conditions in the United States, 2012–2016

Vaccine ◽

10.1016/j.vaccine.2018.10.093 ◽

2018 ◽

Vol 36 (52) ◽

pp. 8047-8053 ◽

Cited By ~ 9

Author(s):

Mei Shang ◽

Jessie R. Chung ◽

Michael L. Jackson ◽

Lisa A. Jackson ◽

Arnold S. Monto ◽

...

Keyword(s):

United States ◽

High Risk ◽

Influenza Vaccine ◽

The United States ◽

Vaccine Effectiveness ◽

Medical Conditions

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150. Relative Effectiveness of High-Dose and Standard-Dose Influenza Vaccine Against Influenza-Related Hospitalization Among Older Adults—United States, 2015–2017

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy209.020 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S10-S10

Author(s):

Joshua Doyle ◽

Lauren Beacham ◽

Elif Alyanak ◽

Manjusha Gaglani ◽

Emily T Martin ◽

...

Keyword(s):

United States ◽

Older Adults ◽

Influenza Vaccine ◽

Influenza A ◽

Standard Dose ◽

Relative Effectiveness ◽

The United States ◽

Vaccine Effectiveness ◽

High Dose ◽

Research Grant

Abstract Background Seasonal influenza causes substantial morbidity and mortality, and older adults are disproportionately affected. Newer vaccines have been developed for use in people 65 years and older, including a trivalent inactivated vaccine with a 4-fold higher dose of antigen (IIV-HD). In recent years, the use of IIV-HD has increased sufficiently to evaluate its effectiveness compared with standard-dose inactivated influenza vaccines (IIV-SD). Methods Hospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at 8 hospitals in 4 states participating in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015–2016 and 2016–2017 influenza seasons. Predominant influenza A virus subtypes were H1N1 and H3N2, respectively, during these seasons. All enrolled patients were tested for influenza virus with polymerase chain reaction. Receipt and type of influenza vaccine was determined from electronic records and chart review. Odds of laboratory-confirmed influenza were compared among vaccinated and unvaccinated patients. Relative odds of laboratory-confirmed influenza were determined for patients who received IIV-HD or IIV-SD, and adjusted for potential confounding variables via logistic regression. Results Among 1,744 enrolled patients aged ≥ 65 years, 1,105 (63%) were vaccinated; among those vaccinated, 621 (56%) received IIV-HD and 484 (44%) received IIV-SD. Overall, 315 (18%) tested positive for influenza, including 97 (6%) who received IIV-HD, 86 (5%) who received IIV-SD, and 132 (8%) who were unvaccinated. Controlling for age, race, sex, enrollment site, date of illness, index of comorbidity, and influenza season, the adjusted odds of influenza among patients vaccinated with IIV-HD vs. IIV-SD were 0.72 (P = 0.06, 95% CI: 0.52 to 1.01). Conclusion Comparison of high-dose vs. standard-dose vaccine effectiveness during 2 recent influenza seasons (1 H1N1 and 1 H3N2-predominant) suggested relative benefit (nonsignificant) of high-dose influenza vaccine in protecting against influenza-associated hospitalization among persons aged 65 years and older; additional years of data are needed to confirm this finding. Disclosures H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.

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