Hospitalized Adult Influenza Vaccine Effectiveness Research Articles

Relevance of RSV in hospitalized adults and the need for continued testing

Background: RSV is underrecognized in hospitalized adults. A better understanding of RSV in this population could help prioritize targeted viral-testing resources. Hospitalization and in-hospital outcomes are widely accepted as markers of clinical severity with respect to acute respiratory illness (ARI). We compared characteristics and clinical outcomes between adults hospitalized with ARI from October 2016 through May 2019. Methods: All hospitalized adults (≥ 18 years) who met a standardized case definition of ARI were prospectively enrolled across 3 respiratory seasons from 9 hospitals participating in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN). Demographic data were collected during enrollment interviews, and electronic medical records (EMRs) were reviewed to extract comorbidity data. Throat and nasal swabs collected at enrollment were tested for ARI pathogens using real-time PCR assays at respective HAIVEN research laboratory sites. Characteristics and clinical outcomes of participants were compared using χ2 or nonparametric tests where appropriate. Multivariable logistic regression models were used to test associations between infection status, characteristics, and clinical outcomes, adjusting for age, sex, race, Charlson comorbidity index (CCI), body mass index (BMI), site, season, and days to admission. Results: In total, 10,311 adults were included, 22.3% (n = 2,300) were aged 18–49 years, 33.2% (n = 3,423) were aged 50–64 years, and 44.5% (n = 4,588) were aged ≥65 years. Moreover, 6% of adults tested positive for RSV (n = 622), 18.8% positive for influenza (n = 1,940), and 75.1% negative for both (n = 7,749). Obesity and age ≥65 years were significantly associated with RSV detection when compared with participants negative for both RSV and influenza. Patients aged 18–49 years and ≥65 years with RSV had significantly higher median CCI scores compared to patients with influenza (Fig. 1.). The proportion of adults with CHF or COPD was significantly (p-value Conclusions: Severe RSV illness may differ from severe influenza illness, and those infected with RSV may have different characteristics than those infected with influenza. Hospitalized adults with RSV infection were more likely to have underlying cardiopulmonary comorbidities and higher CCI scores as well as experience an extended length of hospital stay and need for mechanical ventilation. These data highlight the importance of retaining testing for RSV in older adults hospitalized with ARI.Funding: NoneDisclosures: None

Vaccine Effectiveness Against Acute Respiratory Illness Hospitalizations for Influenza-Associated Pneumonia During the 2015-2016 to 2017-2018 Seasons: US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN).

Evidence for vaccine effectiveness (VE) against influenza-associated pneumonia has varied by season, location, and strain. We estimate VE against hospitalization for radiographically identified influenza-associated pneumonia during 2015-2016 to 2017-2018 seasons in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN). Among adults aged ≥18 years admitted to 10 US hospitals for acute respiratory illness (ARI), clinician-investigators used keywords from reports of chest imaging performed during 3 days around hospital admission to assign a diagnosis of "definite/probable pneumonia." We used a test-negative design to estimate VE against hospitalization for radiographically identified laboratory-confirmed influenza-associated pneumonia, comparing reverse transcriptase-polymerase chain reaction-confirmed influenza cases with test-negative subjects. Influenza vaccination status was documented in immunization records or self-reported, including date and location. Multivariable logistic regression models were used to adjust for age, site, season, calendar-time, and other factors. Of 4843 adults hospitalized with ARI included in the primary analysis, 266 (5.5%) had "definite/probable pneumonia" and confirmed influenza. Adjusted VE against hospitalization for any radiographically confirmed influenza-associated pneumonia was 38% (95% confidence interval [CI], 17-53%); by type/subtype, it was 74% (95% CI, 52-87%) influenza A (H1N1)pdm09, 25% (95% CI, -15% to 50%) A (H3N2), and 23% (95% CI, -32% to 54%) influenza B. Adjusted VE against intensive care for any influenza was 57% (95% CI, 19-77%). Influenza vaccination was modestly effective among adults in preventing hospitalizations and the need for intensive care associated with influenza pneumonia. VE was significantly higher against A (H1N1)pdm09 and was low against A (H3N2) and B.

Waning Vaccine Effectiveness Against Influenza-Associated Hospitalizations Among Adults, 2015-2016 to 2018-2019, United States Hospitalized Adult Influenza Vaccine Effectiveness Network.

We observed decreased effectiveness of influenza vaccine with increasing time since vaccination for prevention of influenza A(H3N2), influenza A(H1N1)pdm09, and influenza B/Yamagata-associated hospitalizations among adults. Maximum vaccine effectiveness (VE) was observed shortly after vaccination, followed by an absolute decline in VE of about 8%-9% per month postvaccination.

22. Description of Hospitalized Patients with Influenza Vaccine Failure

BackgroundDespite influenza vaccination, some patients develop illness and require hospitalization. Many factors contribute to vaccine failure, including mismatch of the vaccine and circulating strains, waning immunity, timing of influenza season, age and patient comorbidities such as immune function. This study compared vaccinated, hospitalized patients with and without influenza.MethodsThis study used 2015–2019 Tennessee data from the US Hospitalized Adult Influenza Vaccine Effectiveness Network database. Enrolled patients were ≥ 18 years vaccinated for the current influenza season and admitted with an acute respiratory illness. Patient or surrogate interviews and medical chart abstractions were performed, and influenza vaccinations were confirmed by vaccine providers. Influenza PCR testing was performed in a research lab. Statistical analyses were performed with STATA and R using Pearson’s chi-squared, Kruskal-Wallis and Wilcoxon rank-sum tests and multivariate logistic regression.Results1236 patients met study criteria, and 235 (19%) tested positive for influenza. Demographics, vaccines and comorbidities were similar between the two groups (Table 1) except for morbid obesity, which was more common in influenza negative patients (13% vs 8%, p = 0.04), and immunosuppression, which was more common in the influenza positive (63% vs 54%, p = 0.01). Logistic regression analysis demonstrated older patients (OR 1.47, 95% CI 1.03–2.10) and immunosuppressed patients (OR 1.56, 1.15–2.12) were at increased risk for influenza (Table 2 and Figure 1). Immunosuppression also increased the risk for influenza A/H3N2 (OR 1.86, 95% CI 1.25–2.75). A sensitivity analysis was performed on patients who self-reported influenza vaccination for the current season without vaccine verification and demonstrated increased risk of influenza in older adults (OR 1.66, 95% CI 1.16–2.39).Table 1: Demographics of influenza positive versus influenza negative patients in influenza vaccinated, hospitalized patients. Table 2: Logistic regression analyses of vaccinated, hospitalized influenza positive patients; vaccinated, hospitalized patients with influenza A subtypes and self-reported vaccinated, hospitalized influenza positive patients. Figure 1: Predicted Probability of Hospitalization with Influenza, Influenza A/H1N1 and Influenza A/H3N2 in Vaccinated Patients by Age. ConclusionOur study demonstrated an increased risk of influenza vaccine failure in older patients and immunosuppressed patients. These groups are also at increased risk for influenza complications. To improve protection of these patients against future influenza illnesses, more effective vaccines are needed, and more research on ring vaccination should be pursued.Disclosures All Authors: No reported disclosures

Vaccine Effectiveness Against Influenza-Associated Hospitalizations Among Adults, 2018-2019, US Hospitalized Adult Influenza Vaccine Effectiveness Network.

We estimated vaccine effectiveness (VE) for prevention of influenza-associated hospitalizations among adults during the 2018-2019 influenza season. Adults admitted with acute respiratory illness to 14 hospitals of the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) and testing positive for influenza were cases; patients testing negative were controls. VE was estimated using logistic regression and inverse probability of treatment weighting. We analyzed data from 2863 patients with a mean age of 63 years. Adjusted VE against influenza A(H1N1)pdm09-associated hospitalization was 51% (95% confidence interval [CI], 25%-68%). Adjusted VE against influenza A(H3N2) virus-associated hospitalization was -2% (95% CI, -65% to 37%) and differed significantly by age, with VE of -130% (95% CI, -374% to -27%) among adults 18 to ≤56 years of age. Although vaccination halved the risk of influenza A(H1N1)pdm09-associated hospitalizations, it conferred no protection against influenza A(H3N2)-associated hospitalizations. We observed negative VE for young and middle-aged adults but cannot exclude residual confounding as a potential explanation.

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

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. 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. 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%). 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.

2785. Respiratory Viral Panel Testing in Intensive Care Units: Effects on Outcomes

BackgroundAcute respiratory viral illnesses cause significant morbidity and mortality leading to high healthcare costs. Delayed viral pathogen diagnosis likely contributes to increases in morbidity and mortality. We aimed to analyze: (1) the use of respiratory viral panel (RVP) testing in adults hospitalized to intensive care units (ICUs) with acute respiratory illness (ARI) during flu season; and (2) if RVP testing is associated with improved outcomes.MethodsData from adults hospitalized to the ICU with ARI during the 2015–2016, 2016–2017, and 2017–2018 influenza seasons at 3 hospitals participating in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) study was analyzed. Details of disease severity, underlying health status, and vaccination status were obtained through enrollment interviews and medical records. Clinical RVP results were recorded. Research swabs for influenza (CDC PCR) were performed in all patients who did not have a clinical sample. Multivariate regression was used to estimate the associations between RVP and in-hospital complications.Results397 patients were enrolled; 263 (66%) had a clinical RVP done. 25% of patients with ≥ 1 CDC-defined high-risk condition for influenza complications did not have an RVP. 36 (9%) of patients had a positive RVP for flu (1 H1N1, 28 H3, 1 A no subtype, and 6 B). Mean time from onset of symptoms to RVP was 2.25 ± 2.24 days and mean time from ICU admission to RVP was 0.85 ± 1.27 days. 11 (8%) of patients who had only a research swab were positive for flu (1 A no subtype, others H3). 4 (36%) of these patients received oseltamivir. Use of antivirals was significantly more common in patients who had RVPs (68 vs 1%, pConclusionOne-third of patients admitted to the ICU with ARI during the flu season did not have an RVP, including 25% of patients with ≥ 1 high-risk condition for influenza complications. Influenza was present in 8% of patients who did not undergo clinical testing and 64% of these patients did not receive antivirals. There is room for improvement in ordering of RVPs in ICUs.Disclosures All authors: No reported disclosures.

2746. Effectiveness of Influenza Vaccine for Prevention of Influenza-associated Hospitalizations Among Immunocompromised Adults—2017–2018

BackgroundImmunocompromised (IC) individuals are at higher risk for severe complications of influenza. Little literature describes vaccine effectiveness (VE) in this population. We evaluated VE for prevention of influenza-associated hospitalization among IC adults.MethodsWe analyzed data from adults hospitalized with acute respiratory illness (ARI) during the 2017–2018 FLU season at 9 hospitals participating in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) study. Details of disease severity, underlying health status, and vaccination status were obtained through enrollment interviews and medical records. Prior year clinical encounter diagnoses and enrollment interviews were used to define IC groups. IC groups were mutually exclusive. VE was evaluated with a test-negative case–control design using multivariate logistic regression with PCR-confirmed influenza as the outcome and vaccination status as the exposure, adjusting for age, race, and other factors, and stratifying by immunocompromising conditions.ResultsOf 3524 adults hospitalized with ARI, 1210 (34%) had an immunocompromising condition. Chronic steroid (n = 397), chemo/radiation therapy (n = 242), hematologic condition (n = 175), and organ transplant (n = 144) were most common. HIV (n = 45) and stem cell transplant (SCT) (n = 28) were least common. IC patients were more likely to be vaccinated than non-IC (60% vs. 55%, P = 0.002). Overall, vaccination reduced risk of influenza hospitalization by 36% (95% CI: 24,46). Among IC adults, VE was 9% (95% CI: −25,34). VE was 32% (95% CI: 5,51) for chemo/radiation therapy, 29% (95% CI: 6,47) for chronic steroids, 29% (95% CI: -6,52) for hematologic conditions, −1% (95% CI: −50,32) for organ transplant, −48% (95% CI: −190,25) for HIV, and −154% (95% CI = −458,−15) for SCT (Figure 1).ConclusionVaccination reduced risk of influenza hospitalization among adults with the most prevalent immunocompromising conditions in our cohort; however, it had little to no effect in other groups, such as in HIV and organ and stem cell transplant recipients. Results support using other preventative strategies in addition to vaccinating adults with immunocompromising conditions, such as vaccination of close contacts. Disclosures All authors: No reported disclosures.

Prevention of Influenza Hospitalization Among Adults in the United States, 2015-2016: Results From the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN).

Evidence establishing effectiveness of influenza vaccination for prevention of severe illness is limited. The US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) is a multiyear test-negative case-control study initiated in 2015-2016 to estimate effectiveness of vaccine in preventing influenza hospitalization among adults. Adults aged ≥18 years admitted to 8 US hospitals with acute respiratory illness and testing positive for influenza by polymerase chain reaction were cases; those testing negative were controls. Vaccine effectiveness was estimated with logistic regression adjusting for age, comorbidities, and other confounding factors and stratified by frailty, 2-year vaccination history, and clinical presentation. We analyzed data from 236 cases and 1231 controls; mean age was 58 years. More than 90% of patients had ≥1 comorbidity elevating risk of influenza complications. Fifty percent of cases and 70% of controls were vaccinated. Vaccination was 51% (95% confidence interval [CI], 29%-65%) and 53% (95% CI, 11%-76%) effective in preventing hospitalization due to influenza A(H1N1)pdm09 and influenza B virus infection, respectively. Vaccine was protective for all age groups. During the 2015-2016 US influenza A(H1N1)pdm09-predominant season, we found that vaccination halved the risk of influenza-association hospitalization among adults, most of whom were at increased risk of serious influenza complications due to comorbidity or age.

995. Effectiveness of Influenza Vaccine for Prevention of Influenza-Associated Hospitalizations Among High-Risk Adults in the United States, 2015–2016

BackgroundIndividuals with cardiopulmonary and other chronic conditions are at increased risk for severe complications of influenza. Few studies have examined influenza vaccine effectiveness (VE) in high-risk groups. We evaluated VE against influenza-associated hospitalization among adults with specific high-risk conditions.MethodsAdults hospitalized with acute respiratory illness (ARI) during the 2015–2016 influenza season were enrolled at eight hospitals participating in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) study. Respiratory specimens were tested for influenza by reverse transcription PCR. Measures of illness severity, underlying health status, and vaccination were obtained from medical records and enrollment interviews. The presence of high-risk conditions was determined from clinical codes assigned to prior year medical encounters. We estimated VE using a test-negative design as (1 − adjusted odds ratio), comparing odds of PCR-confirmed influenza among vaccinated patients vs. unvaccinated controls. Multivariate logistic regression was adjusted for age, sex, and other factors, stratifying by chronic conditions.ResultsOf 1,467 adults hospitalized with ARI, 236 (16%) had PCR-confirmed influenza; 180 (78%) were A(H1N1)pdm09. In all, 1,358 (93%) had ≥1 high-risk medical condition, and 1,026 (70%) had ≥3 conditions. Cardiovascular (n = 835), metabolic (including diabetes) (n = 773) and lung conditions (n = 692) were most common (figure). Patients with ≥1 high-risk conditions were more likely to be vaccinated (70%) vs. patients not at high risk (31%, P < 0.001). Among all patients, VE against any influenza-associated hospitalization was 50% (95% CI: 31–63). VE was similarly high among patients with neurologic (VE = 64%, 95% CI: 26–83), metabolic (VE = 55%, 95% CI: 30–71), and cardiovascular (VE = 53%, 95% CI: 27–69) conditions, though lower for patients with immunosuppression and malignancy (VE = 20%, 95% CI: −42–54).ConclusionVaccination significantly reduced risk of influenza hospitalization among adults with the most prevalent high-risk cardiovascular, metabolic, and lung conditions. Results support the benefit of vaccinating adults with existing specific chronic conditions. 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.

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

BackgroundSeasonal 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).MethodsHospitalized 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.ResultsAmong 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).ConclusionComparison 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.

Estimated Hospitalization Rates for Seasonal Influenza in Adults and Children in Middle Tennessee using a Capture-Recapture Method

BackgroundOngoing surveillance of influenza activity is important to monitor variation in disease severity and vaccine effectiveness, but surveillance systems have limitations. The capture-recapture method aims to more comprehensively estimate disease burden by combining data from independent studies.MethodsResidents of 8 counties in Middle TN hospitalized with influenza during the 2015-16 influenza A(H1N1pdm09)-predominant season were identified using data from 3 independent CDC-sponsored programs. The Influenza Hospitalization Surveillance Network/Emerging Infections Program (FluSurv-Net/EIP) identifies adult and pediatric cases based on a positive clinician-ordered influenza test. The U.S. Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) and the New Vaccine Surveillance Network (NVSN) enroll adults (3 hospitals) and children (1 hospital), respectively, with respiratory symptoms with/without fever, and obtain nasal/throat swabs to identify cases of influenza; 2015–2016 was a pilot year for HAIVEN. Using the numbers of matched and unmatched cases detected by two studies, a capture-recapture analysis estimated the total number (N) of influenza-related hospitalizations in the population (Table 1). Due to small sample size, the Chapman equation was used, where N = ((a + b + 1)(a + c + 1)/(a + 1)) – 1. The capture–recapture estimates were adjusted for the hospitals’ market share for acute respiratory illness in middle TN residents (69.2% for children and 23.9% for adults) based on hospital discharge data.Table 1.Sample 2 × 2 table for capture–recapture Analysis HAIVEN or NVSNFluSurv-Net/EIPDetectedMissedDetected A b Missed c z a = cases identified by both studies (matches); b = cases identified by EIP only; c = cases identified by HAIVEN or NVSN only; z = estimated number of patients hospitalized with influenza not captured by either study. N = a + b + c + z ResultsCapture-recapture analyses based on unadjusted crude data are shown in Figure 1A and 1B. Age-specific rates of hospitalization were then calculated (Figure 1C).ConclusionUsing a capture–recapture method, we estimated influenza hospitalization rates of 0.87 (95% CI 0.06–1.68) and 0.80 (95% CI 0.62–0.98) per 1,000 persons among children and adults, respectively.Disclosures N. B. Halasa, sanofi pasteur: Research Contractor, Research support. Astra Zeneca: Research Contractor, Grant recipient. W. Schaffner, Pfizer: Scientific Advisor, Consulting fee. Merck: Scientific Advisor, Consulting fee. Novavax: Consultant, Consulting fee. Dynavax: Consultant, Consulting fee. Sanofi-pasteur: Consultant, Consulting fee. GSK: Consultant, Consulting fee. Seqirus: Consultant, Consulting fee. H. K. Talbot, Gilead: Investigator, Research support. MedImmune: Investigator, Research support. sanofi pasteur: Investigator, Research support. VaxInnate: Scientific Advisor, Consulting fee. Sequirus: Scientific Advisor, Consulting fee.