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Background Current understanding of severe respiratory syncytial virus (RSV) infections in adults is limited by clinical underrecognition. We compared the prevalence, clinical characteristics, and outcomes of RSV infections vs influenza in adults hospitalized with acute respiratory illnesses (ARIs) in a prospective national surveillance network. Methods Hospitalized adults who met a standardized ARI case definition were prospectively enrolled across 3 respiratory seasons from hospitals participating across all sites of the US Hospitalized Adult Influenza Vaccine Effectiveness Network (2016–2019). All participants were tested for RSV and influenza using real-time reverse-transcription polymerase chain reaction assay. Multivariable logistic regression was used to test associations between laboratory-confirmed infection and characteristics and clinical outcomes. Results Among 10 311 hospitalized adults, 6% tested positive for RSV (n = 622), 18.8% for influenza (n = 1940), and 75.1% negative for RSV and influenza (n = 7749). Congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) was more frequent with RSV than influenza (CHF: 37.3% vs 28.8%, P <.0001; COPD: 47.6% vs 35.8%, P <.0001). Patients with RSV more frequently had longer admissions (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.06–1.80) for stays >1 week) and mechanical ventilation (OR, 1.45; 95% CI, 1.09–1.93) compared with influenza but not compared with the influenza-negative group (OR, 1.03; 95% CI,.82–1.28 and OR, 1.17; 95% CI,.91–1.49, respectively). Conclusions The prevalence of RSV across 3 seasons was considerable. Our findings suggest that those with RSV have worse outcomes compared with influenza and frequently have cardiopulmonary conditions. This study informs future vaccination strategies and underscores a need for RSV surveillance among adults with severe ARI. [ABSTRACT FROM AUTHOR]

Background Relative vaccine effectiveness (rVE) are metrics commonly reported to compare absolute VE (aVE) of 2 vaccine products. Methods Estimates of rVE for enhanced influenza vaccines (eIV) vs standard inactivated influenza vaccine (IIV) have been assessed across different seasons, influenza-specific endpoints, and nonspecific endpoints (eg, all-cause cardiovascular hospitalizations). To illustrate the challenges of comparability across studies, we conducted a scenario analysis to evaluate the effects of varying absolute VE (aVE) of IIV (ie, as compared with placebo) on the interpretation of rVE of eIV vs IIV. Results We show that estimates of rVE might not be comparable across studies because additional benefits commensurate with a given estimate of rVE are dependent on the aVE for the comparator vaccine, which can depend on factors such as host response to vaccine, virus type, and clinical endpoint evaluated. Conclusions These findings have implications for interpretation of rVE across studies and for sample size considerations in future trials. [ABSTRACT FROM AUTHOR]

Background 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). Methods 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. Results 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%). Conclusions 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. [ABSTRACT FROM AUTHOR]

Background Novel coronavirus disease 2019 (COVID-19) is frequently compared with influenza. The Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) conducts studies on the etiology and characteristics of U.S. hospitalized adults with influenza. It began enrolling patients with COVID-19 hospitalizations in March 2020. Patients with influenza were compared with those with COVID-19 in the first months of the U.S. epidemic. Methods Adults aged ≥ 18 years admitted to hospitals in 4 sites with acute respiratory illness were tested by real-time reverse transcription polymerase chain reaction for influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19. Demographic and illness characteristics were collected for influenza illnesses during 3 seasons 2016–2019. Similar data were collected on COVID-19 cases admitted before June 19, 2020. Results Age groups hospitalized with COVID-19 (n = 914) were similar to those admitted with influenza (n = 1937); 80% of patients with influenza and 75% of patients with COVID-19 were aged ≥50 years. Deaths from COVID-19 that occurred in younger patients were less often related to underlying conditions. White non-Hispanic persons were overrepresented in influenza (64%) compared with COVID-19 hospitalizations (37%). Greater severity and complications occurred with COVID-19 including more ICU admissions (AOR = 15.3 [95% CI: 11.6, 20.3]), ventilator use (AOR = 15.6 [95% CI: 10.7, 22.8]), 7 additional days of hospital stay in those discharged alive, and death during hospitalization (AOR = 19.8 [95% CI: 12.0, 32.7]). Conclusions While COVID-19 can cause a respiratory illness like influenza, it is associated with significantly greater severity of illness, longer hospital stays, and higher in-hospital deaths. [ABSTRACT FROM AUTHOR]

Background Yearly influenza immunization is recommended for immunocompromised (IC) individuals, although immune responses are lower than that for the nonimmunocompromised and the data on vaccine effectiveness (VE) in the IC is scarce. We evaluated VE against influenza-associated hospitalization among IC adults. Methods We analyzed data from adults ≥ 18 years hospitalized with acute respiratory illness (ARI) during the 2017–2018 influenza season at 10 hospitals in the United States. IC adults were identified using prespecified case definitions using electronic medical record data. VE was evaluated with a test-negative case-control design using multivariable logistic regression with polymerase chain reaction–confirmed influenza as the outcome and vaccination status as the exposure, adjusting for age, enrolling site, illness onset date, race, days from onset to specimen collection, self-reported health, and self-reported hospitalizations. Results Of 3524 adults hospitalized with ARI, 1210 (34.3%) had an immunocompromising condition. IC adults were more likely to be vaccinated than non-IC (69.5% vs 65.2%) and less likely to have influenza (22% vs 27.8%). The mean age did not differ among IC and non-IC (61.4 vs 60.8 years of age). The overall VE against influenza hospitalization, including immunocompetent adults, was 33% (95% confidence interval [CI], 21–44). VE among IC vs non-IC adults was lower at 5% (95% CI, –29% to 31%) vs 41% (95% CI, 27–52) (P <.05 for interaction term). Conclusions VE in 1 influenza season was very low among IC individuals. Future efforts should include evaluation of VE among the different immunocompromising conditions and whether enhanced vaccines improve the suboptimal effectiveness among the immunocompromised. [ABSTRACT FROM AUTHOR]

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 hospitalization 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 vs test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups.Results: A total of 3116 participants were included, including 18% (n = 553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (n = 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 2 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 VE was observed against the other group (5A + 156K) (-1% [95% CI, -61% to 37%]).Conclusions: In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The 2016-2017 and 2017-2018 influenza seasons were notable for the high number of hospitalizations for influenza A(H3N2) despite vaccine and circulating strain match.Methods: We evaluated vaccine effectiveness (VE) against hospitalization in the test-negative HAIVEN study. Nasal-throat swabs were tested by quantitative reverse transcription polymerase chain reaction (RT-PCR) for influenza and VE was determined based on odds of vaccination by generalized estimating equations. Vaccine-specific antibody was measured in a subset of enrollees.Results: A total of 6129 adults were enrolled from 10 hospitals. Adjusted VE against A(H3N2) was 22.8% (95% confidence interval [CI], 8.3% to 35.0%), pooled across both years and 49.4% (95% CI, 34.3% to 61.1%) against B/Yamagata. In 2017-2018, the A(H3N2) VE point estimate for the cell-based vaccine was 43.0% (95% CI, -36.3% to 76.1%; 56 vaccine recipients) compared to 24.0% (95% CI, 3.9% to 39.9%) for egg-based vaccines. Among 643 with serology data, hemagglutinin antibodies against the egg-based A(H3N2) vaccine strain were increased in influenza-negative individuals.Conclusions: Low VE for the A/Hong Kong/4801/2014 vaccine virus in both A(H3N2) seasons emphasizes concerns for continued changes in H3N2 antigenic epitopes, including changes that may impact glycosylation and ultimately reduce VE. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Statins are used to reduce cardiovascular disease risk. Recent studies suggest that statin use may be associated with an increased influenza risk among influenza vaccinees. We used Medicare data to evaluate associations between statins and risks of influenza-related encounters among vaccinees. Methods In this retrospective cohort study, we identified Medicare beneficiaries aged > 65 years who received high-dose (HD) or standard-dose (SD) influenza vaccines at pharmacies from 2010–2011 through 2014–2015. Statin users were matched to nonusers by vaccine type, demographics, prior medical encounters, and comorbidities. We used multivariable Poisson models to estimate associations between statin use around the time of vaccination and risk of influenza-related encounters. Study outcomes included influenza-related office visits with a rapid test followed by dispensing of oseltamivir and influenza-related hospitalizations (including emergency room visits) during high influenza circulation periods. Results The study included 1403651 statin users matched to nonusers. Cohorts were well balanced, with standardized mean differences ≤0.03 for all measured covariates. For statin users compared to nonusers, the adjusted relative risk was 1.086 (95% confidence interval [CI], 1.025–1.150) for influenza-related visits and 1.096 (95% CI, 1.013–1.185) for influenza-related hospitalizations. The risk difference ranged from ‒0.02 to 0.23 for influenza-related visits and from ‒0.04 to 0.13 for hospitalizations, depending on season severity. Results were similar for HD and SD vaccinees and for nonsynthetic and synthetic statin users. Conclusions Among 2.8 million Medicare beneficiaries, these results suggest that statin use around the time of vaccination does not substantially affect the risk of influenza-related medical encounters among older adults. [ABSTRACT FROM AUTHOR]

Background: The test-negative design (TND) to evaluate influenza vaccine effectiveness is based on patients seeking care for acute respiratory infection, with those who test positive for influenza as cases and the test-negatives serving as controls. This design has not been validated for the inpatient setting where selection bias might be different from an outpatient setting.Methods: We derived mathematical expressions for vaccine effectiveness (VE) against laboratory-confirmed influenza hospitalizations and used numerical simulations to verify theoretical results exploring expected biases under various scenarios. We explored meaningful interpretations of VE estimates from inpatient TND studies.Results: VE estimates from inpatient TND studies capture the vaccine-mediated protection of the source population against laboratory-confirmed influenza hospitalizations. If vaccination does not modify disease severity, these estimates are equivalent to VE against influenza virus infection. If chronic cardiopulmonary individuals are enrolled because of non-infectious exacerbation, biased VE estimates (too high) will result. If chronic cardiopulmonary disease status is adjusted for accurately, the VE estimates will be unbiased. If chronic cardiopulmonary illness cannot be adequately be characterized, excluding these individuals may provide unbiased VE estimates.Conclusions: The inpatient TND offers logistic advantages and can provide valid estimates of influenza VE. If highly vaccinated patients with respiratory exacerbation of chronic cardiopulmonary conditions are eligible for study inclusion, biased VE estimates will result unless this group is well characterized and the analysis can adequately adjust for it. Otherwise, such groups of subjects should be excluded from the analysis. [ABSTRACT FROM AUTHOR]