Timing of influenza antiviral therapy and risk of death in adults hospitalized with influenza-associated pneumonia, FluSurv-NET, 2012-2019.

BACKGROUND: Pneumonia is common in adults hospitalized with laboratory-confirmed influenza, but the association between timeliness of influenza antiviral treatment and severe clinical outcomes in patients with influenza-associated pneumonia is not well characterized. METHODS: We included adults aged ≥18 years hospitalized with laboratory-confirmed influenza and a discharge diagnosis of pneumonia over 7 influenza seasons (2012-2019) sampled from a multi-state population-based surveillance network. We evaluated 3 treatment groups based on timing of influenza antiviral initiation relative to admission date (day 0, day 1, days 2-5). Baseline characteristics and clinical outcomes were compared across groups using unweighted counts and weighted percentages accounting for the complex survey design. Logistic regression models were generated to evaluate the association between delayed treatment and 30-day all-cause mortality. RESULTS: 26,233 adults were sampled in the analysis. Median age was 71 years and most (92.2%) had ≥1 non-immunocompromising condition. Overall, 60.9% started antiviral treatment on day 0, 29.5% on day 1, and 9.7% on days 2-5 (median 2 days). Baseline characteristics were similar across groups. Thirty-day mortality occurred in 7.5%, 8.5%, and 10.2% of patients who started treatment on day 0, day 1, and days 2-5, respectively. Compared to those treated on day 0, adjusted OR for death was 1.14 (95%CI: 1.01-1.27) in those starting treatment on day 1 and 1.40 (95%CI: 1.17-1.66) in those starting on days 2-5. DISCUSSION: Delayed initiation of antiviral treatment in patients hospitalized with influenza-associated pneumonia was associated with higher risk of death, highlighting the importance of timely initiation of antiviral treatment at admission.

Increased Antiviral Treatment Among Hospitalized Children and Adults With Laboratory-Confirmed Influenza, 2010-2015.

(See the Editorial Commentary by Martin on pages 368-9.)Using population-based surveillance data, we analyzed antiviral treatment among hospitalized patients with laboratory-confirmed influenza. Treatment increased after the influenza A(H1N1) 2009 pandemic from 72% in 2010-2011 to 89% in 2014-2015 (P < .001). Overall, treatment was higher in adults (86%) than in children (72%); only 56% of cases received antivirals on the day of admission.

Influenza-Related Hospitalizations and Poverty Levels - United States, 2010-2012.

Annual influenza vaccine is recommended for all persons aged ≥6 months in the United States, with recognition that some persons are at risk for more severe disease (1). However, there might be previously unrecognized demographic groups that also experience higher rates of serious influenza-related disease that could benefit from enhanced vaccination efforts. Socioeconomic status (SES) measures that are area-based can be used to define demographic groups when individual SES data are not available (2). Previous surveillance data analyses in limited geographic areas indicated that influenza-related hospitalization incidence was higher for persons residing in census tracts that included a higher percentage of persons living below the federal poverty level (3-5). To determine whether this association occurs elsewhere, influenza hospitalization data collected in 14 FluSurv-NET sites covering 27 million persons during the 2010-11 and 2011-12 influenza seasons were analyzed. The age-adjusted incidence of influenza-related hospitalizations per 100,000 person-years in high poverty (≥20% of persons living below the federal poverty level) census tracts was 21.5 (95% confidence interval [CI]: 20.7-22.4), nearly twice the incidence in low poverty (<5% of persons living below the federal poverty level) census tracts (10.9, 95% CI: 10.3-11.4). This relationship was observed in each surveillance site, among children and adults, and across racial/ethnic groups. These findings suggest that persons living in poorer census tracts should be targeted for enhanced influenza vaccination outreach and clinicians serving these persons should be made aware of current recommendations for use of antiviral agents to treat influenza (6).

Does Influenza Vaccination Modify Influenza Severity? Data on Older Adults Hospitalized With Influenza During the 2012-2013 Season in the United States.

BACKGROUND: Some studies suggest that influenza vaccination might be protective against severe influenza outcomes in vaccinated persons who become infected. We used data from a large surveillance network to further investigate the effect of influenza vaccination on influenza severity in adults aged ≥50 years who were hospitalized with laboratory-confirmed influenza. METHODS: We analyzed influenza vaccination and influenza severity using Influenza Hospitalization Surveillance Network (FluSurv-NET) data for the 2012-2013 influenza season. Intensive care unit (ICU) admission, death, diagnosis of pneumonia, and hospital and ICU lengths of stay served as measures of disease severity. Data were analyzed by multivariable logistic regression, parametric survival models, and propensity score matching (PSM). RESULTS: Overall, no differences in severity were observed in the multivariable logistic regression model. Using PSM, adults aged 50-64 years (but not other age groups) who were vaccinated against influenza had a shorter length of ICU stay than those who were unvaccinated (hazard ratio for discharge, 1.84; 95% confidence interval, 1.12-3.01). CONCLUSIONS: Our findings show a modest effect of influenza vaccination on disease severity. Analysis of data from seasons with different predominant strains and higher estimates of vaccine effectiveness are needed.

Obesity not associated with severity among hospitalized adults with seasonal influenza virus infection.

We examined seasonal influenza severity [artificial ventilation, intensive care unit (ICU) admission, and radiographic-confirmed pneumonia] by weight category among adults hospitalized with laboratory-confirmed influenza. Using multivariate logistic regression models, we found no association between obesity or severe obesity and artificial ventilation or ICU admission; however, overweight and obese patients had decreased risk of pneumonia. Underweight was associated with pneumonia (adjusted odds ratio 1.31; 95 % confidence interval 1.04, 1.64).

Severity of influenza-associated hospitalisations by influenza virus type and subtype in the USA, 2010-19: a repeated cross-sectional study.

BACKGROUND: Influenza burden varies across seasons, partly due to differences in circulating influenza virus types or subtypes. Using data from the US population-based surveillance system, Influenza Hospitalization Surveillance Network (FluSurv-NET), we aimed to assess the severity of influenza-associated outcomes in individuals hospitalised with laboratory-confirmed influenza virus infections during the 2010-11 to 2018-19 influenza seasons. METHODS: To evaluate the association between influenza virus type or subtype causing the infection (influenza A H3N2, A H1N1pdm09, and B viruses) and in-hospital severity outcomes (intensive care unit [ICU] admission, use of mechanical ventilation or extracorporeal membrane oxygenation [ECMO], and death), we used FluSurv-NET to capture data for laboratory-confirmed influenza-associated hospitalisations from the 2010-11 to 2018-19 influenza seasons for individuals of all ages living in select counties in 13 US states. All individuals had to have an influenza virus test within 14 days before or during their hospital stay and an admission date between Oct 1 and April 30 of an influenza season. Exclusion criteria were individuals who did not have a complete chart review; cases from sites that contributed data for three or fewer seasons; hospital-onset cases; cases with unidentified influenza type; cases of multiple influenza virus type or subtype co-infection; or individuals younger than 6 months and ineligible for the influenza vaccine. Logistic regression models adjusted for influenza season, influenza vaccination status, age, and FluSurv-NET site compared odds of in-hospital severity by virus type or subtype. When missing, influenza A subtypes were imputed using chained equations of known subtypes by season. FINDINGS: Data for 122 941 individuals hospitalised with influenza were captured in FluSurv-NET from the 2010-11 to 2018-19 seasons; after exclusions were applied, 107 941 individuals remained and underwent influenza A virus imputation when missing A subtype (43·4%). After imputation, data for 104 969 remained and were included in the final analytic sample. Averaging across imputed datasets, 57·7% (weighted percentage) had influenza A H3N2, 24·6% had influenza A H1N1pdm09, and 17·7% had influenza B virus infections; 16·7% required ICU admission, 6·5% received mechanical ventilation or ECMO, and 3·0% died (95% CIs had a range of less than 0·1% and are not displayed). Individuals with A H1N1pdm09 had higher odds of in-hospital severe outcomes than those with A H3N2: adjusted odds ratios (ORs) for A H1N1pdm09 versus A H3N2 were 1·42 (95% CI 1·32-1·52) for ICU admission; 1·79 (1·60-2·00) for mechanical ventilation or ECMO use; and 1·25 (1·07-1·46) for death. The adjusted ORs for individuals infected with influenza B versus influenza A H3N2 were 1·06 (95% CI 1·01-1·12) for ICU admission, 1·14 (1·05-1·24) for mechanical ventilation or ECMO use, and 1·18 (1·07-1·31) for death. INTERPRETATION: Despite a higher burden of hospitalisations with influenza A H3N2, we found an increased likelihood of in-hospital severe outcomes in individuals hospitalised with influenza A H1N1pdm09 or influenza B virus. Thus, it is important for individuals to receive an annual influenza vaccine and for health-care providers to provide early antiviral treatment for patients with suspected influenza who are at increased risk of severe outcomes, not only when there is high influenza A H3N2 virus circulation but also when influenza A H1N1pdm09 and influenza B viruses are circulating. FUNDING: The US Centers for Disease Control and Prevention.

Influenza Antiviral Use in Patients Hospitalized With Laboratory-Confirmed Influenza in the United States, FluSurv-NET, 2015-2019.

From surveillance data of patients hospitalized with laboratory-confirmed influenza in the United States during the 2015-2016 through 2018-2019 seasons, initiation of antiviral treatment increased from 86% to 94%, with increases seen across all age groups. However, 62% started therapy ≥3 days after illness onset, driven by late presentation to care.

Association of Chronic Medical Conditions With Severe Outcomes Among Nonpregnant Adults 18-49 Years Old Hospitalized With Influenza, FluSurv-NET, 2011-2019.

Background: Older age and chronic conditions are associated with severe influenza outcomes; however, data are only comprehensively available for adults ≥65 years old. Using data from the Influenza Hospitalization Surveillance Network (FluSurv-NET), we identified characteristics associated with severe outcomes in adults 18-49 years old hospitalized with influenza. Methods: We included FluSurv-NET data from nonpregnant adults 18-49 years old hospitalized with laboratory-confirmed influenza during the 2011-2012 through 2018-2019 seasons. We used bivariate and multivariable logistic regression to determine associations between select characteristics and severe outcomes including intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and in-hospital death. Results: A total of 16 140 patients aged 18-49 years and hospitalized with influenza were included in the analysis; the median age was 39 years, and 26% received current-season influenza vaccine before hospitalization. Obesity, asthma, and diabetes mellitus were the most common chronic conditions. Conditions associated with a significantly increased risk of severe outcomes included age group 30-39 or 40-49 years (IMV, age group 30-39 years: adjusted odds ratio [aOR], 1.25; IMV, age group 40-49 years: aOR, 1.36; death, age group 30-39 years: aOR, 1.28; death, age group 40-49 years: aOR, 1.69), being unvaccinated (ICU: aOR, 1.18; IMV: aOR, 1.25; death: aOR, 1.48), and having chronic conditions including extreme obesity and chronic lung, cardiovascular, metabolic, neurologic, or liver diseases (ICU: range aOR, 1.22-1.56; IMV: range aOR, 1.17-1.54; death: range aOR, 1.43-2.36). Conclusions: To reduce the morbidity and mortality associated with influenza among adults aged 18-49 years, health care providers should strongly encourage receipt of annual influenza vaccine and lifestyle/behavioral modifications, particularly among those with chronic medical conditions.

Spatial and temporal clustering of patients hospitalized with laboratory-confirmed influenza in the United States.

BACKGROUND: Timing of influenza spread across the United States is dependent on factors including local and national travel patterns and climate. Local epidemic intensity may be influenced by social, economic and demographic patterns. Data are needed to better explain how local socioeconomic factors influence both the timing and intensity of influenza seasons to result in national patterns. METHODS: To determine the spatial and temporal impacts of socioeconomics on influenza hospitalization burden and timing, we used population-based laboratory-confirmed influenza hospitalization surveillance data from the CDC-sponsored Influenza Hospitalization Surveillance Network (FluSurv-NET) at up to 14 sites from the 2009/2010 through 2013/2014 seasons (n = 35,493 hospitalizations). We used a spatial scan statistic and spatiotemporal wavelet analysis, to compare temporal patterns of influenza spread between counties and across the country. RESULTS: There were 56 spatial clusters identified in the unadjusted scan statistic analysis using data from the 2010/2011 through the 2013/2014 seasons, with relative risks (RRs) ranging from 0.09 to 4.20. After adjustment for socioeconomic factors, there were five clusters identified with RRs ranging from 0.21 to 1.20. In the wavelet analysis, most sites were in phase synchrony with one another for most years, except for the H1N1 pandemic year (2009-2010), wherein most sites had differential epidemic timing from the referent site in Georgia. CONCLUSIONS: Socioeconomic factors strongly impact local influenza hospitalization burden. Influenza phase synchrony varies by year and by socioeconomics, but is less influenced by socioeconomics than is disease burden.

Impact of pregnancy on observed sex disparities among adults hospitalized with laboratory-confirmed influenza, FluSurv-NET, 2010-2012.

INTRODUCTION: Previous FluSurv-NET studies found that adult females had a higher incidence of influenza-associated hospitalizations than males. To identify groups of women at higher risk than men, we analyzed data from 14 FluSurv-NET sites that conducted population-based surveillance for laboratory-confirmed influenza-associated hospitalizations among residents of 78 US counties. METHODS: We analyzed 6292 laboratory-confirmed, geocodable (96%) adult cases collected by FluSurv-NET during the 2010-12 influenza seasons. We used 2010 US Census and 2008-2012 American Community Survey data to calculate overall age-adjusted and age group-specific female:male incidence rate ratios (IRR) by race/ethnicity and census tract-level poverty. We used national 2010 pregnancy rates to estimate denominators for pregnant women aged 18-49. We calculated male:female IRRs excluding them and IRRs for pregnant:non-pregnant women. RESULTS: Overall, 55% of laboratory-confirmed influenza cases were female. Female:male IRRs were highest for females aged 18-49 of high neighborhood poverty (IRR 1.50, 95% CI 1.30-1.74) and of Hispanic ethnicity (IRR 1.70, 95% CI 1.34-2.17). These differences disappeared after excluding pregnant women. Overall, 26% of 1083 hospitalized females aged 18-49 were pregnant. Pregnant adult females were more likely to have influenza-associated hospitalizations than their non-pregnant counterparts (relative risk [RR] 5.86, 95% CI 5.12-6.71), but vaccination levels were similar (25.5% vs 27.8%). CONCLUSIONS: Overall rates of influenza-associated hospitalization were not significantly different for men and women after excluding pregnant women. Among women aged 18-49, pregnancy increased the risk of influenza-associated hospitalization sixfold but did not increase the likelihood of vaccination. Improving vaccination rates in pregnant women should be an influenza vaccination priority.

Social determinants of influenza hospitalization in the United States.

BACKGROUND: Influenza hospitalizations result in substantial morbidity and mortality each year. Little is known about the association between influenza hospitalization and census tract-based socioeconomic determinants beyond the effect of individual factors. OBJECTIVE: To evaluate whether census tract-based determinants such as poverty and household crowding would contribute significantly to the risk of influenza hospitalization above and beyond individual-level determinants. METHODS: We analyzed 33 515 laboratory-confirmed influenza-associated hospitalizations that occurred during the 2009-2010 through 2013-2014 influenza seasons using a population-based surveillance system at 14 sites across the United States. RESULTS: Using a multilevel regression model, we found that individual factors were associated with influenza hospitalization with the highest adjusted odds ratio (AOR) of 9.20 (95% CI 8.72-9.70) for those ≥65 vs 5-17 years old. African Americans had an AOR of 1.67 (95% CI 1.60-1.73) compared to Whites, and Hispanics had an AOR of 1.21 (95% CI 1.16-1.26) compared to non-Hispanics. Among census tract-based determinants, those living in a tract with ≥20% vs <5% of persons living below poverty had an AOR of 1.31 (95% CI 1.16-1.47), those living in a tract with ≥5% vs <5% of persons living in crowded conditions had an AOR of 1.17 (95% CI 1.11-1.23), and those living in a tract with ≥40% vs <5% female heads of household had an AOR of 1.32 (95% CI 1.25-1.40). CONCLUSION: Census tract-based determinants account for 11% of the variability in influenza hospitalization.

Survey of influenza and other respiratory viruses diagnostic testing in US hospitals, 2012-2013.

BACKGROUND: Little is known about laboratory capacity to routinely diagnose influenza and other respiratory viruses at clinical laboratories and hospitals. AIMS: We sought to assess diagnostic practices for influenza and other respiratory virus in a survey of hospitals and laboratories participating in the US Influenza Hospitalization Surveillance Network in 2012-2013. MATERIALS AND METHODS: All hospitals and their associated laboratories participating in the Influenza Hospitalization Surveillance Network (FluSurv-NET) were included in this evaluation. The network covers more than 80 counties in 15 states, CA, CO, CT, GA, MD, MN, NM, NY, OR, TN, IA, MI, OH, RI, and UT, with a catchment population of ~28 million people. We administered a standardized questionnaire to key personnel, including infection control practitioners and laboratory departments, at each hospital through telephone interviews. RESULTS: Of the 240 participating laboratories, 67% relied only on commercially available rapid influenza diagnostic tests to diagnose influenza. Few reported the availability of molecular diagnostic assays for detection of influenza (26%) and other viral pathogens (≤20%) in hospitals and commercial laboratories. CONCLUSION: Reliance on insensitive assays to detect influenza may detract from optimal clinical management of influenza infections in hospitals.