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Background: While the estimated number of U.S. influenza-associated deaths is reported annually, detailed data on the epidemiology of influenza-associated deaths, including the burden of in-hospital versus post-hospital discharge deaths are limited., Methods: Using data from the 2010-11 through 2018-19 seasons from the Influenza Hospitalization Surveillance Network, we linked cases to death certificates to identify patients who died from any cause during their influenza hospital stay or within 30 days post discharge. We described demographic and clinical characteristics of patients who died in hospital versus post discharge and characterized locations and causes of death (COD)., Results: Among 121,390 cases hospitalized with laboratory-confirmed influenza over 9 seasons, 5.5% died; 76% of deaths were in patients ≥65 years, 71% were non-Hispanic White, and 34% had ≥4 underlying medical conditions. Among all patients with an influenza-associated hospitalization who died, 48% of deaths occurred after hospital discharge; the median days from discharge to death was 9 days (IQR 3-19 days). Post-discharge deaths more often occurred in older patients and among those with underlying medical conditions. Only 37% of patients who died had "influenza" as a COD on their death certificate. Influenza was more frequently listed as a COD among persons who died in-hospital compared with cardiovascular disease among those who died after discharge., Conclusions: All-cause mortality burden is substantial among patients hospitalized with influenza, with almost 50% of deaths occurring within 30 days after hospital discharge. Surveillance systems should consider capture of post-discharge outcomes to better characterize the impact of influenza on all-cause mortality., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Problem/condition: Seasonal influenza accounts for 9.3 million-41 million illnesses, 100,000-710,000 hospitalizations, and 4,900-51,000 deaths annually in the United States. Since 2003, the Influenza Hospitalization Surveillance Network (FluSurv-NET) has been conducting population-based surveillance for laboratory-confirmed influenza-associated hospitalizations in the United States, including weekly rate estimations and descriptions of clinical characteristics and outcomes for hospitalized patients. However, a comprehensive summary of trends in hospitalization rates and clinical data collected from the surveillance platform has not been available., Reporting Period: 2010-11 through 2022-23 influenza seasons., Description of System: FluSurv-NET conducts population-based surveillance for laboratory-confirmed influenza-associated hospitalizations among children and adults. During the reporting period, the surveillance network included 13-16 participating sites each influenza season, with prespecified geographic catchment areas that covered 27 million-29 million persons and included an estimated 8.8%-9.5% of the U.S. population. A case was defined as a person residing in the catchment area within one of the participating states who had a positive influenza laboratory test result within 14 days before or at any time during their hospitalization. Each site abstracted case data from hospital medical records into a standardized case report form, with selected variables submitted to CDC on a weekly basis for rate estimations. Weekly and cumulative laboratory-confirmed influenza-associated hospitalization rates per 100,000 population were calculated for each season from 2010-11 through 2022-23 and stratified by patient age (0-4 years, 5-17 years, 18-49 years, 50-64 years, and ≥65 years), sex, race and ethnicity, influenza type, and influenza A subtype. During the 2020-21 season, only the overall influenza hospitalization rate was reported because case counts were insufficient to estimate stratified rates., Results: During the 2010-11 to 2022-23 influenza seasons, laboratory-confirmed influenza-associated hospitalization rates varied significantly across seasons. 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. After SARS-CoV-2 emerged, the hospitalization rate for 2020-21 was 0.8, and the rate did not return to recent prepandemic levels until 2022-23. Inconsistent seasonality also was observed during 2020-21 through 2022-23, with influenza activity being very low during 2020-21, extending later than usual during 2021-22, and occurring early during 2022-23. Molecular assays, particularly multiplex standard molecular assays, were the most common influenza test type in recent seasons, increasing from 12% during 2017-18 for both pediatric and adult cases to 43% and 55% during 2022-23 for pediatric and adult cases, respectively. During each season, adults aged ≥65 years consistently had the highest influenza-associated hospitalization rate across all age groups, followed in most seasons by children aged 0-4 years. Black or African American and American Indian or Alaska Native persons had the highest age-adjusted influenza-associated hospitalization rates across these seasons. Among patients hospitalized with influenza, the prevalence of at least one underlying medical condition increased with increasing age, ranging from 36.9% among children aged 0-4 years to 95.4% among adults aged ≥65 years. Consistently across each season, the most common underlying medical conditions among children and adolescents were asthma, neurologic disorders, and obesity. The most common underlying medical conditions among adults were hypertension, obesity, chronic metabolic disease, chronic lung disease, and cardiovascular disease. The proportion of FluSurv-NET patients with acute respiratory signs and symptoms at hospital admission decreased from 90.6% during 2018-19 to 83.2% during 2022-23. Although influenza antiviral use increased during the 2010-11 through the 2017-18 influenza seasons, it decreased from 90.2% during 2018-19 to 79.1% during 2022-23, particularly among children and adolescents. 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., Interpretations: Influenza continues to cause severe morbidity and mortality, particularly in older adults, and disparities have persisted in racial and ethnic minority groups. Persons with underlying medical conditions represented a large proportion of patients hospitalized with influenza. Increased use of multiplex tests and other potential changes in facility-level influenza testing practices (e.g., influenza screening at all hospital admissions) could have implications for the detection of influenza infections among hospitalized patients. Antiviral use decreased in recent seasons, and explanations for the decrease should be further evaluated., Public Health Action: Continued robust influenza surveillance is critical to monitor progress in efforts to encourage antiviral treatment and improve clinical outcomes for persons hospitalized with influenza. In addition, robust influenza surveillance can potentially reduce disparities by informing efforts to increase access to preventive measures for influenza and monitoring any subsequent changes in hospitalization rates., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Andrea George reported that her institution (Salt Lake County Health Department) receives grant funds from Council of State and Territorial Epidemiologists. Justin Henderson reported receiving grant funds from CDC to conduct the Michigan Emerging Infections Program; grant funds from Council of State and Territorial Epidemiologists to conduct work on Respiratory Virus Hospitalization Network. Ruth Lynfield reported receiving grant funds for a cooperative agreement between CDC and Minnesota Department of Health to conduct Minnesota Emerging Infections Program; attendance at Council of State and Territorial Epidemiologists, American Academy of Pediatrics Committee on Infections Diseases, National Foundation for Infectious Diseases, and Infectious Diseases Week meetings with support from Council of State and Territorial Epidemiologists, National Foundation for Infectious Diseases, and Infectious Diseases Society of America; voluntary positions of Council of State and Territorial Epidemiologists executive officer, American Academy of Pediatrics Red Book associate editor, National Foundation for Infectious Diseases secretary, and Infectious Diseases Week Program Committee; received fee for work as American Academy of Pediatrics Red Book associate editor; donated to Minnesota Department of Health. James Meek reported receiving grant funds from CDC to conduct the Connecticut Emerging Infections Program. Maya L. Monroe reported receiving grant funds from CDC to conduct the Maryland Emerging Infections Program. Angelle Naquin reported one-time funding support for attending meetings, travel, or both from Council of State and Territorial Epidemiologists. William Schaffner reported his institution receiving grant funds for a cooperative agreement between CDC and Vanderbilt University Medical Center to conduct Tennessee Emerging Infections Program. Yomei P. Shaw reported receiving grant funds from CDC to conduct the New Mexico Emerging Infections Program at New Mexico Department of Health; receives funding from CDC to attend annual surveillance officer and principal investigator meetings. Eli Shiltz reported grant funding for the population-based Influenza Hospitalization Surveillance Project and COVID-NET activities from Council of State and Territorial Epidemiologists; recipient of Epidemiology and Laboratory Capacity and Immunizations and Vaccines for Children grant funding from CDC. Devi Sundaresan reported one-time funding support for attending meetings, travel, or both from Council of State and Territorial Epidemiologists. H. Keipp Talbot reported receiving CDC research grants. Val Tellez Nunez reported receiving grant funds from Council of State and Territorial Epidemiologists. Brenda L. Tesini reported receiving a stipend for participation on Merck Manuals editorial board, independent from pharmaceutical branch of company. Dawud Ujamaa reported one-time funding support for attending meetings, travel, or both from Council of State and Territorial Epidemiologists. Lucy Witt reported participation as a site investigator for Merck & Co. from February 2022 through February 2024 for work not related to this report; unpaid participation on Infection Control Today editorial advisory board, MJH Life Sciences. Kimberly Yousey-Hindes reported receiving grant funds from CDC to conduct the Connecticut Emerging Infections Program. No other conflicts of interest were reported.

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., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)