BACKGROUND: Influenza is a substantial cause of annual morbidity and mortality; however, correctly identifying those patients at increased risk for severe disease is often challenging. Several severity indices have been developed; however, these scores have not been validated for use in patients with influenza. We evaluated the discrimination of three clinical disease severity scores in predicting severe influenza-associated outcomes. METHODS: We used data from the Influenza Hospitalization Surveillance Network to assess outcomes of patients hospitalized with influenza in the United States during the 2017-2018 influenza season. We computed patient scores at admission for three widely used disease severity scores: CURB-65, Quick Sepsis-Related Organ Failure Assessment (qSOFA), and the Pneumonia Severity Index (PSI). We then grouped patients with severe outcomes into four severity tiers, ranging from ICU admission to death, and calculated receiver operating characteristic (ROC) curves for each severity index in predicting these tiers of severe outcomes. RESULTS: Among 8252 patients included in this study, we found that all tested severity scores had higher discrimination for more severe outcomes, including death, and poorer discrimination for less severe outcomes, such as ICU admission. We observed the highest discrimination for PSI against in-hospital mortality, at 0.78. CONCLUSIONS: We observed low to moderate discrimination of all three scores in predicting severe outcomes among adults hospitalized with influenza. Given the substantial annual burden of influenza disease in the United States, identifying a prediction index for severe outcomes in adults requiring hospitalization with influenza would be beneficial for patient triage and clinical decision-making.

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 eight 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 two U.S. 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.

Annual seasonal influenza epidemics of variable severity result in significant morbidity and mortality in the United States (U.S.) and worldwide. In temperate climate countries, including the U.S., influenza activity peaks during the winter months. Annual influenza vaccination is recommended for all persons in the U.S. aged 6 months and older, and among those at increased risk for influenza-related complications in other parts of the world (e.g. young children, elderly). Observational studies have reported effectiveness of influenza vaccination to reduce the risks of severe disease requiring hospitalization, intensive care unit admission, and death. A diagnosis of influenza should be considered in critically ill patients admitted with complications such as exacerbation of underlying chronic comorbidities, community-acquired pneumonia, and respiratory failure during influenza season. Molecular tests are recommended for influenza testing of respiratory specimens in hospitalized patients. Antigen detection assays are not recommended in critically ill patients because of lower sensitivity; negative results of these tests should not be used to make clinical decisions, and respiratory specimens should be tested for influenza by molecular assays. Because critically ill patients with lower respiratory tract disease may have cleared influenza virus in the upper respiratory tract, but have prolonged influenza viral replication in the lower respiratory tract, an endotracheal aspirate (preferentially) or bronchoalveolar lavage fluid specimen (if collected for other diagnostic purposes) should be tested by molecular assay for detection of influenza viruses.Observational studies have reported that antiviral treatment of critically ill adult influenza patients with a neuraminidase inhibitor is associated with survival benefit. Since earlier initiation of antiviral treatment is associated with the greatest clinical benefit, standard-dose oseltamivir (75 mg twice daily in adults) for enteric administration is recommended as soon as possible as it is well absorbed in critically ill patients. Based upon observational data that suggest harms, adjunctive corticosteroid treatment is currently not recommended for children or adults hospitalized with influenza, including critically ill patients, unless clinically indicated for another reason, such as treatment of asthma or COPD exacerbation, or septic shock. A number of pharmaceutical agents are in development for treatment of severe influenza.

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged >/=6 months (https://www.cdc.gov/flu/protect/whoshouldvax.htm). Effectiveness of seasonal influenza vaccine varies by season. During each influenza season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine to prevent laboratory-confirmed influenza associated with medically attended acute respiratory illness (ARI). This interim report uses data from 3,254 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during November 23, 2018-February 2, 2019. During this period, overall adjusted vaccine effectiveness against all influenza virus infection associated with medically attended ARI was 47% (95% confidence interval [CI] = 34%-57%). For children aged 6 months-17 years, overall vaccine effectiveness was 61% (44%-73%). Seventy-four percent of influenza A infections for which subtype information was available were caused by A(H1N1)pdm09 viruses. Vaccine effectiveness was estimated to be 46% (30%-58%) against illness caused by influenza A(H1N1)pdm09 viruses. CDC recommends that health care providers continue to administer influenza vaccine because influenza activity is ongoing and the vaccine can still prevent illness, hospitalization, and death associated with currently circulating influenza viruses, or other influenza viruses that might circulate later in the season. During the 2017-18 influenza season, in which influenza A(H3N2) predominated, vaccination was estimated to prevent 7.1 million illnesses, 3.7 million medical visits, 109,000 hospitalizations, and 8,000 deaths (1). Vaccination can also reduce the severity of influenza-associated illness (2). Persons aged >/=6 months who have not yet been vaccinated this season should be vaccinated.

The U.S. 2017–18 influenza season was a high-severity season, with the highest number of outpatient visits for influenza-like illness* (ILI) since the 2009–10 pandemic and the highest rate of influenza-associated hospitalizations since surveillance expanded to include adult hospitalizations during the 2005–06 season (1). The severe season was characterized by reports of strained emergency departments and hospitals and spot shortages of influenza antiviral medications (2). Influenza activity can vary widely across geographic regions (3), and local severity assessments might better guide public health actions and health care needs and support the development of tailored communication messages to prevent influenza morbidity and mortality. CDC assesses influenza season severity at the national level (4),† but the applicability of this approach at state or local levels has not been tested.

PURPOSE OF REVIEW: Influenza causes a range of illnesses in children, from uncomplicated self-limited illness to severe disease and death. This review provides an update on the severity and burden of influenza in US children over recent seasons. RECENT FINDINGS: The 2017-2018 influenza season was widespread and severe across all ages, including children. Disease severity is influenced by influenza virologic characteristics and host factors, as well as public health interventions such as influenza vaccination and antiviral treatment. In recent influenza A (H3N2)-predominant seasons (2016-2017 and 2017-2018), influenza vaccination effectiveness was higher in younger children compared with older children and adolescents, although the reasons for this are unclear. Interestingly, even in seasons when influenza A (H3N2) viruses predominate, influenza A (H1N1)pdm09 and B viruses can play a large role in severe pediatric disease. Although children less than 5 years of age and those with underlying medical conditions are at increased risk for severe disease, influenza-associated hospitalizations and deaths occur every season in healthy children. SUMMARY: Influenza causes a substantial burden of outpatient visits, hospitalizations, and deaths among children. Ongoing research is important to better characterize factors that contribute to influenza severity, and to identify strategies to improve the impact of influenza vaccination and treatment.