Risk of Severe Influenza Among Adults With Chronic Medical Conditions.

BACKGROUND: Severe influenza illness is presumed more common in adults with chronic medical conditions (CMCs), but evidence is sparse and often combined into broad CMC categories. METHODS: Residents (aged 18-80 years) of Central and South Auckland hospitalized for World Health Organization-defined severe acute respiratory illness (SARI) (2012-2015) underwent influenza virus polymerase chain reaction testing. The CMC statuses for Auckland residents were modeled using hospitalization International Classification of Diseases, Tenth Revision codes, pharmaceutical claims, and laboratory results. Population-level influenza rates in adults with congestive heart failure (CHF), coronary artery disease (CAD), cerebrovascular accidents (CVA), chronic obstructive pulmonary disease (COPD), asthma, diabetes mellitus (DM), and end-stage renal disease (ESRD) were calculated by Poisson regression stratified by age and adjusted for ethnicity. RESULTS: Among 891 276 adults, 2435 influenza-associated SARI hospitalizations occurred. Rates were significantly higher in those with CMCs compared with those without the respective CMC, except for older adults with DM or those aged <65 years with CVA. The largest effects occurred with CHF (incidence rate ratio [IRR] range, 4.84-13.4 across age strata), ESRD (IRR range, 3.30-9.02), CAD (IRR range, 2.77-10.7), and COPD (IRR range, 5.89-8.78) and tapered with age. CONCLUSIONS: Our findings support the increased risk of severe, laboratory-confirmed influenza disease among adults with specific CMCs compared with those without these conditions.

Illness Severity in Hospitalized Influenza Patients by Virus Type and Subtype, Spain, 2010-2017.

We conducted a retrospective cohort study to assess the effect of influenza virus type and subtype on disease severity among hospitalized influenza patients in Spain. We analyzed the cases of 8,985 laboratory-confirmed case-patients hospitalized for severe influenza by using data from a national surveillance system for the period 2010-2017. Hospitalized patients with influenza A(H1N1)pdm09 virus were significantly younger, more frequently had class III obesity, and had a higher risk for pneumonia or acute respiratory distress syndrome than patients infected with influenza A(H3N2) or B (p<0.05). Hospitalized patients with influenza A(H1N1)pdm09 also had a higher risk for intensive care unit admission, death, or both than patients with influenza A(H3N2) or B, independent of other factors. Determining the patterns of influenza-associated severity and how they might differ by virus type and subtype can help guide planning and implementation of adequate control and preventive measures during influenza epidemics.

Impact of Prompt Influenza Antiviral Treatment on Extended Care Needs After Influenza Hospitalization Among Community-Dwelling Older Adults.

BACKGROUND: Patients hospitalized with influenza may require extended care on discharge. We aimed to explore predictors for extended care needs and the potential mitigating effect of antiviral treatment among community-dwelling adults aged ≥ 65 years hospitalized with influenza. METHODS: We used laboratory-confirmed influenza hospitalizations from 3 influenza seasons. Extended care was defined as new placement in a skilled nursing home/long-term/rehabilitation facility on hospital discharge. We focused on those treated with antiviral agents to explore the effect of early treatment on extended care and hospital length of stay using logistic regression and competing risk survival analysis, accounting for time from illness onset to hospitalization. Treatment was categorized as early (≤ 4 days) or late (>4 days) in reference to date of illness onset. RESULTS: Among 6593 community-dwelling adults aged ≥ 65 years hospitalized for influenza, 18% required extended care at discharge. The need for care increased with age and neurologic disorders, intensive care unit admission, and pneumonia were predictors of care needs. Early treatment reduced the odds of extended care after hospital discharge for those hospitalized ≤ 2 or >2 days from illness onset (adjusted odds ratio, 0.38 [95% confidence interval {CI}, .17-.85] and 0.75 [.56-.97], respectively). Early treatment was also independently associated with reduction in length of stay for those hospitalized ≤ 2 days from illness onset (adjusted hazard ratio, 1.81; 95% CI, 1.43-2.30) or >2 days (1.30; 1.20-1.40). CONCLUSIONS: Prompt antiviral treatment decreases the impact of influenza on older adults through shorten hospitalization and reduced extended care needs.

The US Influenza Hospitalization Surveillance Network.

In 2003, surveillance for influenza in hospitalized persons was added to the Centers for Disease Control and Prevention Emerging Infections Program network. This surveillance enabled monitoring of the severity of influenza seasons and provided a platform for addressing priority questions associated with influenza. For enhanced surveillance capacity during the 2009 influenza pandemic, new sites were added to this platform. The combined surveillance platform is called the Influenza Hospitalization Surveillance Network (FluSurv-NET). FluSurv-NET has helped to determine the risk for influenza-associated illness in various segments of the US population, define the severity of influenza seasons and the 2009 pandemic, and guide recommendations for treatment and vaccination programs.

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).

Patients hospitalized with laboratory-confirmed influenza during the 2010-2011 influenza season: exploring disease severity by virus type and subtype.

BACKGROUND: The 2010-2011 influenza season was dominated by influenza A(H3N2) virus, but influenza A(H1N1) pdm09 (pH1N1) and B viruses cocirculated. This provided an opportunity to explore within-season predictors of severity among hospitalized patients, avoiding biases associated with season-to-season differences in strain virulence, population immunity, and healthcare seeking. METHODS: Population-based, laboratory-confirmed influenza hospitalization surveillance data were used to examine the association between virus type/subtype and outcomes in children and adults. Multivariable analysis explored virus type/subtype, prompt antiviral treatment, medical conditions, and age as predictors for severity (intensive care unit admission or death). RESULTS: In children, pH1N1 (adjusted odds ratio [aOR], 2.19; 95% confidence interval [CI], 1.11-4.3), chronic metabolic disease (aOR, 5.23; 95% CI, 1.74-15.69), and neuromuscular disorder (aOR, 4.84; 95% CI, 2.02-11.58) were independently associated with severity. In adults, independent predictors were pH1N1 (aOR, 2.21; 95% CI, 1.66-2.94), chronic lung disease (aOR, 1.46, 95% CI, 1.12-1.89), and neuromuscular disorder (aOR, 1.68; 95% CI, 1.11-2.52).Antiviral treatment reduced the odds of severity among adults (aOR, 0.47; 95% CI, .33-.68). CONCLUSIONS: During the 2010-2011 season, pH1N1 caused more severe disease than H3N2 or B in hospitalized patients. Underlying medical conditions increased severity despite virus strain. Antiviral treatment reduced severity among adults. Our findings underscore the importance of influenza prevention.

Evaluating equity-promoting interventions to prevent race-based inequities in influenza outcomes.

Importance: Seasonal influenza hospitalizations pose a considerable burden in the United States, with BIPOC (Black, Indigenous, and other People of Color) communities being disproportionately affected. Objective: To determine and quantify the effects of different types of mitigation strategies on inequities in influenza outcomes (symptomatic infections and hospitalizations). Design: In this simulation study, we fit a race-stratified agent-based model of influenza transmission to demographic and hospitalization data of the United States. Participants: We consider five racial-ethnic groups: non-Hispanic White persons, non- Hispanic Black persons, non-Hispanic Asian persons, non-Hispanic American Indian or Alaska Native persons, and Hispanic or Latino persons. Setting: We tested five idealized equity-promoting interventions to determine their effectiveness in reducing inequity in influenza outcomes. The interventions assumed (i) equalized vaccination rates, (ii) equalized comorbidities, (iii) work-risk distribution proportional to the distribution of the population, (iv) reduced work contacts for all, or (v) a combination of equalizing vaccination rates and comorbidities and reducing work contacts. Main Outcomes and Measures: Reduction in symptomatic or hospitalization risk ratios, defined as the ratio of the number of symptomatic infections (hospitalizations respectively) in each age- and racial-ethnic group and their corresponding white counterpart. We also evaluated the reduction in the absolute mean number of symptomatic infections or hospitalizations in each age- and racial-ethnic group compared to the fitted scenario (baseline). Results: Our analysis suggests that symptomatic infections were equalized and reduced (by up to 17% in BIPOC adults aged 18-49) by strategies reducing work contacts or equalizing vaccination rates. Reducing comorbidities resulted in significant decreases in hospitalizations, with a reduction of over 40% in BIPOC groups. All tested interventions reduced the inequity in influenza hospitalizations in all racial-ethnic groups, but interventions reducing comorbidities in marginalized populations were the most effective. Notably, these interventions resulted in better outcomes across all racial-ethnic groups, not only those prioritized by the interventions. Conclusions and Relevance: In this simulation modeling study, equalizing vaccination rates and reducing number of work contacts (which are relatively simple strategies to implement) reduced the both the inequity in hospitalizations and the absolute number of symptomatic infections and hospitalizations in all age and racial-ethnic groups.

Time lapses between distribution of influenza vaccines to health authorities and their administration by General Practitioners (GPs) to older adults: a retrospective study over five influenza seasons in Italy.

BACKGROUND: Delays in influenza vaccine delivery and administration can hinder vaccine coverage and protection. This study examines the differentials in distributing and administering adjuvanted trivalent (aTIV) and quadrivalent influenza vaccines (aQIV) to older adults in Italy's primary care setting and its potential impact on hospitalization risk over 5 epidemic seasons. METHODS: Using a primary care database, individuals aged ≥ 65 years were selected. The proportion of vaccine distribution to regional authorities and subsequent administration by GPs was estimated using census data. Using quantile (median) regression, we examined the relationship between velocities of vaccine distribution and administration (doses/week) and the incidence of hospitalizations. RESULTS: Over the 5 influenza seasons, the velocity of distribution and administration of aTIV/aQIV ranged 341-833 and 152-270 median doses/week; no trend was yielded for the difference between these velocities (p = 0.189) or vaccine coverage (p = 0.142). An association was observed for each differential dose/week between distributed and administered vaccines and all-cause hospitalizations with a 10% increase in 2017-2018, 54% in 2018-2019, and 12% in 2020-2021 season. CONCLUSIONS: These findings highlight the importance of minimizing the time lapse between vaccine distribution and administration to mitigate the impact of influenza and address factors that contribute to vaccination barriers.

Influenza burden averted with a cell-based quadrivalent seasonal influenza vaccine compared with egg-based quadrivalent seasonal influenza vaccine.

BACKGROUND: Cell-based quadrivalent inactivated influenza vaccines (IIV4c) avoid egg-adaptive mutations found in egg-based production, improving vaccine effectiveness (VE). Studies demonstrate improved VE for IIV4c relative to egg-based quadrivalent inactivated influenza vaccines (IIV4). RESEARCH DESIGN AND METHODS: We built on a static compartmental model developed by the CDC to estimate the influenza burden in persons 0-64 years that would be additionally averted by vaccination with IIV4c vs. IIV4. Model inputs were based on published data from 2017-2018, 2018-2019, and 2019-2020 Northern Hemisphere influenza seasons for the US. RESULTS: Over 3 influenza seasons, relative to IIV4, IIV4c would avert 31-39% more symptomatic cases, 29-40% more outpatient visits, 29-38% more hospitalizations and ICU admissions, and 34-49% more deaths vs. IIV4. In a deterministic sensitivity analysis, the main drivers were the relative VE of IIV4c vs. IIV4 in the 2017-2018 season and influenza burden estimates for the 2018-2019 and 2019-2020 seasons. Probabilistic sensitivity analysis showed that the interquartile range of symptomatic cases was ± 13% of baseline in 2017-2018, ±8% in 2018-2019, and ± 7% in 2019-2020. CONCLUSIONS: IIV4c prevented significantly more symptomatic cases, outpatient visits, hospitalizations, and deaths than IIV4 in persons aged 0-64 years over 3 influenza seasons.

Using inpatient electronic medical records to study influenza for pandemic preparedness.

BACKGROUND: We assessed the ability to identify key data relevant to influenza and other respiratory virus surveillance in a large-scale US-based hospital electronic medical record (EMR) dataset using seasonal influenza as a use case. We describe characteristics and outcomes of hospitalized influenza cases across three seasons. METHODS: We identified patients with an influenza diagnosis between March 2017 and March 2020 in 140 US hospitals as part of the US FDA's Sentinel System. We calculated descriptive statistics on the presence of high-risk conditions, influenza antiviral administrations, and severity endpoints. RESULTS: Among 5.1 million hospitalizations, we identified 29,520 hospitalizations with an influenza diagnosis; 64% were treated with an influenza antiviral within 2 days of admission, and 25% were treated >2 days after admission. Patients treated >2 days after admission had more comorbidities than patients treated within 2 days of admission. Patients never treated during hospitalization had more documentation of cardiovascular and other diseases than treated patients. We observed more severe endpoints in patients never treated (death = 3%, mechanical ventilation [MV] = 9%, intensive care unit [ICU] = 26%) or patients treated >2 days after admission (death = 2%, MV = 14%, ICU = 32%) than in patients treated earlier (treated on admission: death = 1%, MV = 5%, ICU = 23%, treated within 2 days of admission: death = 1%, MV = 7%, ICU = 27%). CONCLUSIONS: We identified important trends in influenza severity related to treatment timing in a large inpatient dataset, laying the groundwork for the use of this and other inpatient EMR data for influenza and other respiratory virus surveillance.

Severe acute respiratory illness surveillance for influenza in Kenya: Patient characteristics and lessons learnt.

BACKGROUND: We describe the epidemiology and clinical features of Kenyan patients hospitalized with laboratory-confirmed influenza compared with those testing negative and discuss the potential contribution of severe acute respiratory illness (SARI) surveillance in monitoring a broader range of respiratory pathogens. METHODS: We described demographic and clinical characteristics of SARI cases among children (<18 years) and adults, separately. We compared disease severity (clinical features and treatment) of hospitalized influenza positive versus negative cases and explored independent predictors of death among SARI cases using a multivariable logistic regression model. RESULTS: From January 2014 to December 2018, 11,166 persons were hospitalized with SARI and overall positivity for influenza was ~10%. There were 10,742 (96%) children (<18 years)-median age of 1 year, interquartile range (IQR = 6 months, 2 years). Only 424 (4%) of the SARI cases were adults (≥18 years), with median age of 38 years (IQR 28 years, 52 years). There was no difference in disease severity comparing influenza positive and negative cases among children. Children hospitalized with SARI who had an underlying illness had greater odds of in-hospital death compared with those without (adjusted odds ratio 2.11 95% CI 1.09-4.07). No further analysis was done among adults due to the small sample size. CONCLUSION: Kenya's sentinel surveillance for SARI mainly captures data on younger children. Hospital-based platforms designed to monitor influenza viruses and associated disease burden may be adapted and expanded to other respiratory viruses to inform public health interventions. Efforts should be made to capture adults as part of routine respiratory surveillance.