Differentiating severe and non-severe lower respiratory tract illness in patients hospitalized with influenza: Development of the Influenza Disease Evaluation and Assessment of Severity (IDEAS) scale.

BACKGROUND: Experimental studies have shown that vaccination can reduce viral replication to attenuate progression of influenza-associated lower respiratory tract illness (LRTI). However, clinical studies are conflicting, possibly due to use of non-specific outcomes reflecting a mix of large and small airway LRTI lacking specificity for acute lung or organ injury. METHODS: We developed a global ordinal scale to differentiate large and small airway LRTI in hospitalized adults with influenza using physiologic features and interventions (PFIs): vital signs, laboratory and radiographic findings, and clinical interventions. We reviewed the literature to identify common PFIs across 9 existing scales of pneumonia and sepsis severity. To characterize patients using this scale, we applied the scale to an antiviral clinical trial dataset where these PFIs were measured through routine clinical care in adults hospitalized with influenza-associated LRTI during the 2010-2013 seasons. RESULTS: We evaluated 12 clinical parameters among 1020 adults; 210 (21%) had laboratory-confirmed influenza, with a median severity score of 4.5 (interquartile range, 2-8). Among influenza cases, median age was 63 years, 20% were hospitalized in the prior 90 days, 50% had chronic obstructive pulmonary disease, and 22% had congestive heart failure. Primary influencers of higher score included pulmonary infiltrates on imaging (48.1%), heart rate ≥110 beats/minute (41.4%), oxygen saturation <93% (47.6%) and respiratory rate >24 breaths/minute (21.0%). Key PFIs distinguishing patients with severity < or ≥8 (upper quartile) included infiltrates (27.1% vs 90.0%), temperature ≥ 39.1°C or <36.0°C (7.1% vs 27.1%), respiratory rate >24 breaths/minute (7.9% vs 47.1%), heart rate ≥110 beats/minute (29.3% vs 65.7%), oxygen saturation <90% (14.3% vs 31.4%), white blood cell count >15,000 (5.0% vs 27.2%), and need for invasive or non-invasive mechanical ventilation (2.1% vs 15.7%). CONCLUSION: We developed a scale in adults hospitalized with influenza-associated LRTI demonstrating a broad distribution of physiologic severity which may be useful for future studies evaluating the disease attenuating effects of influenza vaccination or other therapeutics.

Racial and Ethnic Disparities in Rates of COVID-19-Associated Hospitalization, Intensive Care Unit Admission, and In-Hospital Death in the United States From March 2020 to February 2021.

Importance: Racial and ethnic minority groups are disproportionately affected by COVID-19. Objectives: To evaluate whether rates of severe COVID-19, defined as hospitalization, intensive care unit (ICU) admission, or in-hospital death, are higher among racial and ethnic minority groups compared with non-Hispanic White persons. Design, Setting, and Participants: This cross-sectional study included 99 counties within 14 US states participating in the COVID-19-Associated Hospitalization Surveillance Network. Participants were persons of all ages hospitalized with COVID-19 from March 1, 2020, to February 28, 2021. Exposures: Laboratory-confirmed COVID-19-associated hospitalization, defined as a positive SARS-CoV-2 test within 14 days prior to or during hospitalization. Main Outcomes and Measures: Cumulative age-adjusted rates (per 100 000 population) of hospitalization, ICU admission, and death by race and ethnicity. Rate ratios (RR) were calculated for each racial and ethnic group compared with White persons. Results: Among 153 692 patients with COVID-19-associated hospitalizations, 143 342 (93.3%) with information on race and ethnicity were included in the analysis. Of these, 105 421 (73.5%) were 50 years or older, 72 159 (50.3%) were male, 28 762 (20.1%) were Hispanic or Latino, 2056 (1.4%) were non-Hispanic American Indian or Alaska Native, 7737 (5.4%) were non-Hispanic Asian or Pacific Islander, 40 806 (28.5%) were non-Hispanic Black, and 63 981 (44.6%) were White. Compared with White persons, American Indian or Alaska Native, Latino, Black, and Asian or Pacific Islander persons were more likely to have higher cumulative age-adjusted rates of hospitalization, ICU admission, and death as follows: American Indian or Alaska Native (hospitalization: RR, 3.70; 95% CI, 3.54-3.87; ICU admission: RR, 6.49; 95% CI, 6.01-7.01; death: RR, 7.19; 95% CI, 6.47-7.99); Latino (hospitalization: RR, 3.06; 95% CI, 3.01-3.10; ICU admission: RR, 4.20; 95% CI, 4.08-4.33; death: RR, 3.85; 95% CI, 3.68-4.01); Black (hospitalization: RR, 2.85; 95% CI, 2.81-2.89; ICU admission: RR, 3.17; 95% CI, 3.09-3.26; death: RR, 2.58; 95% CI, 2.48-2.69); and Asian or Pacific Islander (hospitalization: RR, 1.03; 95% CI, 1.01-1.06; ICU admission: RR, 1.91; 95% CI, 1.83-1.98; death: RR, 1.64; 95% CI, 1.55-1.74). Conclusions and Relevance: In this cross-sectional analysis, American Indian or Alaska Native, Latino, Black, and Asian or Pacific Islander persons were more likely than White persons to have a COVID-19-associated hospitalization, ICU admission, or in-hospital death during the first year of the US COVID-19 pandemic. Equitable access to COVID-19 preventive measures, including vaccination, is needed to minimize the gap in racial and ethnic disparities of severe COVID-19.

Census tract socioeconomic indicators and COVID-19-associated hospitalization rates-COVID-NET surveillance areas in 14 states, March 1-April 30, 2020.

OBJECTIVES: Some studies suggested more COVID-19-associated hospitalizations among racial and ethnic minorities. To inform public health practice, the COVID-19-associated Hospitalization Surveillance Network (COVID-NET) quantified associations between race/ethnicity, census tract socioeconomic indicators, and COVID-19-associated hospitalization rates. METHODS: Using data from COVID-NET population-based surveillance reported during March 1-April 30, 2020 along with socioeconomic and denominator data from the US Census Bureau, we calculated COVID-19-associated hospitalization rates by racial/ethnic and census tract-level socioeconomic strata. RESULTS: Among 16,000 COVID-19-associated hospitalizations, 34.8% occurred among non-Hispanic White (White) persons, 36.3% among non-Hispanic Black (Black) persons, and 18.2% among Hispanic or Latino (Hispanic) persons. Age-adjusted COVID-19-associated hospitalization rate were 151.6 (95% Confidence Interval (CI): 147.1-156.1) in census tracts with >15.2%-83.2% of persons living below the federal poverty level (high-poverty census tracts) and 75.5 (95% CI: 72.9-78.1) in census tracts with 0%-4.9% of persons living below the federal poverty level (low-poverty census tracts). Among White, Black, and Hispanic persons living in high-poverty census tracts, age-adjusted hospitalization rates were 120.3 (95% CI: 112.3-128.2), 252.2 (95% CI: 241.4-263.0), and 341.1 (95% CI: 317.3-365.0), respectively, compared with 58.2 (95% CI: 55.4-61.1), 304.0 (95%: 282.4-325.6), and 540.3 (95% CI: 477.0-603.6), respectively, in low-poverty census tracts. CONCLUSIONS: Overall, COVID-19-associated hospitalization rates were highest in high-poverty census tracts, but rates among Black and Hispanic persons were high regardless of poverty level. Public health practitioners must ensure mitigation measures and vaccination campaigns address needs of racial/ethnic minority groups and people living in high-poverty census tracts.

Update: Influenza Activity in the United States During the 2018-19 Season and Composition of the 2019-20 Influenza Vaccine.

Influenza activity* in the United States during the 2018-19 season (September 30, 2018-May 18, 2019) was of moderate severity (1). Nationally, influenza-like illness (ILI)† activity began increasing in November, peaked during mid-February, and returned to below baseline in mid-April; the season lasted 21 weeks,§ making it the longest season in 10 years. Illness attributed to influenza A viruses predominated, with very little influenza B activity. Two waves of influenza A were notable during this extended season: influenza A(H1N1)pdm09 viruses from October 2018 to mid-February 2019 and influenza A(H3N2) viruses from February through May 2019. Compared with the 2017-18 influenza season, rates of hospitalization this season were lower for adults, but were similar for children. Although influenza activity is currently below surveillance baselines, testing for seasonal influenza viruses and monitoring for novel influenza A virus infections should continue year-round. Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences.

Burden of Pneumonia-Associated Hospitalizations: United States, 2001-2014.

BACKGROUND: The epidemiology of pneumonia has likely evolved in recent years, reflecting an aging population, changes in population immunity, and socioeconomic disparities. METHODS: Using the National (Nationwide) Inpatient Sample, estimated numbers and rates of pneumonia-associated hospitalizations for 2001-2014 were calculated. A pneumonia-associated hospitalization was defined as one in which the discharge record listed a principal diagnosis of pneumonia or a secondary diagnosis of pneumonia if the principal diagnosis was respiratory failure or sepsis. RESULTS: There were an estimated 20,361,181 (SE, 95,601) pneumonia-associated hospitalizations in the United States during 2001-2014 (average annual age-adjusted pneumonia-associated hospitalization rate of 464.8 per 100,000 population [95% CI, 462.5-467.1]). The average annual age-adjusted pneumonia-associated hospitalization rate decreased over the study period (P < .0001). In-hospital death occurred in 7.4% (SE, 0.03) of pneumonia-associated hospitalizations. Non-Hispanic American Indian/Alaskan Natives and non-Hispanic blacks had the highest average annual age-adjusted rates of pneumonia-associated hospitalization of all race/ethnicities at 439.2 (95% CI, 415.9-462.5) and 438.6 (95% CI, 432.5-444.7) per 100,000 population, respectively. During 2001-2014, the proportion of pneumonia-associated hospitalizations colisting an immunocompromising condition increased from 18.7% (SE, 0.2) in 2001 to 29.9% (SE, 0.2) in 2014. Total charges for pneumonia-associated hospitalizations in 2014 were over $84 billion. CONCLUSIONS: Pneumonia is a major cause of morbidity and mortality in the United States. Differences in rates and outcomes of pneumonia-associated hospitalizations between sociodemographic groups warrant further investigation. The immunocompromised population has emerged as a group experiencing a disproportionate burden of pneumonia-associated hospitalizations.

Comparative Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccines Among US Medicare Beneficiaries in Preventing Postinfluenza Deaths During 2012-2013 and 2013-2014.

Background: Recipients of high-dose vs standard-dose influenza vaccines have fewer influenza illnesses. We evaluated the comparative effectiveness of high-dose vaccine in preventing postinfluenza deaths during 2012-2013 and 2013-2014, when influenza viruses and vaccines were similar. Methods: We identified Medicare beneficiaries aged ≥65 years who received high-dose or standard-dose vaccines in community-located pharmacies offering both vaccines. The primary outcome was death in the 30 days following an inpatient or emergency department encounter listing an influenza International of Classification of Diseases, Ninth Revision, Clinical Modification code. Effectiveness was estimated by using multivariate Poisson regression models; effectiveness was allowed to vary by season. Results: We studied 1039645 recipients of high-dose and 1683264 recipients of standard-dose vaccines during 2012-2013, and 1508176 high-dose and 1877327 standard-dose recipients during 2013-2014. Vaccinees were well-balanced for medical conditions and indicators of frail health. Rates of postinfluenza death were 0.028 and 0.038/10000 person-weeks in high-dose and standard-dose recipients, respectively. Comparative effectiveness was 24.0% (95% confidence interval [CI], .6%-42%); there was evidence of variation by season (P = .12). In 2012-2013, high-dose was 36.4% (95% CI, 9.0%-56%) more effective in reducing mortality; in 2013-2014, it was 2.5% (95% CI, -47% to 35%). Conclusions: High-dose vaccine was significantly more effective in preventing postinfluenza deaths in 2012-2013, when A(H3N2) circulation was common, but not in 2013-2014.

Hospitalizations Attributable to Respiratory Infections among Children with Neurologic Disorders.

OBJECTIVES: To characterize respiratory infection hospitalizations in children with neurologic disorders and to compare them with those of the general pediatric population. STUDY DESIGN: We analyzed claims data from commercial insurance and Medicaid enrollees < 19 years of age from July 2006 to June 2011 who had ≥ 1 visit with an International Classification of Diseases, Ninth Revision, diagnosis code for a neurologic disorder. We identified hospitalizations with primary diagnosis codes indicating a respiratory infection and compared hospitalization rates with random samples of children from the commercial and Medicaid databases (comparison groups). RESULTS: Among 33,651923 children, 255,046 (0.76%) had ≥ 1 neurologic condition. Among children with neurologic conditions, 8249 of 68,717 hospitalizations (12%) were attributed to a respiratory infection (rate: 21/1000 person-years), although rates varied by disorder. Children with neurologic disorders had greater rates than children in comparison groups (relative rate: Commercial Claims 7.4 [95% CI 7.1-7.7]; Medicaid 5.0 [95% CI 4.8-5.2]). Children < 2 years were most likely to be hospitalized, although those 10-18 years were 14.5 (95% CI 13.3-16.7) times more likely to be hospitalized than age-matched comparison groups. Co-occurring deafness, blindness, and scoliosis were associated with increased respiratory hospitalization rates. CONCLUSIONS: Children with neurologic disorders are at 5- to 7-fold greater risk for hospitalization from respiratory infections compared with all children, although rates vary widely by disorder type, age, and comorbidities. Children with specific neurologic disorders and those who had co-occurring conditions have the highest rates.

Hospitalizations for severe lower respiratory tract infections.

BACKGROUND: Hospitalization for lower respiratory tract infections (LRTIs) among children have been well characterized. We characterized hospitalizations for severe LRTI among children. METHODS: We analyzed claims data from commercial and Medicaid insurance enrollees (MarketScan) ages 0 to 18 years from 2007 to 2011. LRTI hospitalizations were identified by the first 2 listed International Classification of Diseases, Ninth Revision discharge codes; those with ICU admission and/or receiving mechanical ventilation were defined as severe LRTI. Underlying conditions were determined from out- and inpatient discharge codes in the preceding year. We report insurance specific and combined rates that used both commercial and Medicaid rates and adjusted for age and insurance status. RESULTS: During 2007-2011, we identified 16797 and 12053 severe LRTI hospitalizations among commercial and Medicaid enrollees, respectively. The rates of severe LRTI hospitalizations per 100000 person-years were highest in children aged <1 year (commercial: 244; Medicaid: 372, respectively), and decreased with age. Among commercial enrollees, ≥ 1 condition increased the risk for severe LRTI (1 condition: adjusted relative risk, 2.68; 95% confidence interval, 2.58-2.78; 3 conditions: adjusted relative risk, 4.85; 95% confidence interval, 4.65-5.07) compared with children with no medical conditions. Using commercial/Medicaid combined rates, an estimated 31289 hospitalizations for severe LRTI occurred each year in children in the United States. CONCLUSIONS: Among children, the burden of hospitalization for severe LRTI is greatest among children aged <1 year. Children with underlying medical conditions are at greatest risk for severe LRTI hospitalization.

The Economics of Strategies to Reduce Respiratory Syncytial Virus Hospitalizations in Alaska.

BACKGROUND: Alaska Native infants experience high rates of respiratory syncytial virus (RSV) hospitalizations. Through 2008, Alaska administered a 7-dose (maximum) palivizumab regime to high-risk infants from October to May. In 2009, the maximum was reduced to 3 doses for 32- to 34-week preterm babies and 6 doses for other groups. METHODS: We used 11 years of data and regional Medicaid reimbursement rates to model the cost effectiveness of 4 palivizumab intervention strategies to reduce RSV hospitalizations among Alaskan infants including: current strategy, old strategy (1998-2008), and 2 hypothetical strategies using the current strategy plus 1 or 3 doses to all newborn infants during the RSV season. RESULTS: The current strategy represents 5 hospitalizations averted per year for the palivizumab cohort (∼50-56 children) at ∼$52 846 per hospitalization averted, compared with no intervention. Compared with the old strategy, the mean cost per hospitalization prevented for the current strategy was 63% lower, net program costs were 85% lower, and the mean hospitalizations prevented were 27% lower. Compared with current strategy only, the addition of 1 dose to all newborns during the RSV season could decrease the mean cost per hospitalization prevented by 23%, increase the number of hospitalizations prevented by 2.5-fold, and increase the net programmatic costs by 3.3-fold; administering up to 3 doses to infants further reduced hospitalizations and increased costs. CONCLUSIONS: The current palivizumab strategy improved the cost-effectiveness ratio compared with the old strategy. Further improvement could be obtained by adding doses for Alaskan Native newborns during the RSV season; however, programmatic costs would increase.

The burden and severity of illness due to 2009 pandemic influenza A (H1N1) in a large US city during the late summer and early fall of 2009.

In estimates of illness severity from the spring wave of the 2009 influenza A (H1N1) pandemic, reported case fatality proportions were less than 0.05%. In prior pandemics, subsequent waves of illness were associated with higher mortality. The authors evaluated the burden of the pandemic H1N1 (pH1N1) outbreak in metropolitan Atlanta, Georgia, in the fall of 2009, when increased influenza activity heralded the second wave of the pandemic in the United States. Using data from a community survey, existing surveillance systems, public health laboratories, and local hospitals, they estimated numbers of pH1N1-associated illnesses, emergency department (ED) visits, hospitalizations, intensive care unit (ICU) admissions, and deaths occurring in metropolitan Atlanta during the period August 16, 2009-September 26, 2009. The authors estimated 132,140 pediatric and 132,110 adult symptomatic cases of pH1N1 in metropolitan Atlanta during the investigation time frame. Among children, these cases were associated with 4,560 ED visits, 190 hospitalizations, 51 ICU admissions, and 4 deaths. Among adults, they were associated with 1,130 ED visits, 590 hospitalizations, 140 ICU admissions, and 63 deaths. The combined symptomatic case hospitalization proportion, case ICU admission proportion, and case fatality proportion were 0.281%, 0.069%, and 0.024%, respectively. Influenza burden can be estimated using existing data and local surveys. The increased severity reported for subsequent waves in past pandemics was not evident in this investigation. Nevertheless, the second pH1N1 pandemic wave led to substantial numbers of ED visits, hospitalizations, and deaths in metropolitan Atlanta.

Comprehensive assessment of 2009 pandemic influenza A (H1N1) virus drug susceptibility in vitro.

BACKGROUND: Antiviral drugs are an important option for managing infections caused by influenza viruses. This study assessed the drug susceptibility of 2009 pandemic influenza A (H1N1) viruses collected globally between April 2009 and January 2010. METHODS: Virus isolates were tested for adamantane susceptibility, using pyrosequencing to detect the S31N marker of adamantane resistance in the M2 protein and biological assays to assess viral replication in cell culture. To assess neuraminidase (NA) inhibitor (NAI) susceptibility, virus isolates were tested in chemiluminescent NA inhibition assays and by pyrosequencing to detect the H275Y (H274Y in N2 numbering) marker of oseltamivir resistance in the NA. RESULTS: With the exception of three, all viruses that were tested for adamantane susceptibility (n=3,362) were resistant to this class of drugs. All viruses tested for NAI susceptibility (n=3,359) were sensitive to two US Food and Drug Administration-approved NAIs, oseltamivir (mean ±sd 50% inhibitory concentration [IC(50)] 0.25 ±0.12 nM) and zanamivir (mean IC(50) 0.29 ±0.09 nM), except 23 (0.7%), which were resistant to oseltamivir, but sensitive to zanamivir. Oseltamivir-resistant viruses had the H275Y mutation in their NA and were detected in patients exposed to the drug through prophylaxis or treatment. NA activity of all viruses was inhibited by the NAIs peramivir, laninamivir (R-125489) and A-315675, except for H275Y variants, which exhibited approximately 100-fold reduction in peramivir susceptibility. CONCLUSIONS: This report provides data regarding antiviral susceptibility of 2009 pandemic influenza A (H1N1) surveillance viruses, the majority of which were resistant to adamantanes and sensitive to NAIs. These findings provide information essential for antiviral resistance monitoring and development of novel diagnostic tests for detecting influenza antiviral resistance.

Rates of hospital-acquired respiratory illness in Bangladeshi tertiary care hospitals: results from a low-cost pilot surveillance strategy.

BACKGROUND: Patients hospitalized in resource-poor health care settings are at increased risk for hospital-acquired respiratory infections due to inadequate infrastructure. METHODS: From 1 April 2007 through 31 March 2008, we used a low-cost surveillance strategy to identify new onset of respiratory symptoms in patients hospitalized for >72 h and in health care workers in medicine and pediatric wards at 3 public tertiary care hospitals in Bangladesh. RESULTS: During 46,273 patient-days of observation, we recorded 136 episodes of hospital-acquired respiratory disease, representing 1.7% of all patient hospital admissions; rates by ward ranged from 0.8 to 15.8 cases per 1000 patient-days at risk. We identified 22 clusters of respiratory disease, 3 of which included both patients and health care workers. Of 226 of heath care workers who worked on our surveillance wards, 61 (27%) experienced a respiratory illness during the study period. The cost of surveillance was US$43 per month per ward plus 30 min per day in data collection. CONCLUSIONS: Patients on these study wards frequently experienced hospital-acquired respiratory infections, including 1 in every 20 patients hospitalized for >72 h on 1 ward. The surveillance method was useful in calculating rates of hospital-acquired respiratory illness and could be used to enhance capacity to quickly detect outbreaks of respiratory disease in health care facilities where systems for outbreak detection are currently limited and to test interventions to reduce transmission of respiratory pathogens in resource-poor settings.

Trends in hospitalizations for pneumonia among persons aged 65 years or older in the United States, 1988-2002.

CONTEXT: Pneumonia causes significant mortality and morbidity among persons aged 65 years or older. However, few studies have explored trends according to age groups, which may affect intervention strategies. OBJECTIVES: To examine trends in hospitalizations for pneumonia among persons aged 65 years or older and to compare characteristics, outcomes, and comorbid diagnoses. DESIGN, SETTING, AND PATIENTS: Data from 1988 through 2002 on pneumonia and comorbid diagnoses among patients aged 65 to 74 years, 75 to 84 years, and 85 years or older from the National Hospital Discharge Survey. MAIN OUTCOME MEASURES: Hospitalization rates by first-listed and any-listed discharge codes for pneumonia; proportions of hospitalizations reporting comorbid diagnoses for the 3 age groups (65-74 years, 75-84 years, > or =85 years). RESULTS: Hospitalization rates by both first-listed and any-listed discharge codes for pneumonia increased by 20% from 1988-1990 to 2000-2002 for patients aged 65 to 74 years (P = .01) and for patients aged 75 to 84 years (P<.001). Rates of hospitalization for pneumonia were 2-fold higher for patients aged 85 years or older (51 per 1000 population for first-listed discharge code of pneumonia; 95% confidence interval [CI], 46-55 per 1000 population) than among patients aged 75 to 84 years (26 per 1000 population; 95% CI, 24-28 per 1000 population), but did not significantly increase from 1988-1990 to 2000-2002. The proportion of patients aged 65 years or older diagnosed with pneumonia and a chronic cardiac disease, chronic pulmonary disease, or diabetes mellitus increased from 66% (SE, 1.0%) in 1988-1990 to 77% (SE, 0.8%) in 2000-2002. The risk of death during a hospitalization for pneumonia compared with the risk of death during a hospital stay for the 10 other most frequent causes of hospitalization was 1.5 (95% CI, 1.4-1.7) and remained constant from 1988-1990 to 2000-2002. CONCLUSIONS: Hospitalization rates for pneumonia have increased among US adults aged 64 to 74 years and aged 75 to 84 years during the past 15 years. Among those aged 85 years or older, at least 1 in 20 patients were hospitalized each year due to pneumonia. Concomitantly, the proportion of comorbid chronic diseases has increased. Efforts to prevent pneumonia should include reducing preventable comorbid conditions and improving vaccine effectiveness and vaccination programs in elderly persons.