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.

Hospital-acquired influenza in the United States, FluSurv-NET, 2011-2012 through 2018-2019.

OBJECTIVE: To estimate population-based rates and to describe clinical characteristics of hospital-acquired (HA) influenza. DESIGN: Cross-sectional study. SETTING: US Influenza Hospitalization Surveillance Network (FluSurv-NET) during 2011-2012 through 2018-2019 seasons. METHODS: Patients were identified through provider-initiated or facility-based testing. HA influenza was defined as a positive influenza test date and respiratory symptom onset >3 days after admission. Patients with positive test date >3 days after admission but missing respiratory symptom onset date were classified as possible HA influenza. RESULTS: Among 94,158 influenza-associated hospitalizations, 353 (0.4%) had HA influenza. The overall adjusted rate of HA influenza was 0.4 per 100,000 persons. Among HA influenza cases, 50.7% were 65 years of age or older, and 52.0% of children and 95.7% of adults had underlying conditions; 44.9% overall had received influenza vaccine prior to hospitalization. Overall, 34.5% of HA cases received ICU care during hospitalization, 19.8% required mechanical ventilation, and 6.7% died. After including possible HA cases, prevalence among all influenza-associated hospitalizations increased to 1.3% and the adjusted rate increased to 1.5 per 100,000 persons. CONCLUSIONS: Over 8 seasons, rates of HA influenza were low but were likely underestimated because testing was not systematic. A high proportion of patients with HA influenza were unvaccinated and had severe outcomes. Annual influenza vaccination and implementation of robust hospital infection control measures may help to prevent HA influenza and its impacts on patient outcomes and the healthcare system.

Characteristics and Outcomes of Hospitalized Pregnant Women With Influenza, 2010 to 2019 : A Repeated Cross-Sectional Study.

BACKGROUND: Pregnant women may be at increased risk for severe influenza-associated outcomes. OBJECTIVE: To describe characteristics and outcomes of hospitalized pregnant women with influenza. DESIGN: Repeated cross-sectional study. SETTING: The population-based U.S. Influenza Hospitalization Surveillance Network during the 2010-2011 through 2018-2019 influenza seasons. PATIENTS: Pregnant women (aged 15 to 44 years) hospitalized with laboratory-confirmed influenza identified through provider-initiated or facility-based testing practices. MEASUREMENTS: Clinical characteristics, interventions, and in-hospital maternal and fetal outcomes were obtained through medical chart abstraction. Multivariable logistic regression was used to evaluate the association between influenza A subtype and severe maternal influenza-associated outcomes, including intensive care unit (ICU) admission, mechanical ventilation, extracorporeal membrane oxygenation, or in-hospital death. RESULTS: Of 9652 women aged 15 to 44 years and hospitalized with influenza, 2690 (27.9%) were pregnant. Among the 2690 pregnant women, the median age was 28 years, 62% were in their third trimester, and 42% had at least 1 underlying condition. Overall, 32% were vaccinated against influenza and 88% received antiviral treatment. Five percent required ICU admission, 2% required mechanical ventilation, and 0.3% (n = 8) died. Pregnant women with influenza A H1N1 were more likely to have severe outcomes than those with influenza A H3N2 (adjusted risk ratio, 1.9 [95% CI, 1.3 to 2.8]). Most women (71%) were still pregnant at hospital discharge. Among 754 women who were no longer pregnant at discharge, 96% had a pregnancy resulting in live birth, and 3% experienced fetal loss. LIMITATION: Maternal and fetal outcomes that occurred after hospital discharge were not captured. CONCLUSION: Over 9 influenza seasons, one third of reproductive-aged women hospitalized with influenza were pregnant. Influenza A H1N1 was associated with more severe maternal outcomes. Pregnant women remain a high-priority target group for vaccination. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Covid-19 Rates by Time since Vaccination during Delta Variant Predominance.

BACKGROUND: With the emergence of the delta variant, the United States experienced a rapid increase in Covid-19 cases in 2021. We estimated the risk of breakthrough infection and death by month of vaccination as a proxy for waning immunity during a period of delta variant predominance. METHODS: Covid-19 case and death data from 15 U.S. jurisdictions during January 3 to September 4, 2021 were used to estimate weekly hazard rates among fully vaccinated persons, stratified by age group and vaccine product. Case and death rates during August 1 to September 4, 2021 were presented across four cohorts defined by month of vaccination. Poisson models were used to estimate adjusted rate ratios comparing the earlier cohorts to July rates. RESULTS: During August 1 to September 4, 2021, case rates per 100,000 person-weeks among all vaccine recipients for the January to February, March to April, May to June, and July cohorts were 168.8 (95% confidence interval [CI], 167.5 to 170.1), 123.5 (95% CI, 122.8 to 124.1), 83.6 (95% CI, 82.9 to 84.3), and 63.1 (95% CI, 61.6 to 64.6), respectively. Similar trends were observed by age group for BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccine recipients. Rates for the Ad26.COV2.S (Janssen-Johnson & Johnson) vaccine were higher; however, trends were inconsistent. BNT162b2 vaccine recipients 65 years of age or older had higher death rates among those vaccinated earlier in the year. Protection against death was sustained for the mRNA-1273 vaccine recipients. Across age groups and vaccine types, people who were vaccinated 6 months ago or longer (January-February) were 3.44 (3.36 to 3.53) times more likely to be infected and 1.70 (1.29 to 2.23) times more likely to die from COVID-19 than people vaccinated recently in July 2021. CONCLUSIONS: Our study suggests that protection from SARS-CoV-2 infection among all ages or death among older adults waned with increasing time since vaccination during a period of delta predominance. These results add to the evidence base that supports U.S. booster recommendations, especially for older adults vaccinated with BNT162b2 and recipients of the Ad26.COV2.S vaccine. (Funded by the Centers for Disease Control and Prevention.).

Monitoring Incidence of COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Status - 13 U.S. Jurisdictions, April 4-July 17, 2021.

COVID-19 vaccine breakthrough infection surveillance helps monitor trends in disease incidence and severe outcomes in fully vaccinated persons, including the impact of the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19. Reported COVID-19 cases, hospitalizations, and deaths occurring among persons aged ≥18 years during April 4-July 17, 2021, were analyzed by vaccination status across 13 U.S. jurisdictions that routinely linked case surveillance and immunization registry data. Averaged weekly, age-standardized incidence rate ratios (IRRs) for cases among persons who were not fully vaccinated compared with those among fully vaccinated persons decreased from 11.1 (95% confidence interval [CI] = 7.8-15.8) to 4.6 (95% CI = 2.5-8.5) between two periods when prevalence of the Delta variant was lower (<50% of sequenced isolates; April 4-June 19) and higher (≥50%; June 20-July 17), and IRRs for hospitalizations and deaths decreased between the same two periods, from 13.3 (95% CI = 11.3-15.6) to 10.4 (95% CI = 8.1-13.3) and from 16.6 (95% CI = 13.5-20.4) to 11.3 (95% CI = 9.1-13.9). Findings were consistent with a potential decline in vaccine protection against confirmed SARS-CoV-2 infection and continued strong protection against COVID-19-associated hospitalization and death. Getting vaccinated protects against severe illness from COVID-19, including the Delta variant, and monitoring COVID-19 incidence by vaccination status might provide early signals of changes in vaccine-related protection that can be confirmed through well-controlled vaccine effectiveness (VE) studies.

Rates of Influenza-Associated Hospitalization, Intensive Care Unit Admission, and In-Hospital Death by Race and Ethnicity in the United States From 2009 to 2019.

Importance: Racial and ethnic minority groups, such as Black, Hispanic, American Indian or Alaska Native, and Asian or Pacific Islander persons, often experience higher rates of severe influenza disease. Objective: To describe rates of influenza-associated hospitalization, intensive care unit (ICU) admission, and in-hospital death by race and ethnicity over 10 influenza seasons. Design, Setting, and Participants: This cross-sectional study used data from the Influenza-Associated Hospitalization Surveillance Network (FluSurv-NET), which conducts population-based surveillance for laboratory-confirmed influenza-associated hospitalizations in selected counties, representing approximately 9% of the US population. Influenza hospitalizations from the 2009 to 2010 season to the 2018 to 2019 season were analyzed. Data were analyzed from October 2020 to July 2021. Main Outcomes and Measures: The main outcomes were age-adjusted and age-stratified rates of influenza-associated hospitalization, ICU admission, and in-hospital death by race and ethnicity overall and by influenza season. Results: Among 113 352 persons with an influenza-associated hospitalization (34 436 persons [32.0%] aged ≥75 years; 61 009 [53.8%] women), 70 225 persons (62.3%) were non-Hispanic White (White), 24 850 persons (21.6%) were non-Hispanic Black (Black), 11 903 persons (10.3%) were Hispanic, 5517 persons (5.1%) were non-Hispanic Asian or Pacific Islander, and 857 persons (0.7%) were non-Hispanic American Indian or Alaska Native. Among persons aged younger than 75 years and compared with White persons of the same ages, Black persons were more likely to be hospitalized (eg, age 50-64 years: rate ratio [RR], 2.50 95% CI, 2.43-2.57) and to be admitted to an ICU (eg, age 50-64 years: RR, 2.09; 95% CI, 1.96-2.23). Among persons aged younger than 50 years and compared with White persons of the same ages, American Indian or Alaska Native persons were more likely to be hospitalized (eg, age 18-49 years: RR, 1.72; 95% CI, 1.51-1.96) and to be admitted to an ICU (eg, age 18-49 years: RR, 1.84; 95% CI, 1.40-2.42). Among children aged 4 years or younger and compared with White children, hospitalization rates were higher in Black children (RR, 2.21; 95% CI, 2.10-2.33), Hispanic children (RR, 1.87; 95% CI, 1.77-1.97), American Indian or Alaska Native children (RR, 3.00; 95% CI, 2.55-3.53), and Asian or Pacific Islander children (RR, 1.26; 95% CI, 1.16-1.38), as were rates of ICU admission (Black children: RR, 2.74; 95% CI, 2.43-3.09; Hispanic children: RR, 1.96; 95% CI, 1.73-2.23; American Indian and Alaska Native children: RR, 3.51; 95% CI, 2.45-5.05). In this age group and compared with White children, in-hospital death rates were higher among Hispanic children (RR, 2.98; 95% CI, 1.23-7.19), Black children (RR, 3.39; 95% CI, 1.40-8.18), and Asian or Pacific Islander children (RR, 4.35; 95% CI, 1.55-12.22). Few differences were observed in rates of severe influenza-associated outcomes by race and ethnicity among adults aged 75 years or older. For example, in this age group, compared with White adults, hospitalization rates were slightly higher only among Black adults (RR, 1.05; 95% CI 1.02-1.09). Overall, Black persons had the highest age-adjusted hospitalization rate (68.8 [95% CI, 68.0-69.7] hospitalizations per 100 000 population) and ICU admission rate (11.6 [95% CI, 11.2-11.9] admissions per 100 000 population). Conclusions and Relevance: This cross-sectional study found racial and ethnic disparities in rates of severe influenza-associated disease. These data identified subgroups for whom improvements in influenza prevention efforts could be targeted.

Effectiveness of COVID-19 Vaccines in Preventing Hospitalization Among Adults Aged ≥65 Years - COVID-NET, 13 States, February-April 2021.

Clinical trials of COVID-19 vaccines currently authorized for emergency use in the United States (Pfizer-BioNTech, Moderna, and Janssen [Johnson & Johnson]) indicate that these vaccines have high efficacy against symptomatic disease, including moderate to severe illness (1-3). In addition to clinical trials, real-world assessments of COVID-19 vaccine effectiveness are critical in guiding vaccine policy and building vaccine confidence, particularly among populations at higher risk for more severe illness from COVID-19, including older adults. To determine the real-world effectiveness of the three currently authorized COVID-19 vaccines among persons aged ≥65 years during February 1-April 30, 2021, data on 7,280 patients from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) were analyzed with vaccination coverage data from state immunization information systems (IISs) for the COVID-NET catchment area (approximately 4.8 million persons). Among adults aged 65-74 years, effectiveness of full vaccination in preventing COVID-19-associated hospitalization was 96% (95% confidence interval [CI] = 94%-98%) for Pfizer-BioNTech, 96% (95% CI = 95%-98%) for Moderna, and 84% (95% CI = 64%-93%) for Janssen vaccine products. Effectiveness of full vaccination in preventing COVID-19-associated hospitalization among adults aged ≥75 years was 91% (95% CI = 87%-94%) for Pfizer-BioNTech, 96% (95% CI = 93%-98%) for Moderna, and 85% (95% CI = 72%-92%) for Janssen vaccine products. COVID-19 vaccines currently authorized in the United States are highly effective in preventing COVID-19-associated hospitalizations in older adults. In light of real-world data demonstrating high effectiveness of COVID-19 vaccines among older adults, efforts to increase vaccination coverage in this age group are critical to reducing the risk for COVID-19-related hospitalization.

Hospitalization of Adolescents Aged 12-17 Years with Laboratory-Confirmed COVID-19 - COVID-NET, 14 States, March 1, 2020-April 24, 2021.

Most COVID-19-associated hospitalizations occur in older adults, but severe disease that requires hospitalization occurs in all age groups, including adolescents aged 12-17 years (1). On May 10, 2021, the Food and Drug Administration expanded the Emergency Use Authorization for Pfizer-BioNTech COVID-19 vaccine to include persons aged 12-15 years, and CDC's Advisory Committee on Immunization Practices recommended it for this age group on May 12, 2021.* Before that time, COVID-19 vaccines had been available only to persons aged ≥16 years. Understanding and describing the epidemiology of COVID-19-associated hospitalizations in adolescents and comparing it with adolescent hospitalizations associated with other vaccine-preventable respiratory viruses, such as influenza, offers evidence of the benefits of expanding the recommended age range for vaccination and provides a baseline and context from which to assess vaccination impact. Using the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET), CDC examined COVID-19-associated hospitalizations among adolescents aged 12-17 years, including demographic and clinical characteristics of adolescents admitted during January 1-March 31, 2021, and hospitalization rates (hospitalizations per 100,000 persons) among adolescents during March 1, 2020-April 24, 2021. Among 204 adolescents who were likely hospitalized primarily for COVID-19 during January 1-March 31, 2021, 31.4% were admitted to an intensive care unit (ICU), and 4.9% required invasive mechanical ventilation; there were no associated deaths. During March 1, 2020-April 24, 2021, weekly adolescent hospitalization rates peaked at 2.1 per 100,000 in early January 2021, declined to 0.6 in mid-March, and then rose to 1.3 in April. Cumulative COVID-19-associated hospitalization rates during October 1, 2020-April 24, 2021, were 2.5-3.0 times higher than were influenza-associated hospitalization rates from three recent influenza seasons (2017-18, 2018-19, and 2019-20) obtained from the Influenza Hospitalization Surveillance Network (FluSurv-NET). Recent increased COVID-19-associated hospitalization rates in March and April 2021 and the potential for severe disease in adolescents reinforce the importance of continued COVID-19 prevention measures, including vaccination and correct and consistent wearing of masks by persons not yet fully vaccinated or when required by laws, rules, or regulations.†.

Acute Cardiovascular Events Associated With Influenza in Hospitalized Adults : A Cross-sectional Study.

BACKGROUND: Influenza may contribute to the burden of acute cardiovascular events during annual influenza epidemics. OBJECTIVE: To examine acute cardiovascular events and determine risk factors for acute heart failure (aHF) and acute ischemic heart disease (aIHD) in adults with a hospitalization associated with laboratory-confirmed influenza. DESIGN: Cross-sectional study. SETTING: U.S. Influenza Hospitalization Surveillance Network during the 2010-to-2011 through 2017-to-2018 influenza seasons. PARTICIPANTS: Adults hospitalized with laboratory-confirmed influenza and identified through influenza testing ordered by a practitioner. MEASUREMENTS: Acute cardiovascular events were ascertained using discharge codes from the International Classification of Diseases (ICD), Ninth Revision, Clinical Modification, and ICD, 10th Revision. Age, sex, race/ethnicity, tobacco use, chronic conditions, influenza vaccination, influenza antiviral medication, and influenza type or subtype were included as exposures in logistic regression models, and marginal adjusted risk ratios and 95% CIs were estimated to describe factors associated with aHF or aIHD. RESULTS: Among 89 999 adults with laboratory-confirmed influenza, 80 261 had complete medical record abstractions and available ICD codes (median age, 69 years [interquartile range, 54 to 81 years]) and 11.7% had an acute cardiovascular event. The most common such events (non-mutually exclusive) were aHF (6.2%) and aIHD (5.7%). Older age, tobacco use, underlying cardiovascular disease, diabetes, and renal disease were significantly associated with higher risk for aHF and aIHD in adults hospitalized with laboratory-confirmed influenza. LIMITATION: Underdetection of cases was likely because influenza testing was based on practitioner orders. Acute cardiovascular events were identified by ICD discharge codes and may be subject to misclassification bias. CONCLUSION: In this population-based study of adults hospitalized with influenza, almost 12% of patients had an acute cardiovascular event. Clinicians should ensure high rates of influenza vaccination, especially in those with underlying chronic conditions, to protect against acute cardiovascular events associated with influenza. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.