BACKGROUND: Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States, with sporadic human cases. We describe characteristics of human A(H5N1) cases identified from March through October 2024 in the United States. METHODS: We analyzed data from persons with laboratory-confirmed A(H5N1) virus infection using a standardized case-report form linked to laboratory results from the Centers for Disease Control and Prevention influenza A/H5 subtyping kit. RESULTS: Of 46 case patients, 20 were exposed to infected poultry, 25 were exposed to infected or presumably infected dairy cows, and 1 had no identified exposure; that patient was hospitalized with nonrespiratory symptoms, and A(H5N1) virus infection was detected through routine surveillance. Among the 45 case patients with animal exposures, the median age was 34 years, and all had mild A(H5N1) illness; none were hospitalized, and none died. A total of 42 patients (93%) had conjunctivitis, 22 (49%) had fever, and 16 (36%) had respiratory symptoms; 15 (33%) had conjunctivitis only. The median duration of illness among 16 patients with available data was 4 days (range, 1 to 8). Most patients (87%) received oseltamivir; oseltamivir was started a median of 2 days after symptom onset. No additional cases were identified among the 97 household contacts of case patients with animal exposures. The types of personal protective equipment (PPE) that were most commonly used by workers exposed to infected animals were gloves (71%), eye protection (60%), and face masks (47%). CONCLUSIONS: In the cases identified to date, A(H5N1) viruses generally caused mild illness, mostly conjunctivitis, of short duration, predominantly in U.S. adults exposed to infected animals; most patients received prompt antiviral treatment. No evidence of human-to-human A(H5N1) transmission was identified. PPE use among occupationally exposed persons was suboptimal, which suggests that additional strategies are needed to reduce exposure risk. (Funded by the Centers for Disease Control and Prevention.).

BACKGROUND: The 2023-2024 influenza season had predominant influenza A(H1N1)pdm09 virus activity, but A(H3N2) and B viruses co-circulated. Seasonal influenza vaccine strains were well-matched to these viruses. METHODS: Using health care encounters data from health systems in 8 states, we evaluated influenza vaccine effectiveness (VE) against influenza-associated medical encounters from October 2023-April 2024. Using a test-negative design, we compared the odds of vaccination between patients with an acute respiratory illness (ARI) who tested positive (cases) versus negative (controls) for influenza by molecular assay, adjusting for confounders. VE was stratified by age group, influenza type (overall, influenza A, influenza B), and care setting (hospitalization, emergency department or urgent care [ED/UC] encounter). RESULTS: Overall, 74,000 encounters in children and adolescents aged 6 months - 17 years (3,479 hospitalizations, 70,521 ED/UC encounters) and 267,606 in adults aged ≥18 years (66,828 hospitalizations, 200,778 ED/UC encounters) were included. Across care settings, among children and adolescents 15% (2,758/17,833) of cases versus 32% (18,240/56,167) of controls had received vaccination. Among adults, 25% (11,632/46,614) of cases versus 44% (97,811/220,992) of controls across care settings had received vaccination. VE was 58% (95% confidence interval [95% CI]: 44-69%) against hospitalization and 58% (95% CI: 56-60%) against ED/UC encounters for children and adolescents, and 39% (95% CI: 35-43) against hospitalization and 47% (95% CI: 46-49%) against ED/UC encounters for adults. Across age groups, VE was higher against influenza B than influenza A. CONCLUSIONS: Influenza vaccines provided protection against influenza-associated illness across health care settings and age groups during the 2023-2024 influenza season.

BACKGROUND: clinical guidelines recommend initiation of antiviral therapy as soon as possible for patients hospitalized with confirmed or suspected influenza. METHODS: A multicenter US observational sentinel surveillance network prospectively enrolled adults (aged ≥18 years) hospitalized with laboratory-confirmed influenza at 24 hospitals during October 1, 2022-July 21, 2023. A multivariable proportional odds model was used to compare peak pulmonary disease severity (no oxygen support, standard supplemental oxygen, high-flow oxygen/non-invasive ventilation, invasive mechanical ventilation, or death) after the day of hospital admission among patients starting oseltamivir treatment on the day of admission (early) versus those who did not (late or not treated), adjusting for baseline (admission day) severity, age, sex, site, and vaccination status. Multivariable logistic regression models were used to evaluate the odds of intensive care unit (ICU) admission, acute kidney replacement therapy or vasopressor use, and in-hospital death. RESULTS: A total of 840 influenza-positive patients were analyzed, including 415 (49%) who started oseltamivir treatment on the day of admission, and 425 (51%) who did not. Compared with late or not treated patients, those treated early had lower peak pulmonary disease severity (proportional aOR: 0.60, 95% CI: 0.49-0.72), and lower odds of intensive care unit admission (aOR: 0.24, 95% CI: 0.13-0.47), acute kidney replacement therapy or vasopressor use (aOR: 0.40, 95% CI: 0.22-0.67), and in-hospital death (aOR: 0.36, 95% CI: 0.18-0.72). CONCLUSION: Among adults hospitalized with influenza, treatment with oseltamivir on day of hospital admission was associated reduced risk of disease progression, including pulmonary and extrapulmonary organ failure and death.

Antiviral therapy is underutilized for outpatients at increased risk for severe COVID-19 or influenza. Results from this survey offer insights into treatment barriers from the infectious disease specialist perspective. Further education is needed about the benefits of early antiviral therapy.

IMPORTANCE: Seasonal influenza is associated with substantial disease burden. The relationship between census tract-based social vulnerability and clinical outcomes among patients with influenza remains unknown. OBJECTIVE: To characterize associations between social vulnerability and outcomes among patients hospitalized with influenza and to evaluate seasonal influenza vaccine and influenza antiviral utilization patterns across levels of social vulnerability. DESIGN, SETTING, AND PARTICIPANTS: This retrospective repeated cross-sectional study was conducted among adults with laboratory-confirmed influenza-associated hospitalizations from the 2014 to 2015 through the 2018 to 2019 influenza seasons. Data were from a population-based surveillance network of counties within 13 states. Data analysis was conducted in December 2023. EXPOSURE: Census tract-based social vulnerability. MAIN OUTCOMES AND MEASURES: Associations between census tract-based social vulnerability and influenza outcomes (intensive care unit admission, invasive mechanical ventilation and/or extracorporeal membrane oxygenation support, and 30-day mortality) were estimated using modified Poisson regression as adjusted prevalence ratios. Seasonal influenza vaccine and influenza antiviral utilization were also characterized across levels of social vulnerability. RESULTS: Among 57 964 sampled cases, the median (IQR) age was 71 (58-82) years; 55.5% (95% CI, 51.5%-56.0%) were female; 5.2% (5.0%-5.4%) were Asian or Pacific Islander, 18.3% (95% CI, 18.0%-18.6%) were Black or African American, and 64.6% (95% CI, 64.2%-65.0%) were White; and 6.6% (95% CI, 6.4%-68%) were Hispanic or Latino and 74.7% (95% CI, 74.3%-75.0%) were non-Hispanic or Latino. High social vulnerability was associated with higher prevalence of invasive mechanical ventilation and/or extracorporeal membrane oxygenation support (931 of 13 563 unweighted cases; adjusted prevalence ratio [aPR], 1.25 [95% CI, 1.13-1.39]), primarily due to socioeconomic status (790 of 11 255; aPR, 1.31 [95% CI, 1.17-1.47]) and household composition and disability (773 of 11 256; aPR, 1.20 [95% CI, 1.09-1.32]). Vaccination status, presence of underlying medical conditions, and respiratory symptoms partially mediated all significant associations. As social vulnerability increased, the proportion of patients receiving seasonal influenza vaccination declined (-19.4% relative change across quartiles; P < .001) as did the proportion vaccinated by October 31 (-6.8%; P < .001). No differences based on social vulnerability were found in in-hospital antiviral receipt, but early in-hospital antiviral initiation (-1.0%; P = .01) and prehospital antiviral receipt (-17.3%; P < .001) declined as social vulnerability increased. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, social vulnerability was associated with a modestly increased prevalence of invasive mechanical ventilation and/or extracorporeal membrane oxygenation support among patients hospitalized with influenza. Contributing factors may have included worsened baseline respiratory health and reduced receipt of influenza prevention and prehospital or early in-hospital treatment interventions among persons residing in low socioeconomic areas.

Annually, tens of thousands of U.S. children and adolescents are hospitalized with seasonal influenza virus infection. Both influenza vaccination and early initiation of antiviral treatment can reduce complications of influenza. Using data from two U.S. influenza surveillance networks for children and adolescents aged <18 years with medically attended, laboratory-confirmed influenza for whom antiviral treatment is recommended, the percentage who received treatment was calculated. Trends in antiviral treatment of children and adolescents hospitalized with influenza from the 2017-18 to the 2023-2024 influenza seasons were also examined. Since 2017-18, when 70%-86% of hospitalized children and adolescents with influenza received antiviral treatment, the proportion receiving treatment notably declined. Among children and adolescents with influenza during the 2023-24 season, 52%-59% of those hospitalized received antiviral treatment. During the 2023-24 season, 31% of those at higher risk for influenza complications seen in the outpatient setting in one network were prescribed antiviral treatment. These findings demonstrate that influenza antiviral treatment is underutilized among children and adolescents who could benefit from treatment. All hospitalized children and adolescents, and those at higher risk for influenza complications in the outpatient setting, should receive antiviral treatment as soon as possible for suspected or confirmed influenza.

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.

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.

INTRODUCTION: The current literature suggests that the frequency and complexity of public health emergencies are rising and this trend will likely continue. From 2000 to 2023, seven events have been declared as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO). Organisational models such as the Incident Management System, Incident Response System and Incident Command System or country-specific models are essential in managing PHEIC.The review aims to achieve four key objectives. First, identify and describe the organisational models used in the South-East Asia Region (SEAR) nations defined by WHO as Bangladesh, Bhutan, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, Timor-Leste and DPR Korea for managing PHEICs. Second, explore the indicators used to gauge the effectiveness of these models. Third, assess how these indicators impact the overall success of organisational models. Finally, the review will delve into the implementation aspects gaining a deeper understanding of how the organisational models are put into practice to manage PHEICs in the SEAR region. METHODS AND ANALYSIS: Following Preferred Reporting Items for Systematic review and Meta-Analysis Protocols guidelines, a qualitative evidence synthesis will be conducted. A defined search strategy will be employed to conduct a comprehensive literature search of the following academic databases: PubMed (MEDLINE), Excerpta Medica Database, Cochrane CENTRAL, Cumulative Index to Nursing and Allied Health Literature, WHO Library Database, US Centers for Disease Control and Prevention (CDC), CDC's Morbidity and Mortality Weekly Report and Web of Science; as well as non-academic databases including Google Scholar, Evidence Aid, Epistemonikos, Shodhganga and ResearchGate. This review will employ the SPIDER-D tool for searching qualitative studies. Two reviewers will check the quality of included studies and will be appraised using standard critical appraisal tools. In case of any difference between the two reviewers, a third reviewer will take the decision. ETHICS AND DISSEMINATION: No ethical approval is required. Results will be published in a peer-reviewed journal and disseminated through a workshop for stakeholders and policymakers. PROSPERO REGISTRATION NUMBER: CRD42023394418.

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.

BACKGROUND: The 2022-2023 United States influenza season had unusually early influenza activity with high hospitalization rates. Vaccine-matched A(H3N2) viruses predominated, with lower levels of A(H1N1)pdm09 activity also observed. METHODS: Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022-2023 season against influenza A-associated emergency department/urgent care (ED/UC) visits and hospitalizations from October 2022 to March 2023 among adults (aged ≥18 years) with acute respiratory illness (ARI). VE was estimated by comparing odds of seasonal influenza vaccination among case-patients (influenza A test positive by molecular assay) and controls (influenza test negative), applying inverse-propensity-to-be-vaccinated weights. RESULTS: The analysis included 85 389 ED/UC ARI encounters (17.0% influenza A positive; 37.8% vaccinated overall) and 19 751 hospitalizations (9.5% influenza A positive; 52.8% vaccinated overall). VE against influenza A-associated ED/UC encounters was 44% (95% confidence interval [CI], 40%-47%) overall and 45% and 41% among adults aged 18-64 and ≥65 years, respectively. VE against influenza A-associated hospitalizations was 35% (95% CI, 27%-43%) overall and 23% and 41% among adults aged 18-64 and ≥65 years, respectively. CONCLUSIONS: VE was moderate during the 2022-2023 influenza season, a season characterized with increased burden of influenza and co-circulation with other respiratory viruses. Vaccination is likely to substantially reduce morbidity, mortality, and strain on healthcare resources.

We reviewed the tools that have been developed to characterize and communicate seasonal influenza activity in the United States. Here we focus on systematic surveillance and applied analytics, including seasonal burden and disease severity estimation, short-term forecasting, and longer-term modeling efforts. For each set of activities, we describe the challenges and opportunities that have arisen because of the COVID-19 pandemic. In conclusion, we highlight how collaboration and communication have been and will continue to be key components of reliable and actionable influenza monitoring, forecasting, and modeling activities.

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE against influenza A ranged from 46% to 59% for children and adolescents and from 27% to 46% for adults across settings. VE against influenza B ranged from 64% to 89% for pediatric patients in outpatient settings and from 60% to 78% for all adults across settings. These findings demonstrate that the 2023-24 seasonal influenza vaccine is effective at reducing the risk for medically attended influenza virus infection. CDC recommends that all persons aged ≥6 months who have not yet been vaccinated this season get vaccinated while influenza circulates locally.

Severe outcomes were common among adults hospitalized for COVID-19 or influenza, while the percentage of COVID-19 hospitalizations involving critical care decreased from October 2021 to September 2022. During the Omicron BA.5 period, intensive care unit admission frequency was similar for COVID-19 and influenza, although patients with COVID-19 had a higher frequency of in-hospital death.

Background: Tenofovir Disoproxil Fumarate (TDF) is one of the first-line antiretroviral therapy (ART) recommended for all treatment naïve People Living with HIV (PLHIV). However, evidence indicates increasing TDF-associated nephrotoxicity among PLHIV due to longer duration of treatment and longevity that raises clinical and programmatic concerns. This review aims to understand the extent of TDF-induced nephrotoxicity and associated factors. Methods: The article is based on a comprehensive scoping review of journal articles, reports and guidelines related to the use of TDF-based ART regimens in electronic databases such as the National Library of Medicine (PubMed), Google Scholar, Web of Science, Scopus and other relevant search engines. Results: The review provides evidence on the burden of nephrotoxicity due to TDF among PLHIV and its variations across geographic regions and population groups. The review highlights the key factors associated with TDF-induced nephrotoxicity which include age, gender, nutrition status (BMI), duration of treatment with TDF, baseline creatinine, baseline CD4 count, WHO HIV stage of disease and presence of comorbid conditions. The review also emphasizes the importance of baseline and regular renal monitoring and early detection of TDF-induced nephrotoxicity to avoid irreversible tubulointerstitial damage through simple laboratory investigations such as glomerular filtration rate (GFR), blood urea nitrogen, serum creatinine and creatinine clearance. Conclusion: The burden of TDF-associated nephrotoxicity is well documented. It is critical to consider the risk factors associated with nephrotoxicity while initiating TDF. The review provides evidence for calibrating the dosage of TDF based on body weight and BMI. Considering the high burden of PLHIV in India, prevention of nephrotoxicity through targeted and regular monitoring, early diagnosis and initiation of appropriate clinical management is crucial to reduce avoidable morbidity and mortality. © 2023

BACKGROUND: Older age and chronic conditions are associated with severe influenza outcomes; however, data are only comprehensively available for adults ≥65 years old. Using data from the Influenza Hospitalization Surveillance Network (FluSurv-NET), we identified characteristics associated with severe outcomes in adults 18-49 years old hospitalized with influenza. METHODS: We included FluSurv-NET data from nonpregnant adults 18-49 years old hospitalized with laboratory-confirmed influenza during the 2011-2012 through 2018-2019 seasons. We used bivariate and multivariable logistic regression to determine associations between select characteristics and severe outcomes including intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and in-hospital death. RESULTS: A total of 16 140 patients aged 18-49 years and hospitalized with influenza were included in the analysis; the median age was 39 years, and 26% received current-season influenza vaccine before hospitalization. Obesity, asthma, and diabetes mellitus were the most common chronic conditions. Conditions associated with a significantly increased risk of severe outcomes included age group 30-39 or 40-49 years (IMV, age group 30-39 years: adjusted odds ratio [aOR], 1.25; IMV, age group 40-49 years: aOR, 1.36; death, age group 30-39 years: aOR, 1.28; death, age group 40-49 years: aOR, 1.69), being unvaccinated (ICU: aOR, 1.18; IMV: aOR, 1.25; death: aOR, 1.48), and having chronic conditions including extreme obesity and chronic lung, cardiovascular, metabolic, neurologic, or liver diseases (ICU: range aOR, 1.22-1.56; IMV: range aOR, 1.17-1.54; death: range aOR, 1.43-2.36). CONCLUSIONS: To reduce the morbidity and mortality associated with influenza among adults aged 18-49 years, health care providers should strongly encourage receipt of annual influenza vaccine and lifestyle/behavioral modifications, particularly among those with chronic medical conditions.

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: Antiviral chemoprophylaxis is recommended for use during influenza outbreaks in nursing homes to prevent transmission and severe disease among non-ill residents. Centers for Disease Control and Prevention (CDC) guidance recommends prophylaxis be initiated for all non-ill residents once an influenza outbreak is detected and be continued for at least 14 days and until seven days after the last laboratory-confirmed influenza case is identified. However, not all facilities strictly adhere to this guidance and the impact of such partial adherence is not fully understood. METHODS: We developed a stochastic compartmental framework to model influenza transmission within an average-sized U.S. nursing home. We compared the number of symptomatic illnesses and hospitalizations under varying prophylaxis implementation strategies, in addition to different levels of prophylaxis uptake and adherence by residents and healthcare personnel (HCP). RESULTS: Prophylaxis implemented according to current guidance reduced total symptomatic illnesses and hospitalizations among residents by an average of 12% and 36%, respectively, compared with no prophylaxis. We did not find evidence that alternative implementations of prophylaxis were more effective: compared to full adoption of current guidance, partial adoption resulted in increased symptomatic illnesses and/or hospitalizations, and longer or earlier adoption offered no additional improvements. In addition, increasing uptake and adherence among nursing home residents was effective in reducing resident illnesses and hospitalizations, but increasing HCP uptake had minimal indirect impacts for residents. CONCLUSIONS: The greatest benefits of influenza prophylaxis during nursing home outbreaks will likely be achieved through increasing uptake and adherence among residents and following current CDC guidance.

BACKGROUND: The 2022-2023 United States influenza season had unusually early influenza activity with high hospitalization rates. Vaccine-matched A(H3N2) viruses predominated, with lower levels of A(H1N1)pdm09 activity also observed. METHODS: Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022-2023 season against influenza-A-associated emergency department/urgent care (ED/UC) visits and hospitalizations from October 2022-March 2023 among adults (age ≥18 years) with acute respiratory illness (ARI). VE was estimated by comparing odds of seasonal influenza vaccination among case-patients (influenza A test-positive by molecular assay) and controls (influenza test-negative), applying inverse-propensity-to-be-vaccinated weights. RESULTS: The analysis included 85,389 ED/UC ARI encounters (17.0% influenza-A-positive; 37.8% vaccinated overall) and 19,751 hospitalizations (9.5% influenza-A-positive; 52.8% vaccinated overall). VE against influenza-A-associated ED/UC encounters was 44% (95% confidence interval [95%CI]: 40-47%) overall and 45% and 41% among adults aged 18-64 and ≥65 years, respectively. VE against influenza-A-associated hospitalizations was 35% (95%CI: 27-43%) overall and 23% and 41% among adults aged 18-64 and ≥65 years, respectively. CONCLUSIONS: VE was moderate during the 2022-2023 influenza season, a season characterized with increased burden of influenza and co-circulation with other respiratory viruses. Vaccination is likely to substantially reduce morbidity, mortality, and strain on healthcare resources.

Influenza vaccines have been routinely recommended in the United States for some groups since 1960 and for everyone 6 months of age or older for more than a decade. Yet, annual influenza vaccination coverage has rarely exceeded 50% in children and younger adults or 70% in adults aged 65 years or older (1). Long-standing barriers to influenza vaccine uptake include beliefs that influenza illness is mild or inconsequential and vaccines are not effective, concerns about safety and adverse effects, and distrust of the medical system and disparities in access to vaccines (1, 2). | | During the COVID-19 pandemic, influenza vaccination coverage rates remained low overall and declined in some groups (1, 3). Although the first year of the COVID-19 pandemic temporarily interrupted circulation of seasonal respiratory viruses, the United States experienced high levels of influenza virus, SARS-CoV-2, and respiratory syncytial virus co-circulation during the 2022 to 2023 influenza season, putting a strain on health care resources. As the 2023 to 2024 season begins, internal medicine physicians and other health care professionals play an important role in communicating the benefits of vaccinations against influenza and other respiratory viruses. A health care professional’s recommendation and offer of or referral for vaccination have been shown over many seasons to be one of the strongest factors associated with willingness to get vaccinated (2).

BACKGROUND: During the 2022-2023 influenza season, the United States experienced the highest influenza-associated pediatric hospitalization rate since 2010-2011. Influenza A/H3N2 infections were predominant. METHODS: We analyzed acute respiratory illness (ARI)-associated emergency department or urgent care (ED/UC) encounters or hospitalizations at three health systems among children and adolescents aged 6 months-17 years who had influenza molecular testing during October 2022-March 2023. We estimated influenza A vaccine effectiveness (VE) using a test-negative approach. The odds of vaccination among influenza-A-positive cases and influenza-negative controls were compared after adjusting for confounders and applying inverse-propensity-to-be-vaccinated weights. We developed overall and age-stratified VE models. RESULTS: Overall, 13,547 of 44,787 (30.2%) eligible ED/UC encounters and 263 of 1,862 (14.1%) hospitalizations were influenza-A-positive cases. Among ED/UC patients, 15.2% of influenza-positive versus 27.1% of influenza-negative patients were vaccinated; VE was 48% (95% confidence interval [CI], 44%-52%) overall, 53% (95% CI, 47%-58%) among children aged 6 months-4 years and 38% (95% CI, 30%-45%) among those aged 9-17 years. Among hospitalizations, 17.5% of influenza-positive versus 33.4% of influenza-negative patients were vaccinated; VE was 40% (95% CI, 6%-61%) overall, 56% (95% CI, 23%-75%) among children ages 6 months-4 years and 46% (95% CI, 2%-70%) among those 5-17 years. CONCLUSIONS: During the 2022-2023 influenza season, vaccination reduced the risk of influenza-associated ED/UC encounters and hospitalizations by almost half (overall VE 40-48%). Influenza vaccination is a critical tool to prevent moderate-to-severe influenza illness in children and adolescents.

During the 2022-23 influenza season, early increases in influenza activity, co-circulation of influenza with other respiratory viruses, and high influenza-associated hospitalization rates, particularly among children and adolescents, were observed. This report describes the 2022-23 influenza season among children and adolescents aged <18 years, including the seasonal severity assessment; estimates of U.S. influenza-associated medical visits, hospitalizations, and deaths; and characteristics of influenza-associated hospitalizations. The 2022-23 influenza season had high severity among children and adolescents compared with thresholds based on previous seasons' influenza-associated outpatient visits, hospitalization rates, and deaths. Nationally, the incidences of influenza-associated outpatient visits and hospitalization for the 2022-23 season were similar for children aged <5 years and higher for children and adolescents aged 5-17 years compared with previous seasons. Peak influenza-associated outpatient and hospitalization activity occurred in late November and early December. Among children and adolescents hospitalized with influenza during the 2022-23 season in hospitals participating in the Influenza Hospitalization Surveillance Network, a lower proportion were vaccinated (18.3%) compared with previous seasons (35.8%-41.8%). Early influenza circulation, before many children and adolescents had been vaccinated, might have contributed to the high hospitalization rates during the 2022-23 season. Among symptomatic hospitalized patients, receipt of influenza antiviral treatment (64.9%) was lower than during pre-COVID-19 pandemic seasons (80.8%-87.1%). CDC recommends that all persons aged ≥6 months without contraindications should receive the annual influenza vaccine, ideally by the end of October.

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.

INTRODUCTION: Influenza remains an important cause of hospitalizations in the United States. Estimating the number of influenza hospitalizations is vital for public health decision making. Combining existing surveillance systems through capture-recapture methods allows for more comprehensive burden estimations. METHODS: Data from independent surveillance systems were combined using capture-recapture methods to estimate influenza hospitalization rates for children and adults in Middle Tennessee during consecutive influenza seasons from 2016-17 through 2019-20. EIP identified cases through surveillance of laboratory results for hospitalized children and adults. HAIVEN and NVSN recruited hospitalized patients with respiratory symptoms or fever. Population-based influenza rates and the proportion of cases detected by each surveillance system were calculated. RESULTS: Estimated overall influenza hospitalization rates ranged from 23 influenza-related hospitalizations per 10,000 persons in 2016-17 to 40 per 10,000 persons in 2017-18. Adults age ≥65 years had the highest hospitalization rates across seasons and experienced a rate of 170 hospitalizations per 10,000 persons during the 2017-18 season. EIP consistently identified a higher proportion of influenza cases for adults and children compared with HAIVEN and NVSN, respectively. CONCLUSION: Current surveillance systems underestimate the influenza burden. Capture-recapture provides an alternative approach to use data from independent surveillance systems and complement population-based burden estimates.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect (CHD) characterized by hypoplasia of the left ventricle and aorta along with stenosis or atresia of the aortic and mitral valves. HLHS represents only ∼4%-8% of all CHDs but accounts for ∼25% of deaths. HLHS is an isolated defect (i.e., iHLHS) in 70% of families, the vast majority of which are simplex. Despite intense investigation, the genetic basis of iHLHS remains largely unknown. We performed exome sequencing on 331 families with iHLHS aggregated from four independent cohorts. A Mendelian-model-based analysis demonstrated that iHLHS was not due to single, large-effect alleles in genes previously reported to underlie iHLHS or CHD in >90% of families in this cohort. Gene-based association testing identified increased risk for iHLHS associated with variation in CAPN2 (p = 1.8 × 10(-5)), encoding a protein involved in functional adhesion. Functional validation studies in a vertebrate animal model (Xenopus laevis) confirmed CAPN2 is essential for cardiac ventricle morphogenesis and that in vivo loss of calpain function causes hypoplastic ventricle phenotypes and suggest that human CAPN2(707C>T) and CAPN2(1112C>T) variants, each found in multiple individuals with iHLHS, are hypomorphic alleles. Collectively, our findings show that iHLHS is typically not a Mendelian condition, demonstrate that CAPN2 variants increase risk of iHLHS, and identify a novel pathway involved in HLHS pathogenesis.

BACKGROUND: The epidemiology of COVID-19 continues to develop with emerging variants, expanding population-level immunity, and advances in clinical care. We describe changes in the clinical epidemiology of hospitalized COVID-19 and risk factors for critical outcomes over time. METHODS: We included adults aged ≥18 years from 10 states hospitalized with COVID-19 June 2021-March 2023 when multiple SARS-CoV-2 variants or sub-lineages predominated. We evaluated changes in baseline demographic and clinical characteristics and critical outcomes (intensive care unit admission and/or death) and used regression models to evaluate critical outcomes risk factors (risk ratios) stratified by COVID-19 vaccination status. RESULTS: 60,488 COVID-19-associated hospitalizations were included in the analysis. Among those hospitalized, from Delta period (June-December 2021) to the Omicron post-BA.4/BA.5 period (September 2022-March 2023), median age increased from 60 to 75 years, proportion vaccinated increased from 18.2% to 70.1%, while critical outcomes declined from 24.8% to 19.4% (all p < 0.001). Compared to all hospitalization events, those with critical outcomes had a higher proportion of four or more categories of medical conditions categories assessed (32.8% critical versus 23.0% all hospitalized). Critical outcome risk factors were similar for unvaccinated and vaccinated populations; presence of ≥4 medical condition categories was most strongly associated with risk of critical outcomes regardless of vaccine status (unvaccinated aRR 2.27 [95% CI: 2.14-2.41]; vaccinated aRR 1.73 [95% CI: 1.56-1.92]) across periods. CONCLUSION: The proportion of adults hospitalized with COVID-19 who experienced critical outcomes decreased with time and median patient age increased with time. Multimorbidity was mostly strongly associated with critical outcomes.

Cardiovascular diseases (CVD), principally ischemic heart disease (IHD) and stroke, are the leading causes of death (18. 6 million deaths annually) and disability (393 million disability-adjusted life-years lost annually), worldwide. High blood pressure is the most important preventable risk factor for CVD and deaths, worldwide (10.8 million deaths annually). In 2016, the World Health Organization (WHO) and the United States Centers for Disease Control (CDC) launched the Global Hearts initiative to support governments in their quest to prevent and control CVD. HEARTS is the core technical package of the initiative and takes a public health approach to treating hypertension and other CVD risk factors at the primary health care level. The HEARTS Partner Forum, led by WHO, brings together the following 11 partner organizations: American Heart Association (AHA), Center for Chronic Disease Control (CCDC), International Society of Hypertension (ISH), International Society of Nephrology (ISN), Pan American Health Organization (PAHO), Resolve to Save Lives (RTSL), US CDC, World Hypertension League (WHL), World Heart Federation (WHF) and World Stroke Organization (WSO). The partners support countries in their implementation of the HEARTS technical package in various ways, including providing technical expertise, catalytic funding, capacity building and evidence generation and dissemination. HEARTS has demonstrated the feasibility and acceptability of a public health approach, with more than seven million people already on treatment for hypertension using a simple, algorithmic HEARTS approach. Additionally, HEARTS has demonstrated the feasibility of using hypertension as a pathfinder to universal health coverage and should be a key intervention of all basic benefit packages. The partner forum continues to find ways to expand support and reinvigorate enthusiasm and attention on preventing CVD. Proposed future HEARTS Partner Forum activities are related to more concrete information sharing between partners and among countries, expanded areas of partner synergy, support for implementation, capacity building, and advocacy with country ministries of health, professional societies, academy and civil societies organizations. Advancing toward the shared goals of the HEARTS partners will require a more formal, structured approach to the forum and include goals, targets and published reports. In this way, the HEARTS Partner Forum will mirror successful global partnerships on communicable diseases and assist countries in reducing CVD mortality and achieving global sustainable development goals (SDGs).

Background The COVID-19 pandemic has caused substantial morbidity and mortality.Objectives To describe monthly demographic and clinical trends among adults hospitalized with COVID-19.Design Pooled cross-sectional.Setting 99 counties within 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET).Patients U.S. adults (aged ≥18 years) hospitalized with laboratory-confirmed COVID-19 during March 1-December 31, 2020.Measurements Monthly trends in weighted percentages of interventions and outcomes including length of stay (LOS), intensive care unit admissions (ICU), invasive mechanical ventilation (IMV), vasopressor use and in-hospital death (death). Monthly hospitalization, ICU and death rates per 100,000 population.Results Among 116,743 hospitalized adults, median age was 62 years. Among 18,508 sampled adults, median LOS decreased from 6.4 (March) to 4.6 days (December). Remdesivir and systemic corticosteroid use increased from 1.7% and 18.9% (March) to 53.8% and 74.2% (December), respectively. Frequency of ICU decreased from 37.8% (March) to 20.5% (December). IMV (27.8% to 8.7%), vasopressors (22.7% to 8.8%) and deaths (13.9% to 8.7%) decreased from March to October; however, percentages of these interventions and outcomes remained stable or increased in November and December. Percentage of deaths significantly decreased over time for non-Hispanic White patients (p-value &lt;0.01) but not non-Hispanic Black or Hispanic patients. Rates of hospitalization (105.3 per 100,000), ICU (20.2) and death (11.7) were highest during December.Limitations COVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country.Conclusions After initial improvement during April-October 2020, trends in interventions and outcomes worsened during November-December, corresponding with the 3rd peak of the U.S. pandemic. These data provide a longitudinal assessment of trends in COVID-19-associated outcomes prior to widespread COVID-19 vaccine implementation.Competing Interest StatementDr. Evan Anderson reports grants from Pfizer, grants from Merck, grants from PaxVax, grants from Micron, grants from Sanofi-Pasteur, grants from Janssen, grants from MedImmune, grants from GSK, personal fees from Sanofi-Pasteur, personal fees from Pfizer, personal fees from Medscape, personal fees from Kentucky Bioprocessing, Inc, personal fees from Sanofi-Pasteur, outside the submitted work. Dr. William Schaffner reports personal fees from VBI Vaccines, outside the submitted work. Funding StatementThis work was supported by the Centers of Disease Control and Prevention through an Emerging Infections Program cooperative agreement (grant CK17-1701) and through a Council of State and Territorial Epidemiologists cooperative agreement (grant NU38OT000297-02-00).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. Sites participating in COVID-NET obtained approval from their respective state and local Institutional Review Boards, as applicable.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting check ist(s) and other pertinent material as supplementary files, if applicable.YesPublicly available data referred to in this analysis can be found at: https://gis.cdc.gov/grasp/covidnet/covid19_3.html https://gis.cdc.gov/grasp/covidnet/covid19_3.html

Background Identification of risk factors for COVID-19-associated hospitalization is needed to guide prevention and clinical care.Objective To examine if age, sex, race/ethnicity, and underlying medical conditions is independently associated with COVID-19-associated hospitalizations.Design Cross-sectional.Setting 70 counties within 12 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET) and a population-based sample of non-hospitalized adults residing in the COVID-NET catchment area from the Behavioral Risk Factor Surveillance System.Participants U.S. community-dwelling adults (≥18 years) with laboratory-confirmed COVID-19-associated hospitalizations, March 1- June 23, 2020.Measurements Adjusted rate ratios (aRR) of hospitalization by age, sex, race/ethnicity and underlying medical conditions (hypertension, coronary artery disease, history of stroke, diabetes, obesity [BMI ≥30 kg/m2], severe obesity [BMI≥40 kg/m2], chronic kidney disease, asthma, and chronic obstructive pulmonary disease).Results Our sample included 5,416 adults with COVID-19-associated hospitalizations. Adults with (versus without) severe obesity (aRR:4.4; 95%CI: 3.4, 5.7), chronic kidney disease (aRR:4.0; 95%CI: 3.0, 5.2), diabetes (aRR:3.2; 95%CI: 2.5, 4.1), obesity (aRR:2.9; 95%CI: 2.3, 3.5), hypertension (aRR:2.8; 95%CI: 2.3, 3.4), and asthma (aRR:1.4; 95%CI: 1.1, 1.7) had higher rates of hospitalization, after adjusting for age, sex, and race/ethnicity. In models adjusting for the presence of an individual underlying medical condition, higher hospitalization rates were observed for adults ≥65 years, 45-64 years (versus 18-44 years), males (versus females), and non-Hispanic black and other race/ethnicities (versus non-Hispanic whites).Limitations Interim analysis limited to hospitalizations with underlying medical condition data.Conclusion Our findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions.Competing Interest StatementDr. Anderson reports personal fees from AbbVie, personal fees from Pfizer, grants from Pfizer, grants from Merck, grants from Micron, grants from Paxvax, grants from Sanofi Pasteur, grants from Novavax, grants from MedImmune, grants from Regeneron, grants from GSK, outside the submitted work. Mr. Henderson, Ms. Kim, Ms. George, and Ms. Hill report grants from Council of State and Territorial Epidemiologists (CSTE), during the conduct of the study. Dr. Lynfield reports grants from CDC- Emerging Infections Program, during the conduct of the study; and Royalties from a book on infectious disease surveillance and compensation for AAP Red Book (Report from Committee on Infectious Disease) donated to Minnesota Dept of Health. Dr. Schaffner reports grants from CDC, during the conduct of the study; personal fees from VBI Vaccines, outside the submitted work. Dr. Talbot reports other from Seqirus, outside the submitted work.Funding StatementThis work was supported by the Centers of Disease Control and Prevention through an Emerging Infections Program cooperative agreement (grant CK17-1701) and through a Council of State and Territorial Epidemiologists cooperative agreement (grant NU38OT000297-02-00).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This analysis was exempt from CDC's Institutional Review Board, as it was considered part of public health surveillance and emergency response. Participating sites obtained approval for the COVID-NET surveillance protocol from their respective state and local IRBs, as required.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved regi try, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData is not publically available at this time.