Last data update: Oct 07, 2024. (Total: 47845 publications since 2009)
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Organisational models for managing Public Health Emergencies of International Concern (PHEICs) in the South-East Asia Region (SEAR) nations: protocol for a systematic review
Sharma R , Chauhan H , Parkash S , Verma P , Sunthlia A , Verma N , Bhawalpuria N , Kathait A , Dogra A , Garg R , Kishore J , Jain S , Bhumika TV , Gokhale RH , Desai M , Ratnoo R , Goel A . BMJ Open 2024 14 (9) e084673 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. |
Timing of influenza antiviral therapy and risk of death in adults hospitalized with influenza-associated pneumonia, FluSurv-NET, 2012-2019
Tenforde MW , Noah KP , O'Halloran AC , Kirley PD , Hoover C , Alden NB , Armistead I , Meek J , Yousey-Hindes K , Openo KP , Witt LS , Monroe ML , Ryan PA , Falkowski A , Reeg L , Lynfield R , McMahon M , Hancock EB , Hoffman MR , McGuire S , Spina NL , Felsen CB , Gaitan MA , Lung K , Shiltz E , Thomas A , Schaffner W , Talbot HK , Crossland MT , Price A , Masalovich S , Adams K , Holstein R , Sundaresan D , Uyeki TM , Reed C , Bozio CH , Garg S . Clin Infect Dis 2024 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. |
Influenza vaccine effectiveness against influenza a-associated emergency department, urgent care, and hospitalization encounters among US Adults, 2022-2023
Tenforde MW , Weber ZA , Yang DH , DeSilva MB , Dascomb K , Irving SA , Naleway AL , Gaglani M , Fireman B , Lewis N , Zerbo O , Goddard K , Timbol J , Hansen JR , Grisel N , Arndorfer J , McEvoy CE , Essien IJ , Rao S , Grannis SJ , Kharbanda AB , Natarajan K , Ong TC , Embi PJ , Ball SW , Dunne MM , Kirshner L , Wiegand RE , Dickerson M , Patel P , Ray C , Flannery B , Garg S , Adams K , Klein NP . J Infect Dis 2024 230 (1) 141-151 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. |
Outbreak of highly pathogenic avian influenza A(H5N1) viruses in U.S. dairy cattle and detection of two human cases - United States, 2024
Garg S , Reed C , Davis CT , Uyeki TM , Behravesh CB , Kniss K , Budd A , Biggerstaff M , Adjemian J , Barnes JR , Kirby MK , Basler C , Szablewski CM , Richmond-Crum M , Burns E , Limbago B , Daskalakis DC , Armstrong K , Boucher D , Shimabukuro TT , Jhung MA , Olsen SJ , Dugan V . MMWR Morb Mortal Wkly Rep 2024 73 (21) 501-505 |
Responding to the return of influenza in the United States by applying Centers for Disease Control and Prevention surveillance, analysis, and modeling to inform understanding of seasonal influenza
Borchering RK , Biggerstaff M , Brammer L , Budd A , Garg S , Fry AM , Iuliano AD , Reed C . JMIR Public Health Surveill 2024 10 e54340 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. |
Interim estimates of 2023-24 seasonal influenza vaccine effectiveness - United States
Frutos AM , Price AM , Harker E , Reeves EL , Ahmad HM , Murugan V , Martin ET , House S , Saade EA , Zimmerman RK , Gaglani M , Wernli KJ , Walter EB , Michaels MG , Staat MA , Weinberg GA , Selvarangan R , Boom JA , Klein EJ , Halasa NB , Ginde AA , Gibbs KW , Zhu Y , Self WH , Tartof SY , Klein NP , Dascomb K , DeSilva MB , Weber ZA , Yang DH , Ball SW , Surie D , DeCuir J , Dawood FS , Moline HL , Toepfer AP , Clopper BR , Link-Gelles R , Payne AB , Chung JR , Flannery B , Lewis NM , Olson SM , Adams K , Tenforde MW , Garg S , Grohskopf LA , Reed C , Ellington S . MMWR Morb Mortal Wkly Rep 2024 73 (8) 168-174 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. |
Clinical outcomes of US adults hospitalized for COVID-19 and influenza in the Respiratory Virus Hospitalization Surveillance Network, October 2021-September 2022
Kojima N , Taylor CA , Tenforde MW , Ujamaa D , O'Halloran A , Patel K , Chai SJ , Daily Kirley P , Alden NB , Kawasaki B , Meek J , Yousey-Hindes K , Anderson EJ , Openo KP , Reeg L , Tellez Nunez V , Lynfield R , Como-Sabetti K , Ropp SL , Shaw YP , Spina NL , Barney G , Bushey S , Popham K , Moran NE , Shiltz E , Sutton M , Abdullah N , Talbot HK , Schaffner W , Chatelain R , Price A , Garg S , Havers FP , Bozio CH . Open Forum Infect Dis 2024 11 (1) ofad702 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. |
A review of Tenofovir Disoproxil Fumarate associated nephrotoxicity among People Living with HIV: Burden, risk factors and solutions
Asirvatham ES , Ranjan V , Garg C , Sarman CJ , Periasamy M , Yeldandi V , Upadhyaya S , Rao B . Clin Epidemiol Global Health 2024 25 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 |
Association of chronic medical conditions with severe outcomes among nonpregnant adults 18-49 years old hospitalized with influenza, FluSurv-NET, 2011-2019
Famati EA , Ujamaa D , O'Halloran A , Kirley PD , Chai SJ , Armistead I , Alden NB , Yousey-Hindes K , Openo KP , Ryan PA , Monroe ML , Falkowski A , Kim S , Lynfield R , McMahon M , Angeles KM , Khanlian SA , Spina NL , Bennett NM , Gaitán MA , Shiltz E , Lung K , Thomas A , Talbot HK , Schaffner W , George A , Staten H , Bozio CH , Garg S . Open Forum Infect Dis 2023 10 (12) ofad599 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. |
Performance of established disease severity scores in predicting severe outcomes among adults hospitalized with influenza-FluSurv-NET, 2017-2018
Doyle JD , Garg S , O'Halloran AC , Grant L , Anderson EJ , Openo KP , Alden NB , Herlihy R , Meek J , Yousey-Hindes K , Monroe ML , Kim S , Lynfield R , McMahon M , Muse A , Spina N , Irizarry L , Torres S , Bennett NM , Gaitan MA , Hill M , Cummings CN , Reed C , Schaffner W , Talbot HK , Self WH , Williams D . Influenza Other Respir Viruses 2023 17 (12) e13228 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. |
Modeling the impacts of antiviral prophylaxis strategies in mitigating seasonal influenza outbreaks in nursing homes
Morris SE , Zipfel CM , Peer K , Madewell ZJ , Brenner S , Garg S , Paul P , Slayton RB , Biggerstaff M . Clin Infect Dis 2023 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. |
Influenza vaccine effectiveness against influenza-A-associated emergency department, urgent care, and hospitalization encounters among U.S. adults, 2022-2023
Tenforde MW , Weber ZA , Yang DH , DeSilva MB , Dascomb K , Irving SA , Naleway AL , Gaglani M , Fireman B , Lewis N , Zerbo O , Goddard K , Timbol J , Hansen JR , Grisel N , Arndorfer J , McEvoy CE , Essien IJ , Rao S , Grannis SJ , Kharbanda AB , Natarajan K , Ong TC , Embi PJ , Ball SW , Dunne MM , Kirshner L , Wiegand RE , Dickerson M , Patel P , Ray C , Flannery B , Garg S , Adams K , Klein NP . J Infect Dis 2023 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. |
Communicating the value of influenza vaccines to patients: Translating vaccine effectiveness to acceptance
Tenforde MW , Dawood FS , Ellington SR , Grohskopf LA , Flannery B , Garg S , Reed C . Ann Intern Med 2023 176 (12) 1670-1671 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). |
Vaccine effectiveness against pediatric influenza-a-associated urgent care, emergency department, and hospital encounters during the 2022-2023 Season, VISION Network
Adams K , Weber ZA , Yang DH , Klein NP , DeSilva MB , Dascomb K , Irving SA , Naleway AL , Rao S , Gaglani M , Flannery B , Garg S , Kharbanda AB , Grannis SJ , Ong TC , Embi PJ , Natarajan K , Fireman B , Zerbo O , Goddard K , Timbol J , Hansen JR , Grisel N , Arndorfer J , Ball SW , Dunne MM , Kirshner L , Chung JR , Tenforde MW . Clin Infect Dis 2023 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. |
High influenza incidence and disease severity among children and adolescents aged <18 years - United States, 2022-23 season
White EB , O'Halloran A , Sundaresan D , Gilmer M , Threlkel R , Colón A , Tastad K , Chai SJ , Alden NB , Yousey-Hindes K , Openo KP , Ryan PA , Kim S , Lynfield R , Spina N , Tesini BL , Martinez M , Schmidt Z , Sutton M , Talbot HK , Hill M , Biggerstaff M , Budd A , Garg S , Reed C , Iuliano AD , Bozio CH . MMWR Morb Mortal Wkly Rep 2023 72 (41) 1108-1114 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. |
Severity of influenza-associated hospitalisations by influenza virus type and subtype in the USA, 2010-19: a repeated cross-sectional study
Sumner KM , Masalovich S , O'Halloran A , Holstein R , Reingold A , Kirley PD , Alden NB , Herlihy RK , Meek J , Yousey-Hindes K , Anderson EJ , Openo KP , Monroe ML , Leegwater L , Henderson J , Lynfield R , McMahon M , McMullen C , Angeles KM , Spina NL , Engesser K , Bennett NM , Felsen CB , Lung K , Shiltz E , Thomas A , Talbot HK , Schaffner W , Swain A , George A , Rolfes MA , Reed C , Garg S . Lancet Microbe 2023 4 (11) e903-e912 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. |
Estimating the burden of influenza hospitalizations across multiple seasons using capture-recapture
Howa AC , Zhu Y , Wyatt D , Markus T , Chappell JD , Halasa N , Trabue CH , Olson S , Ferdinands J , Garg S , Schaffner W , Grijalva CG , Talbot HK . J Infect Dis 2023 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. |
Rare variants in CAPN2 increase risk for isolated hypoplastic left heart syndrome
Blue EE , White JJ , Dush MK , Gordon WW , Wyatt BH , White P , Marvin CT , Helle E , Ojala T , Priest JR , Jenkins MM , Almli LM , Reefhuis J , Pangilinan F , Brody LC , McBride KL , Garg V , Shaw GM , Romitti PA , Nembhard WN , Browne ML , Werler MM , Kay DM , Mital S , Chong JX , Nascone-Yoder NM , Bamshad MJ . HGG Adv 2023 4 (4) 100232 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. |
Clinical epidemiology and risk factors for critical outcomes among vaccinated and unvaccinated adults hospitalized with COVID-19-VISION Network, 10 States, June 2021-March 2023
Griggs EP , Mitchell PK , Lazariu V , Gaglani M , McEvoy C , Klein NP , Valvi NR , Irving SA , Kojima N , Stenehjem E , Crane B , Rao S , Grannis SJ , Embi PJ , Kharbanda AB , Ong TC , Natarajan K , Dascomb K , Naleway AL , Bassett E , DeSilva MB , Dickerson M , Konatham D , Fireman B , Allen KS , Barron MA , Beaton M , Arndorfer J , Vazquez-Benitez G , Garg S , Murthy K , Goddard K , Dixon BE , Han J , Grisel N , Raiyani C , Lewis N , Fadel WF , Stockwell MS , Mamawala M , Hansen J , Zerbo O , Patel P , Link-Gelles R , Adams K , Tenforde MW . Clin Infect Dis 2023 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. |
The HEARTS partner forum-supporting implementation of HEARTS to treat and control hypertension
Khan T , Moran AE , Perel P , Whelton PK , Brainin M , Feigin V , Kostova D , Richter P , Ordunez P , Hennis A , Lackland DT , Slama S , Pineiro D , Martins S , Williams B , Hofstra L , Garg R , Mikkelsen B . Front Public Health 2023 11 1146441 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). |
Clinical Trends Among U.S. Adults Hospitalized with COVID-19, March-December 2020 (preprint)
Garg S , Patel K , Pham H , Whitaker M , O'Halloran A , Milucky J , Anglin O , Kirley PD , Reingold A , Kawasaki B , Herlihy R , Yousey-Hindes K , Maslar A , Anderson EJ , Openo KP , Weigel A , Teno K , Ryan PA , Monroe ML , Reeg L , Kim S , Como-Sabetti K , Bye E , Shrum Davis S , Eisenberg N , Muse A , Barney G , Bennett NM , Felsen CB , Billing L , Shiltz J , Sutton M , Abdullah N , Talbot HK , Schaffner W , Hill M , Chatelain R , Wortham J , Taylor C , Hall A , Fry AM , Kim L , Havers FP . medRxiv 2021 2021.04.21.21255473 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 <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 |
Risk Factors for COVID-19-associated hospitalization: COVID-19-Associated Hospitalization Surveillance Network and Behavioral Risk Factor Surveillance System (preprint)
Ko JY , Danielson ML , Town M , Derado G , Greenlund KJ , Daily Kirley P , Alden NB , Yousey-Hindes K , Anderson EJ , Ryan PA , Kim S , Lynfield R , Torres SM , Barney GR , Bennett NM , Sutton M , Talbot HK , Hill M , Hall AJ , Fry AM , Garg S , Kim L . medRxiv 2020 2020.07.27.20161810 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. |
Interim Analysis of Risk Factors for Severe Outcomes among a Cohort of Hospitalized Adults Identified through the U.S. Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET) (preprint)
Kim L , Garg S , O'Halloran A , Whitaker M , Pham H , Anderson EJ , Armistead I , Bennett NM , Billing L , Como-Sabetti K , Hill M , Kim S , Monroe ML , Muse A , Reingold AL , Schaffner W , Sutton M , Talbot HK , Torres SM , Yousey-Hindes K , Holstein R , Cummings C , Brammer L , Hall AJ , Fry AM , Langley GE . medRxiv 2020 2020.05.18.20103390 Background As of May 15, 2020, the United States has reported the greatest number of coronavirus disease 2019 (COVID-19) cases and deaths globally.Objective To describe risk factors for severe outcomes among adults hospitalized with COVID-19.Design Cohort study of patients identified through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network.Setting 154 acute care hospitals in 74 counties in 13 states.Patients 2491 patients hospitalized with laboratory-confirmed COVID-19 during March 1-May 2, 2020.Measurements Age, sex, race/ethnicity, and underlying medical conditions.Results Ninety-two percent of patients had ≥1 underlying condition; 32% required intensive care unit (ICU) admission; 19% invasive mechanical ventilation; 15% vasopressors; and 17% died during hospitalization. Independent factors associated with ICU admission included ages 50-64, 65-74, 75-84 and ≥85 years versus 18-39 years (adjusted risk ratio (aRR) 1.53, 1.65, 1.84 and 1.43, respectively); male sex (aRR 1.34); obesity (aRR 1.31); immunosuppression (aRR 1.29); and diabetes (aRR 1.13). Independent factors associated with in-hospital mortality included ages 50-64, 65-74, 75-84 and ≥85 years versus 18-39 years (aRR 3.11, 5.77, 7.67 and 10.98, respectively); male sex (aRR 1.30); immunosuppression (aRR 1.39); renal disease (aRR 1.33); chronic lung disease (aRR 1.31); cardiovascular disease (aRR 1.28); neurologic disorders (aRR 1.25); and diabetes (aRR 1.19). Race/ethnicity was not associated with either ICU admission or death.Limitation Data were limited to patients who were discharged or died in-hospital and had complete chart abstractions; patients who were still hospitalized or did not have accessible medical records were excluded.Conclusion In-hospital mortality for COVID-19 increased markedly with increasing age. These data help to characterize persons at highest risk for severe COVID-19-associated outcomes and define target groups for prevention and treatment strategies.Funding Source This work was supported by grant CK17-1701 from the Centers of Disease Control and Prevention through an Emerging Infections Program cooperative agreement and by Cooperative Agreement Number NU38OT000297-02-00 awarded to the Council of State and Territorial Epidemiologists from the Centers for Disease Control and Prevention.Competing Interest StatementH. Keipp Talbot reports personal fees from Seqirus outside the submitted work. William Schaffner reports personal fees from Pfizer and personal fees from Roche Diagnostics outside the submitted work. Evan Anderson reports personal fees from Abbvie and Pfizer outside the submitted work. H. Keipp Talbot reports grants from Sanofi outside the submitted work; Mary Hill reports grants from CSTE, during the conduct of the study; Melissa Sutton reports grants from CDC Emerging Infections Program during the conduct of the study; William Schaffner reports grants from CDC during the conduct of the study. Sue Kim reports grants from CSTE during the conduct of the study. Evan Anderson reports grants from Pfizer, grants from MedImmune, grants from Regeneron, grants from PaxVax, grants from Merck, grants from Novavax, grants from Sanofi-Pasteur, grants from Micron, outside the submitted work. Laurie Billing reports grants from the Council of State and Territorial Epidemiologists (CSTE) and the Centers for Disease Control and Prevention (CDC) during the conduct of the study.Funding StatementThis work was supported by grant CK17-1701 from the Centers of Disease Control and Prevention through an Emerging Infections Program cooperative agreement and by Cooperative Agreement Number NU38OT000297-02-00 awarded to the Council of State and Territorial Epidemiologists from the Centers for Disease Control and Prevention.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that al 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 checklist(s) and other pertinent material as supplementary files, if applicable.YesAggregate data is available on CDC’s COVID-NET Interactive website. https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html https://gis.cdc.gov/grasp/COVIDNet/COVID19_5.html |
A multicenter retrospective cohort study to characterize patients hospitalized with MIS-A and COVID-19 in the United States, 2020-2021
Melgar M , Abrams JY , Godfred-Cato S , Shah AB , Garg A , Strunk A , Narasimhan M , Koptyev J , Norden A , Musheyev D , Rashid F , Tannenbaum R , Estrada YMartin RM , Patel B , Karanth S , Achenbach CJ , Hall GT , Hockney SM , Caputo M , Abbo LM , Beauchamps L , Morris SB , Cifuentes RO , de St Maurice A , Bell DS , Prabaker KK , Sanz Vidorreta FJ , Bryant E , Cohen DK , Mohan R , Libby CP , SooHoo S , Domingo TJ , Campbell AP , Belay ED . Clin Infect Dis 2023 BACKGROUND: The diagnosis of SARS-CoV-2-associated multisystem inflammatory syndrome in adults (MIS-A) requires distinguishing it from acute COVID-19 and may impact clinical management. METHODS: In this retrospective cohort study, we applied the U.S. Centers for Disease Control and Prevention case definition to identify adults hospitalized with MIS-A at six academic medical centers during March 1, 2020-December 31, 2021. MIS-A patients were matched on age group, sex, site, and admission date at a 1:2 ratio to patients hospitalized with acute symptomatic COVID-19. Conditional logistic regression was used to compare demographics, presenting symptoms, laboratory and imaging results, treatments administered, and outcomes between cohorts. RESULTS: Through medical record review of 10,223 patients hospitalized with SARS-CoV-2-associated illness, we identified 53 MIS-A cases. Compared with 106 matched COVID-19 patients, MIS-A patients were more likely to be non-Hispanic Black and less likely to be non-Hispanic White. MIS-A patients more likely had laboratory-confirmed COVID-19 ≥ 14 days prior to hospitalization, more likely had positive in-hospital SARS-CoV-2 serologic testing, and more often presented with gastrointestinal symptoms and chest pain. They were less likely to have underlying medical conditions and to present with cough and dyspnea. On admission, MIS-A patients had higher neutrophil-to-lymphocyte ratio, C-reactive protein, ferritin, procalcitonin and D-dimer, compared with COVID-19 patients. MIS-A patients had longer hospitalization and more likely required intensive care admission, invasive mechanical ventilation, and vasopressors. Mortality was 6% in both cohorts. CONCLUSIONS: Compared with patients with acute symptomatic COVID-19, adults with MIS-A more often manifest certain symptoms and laboratory findings early during hospitalization. These features may facilitate diagnosis and management. |
Severity of Disease Among Adults Hospitalized with Laboratory-Confirmed COVID-19 Before and During the Period of SARS-CoV-2 B.1.617.2 (Delta) Predominance - COVID-NET, 14 States, January-August 2021.
Taylor CA , Patel K , Pham H , Whitaker M , Anglin O , Kambhampati AK , Milucky J , Chai SJ , Kirley PD , Alden NB , Armistead I , Meek J , Yousey-Hindes K , Anderson EJ , Openo KP , Teno K , Weigel A , Monroe ML , Ryan PA , Henderson J , Nunez VT , Bye E , Lynfield R , Poblete M , Smelser C , Barney GR , Spina NL , Bennett NM , Popham K , Billing LM , Shiltz E , Abdullah N , Sutton M , Schaffner W , Talbot HK , Ortega J , Price A , Garg S , Havers FP , COVID-NET Surveillance Team . MMWR Morb Mortal Wkly Rep 2021 70 (43) 1513-1519 In mid-June 2021, B.1.671.2 (Delta) became the predominant variant of SARS-CoV-2, the virus that causes COVID-19, circulating in the United States. As of July 2021, the Delta variant was responsible for nearly all new SARS-CoV-2 infections in the United States.* The Delta variant is more transmissible than previously circulating SARS-CoV-2 variants (1); however, whether it causes more severe disease in adults has been uncertain. Data from the CDC COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system for COVID-19-associated hospitalizations, were used to examine trends in severe outcomes in adults aged ≥18 years hospitalized with laboratory-confirmed COVID-19 during periods before (January-June 2021) and during (July-August 2021) Delta variant predominance. COVID-19-associated hospitalization rates among all adults declined during January-June 2021 (pre-Delta period), before increasing during July-August 2021 (Delta period). Among sampled nonpregnant hospitalized COVID-19 patients with completed medical record abstraction and a discharge disposition during the pre-Delta period, the proportion of patients who were admitted to an intensive care unit (ICU), received invasive mechanical ventilation (IMV), or died while hospitalized did not significantly change from the pre-Delta period to the Delta period. The proportion of hospitalized COVID-19 patients who were aged 18-49 years significantly increased, from 24.7% (95% confidence interval [CI] = 23.2%-26.3%) of all hospitalizations in the pre-Delta period, to 35.8% (95% CI = 32.1%-39.5%, p<0.01) during the Delta period. When examined by vaccination status, 71.8% of COVID-19-associated hospitalizations in the Delta period were in unvaccinated adults. Adults aged 18-49 years accounted for 43.6% (95% CI = 39.1%-48.2%) of all hospitalizations among unvaccinated adults during the Delta period. No difference was observed in ICU admission, receipt of IMV, or in-hospital death among nonpregnant hospitalized adults between the pre-Delta and Delta periods. However, the proportion of unvaccinated adults aged 18-49 years hospitalized with COVID-19 has increased as the Delta variant has become more predominant. Lower vaccination coverage in this age group likely contributed to the increase in hospitalized patients during the Delta period. COVID-19 vaccination is critical for all eligible adults, including those aged <50 years who have relatively low vaccination rates compared with older adults. |
Changes in influenza and other respiratory virus activity during the COVID-19 pandemic-United States, 2020-2021.
Olsen SJ , Winn AK , Budd AP , Prill MM , Steel J , Midgley CM , Kniss K , Burns E , Rowe T , Foust A , Jasso G , Merced-Morales A , Davis CT , Jang Y , Jones J , Daly P , Gubareva L , Barnes J , Kondor R , Sessions W , Smith C , Wentworth DE , Garg S , Havers FP , Fry AM , Hall AJ , Brammer L , Silk BJ . Am J Transplant 2021 21 (10) 3481-3486 The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced the transmission of some viral respiratory pathogens.1 In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020,2 and remained low during October 2020–May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1–4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities. |
Acute cardiac events during COVID-19-associated hospitalizations
Woodruff RC , Garg S , George MG , Patel K , Jackson SL , Loustalot F , Wortham JM , Taylor CA , Whitaker M , Reingold A , Alden NB , Meek J , Anderson EJ , Weigel A , Henderson J , Bye E , Davis SS , Barney G , Bennett NM , Shiltz E , Sutton M , Talbot HK , Price A , Sperling LS , Havers FP . J Am Coll Cardiol 2023 81 (6) 557-569 BACKGROUND: COVID-19 is associated with cardiac complications. OBJECTIVES: The purpose of this study was to estimate the prevalence, risk factors, and outcomes associated with acute cardiac events during COVID-19-associated hospitalizations among adults. METHODS: During January 2021 to November 2021, medical chart abstraction was conducted on a probability sample of adults hospitalized with laboratory-confirmed SARS-CoV-2 infection identified from 99 U.S. counties in 14 U.S. states in the COVID-19-Associated Hospitalization Surveillance Network. We calculated the prevalence of acute cardiac events (identified by International Classification of Diseases-10th Revision-Clinical Modification codes) by history of underlying cardiac disease and examined associated risk factors and disease outcomes. RESULTS: Among 8,460 adults, 11.4% (95% CI: 10.1%-12.9%) experienced an acute cardiac event during a COVID-19-associated hospitalization. Prevalence was higher among adults who had underlying cardiac disease (23.4%; 95% CI: 20.7%-26.3%) compared with those who did not (6.2%; 95% CI: 5.1%-7.6%). Acute ischemic heart disease (5.5%; 95% CI: 4.5%-6.5%) and acute heart failure (5.4%; 95% CI: 4.4%-6.6%) were the most prevalent events; 0.3% (95% CI: 0.1%-0.5%) experienced acute myocarditis or pericarditis. Risk factors varied by underlying cardiac disease status. Patients with ≥1 acute cardiac event had greater risk of intensive care unit admission (adjusted risk ratio: 1.9; 95% CI: 1.8-2.1) and in-hospital death (adjusted risk ratio: 1.7; 95% CI: 1.3-2.1) compared with those who did not. CONCLUSIONS: Acute cardiac events were common during COVID-19-associated hospitalizations, particularly among patients with underlying cardiac disease, and are associated with severe disease outcomes. Persons at greater risk for experiencing acute cardiac events during COVID-19-associated hospitalizations might benefit from more intensive clinical evaluation and monitoring during hospitalization. |
Influenza antiviral use in patients hospitalized with laboratory-confirmed influenza in the United States, FluSurv-NET, 2015-2019
Tenforde MW , Cummings CN , O'Halloran AC , Rothrock G , Kirley PD , Alden NB , Meek J , Yousey-Hindes K , Openo KP , Anderson EJ , Monroe ML , Kim S , Nunez VT , McMahon M , McMullen C , Khanlian SA , Spina NL , Muse A , Gaitán MA , Felsen CB , Lung K , Shiltz E , Sutton M , Thomas A , Talbot HK , Schaffner W , Price A , Chatelain R , Reed C , Garg S . Open Forum Infect Dis 2023 10 (1) ofac681 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. |
Developing a sampling methodology for timely reporting of population-based COVID-19-associated hospitalization surveillance in the United States, COVID-NET 2020-2021
O'Halloran A , Whitaker M , Patel K , Allen AE , Copeland KR , Reed C , Reynolds S , Taylor CA , Havers F , Kim L , Wolter K , Garg S . Influenza Other Respir Viruses 2023 17 (1) e13089 BACKGROUND: The COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) required a sampling methodology that allowed for production of timely population-based clinical estimates to inform the ongoing US COVID-19 pandemic response. METHODS: We developed a flexible sampling approach that considered reporting delays, differential hospitalized case burden across surveillance sites, and changing geographic and demographic trends over time. We incorporated weighting methods to adjust for the probability of selection and non-response, and to calibrate the sampled case distribution to the population distribution on demographics. We additionally developed procedures for variance estimation. RESULTS: Between March 2020 and June 2021, 19,293 (10.4%) of all adult hospitalized cases were sampled for chart abstraction. Variance estimates for select variables of interest were within desired ranges. CONCLUSIONS: COVID-NET's sampling methodology allowed for reporting of robust and timely, population-based data on the clinical epidemiology of COVID-19-associated hospitalizations and evolving trends over time, while attempting to reduce data collection burden on surveillance sites. Such methods may provide a general framework for other surveillance systems needing to quickly and efficiently collect and disseminate data for public health action. |
Timing and predictors of incident cardiovascular disease in systemic lupus erythematosus: Risk occurs early and highlights racial disparities
Garg S , Bartels CM , Bao G , Helmick CG , Drenkard C , Lim SS . J Rheumatol 2023 50 (1) 84-92 OBJECTIVE: Systemic lupus erythematosus (SLE) affects Black people 2 to 3 times more frequently than non-Black people and is associated with higher morbidity and mortality. In total, 4 studies with predominantly non-Black SLE cohorts highlighted that cardiovascular disease (CVD) is no longer primarily a late complication of SLE. This study assessed the timing and predictors of incident CVD in a predominantly Black population-based SLE cohort. METHODS: Incident SLE cases from the population-based Georgia Lupus Registry were validated as having a CVD event through review of medical records and matching with the Georgia Hospital Discharge Database and the National Death Index. The surveillance period for an incident CVD event spanned a 15-year period, starting from 2 years prior to SLE diagnosis. RESULTS: Among 336 people with SLE, 253 (75%) were Black and 56 (17%) had an incident CVD event. The frequency of CVD events peaked in years 2 and 11 after SLE diagnosis. There was a 7-fold higher risk of incident CVD over the entire 15-year period; this risk was 19-fold higher in the first 12 years in Black people as compared to non-Black people with SLE. Black people with SLE (P < 0.001) and those with discoid rash (hazard ratio 3.2, 95% CI 1.4-7.1) had a higher risk of incident CVD events. CONCLUSION: The frequency of incident CVD events peaked in years 2 and 11 after SLE diagnosis. Being Black or having a discoid rash were strong predictors of an incident CVD event. Surveillance for CVD and preventive interventions, directed particularly toward Black people with recent SLE diagnoses, are needed to reduce racial disparities. |
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