Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-30 (of 99 Records) |
Query Trace: Mack K [original query] |
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Vital signs: Drowning death rates, self-reported swimming skill, swimming lesson participation, and recreational water exposure - United States, 2019-2023
Clemens T , Moreland B , Mack KA , Thomas K , Bergen G , Lee R . MMWR Morb Mortal Wkly Rep 2024 73 (20) 467-473 INTRODUCTION: Drowning is the cause of approximately 4,000 U.S. deaths each year and disproportionately affects some age, racial, and ethnic groups. Infrastructure disruptions during the COVID-19 pandemic, including limited access to supervised swimming settings, might have affected drowning rates and risk. Data on factors that contribute to drowning risk are limited. To assess the potential impact of the pandemic on drowning death rates, pre- and post-COVID-19 pandemic rates were compared. METHODS: National Vital Statistics System data were used to compare unintentional drowning death rates in 2019 (pre-COVID-19 pandemic onset) with those in 2020, 2021, and 2022 (post-pandemic onset) by age, sex, and race and ethnicity. National probability-based online panel survey (National Center for Health Statistics Rapid Surveys System) data from October-November 2023 were used to describe adults' self-reported swimming skill, swimming lesson participation, and exposure to recreational water. RESULTS: Unintentional drowning death rates were significantly higher during 2020, 2021, and 2022 compared with those in 2019. In all years, rates were highest among children aged 1-4 years; significant increases occurred in most age groups. The highest drowning rates were among non-Hispanic American Indian or Alaska Native and non-Hispanic Black or African American persons. Approximately one half (54.7%) of U.S. adults reported never having taken a swimming lesson. Swimming skill and swimming lesson participation differed by age, sex, and race and ethnicity. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Recent increases in drowning rates, including those among populations already at high risk, have increased the urgency of implementing prevention strategies. Basic swimming and water safety skills training can reduce the risk for drowning. Addressing social and structural barriers that limit access to this training might reduce drowning deaths and inequities. The U.S. National Water Safety Action Plan provides recommendations and tools for communities and organizations to enhance basic swimming and water safety skills training. |
Emerging trends of self-harm using sodium nitrite in an online suicide community: Observational study using natural language processing analysis
Das S , Walker D , Rajwal S , Lakamana S , Sumner SA , Mack KA , Kaczkowski W , Sarker A . JMIR Ment Health 2024 11 e53730 BACKGROUND: There is growing concern around the use of sodium nitrite (SN) as an emerging means of suicide, particularly among younger people. Given the limited information on the topic from traditional public health surveillance sources, we studied posts made to an online suicide discussion forum, "Sanctioned Suicide," which is a primary source of information on the use and procurement of SN. OBJECTIVE: This study aims to determine the trends in SN purchase and use, as obtained via data mining from subscriber posts on the forum. We also aim to determine the substances and topics commonly co-occurring with SN, as well as the geographical distribution of users and sources of SN. METHODS: We collected all publicly available from the site's inception in March 2018 to October 2022. Using data-driven methods, including natural language processing and machine learning, we analyzed the trends in SN mentions over time, including the locations of SN consumers and the sources from which SN is procured. We developed a transformer-based source and location classifier to determine the geographical distribution of the sources of SN. RESULTS: Posts pertaining to SN show a rise in popularity, and there were statistically significant correlations between real-life use of SN and suicidal intent when compared to data from the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research (⍴=0.727; P<.001) and the National Poison Data System (⍴=0.866; P=.001). We observed frequent co-mentions of antiemetics, benzodiazepines, and acid regulators with SN. Our proposed machine learning-based source and location classifier can detect potential sources of SN with an accuracy of 72.92% and showed consumption in the United States and elsewhere. CONCLUSIONS: Vital information about SN and other emerging mechanisms of suicide can be obtained from online forums. |
Durability of original monovalent mRNA vaccine effectiveness against COVID-19 Omicron-associated hospitalization in children and adolescents - United States, 2021-2023
Zambrano LD , Newhams MM , Simeone RM , Payne AB , Wu M , Orzel-Lockwood AO , Halasa NB , Calixte JM , Pannaraj PS , Mongkolrattanothai K , Boom JA , Sahni LC , Kamidani S , Chiotos K , Cameron MA , Maddux AB , Irby K , Schuster JE , Mack EH , Biggs A , Coates BM , Michelson KN , Bline KE , Nofziger RA , Crandall H , Hobbs CV , Gertz SJ , Heidemann SM , Bradford TT , Walker TC , Schwartz SP , Staat MA , Bhumbra SS , Hume JR , Kong M , Stockwell MS , Connors TJ , Cullimore ML , Flori HR , Levy ER , Cvijanovich NZ , Zinter MS , Maamari M , Bowens C , Zerr DM , Guzman-Cottrill JA , Gonzalez I , Campbell AP , Randolph AG . MMWR Morb Mortal Wkly Rep 2024 73 (15) 330-338 Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%-32%) if the interval was 120-364 days. VE of the original monovalent vaccine against COVID-19-related hospitalization was 31% (95% CI = 18%-43%) if the last dose was received any time within the previous year. VE against critical COVID-19-related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%-76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received 120-364 days before hospitalization, and 38% (95% CI = 15%-55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19. |
Special Report from the CDC: Suicide rates, sodium nitrite-related suicides, and online content, United States
Mack KA , Kaczkowski W , Sumner S , Law R , Wolkin A . J Saf Res 2024 Background: In 2022, suicide ranked as the 11th leading cause of death in the United States with 49,513 deaths. Provisional mortality data from 2022 indicate a 2.8% increase in the number of suicides compared to 2021. This paper examines overall suicide trends, sodium nitrite ingestion as an emerging suicide method, and the role that online forums play in sharing information about suicide methods (including sodium nitrite ingestion). Methods: Suicides were identified from CDC's National Vital Statistics System (2018-July 2023 provisional) multiple cause-of-death mortality files using International Classification of Diseases (ICD), Tenth Revision underlying cause-of-death codes U03, X60–X84, and Y87.0 and T code T50.6 (antidotes and chelating agents). Google search popularity metrics were captured from January 2019 to January 2023. Case reports of sodium nitrite related suicide and suicide attempts (through February 2024) were identified in the medical and forensic literature. Results: At least 768 suicides involving antidotes and chelating agents (including sodium nitrite) occurred between 2018 and July 2023, set in the context of 268,972 total suicides during that period. Overall, suicides involving antidotes and chelating agents (including sodium nitrite) represent <1% of all suicides, however, numbers are rising. Conclusions: Suicide methods are known to change over time. These changes can be influenced by, among other factors, online forums and means accessibility, such as internet purchase availability. CDC remains committed to prevention through comprehensive public health strategies that protect individuals, families, and communities. Practical Applications: States and community partners might consider leveraging physicians, emergency responders, and other appropriate crisis response groups to disseminate information on sodium nitrite self-poisoning and its antidote, methylene blue. Efforts should be part of a comprehensive public health approach to suicide prevention. © 2024 |
Pre-existing immunocompromising conditions and outcomes of acute COVID-19 patients admitted for pediatric intensive care
Rowan CM , LaBere B , Young CC , Zambrano LD , Newhams MM , Kucukak S , McNamara ER , Mack EH , Fitzgerald JC , Irby K , Maddux AB , Schuster JE , Kong M , Dapul H , Schwartz SP , Bembea MM , Loftis LL , Kolmar AR , Babbitt CJ , Nofziger RA , Hall MW , Gertz SJ , Cvijanovich NZ , Zinter MS , Halasa NB , Bradford TT , McLaughlin GE , Singh AR , Hobbs CV , Wellnitz K , Staat MA , Coates BM , Crandall HR , Maamari M , Havlin KM , Schwarz AJ , Carroll CL , Levy ER , Moffitt KL , Campbell AP , Randolph AG , Chou J . Clin Infect Dis 2024 BACKGROUND: We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. METHODS: 55 hospitals in 30 U.S. states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted March 12, 2020-December 30, 2021 to the pediatric intensive care unit (PICU) or high acuity unit for acute COVID-19 were included. RESULTS: Of 1,274 patients, 105 (8.2%) had an ICC including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid organ transplantation, 16 (15.2%) solid tumors and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs. 4.6%, p = 0.005) and hospitalization was longer (p = 0.01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, p = 0.40). In patients with ICC, bacterial co-infection was more common in those with life-threatening COVID-19. CONCLUSIONS: In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities. |
Suicidal thoughts and behaviors among high school students - Youth Risk Behavior Survey, United States, 2021
Gaylor EM , Krause KH , Welder LE , Cooper AC , Ashley C , Mack KA , Crosby AE , Trinh E , Ivey-Stephenson AZ , Whittle L . MMWR Suppl 2023 72 (1) 45-54 Suicide is the third leading cause of death among high school-aged youths aged 14-18 years. The 2021 suicide rate for this age group was 9.0 per 100,000 population. Updating a previous analysis of the Youth Risk Behavior Survey during 2009-2019, this report uses 2019 and 2021 data to examine high school students' reports of suicidal thoughts and behaviors. Prevalence estimates are reported by grade, race and ethnicity, sexual identity, and sex of sexual contacts. Unadjusted logistic regression models were used to calculate prevalence differences comparing 2019 to 2021 and prevalence ratios comparing suicidal behavior between subgroups across demographic characteristics to a referent group. From 2019 to 2021, female students had an increased prevalence of seriously considered attempting suicide (from 24.1% to 30%), an increase in making a suicide plan (from 19.9% to 23.6%), and an increase in suicide attempts (from 11.0% to 13.3%). In addition, from 2019 to 2021, Black or African American (Black), Hispanic or Latino (Hispanic), and White female students had an increased prevalence of seriously considered attempting suicide. In 2021, Black female students had an increased prevalence of suicide attempts and Hispanic female students had an increased prevalence of suicide attempts that required medical treatment compared with White female students. Prevalence of suicidal thoughts and behaviors remained stable overall for male students from 2019 to 2021. A comprehensive approach to suicide prevention with a focus on health equity is needed to address these disparities and reduce prevalence of suicidal thoughts and behaviors for all youths. School and community-based strategies include creating safe and supportive environments, promoting connectedness, teaching coping and problem solving, and gatekeeper training. |
Autoimmune hepatitis: Brighton Collaboration case definition and guidelines for data collection, analysis, and presentation of immunisation safety data
Kochhar S , Assis DN , Mack C , Izurieta HS , Muratori L , Munoz A , Nordenberg D , Gidudu JF , Blau EF , Vierling JM . Vaccine 2024 This report introduces a Brighton Collaboration (BC) case definition for autoimmune hepatitis (AIH), which has been classified as a priority adverse event of special interest (AESI), as there were possible cases seen following COVID-19 vaccination. The case definition was developed by a group of subject matter and BC process experts to facilitate safety data comparability across pre- and post-licensure clinical trials, as well as pharmacovigilance activities in multiple settings with diverse resources and healthcare access. The usual BC case definition development process was followed in an expedited manner, and took two months to complete, including finalising the manuscript for publication, instead of the usual 1 year development time. It includes a systematic review of the literature and an expert consensus to define levels of diagnostic certainty for AIH, and provides specific guidelines for data collection and analysis. Histology, serological and biochemical tests and exclusion of alternate diagnosis were considered necessary to define the levels of certainty (definitive, probable and possible). AEFI reports of suspected AIH were independently classified by the WG members to test its useability and these classifications were used to finalise the case definition. The document underwent peer review by external AIH experts and a Reference Group of vaccine safety stakeholders in high-, low- and middle-income countries to ensure case definition useability, applicability, and scientific integrity. The expedited process can be replicated for development of other standardised case definitions for priority AESIs for endemics and epidemics. While applicable to cases reported following immunisation, the case definition is independent of lapsed time following vaccination and, as such, can also be used to determine background incidence for vaccinated and unvaccinated control groups in studies of causal association. While use of this case definition is also appropriate for the study of safety of other products including drugs, it is not meant to guide clinical case management. |
Research, practice, and data informed investigations of child and youth suicide: A science to service and service to science approach
Colpe L , Blair JM , Kurikeshu R , Mack KA , Nashelsky M , O'Connor S , Pearson J , Pilkey D , Warner M , Weintraub B . J Safety Res 2024 Background: Suicide rates for children and adolescents have been increasing over the past 2 decades. In April 2023, the National Institute of Mental Health (NIMH) convened a two-day workshop to address child and youth suicide. Purpose: The workshop focus was to discuss the state of the science and stimulate a collaborative response between researchers, death investigators, and data collection teams to build a science to service and service to science approach toward understanding - and ultimately preventing – this growing problem of child and youth suicide. Highlights: Topics that meeting participants highlighted as worthy of further consideration for research and practice were: increasing awareness among death investigators, medical examiners, and coroners that child suicide deaths under age 10 years do occur and should be investigated and documented accordingly; emphasizing the value of science based protocols for child and youth death investigations to enhance consistency of approaches; and articulating needs for postvention services to suicide loss survivors. Outcomes: The importance of collecting an accurate and complete cause and manner of death (i.e., unintentional, suicide, homicide, undetermined) among all child decedents, and demographic information such as race, ethnicity, and sexual/gender minority status was underscored as critical for enhanced surveillance. For prevention efforts, approaches to assessing and understanding suicidal thoughts and behaviors among diverse groups of children, and the variability in proximal and distal risk factors are needed to inform opportunities for preventive interventions for diverse communities. The need for consistent measures and processes to improve death investigations, fatality review committees, and coordination between data collection systems and agencies was also raised. Practical applications: Collaborations among researchers, death investigators, and data collection teams can help to fully describe the child and youth suicide crisis and provide actionable information for new research, and prevention and response efforts. © 2023 |
Characteristics and clinical outcomes of vaccine-eligible US children under-5 years hospitalized for acute COVID-19 in a national network
Zambrano LD , Newhams MM , Simeone RM , Fleming-Dutra KE , Halasa N , Wu M , Orzel-Lockwood AO , Kamidani S , Pannaraj PS , Chiotos K , Cameron MA , Maddux AB , Schuster JE , Crandall H , Kong M , Nofziger RA , Staat MA , Bhumbra SS , Irby K , Boom JA , Sahni LC , Hume JR , Gertz SJ , Maamari M , Bowens C , Levy ER , Bradford TT , Walker TC , Schwartz SP , Mack EH , Guzman-Cottrill JA , Hobbs CV , Zinter MS , Cvijanovich NZ , Bline KE , Hymes SR , Campbell AP , Randolph AG . Pediatr Infect Dis J 2023 BACKGROUND AND OBJECTIVES: In June 2022, the mRNA COVID-19 vaccination was recommended for young children. We examined clinical characteristics and factors associated with vaccination status among vaccine-eligible young children hospitalized for acute COVID-19. METHODS: We enrolled inpatients aged 8 months to <5 years with acute community-acquired COVID-19 across 28 US pediatric hospitals from September 20, 2022 to May 31, 2023. We assessed demographic and clinical factors, including the highest level of respiratory support, and vaccination status defined as unvaccinated, incomplete, or complete primary series [at least 2 (Moderna) or 3 (Pfizer-BioNTech) mRNA vaccine doses ≥14 days before hospitalization]. RESULTS: Among 597 children, 174 (29.1%) patients were admitted to the intensive care unit and 75 (12.6%) had a life-threatening illness, including 51 (8.5%) requiring invasive mechanical ventilation. Children with underlying respiratory and neurologic/neuromuscular conditions more frequently received higher respiratory support. Only 4.5% of children hospitalized for COVID-19 (n = 27) had completed their primary COVID-19 vaccination series and 7.0% (n = 42) of children initiated but did not complete their primary series. Among 528 unvaccinated children, nearly half (n = 251) were previously healthy, 3 of them required extracorporeal membrane oxygenation for acute COVID-19 and 1 died. CONCLUSIONS: Most young children hospitalized for acute COVID-19, including most children admitted to the intensive care unit and with life-threatening illness, had not initiated COVID-19 vaccination despite being eligible. Nearly half of these children had no underlying conditions. Of the small percentage of children who initiated a COVID-19 primary series, most had not completed it before hospitalization. |
Risk factors for health impairments in children after hospitalization for acute COVID-19 or MIS-C
Maddux AB , Young CC , Kucukak S , Zambrano LD , Newhams MM , Rollins CK , Halasa NB , Gertz SJ , Mack EH , Schwartz S , Kong M , Loftis LL , Irby K , Rowan CM , Tarquinio KM , Zinter MS , Crandall H , Cvijanovich NZ , Schuster JE , Fitzgerald JC , Staat MA , Hobbs CV , Nofziger RA , Shein S , Flori H , Cullimore ML , Chatani BM , Levy ER , Typpo KV , Hume JR , Campbell AP , Randolph AG . Front Pediatr 2023 11 1260372 OBJECTIVE: To identify risk factors for persistent impairments after pediatric hospitalization for acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic. METHODS: Across 25 U.S. Overcoming COVID-19 Network hospitals, we conducted a prospective cohort study of patients <21-years-old hospitalized for acute COVID-19 or MIS-C (May 2020 to March 2022) surveyed 2- to 4-months post-admission. Multivariable regression was used to calculate adjusted risk ratios (aRR) and 95% confidence intervals (CI). RESULTS: Of 232 children with acute COVID-19, 71 (30.6%) had persistent symptoms and 50 (21.6%) had activity impairments at follow-up; for MIS-C (n = 241), 56 (23.2%) had persistent symptoms and 58 (24.1%) had activity impairments. In adjusted analyses of patients with acute COVID-19, receipt of mechanical ventilation was associated with persistent symptoms [aRR 1.83 (95% CI: 1.07, 3.13)] whereas obesity [aRR 2.18 (95% CI: 1.05, 4.51)] and greater organ system involvement [aRR 1.35 (95% CI: 1.13, 1.61)] were associated with activity impairment. For patients with MIS-C, having a pre-existing respiratory condition was associated with persistent symptoms [aRR 3.04 (95% CI: 1.70, 5.41)] whereas obesity [aRR 1.86 (95% CI: 1.09, 3.15)] and greater organ system involvement [aRR 1.26 (1.00, 1.58)] were associated with activity impairments. DISCUSSION: Among patients hospitalized, nearly one in three hospitalized with acute COVID-19 and one in four hospitalized with MIS-C had persistent impairments for ≥2 months post-hospitalization. Persistent impairments were associated with more severe illness and underlying health conditions, identifying populations to target for follow-up. |
Effectiveness of maternal mRNA COVID-19 vaccination during pregnancy against COVID-19-associated hospitalizations in infants aged <6 months during SARS-cov-2 Omicron predominance - 20 states, March 9, 2022-May 31, 2023
Simeone RM , Zambrano LD , Halasa NB , Fleming-Dutra KE , Newhams MM , Wu MJ , Orzel-Lockwood AO , Kamidani S , Pannaraj PS , Irby K , Maddux AB , Hobbs CV , Cameron MA , Boom JA , Sahni LC , Kong M , Nofziger RA , Schuster JE , Crandall H , Hume JR , Staat MA , Mack EH , Bradford TT , Heidemann SM , Levy ER , Gertz SJ , Bhumbra SS , Walker TC , Bline KE , Michelson KN , Zinter MS , Flori HR , Campbell AP , Randolph AG . MMWR Morb Mortal Wkly Rep 2023 72 (39) 1057-1064 Infants aged <6 months are not eligible for COVID-19 vaccination. Vaccination during pregnancy has been associated with protection against infant COVID-19-related hospitalization. The Overcoming COVID-19 Network conducted a case-control study during March 9, 2022-May 31, 2023, to evaluate the effectiveness of maternal receipt of a COVID-19 vaccine dose (vaccine effectiveness [VE]) during pregnancy against COVID-19-related hospitalization in infants aged <6 months and a subset of infants aged <3 months. VE was calculated as (1 - adjusted odds ratio) x 100% among all infants aged <6 months and <3 months. Case-patients (infants hospitalized for COVID-19 outside of birth hospitalization and who had a positive SARS-CoV-2 test result) and control patients (infants hospitalized for COVID-19-like illness with a negative SARS-CoV-2 test result) were compared. Odds ratios were determined using multivariable logistic regression, comparing the odds of receipt of a maternal COVID-19 vaccine dose (completion of a 2-dose vaccination series or a third or higher dose) during pregnancy with maternal nonvaccination between case- and control patients. VE of maternal vaccination during pregnancy against COVID-19-related hospitalization was 35% (95% CI = 15%-51%) among infants aged <6 months and 54% (95% CI = 32%-68%) among infants aged <3 months. Intensive care unit admissions occurred in 23% of all case-patients, and invasive mechanical ventilation was more common among infants of unvaccinated (9%) compared with vaccinated mothers (1%) (p = 0.02). Maternal vaccination during pregnancy provides some protection against COVID-19-related hospitalizations among infants, particularly those aged <3 months. Expectant mothers should remain current with COVID-19 vaccination to protect themselves and their infants from hospitalization and severe outcomes associated with COVID-19. |
Infants admitted to US intensive care units for RSV infection during the 2022 seasonal peak
Halasa N , Zambrano LD , Amarin JZ , Stewart LS , Newhams MM , Levy ER , Shein SL , Carroll CL , Fitzgerald JC , Michaels MG , Bline K , Cullimore ML , Loftis L , Montgomery VL , Jeyapalan AS , Pannaraj PS , Schwarz AJ , Cvijanovich NZ , Zinter MS , Maddux AB , Bembea MM , Irby K , Zerr DM , Kuebler JD , Babbitt CJ , Gaspers MG , Nofziger RA , Kong M , Coates BM , Schuster JE , Gertz SJ , Mack EH , White BR , Harvey H , Hobbs CV , Dapul H , Butler AD , Bradford TT , Rowan CM , Wellnitz K , Staat MA , Aguiar CL , Hymes SR , Randolph AG , Campbell AP . JAMA Netw Open 2023 6 (8) e2328950 IMPORTANCE: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide. OBJECTIVE: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection. EXPOSURE: Respiratory syncytial virus. MAIN OUTCOMES AND MEASURES: Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity. RESULTS: The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness. |
A distinct cross-reactive autoimmune response in multisystem inflammatory syndrome in children (MIS-C) (preprint)
Bodansky A , Sabatino JJ , Vazquez SE , Chou J , Novak T , Moffitt KL , Miller HS , Kung AF , Rackaityte E , Zamecnik CR , Rajan JV , Kortbawi H , Mandel-Brehm C , Mitchell A , Wang CY , Saxena A , Zorn K , Yu DJL , Asaki J , Pluvinage JV , Wilson MR , Loftis LL , Hobbs CV , Tarquinio KM , Kong M , Fitzgerald JC , Espinal PS , Walker TC , Schwartz SP , Crandall H , Irby K , Staat MA , Rowan CM , Schuster JE , Halasa NB , Gertz SJ , Mack EH , Maddux AB , Cvijanovich NZ , Zinter MS , Zambrano LD , Campbell AP , Randolph AG , Anderson MS , DeRisi JL , Kelley H , Murdock M , Colston C , Typpo KV , Sanders RC , Yates M , Smith C , Port E , Mansour R , Shankman S , Baig N , Zorensky F , Chatani B , McLaughlin G , Jones K , Coates BM , Newhams MM , Kucukak S , McNamara ER , Moon HK , Kobayashi T , Melo J , Jackson SR , Rosales MKE , Young C , Chen SR , Da Costa Aguiar R , Gutierrez-Arcelus M , Elkins M , Williams D , Williams L , Cheng L , Zhang Y , Crethers D , Morley D , Steltz S , Zakar K , Armant MA , Ciuculescu F , Flori HR , Dahmer MK , Levy ER , Behl S , Drapeau NM , Kietzman A , Hill S , Cullimore ML , McCulloh RJ , Nofziger RA , Rohlfs CC , Burnett R , Bush J , Reed N , Ampofo KK , Patel MM . medRxiv 2023 30 Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of MIS-C patient samples (n=199) to identify a distinct set of host proteins that are differentially targeted by patient autoantibodies relative to matched controls. We identified an autoreactive epitope within SNX8, a protein expressed primarily in immune cells which regulates an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed the SARS-CoV-2 proteome-wide MIS-C patient antibody response and found it to be differentially reactive to a distinct domain of the SARS-CoV-2 nucleocapsid (N) protein relative to controls. This viral N region and the mapped SNX8 epitope bear remarkable biochemical similarity. Furthermore, we find that many children with anti-SNX8 autoantibodies also have T-cells cross-reactive to both SNX8 and this distinct domain of the SARS-CoV-2 N protein. Together, these findings suggest that MIS-C patients develop a distinct immune response against the SARS-CoV-2 N protein that is associated with cross reactivity to the self-protein SNX8, demonstrating a link from the infection to the inflammatory syndrome. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. |
Implementation and Evolution of Mitigation Measures, Testing, and Contact Tracing in the National Football League, August 9-November 21, 2020.
Mack CD , Wasserman EB , Perrine CG , MacNeil A , Anderson DJ , Myers E , Smith S , McDonald LC , Osterholm M , Solomon GS , Mayer T , Sills A , NFL COVID-19 Advisory and Operational Team . MMWR Morb Mortal Wkly Rep 2021 70 (4) 130-135 The National Football League (NFL) and the NFL Players Association (NFLPA) began the 2020 football season in July, implementing extensive mitigation and surveillance measures in facilities and during travel and gameplay. Mitigation protocols* were evaluated and modified based on data from routine reverse transcription-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2, the virus that causes coronavirus 2019 (COVID-19); proximity tracking devices; and detailed interviews. Midseason, transmission was observed in persons who had cumulative interactions of <15 minutes' duration, leading to a revised definition of high-risk contacts that required consideration of mask use, setting and room ventilation in addition to proximity and duration of interaction. The NFL also developed an intensive protocol that imposed stricter infection prevention precautions when a case was identified at an NFL club. The intensive protocol effectively prevented the occurrence of high-risk interactions, with no high-risk contacts identified for 71% of traced cases at clubs under the intensive protocol. The incorporation of the nature and location of the interaction, including mask use, indoor versus outdoor setting, and ventilation, in addition to proximity and duration, likely improved identification of exposed persons at higher risk for SARS-CoV-2 infection. Quarantine of these persons, along with testing and intensive protocols, can reduce spread of infection. |
Effectiveness of Pfizer-BioNTech mRNA Vaccination Against COVID-19 Hospitalization Among Persons Aged 12-18 Years - United States, June-September 2021.
Olson SM , Newhams MM , Halasa NB , Price AM , Boom JA , Sahni LC , Irby K , Walker TC , Schwartz SP , Pannaraj PS , Maddux AB , Bradford TT , Nofziger RA , Boutselis BJ , Cullimore ML , Mack EH , Schuster JE , Gertz SJ , Cvijanovich NZ , Kong M , Cameron MA , Staat MA , Levy ER , Chatani BM , Chiotos K , Zambrano LD , Campbell AP , Patel MM , Randolph AG , Overcoming COVID-19 Investigators . MMWR Morb Mortal Wkly Rep 2021 70 (42) 1483-1488 Pfizer-BioNTech COVID-19 vaccine is authorized for use in children and adolescents aged 12-15 years and is licensed by the Food and Drug Administration (FDA) for persons aged ≥16 (1). A randomized placebo-controlled trial demonstrated an efficacy of 100% (95% confidence interval [CI] = 75.3%-100%) in preventing outpatient COVID-19 in persons aged 12-15 years (2); however, data among adolescents on vaccine effectiveness (VE) against COVID-19 in real-world settings are limited, especially among hospitalized patients. In early September 2021, U.S. pediatric COVID-19 hospitalizations reached the highest level during the pandemic (3,4). In a test-negative, case-control study at 19 pediatric hospitals in 16 states during June 1-September 30, 2021, the effectiveness of 2 doses of Pfizer-BioNTech vaccine against COVID-19 hospitalization was assessed among children and adolescents aged 12-18 years. Among 464 hospitalized persons aged 12-18 years (179 case-patients and 285 controls), the median age was 15 years, 72% had at least one underlying condition, including obesity, and 68% attended in-person school. Effectiveness of 2 doses of Pfizer-BioNTech vaccine against COVID-19 hospitalization was 93% (95% CI = 83%-97%), during the period when B.1.617.2 (Delta) was the predominant variant. This evaluation demonstrated that 2 doses of Pfizer-BioNTech vaccine are highly effective at preventing COVID-19 hospitalization among persons aged 12-18 years and reinforces the importance of vaccination to protect U.S. youths against severe COVID-19. |
Extracorporeal membrane oxygenation characteristics and outcomes in children and adolescents with COVID-19 or multisystem inflammatory syndrome admitted to U.S. ICUs
Bembea MM , Loftis LL , Thiagarajan RR , Young CC , McCadden TP , Newhams MM , Kucukak S , Mack EH , Fitzgerald JC , Rowan CM , Maddux AB , Kolmar AR , Irby K , Heidemann S , Schwartz SP , Kong M , Crandall H , Havlin KM , Singh AR , Schuster JE , Hall MW , Wellnitz KA , Maamari M , Gaspers MG , Nofziger RA , Lim PPC , Carroll RW , Coronado Munoz A , Bradford TT , Cullimore ML , Halasa NB , McLaughlin GE , Pannaraj PS , Cvijanovich NZ , Zinter MS , Coates BM , Horwitz SM , Hobbs CV , Dapul H , Graciano AL , Butler AD , Patel MM , Zambrano LD , Campbell AP , Randolph AG . Pediatr Crit Care Med 2023 24 (5) 356-71 OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed. DESIGN: Case series of patients from the Overcoming COVID-19 public health surveillance registry. SETTING: Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021. PATIENTS: Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria for MIS-C or acute COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The final cohort included 2,733 patients with MIS-C (n = 1,530; 37 [2.4%] requiring ECMO) or acute COVID-19 (n = 1,203; 71 [5.9%] requiring ECMO). ECMO patients in both groups were older than those without ECMO support (MIS-C median 15.4 vs 9.9 yr; acute COVID-19 median 15.3 vs 13.6 yr). The body mass index percentile was similar in the MIS-C ECMO versus no ECMO groups (89.9 vs 85.8; p = 0.22) but higher in the COVID-19 ECMO versus no ECMO groups (98.3 vs 96.5; p = 0.03). Patients on ECMO with MIS-C versus COVID-19 were supported more often with venoarterial ECMO (92% vs 41%) for primary cardiac indications (87% vs 23%), had ECMO initiated earlier (median 1 vs 5 d from hospitalization), shorter ECMO courses (median 3.9 vs 14 d), shorter hospital length of stay (median 20 vs 52 d), lower in-hospital mortality (27% vs 37%), and less major morbidity at discharge in survivors (new tracheostomy, oxygen or mechanical ventilation need or neurologic deficit; 0% vs 11%, 0% vs 20%, and 8% vs 15%, respectively). Most patients with MIS-C requiring ECMO support (87%) were admitted during the pre-Delta (variant B.1.617.2) period, while most patients with acute COVID-19 requiring ECMO support (70%) were admitted during the Delta variant period. CONCLUSIONS: ECMO support for SARS-CoV-2-related critical illness was uncommon, but type, initiation, and duration of ECMO use in MIS-C and acute COVID-19 were markedly different. Like pre-pandemic pediatric ECMO cohorts, most patients survived to hospital discharge. |
Characteristics associated with successful foodborne outbreak investigations involving United States retail food establishments (2014-2016)
Holst MM , Kramer A , Hoover ER , Dewey-Mattia D , Mack J , Hawkins T , Brown LG . Epidemiol Infect 2023 151 1-21 This study examined relationships between foodborne outbreak investigation characteristics, | such as the epidemiological methods used, and the success of the investigation, as determined by | whether the investigation identified an outbreak agent (i.e., pathogen), food item, and contributing | factor. This study used data from the Centers for Disease Control and Prevention’s (CDC) National | Outbreak Reporting System (NORS) and National Environmental Assessment Reporting System (NEARS) | to identify outbreak investigation characteristics associated with outbreak investigation success. We | identified investigation characteristics that increase the probability of successful outbreak | investigations: a rigorous epidemiology investigation method; a thorough environmental assessment, as | measured by number of visits to complete the assessment; and the collection of clinical samples. This | research highlights the importance of a comprehensive outbreak investigation, which includes | epidemiology, environmental health, and laboratory personnel working together to solve the outbreak. |
Variation in early anakinra use and short-term outcomes in multisystem inflammatory syndrome in children
Chang JC , Young CC , Muscal E , Sexson Tejtel SK , Newhams MM , Kucukak S , Crandall H , Maddux AB , Rowan CM , Halasa NB , Harvey HA , Hobbs CV , Hall MW , Kong M , Aguiar CL , Schuster JE , Fitzgerald JC , Singh AR , Wellnitz K , Nofziger RA , Cvijanovich NZ , Mack EH , Schwarz AJ , Heidemann S , Newburger JW , Zambrano LD , Campbell AP , Patel MM , Randolph AG , Son MBF . Arthritis Rheumatol 2023 75 (8) 1466-1476 OBJECTIVE: Evidence regarding effectiveness of interleukin-1 receptor antagonism in Multisystem Inflammatory Syndrome in Children (MIS-C) is lacking. We characterized variation in initial treatment with anakinra and evaluated cardiovascular outcomes associated with adding anakinra to standard initial therapy. METHODS: We conducted a retrospective cohort study of MIS-C cases in a U.S. surveillance registry November 2020-December 2021. Day 0 was the first calendar day of immunomodulatory treatment. Factors associated with initial anakinra use (days 0-1) were identified. We compared cases ages 2-20 years receiving intravenous immunoglobulin (IVIG) and glucocorticoids vs. anakinra plus IVIG and/or glucocorticoids (days 0-1), using inverse probability weighting to balance severity. Primary outcomes were vasopressor requirement (day 3) and impaired left ventricular ejection fraction (days 3-4). The secondary outcome was 50% reduction in C-reactive protein (day 3). RESULTS: Among 1516 MIS-C cases (44 sites), 193 (13%) received anakinra alone or with other immunomodulators as initial treatment (range 0-74% by site). Site accounted for 59% of residual variance in anakinra use. After balancing severity, initial treatment with anakinra plus IVIG and/or glucocorticoids (N=121) vs. IVIG and glucocorticoids (N=389) was not associated with significant differences in vasopressor requirement (25.6% vs. 20.1%; RR 1.27, 95% CI [0.88-1.84]), ventricular dysfunction (33.7% vs. 25.7%; RR 1.31, 95% CI [0.98-1.75]), or C-reactive protein reduction. CONCLUSIONS: We identified substantial variation in initial anakinra use in a real-world population of children with MIS-C, but no average short-term improvement in cardiovascular outcomes associated with early addition of anakinra to IVIG and/or glucocorticoids compared to IVIG and glucocorticoids alone. |
Notes from the field: Recent changes in suicide rates, by race and ethnicity and age group - United States, 2021
Stone DM , Mack KA , Qualters J . MMWR Morb Mortal Wkly Rep 2023 72 (6) 160-162 Suicide is a serious public health problem in the United States. After 2 consecutive years of declines in suicide (47,511 in 2019 and 45,979 in 2020), 2021 data indicate an increase in suicide to 48,183, nearly returning to the 2018 peak (48,344) with an age-adjusted rate of 14.1 suicides per 100,000 population (versus 14.2 in 2018).* To understand how this increase is distributed across racial and ethnic groups, CDC analyzed changes in racial and ethnic age-adjusted and age-specific suicide rates during 2018–2021. | | Suicides were identified from the National Vital Statistics System multiple cause-of-death mortality files for 2018–2021. Age-adjusted rates and 95% CIs were calculated using the direct method and the 2000 U.S. standard population. Hispanic or Latino (Hispanic) persons could be of any race, and racial groups excluded persons of Hispanic ethnicity. Persons with unknown ethnicity were excluded from race and ethnicity groups but were included in the overall total. Differences in rates from 2018 to 2021 were compared using z-tests when deaths were ≥100; p-values <0.05 were considered statistically significant. When deaths were <100, differences in rates were considered significant if CIs based on a gamma distribution did not overlap. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.† |
NFKB2 haploinsufficiency identified via screening for IFNα2 autoantibodies in children and adolescents hospitalized with SARS-CoV-2-related complications.
Bodansky A , Vazquez SE , Chou J , Novak T , Al-Musa A , Young C , Newhams M , Kucukak S , Zambrano LD , Mitchell A , Wang CY , Moffitt K , Halasa NB , Loftis LL , Schwartz SP , Walker TC , Mack EH , Fitzgerald JC , Gertz SJ , Rowan CM , Irby K , Sanders RC Jr , Kong M , Schuster JE , Staat MA , Zinter MS , Cvijanovich NZ , Tarquinio KM , Coates BM , Flori HR , Dahmer MK , Crandall H , Cullimore ML , Levy ER , Chatani B , Nofziger R , Geha RS , DeRisi J , Campbell AP , Anderson M , Randolph AG . J Allergy Clin Immunol 2023 151 (4) 926-930.e2 BACKGROUND: Autoantibodies against type I IFNs occur in approximately 10% of adults with life-threatening coronavirus disease 2019 (COVID-19). The frequency of anti-IFN autoantibodies in children with severe sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. OBJECTIVE: We quantified anti-type I IFN autoantibodies in a multicenter cohort of children with severe COVID-19, multisystem inflammatory syndrome in children (MIS-C), and mild SARS-CoV-2 infections. METHODS: Circulating anti-IFN-α2 antibodies were measured by a radioligand binding assay. Whole-exome sequencing, RNA sequencing, and functional studies of peripheral blood mononuclear cells were used to study any patients with levels of anti-IFN-α2 autoantibodies exceeding the assay's positive control. RESULTS: Among 168 patients with severe COVID-19, 199 with MIS-C, and 45 with mild SARS-CoV-2 infections, only 1 had high levels of anti-IFN-α2 antibodies. Anti-IFN-α2 autoantibodies were not detected in patients treated with intravenous immunoglobulin before sample collection. Whole-exome sequencing identified a missense variant in the ankyrin domain of NFKB2, encoding the p100 subunit of nuclear factor kappa-light-chain enhancer of activated B cells, aka NF-κB, essential for noncanonical NF-κB signaling. The patient's peripheral blood mononuclear cells exhibited impaired cleavage of p100 characteristic of NFKB2 haploinsufficiency, an inborn error of immunity with a high prevalence of autoimmunity. CONCLUSIONS: High levels of anti-IFN-α2 autoantibodies in children and adolescents with MIS-C, severe COVID-19, and mild SARS-CoV-2 infections are rare but can occur in patients with inborn errors of immunity. |
Changes in Distribution of Severe Neurologic Involvement in US Pediatric Inpatients With COVID-19 or Multisystem Inflammatory Syndrome in Children in 2021 vs 2020.
LaRovere KL , Poussaint TY , Young CC , Newhams MM , Kucukak S , Irby K , Kong M , Schwartz SP , Walker TC , Bembea MM , Wellnitz K , Havlin KM , Cvijanovich NZ , Hall MW , Fitzgerald JC , Schuster JE , Hobbs CV , Halasa NB , Singh AR , Mack EH , Bradford TT , Gertz SJ , Schwarz AJ , Typpo KV , Loftis LL , Giuliano JSJr , Horwitz SM , Biagas KV , Clouser KN , Rowan CM , Maddux AB , Soma VL , Babbitt CJ , Aguiar CL , Kolmar AR , Heidemann SM , Harvey H , Zambrano LD , Campbell AP , Randolph AG . JAMA Neurol 2022 80 (1) 91-98 IMPORTANCE: In 2020 during the COVID-19 pandemic, neurologic involvement was common in children and adolescents hospitalized in the United States for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complications. OBJECTIVE: To provide an update on the spectrum of SARS-CoV-2-related neurologic involvement among children and adolescents in 2021. DESIGN, SETTING, AND PARTICIPANTS: Case series investigation of patients reported to public health surveillance hospitalized with SARS-CoV-2-related illness between December 15, 2020, and December 31, 2021, in 55 US hospitals in 31 states with follow-up at hospital discharge. A total of 2253 patients were enrolled during the investigation period. Patients suspected of having multisystem inflammatory syndrome in children (MIS-C) who did not meet criteria (n=85) were excluded. Patients (<21 years) with positive SARS-CoV-2 test results (reverse transcriptase-polymerase chain reaction and/or antibody) meeting criteria for MIS-C or acute COVID-19 were included in the analysis. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening neurologic involvement was adjudicated by experts based on clinical and/or neuroradiological features. Type and severity of neurologic involvement, laboratory and imaging data, vaccination status, and hospital discharge outcomes (death or survival with new neurologic deficits). RESULTS: Of 2168 patients included (58% male; median age, 10.3 years), 1435 (66%) met criteria for MIS-C, and 476 (22%) had documented neurologic involvement. Patients with neurologic involvement vs without were older (median age, 12 vs 10 years) and more frequently had underlying neurologic disorders (107 of 476 [22%] vs 240 of 1692 [14%]). Among those with neurologic involvement, 42 (9%) developed acute SARS-CoV-2-related life-threatening conditions, including central nervous system infection/demyelination (n=23; 15 with possible/confirmed encephalitis, 6 meningitis, 1 transverse myelitis, 1 nonhemorrhagic leukoencephalopathy), stroke (n=11), severe encephalopathy (n=5), acute fulminant cerebral edema (n=2), and Guillain-Barr syndrome (n=1). Ten of 42 (24%) survived with new neurologic deficits at discharge and 8 (19%) died. Among patients with life-threatening neurologic conditions, 15 of 16 vaccine-eligible patients (94%) were unvaccinated. CONCLUSIONS AND RELEVANCE: SARS-CoV-2-related neurologic involvement persisted in US children and adolescents hospitalized for COVID-19 or MIS-C in 2021 and was again mostly transient. Central nervous system infection/demyelination accounted for a higher proportion of life-threatening conditions, and most vaccine-eligible patients were unvaccinated. COVID-19 vaccination may prevent some SARS-CoV-2-related neurologic complications and merits further study. |
Factors associated with COVID-19 non-vaccination in adolescents hospitalized without COVID-19.
Sahni LC , Price AM , Olson SM , Newhams MM , Pannaraj PS , Maddux AB , Halasa NB , Bline KE , Cameron MA , Schwartz SP , Walker TC , Irby K , Chiotos K , Nofziger RA , Mack EH , Smallcomb L , Bradford TT , Kamidani S , Tarquinio KM , Cvijanovich NZ , Schuster JE , Bhumbra SS , Levy ER , Hobbs CV , Cullimore ML , Coates BM , Heidemann SM , Gertz SJ , Kong M , Flori HR , Staat MA , Zinter MS , Hume JR , Chatani BM , Gaspers MG , Maamari M , Randolph AG , Patel MM , Boom JA . J Pediatric Infect Dis Soc 2022 12 (1) 29-35 BACKGROUND: Pfizer-BioNTech COVID-19 vaccine received emergency use authorization for persons ≥16 years in December 2020 and for adolescents 12-15 years in May 2021. Despite the clear benefits and favorable safety profile, vaccine uptake in adolescents has been suboptimal. We sought to assess factors associated with COVID-19 non-vaccination in adolescents 12-18 years of age. METHODS: Between June 1, 2021 and April 29, 2022, we assessed factors associated with COVID-19 non-vaccination in hospitalized adolescents ages 12-18 years enrolled in the Overcoming COVID-19 vaccine effectiveness network. Demographic characteristics and clinical information were captured through parent interview and/or electronic medical record abstraction; COVID-19 vaccination was assessed through documented sources. We assessed associations between receipt of COVID-19 vaccine and demographic and clinical factors using univariate and multivariable logistic regression and estimated adjusted odds ratios (aOR) for each factor associated with non-vaccination. RESULTS: Among 1,665 hospitalized adolescents without COVID-19, 56% were unvaccinated. Unvaccinated adolescents were younger (median age 15.1 years vs. 15.4 years, p<0.01) and resided in areas with higher social vulnerability index (SVI) scores (median 0.6 vs 0.5, p<0.001) than vaccinated adolescents. Residence in the Midwest [aOR 2.60 (95% CI: 1.80, 3.79)] or South [aOR 2.49 (95% CI: 1.77, 3.54)] US census regions, rarely or never receiving influenza vaccine [aOR 5.31 (95% CI: 3.81, 7.47)], and rarely or never taking precautions against COVID-19 [aOR 3.17 (95% CI: 1.94, 5.31)] were associated with non-vaccination against COVID-19. CONCLUSIONS: Efforts to increase COVID-19 vaccination of adolescents should focus on persons with geographic, socioeconomic, and medical risk factors associated with non-vaccination. |
BNT162b2 mRNA Vaccination Against COVID-19 is Associated with Decreased Likelihood of Multisystem Inflammatory Syndrome in U.S. Children Ages 5-18 Years.
Zambrano LD , Newhams MM , Olson SM , Halasa NB , Price AM , Orzel AO , Young CC , Boom JA , Sahni LC , Maddux AB , Bline KE , Kamidani S , Tarquinio KM , Chiotos K , Schuster JE , Cullimore ML , Heidemann SM , Hobbs CV , Nofziger RA , Pannaraj PS , Cameron MA , Walker TC , Schwartz SP , Michelson KN , Coates BM , Flori HR , Mack EH , Smallcomb L , Gertz SJ , Bhumbra SS , Bradford TT , Levy ER , Kong M , Irby K , Cvijanovich NZ , Zinter MS , Bowens C , Crandall H , Hume JR , Patel MM , Campbell AP , Randolph AG . Clin Infect Dis 2022 76 (3) e90-e100 BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), linked to antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with considerable morbidity. Prevention of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) by vaccination might also decrease MIS-C likelihood. METHODS: In a multicenter case-control public health investigation of children ages 5-18 years hospitalized from July 1, 2021 to April 7, 2022, we compared the odds of being fully vaccinated (two doses of BNT162b2 vaccine 28 days before hospital admission) between MIS-C case-patients and hospital-based controls who tested negative for SARS-CoV-2. These associations were examined by age group, timing of vaccination, and periods of Delta and Omicron variant predominance using multivariable logistic regression. RESULTS: We compared 304 MIS-C case-patients (280 [92%] unvaccinated) with 502 controls (346 [69%] unvaccinated). MIS-C was associated with decreased likelihood of vaccination (aOR, 0.16 95% CI, 0.10-0.26), including among children ages 5-11 years (aOR, 0.22 95% CI, 0.10-0.52), ages 12-18 years (aOR, 0.10 95% CI, 0.05-0.19), and during the Delta (aOR, 0.06 95% CI, 0.02-0.15) and Omicron (aOR, 0.22 95% CI, 0.11-0.42) variant-predominant periods. This association persisted beyond 120 days after the second dose (aOR, 0.08, 95% CI, 0.03-0.22) in 12-18 year-olds. Among all MIS-C case-patients, 187 (62%) required intensive care unit admission and 280 (92%) vaccine-eligible patients were unvaccinated. CONCLUSIONS: Vaccination with two doses of BNT162b2 is associated with reduced likelihood of MIS-C in children ages 5-18 years. Most vaccine eligible hospitalized patients with MIS-C were unvaccinated. |
Health Impairments in Children and Adolescents After Hospitalization for Acute COVID-19 or MIS-C.
Maddux AB , Berbert L , Young CC , Feldstein LR , Zambrano LD , Kucukak S , Newhams MM , Miller K , FitzGerald MM , He J , Halasa NB , Cvijanovich NZ , Loftis LL , Walker TC , Schwartz SP , Gertz SJ , Tarquinio KM , Fitzgerald JC , Kong M , Schuster JE , Mack EH , Hobbs CV , Rowan CM , Staat MA , Zinter MS , Irby K , Crandall H , Flori H , Cullimore ML , Nofziger RA , Shein SL , Gaspers MG , Hume JR , Levy ER , Chen SR , Patel MM , Tenforde MW , Weller E , Campbell AP , Randolph AG . Pediatrics 2022 150 (3) OBJECTIVE: To evaluate risk factors for post-discharge sequelae in children and adolescents after hospitalization for acute COVID-19 or multisystem inflammatory syndrome in children (MIS-C). METHODS: Multicenter prospective observational cohort study conducted in 25 US pediatric hospitals. Patients <21-years-old, hospitalized May 2020 to May 2021 for acute COVID-19 or MIS-C with follow-up 2-4 months after admission. We assessed readmissions, caregiver-reported persistent symptoms or activity impairment, and new morbidities identified by the Functional Status Scale. Multivariable regression was used to calculate adjusted risk ratios (aRR). RESULTS: Of 358 eligible patients, 2-4 month survey data were available for 119/155 (76.8%) with acute COVID-19 and 160/203 (78.8%) with MIS-C. Thirteen (11%) patients with acute COVID-19 and 12 (8%) with MIS-C had a readmission. Thirty-two (26.9%) patients with acute COVID-19 had persistent symptoms (22.7%) or activity impairment (14.3%) and 48 (30.0%) patients with MIS-C had persistent symptoms (20.0%) or activity impairment (21.3%). For patients with acute COVID-19, persistent symptoms (aRR, 1.29[95% CI, 1.04-1.59]) and activity impairment (aRR, 1.37[95% CI, 1.06-1.78]) were associated with more organs systems involved. Patients with MIS-C and pre-existing respiratory conditions more frequently had persistent symptoms (aRR, 3.09[95% CI, 1.55-6.14]) and those with obesity more frequently had activity impairment (aRR, 2.52[95% CI, 1.35-4.69]). New morbidities were infrequent (9% COVID-19 and 1% MIS-C). CONCLUSIONS: Over one in four children hospitalized with acute COVID-19 or MIS-C experienced persistent symptoms or activity impairment for at least 2 months. Patients with MIS-C and respiratory conditions or obesity are at higher risk of prolonged recovery. |
Effect of the ABCA1 agonist CS-6253 on amyloid- and lipoprotein metabolism in cynomolgus monkeys
Noveir SD , Kerman BE , Xian H , Meuret C , Smadi S , Martinez AE , Johansson J , Zetterberg H , Parks BA , Kuklenyik Z , Mack WJ , Johansson JO , Yassine HN . Alzheimers Res Ther 2022 14 (1) 87 BACKGROUND: Inducing brain ATP-binding cassette 1 (ABCA1) activity in Alzheimer's disease (AD) mouse models is associated with improvement in AD pathology. The purpose of this study was to investigate the effects of the ABCA1 agonist peptide CS-6253 on amyloid-β peptides (Aβ) and lipoproteins in plasma and cerebrospinal fluid (CSF) of cynomolgus monkeys, a species with amyloid and lipoprotein metabolism similar to humans. METHODS: CS-6253 peptide was injected intravenously into cynomolgus monkeys at various doses in three different studies. Plasma and CSF samples were collected at several time points before and after treatment. Levels of cholesterol, triglyceride (TG), lipoprotein particles, apolipoproteins, and Aβ were measured using ELISA, ion-mobility analysis, and asymmetric-flow field-flow fractionation (AF4). The relationship between the change in levels of these biomarkers was analyzed using multiple linear regression models and linear mixed-effects models. RESULTS: Following CS-6253 intravenous injection, within minutes, small plasma high-density lipoprotein (HDL) particles were increased. In two independent experiments, plasma TG, apolipoprotein E (apoE), and Aβ42/40 ratio were transiently increased following CS-6253 intravenous injection. This change was associated with a non-significant decrease in CSF Aβ42. Both plasma total cholesterol and HDL-cholesterol levels were reduced following treatment. AF4 fractionation revealed that CS-6253 treatment displaced apoE from HDL to intermediate-density- and low density-lipoprotein (IDL/LDL)-sized particles in plasma. In contrast to plasma, CS-6253 had no effect on the assessed CSF apolipoproteins or lipids. CONCLUSIONS: Treatment with the ABCA1 agonist CS-6253 appears to favor Aβ clearance from the brain. |
Life-Threatening Complications of Influenza versus COVID-19 in U.S. Children.
Halasa NB , Spieker AJ , Young CC , Olson SM , Newhams MM , Amarin JZ , Moffitt KL , Nakamura MM , Levy ER , Soma VL , Talj R , Weiss SL , Fitzgerald JC , Mack EH , Maddux AB , Schuster JE , Coates BM , Hall MW , Schwartz SP , Schwarz AJ , Kong M , Spinella PC , Loftis LL , McLaughlin GE , Hobbs CV , Rowan CM , Bembea MM , Nofziger RA , Babbitt CJ , Bowens C , Flori HR , Gertz SJ , Zinter MS , Giuliano JS , Hume JR , Cvijanovich NZ , Singh AR , Crandall HA , Thomas NJ , Cullimore ML , Patel MM , Randolph AG . Clin Infect Dis 2022 76 (3) e280-e290 BACKGROUND: Clinical differences between critical illness from influenza infection versus coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients. METHODS: We compared U.S. children (8 months to 17 years) admitted to the intensive care or high acuity unit with influenza (17 hospitals, 12/19/2019-3/9/2020) or COVID-19 (52 hospitals, 3/15/2020-12/31/2020). We compared demographics, underlying conditions, clinical presentation, severity, and outcomes. Using mixed-effects models, we assessed the odds of death or requiring life-support for influenza versus COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity. RESULTS: Children with influenza (n = 179) were younger than those with COVID-19 (n = 381; median 5.2 vs. 13.8 years), less likely to be non-Hispanic black (14.5% vs. 27.6%) or Hispanic (24.0% vs. 36.2%), and less likely to have ≥1 underlying condition (66.4% vs. 78.5%) or be obese (21.4% vs. 42.2%). They were similarly likely to require invasive mechanical ventilation (both 30.2%), vasopressor support (19.6% and 19.9%), or extracorporeal membrane oxygenation (2.2% and 2.9%). Four children with influenza (2.2%) and 11 children with COVID-19 (2.9%) died. The odds of death or requiring life-support in children with influenza vs. COVID-19 were similar (adjusted odds ratio, 1.30 [95% CI: 0.78-2.15; P = 0.32]). Median duration of hospital stay was shorter for influenza than COVID-19 (5 versus 7 days). CONCLUSIONS: Despite differences in demographics and clinical characteristics of children with influenza or COVID-19, the frequency of life-threatening complications was similar. Our findings highlight the importance of implementing prevention measures to reduce transmission and disease severity of influenza and COVID-19. |
Maternal Vaccination and Risk of Hospitalization for Covid-19 among Infants.
Halasa NB , Olson SM , Staat MA , Newhams MM , Price AM , Pannaraj PS , Boom JA , Sahni LC , Chiotos K , Cameron MA , Bline KE , Hobbs CV , Maddux AB , Coates BM , Michelson KN , Heidemann SM , Irby K , Nofziger RA , Mack EH , Smallcomb L , Schwartz SP , Walker TC , Gertz SJ , Schuster JE , Kamidani S , Tarquinio KM , Bhumbra SS , Maamari M , Hume JR , Crandall H , Levy ER , Zinter MS , Bradford TT , Flori HR , Cullimore ML , Kong M , Cvijanovich NZ , Gilboa SM , Polen KN , Campbell AP , Randolph AG , Patel MM . N Engl J Med 2022 387 (2) 109-119 BACKGROUND: Infants younger than 6 months of age are at high risk for complications of coronavirus disease 2019 (Covid-19) and are not eligible for vaccination. Transplacental transfer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after maternal Covid-19 vaccination may confer protection against Covid-19 in infants. METHODS: We used a case-control test-negative design to assess the effectiveness of maternal vaccination during pregnancy against hospitalization for Covid-19 among infants younger than 6 months of age. Between July 1, 2021, and March 8, 2022, we enrolled infants hospitalized for Covid-19 (case infants) and infants hospitalized without Covid-19 (control infants) at 30 hospitals in 22 states. We estimated vaccine effectiveness by comparing the odds of full maternal vaccination (two doses of mRNA vaccine) among case infants and control infants during circulation of the B.1.617.2 (delta) variant (July 1, 2021, to December 18, 2021) and the B.1.1.259 (omicron) variant (December 19, 2021, to March 8, 2022). RESULTS: A total of 537 case infants (181 of whom had been admitted to a hospital during the delta period and 356 during the omicron period; median age, 2 months) and 512 control infants were enrolled and included in the analyses; 16% of the case infants and 29% of the control infants had been born to mothers who had been fully vaccinated against Covid-19 during pregnancy. Among the case infants, 113 (21%) received intensive care (64 [12%] received mechanical ventilation or vasoactive infusions). Two case infants died from Covid-19; neither infant's mother had been vaccinated during pregnancy. The effectiveness of maternal vaccination against hospitalization for Covid-19 among infants was 52% (95% confidence interval [CI], 33 to 65) overall, 80% (95% CI, 60 to 90) during the delta period, and 38% (95% CI, 8 to 58) during the omicron period. Effectiveness was 69% (95% CI, 50 to 80) when maternal vaccination occurred after 20 weeks of pregnancy and 38% (95% CI, 3 to 60) during the first 20 weeks of pregnancy. CONCLUSIONS: Maternal vaccination with two doses of mRNA vaccine was associated with a reduced risk of hospitalization for Covid-19, including for critical illness, among infants younger than 6 months of age. (Funded by the Centers for Disease Control and Prevention.). |
BNT162b2 Protection against the Omicron Variant in Children and Adolescents.
Price AM , Olson SM , Newhams MM , Halasa NB , Boom JA , Sahni LC , Pannaraj PS , Irby K , Bline KE , Maddux AB , Nofziger RA , Cameron MA , Walker TC , Schwartz SP , Mack EH , Smallcomb L , Schuster JE , Hobbs CV , Kamidani S , Tarquinio KM , Bradford TT , Levy ER , Chiotos K , Bhumbra SS , Cvijanovich NZ , Heidemann SM , Cullimore ML , Gertz SJ , Coates BM , Staat MA , Zinter MS , Kong M , Chatani BM , Hume JR , Typpo KV , Maamari M , Flori HR , Tenforde MW , Zambrano LD , Campbell AP , Patel MM , Randolph AG . N Engl J Med 2022 386 (20) 1899-1909 BACKGROUND: Spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant, which led to increased U.S. hospitalizations for coronavirus disease 2019 (Covid-19), generated concern about immune evasion and the duration of protection from vaccines in children and adolescents. METHODS: Using a case-control, test-negative design, we assessed vaccine effectiveness against laboratory-confirmed Covid-19 leading to hospitalization and against critical Covid-19 (i.e., leading to receipt of life support or to death). From July 1, 2021, to February 17, 2022, we enrolled case patients with Covid-19 and controls without Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2 messenger RNA vaccine) at least 14 days before illness among case patients and controls, according to time since vaccination for patients 12 to 18 years of age and in periods coinciding with circulation of B.1.617.2 (delta) (July 1, 2021, to December 18, 2021) and omicron (December 19, 2021, to February 17, 2022) among patients 5 to 11 and 12 to 18 years of age. RESULTS: We enrolled 1185 case patients (1043 [88%] of whom were unvaccinated, 291 [25%] of whom received life support, and 14 of whom died) and 1627 controls. During the delta-predominant period, vaccine effectiveness against hospitalization for Covid-19 among adolescents 12 to 18 years of age was 93% (95% confidence interval [CI], 89 to 95) 2 to 22 weeks after vaccination and was 92% (95% CI, 80 to 97) at 23 to 44 weeks. Among adolescents 12 to 18 years of age (median interval since vaccination, 162 days) during the omicron-predominant period, vaccine effectiveness was 40% (95% CI, 9 to 60) against hospitalization for Covid-19, 79% (95% CI, 51 to 91) against critical Covid-19, and 20% (95% CI, -25 to 49) against noncritical Covid-19. During the omicron period, vaccine effectiveness against hospitalization among children 5 to 11 years of age was 68% (95% CI, 42 to 82; median interval since vaccination, 34 days). CONCLUSIONS: BNT162b2 vaccination reduced the risk of omicron-associated hospitalization by two thirds among children 5 to 11 years of age. Although two doses provided lower protection against omicron-associated hospitalization than against delta-associated hospitalization among adolescents 12 to 18 years of age, vaccination prevented critical illness caused by either variant. (Funded by the Centers for Disease Control and Prevention.). |
Results from a Test-to-Release from Isolation Strategy Among Fully Vaccinated National Football League Players and Staff Members with COVID-19 - United States, December 14-19, 2021.
Mack CD , Wasserman EB , Killerby ME , Soelaeman RH , Hall AJ , MacNeil A , Anderson DJ , Walton P , Pasha S , Myers E , O'Neal CS , Hostler CJ , Singh N , Mayer T , Sills A . MMWR Morb Mortal Wkly Rep 2022 71 (8) 299-305 During December 2021, the United States experienced a surge in COVID-19 cases, coinciding with predominance of the SARS-CoV-2 B.1.1.529 (Omicron) variant (1). During this surge, the National Football League (NFL) and NFL Players Association (NFLPA) adjusted their protocols for test-to-release from COVID-19 isolation on December 16, 2021, based on analytic assessments of their 2021 test-to-release data. Fully vaccinated* persons with COVID-19 were permitted to return to work once they were asymptomatic or fever-free and experiencing improving symptoms for ≥24 hours, and after two negative or high cycle-threshold (Ct) results (Ct≥35) from either of two reverse transcription-polymerase chain reaction (RT-PCR) tests(†) (2). This report describes data from NFL's SARS-CoV-2 testing program (3) and time to first negative or Ct≥35 result based on serial COVID-19 patient testing during isolation. Among this occupational cohort of 173 fully vaccinated adults with confirmed COVID-19 during December 14-19, 2021, a period of Omicron variant predominance, 46% received negative test results or had a subsequent RT-PCR test result with a Ct≥35 by day 6 postdiagnosis (i.e., concluding 5 days of isolation) and 84% before day 10. The proportion of persons with positive test results decreased with time, with approximately one half receiving positive RT-PCR test results after postdiagnosis day 5. Although this test result does not necessarily mean these persons are infectious (RT-PCR tests might continue to return positive results long after an initial positive result) (4), these findings indicate that persons with COVID-19 should continue taking precautions, including correct and consistent mask use, for a full 10 days after symptom onset or initial positive test result if they are asymptomatic. |
Non-fatal injury data: characteristics to consider for surveillance and research
Carmichael AE , Ballesteros MF , Qualters JR , Mack KA . Inj Prev 2022 28 (3) 262-268 BACKGROUND: All data systems used for non-fatal injury surveillance and research have strengths and limitations that influence their utility in understanding non-fatal injury burden. The objective of this paper was to compare characteristics of major data systems that capture non-fatal injuries in the USA. METHODS: By applying specific inclusion criteria (eg, non-fatal and non-occupational) to well-referenced injury data systems, we created a list of commonly used non-fatal injury data systems for this study. Data system characteristics were compiled for 2018: institutional support, years of data available, access, format, sample, sampling method, injury definition/coding, geographical representation, demographic variables, timeliness (lag) and further considerations for analysis. RESULTS: Eighteen data systems ultimately fit the inclusion criteria. Most data systems were supported by a federal institution, produced national estimates and were available starting in 1999 or earlier. Data source and injury case coding varied between the data systems. Redesigns of sampling frameworks and the use of International Classification of Diseases, 9th Revision, Clinical Modification/International Classification of Diseases, 10th Revision, Clinical Modification coding for some data systems can make longitudinal analyses complicated for injury surveillance and research. Few data systems could produce state-level estimates. CONCLUSION: Thoughtful consideration of strengths and limitations should be exercised when selecting a data system to answer injury-related research questions. Comparisons between estimates of various data systems should be interpreted with caution, given fundamental system differences in purpose and population capture. This research provides the scientific community with an updated starting point to assist in matching the data system to surveillance and research questions and can improve the efficiency and quality of injury analyses. |
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