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BACKGROUND: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).
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Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/virologia , Adolescente , Betacoronavirus , COVID-19 , Centers for Disease Control and Prevention, U.S. , Criança , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Cuidados Críticos , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunomodulação , Inflamação , Tempo de Internação , Masculino , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/terapia , Síndrome de Linfonodos Mucocutâneos/virologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Estudos Prospectivos , Respiração Artificial , Estudos Retrospectivos , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica/terapia , Estados UnidosRESUMO
OBJECTIVES: To describe trends in critical illness from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children over the course of the COVID-19 pandemic. We hypothesized that PICU admission rates were higher in the Omicron period compared with the original outbreak but that fewer patients needed endotracheal intubation. DESIGN: Retrospective cohort study. SETTING: This study took place in nine U.S. PICUs over 3 weeks in January 2022 (Omicron period) compared with 3 weeks in March 2020 (original period). PATIENTS: Patients less than or equal to 21 years old who screened positive for SARS-CoV-2 infection by polymerase chain reaction or hospital-based rapid antigen test and were admitted to a PICU or intermediate care unit were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 267 patients (239 Omicron and 28 original) were reviewed. Forty-five patients in the Omicron cohort had incidental SARS-CoV-2 and were excluded from analysis. The Omicron cohort patients were younger compared with the original cohort patients (median [interquartile range], 6 yr [1.3-13.3 yr] vs 14 yr [8.3-17.3 yr]; p = 0.001). The Omicron period, compared with the original period, was associated with an average increase in COVID-19-related PICU admissions of 13 patients per institution (95% CI, 6-36; p = 0.008), which represents a seven-fold increase in the absolute number admissions. We failed to identify an association between cohort period (Omicron vs original) and odds of intubation (odds ratio, 0.7; 95% CI, 0.3-1.7). However, we cannot exclude the possibility of up to 70% reduction in intubation. CONCLUSIONS: COVID-19-related PICU admissions were seven times higher in the Omicron wave compared with the original outbreak. We could not exclude the possibility of up to 70% reduction in use of intubation in the Omicron versus original epoch, which may represent differences in PICU/hospital admission policy in the later period, or pattern of disease, or possibly the impact of vaccination.
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COVID-19 , SARS-CoV-2 , Criança , Humanos , Estados Unidos/epidemiologia , COVID-19/epidemiologia , Estudos Retrospectivos , Estudos de Coortes , Pandemias , Estado Terminal , Gravidade do PacienteRESUMO
The lifecycle of black carbon (BC)-containing particles from biomass burns is examined using aircraft and surface observations of the BC mixing state for plume ages from â¼15 min to 10 days. Because BC is nonvolatile and chemically inert, changes in the mixing state of BC-containing particles are driven solely by changes in particle coating, which is mainly secondary organic aerosol (SOA). The coating mass initially increases rapidly (kgrowth = 0.84 h-1), then remains relatively constant for 1-2 days as plume dilution no longer supports further growth, and then decreases slowly until only â¼30% of the maximum coating mass remains after 10 days (kloss = 0.011 h-1). The mass ratio of coating-to-core for a BC-containing particle with a 100 nm mass-equivalent diameter BC core reaches a maximum of â¼20 after a few hours and drops to â¼5 after 10 days of aging. The initial increase in coating mass can be used to determine SOA formation rates. The slow loss of coating material, not captured in global models, comprises the dominant fraction of the lifecycle of these particles. Coating-to-core mass ratios of BC particles in the stratosphere are much greater than those in the free troposphere indicating a different lifecycle.
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Poluentes Atmosféricos , Aerossóis/química , Poluentes Atmosféricos/análise , Biomassa , Carbono/química , Monitoramento Ambiental , FuligemRESUMO
Biomass burning (BB) emits enormous amounts of aerosol particles and gases into the atmosphere and thereby significantly influences regional air quality and global climate. A dominant particle type from BB is spherical organic aerosol particles commonly referred to as tarballs. Currently, tarballs can only be identified, using microscopy, from their uniquely spherical shapes following impaction onto a grid. Despite their abundance and potential significance for climate, many unanswered questions related to their formation, emission inventory, removal processes, and optical properties still remain. Here, we report analysis that supports tarball formation in which primary organic particles undergo chemical and physical processing within â¼3 h of emission. Transmission electron microscopy analysis reveals that the number fractions of tarballs and the ratios of N and O relative to K, the latter a conserved tracer, increase with particle age and that the more-spherical particles on the substrates had higher ratios of N and O relative to K. Scanning transmission X-ray spectrometry and electron energy loss spectrometry analyses show that these chemical changes are accompanied by the formation of organic compounds that contain nitrogen and carboxylic acid. The results imply that the chemical changes increase the particle sphericity on the substrates, which correlates with particle surface tension and viscosity, and contribute to tarball formation during aging in BB smoke. These findings will enable models to better partition tarball contributions to BB radiative forcing and, in so doing, better help constrain radiative forcing models of BB events.
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Poluentes Atmosféricos/química , Biomassa , Material Particulado/química , Fumaça/análise , Alcatrões/química , Aerossóis/química , Clima , Compostos Orgânicos/análise , Tensão Superficial , ViscosidadeRESUMO
PURPOSE: Explore factors associated with flourishing and family resilience among children aged 6 months to 5 years old in the 2016 National Survey of Children's Health (NSCH). DESIGN AND METHODS: Cross-sectional analysis of the 2016 NSCH was conducted using Kleinman and Norton's Regression Risk Analysis method to derive adjusted risk measures for logistic regression models to assess factors contributing to (1) child flourishing and (2) child flourishing stratified between resilient and non-resilient families. RESULTS: In multivariable models, resilient families less often reported a child with two or more lifetime ACE exposures (ARD -0.11, 95% CI -0.15, -0.08), more likely to live in a supportive neighborhood (ARD 0.08, 95% CI 0.05,0.11), and more likely to report emotional support in raising children (ARD 0.07, 95% CI 0.12, 0.40). Accounting for ACE exposures, within resilient families, child flourishing was more likely when the child lived in a supportive neighborhood (ARD 0.09, 95% CI 0.03, 0.15), received care in a patient centered medical home (ARD 0.09, 95% CI 0.02,0.15), and when parents reported having emotional support in raising children (ARD 0.10, 95% CI 0.05, 0.17) Within non-resilient families, child flourishing was more likely when parents had emotional support in raising children (ARD 0.15, 95% CI 0.04,0.27). CONCLUSION: Promoting emotional support for parents may bolster family resilience and help young children to flourish despite adversity. PRACTICE IMPLICATIONS: Further research and innovative models of care are needed to optimize the role of pediatric primary care in promoting safe, stable, nurturing relationships and environments for children and families.
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Saúde da Criança , Resiliência Psicológica , Criança , Pré-Escolar , Estudos Transversais , Família , Saúde da Família , HumanosRESUMO
Video-electroencephalogram (EEG) monitoring in the epilepsy monitoring unit (EMU) is essential for managing epilepsy and seizure mimics. Evaluation of care in the EMU would benefit from a validated code set capable of identifying EMU admissions from administrative databases comprised of large, diverse cohorts. We assessed the ability of code-based queries to parse EMU admissions from administrative billing records in a large academic medical center over a four-year period, 2016-2019. We applied prespecified queries for admissions coded as follows: 1) elective, 2) receiving video-EEG monitoring, and 3) including diagnoses typically required by major US healthcare payers for EMU admission. Sensitivity (Sn), specificity (Sp), and predictive value positive/negative (PVP, PVN) were determined. Two approaches were highly effective. Incorporating epilepsy, seizure, or seizure mimic codes as the admitting diagnosis (assigned at admission; Sn 96.3%, Sp 100.0%, PVP 98.3%, and PVN 100.0%) or the principal diagnosis (assigned after discharge; Sn 94.9%, Sp 100.0%, PVP 98.8%, and PVN 100.0%) identified elective adult EMU admissions with comparable reliability (pâ¯=â¯0.096). The addition of surgical procedure codes further separated EMU admissions for intracranial EEG monitoring. When applied to larger, more comprehensive datasets, these code-based queries should enhance our understanding of EMU utilization and access to care on a scalable basis.
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Bases de Dados Factuais/normas , Eletroencefalografia/normas , Epilepsia/diagnóstico , Administração Hospitalar/normas , Classificação Internacional de Doenças/normas , Admissão do Paciente/normas , Adulto , Estudos de Coortes , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Feminino , Administração Hospitalar/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: To examine the range of prevalence of pediatric polypharmacy in literature through a scoping review, focusing on factors that contribute to its heterogeneity in order to improve the design and reporting of quality improvement, pharmacovigilance, and research studies. METHODS: We searched Ovid Medline, PubMed, EMBASE, CINAHL, Ovid PsycINFO, Cochrane CENTRAL, and Web of Science Core Collection databases for studies with concepts of children and polypharmacy, along with a hand search of the bibliographies of six reviews and 30 included studies. We extracted information regarding study design, disease conditions, and prevalence of polypharmacy. RESULTS: Two hundred eighty-four studies reported prevalence of polypharmacy. They were more likely to be conducted in North America (37.7%), published after 2010 (44.4%), cross-sectional (67.3%), in outpatient settings (59.5%). Prevalence ranged from 0.9% to 98.4%, median 39.7% (interquartile range [IQR] 22.0%-54.0%). Studies from Asia reported the highest median prevalence of 45.4% (IQR 27.3%-61.0%) while studies from North America reported the lowest median prevalence of 30.4% (IQR 14.7%-50.2%). Prevalence decreased over time: median 45.6% before 2001, 38.1% during 2001 to 2010, and 34% during 2011 to 2017. Studies involving children under 12 years had a higher median prevalence (46.9%) than adolescent studies (33.7%). Inpatient setting studies had a higher median prevalence (50.3%) than studies in outpatient settings (38.8%). Community level samples, higher number and duration of medications defining polypharmacy, and psychotropic medications were associated with lower prevalence. CONCLUSIONS: The prevalence of pediatric polypharmacy is high and variable. Studies reporting pediatric polypharmacy should account for context, design, polypharmacy definition, and medications evaluated.
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Polimedicação , Adolescente , Serviços de Saúde do Adolescente , Criança , Serviços de Saúde da Criança , Feminino , Saúde Global , Humanos , Masculino , Farmacoepidemiologia , Farmacovigilância , PrevalênciaRESUMO
INTRODUCTION: Various methods have been used to interpret the reports of pediatric polypharmacy across the literature. This is the first scoping review that explores outcome measures in pediatric polypharmacy research. OBJECTIVES: The aim of our study was to describe outcome measures assessed in pediatric polypharmacy research. METHODS: A search of electronic databases was conducted in July 2017, including Ovid Medline, PubMed, Elsevier Embase, Wiley Cochrane Central Register of Controlled Trials (CENTRAL), EBSCO CINAHL, Ovid PsyclNFO, Web of Science Core Collection, ProQuest Dissertations and Thesis A&I. Data were extracted about study characteristics and outcome measures, and also synthesized by harms or benefits mentioned. RESULTS: The search strategy initially identified 8169 titles and screened 4398 using the inclusion criteria after de-duplicating. After the primary screening, a total of 363 studies were extracted for the data analysis. Polypharmacy (prevalence) was identified as an outcome in 31.4% of the studies, prognosis-related outcomes in 25.6%, and adverse drug reactions in 16.5%. A total of 265 articles (73.0%) mentioned harms, including adverse drug reactions (26.4%), side effects (24.2%), and drug-drug interactions (20.9%). A total of 83 studies (22.9%) mentioned any benefit, 48.2% of which identified combination for efficacy, 24.1% combination for treatment of complex diseases, and 19.3% combination for treatment augmentation. Thirty-eight studies reported adverse drug reaction as an outcome, where polypharmacy was a predictor, with various designs. CONCLUSIONS: Most studies of pediatric polypharmacy evaluate prevalence, prognosis, or adverse drug reaction-related out-comes, and underscore harms related to polypharmacy. Clinicians should carefully weigh benefits and harms when introducing medications to treatment regimens.
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BACKGROUND: Polypharmacy can be either beneficial or harmful to children. We conducted a scoping review to examine the concept of pediatric polypharmacy: its definition, prevalence, extent and gaps in research. In this manuscript, we report our transdisciplinary scoping review methodology. METHODS: After establishing a transdisciplinary team, we iteratively developed standard operating procedures for the study's search strategy, inclusion/exclusion criteria, screening, and data extraction. We searched eight bibliographic databases, screened abstracts and full text articles, and extracted data from included studies using standardized forms. We held regular team meetings and performed ongoing internal validity measurements to maintain consistent and quality outputs. RESULTS: With the aid of EPPI Reviewer collaborative software, our transdisciplinary team of nine members performed dual reviews of 363 included studies after dual screening of 4398 abstracts and 1082 full text articles. We achieved overall agreement of 85% and a kappa coefficient of 0.71 (95% CI 0.68-0.74) while screening full text articles. The screening and review processes required about seven hours per extracted study. The two pharmacists, an epidemiologist, a neurologist, and a librarian on the review team provided internal consultation in these key disciplines. A stakeholder group of 10 members with expertise in evidence synthesis, research implementation, pediatrics, mental health, epilepsy, pharmacoepidemiology, and pharmaceutical outcomes were periodically consulted to further characterize pediatric polypharmacy. CONCLUSIONS: A transdisciplinary approach to scoping reviews, including internal and external consultation, should be considered when addressing complex cross-disciplinary questions.
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Comportamento Cooperativo , Equipe de Assistência ao Paciente/estatística & dados numéricos , Pediatria/métodos , Polimedicação , Criança , Bases de Dados Bibliográficas/estatística & dados numéricos , Atenção à Saúde/métodos , Atenção à Saúde/estatística & dados numéricos , Atenção à Saúde/tendências , Humanos , Comunicação Interdisciplinar , Equipe de Assistência ao Paciente/organização & administração , Equipe de Assistência ao Paciente/tendências , Literatura de Revisão como AssuntoAssuntos
Grupos Raciais , População Branca , Hospitais , Humanos , Recém-Nascido , Qualidade da Assistência à SaúdeRESUMO
Wildfires are important contributors to atmospheric aerosols and a large source of emissions that impact regional air quality and global climate. In this study, the regional and nearfield influences of wildfire emissions on ambient aerosol concentration and chemical properties in the Pacific Northwest region of the United States were studied using real-time measurements from a fixed ground site located in Central Oregon at the Mt. Bachelor Observatory (â¼2700 m a.s.l.) as well as near their sources using an aircraft. The regional characteristics of biomass burning aerosols were found to depend strongly on the modified combustion efficiency (MCE), an index of the combustion processes of a fire. Organic aerosol emissions had negative correlations with MCE, whereas the oxidation state of organic aerosol increased with MCE and plume aging. The relationships between the aerosol properties and MCE were consistent between fresh emissions (â¼1 h old) and emissions sampled after atmospheric transport (6-45 h), suggesting that biomass burning organic aerosol concentration and chemical properties were strongly influenced by combustion processes at the source and conserved to a significant extent during regional transport. These results suggest that MCE can be a useful metric for describing aerosol properties of wildfire emissions and their impacts on regional air quality and global climate.
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Aerossóis/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Incêndios , Biomassa , OregonRESUMO
Objectives To examine relationships between parental perceptions of child weight and overall health, reported lifestyle behaviors and measured body mass index (BMI). Methods Using community-partnered methods, we surveyed families residing in a two census tract area identified for targeted interventions to decrease diabetes related disparities. The survey included demographics, child dietary and physical activity behaviors, and parental perception of child's health and weight. We measured child BMI using a standardized protocol. Results We surveyed parents of 116 children with a mean age of 7 years (range 3-15) with 51 % boys, 74 % Hispanic, and 26 % Black. Over half of the children (55 %) were overweight or obese. Half (50 %) of the parents underestimated their children's weight. Reported daily hours of walking and/or running trended higher (3.6 vs. 2.6 h, p = 0.08) for children perceived to be of normal weight. Parents who correctly estimated their child's weight status reported more hours of daily walking/running than parents who underestimated child weight status, 4.5 versus 2.4 h, p = 0.0002. Parents of healthy weight children were more likely to report that children were in excellent or very good health compared to parents of overweight/obese children, 75 versus 56 % respectively (p = 0.04). We found significant racial/ethnic differences in reported diet and physical activity behaviors and perception of overall health. Conclusions for Practice Parental perceptions of child health and physical activity level may be related to perceptions of their child's weight status. Study findings informed community-based initiatives for reducing diabetes risk among children.
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Exercício Físico , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Obesidade/etnologia , Pais/psicologia , Percepção , Adulto , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , Índice de Massa Corporal , Criança , Pré-Escolar , Pesquisa Participativa Baseada na Comunidade , Diabetes Mellitus/prevenção & controle , Dieta , Feminino , Georgia/epidemiologia , Hispânico ou Latino/psicologia , Hispânico ou Latino/estatística & dados numéricos , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Sobrepeso/etnologia , População Rural , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
Worldwide, hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths and the ninth in the US. Hepatitis B and C make up almost 80% of HCC cases. Based on our Hepatitis Outreach Network screening program data, approximately 40% of at-risk foreign-born community members who tested positive for viral hepatitis B and/or C did not follow up for additional care. Our aim was to use theory-driven qualitative research to identify barriers and facilitators to follow-up after viral hepatitis diagnosis among these community members from the viewpoint of primary care providers (PCPs). As viral hepatitis is a precursor of liver cancer, timely treatment of the virus has the potential to reduce the incidence and burden of liver cancer. We performed semi-structured key informant interviews with 20 primary care physicians who predominantly serve Korean, Chinese, Egyptian, and Russian communities. Barriers detected included cultural factors commonly seen amongst immigrant populations such as busy work schedules and non-English language. Common facilitators include increased primary care physician involvement and linkages to care within communities in which patients reside. Providers perceived that they are gatekeepers to specialty care for their patients and therefore key persons to engage in viral hepatitis evaluation and management by specialists. This initial study suggests that re-focusing energy into primary care physicians might offer promise for improved care for individuals from immigrant communities who have viral hepatitis to help them engage in care and thereby reduce the burden of liver cancer.
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Carcinoma Hepatocelular/prevenção & controle , Etnicidade , Hepatite B Crônica/terapia , Neoplasias Hepáticas/prevenção & controle , Navegação de Pacientes , Padrões de Prática Médica , Encaminhamento e Consulta/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/psicologia , Vírus da Hepatite B , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/epidemiologia , Humanos , Incidência , Programas de Rastreamento , Atenção Primária à Saúde , Fatores de RiscoRESUMO
BACKGROUND: Behavioral or mental health disorders are common in children, adolescents, and young adults. Medication use is increasingly common, with few data describing drug-drug combinations in ambulatory settings. The objectives of this study were to describe the pharmaco-epidemiology of behavioral and mental health (BMH) medications among children, adolescents, and young adults in New York Medicaid and assess the prevalence of contraindicated drug pairs within this population. METHODS: This observational cross-sectional study evaluated New York State Medicaid managed care and fee-for-service enrollees under 21 years of age dispensed BMH medications in 2014. Main outcomes included number of members with prescriptions filled; number filling > 1 medication prescription concurrently for ≥ 30 days (polypharmacy), and number and nature of potentially contraindicated drug pairs. RESULTS: Of 2,430,434 children, adolescents, and young adults, 422,486 (17.4%) had a visit associated with a BMH diagnosis and 141,363 (5.8%) received one or more BMH medications. With 84 distinct medications evaluated, polypharmacy was common, experienced by 53,388 individuals (37.8% of those with a prescription filled), generating 11,115 distinct drug combinations. 392 individuals filled prescriptions for a contraindicated pair of ≥ 2 BMH medications for 30 days or longer. With ≥ 1 day overlap, 651 were exposed to contraindicated medications. The most common contraindicated pairs increased potential risk for prolonged QT interval and serotonin syndrome (n = 378 and n = 250 patients, respectively). Most combinations involved ziprasidone (3247.1 per 10,000 ziprasidone prescriptions filled). CONCLUSIONS: With nearly 6% of members dispensed a BMH medication, contraindicated drug pairs were uncommon. However, any of those combinations represent a potential risk. Clinicians should attend to the balance of potential risks and benefits before contraindicated pairs are dispensed. The methodology described could serve as a basis for monitoring such rare instances and might reduce harm.
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Contraindicações de Medicamentos , Transtornos Mentais , Polimedicação , Humanos , Adolescente , Criança , Masculino , Feminino , Estudos Transversais , Pré-Escolar , Adulto Jovem , New York/epidemiologia , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/epidemiologia , Estados Unidos/epidemiologia , Lactente , Medicaid/estatística & dados numéricos , Prevalência , Psicotrópicos/uso terapêutico , Antipsicóticos/uso terapêuticoRESUMO
Dysregulated innate immune responses contribute to multisystem inflammatory syndrome in children (MIS-C), characterized by gastrointestinal, mucocutaneous, and/or cardiovascular injury occurring weeks after SARS-CoV-2 exposure. To investigate innate immune functions in MIS-C, we stimulated ex vivo peripheral blood cells from MIS-C patients with agonists of Toll-like receptors (TLR), key innate immune response initiators. We found severely dampened cytokine responses and elevated gene expression of negative regulators of TLR signaling. Increased plasma levels of zonulin, a gut leakage marker, were also detected. These effects were also observed in children enrolled months after MIS-C recovery. Moreover, cells from MIS-C children carrying rare genetic variants of lysosomal trafficking regulator (LYST) were less refractory to TLR stimulation and exhibited lysosomal and mitochondrial abnormalities with altered energy metabolism. Our results strongly suggest that MIS-C hyperinflammation and/or excessive or prolonged stimulation with gut-originated TLR ligands drive immune cells to a lasting refractory state. TLR hyporesponsiveness is likely beneficial, as suggested by excess lymphopenia among rare LYST variant carriers. Our findings point to cellular mechanisms underlying TLR hyporesponsiveness; identify genetic determinants that may explain the MIS-C clinical spectrum; suggest potential associations between innate refractory states and long COVID; and highlight the need to monitor long-term consequences of MIS-C.
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Estimates of post-acute sequelae of SARS-CoV-2 infection (PASC) incidence, also known as Long COVID, have varied across studies and changed over time. We estimated PASC incidence among adult and pediatric populations in three nationwide research networks of electronic health records (EHR) participating in the RECOVER Initiative using different classification algorithms (computable phenotypes). Overall, 7% of children and 8.5%-26.4% of adults developed PASC, depending on computable phenotype used. Excess incidence among SARS-CoV-2 patients was 4% in children and ranged from 4-7% among adults, representing a lower-bound incidence estimation based on two control groups - contemporary COVID-19 negative and historical patients (2019). Temporal patterns were consistent across networks, with peaks associated with introduction of new viral variants. Our findings indicate that preventing and mitigating Long COVID remains a public health priority. Examining temporal patterns and risk factors of PASC incidence informs our understanding of etiology and can improve prevention and management.
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IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/virologia , Adolescente , Criança , Pré-Escolar , Feminino , Adulto Jovem , Adulto , Masculino , Lactente , SARS-CoV-2/isolamento & purificação , Recém-Nascido , Estudos Prospectivos , Projetos de Pesquisa , Estudos de Coortes , Síndrome de COVID-19 Pós-AgudaRESUMO
The need to understand how Community-based disparities impact morbidity and mortality in pediatric critical illness, such as traumatic brain injury. Test the hypothesis that ZIP code-based disparities in hospital utilization, including length of stay (LOS) and hospital costs, exist in a cohort of children with traumatic brain injury (TBI) admitted to a PICU using the Child Opportunity Index (COI). DESIGN: Multicenter retrospective cohort study. SETTING: Pediatric Health Information System (PHIS) database. PATIENTS: Children 0-18 years old admitted to a PHIS hospital with a diagnosis of TBI from January 2016 to December 2020 requiring PICU care. To identify the most severely injured children, a study-specific definition of "Complicated TBI" was created based on radiology, pharmacy, and procedure codes. INTERVENTIONS: None. Main Outcomes and Measures: Using nationally normed ZIP code-level COI data, patients were categorized into COI quintiles. A low COI ZIP code has low childhood opportunity based on weighted indicators within educational, health and environmental, and social and economic domains. Population-averaged generalized estimating equation (GEE) models, adjusted for patient and clinical characteristics examined the association between COI and study outcomes, including hospital LOS and accrued hospital costs. The median age of this cohort of 8,055 children was 58 months (interquartile range [IQR], 8-145 mo). There were differences in patient demographics and rates of Complicated TBI between COI levels. The median hospital LOS was 3.0 days (IQR, 2.0-6.0 d) and in population-averaged GEE models, children living in very low COI ZIP codes were expected to have a hospital LOS 10.2% (95% CI, 4.1-16.8%; p = 0.0142) longer than children living in very high COI ZIP codes. For the 11% of children with a Complicated TBI, the relationship between COI and LOS was lost in multivariable models. COI level was not predictive of accrued hospital costs in this study. CONCLUSIONS: Children with TBI requiring PICU care living in low-opportunity ZIP codes have higher injury severity and longer hospital LOS compared with children living in higher-opportunity ZIP codes. Additional studies are needed to understand why these differences exist.