Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2.

2020

2020 Jul 30

1558-8238

<p><strong>BACKGROUND: </strong>Initial reports from the Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to Coronavirus Disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed Multisystem Inflammatory Syndrome in Children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology.</p>

<p><strong>METHODS: </strong>We prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data. Twenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8 and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. Cts and burr cells on blood smears also differentiated between patients with severe COVID-19 and those with MIS-C.</p>

<p><strong>CONCLUSION: </strong>Pediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and severe COVID-19.</p>

10.1172/JCI140970

J. Clin. Invest.

32730233

Initial effects of the COVID-19 pandemic on pediatric asthma emergency department utilization.

2020

2020 Jun 06

2213-2201

<p>Compared with historical trends, we describe a dramatic decrease in pediatric asthma-related emergency department utilization for all levels of acuity coincident with coronavirus disease 2019&nbsp;emergence. These findings have implications for clinicians and researchers seeking to understand the drivers of asthma exacerbations.</p>

10.1016/j.jaip.2020.05.045

J Allergy Clin Immunol Pract

32522565

Variability in Diagnosed Asthma in Young Children in a Large Pediatric Primary Care Network.

2020

2020 Feb 07

1876-2867

<p><strong>OBJECTIVES: </strong>Our objectives were to (1) quantify the frequency of wheezing episodes and asthma diagnosis in young children in a large pediatric primary care network and (2) assess the variability in practice-level asthma diagnosis, accounting for common asthma risk factors and comorbidities. We hypothesized that significant variability in practice-level asthma diagnosis rates would remain after adjusting for associated predictors.</p>

<p><strong>METHODS: </strong>We generated a retrospective longitudinal birth cohort of children who visited one of 31 pediatric primary care practices within the first 6 months of life from 1/2005-12/2016. Children were observed for up to 8 years or until the end of the observation window. We used multivariable discrete time survival models to evaluate predictors of asthma diagnosis by 3-month age intervals. We compared unadjusted and adjusted proportions of children diagnosed with asthma by practice.</p>

<p><strong>RESULTS: </strong>Of the 161,502 children in the cohort, 34,578 children (21%) received at least one asthma diagnosis. In multivariable modeling, male gender, minority race/ethnicity, gestational age &lt;34 weeks, allergic rhinitis, food allergy, and prior wheezing episodes were associated with asthma diagnosis. After adjusting for variation in these predictors across practices, the cumulative incidence of asthma diagnosis by practice by age 6 years ranged from 11-47% (interquartile range (IQR): 24-29%).</p>

<p><strong>CONCLUSIONS: </strong>Across pediatric primary care practices, adjusted incidence of asthma diagnosis by age 6 years ranged widely, though variation gauged by the IQR was more modest. Potential sources of practice-level variation, such as differing diagnosis thresholds and labeling of different wheezing phenotypes as "asthma", should be further investigated.</p>

10.1016/j.acap.2020.02.003

Acad Pediatr

32044466

Genomic Circuitry Underlying Immunological Response to Pediatric Acute Respiratory Infection.

2018

411-426

2018 Jan 09

2211-1247

<p>Acute respiratory tract viral infections (ARTIs) cause significant morbidity and mortality. CD8 T&nbsp;cells are fundamental to host responses, but transcriptional alterations underlying anti-viral mechanisms and links to clinical characteristics remain unclear. CD8 T&nbsp;cell transcriptional circuitry in acutely ill pediatric patients with influenza-like illness was distinct for&nbsp;different viral pathogens. Although changes included expected upregulation of interferon-stimulated genes (ISGs), transcriptional downregulation was prominent upon exposure to innate immune signals in early IFV infection. Network analysis linked changes to severity of infection, asthma, sex, and age. An influenza pediatric signature (IPS) distinguished acute influenza from other ARTIs and outperformed other influenza prediction gene lists. The IPS allowed a deeper investigation of the connection between transcriptional alterations and clinical characteristics of acute illness, including age-based differences in circuits connecting the STAT1/2 pathway to ISGs. A CD8 T&nbsp;cell-focused systems immunology approach in pediatrics identified age-based alterations in ARTI host response pathways.</p>

10.1016/j.celrep.2017.12.043

Cell Rep

29320737