IMPORTANCEUnderstanding of SARS-CoV-2 infection in US children has been limited by the lack of large, multicenter studies with granular data. OBJECTIVE To examine the characteristics, changes over time, outcomes, and severity risk factors of children with SARS-CoV-2 within the National COVID Cohort Collaborative (N3C). DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study of encounters with end dates before September 24, 2021, was conducted at 56 N3C facilities throughout the US. Participants included children younger than 19 years at initial SARS-CoV-2 testing. MAIN OUTCOMES AND MEASURES Case incidence and severity over time, demographic and comorbidity severity risk factors, vital sign and laboratory trajectories, clinical outcomes, and acute COVID-19 vs multisystem inflammatory syndrome in children (MIS-C), and Delta vs pre-Delta variant differences for children with SARS-CoV-2. RESULTS A total of 1 068 410 children were tested for SARS-CoV-2 and 167 262 test results (15.6%) were positive (82 882 [49.6%] girls; median age, 11.9 [IQR, 6.0-16.1] years). Among the 10 245 children (6.1%) who were hospitalized, 1423 (13.9%) met the criteria for severe disease: mechanical ventilation (796 [7.8%]), vasopressor-inotropic support (868 [8.5%]), extracorporeal membrane oxygenation (42 [0.4%]), or death (131 [1.3%]). Male sex (odds ratio [OR], 1.37; 95% CI, 1.21-1.56),

This cohort study uses data from the US National COVID Cohort Collaborative to evaluate upper airway infections in children during the surge of the Omicron (B.1.1.529) variant of SARS-CoV-2 in the US.

Electronic Health Record (EHR) systems typically define laboratory test results using the Laboratory Observation Identifier Names and Codes (LOINC) and can transmit them using Fast Healthcare Interoperability Resource (FHIR) standards. LOINC has not yet been semantically integrated with computational resources for phenotype analysis. Here, we provide a method for mapping LOINC-encoded laboratory test results transmitted in FHIR standards to Human Phenotype Ontology (HPO) terms. We annotated the medical implications of 2923 commonly used laboratory tests with HPO terms. Using these annotations, our software assesses laboratory test results and converts each result into an HPO term. We validated our approach with EHR data from 15,681 patients with respiratory complaints and identified known biomarkers for asthma. Finally, we provide a freely available SMART on FHIR application that can be used within EHR systems. Our approach allows readily available laboratory tests in EHR to be reused for deep phenotyping and exploits the hierarchical structure of HPO to integrate distinct tests that have comparable medical interpretations for association studies.

Additional research is needed to establish the sensitivity and specificity of PCT for the diagnosis of KD. PCT may be of value in predicting which children are at increased risk for IVIG-resistant disease.

Background Kawasaki Disease (KD), a systemic vasculitis of medium sized vessels, is the most common cause of acquired heart disease among children in the developed world. Some KD patients demonstrate echocardiographic evidence of depressed myocardial mechanics. However, the incidence, etiology, and reversibility of abnormal mechanics in KD patients remain undefined. Methods and results We retrospectively studied 41 KD patients and measured myocardial strain and strain rate by velocity vector imaging from pre-treatment and convalescent echocardiograms. Pre-treatment procalcitonin, C-reactive protein (CRP), and coronary artery z-scores were obtained in all patients and compared between the groups with preserved versus depressed acute phase mechanics. The change in mechanics between the acute and convalescent phases was also assessed. Patients with initially low longitudinal strain improved by the convalescent period (mean difference - 4.0%; p<0.005) with the greatest improvement occurring in patients with the lowest initial strain (−7.3%; p<0.05). Patients with higher initial strain did not change significantly by the convalescent period. Patients with lower longitudinal and circumferential strain demonstrated higher median procalcitonin levels (1.2 vs. 0.3 ng/mL; p<0.05 and 1.8 vs. 0.4 ng/mL; p<0.05 respectively) and a trend towards higher CRP, but no difference in coronary artery z-scores. Strain rate was not associated with inflammatory markers or coronary artery z-scores. Conclusions The range of strain found in our cohort was large. Improvement in mean strain was driven primarily by patients with lower initial strain. Lower strain was associated with increased markers of systemic inflammation, but not proximal coronary artery changes.

Importance: SARS-CoV-2 Objective: To determine the characteristics, changes over time, outcomes, and severity risk factors of SARS-CoV-2 affected children within the National COVID Cohort Collaborative (N3C) Design: Prospective cohort study of encounters with end dates before May 27th, 2021. Setting: 45 N3C institutions Participants: Children < 19-years-old at initial SARS-CoV-2 testing Main Outcomes and Measures: Case incidence and severity over time, demographic and comorbidity severity risk factors, vital sign and laboratory trajectories, clinical outcomes, and acute COVID-19 vs MIS-C contrasts for children infected with SARS-CoV-2. Results: 728,047 children in the N3C were tested for SARS-CoV-2; of these, 91,865 (12.6%) were positive. Among the 5,213 (6%) hospitalized children, 685 (13%) met criteria for severe disease: mechanical ventilation (7%), vasopressor/inotropic support (7%), ECMO (0.6%), or death/discharge to hospice (1.1%). Male gender, African American race, older age, and several pediatric complex chronic condition (PCCC) subcategories were associated with higher clinical severity (p ≤ 0.05). Vital signs (all p ≤ 0.002) and many laboratory tests from the first day of hospitalization were predictive of peak disease severity. Children with severe (vs moderate) disease were more likely to receive antimicrobials (71% vs 32%, p < 0.001) and immunomodulatory medications (53% vs 16%, p < 0.001). Compared to those with acute COVID-19, children with MIS-C were more likely to be male, Black/African American, 1-to-12-years-old, and less likely to have asthma, diabetes, or a PCCC (p < 0.04). MIS-C cases demonstrated a more inflammatory laboratory profile and more severe clinical phenotype with higher rates of invasive ventilation (12% vs 6%) and need for vasoactive-inotropic support (31% vs 6%) compared to acute COVID-19 cases, respectively (p <0.03). Conclusions: In the largest U.S. SARS-CoV-2-positive pediatric cohort to date, we observed differences in demographics, pre-existing comorbidities, and initial vital sign and laboratory test values between severity subgroups. Taken together, these results suggest that early identification of children likely to progress to severe disease could be achieved using readily available data elements from the day of admission. Further work is needed to translate this knowledge into improved outcomes.

The overwhelming majority of pediatric cases of SARS-CoV-2 infection are mild or asymptomatic with only a handful of pediatric deaths reported. We present a case of severe COVID-19 infection in a pediatric patient with signs of hyperinflammation and consumptive coagulopathy requiring intubation and extracorporeal membrane oxygenation (ECMO) and eventual death due to ECMO complications.

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