Children with SARS-CoV-2 in the National COVID Cohort Collaborative (N3C)

Abstract

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.

Association between Coagulation Profile and Clinical Outcome in Children with SARS-CoV-2 Infection or MIS-C: A Multicenter Cross-Sectional Study

“…With the increase in the number of cases of COVID-19, the need to better understand this pathology appears increasingly urgent; in this sense, identifying risk factors of severity certainly represents one of the most important objectives. As for the general characteristics, our data confirm what has already been reported in the literature, highlighting how older age and the diagnosis of MIS-C are more frequently present in patients admitted to the PICU [ 21 ]. On the other hand, there were no statistically significant differences according to gender and the presence or absence of comorbidities, differently from what was reported in other studies [ 22 ].…”

Risk of adverse events after covid-19 in Danish children and adolescents and effectiveness of BNT162b2 in adolescents: cohort study

“…We found that neuroimmune complications were exceedingly rare, whereas MIS-C occurred in 0.05% of confirmed SARS-CoV-2 infections, which is similar to other population based estimates. 28 29 30 Previous studies have identified obesity and black and Hispanic race as important risk factors for severe covid-19 and MIS-C. 24 25 30 This needs to be considered when generalising our results, as Denmark is predominantly a society of white ethnicity with a low prevalence of childhood obesity. 31 …”

“…22 Compared with the few previous studies providing population based data on the risk of hospital admission after SARS-CoV-2 infection, the reported risks were similar to those of Israel and Spain (0.2% to 0.5%), but lower than those reported from the UK (1.3%) and US (5.7%). 7 23 24 25 Both the case fatality rate and the risk of hospital admissions are, however, influenced by access to testing for SARS-CoV-2 and are likely to be overestimates of the true risk. Recent Danish SARS-CoV-2 seroprevalence studies have estimated that the true prevalence of SARS-CoV-2 infection among adolescents is up to threefold higher than that detected by national RT-PCR tests.…”

Pediatric COVID-19: Immunopathogenesis, Transmission and Prevention

“…Notably, the UK recently decided to restrict vaccination to adolescents who are at risk of severe COVID-19 and to those who are household contacts of immunosuppressed patients (https://www.gov.uk/government/news/ jcvi-issues-advice-on-COVID-19-vaccination-of-children-and-young-people, accessed on 31 July 2021) As for any vaccine in any target population, the decision to recommend and implement COVID-19 vaccination of adolescents and younger children is based on benefit-risk analyses [120][121][122][123]. Although most children remain asymptomatic, 6% of children are hospitalized; 13% of those hospitalized meet the criteria for severe disease with a fatality rate of 1%, while others suffer from prolonged symptoms (long COVID) and could, therefore, benefit from vaccination [124]. This benefit is stronger for vulnerable children who are at risk of severe COVID-19.…”