Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children From Wild-type to Population Immunity: A Prospective Multicenter Cohort Study With Real-time Reporting

Abstract

Background: SARS-CoV-2 variant evolution and increasing immunity altered the impact of pediatric SARS-CoV-2 infection. Public health decision-making relies on accurate and timely reporting of clinical data.

Methods: This international hospital-based multicenter, prospective cohort study with real-time reporting was active from March 2020 to December 2022. We evaluated longitudinal incident rates and risk factors for disease severity.

Results: We included 564 hospitalized children with acute COVID-19 (n = 375) or multisystem inflammatory syndrome in children (n = 189) from the Netherlands, Curaçao and Surinam. In COVID-19, 134/375 patients (36%) needed supplemental oxygen therapy and 35 (9.3%) required intensive care treatment. Age above 12 years and preexisting pulmonary conditions were predictors for severe COVID-19. During omicron, hospitalized children had milder disease. During population immunity, the incidence rate of pediatric COVID-19 infection declined for older children but was stable for children below 1 year. The incidence rate of multisystem inflammatory syndrome in children was highest during the delta wave and has decreased rapidly since omicron emerged. Real-time reporting of our data impacted national pediatric SARS-CoV-2 vaccination- and booster-policies.

Conclusions: Our data supports the notion that similar to adults, prior immunity protects against severe sequelae of SARS-CoV-2 infections in children. Real-time reporting of accurate and high-quality data is feasible and impacts clinical and public health decision-making. The reporting framework of our consortium is readily accessible for future SARS-CoV-2 waves and other emerging infections.

FIGURE 1.

Summary panel of real-time reporting. Epidemiologic and demographic characteristics of the study cohort, as presented on the online dashboard. A: Date of first symptoms in patients with COVID-19 (blue) and MIS-C (orange). The black line shows overall (children and adults) national SARS-CoV-2 positive hospital admissions. Dominant SARS-CoV-2 variants (>80% of infections) are shown in the upper band. B: Geographical distribution of patients per 100,000 inhabitants in the Netherlands, Curaçao and Surinam. The Caribbean countries are not depicted to scale. C: Age distribution of study cohort. Patients with “Respiratory COVID-19” had predominantly respiratory symptoms at presentation. Patients with “Nonrespiratory COVID-19” had predominantly nonspecific symptoms at presentation, such as isolated fever or gastrointestinal complaints. Left pane: 0–18 years of age. Right pane: 0–12 months of age.

FIGURE 2.

Risk factors of severe disease in COVID-19 and MIS-C. Demographic, epidemiologic and clinical characteristics of children admitted with COVID-19 or MIS-C. Results from a univariate logistic regression model, with disease severity as a dependent variable, are presented in the forest plot, with corresponding odds ratio, confidence intervals and P value. Proportions of severe cases over all observations in that group are shown with counts and percentages. P values were corrected using the Benjamini–Hochberg procedure (P values: ≥0.05 ns, <0.05*, <0.01**, <0.001***). CI indicates confidence interval; MIS-C, multisystem inflammatory syndrome in children.

FIGURE 3.

Patient dynamics throughout COVID-19 pandemic phases. Demographic and clinical characteristics of hospitalized COVID-19 and MIS-C patients during pandemic course by date of disease onset. Dominant SARS-CoV-2 variants (>80% of infections) are shown in the upper band. A: Disease severity. B: Age (stratified). C: Preexisting medical history. D: Hospital stay in days. IC indicates intensive care; MIS-C, multisystem inflammatory syndrome in children; NDA, neurocognitive developmental abnormalities.