Risk factors for severe COVID-19 disease course in children and adolescents with underlying cardiovascular disease

ABSTRACT

Background: While SARS-CoV-2 infections in children are usually mild to asymptomatic, severe disease manifestation has been described in patients with comorbidities. We aimed to assess the risk for severe disease courses in children and adolescents with underlying cardiovascular disease (CVD). Method: Analysis of the national prospective registry for children and adolescents hospitalized with a SARS-CoV-2 infection from March 2020 to April 2021. Regression analyses were used to estimate the risk for severe disease course defined as admission to a pediatric intensive care unit (PICU) or death. Results: Overall 1,501 hospitalized children were included in the registry with confirmed SARS-CoV-2 infection. Of these, 73 had underlying CVD (median age = 12 [IQR 3-15];49 [67%] male). Also, 33/73 (45%) had relevant associated comorbidities including syndromic disease in 20/73 (27%), including 7 patients with trisomy 21. Congenital heart disease (CHD) was present in 32 (44%) and pulmonary hypertension (PH) in 9 (12%) patients. Eleven of 32 underwent cardiac surgery for their CHD. Analysis of the PH subgroup showed that the need for intensive care therapy (56 vs. 16%;p = 0.006) and ventilatory support (56 vs. 11%, p < 0.001) was higher in the PH group. Two children (3%) died in the non-PH cohort (both on a palliative care track). In addition, one child (11%) with PH died 4 weeks after confirmed SARS-CoV-2 infection from vasculitis with brainstem involvement. Overall, CVD was associated with an increased risk for PICU admission (RR = 3.0;95% CI 1.84-4.93). In the CVD subgroup analysis, male gender (OR = 9.2;95% CI 1.1-74.8;p = 0.04), syndromic disease (OR = 4.4;1.3-14.5;p = 0.02), trisomy 21 (OR = 14;2.4-82.4;p = 0.004), respiratory disease (OR = 7.7;2.2-26.7;p = 0.001), or PH (OR = 6.8;1.5-29.6;p = 0.01) were significantly associated with disease severity requiring PICU support. In addition, a trend toward increased risk for CHD was found (OR = 3.3;0.99-10.8;p = 0.052). Patients after cardiac surgery showed a significantly increased risk (OR = 4.3;1.1-17.0;p = 0.04). Conclusion: Children and adolescents with CVD are at higher risk of severe SARS-CoV-2 course. During SARS-CoV2- infection, children with associated disease, syndromes, or PH had a significantly higher risk for intensive care support compared with patients with other associated CVD. Although overall mortality and morbidity of hospitalized SARS-CoV-2 children is low, these vulnerable cohorts may require specific attention and prevention measures.