BACKGROUND In spring 2020, a novel hyperinflammatory process associated with severe acute respiratory syndrome coronavirus 2 multisystem inflammatory syndrome in children (MIS-C) was described. The long-term impact remains unknown. We report longitudinal outcomes from a New York interdisciplinary follow-up program. METHODS All children <21 years of age, admitted to NewYork-Presbyterian with MIS-C in 2020, were included. Children were followed at 1 to 4 weeks, 1 to 4 months, and 4 to 9 months postdischarge. RESULTS In total, 45 children were admitted with MIS-C. The median time to last follow-up was 5.8 months (interquartile range 1.3–6.7). Of those admitted, 76% required intensive care and 64% required vasopressors and/or inotropes. On admission, patients exhibited significant nonspecific inflammation, generalized lymphopenia, and thrombocytopenia. Soluble interleukin (IL) IL-2R, IL-6, IL-10, IL-17, IL-18, and C-X-C Motif Chemokine Ligand 9 were elevated. A total of 80% (n = 36) had at least mild and 44% (n = 20) had moderate-severe echocardiographic abnormalities including coronary abnormalities (9% had a z score of 2–2.5; 7% had a z score > 2.5). Whereas most inflammatory markers normalized by 1 to 4 weeks, 32% (n = 11 of 34) exhibited persistent lymphocytosis, with increased double-negative T cells in 96% of assessed patients (n = 23 of 24). By 1 to 4 weeks, only 18% (n = 7 of 39) had mild echocardiographic findings; all had normal coronaries. At 1 to 4 months, the proportion of double-negative T cells remained elevated in 92% (median 9%). At 4 to 9 months, only 1 child had persistent mild dysfunction. One had mild mitral and/or tricuspid regurgitation. CONCLUSIONS Although the majority of children with MIS-C present critically ill, most inflammatory and cardiac manifestations in our cohort resolved rapidly.

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Background We sought to assess the impact and predictors of Coronavirus Disease 2019 (COVID‐19) infection and severity in a cohort of congenital heart disease (CHD) patients at a large CHD center in New York City. Methods and Results We performed a retrospective review of all individuals with CHD followed at Columbia University Irving Medical Center who were diagnosed with COVID‐19 between 3/1/2020 and 7/1/2020. The primary endpoint was moderate/severe response to COVID‐19 infection defined as a) death during COVID‐19 infection; or 2) need for hospitalization and/or respiratory support secondary to COVID‐19 infection. Among 53 COVID‐19 positive patients with CHD, 10 (19%) were <18 years old (median age 34 years). 31 (58%) had complex congenital anatomy including 10 (19%) with a Fontan repair. Eight (15%) had a genetic syndrome, six (11%) had pulmonary hypertension (PH), and nine (17%) were obese. Among adults, 18 (41%) were physiologic class C or D. For the entire cohort, nine (17%) had a moderate/severe infection, including three deaths (6%). After correcting for multiple comparisons, the presence of a genetic syndrome (OR=35.82: p=0.0002), and in adults, physiological Stage C or D (OR=19.38: p=0.002) were significantly associated with moderate/severe infection. Conclusions At our CHD center, the number of symptomatic COVID‐19 patients was relatively low. CHD patients with a genetic syndrome and adults at advanced physiological stage were at highest risk for moderate/severe infection.

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) has spread through the pediatric population during the coronavirus disease 2019 pandemic. Our objective for the study was to report the prevalence of conduction anomalies in MIS-C and identify predictive factors for the conduction abnormalities. METHODS: We performed a single-center retrospective cohort study of pediatric patients &lt;21 years of age presenting with MIS-C over a 1-month period. We collected clinical outcomes, laboratory findings, and diagnostic studies, including serial electrocardiograms, in all patients with MIS-C to identify those with first-degree atrioventricular block (AVB) during the acute phase and assess for predictive factors. RESULTS: Thirty-two patients met inclusion criteria. Median age at admission was 9 years. Six of 32 patients (19%) were found to have first-degree AVB, with a median longest PR interval of 225 milliseconds (interquartile range 200–302), compared with 140 milliseconds (interquartile range 80–178) in patients without first-degree AVB. The onset of AVB occurred at a median of 8 days after the initial symptoms and returned to normal 3 days thereafter. No patients developed advanced AVB, although 1 patient developed a PR interval &gt;300 milliseconds. Another patient developed new-onset right bundle branch block, which resolved during hospitalization. Cardiac enzymes, inflammatory markers, and cardiac function were not associated with AVB development. CONCLUSIONS: In our population, there is a 19% prevalence of first-degree AVB in patients with MIS-C. All patients with a prolonged PR interval recovered without progression to high-degree AVB. Patients admitted with MIS-C require close electrocardiogram monitoring during the acute phase.

SARS-CoV-2 infection for most children results in mild or minimal symptoms, though in rare cases severe disease can develop, including a multisystem inflammatory syndrome (MIS-C) with myocarditis. Here, we present longitudinal profiling of immune responses during acute disease and following recovery in children who developed MIS-C, relative to children who experienced more typical symptoms of COVID-19. T cells in acute MIS-C exhibited transient signatures of activation, inflammation, and tissue residency which correlated with cardiac disease severity, while T cells in acute COVID-19 upregulated markers of follicular helper T cells for promoting antibody production. The resultant memory immune response in recovery showed increased frequencies of virus-specific memory T cells with pro-inflammatory functions in children with prior MIS-C compared to COVID-19 while both cohorts generated comparable antibody responses. Together our results reveal distinct effector and memory T cell responses in pediatric SARS-CoV-2 infection delineated by clinical syndrome, and a potential role for tissue-derived T cells in the immune pathology of systemic disease.