Longitudinal Outcomes for Multisystem Inflammatory Syndrome in Children

Abstract

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.

In‐depth cardiovascular and pulmonary assessments in children with multisystem inflammatory syndrome after SARS‐CoV‐2 infection: A case series study

“…All patients showed signs suggesting normal coronary arteries (all score‐ z ≥2.5) (Farooqi et al, 2021) by standard echocardiogram at post‐discharge, except for one patient (P4).…”

“…Standard transthoracic echocardiography was performed according to the recommendations of the American Society of Echocardiography (Farooqi et al, 2021). Cardiac chamber dimensions were obtained using two‐dimensional mode and left ventricle ejection fraction (LVEF) was calculated by Simpson's method (normal LV EF ≥55%) (Farooqi et al, 2021). The z ‐score values of cardiac chambers were calculated according to Lopez et al (normal values between 2 and < +2.5).…”

Who Would Have Predicted Multisystem Inflammatory Syndrome in Children?

“…Systemic inflammation has been shown to rapidly improve with appropriate treatment, including two studies of 46 and 45 MIS-C patients showing normalization of C-reactive protein, platelet count, liver enzyme levels, albumin levels, and d-dimer levels in the vast majority by 4-6 months, and in some by as early as 6 weeks [65,66]. Cardiac function abnormalities have been shown to improve in a similar manner.…”

“…Coronary artery dilatation (z > 2) has been reported in 9-24.1% of MIS-C cases [11, 12, 13•, 14]. However, in multiple follow-up studies, coronary changes have been shown to resolve with appropriate treatment-one study reported 7 out of 45 (15.6%) patients with coronary changes on admission, all resolved within 1-4 weeks [66], and another study demonstrated coronary changes in 12 out of 50 (24%) patients that resolved by 8 weeks…”

In-depth cardiovascular and pulmonary assessments in children with multisystem inflammatory syndrome after SARS-CoV-2 infection: a case series study

“…Multisystem in ammatory syndrome in children (MIS-C) is a hyperin ammatory response that commonly develops within 2-6 weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, requiring hospitalization in the acute phase (8). While multiple cohorts have shown that MIS-C patients may present with heterogenous signs that include hemodynamic instability, tachycardia, left ventricular dysfunction, and respiratory distress, possibly primary or caused by cardiac dysfunction, (7,13) the pathophysiology of MIS-C and its natural course are yet to be fully elucidated.…”