Multisystem Inflammatory Syndrome Following SARS-CoV-2 Infection in Children: One Year after the Onset of the Pandemic in a High-Incidence Area

Abstract

SARS-CoV-2 infection in children can trigger cardiovascular manifestations potentially requiring an intensive treatment and defining a new entity named Multisystem Inflammatory Syndrome in Children (MIS-C), whose features partially overlap with Kawasaki Disease (KD). A cross-sectional study including all diagnoses of MIS-C and KD from April 2020 to May 2021 in our metropolitan area was conducted evaluating clinical, laboratory (including immunological response, cytokines, and markers of myocardial damage), and cardiac (coronary and non-coronary) features at onset of the diseases. Evolution of ventricular dysfunction, valve regurgitations, and coronary lesions was documented. The severity of the disease was also considered based on the need for inotropic support and ICU admission. Twenty-four MIS-C were diagnosed (14 boys, median age 82 months): 13/24 cases (54.17%) presented left ventricular dysfunction, 12/24 (50%) required inotropic support, and 10/24 (41.67%) developed coronary anomalies (CALs). All patients received steroids and IVIG at a median time of 5 days (IQR1:4, IQR3:6.5) from onset of fever and heart function normalized 6 days (IQR1: 5, IQR3: 7) after therapy, while CALs persisted in one. One patient (12.5%) required infliximab because of refractory disease and still presented CALs 18 days after therapy. During the same study period, 15 KD were diagnosed: none had ventricular dysfunction, while 7/15 (46.67%) developed CALs. Three out of 15 patients (20%) still presented CALs 46 days from onset. Compared to KD, MIS-C pts have significantly higher IL8 and similar lymphocytes subpopulations. Despite a more severe presentation and initial cardiac findings compared to KD, the myocardial injury in MIS-C has a rapid response to immunomodulatory treatment (median time 6 days), in terms of ventricular function, valve regurgitations, and troponin. Incidence of CALs is similar at onset, but it tends to regress in most of the cases of MIS-C differently than in KD where CALs persist in up to 40% in the subacute stage after treatment.

The Effect of Vitamin D Levels in Multisystem Inflammatory Syndrome in Children

“…Additionally, patients have elevated inflammatory markers (CRP, procalcitonin, sedimentation, D-dimer, and ferritin) 1 17 22 23 and NT-proBNP. 1 10 16 Moreover, higher CRP, D-dimer, NT-proBNP, and lower lymphocyte count were detected in patients in the ICU. 24 In pediatric MIS-C case series, higher CRP and neutrophil counts as well as lower lymphocyte counts and albumin levels, were associated with children who developed shock.…”

“…The Kawasaki disease is a childhood inflammatory disease and resembles MIS-C. 16 In studies conducted in children diagnosed with the Kawasaki syndrome, it was found that the patients with vitamin D levels of < 20 ng/mL were more resistant to IVIG treatment ( p = 0.023). 15 In the present study, most of our patients responded well to a single dose of the IVIG therapy (first-line treatment).…”

“…15 Considering the information available in relevant literature, it is understood that vitamin D deficiency may cause many negative effects on Kawasaki disease. However, we know that the clinical features of Kawasaki disease resemble those of MIS-C. 1,9,16 Previous studies on this subject are limited. Therefore, it is a good question whether vitamin D deficiency will cause the same effects in the case of MIS-C as in the case of Kawasaki disease.…”

Global Myocardial Strain in Multisystem Inflammatory Syndrome in Children, Kawasaki Disease, and Healthy Children: A Network Meta-Analysis

“…Several studies focused on the recovery of MIS-C with follow-up for short-term ( 38 , 39 ), mid-term ( 19 , 40 , 41 ), and 1-year using conventional echocardiography ( 42 ). In total, 91.0% of patients with MIS-C had a normal LVEF by 30 days ( 19 ).…”

Overview of infections as an etiologic factor and complication in patients with vasculitides

“…This syndrome can also be found in adult patients (MIS-A), usually four months after the acute phase of COVID-19, presenting with multiorgan dysfunction frequently requiring intensive care unit admission, while a minority of patients may present with Kawasaki disease [59]. It should be stressed, however, that prompt immunomodulatory treatment may lead to the regression of myocardial injury and the reversibility of left ventricular dysfunction [60].…”