Distinct clinical and immunological features of SARS–CoV-2–induced multisystem inflammatory syndrome in children

Abstract

BACKGROUND. Pediatric SARS-CoV-2 infection can be complicated by a dangerous hyperinflammatory condition termed multisystem inflammatory syndrome in children (MIS-C). The clinical and immunologic spectrum of MIS-C and its relationship to other inflammatory conditions of childhood have not been studied in detail. METHODS.We retrospectively studied confirmed cases of MIS-C at our institution from March to June 2020. The clinical characteristics, laboratory studies, and treatment response were collected. Data were compared with historic cohorts of Kawasaki disease (KD) and macrophage activation syndrome (MAS). RESULTS.Twenty-eight patients fulfilled the case definition of MIS-C. Median age at presentation was 9 years (range: 1 month to 17 years); 50% of patients had preexisting conditions. All patients had laboratory confirmation of SARS-CoV-2 infection. Seventeen patients (61%) required intensive care, including 7 patients (25%) who required inotrope support. Seven patients (25%) met criteria for complete or incomplete KD, and coronary abnormalities were found in 6 cases. Lymphopenia, thrombocytopenia, and elevation in inflammatory markers, D-dimer, B-type natriuretic peptide, IL-6, and IL-10 levels were common but not ubiquitous. Cytopenias distinguished MIS-C from KD and the degree of hyperferritinemia and pattern of cytokine production differed between MIS-C and MAS. Immunomodulatory therapy given to patients with MIS-C included intravenous immune globulin (IVIG) (71%), corticosteroids (61%), and anakinra (18%). Clinical and laboratory improvement were observed in all cases, including 6 cases that did not require immunomodulatory therapy. No mortality was recorded in this cohort. CONCLUSION. MIS-C encompasses a broad phenotypic spectrum with clinical and laboratory features distinct from KD and MAS.

Deep Immune Profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19

“…Patients with MIS-C were treated with intravenous immunoglobulin (IVIg) and most were treated with steroids (Supplementary Table 1). Consistent with previous reports [34][35][36]43 , the maximum values for clinical measures of inflammation (including LDH, ferritin, CRP, etc) varied but were elevated in most subjects (Fig 1B). Although inflammatory markers in COVID-19 and MIS-C were comparable, measures of inflammation were more often obtained for patients admitted to the intensive care unit (ICU) and for patients with MIS-C; as a result, patients with less severe COVID-19 and possibly lower inflammation are underrepresented (Supplementary Table 1).…”

Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management

“…Feldstein et al have shown that 80% patients required intensive care, 20% required mechanical ventilation and 4% received extracorporeal membrane oxygenation (ECMO) [11]. Due to the ongoing hyper-inflammatory state, chances of development of macrophage activation syndrome (MAS) are high in these patients [8,45].…”

Hematological manifestations of SARS‐CoV‐2 in children

“…The original studies 5,39,[56][57][58][59][60][61][62][63][64] on the laboratory findings on children with MIS during the COVID-19 pandemic are shown in Table 2.…”