Coronavirus disease 2019 (COVID-19) in children in most cases is asymptomatic or mild, and its most severe late complication is multisystem inflammatory syndrome in children (MIS-C). The aim of the study is to find clinical, laboratory and instrumental characteristics, description of therapeutic tactics, including determination of the profile of patients requiring Tocilizumab prescription and the outcomes of MIS-C associated with COVID-19. Materials and methods of research: 245 children aged 3 months – 17 years old were included in the pilot prospective multicenter open-label comparative study with MIS-C associated with COVID-19, verified based on CDC criteria (2020). Results: the median age of patients was 8 [5; 10] years, boys predominated among the patients (57.1%); MIS-C manifested itself as a combination of the symptom complex of Kawasaki disease (KD, 53.1% of patients), more often of atypical form, cardiovascular (66.1%), gastrointestinal (61.2%), neurological (27.3%) symptoms and signs of detection of the urinary (29.4%) and respiratory (19.6%) systems; macrophage activation syndrome (MAS) was diagnosed in 19.5% of patients. Therapy included glucocorticosteroids (97.6%), antibiotics (95.5%), anticoagulants (93.9%), intravenous immunoglobulin (34.7%), vasoactive/vasopressor support (31.8%), Tocilizumab (15.1%), mechanical ventilation (2.4%), extracorporeal membrane oxygenation (0.4%). Patients receiving Tocilizumab, statistically significantly more often compared with patients without this therapy, were in the intensive care unit (ICU, 86.5% versus 40.9%, p<0.001), more often required vasopressor therapy (70.3% versus 25%, p<0.001), had statistically significantly higher markers of laboratory inflammatory activity. Treatment in 47.8% of cases was carried out in an ICU; one child has died. In 4.1%, according to echocardiography, coronaritis, ectasia of the coronary arteries without the formation of persistent aneurysms were detected. Conclusion: MIS-C associated with COVID-19 has clinical signs of KD, often of the incomplete form, accompanied by arterial hypotension/shock, MAS, which requires intensive therapy, and the prescription of Tocilizumab.
The most severe manifestation of the new coronavirus infection COVID-19 in children is the multisystem inflammatory syndrome in children (MIS-C). A systematic review of foreign publications as of July 25, 2020 contains an analysis of the disease course in 662 children with this syndrome and is used for comparison with the data obtained. Objective of the research: to characterize clinical manifestation, results of laboratory and instrumental studies, therapy, outcomes and consequences of the COVID-19- associated MIS-C, based on the observation of patients hospitalized to Morozov Children's City Clinical Hospital and Children’s clinical hospital of infectious diseases № 6 from May 1 to September 15, 2020. Materials and methods: the pilot study included 32 children aged 9 months – 15 years with COVID-19-associated MIS-C, verified based on WHO criteria (2020), including symptoms of Kawasaki disease (KD), arterial hypotension/shock, laboratory and instrumental signs of heart damage, signs of coagulopathy, gastrointestinal symptoms, increased inflammation markers, COVID-19 markers. Results: the median age of patients was 6 years, boys predominated among the patients (66%), all patients had antibodies to SARS-CoV-2 (31 children of the IgG class); MIS-C manifested itself as a combination of KD symptom complex (75% of patients) with arterial hypotension/shock (28%), neurological (50%), respiratory (41%), gastrointestinal (59%) symptoms; macrophage activation syndrome (MAS) was verified in 16% of patients. Therapy included intravenous immunoglobulin (75%), systemic glucocorticosteroids (88%), anticoagulants (91%), vasoactive/vasopressor support (31%). In 38% of cases treatment was performed in intensive care unit; one child died. According to echocardiography, 16% of patients had coronariitis, ectasia, and coronary arteries aneurysms. Conclusion: COVID-19-associated MIS-C is characterized by a severe course, cross-features with KD, shock syndrome with KD, MAS which requires intensive therapy and can cause acquired pathology of the cardiovascular system in children.
Kawasaki disease (KD) is a multifactorial disease with a genetic predisposition, systemic vasculitis complicated by the formation of coronary artery aneurysms (CAA). Its pathogenesis is based on immune inflammation with an increase in the concentration of pro-inflammatory cytokines, the level of C-reactive protein (CRP), and coagulation disorder. Objective of the study: to search for polymorphisms of genes interleukin-6 (IL6), vascular endothelial growth factor A (VEGFA), cluster of differentiation CD14, CRP, fibrinogen beta chain (FGB), associated with the KD development and a predisposition to the CAA formation among patients with KD living in Moscow and the Moscow region. Materials and methods: genotyping for gene polymorphisms IL6 –174G>C (rs1800795), VEGFA –634 C>G (rs2010963), CD14 –159 C>T (rs2569190), CRP 3872 C>T (rs1205), FGB – 455 G>A (rs1800790) by PCR in 31 children 1 month – 10 years old (median age 19 months [9,0; 38,5]) with KD, among them, in 10 patients the disease was complicated by CAA formation according to echocardiography, and 30 children of the control group. Results: statistically significant differences (p<0,05) were revealed in the distribution of genotypes for polymorphisms of the CD14 –159 C>T, CRP 3872 C>T and FGB –455 G>A genes among patients with KD and children of the control group; when comparing the results of KD patients with CAA and the control group, statistically significant differences (p<0,05) were revealed only in the polymorphism CD14 –159 C>T. Conclusion: it can be assumed that these polymorphisms are associated with the development of KD and CAA in these patients.
For the first time in the domestic literature, the article presents a clinical observation of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 in the 6-year-old patient with manifestation of type 1 diabetes mellitus (T1DM) in the form of diabetic ketoacidosis. Anamnestic, clinical and laboratory data are presented on the basis of which two life-threatening diseases was diagnosed, as well as tactics of therapy, which made it possible to achieve a positive result. This clinical observation is compared with observations of foreign colleagues. Possible pathogenetic mechanisms of MIS-C and T1DM comorbidity are discussed.
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