Multisystem Inflammatory Syndrome in Children Associated With Covid-19: Results of a Multicenter Study

Abstract

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.

Severe Course of COVID-19 and Long-COVID-19 in Children: Difficulties in Diagnosis

“…Russian scientists have noted that in boys, the course of MIS-C was also the most severe in 57% of cases. The syndrome was diagnosed in 64% of children of the Eastern European population, but there was no correlation with the severity of MIS-C [ 21 ]. The conducted studies showed the significance of an increase in ESR in 69%, procalcitonin in 69%, ferritin in 77%, and CRP in 98% [ 18 ].…”

“…It described results where 245 children with MIS-C were treated. Their age ranged from 3 months to 17 years [ 21 ]. It was shown that patients had damage to the cardiovascular system (66%), as well as gastrointestinal disorders (61%), every fourth patient had neurological disorders (27%) and signs of respiratory failure (19%).…”

Rationale for use for monoclonal antibody therapy in multisystem inflammatory syndrome in children: a systematic review

“…The choice of monoclonal antibody therapy may be related to the severity of presentation, but this is generally unclear from the papers reviewed 29 . In a study by Novikova et al, they found that children receiving monoclonal antibodies experienced a severe course of disease compared to patients who were not administered monoclonal antibodies 22 . The choice of population in which monoclonal antibodies are used may therefore skew our understanding of the e cacy and outcome of their use.…”

“…Rationale for monoclonal antibody therapy was MIS-C refractory to the initial therapy of IVIG and steroids [14][15][16][17][18][20][21][22][23][24][25][26][27][29][30][31] . Very rarely were monoclonal antibodies utilized as rst line therapy.…”

“…Very rarely were monoclonal antibodies utilized as rst line therapy. Those given monoclonal antibodies received them in ICU (86.5% vs. 41%, p<0.001) or with vasoactive therapy (70.3% vs. 25%, p<0.001) 22 . In two studies, initial biologics utilized were changed to a second monoclonal antibody 14,31 .…”