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Background: Macrophage activation syndrome (MAS) can be regarded as a key factor determining the severity of multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C), and often requires treatment in the intensive care unit (ICU) to avoid life-threatening complications. No reputable specific criteria for the diagnosis of MAS in MIS-C patients have yet been identified, and criteria currently used for the diagnosis of hemophagocytic syndromes, such as HLH-2004, MAS-2005, and MAS-2016, are not sufficient for MAS in MIS-C. Our goal in this study was to work out the criteria for the early diagnosis of MAS in MIS-C. Methods: One hundred and sixty-six (166) patients with MIS-C were assessed retrospectively. The two most experienced experts independently identified patients with MAS. The patients were divided into three cohorts: MAS ( n = 19), without MAS ( n = 78), and probable MAS ( n = 67). The latter included patients diagnosed with MAS by only one expert, and it was excluded from the analysis. Results: The age of patients with MAS was much higher, and they more frequently had edematous syndrome, hypotension and/or shock, splenomegaly, and CNS involvement. In their blood tests, thrombocytopenia, hypoalbuminemia, and hypertriglyceridemia occurred more often. The level of biomarkers of inflammation, such as ferritin, CRP, troponin, AST, and ALT, was also higher in this group. Increased fibrinogen and D-dimer were also found, demonstrating hypercoagulation in the MAS-MIS-C group. We chose 21 continuous and categorical variables with statistical significance, out of which 2-ferritin > 469 μg/L or platelets < 114 × 10 9 /L-allowed us to discriminate MAS patients. Conclusions: Ferritin > 469 μg/L or platelets < 114 × 10 9 /L can be regarded as key signs to differentiate MAS in MIS-C patients with a sensitivity of 100% and specificity of 94.9%, and they can be used along with other diagnostic methods.

Hemophagocytic syndrome is a key point in the pathogenesis of severe forms of multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C). The factors associated with hemophagocytosis in patients with MIS-C were assessed in the present study of 94 boys and 64 girls ranging in age from 4 months to 17 years, each of whose HScore was calculated. In accordance with a previous analysis, patients with HScore ≤ 91 ( n = 79) and HScore > 91 ( n = 79) were compared. Patients with HScore > 91 had a higher frequency of symptoms such as cervical lymphadenopathy, dry cracked lips, bright mucous, erythema/swelling of hands and feet, peeling of fingers, edematous syndrome, hepatomegaly, splenomegaly, and hypotension/shock. They also had a higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and D-dimer levels, and a tendency to anemia, thrombocytopenia, and hypofibrinogenemia. They more often needed acetylsalicylic acid and biological treatment and were admitted to ICU in 70.9% of cases. Conclusion: The following signs of severe MIS-C were associated with HScore > 91: myocardial involvement, pericarditis, hypotension/shock, and ICU admission.

Background: The causative agent of the new coronavirus infection SARS-CoV-2 has unique properties causing hyperinflammatory syndrome and cytokine storm, as well as widespread endotheliitis and thrombotic microangiopathy, initially detected in the lungs of adult patients who died from a severe form of the disease. Venous and arterial thrombosis in adults were identified as common causes of severe complications and deaths in new coronavirus infections. There are very few reports of thrombotic events in children with COVID-19 in the literature. Methods: We conducted a retrospective analysis of the histories of 60 patients in the Irkutsk Regional Children's Clinical Hospital from November 2020 to November 2022 with a MIS-C diagnosis established according to WHO criteria, of which 8 (13.3%) were diagnosed with venous and/or arterial thrombosis, confirmed by laboratory and ultrasound and/or X-ray methods. Results: The average age of children with thrombosis (Me) was 7.5 years (min 4 months, max 17 years), with a M:F ratio of 3.0. Venous thrombosis was detected in six of the eight patients, including in the deep veins of the lower extremities in four. Pulmonary embolism occurred in two (one of them was fatal), and cerebral venous sinus thrombosis and thrombosis of the branches of the upper and lower vena cava were found in one patient. Extensive bilateral stroke due to thrombosis of the large cerebral arteries occurred in two patients, including one in combination with distal gangrene. Secondary thrombotic renal microangiopathy took place in three of the eight patients. Among these three, atypical HUS was diagnosed in one case. Multiple thrombosis involving the venous and arterial bed was detected in four of the eight patients. High levels of D-dimer, thrombocytopenia, increased NT-proBNP, cerebral coma, and aseptic meningitis were the events most often associated with thrombosis. All patients received immunomodulatory therapy (immunoglobulin, dexamethasone/methylprednisolone), pathogenetic therapy for multiorgan failure, anticoagulant therapy with heparin/LMWH, and acetylsalicylic acid. Biologics were used in two patients. Conclusions: The main predictors of thrombosis in children with MIS-C were increased D-dimer, thrombocytopenia, hospitalization in the ICU, and noncardiogenic pulmonary edema. Thrombosis of the deep veins of the lower extremities, large cerebral arteries, and secondary thrombotic microangiopathy was common. There was a single death (12.5% of the eight patients), associated with PE.