Multisystem Inflammatory Syndrome in Children (MIS-C) associated with new coronavirus infection (COVID-19), with signs of Kawasaki disease (KD) and toxic shock syndrome, well-defined diagnostic criteria, is the most severe manifestation of COVID-19 in pediatric patients. MIS-C is analogous to the cytokine storm in children with COVID-19. The article presents a clinical observation of a child with MIS-C with a lethal outcome. Clinical and anamnestic data, the results of laboratory and instrumental research allowed to diagnose MIS-C in a 2-year-old girl with full KD form. Autopsy results, detailed microscopic examination, which revealed systemic vasculitis of small and mediumsized vessels, inflammatory infiltrates in different organs, are presented, clinical and morphological comparisons are made.

Experts of the Union of Pediatricians of Russia have developed modern guidelines on management of children with acute respiratory viral infection. The term “acute respiratory viral infection” (ARVI) combines following nosological forms: acute nasopharyngitis, acute pharyngitis, acute laryngitis, acute tracheitis, acute laryngopharyngitis, upper respiration tract infection (unspecified). The issues of epidemiology, diagnosis, treatment, and prevention have been considered in detail.

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Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 is a rare life-threatening immunopathological complication of COVID-19 that develops 1-6 weeks after the acute coronavirus infection. MIS-C is characterized by fever and multiorgan inflammation.We present a clinical case of a 10-year-old boy with skin lesions at the onset of MIS-C (erythematous malar rash, lacelike rash on the trunk and extremities and petechiae) with macrophage activation syndrome development and the early stage of primary Epstein-Barr virus infection (EBV infection) which required the exclusion of X-linked lymphoproliferative disease.This clinical case demonstrates the complexity of diagnosis in MIS-C with skin manifestations at the onset of the disease, especially with concurrent activation of other infections, particularly EBV infection.

Rationale. Children with rheumatic diseases receiving immunosuppressants and/or genetically engineered biopharmaceutical drugs (GEBDs) and/or glucocorticosteroids (GCs) are at high risk of developing severe and/or long-term symptoms of novel coronavirus infection. The possibilities of pre-exposure prophylaxis of COVID-19 in this patient population are significantly limited due to the risks of insufficient immunogenicity of the vaccine in the presence of secondary immunodeficiency developed under the conditions of immunosuppressive therapy and exacerbations/increasing activity of the underlying disease after vaccination. The use of a combination of two monoclonal antibodies against SARS-CoV-2 (tixagevimab/cilgavimab) may become a priority method for the pre-exposure prevention of COVID-19 in children with rheumatic diseases. Objective. To evaluate the efficacy and safety of using a combination of two monoclonal antibodies against SARS-CoV-2 (tixagevimab/cilgavimab) in the pre-exposure prophylaxis of novel coronavirus infection in immunocompromised pediatric patients with rheumatic diseases. Patients and methods. This study enrolled 234 patients aged 12 to 17 years and 11 months with body weight ≥40 kg and a confirmed diagnosis of rheumatic disease. Indications for the use of tixagevimab/cilgavimab for the pre-exposure prophylaxis of COVID-19, as stated in the medication information leaflet, included individuals not infected with SARS-CoV-2 and who had no contact with a person infected with SARS-CoV-2. An additional inclusion criterion was a moderate or severe decrease in immunity due to a pathological condition and/or the use of immunosuppressive medications in patients observed at the National Medical Research Center for Children’s Health and the Morozov Children’s City Clinical Hospital. The tixagevimab/cilgavimab medication was administered intramuscularly as two consecutive injections of each component at a dose of 300 mg (150 mg of each component) to 153 patients, 600 mg (300 mg of each component) to 81 patients. Endpoints used in this study were: • considering efficacy: the incidence rate of novel coronavirus infection in 3 and 6 months after pre-exposure prophylaxis with tixagevimab/cilgavimab in children with rheumatic diseases; • considering safety: exacerbation rates of the underlying disease after pre-exposure prophylaxis with tixagevimab/cilgavimab; the nature, frequency, severity, and outcomes of adverse events, including serious ones directly related to the drug administration. Results. This prospective observational cohort study involved 234 patients with rheumatic diseases, among them were 140 (60%) girls and 94 (40%) boys aged 12 to 17 years and 11 months (median (IQR): 14.79 (13.00, 16.17) years); 168 patients (71.79%) with various types of juvenile arthritis, 66 (28.21%) with systemic connective tissue disorders (SLE, dermatomyositis, systemic sclerosis, vasculitis), 171 (73.08%) with the underlying disease in remission and 63 (26.92%) with exacerbations. All patients received disease-modifying antirheumatic drugs (DMARDs) (methotrexate/mycophenolate, mofetil/cyclophosphamide/sulfasalazine) and/or biological DMARDs (inhibitors of TNF-α/CD20+B-lymphocytes/IL-1, IL-6/IL-17 receptor/T-cell co-stimulation), or targeted synthetic DMARDs (tofacitinib/upadacitinib); 71 (30.34%) patients received oral GCs; 160 (68.37%) patients received 2 to 4 antirheumatic drugs. Before inclusion in the study, 140 (59.83%) children had COVID-19. Within 3 months of preexposure prophylaxis, 2 cases of COVID-19 were reported (0.85%). No exacerbations/increasing activity of the rheumatic disease were recorded in patients immunized in the remission/exacerbation stage with tixagevimab/cilgavimab at doses of 300 mg and 600 mg, respectively. No adverse events directly related to the drug administration were observed. Conclusion. Preliminary results of a prospective observational cohort study indicate a high efficacy and a favorable safety profile of a combination of two monoclonal antibodies against SARS-CoV-2 (tixagevimab/cilgavimab) in the pre-exposure prevention of novel coronavirus infection in immunocompromised pediatric patients with rheumatic diseases. Key words: COVID-19, SARS-CoV-2, monoclonal antibodies, pre-exposure prophylaxis, tixagevimab, cilgavimab, rheumatic diseases, children