Algorithm for the diagnosis and management of the multisystem inflammatory syndrome in children associated with COVID-19.

OBJECTIVE: Although the initial reports of COVID-19 cases in children described that children were largely protected from severe manifestations, clusters of paediatric cases of severe systemic hyperinflammation and shock related to severe acute respiratory syndrome coronavirus 2 infection began to be reported in the latter half of April 2020. A novel syndrome called "multisystem inflammatory syndrome in children" (MIS-C) shares common clinical features with other well-defined syndromes, including Kawasaki disease, toxic shock syndrome and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Our objective was to develop a protocol for the evaluation, treatment and follow-up of patients with MIS-C. METHODS: The protocol was developed by a multidisciplinary team. We convened a multidisciplinary working group with representation from the departments of paediatric critical care, cardiology, rheumatology, surgery, gastroenterology, haematology, immunology, infectious disease and neurology. Our protocol and recommendations were based on the literature and our experiences with multisystem inflammatory syndrome in children. After an agreement was reached and the protocol was implemented, revisions were made on the basis of expert feedback. CONCLUSION: Children may experience acute cardiac decompensation or other organ system failure due to this severe inflammatory condition. Therefore, patients with severe symptoms of MIS-C should be managed in a paediatric intensive care setting, as rapid clinical deterioration may occur. Therapeutic approaches for MIS-C should be tailored depending on the patients' phenotypes. Plasmapheresis may be useful as a standard treatment to control hypercytokinemia in cases of MIS-C with severe symptoms. Long-term follow-up of patients with cardiac involvement is required to identify any sequelae of MIS-C.

Role of Biological Agents in the Treatment of SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children.

OBJECTIVES: The aims of this study were to evaluate the role of biological agents in the treatment of severe multisystem inflammatory syndrome in children (MIS-C) and to assess the current application, outcomes, and adverse effects in patients who are followed up in a pediatric intensive care unit (PICU). PATIENTS AND METHODS: This observational, descriptive, medical records review study was performed on patients with MIS-C admitted to the PICU between September 1 and November 1, 2020. Through medical records review, we confirmed that patients were positive for current or recent SARS-CoV-2 infection or for COVID-19 exposure history within the 4 weeks before the onset of symptoms. RESULTS: A total of 33 patients with severe MIS-C were included (21 male) with a median age of 9 years. The most common signs and symptoms during disease course were fever (100%) and abdominal pain (75.5%). Clinical features of 63.6% patients were consistent with Kawasaki disease/Kawasaki disease shock syndrome, and 36.4% were consistent with secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Myocardial dysfunction and/or coronary artery abnormalities were detected in 18 patients during the PICU stay. Intravenous immunoglobulin and corticosteroids were given to 33 patients. Anakinra was administered to 23 patients (69.6%). There was a significant increase in lymphocyte and platelet counts and a significant decrease in ferritin, B-type natriuretic peptide, and troponin levels at the end of the first week of treatment in patients who were given biological therapy. Two patients were switched to tocilizumab because of an insufficient response to anakinra. The mortality rate of MIS-C patients admitted in PICU was 6.0%. CONCLUSIONS: Management of systemic inflammation and shock is important to decrease mortality and the development of persistent cardiac dysfunction in MIS-C. The aggressive treatment approach, including biological agents, may be required in patients with severe symptoms and cardiac dysfunction.

Therapeutic plasma exchange: A potential management strategy for critically ill MIS-C patients in the pediatric intensive care unit.

This study aimed to evaluate the effectiveness and the role of therapeutic plasma exchange (TPE) in treatment of children with severe MIS-C. In addition, we assessed demographic data, clinical features, laboratory abnormalities, underlying conditions, treatments, and outcomes. Patients with severe MIS-C who were admitted to the pediatric intensive care unit (PICU) between September 01 and October 05, 2020 were included in this observational, descriptive, retrospective study. The data collected included the patients' demographic data, presenting symptoms, clinical features, laboratory parameters, diagnostic investigations, and medications. Of 27 children with MIS-C, 63 % were male. The median age of the patients was nine years. Intravenous immunoglobulin and corticosteroids were used for treatment in 100 % of the patients, anakinra in 51.8 %, vasopressors in 85.1 %, noninvasive mechanical ventilation in 25.9 %, and invasive mechanical ventilation in 18.5 %. Ten of the 27 patients (37 %) underwent TPE. In the patients who underwent TPE, the median PELOD score was 21 (IQR: 11-30.25) before TPE and 10 (IQR: 10-11) after TPE (p < 0.001). Moreover, their median left ventricular ejection fraction (LVEF) was 52 % (IQR: 49.25 %-55 %) before TPE and median LVEF was 66.5 (IQR: 58 %-68.5 %) after TPE (p = 0.012). The median number of TPE sessions was three (IQR: 2-4.75). The mortality rate of the patients with severe MIS-C admitted to the PICU was 7.4 %. We suggest that TPE should be considered as a therapeutic option in children with severe MIS-C. Early initiation of TPE followed by immunomodulatory therapy in critically ill children with MIS-C may help improve clinical and laboratory outcomes.