• Clinical and Experimental Pediatrics
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• v.64 no.2
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• pp.68-75
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• 2021

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading worldwide since December 2019. Hundreds of cases of children and adolescents with Kawasaki disease (KD)-like hyperinflammatory illness have been reported in Europe and the United States during the peak of the COVID-19 pandemic with or without shock and cardiac dysfunction. These patients tested positive for the polymerase chain reaction or antibody test for SARS-CoV-2 or had a history of recent exposure to COVID-19. Clinicians managing such patients coined new terms for this new illness, such as COVID-19-associated hyperinflammatory response syndrome, pediatric inflammatory multisystem syndrome temporally associated with COVID-19, or COVID-19-associated multisystem inflammatory syndrome in children (MIS-C). The pathogenesis of MIS-C is unclear; however, it appears similar to that of cytokine storm syndrome. MIS-C shows clinical features similar to KD, but differences between them exist with respect to age, sex, and racial distributions and proportions of patients with shock or cardiac dysfunction. Recommended treatments for MIS-C include intravenous immunoglobulin, corticosteroids, and inotropic or vasopressor support. For refractory patients, monoclonal antibody to interleukin-6 receptor (tocilizumab), interleukin-1 receptor antagonist (anakinra), or monoclonal antibody to tumor necrosis factor (infliximab) may be recommended. Patients with coronary aneurysms require aspirin or anticoagulant therapy. The prognosis of MIS-C seemed favorable without sequelae in most patients despite a reported mortality rate of approximately 1.5%.

• Clinical and Experimental Pediatrics
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• v.64 no.10
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• pp.531-537
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• 2021

Background: Multisystem inflammatory syndrome in children (MIS-C) is a new hyperinflammatory variant that evolved during the coronavirus disease 2019 pandemic. Although the precise pathophysiology of MIS-C is uncertain, it is thought to be due to immune dysregulation occurring after recovery from acute infection. Purpose: Our study aimed to analyze the clinical spectrum, laboratory parameters, imaging characteristics, treatment strategies, and short-term outcomes of children with a diagnosis of MIS-C. Methods: This retrospective and prospective observational study included children less than 16 years of age who were admitted to the pediatric unit of a tertiary care teaching hospital in south India between August 2020 to January 2021 with a diagnosis of MIS-C according to World Health Organization criteria. Results: Twenty-one children were included in the analysis; all had fever with variable combinations of other symptoms. The mean age was 6.9 years; 71.4% were male. Gastrointestinal (80.9%) and cardiovascular (80.9%) systems were the most commonly affected. The majority of children had elevated inflammatory markers, and 16 (76.2%) had echocardiographic abnormalities mimicking Kawasaki disease. Eleven children (52.4%) required intensive care admission, 3 (14.3%) required supplemental oxygen, and 4 (19%) required inotropes. Nine (42.9%) were treated with intravenous immunoglobulin alone, 6 (28.6%) with steroids alone, and 3 (14.3%) with steroids and immunoglobulin. The median hospital stay was 6 days; there were no fatalities. Overweight/obesity, elevated ferritin, and mucocutaneous involvement were significantly associated with a prolonged hospital stay (≥7 days). Sixteen children (76.2%) were followed up till now and all of them had no clinical concerns. Conclusion: MIS-C is an emerging disease with variable presentation. A high index of suspicion is necessary for its early identification and appropriate management. Further research is essential for developing optimal treatment strategies.

• Clinical and Experimental Pediatrics
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• v.64 no.5
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• pp.225-226
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• 2021

• Clinical and Experimental Pediatrics
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• v.64 no.11
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• pp.599-601
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• 2021

• Pediatric Infection and Vaccine
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• v.28 no.2
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• pp.66-81
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• 2021

The coronavirus disease 2019 pandemic has been continuously spreading throughout the world. As of July 15, 2021, there have been more than 188 million confirmed cases and more than 4.06 million deaths. Although the incidence of severe infections is relatively low in children and adolescents compared to adults, a complication called multisystem inflammatory syndrome in children (MIS-C) may occur in some cases at approximately 2-6 weeks after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. MIS-C can be seen in patients of various ages, from young infants to adolescents, and may present with diverse clinical manifestations. While fever present in a great majority of patients, symptoms suggesting the involvement of the digestive or nervous system and the skin and mucous membranes (Kawasaki disease-like symptoms) also appear in many cases. Cardiac involvement may also be observed, including left ventricular dysfunction, myocarditis, coronary artery dilatation, and coronary aneurysm. In some cases, hypotension or shock can occur, and mechanical ventilation or treatment in the intensive care unit may be necessary. Fortunately, recovery is generally reported after appropriate treatment. MIS-C is a rare but important complication of SARS-CoV-2 infection in children and adolescents. As such, it is important to recognize the clinical symptoms and provide appropriate treatment at an early stage. In this review, the epidemiology, clinical symptoms, suggested pathophysiology, diagnostic approach, and treatment of MIS-C will be discussed.

• Clinical and Experimental Pediatrics
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• v.65 no.4
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• pp.153-166
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• 2022

During the coronavirus disease 2019 (COVID-19) pandemic, a novel multisystem inflammatory syndrome in children (MIS-C) has been reported worldwide since the first cases were reported in Europe in April 2020. MIS-C is temporally associated with severe acute respiratory syndrome coronavirus 2 infection and shows Kawasaki disease (KD)-like features. The epidemiological and clinical characteristics in COVID-19, KD, and MIS-C differ, but severe cases of each disease share similar clinical and laboratory findings such as a protracted clinical course, multiorgan involvement, and similar activated biomarkers. These findings suggest that a common control system of the host may act against severe disease insult. To solve the enigmas, we proposed the protein-homeostasis-system hypothesis in that every disease involves etiological substances and the host's immune system controls them by their size and biochemical properties. Also, it is proposed that the etiological agents of KD and MIS-C might be certain strains in the microbiota of human species and etiological substances in severe COVID-19, KD, and MIS-C originate from pathogen-infected cells. Since disease severity depends on the amounts of inflammation-inducing substances and corresponding immune activation in the early stage of the disease, an early proper dose of corticosteroids and/or intravenous immunoglobulin (IVIG) may help reduce morbidity and possibly mortality among patients with these diseases. Corticosteroids are low cost and an analogue of host-origin cortisol among immune modulators. This study's findings will help clinicians treating severe COVID-19, KD, and MIS-C, especially in developing countries, where IVIG and biologics supplies are insufficient.

• Pediatric Infection and Vaccine
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• v.28 no.3
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• pp.173-180
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• 2021

After initial reports of multisystem inflammatory syndrome in children (MIS-C) in April 2020 in Europe, this disease has been known to occur in children with recent history of coronavirus disease 2019 (COVID-19) and most cases have been reported in Europe and the Unites States of America. We report a case of a 14-year-old girl who was diagnosed with MIS-C with acute myocarditis and successfully treated with intravenous immunoglobulin (IVIG), methylprednisolone, and anakinra. At initial presentation, she had persistent high fever, generalized rash, generalized swelling, abdominal pain, and low blood pressure. She showed a remarkably elevated level of inflammation and cardiac enzyme markers and had a previous history of COVID-19 5 weeks before the initial presentation. After extensive work up, other infectious and non-infectious causes were excluded. She was diagnosed with MIS-C and initially treated with IVIG and high-dose methylprednisolone; however, despite treatment, her heart function deteriorated and coronary artery dilatation progressed. Therefore, anakinra, an interleukin-1 receptor antagonist, was administered on hospital day 6, after which her cardiac function exhibited improvement. She was discharged on hospital day 19 without any symptoms, and follow-up echocardiography after 1 month revealed fully recovered heart function with normal coronary arteries.

• Pediatric Infection and Vaccine
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• v.31 no.1
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• pp.140-146
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• 2024

Multisystem inflammatory syndrome in children (MIS-C) is a rare complication of coronavirus disease 2019 (COVID-19), causing multi-organ damage affecting the heart, lungs, kidneys, digestive tract, and nervous system. As the cases of MIS-C have been increasing following the COVID-19 pandemic, the importance of appropriate management for MIS-C is becoming increasingly apparent. Immunomodulating agents such as anakinra, infliximab, and steroids are regarded as supplementary therapy to the first-line treatment with intravenous immunoglobulin. However, these immunomodulating therapies can potentially precipitate opportunistic infections, including those caused by cytomegalovirus (CMV), Epstein-Barr virus, and tuberculosis, or increase the risk of co-infections. Herein, we report a case of a 3-year-old boy who was treated with immunoglobulin, infliximab, and high-dose methylprednisolone for MIS-C, and subsequently developed a persistent fever lasting 32 days caused by a CMV infection.

• Pediatric Infection and Vaccine
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• v.29 no.3
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• pp.155-160
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• 2022

Children and adolescents with coronavirus disease 2019 (COVID-19) generally have mild symptoms. Severe infection due to severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) involving multiorgan dysfunction is rare in this population. Herein, we present an unusual case of severe SARS-CoV-2 infection with multiorgan involvement followed by multisystem inflammatory syndrome in children (MIS-C) in a vaccinated 16-year-old boy. The patient was unconscious on initial presentation, and had severe paralytic ileus. On laboratory examination, there was severe metabolic acidosis, lymphocytopenia, thrombocytopenia, elevated inflammatory markers, elevated liver enzymes, and evidence of acute kidney injury with proteinuria and hematuria. His symptoms improved with the administration of remdesivir and dexamethasone. The patient briefly experienced MIS-C 2 weeks after the diagnosis of COVID-19, but the patient was discharged without any complications.