Challenges in diagnostic research of multisystem inflammatory syndrome in children associated with COVID-19 in combination with the early stage of Epstein-Barr virus infection

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.

[Differential diagnosis of parapharyngeal abscess with multisystem inflammatory syndrome in children associated with COVID-19]. / O differentsial'noi diagnostike parafaringeal'nogo abstsessa s detskim mul'tisistemnym vospalitel'nym sindromom, assotsiirovannym s novoi koronavirusnoi infektsiei (COVID-19).

The pandemic of the new coronavirus infection (COVID-19) has identified new diagnostic and medical tasks before different doctors. As observations show, children have the flow of infection easier than adults. However, in some cases, COVID-19 in children proceeds extremely difficult, with fever and multisystem inflammation, possibly requiring treatment in the resuscitation department. In domestic practice, the term "Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19" is used to indicate the disease. Among the local symptoms of MIS are inflammations of the skin and mucous membranes, as well as various lymphadenopathy. The article presents the results of our clinic's observation of 205 patients with MIS for the period from May 2020 to May 2021. In some patients, the clinical manifestations of MIS-C required differential diagnosis with parapharyngeal abscesses (PPA). For this purpose, the children were consulted by an otorhinolaryngologist and a CT scan of the neck with contrast enhancement was performed. Despite the striking clinical manifestations similar to PPA, in no case was a pharyngeal abscess revealed. Both of these diseases are potentially fatal if treatment is not started on time, and therefore we believe that the awareness of otorhinolaryngologists about the manifestations of MIS-C will be useful in modern clinical practice.

Multisystem inflammatory syndrome in children (MIS-C) temporarily associated with the new coronavirus infection COVID-2019 and its short-and long-term consequence

Background: Children develop severe COVID-19 much less often than adults. However, a small proportion of children present with a complication, known as a multisystem inflammatory syndrome (MIS-C) sometimes associated with admission to an intensive care unit or death. Clinical presentation and consequences of MIS-C are still unclear. The aim of our study is to assess the features of MIS-C and its consequences on a child's health. Method: An observational longitudinal study of children and adolescents hospitalised from May 17 to October 26, 2020, with MIS-C to Morozovskaya Children's City Clinical Hospital, Moscow Department of Health Care, Moscow, Russia. Results: 37 children with MIS-C (meeting WHO, CDC, or RCPCH criteria) were hospitalised. The median age was 6 years (interquartile range 3.3-9.9 years), and 22 patients (59.5%) were male. The most common symptoms on admission were fever (97.3%), fatigue (86.5%), scleritis (85%), oral mucosal inflammation (83.8%), rash (70.3%), tachycardia (51.4%), nausea (51.4%), bilateral conjunctivitis (43.2%), cervical lymphadenopathy (43.2%). The most common laboratory abnormalities detected during hospitalization were elevated CRP (100%), ferritin (100%), D-dimer (89.19%), CRP (86.49%), platelets (85.49%), hypoalbuminemia (100%) and anemia (95.59%). EchoCG abnormalities were present in 6 (16.2%) children with evidence of myocardial dysfunction, 5 (13.5%)-pericarditis, and 3 (8.1%) with a coronary anomaly. The median time from discharge to the first follow-up was 15 days (interquartile range, 14-18 days) to the second follow-up was 47 days (interquartile range, 41-52 days). At the first follow-up, 7/33 (21.21%) children had at least 1 symptom, of whom 5 (15.15%) reported fatigue. At the second follow-up, only 1 child reported a symptom (rash). The normalisation of laboratory values and EchoCG findings was noted in all the children. Conclusion: In spite of the MIS-C severity, the tendency to fast regression of symptoms and laboratory and instrumental indexes is traced, which suggests recovery of children and adolescents from MIS-C without long-term consequences. Further long-term follow-up of patients with MIS-C is necessary since data on long-term health outcomes are limited.

Multisystem inflammatory syndrome in children associated with COVID-19 in the 6-year-old patient with manifestation of type 1 diabetes mellitus with diabetic ketoacidosis

For the first time in the domestic literature, the article presents a clinical observation of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 in the 6-year-old patient with manifestation of type 1 diabetes mellitus (T1DM) in the form of diabetic ketoacidosis. Anamnestic, clinical and laboratory data are presented on the basis of which two life-threatening diseases was diagnosed, as well as tactics of therapy, which made it possible to achieve a positive result. This clinical observation is compared with observations of foreign colleagues. Possible pathogenetic mechanisms of MIS-C and T1DM comorbidity are discussed.

Multisystem inflammatory syndrome in children associated with new coronavirus infection (COVID-19): clinical and morphological comparisons

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. Детский мультисистемный воспалительный синдром (ДМВС), ассоциированный с новой коронавирусной инфекцией (COVID-19), имеющий признаки болезни Кавасаки (БК) и синдрома токсического шока, четко очерченные диагностические критерии, - самое тяжелое проявление COVID-19 в детском возрасте. ДМВС является аналогом цитокинового шторма при COVID-19 у детей. В статье представлено клиническое наблюдение ребенка с ДМВС с летальным исходом. Клинико-анамнестические данные, результаты лабораторно-инструментальных методов исследования позволили диагностировать ДМВС у девочки 2 лет с полной формой БК. Приведены результаты аутопсии, подробного микроскопического исследования, выявившего системный васкулит сосудов мелкого и среднего калибра, воспалительные инфильтраты в разных органах, проведены клинико-морфологические сопоставления.

Clinical, laboratory-instrumental characteristics, course and therapy of pediatric multisystem inflammatory syndrome associated with COVID-19

The most severe manifestation of the new coronavirus infection COVID-19 in children is the multisystem inflammatory syndrome in children (MIS-C). A systematic review of foreign publications as of July 25, 2020 contains an analysis of the disease course in 662 children with this syndrome and is used for comparison with the data obtained. Objective of the research: to characterize clinical manifestation, results of laboratory and instrumental studies, therapy, outcomes and consequences of the COVID-19- associated MIS-C., based on the observation of patients hospitalized to Morozov Children's City Clinical Hospital and Children’s clinical hospital of infectious diseases № 6 from May 1 to September 15, 2020. Materials and methods: the pilot study included 32 children aged 9 months -15 years with COVID-19-associated MIS-C., verified based on WHO criteria (2020), including symptoms of Kawasaki disease (KD), arterial hypotension/shock, laboratory and instrumental signs of heart damage, signs of coagulopathy, gastrointestinal symptoms, increased inflammation markers, COVID-19 markers. Results: the median age of patients was 6 years, boys predominated among the patients (66%), all patients had antibodies to SARS-CoV-2 (31 children of the IgG class);MIS-C manifested itself as a combination of KD symptom complex (75% of patients) with arterial hypotension/shock (28%), neurological (50%), respiratory (41%), gastrointestinal (59%) symptoms;macrophage activation syndrome (MAS) was verified in 16% of patients. Therapy included intravenous immunoglobulin (75%), systemic glucocorticosteroids (88%), anticoagulants (91%), vasoactive/vasopressor support (31%). In 38% of cases treatment was performed in intensive care unit;one child died. According to echocardiography, 16% of patients had coronariitis, ectasia, and coronary arteries aneurysms. Conclusion: COVID-19-associated MIS-C is characterized by a severe course, cross-features with KD, shock syndrome with KD, MAS which requires intensive therapy and can cause acquired pathology of the cardiovascular system in children. Самым тяжелым проявлением новой коронавирусной инфекции COVID-19 у детей является ассоциированный с ней детский мультисистемный воспалительный синдром (ДМВС). Систематический обзор зарубежных публикаций по состоянию на 25 июля 2020 г. содержит анализ течения заболевания у 662 детей с данным синдромом и используется для сравнения с полученными данными. Цель исследования - характеристика клинической манифестации, результатов лабораторно-инструментальных исследований, терапии, исходов и последствий ДМВС, ассоциированного с COVID-19, основанная на наблюдении пациентов, госпитализированных в период с 1 мая по 15 сентября 2020 г. в Морозовскую ДГКБ и ДИКБ № 6 ДЗМ. Материалы и методы исследования: в пилотное исследование были включены 32 ребенка в возрасте 9 мес. - 15 лет с ДМВС, ассоциированным с COVID-19, верифицированным на основании критериев ВОЗ (2020), включающих симптомы болезни Кавасаки (БК), артериальную гипотензию/шок, лабораторно-инструментальные признаки поражения сердца, признаки коагулопатии, гастроинтестинальные симптомы, повышение маркеров воспаления, маркеры COVID-19. Результаты: медиана возраста больных составила 6 лет, среди больных преобладали мальчики (66%), у всех пациентов были обнаружены антитела к SARS-CoV-2 (у 31 ребенка класса IgG);ДМВС манифестировал в виде комбинации симптомокомплекса БК (75% больных) с артериальной гипотензией/шоком (28%), неврологическими (50%), респираторными (41%), гастроинтестинальными (59%) симптомами;у 16% пациентов был верифицирован синдром активации макрофагов (САМ). Терапия включала иммуноглобулин для внутривенного введения (75%), системные глюкокортикостероиды (88%), антикоагулянты (91%), вазоактивную/ вазопрессорную поддержку (31%). Лечение в 38% случаев проводилось в условиях отделения реанимации и интенсивной терапии;один ребенок погиб. У 16% по данным эхокардиографии были выявлены коронариит, эктазии, аневризмы коронарных артерий. Заключение: ДМВС, ассоциированный с COVID-19, характеризуется тяжелым течением, перекрестными чертами с БК, синдромом шока при БК, САМ, что требует проведения интенсивной терапии и может стать причиной приобретенной патологии сердечно-сосудистой системы у детей.