Multisystem Inflammatory Syndrome in Children

Multisystem inflammatory syndrome in children (MIS-C) is an uncommon but emerging syndrome related to SARS-CoV-2 infection. While the presentation of MIS-C is generally delayed after exposure to the virus that causes coronavirus 2019, both MIS-C and Kawasaki disease (KD) share similar clinical features. Multisystem inflammatory syndrome in children poses a diagnostic and therapeutic challenge given the lack of definitive diagnostic tests and a paucity of evidence regarding treatment modalities. We review the clinical presentation, diagnostic evaluations, and management of MIS-C and compare its clinical features to those of KD.

Post-COVID-19 Kawasaki-Like Syndrome.

A 42-year-old man was referred for a week history of severe dysphagia, odynophagia, fever (39 °C), fatigue, abdominal pain, pharyngeal swelling, and multiple neck lymphadenopathies. The medical history reported a mild form of COVID-19 one month ago. The biology reported an unspecified inflammatory syndrome. The patient developed peritonitis, myocarditis, and hepatitis. A myocardium biopsy was performed. A diagnosis of Kawasaki-like disease (KLD) was performed. The occurrence of KLD in adults is rare but has to be known by otolaryngologists regarding the otolaryngological clinical presentation that may precede the multiple organ failure.

Multisystem inflammatory syndrome in children related with 2019 Novel Coronavirus infection.

Multisystem inflammatory syndrome in children (MIS-C) reported in the United States and European countries is a disease with multi-organ involved symptoms related with 2019 Novel Coronavirus infection, which has never been reported in China. Although its symptoms are similar to Kawasaki disease, MIS-C has characteristics of higher frequency in older children and adolescents, gastrointestinal symptoms, haemodynamic instability, myocarditis and elevated inflammatory markers. Most of the children need intensive care. The pathogenesis and long-term prognosis of the disease need further study.Copyright © 2020 by the Chinese Medical Association.

Kawasaki Disease in Children and Pediatric Multisystem Inflammatory Syndrome Associated with SARS-CoV-2 During the Pandemic (Clinical Lecture).

The article presents modern data about Kawasaki disease, which is a genetically determined systemic vasculitis with damage to the coronary arteries and multisystem manifestations. The etiology is not fully understood, but there is considered a possible role of viruses in the initiation of the aggravated immune response with possible development of macrophage activation syndromes and shock, which can lead to death. There are difficulties in diagnosing Kawasaki disease due to a variety of symptoms that are typical for a lot of infectious and autoimmune diseases (scarlet fever, measles, yersiniosis, systemic juvenile idiopathic arthritis). Early diagnosis and treatment (in the first 10 days of illness) using high doses of intravenous immunoglobulin and aspirin are associated with a low risk of development of coronary aneurysms and other complications. The authors also presented the data on the characteristics of severe Kawasaki-like diseases, which were recorded in several countries of Europe and America at the peak of the COVID-19 pandemic, and diagnostic criteria for the pediatric multisystem inflammatory syndrome associated with SARS-CoV-2, proposed by the Royal College of Pediatrics and Children Health (UK).Copyright © 2020, Professionalnye Izdaniya. All rights reserved.

Kawasaki Disease in Children and Pediatric Multisystem Inflammatory Syndrome Associated with SARS-CoV-2 During the Pandemic (Clinical Lecture).

The article presents modern data about Kawasaki disease, which is a genetically determined systemic vasculitis with damage to the coronary arteries and multisystem manifestations. The etiology is not fully understood, but there is considered a possible role of viruses in the initiation of the aggravated immune response with possible development of macrophage activation syndromes and shock, which can lead to death. There are difficulties in diagnosing Kawasaki disease due to a variety of symptoms that are typical for a lot of infectious and autoimmune diseases (scarlet fever, measles, yersiniosis, systemic juvenile idiopathic arthritis). Early diagnosis and treatment (in the first 10 days of illness) using high doses of intravenous immunoglobulin and aspirin are associated with a low risk of development of coronary aneurysms and other complications. The authors also presented the data on the characteristics of severe Kawasaki-like diseases, which were recorded in several countries of Europe and America at the peak of the COVID-19 pandemic, and diagnostic criteria for the pediatric multisystem inflammatory syndrome associated with SARS-CoV-2, proposed by the Royal College of Pediatrics and Children Health (UK).Copyright © 2020, Professionalnye Izdaniya. All rights reserved.

Intestinal ischemia secondary to Covid-19.

With the wide spread of the current SARS-Cov (Covid-19), It was found that about 2% of children was affected according to several studies, it should be mentioned that Those children are most often asymptomatic, but the current concern is about a vascular inflammatory disease which is similar to Kawasaki disease observed in children with Covid-19. we report a case of a 9-year-old girl, known to have idiopathic medullar aplasia, admitted to the emergency department for a pseudo appendicular syndrome with shock, neurological abnormalities and skin lesions. She underwent an emergency surgery; the peroperative exploration suggested an ischemic bowel lesion of the ileal loop and a healthy appendix. The link involving a Covid-19 infection was well established (RT-PCR +). We shared in common our clinical, radiological, biological and pathological data to draw attention towards the intestinal vasculitis that can be a part in the MIS-C related to Covid 19. To our best knowledge, this is the first case encountered of combination between Covid-19 with intestinal ischemic in children.

A Young Adult With Multisystem Inflammatory Syndrome in Adults With Concomitant Mycoplasma Infection: A Case Report.

Several cases of Multisystem Inflammatory Syndrome in Adults (MIS-A) have been reported in adults since June 2020 after COVID-19 was first reported in December 2019. It was initially reported in children as MIS-C with Kawasaki-like disease, but a similar condition has been well recognized in adults. Although Mycoplasma co-infection has been reported with COVID-19, to our knowledge, concomitant Mycoplasma pneumoniae infection has not been reported together with MIS-A. We present a case of MIS-A with concomitant M. pneumoniae infection. It is unclear if concomitant Mycoplasma infection resulted in increased severity of the patient's illness or if it resulted in inciting the immune response in our patient who had recently recovered from COVID-19 infection. This case highlights the need to diagnose a patient with a typical presentation of MIS-A and any concomitant infection or illnesses.

Clinical Case: Postcovid Multisystem Syndrome in a 7 Month Old Child

The article presents a clinical case of multisystem inflammatory syndrome as a relsult of a new coronavirus infection in a 7 months old child. The clinical picture is similar to Kawasaki syndrome.

Methylprednisolone pulses as an initial treatment in hyperinflammatory syndrome after COVID-19 in children: evaluation of laboratory data, serial echocardiography and outcome: a case series.

BACKGROUND: Hyper-inflammatory syndrome in children and young adult occur 2-6 weeks after COVID-19 infection or closed contact with COVID-19 persons. In this study, the laboratory data and echocardiography and abdominal ultrasonography assessments were evaluated before and after Methylprednisolone pulse as an initial treatment of hyper-inflammatory syndrome. Therefore, the aim of this study is to assessment the clinical manifestations and laboratory data and outcome after methylprednisolone pulse as an initial treatment. METHOD: In this retrospective study, the demographic status, clinical features, laboratory data, echocardiography, abdominal ultrasound, treatment and outcome of 31 pediatric patients under 16 years old, with inflammatory process after COVID-19 were evaluated. The clinical assessments, laboratory data, sonography and echocardiography were evaluated before and after methylprednisolone pulse. The patients were divided in two age group < and ≥ 7 years old and the clinical manifestations were compared with each other. The Mann-Whitney U test was used to assess the difference in quantitative variables between two groups. To compare pre- and post- treatment values, Wilcoxol test was used. To assess the correlation between qualitative variables chi-square test was used. The level of significant was considered 0.05. These patients with fever and hyper-inflammation features admitted to the referral pediatric rheumatology ward in Children Medical Center of Tehran University of medical sciences, from April 2020 to May 2021 were assessed. RESULT: The mean age ± SD were (5.94 ± 3) and 51.6% (16) patients were male and 48.4% (15) patients were female. The most documented of previous COVID infection were antibody positive in about 27 (87%) patients. Moreover, 1 (3.8%) was PCR positive, 2 (7.7%) were positive in both PCR and serology and 3(11.5%) had closed contact with COVID-19 patients. About 9(29%) of patients were admitted in Intensive Care Unit (ICU). There were significant correlation between days of delay in starting treatment and ICU admission (P-value = 0.02). The mortality rate was negative in patients and no re-hospitalization was documented. There were significant differences (P-value < 0.05) between lymphocytes, platelet, Erythrocyte Sedimentation rate, C-reactive protein, Aspartate transaminase, Alanine transaminase and ferritin before and after treatment. Skin rashes and cardiac involvement totally as carditis (myocarditis, vulvulitis and pericarditis) (33.3%) and coronary involvements (53.3%) were the most prominent initial presentation in patients. There were near significant correlation (P-value = 0.066) between ferritin level and carditis before treatment. Cervical lymphadenopathy was seen significantly more in ≥ 7 years old (P-value = 0.01). CONCLUSION: Multisystem inflammatory system in children as a hyperinflammatory syndrome could be treated with first step methylprednisolone pulse with decreasing inflammation in laboratory data and cardiac involvements and good outcome. Furthermore, the ferritin level may be one of the predictor of severe hyper-inflammatory syndrome leading to aggressive and urgent treatment with methylprednisolone pulse.

Kawasaki Disease and COVID-19.

The recent passing away of Dr. Tomisaku Kawasaki, who first described what is now known as Kawasaki Disease (KD), and recent reports of a multisystem inflammatory disease in children associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (MIS-C), makes a review on KD and MIS-C timely. Kawasaki Disease is a systemic vasculitis with predilection for coronary arteries occurring mostly in early childhood. The main features are high fever, extensive skin rash, cheilitis with red, cracking, bleeding lips and strawberry tongue, conjunctivitis, erythema and induration of hands and feet, subsiding with periungual peeling, cervical lymphadenopathy, and coronary artery dilation/aneurysms. Treatment consists of intravenous (IV) immunoglobulin (Ig) plus acetylsalicylic acid. MIS-C is considered a cytokine storm with high fever, inflammation, multi-organ dysfunction, that shares features with KD, toxic shock, and macrophage activation syndrome. Many children require admission to paediatric intensive care units for circulatory support. Bacterial sepsis, staphylococcal toxic shock syndrome, and enterovirus-causing myocarditis should be excluded. Treatment is not standardized and includes IVIg, IV methylprednisolone and IL-6 and IL-1 inhibitors.

Preliminary results of follow-up of patients with multisystem inflammatory syndrome associated with COVID-19

Background and Aim: Kawasaki-like (multisystem inflammatory) syndrome associated with SARS-CoV-2 infection is characterized by acute severe systemic vasculitis, often with multi-organ dys-function and cardiac involvement. Although most patients recover, long-term outcomes are poorly studied [Gema de Lama Caro-Paton et al., 2021;Guimaraes D. et et al., 2021;Sharma C. et al., 2021]. Method(s): We analyzed the results of laboratory, clinical, radiologi-cal, ECG and EchoCG data in the dynamic observation of 15 patients (M 9, 1.5-16 yo, m = 7) in 3 months after the suffered MIS-C. Result(s): At the disease onset high refractory fever was observed in all cases, symptoms of Kawasaki disease in 12 (80%) of them, shock with multi-organ dysfunction-in 8 (53.3%), including symptoms of acute heart failure-in 5 (33%), concomitant in two cases with severe left ventricular dilatation with low LV EF. Myocardial damage was seen in 11 patients (73%), pericarditis in 12 (80%), coronary dilatation in two (13%);troponin level increased in 5 (33%), CK-MB-in 5 (33%), BNP-in 3 (25%). After 3 months, there were no signs of myocardial dysfunction and/or cardiomegaly in any patient, troponin and BNP levels normalized in all patients, a moderate increase of CK-MB was seen in 8 (53%), and coronary dilatation persisted in one patient. Arrhythmias were documented at onset in 9 (60%) patients, 3 (20%) after 3 months (p = 0.028). Conclusion(s): preliminary results of follow-up of children after MIS-C demonstrate favorable course in the majority of patients by clinical, laboratory, ECG and echocardiographic data. Further observations are needed to determine the long-term prognosis.

Novel coronavirus infection and Kawasaki disease.

There is a global problem of increment of the number of children with clinical features that mimic Kawasaki Disease (KD) during the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. The disease was first reported by Tomisaku Kawasaki, a Japanese pediatrician, in a four-year-old child with a rash and fever at the Red Cross Hospital in Tokyo in January 1961. Now Kawasaki disease is recognized worldwide. The complexity of symptoms was defined as an «acute febrile mucocutaneous lymphnode syndrome". At the moment, it is still unclear whether the coronavirus itself can lead to development of mucocutaneous lymph node syndrome. However, it is believed that COVID-19 virus infection worsens the course of Kawasaki disease, and in some cases, children affected by SARS-V-2 may develop a disease that has a clinical picture similar to Kawasaki disease.

Incidental Finding of Coronary Artery Dilatation in Children With History of COVID-19 Having Minimal or No Symptoms: Raising Red Flag.

Coronary artery dilatation has been observed with coronavirus disease 2019 (COVID-19)-associated multisystem inflammatory syndrome in children (MIS-C), which is more common in those with Kawasaki-like disease. MIS-C is a clinical syndrome in children and adolescents; its signs and symptoms, as well as cardiac manifestations, are similar to Kawasaki diseases, such as coronary artery dilation, coronary aneurysms, and ventricular dysfunction. The occurrence of coronary artery dilatation in asymptomatic pediatric patients following COVID-19 infection has not been well documented in the literature. Thus, in this article, we present four cases of coronary artery dilation in children with a past history of COVID-19 infection who had very few or no symptoms and were referred to us for vague chest pain and palpitation. As a result, a high index of suspicion is required, and any patient complaining of chest pain and palpitation with a history of COVID-19 exposure should not be ignored and be given proper coronary artery evaluation. This article also raises the question of whether every child infected with COVID-19 should have an echocardiogram.

Comparison of Laboratory Data between Children with Kawasaki Disease and COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been an emerging, rapidly evolving situation in China since late 2019 and has even become a worldwide pandemic. The first case of severe childhood novel coronavirus pneumonia in China was reported in March 2020 in Wuhan. The severity differs between adults and children, with lower death rates and decreased severity for individuals under the age of 20 years. Increased cases of Kawasaki disease (KD) have been reported from New York City and some areas of Italy and the U.K., with almost a 6-10 times increase when compared to previous years. We conducted this study to compare characteristics and laboratory data between KD and COVID-19 in children. METHODS: We obtained a total of 24 children with COVID-19 from a literature review and 268 KD cases from our hospital via retrospective chart review. RESULTS: We found that patients with KD have higher levels of white blood cells (WBCs), platelets, neutrophil percentage, C-reactive protein (CRP), procalcitonin, and aspartate aminotransferase (AST) and a higher body temperature, while patients with COVID-19 have a higher age, hemoglobin levels, and lymphocyte percentage. After performing multiple logistic regression analysis, we found that age, WBCs, platelets, procalcitonin, and AST are identical markers for distinguishing COVID-19 from KD in children. CONCLUSION: In this COVID-19 pandemic period, clinicians should pay attention to children with COVID-19 infection when high WBC, platelet, procalcitonin, and AST values are present in order to provide early diagnosis for KD or multisystem inflammatory syndrome in children (MIS-C).

A Review of Coronaviruses Associated With Kawasaki Disease: Possible Implications for Pathogenesis of the Multisystem Inflammatory Syndrome Associated With COVID-19.

Multisystem Inflammatory Syndrome in Children (MIS-C), representing a new entity in the spectrum of manifestations of COVID-19, bears symptomatic resemblance with Kawasaki Disease (KD). This review explores the possible associations between KD and the human coronaviruses and discusses the pathophysiological similarities between KD and MIS-C and proposes implications for the pathogenesis of MIS-C in COVID-19. Since 2005, when a case-control study demonstrated the association of a strain of human coronavirus with KD, several studies have provided evidence regarding the association of different strains of the human coronaviruses with KD. Thus, the emergence of the KD-like disease MIS-C in COVID-19 may not be an unprecedented phenomenon. KD and MIS-C share a range of similarities in pathophysiology and possibly even genetics. Both share features of a cytokine storm, leading to a systemic inflammatory response and oxidative stress that may cause vasculitis and precipitate multi-organ failure. Moreover, antibody-dependent enhancement, a phenomenon demonstrated in previous coronaviruses, and the possible superantigenic behavior of SARS-CoV-2, possibly may also contribute toward the pathogenesis of MIS-C. Lastly, there is some evidence of complement-mediated microvascular injury in COVID-19, as well as of endotheliitis. Genetics may also represent a possible link between MIS-C and KD, with variations in FcγRII and IL-6 genes potentially increasing susceptibility to both conditions. Early detection and treatment are essential for the management of MIS-C in COVID-19. By highlighting the potential pathophysiological mechanisms that contribute to MIS-C, our review holds important implications for diagnostics, management, and further research of this rare manifestation of COVID-19.

Cardiovascular Spectrum and Cardiac Biomarkers in Pediatric Inflammatory Multisystem Syndrome with Kawasaki-Like Disease-Our Experience During the COVID-19 Pandemic in the West Part of Romania

Aim. In COVID-19 Pandemic, a new hyperinflammatory syndrome was reported with clinical features of Kawasaki disease, named PIMS-TS. We want to present a single center experience where the patients were diagnosed with Kawasaki-like in PIMS-TS with cardiac affliction. Material and method: The study was observational and retrospective, enrolled 14 patients fulfilling the criteria of PIMS-TS with the median age of 9 (IQR, 1.6-11), 9 male (64.2 %) and 5 female (35.8 %). Results: ECG revealed tachycardia and ST-T changes in 60% of patients. In evolution, ECG modified in 20% and consisted of long QT in 7% of cases, bradycardia in 7%, 3% transitory sick sinus syndrome and 3% grade I/II Atrio-Ventricular block. Cardiac disfunction was evidenced in 4 patients (28%), with reduced ejection fraction under 50%, mitral insufficiency in 6 (42.8%), pericardial fluid in 8 (57.1%) and perivascular brightness in 8 (57.1%). The cardiac biomarkers: NT-proBNP (increased in 9), cTroponin T (increased in 7) and cTroponin I (increased in 5) confirmed heart dysfunction. During the hospitalization and under medical treatment, all the modifications recover. Evolution was good for 12 children. Conclusions: Cardiac dysfunction and myocardial injury were confirmed by elevated cardiac biomarkers. Rapid recognition allows prompt treatment for a good outcome. NT-proBNP, cTroponin T and I are of capital significance in monitoring the myocardial injury, the treatment and evolution of these patients. © 2021, MediaMed Publicis. All rights reserved.

["Pediatric inflammatory multisystem syndrome"-Experiences from a Berlin Children's Hospital]. / "Pediatric inflammatory multisystem syndrome" ­ Erfahrungen aus einer Berliner Kinderklinik.

BACKGROUND: Since the beginning of the SARS-CoV­2 pandemic, cases of the hyperinflammatory syndrome pediatric inflammatory multisystem syndrome (PIMS) have been accumulating. The clinical presentation is variable and it occurs 2-6 weeks after infection with SARS-CoV­2. As of today, immunoglobulins and/or steroids as well as ASS are used for medication. METHOD: In our clinic 11 patients presented with PIMS between 06/2020 and 06/2021, whose data were retrospectively collected and analyzed. RESULTS: Of the 11 patients 6 were male, the age distribution ranged from 4-18 years and 7 were overweight or obese. Almost all patients showed gastrointestinal and cardiovascular involvement, 4 had respiratory symptoms, 6 showed signs of nephritis. All showed blood count changes with anemia or leukocytosis and coagulopathy. CRP, ferritin, and soluble IL2 receptor were highly elevated in all patients. Only 2 patients had neither troponin­T nor NT-pro-BNP elevation and 7 patients had impaired left ventricular function. Positive SARS-CoV­2 serology was found in 10, and positive SARS-CoV­2 PCR via nasopharyngeal swabs in 2.All were initially treated with antibiotics, 3 patients required O2 supplementation, 6 required intensive care and 5 required vasoactive agents. All but one patient received immunoglobulins and ASS, 5 received prednisolone. Length of stay ranged from 4-51 days. CONCLUSION: PIMS is a severe acute hyperinflammatory disease, which was secured in 11 patients in our clinic. In some cases, there was a need for intensive care. Under anti-inflammatory therapy there was a good response without exception.

COVID 19 Vaccine for Adolescents. Concern about Myocarditis and Pericarditis.

The alarming onset of some cases of myocarditis and pericarditis following the administration of Pfizer-BioNTech and Moderna COVID-19 mRNA-based vaccines in adolescent males has recently been highlighted. All occurred after the second dose of the vaccine. Fortunately, none of patients were critically ill and each was discharged home. Owing to the possible link between these cases and vaccine administration, the US and European health regulators decided to continue to investigate the potential causal relationship between COVID-19 mRNA vaccines and myocarditis. In any case, none of the patients fulfilled the criteria for multi-system inflammatory syndrome or Kawasaki-like disease and there was no evidence of acute SARS-CoV-2 infection.

Is the composition of exhaled breath condensate a key to explain the course of COVID-19 in children?

INTRODUCTION: The relative resistance of children to severe course of the novel coronavirus infection remains unclear. We hypothesized that there might be a link between this phenomenon and observation from our previous studies concerning an inhibitory or cytotoxic effect of exhaled breath condensate (EBC) on endothelial cell cultures in children. AIM: Since we could not find any data on the similar effect caused by EBC in adults, the aim of our study was to evaluate and compare the biological activity of EBC in adults and children in an experimental in vitro model. Furthermore, in order to identify a putative agent responsible for these properties of EBC in children, we attempted to analyse the composition of selected EBC samples. MATERIAL AND METHODS: The influence of EBC samples on metabolic activity of endothelial cell line C-166 was assessed using colorimetric tetrazolium salt reduction assay (MTT assay). Selected EBC samples were fractionated using size exclusion chromatography and subjected to mass spectrometry analysis. RESULTS: Exhaled breath condensates in healthy children, but not in adults, revealed a cytotoxic effect on in vitro cell cultures. This effect was most significant in condensate fraction, which contained a prominent 4.8 kDa peak in the mass spectra. CONCLUSIONS: Breath condensates of healthy children contain the factor which reveals the inhibitory/cytotoxic effect on endothelial cell cultures. Although the physiological role of this agent remains unclear, its identification may potentially be useful in ongoing research on SARS-CoV-2/COVID-19.