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.

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.

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.

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.

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.

Overlaping syndromes: Kawasaki-like disease in pediatric multisystem inflammatory syndrome vs atypical kawasaki disease. british or american? one case, many possibilities

Kawasaki disease is a challenging diagnosis even in typical forms of presentation. The features are represented by long lasting fever, specific mucocutaneous signs and coronary artery dilations as expression of medium artery vasculitis of unknown origin. Kawasaki-like disease emerged as a variant of pediatric multisystem inflammatory syndrome (PMIS) associated with COVID-19 infection. A 1 year 9-month-old boy who presented with fever, semi-consistent stools, vomiting, facial edema and hepatomegaly was transferred in our hospital with suspicion of myocarditis due to the clinical presentation, inflammatory markers and systolic dysfunction. In a few days after presentation, also, dilation of the coronary artery appeared while the child had persistent constant symptomatology. Gradually, a pediatric multisystem inflammatory syndrome (PMIS) developed, but without positive markers of COVID-19 infection, which remained negative (both antigen and antibodies). So, in front of all elements of PMIS except exposure to SARS-CoV-2, we concluded for an atypical Kawasaki disease with elements of PMIS. But the debate between the elaborated criteria British and American for PMIS are circling around the demonstration of the infection, past or present, making some cases difficult to diagnose. In this high affluence of Kawasaki-like disease, with intricated elements of myocarditis and multisystem inflammatory syndrome it is more and more difficult to establish a clear diagnosis. While the diagnosis looks complex, the curative treatment goes in the same direction – immunoglobulin, immunosuppressive treatment, inotropic and antiaggregant or anticoagulant treatment. © 2021, MediaMed Publicis. All rights reserved.

Síndrome inflamatorio multisistémico en un adulto secundario a infección por SARS CoV2. ¨Reporte de caso

Resumen En informes recientes se describe el síndrome de inflamación multisistémico secundario en niños (MIS-C) después de una infección COVID-19 previa, que han presentado características de la Enfermedad de Kawasaki. Se han reportado pocos casos de esta entidad en adultos, pero se ha observado en pacientes posterior a exposición por SARS-CoV2. El siguiente caso describe paciente masculino de 27 años de edad, con antecedente de infección previa por COVID 19 diagnosticada con prueba RT-PCR COVID 19, presentó evacuaciones diarreicas, nauseas, vómitos, proceso febril, inestabilidad hemodinámica e insuficiencia respiratoria. Al examen físico se encuentra inyección conjuntival en ambos ojos y rash en miembros superiores. Los exámenes de laboratorio demostraron proceso infeccioso e inflamatorio. Hallazgos similares de trastorno inflamatorio similar a Enfermedad de Kawasaki, con exposición previa por SARS CoV2 y con buena respuesta a tratamiento con inmunoglobulina humana (IVIG), esteroide y tocilizumab. El reporte de estos casos clínicos contribuye a la comunidad científica medica a tener siempre la sospecha clínica y aplicar los criterios diagnósticos establecidos por el CDC para pacientes adultos, de esta manera se instauran tratamientos tempranos a dichos pacientes. Dentro de nuestro conocimiento presentamos el primer caso de síndrome inflamatorio multisistémico en el adulto secundario a infección por SARS CoV2 en El Salvador. Recent reports describe multisystemic inflammation syndrome in children (MIS-C) after COVID-19 infection, who have presented features of Kawasaki disease. Few cases have been reported of this entity in adults, but it has been observed in patients after exposure to SARS CoV2. The following case describes a 27-year-old male patient, with a history of previous COVID 19 infection diagnosed with the COVID 19 RT-PCR test, who presented with diarrhoeal stools, nausea, vomiting, febrile process, haemodynamic instability, and respiratory failure. The physical examination revealed a conjunctival injection in both eyes and a rash in the upper limbs. Laboratory tests demonstrated an infectious and inflammatory process. Findings of an inflammatory disorder similar to Kawasaki disease, with previous exposure to SARS CoV2, and with good response to treatment with human immunoglobulin (IVIG), steroid, and tocilizumab. Reporting these clinical cases alerts the medical scientific community to always have clinical suspicion and apply the diagnostic criteria established by the CDC for adult patients, thus prompt treatment is established for these patients. To the best of our knowledge, we present the first case of multisystemic inflammatory syndrome in adults secondary to SARS CoV2 infection in El Salvador.

[Consensus on treatment of multisystemic inflammatory syndrome associated with COVID-19]. / Consenso sobre el tratamiento del síndrome inflamatorio multisistémico asociado a COVID-19.

The pandemic caused by the SARS-CoV-2 virus declared by the WHO in March 11th 2020, affects a small number of pediatric patients, who mostly present mild respiratory compromise and favorable evolution. However began to be observed in previously healthy children, an increase in cases defined as "Multisystemic Inflammatory Syndrome" (MIS-C) or "Kawasaki-like" post-COVID 19 (KLC) that evolve to shock and require hospitalization in the Pediatric Intensive Care Unit. MIS-C and KL-C are characterized by fever; signs of inflammation, gastrointestinal symptoms, and cardiovascular dysfunction, associated with sever forms of presentation with higher incidence of hypotension and/or shock. In the laboratory, markers of inflammation, hypercoagulability and myocardial damage are observed. Firstline drug treatment consists of intravenous immunoglobulin plus oral acetylsalicylic acid. A multidisciplinary approach is recommended for an accurate diagnosis and an early and effective treatment, in order to reduce morbidity and mortality.

La pandemia ocasionada por el nuevo coronavirus (SARS-CoV-2), declarada por la Organización Mundial de la Salud OMS) en marzo de 2020, afecta a un reducido número de pacientes pediátricos, quienes presentan, en su mayoría, compromiso respiratorio leve y evolución favorable. Sin embargo, en niños previamente sanos, comenzó a observarse un aumento de casos definidos como síndrome inflamatorio multisistémico (SIM-C) o similar a Kawasaki (Kawasaki-like) asociado a la enfermedad por el nuevo coronavirus (COVID-19) (KL-C) que evolucionan al shock y requieren internación en la unidad de cuidados intensivos. Los cuadros de SIM-C y los KL-C se caracterizan por fiebre, signos de inflamación, síntomas gastrointestinales y disfunción cardiovascular; las formas graves de presentación tienen mayor incidencia de hipotensión y/o shock. En el laboratorio se observan marcadores de inflamación, hipercoagulabilidad y daño miocárdico. El tratamiento farmacológico de primera línea consiste en la administración de inmunoglobulina por vía intravenosa más ácido acetilsalicílico por vía oral. Se recomienda un abordaje multidisciplinario para un diagnóstico certero y un tratamiento temprano y eficaz para disminuir la morbimortalidad.

How Children Are Protected From COVID-19? A Historical, Clinical, and Pathophysiological Approach to Address COVID-19 Susceptibility.

The origin and the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) in early 2020 was accompanied by high rates of mortality in regions belonging to the ancient silk road, such as the south of China, Iran, Turkey and the northern parts of Italy. However, children seem to be spared in the epidemic as very small percentage worldwide being ill. The protection of children and neonates suggests the involvement of a specific component of adaptive immunity present at early development. Native immunoglobulin belonging to the class of IgM is abundantly present in neonates and children and is known for its recognition of self- and altered self-antigens. Native IgM may be able to neutralize virus by the recognition of endogenous "danger signal" encoded in the viral envelope and originally imprinted in the membranes of infected and stressed cells. Noteworthy, thrombosis and vasculitis, two symptoms in severely affected adult and pediatric patients are shared between COVID-19 and patients with Behcet's disease, an autoimmune disorder exhibiting a region-specific prevalence in countries of the former silk road. Molecular mechanisms and clinical indicators suggest reactive oxygen species as trigger factor for severe progression of COVID-19 and establish a link to the innate immune defense against bacteria. The selective pressure exerted by bacterial pathogens may have shaped the genetics of inhabitants at this ancient trade route in favor of bacterial defense, to the detriment of severe COVID-19 progression in the 21th century.

Kawasaki like illness due to COVID-19: a review of the literature.

INTRODUCTION: Viral infections have been described as triggers for Kawasaki Disease (KD), a medium vessel vasculitis that affects young children. Akin to the H1N1 pandemic in 2009, there is a similar rise in the incidence of KD in children affected with Coronavirus disease 2019 (COVID-19). Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) has been reported to induce an exaggerated systemic inflammatory response resulting in multi-organ involvement, particularly initiated with pulmonary parenchymal damage. This review article will discuss KD-like manifestations in COVID-19 patients in the pediatric cohort. METHODOLOGY: Search terms "Kawasaki" "COVID-19" "SARS-COV-2" "PIM-TS" and "MIS-C" were used to look for relevant articles in PubMed and Google Scholar published in the last 5 years. RESULTS: There is some evidence to suggest that SARS-CoV-2 stimulates dysfunctional and hyperactive immune reactions mimicking KD in young patients. CONCLUSIONS: Therapeutic options, both investigational and repurposed, include intravenous immunoglobulins, steroids and anticoagulation. More studies are required to evaluate the effectiveness of these treatment options.

Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management.

Multisystem inflammatory syndrome (MIS-C) is a pediatric hyperinflammation disorder caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It has now been reported from several countries the world over. Some of the clinical manifestations of MIS-C mimic Kawasaki disease (KD) shock syndrome. MIS-C develops 4-6 weeks following SARS-CoV-2 infection, and is presumably initiated by adaptive immune response. Though it has multisystem involvement, it is the cardiovascular manifestations that are most prominent. High titres of anti-SARS-CoV-2 antibodies are seen in these patients. As this is a new disease entity, its immunopathogenesis is not fully elucidated. Whether it has some overlap with KD is still unclear. Current treatment guidelines recommend use of intravenous immunoglobulin and high-dose corticosteroids as first-line treatment. Mortality rates of MIS-C are lower compared to adult forms of severe COVID-19 disease.

Severe acute respiratory syndrome coronavirus 2-induced multisystem inflammatory syndrome in children.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced multisystem inflammatory syndrome in children (MIS-C) is a life-threatening illness that has been reported in the United States and Europe. It affects multiple organ systems and often requires patient admission to an intensive care unit. Although some features of MIS-C overlap with Kawasaki disease, MIS-C is more common among older children and adolescents, more often affects cardiovascular and gastrointestinal systems, and more frequently presents with elevated inflammatory markers. Rapid and complete clinical recovery is possible in nearly all patients following immunomodulation therapy. Thus far, MIS-C pathophysiology and long-term prognosis are not sufficiently clear; further studies are needed.

The wide spectrum of Kawasaki-like disease associated with SARS-CoV-2 infection.

Introduction: On June 2020, the first case of concurrent Covid-19 and Kawasaki disease (KD) was published. After this first description, further works reported new cases of children affected by KD and KD-like syndrome after SARS-CoV-2 infection. The clinical and biochemical features of these patients differed from the historical cohorts of KD, suggesting the possibility of a new multi-systemic inflammatory syndrome. Is still unclear if this new clinical entity, often referred as pediatric inflammatory multisystem syndrome (PIMS) or multi-system inflammatory syndrome in children (MIS-C), could be considered as part of the KD spectrum or is a new disease with different pathogenic mechanisms and uniquely linked to SARS-CoV-2 infection. The authors searched the available literature in MedLine (via Pubmed) with the terms ('coronaviruses' OR 'coronavirus') AND ('Kawasaki disease') for English studies without any temporal limit. Areas covered: This review aims to comprehensively describe multisystem inflammatory syndromes affecting children during Coronaviruses outbreak, and to evaluate the possible pathogenic role of human Coronaviridae in KD and KD-like syndromes. Expert opinion: An increased incidence of PIMS-TS, during the Covid-19 pandemic has been reported, suggesting that SARS-CoV-2 may trigger a severe hyper-inflammatory syndrome in childhood. The pathophysiological mechanisms of this disease are still unclear. Based on these findings, SARS-CoV-2 may be considered another trigger in the complex mosaic about the relationship among infectious agents and the occurrence of systemic hyper-inflammation related syndromes.

Association between SARS-CoV-2 infection and Kawasaki-like multisystem inflammatory syndrome: a retrospective matched case-control study, Paris, France, April to May 2020.

We assessed the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and Kawasaki disease (KD)-like multisystem inflammatory syndrome in a retrospective case-control study in France. RT-PCR and serological tests revealed SARS-CoV-2 infection in 17/23 cases vs 11/102 controls (matched odds ratio: 26.4; 95% confidence interval: 6.0-116.9), indicating strong association between SARS-CoV-2 infection and KD-like illness. Clinicians should keep a high level of suspicion for KD-like illness during the COVID-19 pandemic.