scholarly journals Diversity of Cardiac and Gastrointestinal Presentations of Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: A Case Series

2021 ◽  
Vol 8 ◽  
pp. 2333794X2199661
Author(s):  
Anuja R. Shikhare ◽  
Rimsha M. Iqbal ◽  
Rabail Tariq ◽  
Daniel R. Turner ◽  
Bassam M. Gebara ◽  
...  

COVID-19 is generally a benign or asymptomatic infection in children, but can occasionally be severe or fatal. Delayed presentation of COVID-19 with hyperinflammation and multi-organ involvement was recently recognized, designated the Multisystem Inflammatory Syndrome in Children (MIS-C). Six children with MIS-C with molecular and serologic evidence of SARS-CoV-2 infection were admitted to our hospital between May 5, 2020 and June 25, 2020. All had fever and weakness; 4/6 presented with gastrointestinal symptoms. Two children had features of complete Kawasaki disease, 3 had incomplete Kawasaki disease, while 1 had terminal ileitis with delayed onset of circulatory shock. Treatment consisted of intravenous immunoglobulin and aspirin for Kawasaki-like disease. Remdesivir, corticosteroids, and infliximab were used when indicated. Median hospitalization was 7 days. Immediate treatment resulted in rapid clinical improvement. In children presenting with hyperinflammatory syndromes without cardiac manifestations, testing for SARS-CoV-2 RNA and antibodies, with close cardiac monitoring should be pursued due to the manifold presentations of SARS-CoV-2 infection in children.

2021 ◽  
Vol 26 (4) ◽  
pp. 318-338
Author(s):  
Van L. Tran ◽  
Sarah Parsons ◽  
Andrew Nuibe

Multisystem Inflammatory Syndrome in Children (MIS-C) was first recognized as a novel illness in 2020 with manifestations similar to other hyperinflammatory syndromes, such as Kawasaki disease or macrophage activation syndrome. Severity varies from a self-limited febrile illness to shock requiring inotropes and mechanical ventilation. Gastrointestinal symptoms and persistent fevers are the most common clinical symptoms, with the addition of cardiac manifestations inclusive of ventricular dysfunction and coronary artery aneurysms. With no controlled trials or comparative effectiveness studies evaluating treatment of MIS-C to date, current treatment with immunomodulatory agents has mainly been derived from previous experience treating Kawasaki disease. This article provides a comprehensive review summarizing published data for the evaluation and management of MIS-C, with a focus on pharmacotherapy treatment considerations.


Author(s):  
Gian Paolo Ciccarelli ◽  
Eugenia Bruzzese ◽  
Gaetano Asile ◽  
Edoardo Vassallo ◽  
Luca Pierri ◽  
...  

Abstract Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare life-threatening clinical condition that can develop in patients younger than 21 years of age with a history of infection/exposure to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The cardiovascular system is a main target of the inflammatory process that frequently causes myocardial dysfunction, myopericarditis, coronary artery dilation, hypotension, and shock. MIS-C-associated myocarditis is usually characterized by fever, tachycardia, nonspecific ECG abnormalities and left ventricular dysfunction, but serious tachyarrhythmias may also occur. We report 2 cases of patients with MIS-C-associated myocarditis who developed severe bradycardia. Case summary Two female adolescents with recent history of COVID-19 were initially hospitalized for long-lasting high-grade fever and severe gastrointestinal symptoms. Both patients were diagnosed with MIS-C-associated myocarditis for elevation of markers of myocardial injury (mean highly-sensitive cardiac Troponin 2663 pg/ml, mean NT-pro-BNP 5097 pg/ml) and left ventricular dysfunction, which was subsequently confirmed by cardiac magnetic resonance. Both patients developed a severe sinus bradycardia (lowest HR 36 and 42, respectively), that appeared refractory to the treatment with intravenous Methylprednisolone and Immunoglobulins, despite a clinical and biochemical improvement. The use of Anakinra (a recombinant IL-1 receptor antagonist), was associated with a rapid improvement of cardiac rhythm and excellent clinical outcome at 6 months follow-up. Discussion In patients with MIS-C-associated myocarditis, a continuous cardiac monitoring is mandatory to promptly identify potential conduction abnormalities. Adolescents may present bradycardia as a rhythm complication. We experienced a rapid recovery after treatment with Anakinra, to be considered as add-on therapy in cases refractory to standard anti-inflammatory treatment.


Author(s):  
Esther Orlanski-Meyer ◽  
Dotan Yogev ◽  
Adi Auerbach ◽  
Orli Megged ◽  
Daniel Glikman ◽  
...  

Abstract We describe an 8-week-old infant with severe gastrointestinal symptoms, significant hypoalbuminemia, and mild carditis following asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infant’s symptoms, including their temporal appearance, were consistent with multisystem inflammatory syndrome in children (MIS-C). A unique finding on colonic histology which may shed light on the pathogenesis of MIS-C was identified. The patient improved significantly following several anti-inflammatory treatments. The lag between the presentation of MIS-C and initial SARS-CoV-2 exposure, which may often be asymptomatic, together with the young age of our patient, makes this a challenging diagnosis. Clinicians should be aware of this entity, even in the neonatal and infantile age groups, to facilitate timely identification and treatment.


2020 ◽  
Vol 99 (6) ◽  
pp. 209-219
Author(s):  
L.V. Bregel ◽  
◽  
M.M. Kostik ◽  
L.Z. Fell ◽  
O.S. Efremova ◽  
...  

During the COVD-19 pandemic, some pediatric patients in many countries around the world experienced a syndrome resembling a severe Kawasaki disease (KD), often accompanied by shock. Due to the incomplete signs of the classic KD in the era before the present pandemic, in many publications from European countries and the United States, this condition was called «multisystem inflammatory syndrome in children – MIS-C» or «hyperinflammatory shock» or «Kawasaki-like syndrome». This syndrome with a new coronavirus infection is characterized by refractory fever, frequent gastrointestinal symptoms, heart damage (including coronary dilation in some patients, and acute left ventricular failure in the majority), increased ESR and CRP levels, neutrophilia, extremely high troponin levels, increased ferritin, AST, ALT, lactate dehydrogenase, creatine phosphate kinase, interleukin-6 and interleukin-10, coagulopathy with an increase in D-dimer and fibrinogen, thrombocytopenia, sometimes procalcitonin increase. The manifestations of a cytokine storm may meet the criteria for secondary hemophagocytic syndrome. The mechanism of myocardial damage remains unclear. Treatment with high-dose intravenous immunoglobulin is effective, and in the presence of signs of hemophagocytic syndrome, dexamethasone or methylprednisolone. Further research is needed to understand the pathogenesis, resemblance and differences of this syndrome with classic KD, understanding of heart injuiry and early recognition for the need of urgent care.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Carles Bautista ◽  
Joan Sanchez-de-Toledo ◽  
Clark C Bradley ◽  
Jetrho Herberg ◽  
Fanny Bajolle ◽  
...  

Introduction: Following the SARS-CoV-2 pandemic peak, children suffering from a multiorgan inflammatory disease that often leads to shock have been reported. This condition shares features with Kawasaki disease, but its etiopathogenesis is unknown. Hypothesis: We aimed to describe presentation and hospital course for this pediatric inflammatory multisystemic syndrome associated with COVID-19 (PIMS-TS). Methods: Data were collected from a retrospective review of children from 33 participating European, Asian and American sites. Results: We included 183 patients (109 males, 59·6%) with PIMS-TS, at a mean age of 7·0 (±4·7) years. Fifty-six (30·6%) had black ethnicity and obesity was present in 48 (26·2%) cases. Overall, 114/183 (62·3%) had biological evidence of current or recent SARS-CoV-2 infection. At admission, all presented with fever, 117/183 (63·9%) with gastrointestinal symptoms and 79/183 (43·2%) with shock, that was associated with more frequent black ethnicity, higher inflammatory markers and more cardiac involvement. Twenty-seven patients (14·7%) fulfilled criteria for Kawasaki disease. They were younger with no shock, fewer gastrointestinal, cardio-respiratory and neurological symptoms. Among the remaining PIMS-TS patients, 77 (49·3%) had mainly fever and inflammation with less cardiac involvement. For the entire cohort of 183 patients, the mean duration of admission was 8·6 (±5·6) days. Inotropic support, mechanical ventilation and ECMO were indicated in 72 (39·3%), 43 (23·5%) and 4 (2·2%) patients, respectively. Three patients (1·6%) died. A shorter duration of symptoms before admission was a risk factor for worse outcome and for ECMO/death, with 63% increased risk per day reduction (95%CI 0·39-0·93, p=0·03) and with 51·4% increased risk per day reduction (95%CI 0·36-0·9, p=0·03), respectively. Conclusions: We describe the first largest international series of children with PIMS-TS. Life-threatening shock is a common presentation. A shorter duration of symptoms prior to admission characterizes the fulminant form of the disease with potentially worse outcome.


2021 ◽  
Vol 12 ◽  
Author(s):  
Men-Ren Chen ◽  
Ho-Chang Kuo ◽  
Yann-Jinn Lee ◽  
Hsin Chi ◽  
Sung Chou Li ◽  
...  

Coronavirus disease-19 (COVID-19) in children is usually mild but some are susceptible to a Kawasaki disease (KD)-like multisystem inflammatory syndrome in children (MIS-C) in the convalescent stage, posing a need to differentiate the phenotype, susceptibility, autoimmunity, and immunotherapy between KD and MIS-C, particularly in the upcoming mass vaccination of COVID-19. Patients with MIS-C are prone to gastrointestinal symptoms, coagulopathy, and shock in addition to atypical KD syndrome with fever, mucocutaneous lesions, lymphadenopathy, and/or cardiovascular events. MIS-C manifests KD-like symptoms that alert physicians to early recognize and adopt the KD treatment regimen for patients with MIS-C. MIS-C linked to COVID-19 teaches us infection-associated autoimmune vasculitis and vice versa. Studies on genetic susceptibility have identified certain human leukocyte antigen (HLA) locus and toll-like receptor (TLR) associated with KD and/or COVID-19. Certain HLA subtypes, such as HLA-DRB1 and HLA-MICA A4 are associated with KD. HLA-B*46:01 is proposed to be the risk allele of severe COVID-19 infection, and blood group O type is a protective factor of COVID-19. The autoimmune vasculitis of KD, KD shock syndrome (KDSS), or MIS-C is mediated by a genetic variant of HLA, FcγR, and/or antibody-dependent enhancement (ADE) resulting in hyperinflammation with T helper 17 (Th17)/Treg imbalance with augmented Th17/Th1 mediators: interleukin-6 (IL-6), IL-10, inducible protein-10 (IP-10), Interferon (IFNγ), and IL-17A, and lower expression of Treg-signaling molecules, FoxP3, and transforming growth factor (TGF-β). There are certain similarities and differences in phenotypes, susceptibility, and pathogenesis of KD, KDSS, and MIS-C, by which a physician can make early protection, prevention, and precision treatment of the diseases. The evolution of immunotherapies for the diseases has shown that intravenous immunoglobulin (IVIG) alone or combined with corticosteroids is the standard treatment for KD, KDSS, and MIS-C. However, a certain portion of patients who revealed a treatment resistance to IVIG or IVIG plus corticosteroids, posing a need to early identify the immunopathogenesis, to protect hosts with genetic susceptibility, and to combat Th17/Treg imbalance by anti-cytokine or pro-Treg for reversal of the hyperinflammation and IVIG resistance. Based on physiological and pathological immunity of the diseases under genetic susceptibility and host milieu conditions, a series of sequential regimens are provided to develop a so-called “Know thyself, enemy (pathogen), and ever-victorious” strategy for the prevention and immunotherapy of KD and/or MIS-C.


2021 ◽  
Vol 22 (Supplement 1 3S) ◽  
pp. 356-356
Author(s):  
A. García-Salido ◽  
I. Leoz-Gordillo ◽  
M. Cabrero-Hernández ◽  
G. De Lama Caro-Patón ◽  
S. Cuenca-Carcelén ◽  
...  

2021 ◽  
Vol 9 ◽  
Author(s):  
Parham Mardi ◽  
Marzieh Esmaeili ◽  
Parisa Iravani ◽  
Mohammad Esmail Abdar ◽  
Kumars Pourrostami ◽  
...  

Recent studies have shown that several children diagnosed with COVID-19 have developed Kawasaki Disease (KD)-like symptoms. This systematic review aims to assess the demographic, laboratory, and clinical characteristics of children with KD-like syndrome during the COVID-19 pandemic and evaluate efficacy of treatments and patients' outcome. A comprehensive search was carried out systematically through PubMed, Scopus, and Web of Science (WoS), medRxiv, and bioRxiv by two reviewers independently for all studies or preprints data on the demographic, laboratory, and clinical characteristics of children with K.D-like signs during the COVID-19 outbreak. Overall, 378 studies were identified by the systematic search, of which 25 studies were included in the study. The included studies involved 599 patients in total. Thirteen studies (52%) were case reports or case series, and the rest (48%) were cohort studies. In 19 studies, patients were diagnosed with Multisystem inflammatory syndrome in children (MIS-C). In 16 studies COVID-19 was diagnosed in all patients based on their polymerase chain reaction result, serological findings, and computed tomography results. Higher C-reactive protein and erythrocyte sedimentation rate level were the most prevalent laboratory findings. In most studies, patients had leucopenia with marked lymphopenia, hypoalbuminemia, and increased ferritin, as well as hyponatremia. Abnormal echocardiography and respiratory outcomes were the most common clinical outcomes. In 11 studies, all patients required intensive care unit admission. Findings of the present systematic review show that the incidence of KD-like syndrome in the COVID-19 pandemic increased significantly. Moreover, this study offers new insights in the KD-like syndrome pathogenesis and clinical spectrum during COVID-19 pandemic.


2021 ◽  
Vol 9 ◽  
Author(s):  
Satoshi Takasago ◽  
Aiko Sakai ◽  
Masaya Sugiyama ◽  
Masashi Mizokami ◽  
Hiromichi Hamada ◽  
...  

Multisystem inflammatory syndrome in children (MIS-C) is a severe disease that is reportedly linked to coronavirus disease 2019. Affected patients present with gastrointestinal symptoms and cardiovascular dysfunction, in addition to Kawasaki disease-like features, suggesting the potential for overlapping disease mechanisms. Kawasaki disease has been reported among individuals of East Asian ethnicities, whereas there is minimal clinical literature regarding the occurrence of MIS-C among individuals of Asian ethnicities. A few reports thus far have described changes in cytokine kinetics during the course of disease in patients with MIS-C. We followed the temporal cytokine kinetics in a 9-year-old Japanese girl who exhibited a classical trajectory of MIS-C. The patient exhibited right cervical swelling and pain, abdominal pain, vomiting, and lip reddening, which developed 31 days after she was diagnosed with severe acute respiratory syndrome coronavirus-2 infection. The patient was diagnosed with Kawasaki disease on her fifth day of illness; because she fulfilled the criteria for MIS-C, she was also diagnosed with this disease on her fifth day of illness. Her fever rapidly resolved upon administration of intravenous immunoglobulin, aspirin, and prednisolone. On the patient's sixth day of illness, she developed acute myocarditis, which was treated with two diuretics and one vasodilator; the myocarditis ameliorated within a few days. Analyses of temporal kinetics for 71 serum cytokines revealed several patterns of cytokine changes that were consistent with the patient's clinical course of disease. Importantly, there was a clear distinction between cytokines that did and did not decrease rapidly following post-treatment fever resolution. These findings may be useful for the assessment of disease status and selection of therapy in patients with similar symptoms; they may also provide insights for basic and clinical research regarding MIS-C.


2020 ◽  
pp. 088506662096935
Author(s):  
Gema de Lama Caro-Patón ◽  
Amelia Martínez de Azagra-Garde ◽  
Alberto García-Salido ◽  
Marta Cabrero-Hernández ◽  
Amalia Tamariz ◽  
...  

Background: Multisystem inflammatory syndrome associated with SARS-CoV-2 infection can lead to myocardial injury and shock in children, likely the result of a severe inflammatory state, and can mimic Kawasaki disease. Objective: To describe the characteristics of shock and myocardial injury in children with confirmed or suspeted COVID-19 during the SARS-CoV-2 pandemic in Spain, including clinical presentation, laboratory and imaging findings, treatment, disease course, and outcome. An extensive literature review is provided. Methods: Retrospective case series including all children (age 1 month–18 years) admitted to a pediatric intensive care unit in Madrid, Spain, between March 15 and April 30, 2020 with suspected or confirmed SARS-CoV-2 infection and shock. Results: Twelve previously healthy patients with shock, age 5 to 14 years, were included. All required volume resuscitation and 75% required vasoactive/inotropic support. Distributive shock was present on admission in 67% (n = 8), and 4 patients (33%) showed features of cardiogenic shock. Myocardial injury was diagnosed in 67% (n = 8) and ventricular dysfunction in 33% (n = 4). The most common symptoms on presentation were fever (100%), anorexia (100%), diarrhea (75%), and vomiting (75%). Five patients showed signs of Kawasaki disease but none met the criteria for the classic form. Laboratory findings revealed lymphopenia (83%), thrombocytopenia (83%), and increased inflammatory markers (100%). Respiratory status was not significantly impacted. Chest X-ray showed bilateral alveolar infiltrates in 7 (58%) and bilateral pneumonia in 3 (25%). COVID-19 was confirmed in 11 cases (92%). All received empirical therapy against COVID-19, thromboprophylaxis and immunomodulation. Median stay in the PICU and inpatient ward was 4.5 and 10 days, respectively. No patients died. Conclusion: Multisystem inflammatory syndrome in children with COVID-19 can mimic Kawasaki disease and lead to a combination of distributive and cardiogenic shock, probably secondary to a hyperinflammatory state that remains to be precisely defined. Treatment strategies include hemodynamic support, empirical therapies against COVID-19, thromboprophylaxis, and immunomodulation.


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