Timely Recognition and Early Multi-Step Antinflammatory Therapy May Prevent ICU Admission of Patients With MIS-C: Proposal for a Severity Score

Brisca, Giacomo; Consolaro, Alessandro; Caorsi, Roberta; Pirlo, Daniela; Tuo, Giulia; Campanello, Claudia; Castagnola, Elio; Moscatelli, Andrea; Gattorno, Marco; Ravelli, Angelo

doi:10.3389/fped.2021.783745

Cited by 31 publications

(42 citation statements)

References 31 publications

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“…Although IVIG is the first preferred one, steroids, and biological drugs such as anakinra and tocilizumab are also among the main treatment options. Steroids may be considered as a treatment option in milder forms, while severe or refractory cases should receive more intensive treatment [ 18 , 19 ]. Accordingly, patients in clusters II and III more commonly required intensive care, pulse steroid, anakinra, and inotropic agents.…”

Section: Discussionmentioning

confidence: 99%

The Multifaceted Presentation of the Multisystem Inflammatory Syndrome in Children: Data from a Cluster Analysis

Sönmez

Çağlayan

Yener

et al. 2022

JCM

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Background: The aim of this study was to evaluate the outcomes of patients with the multisystem inflammatory syndrome in children (MIS-C) according to phenotypes of disease and define the prognostic factors for the severe course. Methods: This cross-sectional study included 293 patients with MIS-C from seven pediatric rheumatology centers. A two-step cluster analysis was performed to define the spectrum of disease and their outcomes were compared between each group. Results: Four subgroups were identified as follows: cluster I, predominantly Kawasaki-like features (n = 100); cluster II, predominantly MAS-like features (n = 34); cluster III, predominantly LV dysfunction (n = 47); cluster IV, other presentations (n = 112). The duration of fever was longer in cluster II and the length of hospitalization was longer in both clusters II and III. Laboratory findings revealed lower lymphocyte and platelet counts and higher acute phase reactants (APRs) in cluster II, while patients in cluster IV showed less inflammation with lower APRs. The resolution of abnormal laboratory findings was longer in clusters II and III, while it was shortest in cluster IV. Seven patients died. Among them, four belonged to cluster II, while three were labeled as cluster III. Patients with severe course had higher levels of neutrophil–lymphocyte ratio, mean platelet volume, procalcitonin, ferritin, interleukin-6, fibrinogen, D-Dimer, BNP, and troponin-I, and lower levels of lymphocyte and platelet counts. Conclusion: As shown, MIS-C is not a single disease presenting with various clinical features and outcomes. Understanding the disease spectrum will provide individualized management.

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Section: Discussionmentioning

confidence: 99%

The Multifaceted Presentation of the Multisystem Inflammatory Syndrome in Children: Data from a Cluster Analysis

Sönmez

Çağlayan

Yener

et al. 2022

JCM

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show abstract

“…One explanation for the good response to steroids might be biological similiarities to toxic shock syndrome, involving the T-cells, as recently described by Sacco et al (24). Furthermore, recently appeared evidence supports early start of anti-inflammatory treatment (25,26). Our patients showed excellent response with improved blood pressure to initial volume administration, immunomodulatory and antiinflammatory treatment.…”

Section: Discussionmentioning

confidence: 83%

SARS-CoV-2 Associated Pediatric Inflammatory Multisystem Syndrome With a High Prevalence of Myocarditis – A Multicenter Evaluation of Clinical and Laboratory Characteristics, Treatment and Outcome

et al. 2022

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IntroductionPediatric inflammatory multisystem syndrome – temporally associated with SARS-CoV-2 infection (PIMS –TS) comprises a new disease entity having emerged after the COVID-19 outbreak in 2019.Materials and MethodsFor this multicenter, retrospective study children between 0 and 18 years with PIMS-TS between March 2020 and May 2021 were included, before availability of vaccination for children. Frequent SARS-CoV-2 variants at that period were the wildtype virus, alpha, beta and delta variants. Inclusion criteria were according to the PIMS-TS criteria, proposed by the Royal College of Pediatrics and WHO. Study aim was to review their clinical, laboratory and echocardiographic data with a focus on cardiac involvement.ResultsWe report 45 patients, median age 9 years, 64% male. SARS-CoV-2 antibodies were positive in 35/41 (85%). PIMS occurrence followed local COVID-19 peak incidence periods with a time lag. The most common symptoms at presentation were fever (98%), abdominal pain (89%) and rash (80%). Fever history of > 5 days was associated with decreased left ventricular function (p = 0.056). Arterial hypotension and cardiac dysfunction were documented in 72% patients, increased brain natriuretic peptide in 96% and increased cardiac troponin in 64% of the children. Echocardiography revealed mitral valve regurgitation (64%), coronary abnormalities (36%) and pericardial effusions (40%). Increased NT-proBNP was significantly associated with the need of inotropics (p < 0.05), which were necessary in 40% of the patients. Treatment comprised intravenous immunoglobulin (93%), systemic steroids (84%) and acetylsalicylic acid (100%; 26/45 started with high dosages). For insufficient response to this treatment, five (11%) children received the interleukin-1 receptor antagonist anakinra. All patients were discharged with almost resolved cardiac signs.ConclusionOur analysis of non-vaccinated children with PIMS-TS demonstrates that a considerable number have associated myocarditis requiring intensive care and inotropic support. Most children showed adequate response to intravenous immunoglobulin and steroids and good recovery. Further evaluation of pediatric patients with COVID-19 associated diseases is required to evaluate the impact of new virus variants.

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“…A review of the CDC MIS-C database 99 identified other factors associated with poor outcomes. Children ˃5 years, black or Hispanic ethnicity, and the presence of thrombocytopenia and lymphopenia were associated with worse outcomes.…”

Section: Resultsmentioning

confidence: 99%

Multisystem Inflammatory Syndrome in Children Associated with COVID-19 Infection: A Comprehensive Review

Meza-Contreras

Galdos-Bejar

Escalante-Kanashiro

2022

J Pediatr Intensive Care

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The Multisystem Inflammatory Syndrome in Children (MIS-C) is a postinfectious syndrome associated with coronavirus disease 2019 (COVID-19) disease in children. The aim of this study is to conduct a thorough review to assist health care professionals in diagnosis and management of this complication of COVID-19 disease in children. A thorough systematic review was conducted through an on-line search based on MIS-C with the primary focus on epidemiology, clinical characteristics, diagnosis, pathophysiology, management, and long-term follow-up. This syndrome is characterized by an exaggerated and uncontrolled release of proinflammatory cytokines involving dysfunction of both innate and adaptive immunity. In this review, a summary of observational studies and case reports was conducted, in which we found that MIS-C generates multiple-organ failure frequently presenting with hemodynamic instability further characterized by Kawasaki-like symptoms (such as persistent high fever, polymorphic rash, and bilateral conjunctivitis) and predominance of gastrointestinal and cardiovascular signs and symptoms. Keys to effective management involve early diagnosis, timely treatment and re-evaluation following hospital discharge. Diagnosis is marked by significant elevation of inflammatory biomarkers, laboratory evidence of COVID-19 infection or history of recent exposure, and absence of any other plausible explanation for the associated signs, symptoms, and presentation. Management includes hemodynamic stabilization, empiric antibiotic therapy (de-escalation if cultures and polymerase chain reaction studies indicate no bacterial co-infection), immunomodulatory therapy (methylprednisolone, intravenous immunoglobulin, anakinra, tocilizumab, siltuximab, Janus kinase inhibitors, tumor necrosis factor-α inhibitors), antivirals (remdesivir), and anticoagulation (acetylsalicylic acid, unfractionated or low-molecular-weight heparin or new oral anticoagulants). In addition, we identified poor prognostic risk factors to include concurrent comorbidities, blood-component consumption and marrow suppression (lymphopenia, thrombocytopenia), depletion of homeostatic components (hypoalbuminemia), and marked evidence of a hyperinflammatory response to include elevated values of ferritin, C-reactive protein, and D-dimer. MIS-C constitutes a postinfectious syndrome characterized by a marked cytokine storm, characterized by fever, bilateral conjunctivitis, and multiple organ dysfunction. Promoting future research and long-term follow-up will be essential for the development of guidelines and recommendations leading to effective identification and management of MIS-C.

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Timely Recognition and Early Multi-Step Antinflammatory Therapy May Prevent ICU Admission of Patients With MIS-C: Proposal for a Severity Score

Cited by 31 publications

References 31 publications

The Multifaceted Presentation of the Multisystem Inflammatory Syndrome in Children: Data from a Cluster Analysis

The Multifaceted Presentation of the Multisystem Inflammatory Syndrome in Children: Data from a Cluster Analysis

SARS-CoV-2 Associated Pediatric Inflammatory Multisystem Syndrome With a High Prevalence of Myocarditis – A Multicenter Evaluation of Clinical and Laboratory Characteristics, Treatment and Outcome

Multisystem Inflammatory Syndrome in Children Associated with COVID-19 Infection: A Comprehensive Review

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