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Multisystem inflammatory syndrome in children (MIS-C) and neonates (MIS-N) associated with COVID-19: optimizing
Eleanor J Molloy1,2,3, Natasha Nakra4, Chris Gale5
1Discipline of Paediatrics, Trinity College Dublin, the University of Dublin, Trinity Research in Childhood Centre (TRICC) and Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin, Ireland. Eleanor.molloy@tcd.ie.
Insights
Multisystem inflammatory syndrome in children (MIS-C) and neonates (MIS-N) post COVID-19 present unique challenges. Further research is needed for standardized definitions and treatments to improve outcomes.
Area of Science:
- Pediatric Infectious Diseases
- Immunology
- Cardiology
Background:
- Children and neonates generally exhibit milder COVID-19 symptoms due to innate immunity.
- However, multisystem inflammatory syndrome in children (MIS-C) and neonates (MIS-N) have emerged, characterized by severe inflammation and multi-organ dysfunction, particularly cardiac issues.
- MIS-C shares similarities with Kawasaki disease, suggesting a spectrum of inflammatory conditions.
Purpose of the Study:
- To review the latest understanding of the pathophysiology, clinical presentation, and management of MIS-C and MIS-N.
- To highlight the need for standardized definitions and international datasets for improved diagnosis and treatment.
- To explore how understanding immunological responses can aid in patient stratification and targeted therapies.
Main Methods:
- Literature review of recent studies on MIS-C and MIS-N.
- Analysis of clinical information, pathophysiology, and management strategies.
- Examination of immunological findings and their relation to inflammatory conditions.
Main Results:
- COVID-19 can lead to severe inflammatory syndromes in children and neonates, including cardiac complications.
- Current definitions and management protocols for MIS-C and MIS-N vary, necessitating international consensus.
- Immunological responses play a crucial role in disease presentation and severity.
Conclusions:
- Standardized international definitions and data collection for MIS-C and MIS-N are essential for effective management and clinical trials.
- Further research into the pathophysiology of these syndromes is critical for developing targeted therapies.
- Improved understanding of immunological responses will facilitate accurate diagnosis, prognostication, and optimal immunomodulatory treatments.
Abstract:
During the SARS-CoV-2-associated infection (COVID-19), pandemic initial reports suggested relative sparing of children inversely related to their age. Children and neonates have a decreased incidence of SARS-CoV-2 infection, and if infected they manifested a less severe phenotype, in part due to enhanced innate immune response. However, a multisystem inflammatory syndrome in children (MIS-C) or paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 emerged involving coronary artery aneurysms, cardiac dysfunction, and multiorgan inflammatory manifestations. MIS-C has many similarities to Kawasaki disease and other inflammatory conditions and may fit within a spectrum of inflammatory conditions based on immunological results. More recently neonates born to mothers with SARS-CoV-2 infection during pregnancy demonstrated evidence of a multisystem inflammatory syndrome with raised inflammatory markers and multiorgan, especially cardiac dysfunction that has been described as multisystem inflammatory syndrome in neonates (MIS-N). However, there is a variation in definitions and management algorithms for MIS-C and MIS-N. Further understanding of baseline immunological responses to allow stratification of patient groups and accurate diagnosis will aid prognostication, and inform optimal immunomodulatory therapies. IMPACT: Multisystem inflammatory system in children and neonates (MIS-C and MIS-N) post COVID require an internationally recognized consensus definition and international datasets to improve management and plan future clinical trials. This review incorporates the latest review of pathophysiology, clinical information, and management of MIS-C and MIS-N. Further understanding of the pathophysiology of MIS-C and MIS-N will allow future targeted therapies to prevent and limit clinical sequelae.
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