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Article ; Online: Pediatric Coronavirus Disease-2019-Associated Multisystem Inflammatory Syndrome.

Shulman, Stanford T

Journal of the Pediatric Infectious Diseases Society

2020 Volume 9, Issue 3, Page(s) 285–286

MeSH term(s)	Betacoronavirus ; COVID-19 ; Child ; Coronavirus Infections/complications ; Coronavirus Infections/epidemiology ; Humans ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/epidemiology ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome/epidemiology ; Systemic Inflammatory Response Syndrome/virology ; United States/epidemiology
Keywords	covid19
Language	English
Publishing date	2020-05-22
Publishing country	England
Document type	Editorial
ZDB-ID	2668791-4
ISSN	2048-7207 ; 2048-7193
ISSN (online)	2048-7207
ISSN	2048-7193
DOI	10.1093/jpids/piaa062
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Article: Pediatric Coronavirus Disease-2019-Associated Multisystem Inflammatory Syndrome

Shulman, Stanford T

J Pediatric Infect Dis Soc

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #342878
Database	COVID19

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Article: Fatal Arrhythmic Complications of Multisystemic Inflammatory Syndrome (MIS-C) in a Pediatric Patient.

Oragui, Chika C / Dilibe, Arthur

Cureus

2024 Volume 16, Issue 5, Page(s) e60927

Abstract: In 2019, the emergence of the coronavirus disease 2019 (COVID-19) virus triggered a global pandemic ... This syndrome was later classified as multisystem inflammatory syndrome in children (MIS-C) by the Pediatric ... syndrome affecting multiple organ systems emerged, sharing similarities with Kawasaki's disease ...

Abstract	In 2019, the emergence of the coronavirus disease 2019 (COVID-19) virus triggered a global pandemic, reminiscent of the magnitude witnessed during the flu pandemic of 1918. Initially, children often presented with either asymptomatic or mild upper respiratory tract infection symptoms. However, in the post-acute phase, a distinct syndrome affecting multiple organ systems emerged, sharing similarities with Kawasaki's disease. This syndrome was later classified as multisystem inflammatory syndrome in children (MIS-C) by the Pediatric Intensive Care Society in April 2020. Notably, cardiac manifestations and complications associated with COVID-19 constitute a significant source of morbidity and mortality, characterized by left ventricular dysfunction, cardiac conduction abnormalities, and arrhythmias. Although cases of arrhythmias with MIS-C are rare in the literature, we present a unique case involving a 14-year-old without known cardiac risk factors who presented with conduction abnormalities and fatal arrhythmias secondary to MIS-C.
Language	English
Publishing date	2024-05-23
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.60927
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Article ; Online: Severe pediatric COVID-19: a review from the clinical and immunopathophysiological perspectives.

Sun, Yi-Kan / Wang, Can / Lin, Pei-Quan / Hu, Lei / Ye, Jing / Gao, Zhi-Gang / Lin, Ru / Li, Hao-Min / Shu, Qiang / Huang, Li-Su / Tan, Lin-Hua

World journal of pediatrics : WJP

2024 Volume 20, Issue 4, Page(s) 307–324

Abstract: Background: Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children ... manifestations. Multisystem inflammatory syndrome in children (MIS-C), a potentially life-threatening immune ... mediated condition chronologically associated with COVID-19 exposure, denotes another scientific and ...

Abstract	Background: Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children. However, severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times, meriting further attention from clinicians. Meanwhile, the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely understood. Data sources: A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed, Embase, and Wanfang databases. Searched keywords included "COVID-19 in children", "severe pediatric COVID-19", and "critical illness in children with COVID-19". Results: Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated status. Acute respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations, while various forms of cardiovascular and neurological involvement may also be seen. Multiple immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways, whose dysregulation in severe and critical diseases translates into adverse clinical manifestations. Multisystem inflammatory syndrome in children (MIS-C), a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure, denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric immunity. Despite the considerable dissimilarities between the pediatric and adult immune systems, clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult guidelines. Conclusions: Severe pediatric COVID-19 can affect multiple organ systems. The dysregulated immune pathways in severe COVID-19 shape the disease course, epitomize the vast functional diversity of the pediatric immune system and highlight the immunophenotypical differences between children and adults. Consequently, further research may be warranted to adequately address them in pediatric-specific clinical practice guidelines.
MeSH term(s)	Humans ; COVID-19/immunology ; COVID-19/complications ; Child ; Systemic Inflammatory Response Syndrome/immunology ; Systemic Inflammatory Response Syndrome/physiopathology ; Severity of Illness Index
Language	English
Publishing date	2024-02-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2236681-7
ISSN	1867-0687 ; 1708-8569
ISSN (online)	1867-0687
ISSN	1708-8569
DOI	10.1007/s12519-023-00790-y
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Article ; Online: Longitudinal Echocardiographic Follow-Up of a Pediatric Multisystem Inflammatory Syndrome Cohort.

Ramamoorthy, Jaikumar Govindaswamy / Avinash, Anantharaj / Karunakar, Pediredla / Parale, Chinmay / Velayutham, Ramanathan / Sukumaran, Suresh Kumar / Balaguru, Sridhar / Parameswaran, Narayanan / M, Mugunthan / Dhodapkar, Rahul / Basu, Debdatta / Selvaraj, Raja / Satheesh, Santhosh / Biswal, Niranjan

Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir

2024 Volume 52, Issue 3, Page(s) 189–198

Abstract: ... at admission, 1.5 months, and 3 months. Coronavirus Disease 2019 (COVID-19) antibody titers were assessed ... of patients who were tested, 88.9% tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS ... inflammatory syndrome in children (MIS-C). This study aimed to examine the recovery of affected cardiovascular ...

Title translation	Pediatrik Multisistem İnflamatuvar Sendrom Kohortunun Uzun Dönemli Ekokardiyografik İzlemi.
Abstract	Objective: Significant involvement of the cardiovascular system is known in multisystem inflammatory syndrome in children (MIS-C). This study aimed to examine the recovery of affected cardiovascular parameters over a medium-term follow-up. Methods: A cohort of 69 children was studied prospectively. Assessments of left ventricular (LV) function and coronary artery abnormalities (CAA) were conducted at admission, 1.5 months, and 3 months. Coronavirus Disease 2019 (COVID-19) antibody titers were assessed at these three time points. Echocardiographic and antibody parameters (rising/decreasing) were analyzed for correlation. Outcomes were assessed using logistic regression. Results: At admission, among the 78.2% of patients who were tested, 88.9% tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). A quarter of the patients had pericardial effusion, and half had valvulitis. Decreased ejection fraction, global circumferential strain (GCS), and global longitudinal strain (GLS) were seen in 54.4%, 68.6%, and 35.8% of patients, respectively. CAAs were observed in 27.78% of patients. Systolic dysfunction was significantly associated with older age. During follow-up, severe LV dysfunction normalized within 6-7 weeks, while mild to moderate dysfunction reached normalcy by two weeks. Both GCS and GLS reached normalcy within a median of two weeks. Diastolic parameters recovered by six weeks. Most small and moderate coronary aneurysms resolved, but a giant aneurysm in an infant remained large even after 15 months. Trends in antibodies and ejection fraction (EF) at three months were significantly correlated. Admission EF, GLS (at 6 weeks) and deceleration time (at 3 months) were significantly associated with intensive care unit (ICU) admission. The median segmental strain of the cohort remained low in certain segments at three months. Conclusion: Smaller CAAs resolve, whereas giant CAAs persist. EF and GLS are important predictors of Pediatric Intensive Care Unit (PICU) stay. The residual impairment of median segmental strain and persistent diastolic dysfunction at three months indicate the need for long-term follow-up.
MeSH term(s)	Infant ; Humans ; Child ; Follow-Up Studies ; Echocardiography ; COVID-19/diagnostic imaging ; COVID-19/complications ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome
Language	English
Publishing date	2024-04-04
Publishing country	Turkey
Document type	Journal Article
ZDB-ID	1215217-1
ISSN	1308-4488 ; 1016-5169
ISSN (online)	1308-4488
ISSN	1016-5169
DOI	10.5543/tkda.2023.60940
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Zs.A 4156: Show issues

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Article ; Online: COVID 19 infection: Pediatric perspectives.

Adeyinka, Adebayo / Bailey, Keneisha / Pierre, Louisdon / Kondamudi, Noah

Journal of the American College of Emergency Physicians open

2021 Volume 2, Issue 1, Page(s) e12375

Abstract: ... Recently, a new entity associated with COVID-19 called multisystem inflammatory syndrome in children (MIS-C ... The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome ... coronavirus 2 (SARS-CoV-2) has rapidly spread across the globe, causing innumerable deaths and a massive ...

Abstract	The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the globe, causing innumerable deaths and a massive economic catastrophe. Exposure to household members with confirmed COVID-19 is the most common source of infection among children. Children are just as likely as adults to get infected with SARS-CoV-2. Most children are asymptomatic and when symptoms occur, they are usually mild. Infants <12 months old are at a higher risk for severe or critical disease. COVID-19 is diagnosed the same way in pediatric population as adults by testing specimen obtained from upper respiratory tract for nucleic acid amplification test (NAAT) using reverse transcriptase viral polymerase chain reaction (RT-PCR). The common laboratory findings in hospitalized patient include leukopenia, lymphopenia, and increased levels of inflammatory markers. Chest X-ray findings are variable and computed tomography scans of the chest may show ground glass opacities similar to adults or non-specific findings. Prevention is the primary intervention strategy. Recently the U.S. Food and Drug Administration (FDA) has provided emergency authorization of the Pfizer-BioNTech COVID-19 vaccine and many other vaccine candidates are in the investigational stage. There is limited data in children on the use of antivirals, hydroxychloroquine, azithromycin, monoclonal antibody, and convalescent plasma. Oxygen therapy is required in hypoxic children (saturation <92%). Similar to adults, other measures to maintain oxygenation such as high flow nasal cannula, CPAP, or ventilatory support may be needed. Ventilatory management strategies should include use of low tidal volumes (5-6 cc/kg), high positive expiratory pressure, adequate sedation, paralysis, and prone positioning. Recently, a new entity associated with COVID-19 called multisystem inflammatory syndrome in children (MIS-C) has emerged. Clinical, laboratory, and epidemiological criteria are the basis for this diagnosis. Management options include ICU admission, steroids, intravenous gamma globulin, aspirin, anakinra, and anticoagulants. Vasoactive-inotropic score (VIS) is used to guide vasopressor support.
Language	English
Publishing date	2021-01-29
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2688-1152
ISSN (online)	2688-1152
DOI	10.1002/emp2.12375
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Article ; Online: Ocular manifestations of COVID-19 in the pediatric age group.

Alnahdi, Muhannad A / Alkharashi, Maan

European journal of ophthalmology

2022 , Page(s) 11206721221116210

Abstract: The coronavirus disease 2019 (COVID-19) is now known to be associated with several ocular ... in the new multisystem inflammatory syndrome in children (MIS-C), a novel entity associated by COVID-19 ... in the pediatric age group. We aim to outline the various pediatric ocular manifestations described ...

Abstract	The coronavirus disease 2019 (COVID-19) is now known to be associated with several ocular manifestations. The literature thoroughly discussed those that affect adults, with a lesser focus in the pediatric age group. We aim to outline the various pediatric ocular manifestations described in the literature. The manifestations may be divided into isolated events attributed to COVID-19 or occurring in the new multisystem inflammatory syndrome in children (MIS-C), a novel entity associated by COVID-19 infection. Ocular manifestations have virtually affected all ages. They manifested in neonates, infants, children, and adolescents. Episcleritis, conjunctivitis, optic neuritis, cranial nerve palsies, retinal vein occlusion, retinal vasculitis, retinal changes, orbital myositis, orbital cellulitis were reported in the literature with this emerging viral illness. Conjunctivitis was the most common ocular manifestation in MIS-C in nearly half of the patients. Other ocular manifestations in MIS-C were anterior uveitis, corneal epitheliopathy, optic neuritis, idiopathic intracranial hypertension, and retinitis. The clinical outcome was favorable, and children regain their visual ability with minimal or no deficits in most of the cases. Further follow-up may be warranted to better understand the long-term effects and visual prognosis.
Language	English
Publishing date	2022-07-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	1089461-5
ISSN	1724-6016 ; 1120-6721
ISSN (online)	1724-6016
ISSN	1120-6721
DOI	10.1177/11206721221116210
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Zs.A 3342: Show issues

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Article ; Online: Severe acute respiratory syndrome coronavirus-2-related and imputable deaths in children: results from the French pediatric national registry.

Lockhart-Bouron, Marguerite / Vanel, Noémie / Levy, Michael / Briant, Anaïs R / Javouhey, Etienne / Breinig, Sophie / Dina, Julia / Caseris, Marion / Angoulvant, François / Leteurtre, Stéphane / Recher, Morgan / Brossier, David W

World journal of pediatrics : WJP

2024

Abstract: ... inflammatory multisystem syndrome (PIMS) recorded in the French PICU registry (PICURe) between September 1 ... Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible ... PCRs) [acute corona virus disease 2019 (COVID-19) or incidental SARS-CoV-2 infection] and/or pediatric ...

Abstract	Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for an important mortality rate worldwide. We aimed to evaluate the actual imputability of SARS-CoV-2 on the mortality rate associated with SARS-CoV-2-related illnesses in the pediatric intensive care unit (PICU). Secondary objectives were to identify risk factors for death. Methods: This national multicenter comparative study comprised all patients under 18 years old with positive SARS-CoV-2 polymerase chain reactions (PCRs) [acute corona virus disease 2019 (COVID-19) or incidental SARS-CoV-2 infection] and/or pediatric inflammatory multisystem syndrome (PIMS) recorded in the French PICU registry (PICURe) between September 1, 2021, and August 31, 2022. Included patients were classified and compared according to their living status at the end of their PICU stay. Deceased patients were evaluated by four experts in the field of pediatric infectiology and/or pediatric intensive care. The imputability of SARS-CoV-2 as the cause of death was classified into four categories: certain, very probable, possible, or unlikely, and was defined by any of the first three categories. Results: There were 948 patients included of which 43 died (4.5%). From this, 26 deaths (67%) could be attributed to SARS-CoV-2 infection, with an overall mortality rate of 2.8%. The imputability of death to SARS-CoV-2 was considered certain in only one case (0.1%). Deceased patients suffered more often from comorbidities, especially heart disease, neurological disorders, hematological disease, cancer, and obesity. None of the deceased patients were admitted for pediatric inflammatory multisystem syndrome (PIMS). Mortality risk factors were male gender, cardiac comorbidities, cancer, and acute respiratory distress syndrome. Conclusions: SARS-CoV-2 mortality in the French pediatric population was low. Even though the imputability of SARS-CoV-2 on mortality was considered in almost two-thirds of cases, this imputability was considered certain in only one case.
Language	English
Publishing date	2024-03-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2236681-7
ISSN	1867-0687 ; 1708-8569
ISSN (online)	1867-0687
ISSN	1708-8569
DOI	10.1007/s12519-023-00791-x
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Article: Kidney involvement in multisystem inflammatory syndrome in children: a pediatric nephrologist's perspective.

Sethi, Sidharth Kumar / Rana, Abhyuday / Adnani, Harsha / McCulloch, Mignon / Alhasan, Khalid / Sultana, Azmeri / Safadi, Rama / Agrawal, Nirav / Raina, Rupesh

Clinical kidney journal

2021 Volume 14, Issue 9, Page(s) 2000–2011

Abstract: ... morbidity and mortality. There are several reports of a direct viral tropism of coronavirus disease 2019 and ... The initial report of the multisystem inflammatory syndrome in children (MIS-C) was from the UK ... ranging from 10% to 46%. Kidney involvement following severe acute respiratory syndrome coronavirus 2 ...

Abstract	The initial report of the multisystem inflammatory syndrome in children (MIS-C) was from the UK in April 2020; since then, cases have been reported worldwide. Renal involvement has been seen commonly, ranging from 10% to 46%. Kidney involvement following severe acute respiratory syndrome coronavirus 2 infection in children with MIS-C is more common than initially thought and is associated with higher morbidity and mortality. There are several reports of a direct viral tropism of coronavirus disease 2019 and MIS-C-associated renal damage. This study's objective was to systematically review the current understanding of kidney involvement in children suffering from MIS-C. Based on our systemic literature search, 19 studies have either partially or fully discussed kidney involvement in MIS-C patients. Furthermore, we discuss the multifactorial pathogenesis contributing to acute kidney injury (AKI) development in MIS-C. The current review gives a pediatric nephrologist's perspective of the renal involvement in MIS-C, the incidence of AKI, the pathophysiology of AKI in MIS-C and the proposed therapeutic regimens available, including the need for kidney replacement therapy for a child with AKI associated with MIS-C. As the disease is rapidly evolving, more detailed clinical prospective studies are required to understand MIS-C and its role in AKI better.
Language	English
Publishing date	2021-04-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2655800-2
ISSN	2048-8513 ; 2048-8505
ISSN (online)	2048-8513
ISSN	2048-8505
DOI	10.1093/ckj/sfab073
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Article ; Online: Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19.

Sacco, Keith / Castagnoli, Riccardo / Vakkilainen, Svetlana / Liu, Can / Delmonte, Ottavia M / Oguz, Cihan / Kaplan, Ian M / Alehashemi, Sara / Burbelo, Peter D / Bhuyan, Farzana / de Jesus, Adriana A / Dobbs, Kerry / Rosen, Lindsey B / Cheng, Aristine / Shaw, Elana / Vakkilainen, Mikko S / Pala, Francesca / Lack, Justin / Zhang, Yu /

Fink, Danielle L / Oikonomou, Vasileios / Snow, Andrew L / Dalgard, Clifton L / Chen, Jinguo / Sellers, Brian A / Montealegre Sanchez, Gina A / Barron, Karyl / Rey-Jurado, Emma / Vial, Cecilia / Poli, Maria Cecilia / Licari, Amelia / Montagna, Daniela / Marseglia, Gian Luigi / Licciardi, Francesco / Ramenghi, Ugo / Discepolo, Valentina / Lo Vecchio, Andrea / Guarino, Alfredo / Eisenstein, Eli M / Imberti, Luisa / Sottini, Alessandra / Biondi, Andrea / Mató, Sayonara / Gerstbacher, Dana / Truong, Meng / Stack, Michael A / Magliocco, Mary / Bosticardo, Marita / Kawai, Tomoki / Danielson, Jeffrey J / Hulett, Tyler / Askenazi, Manor / Hu, Shaohui / Cohen, Jeffrey I / Su, Helen C / Kuhns, Douglas B / Lionakis, Michail S / Snyder, Thomas M / Holland, Steven M / Goldbach-Mansky, Raphaela / Tsang, John S / Notarangelo, Luigi D

Nature medicine

2022 Volume 28, Issue 5, Page(s) 1050–1062

Abstract: Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children ... infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem ... inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional ...

Abstract	Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n = 110) and MIS-C (n = 76), along with pediatric healthy controls (pHCs; n = 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-κB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A02, B35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy.
MeSH term(s)	COVID-19/complications ; COVID-19/genetics ; Child ; Humans ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome/genetics ; T-Lymphocytes
Language	English
Publishing date	2022-02-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-022-01724-3
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