SARS-CoV-2-associated multisystem inflammatory syndrome in children: clinical manifestations and the role of infliximab treatment

Abdel‐Haq, Nahed; Asmar, Basim I.; León, María Paz; McGrath, Eric; Arora, Harbir; Cashen, Katherine; Tilford, Bradley; Eddine, Ahmad Charaf; Sethuraman, Usha; Ang, Jocelyn Y.

doi:10.1007/s00431-021-03935-1

Cited by 61 publications

(65 citation statements)

References 30 publications

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“…Of these, 2055 duplicate studies were removed; 1663 studies were excluded after title and abstract screening, and 202 were excluded following full text screening based on the set inclusion criteria. Twenty-four studies [ [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] ] were ultimately included in the meta-analysis ( Fig. 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Fifteen studies [ 14 , 15 , [20] , [21] , [22] , [23] , [24] , [28] , [29] , [30] , [31] , [32] , [33] , 35 , 37 ] compared MIS-C and COVID-19, and nine of these studies [ 14 , 15 , [22] , [23] , [24] , 30 , 31 , 33 , 37 ] compared MIS-C with severe COVID-19. Eight studies [ [16] , [17] , [18] , [25] , [26] , [27] , 34 , 35 ] compared severe MIS-C with non-severe MIS-C, and three studies [ 17 , 19 , 26 ] compared MIS-C with CAA and MIS-C without CAA. The quality scores of the included studies ranged from 6 to 9, with three studies of moderate quality and 21 studies of high quality.…”

Section: Resultsmentioning

confidence: 99%

“…This analysis revealed that the study of Pouletty [ 25 ] was a major source of heterogeneity. After exclusion of this study, the result of REM [ [16] , [17] , [18] , 34 , 35 ] with moderate heterogeneity ( p < 0.05 , I 2 = 58.6%) indicated that the BNP levels of severe MIS-C patients were higher [SMD ( 95% CI ): 0.26 (0.04, 0.48), p < 0.05] than those of non-severe MIS-C patients.

Fig.…”

Section: Resultsmentioning

confidence: 99%

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Cardiac markers of multisystem inflammatory syndrome in children (MIS-C) in COVID-19 patients: A meta-analysis

Zhao

Patel

Huang

et al. 2021

The American Journal of Emergency Medicine

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Objective A meta-analysis of laboratory cardiac markers for multisystem inflammatory syndrome in children (MIS-C) was performed in patients with coronavirus disease 2019 (COVID-19). Methods Eight databases were searched until April 10, 2021, for studies on cardiac markers, including B-type natriuretic peptide (BNP)/N-terminal pro-BNP (NT-proBNP), troponin, aspartate aminotransferase (AST), in MIS-C patients. Results Of the 2583 participants enrolled in 24 studies, 1613 patients were diagnosed with MIS-C. MIS-C patients exhibited higher BNP levels than patients with non-severe COVID-19 [SMD ( 95% CI ): 1.13 (0.48, 1.77), p < 0.05]. No significant differences in BNP levels were observed between patients with MIS-C and severe COVID-19 [SMD ( 95% CI ): 0.29 (−0.07, 0.65), p = 0.117]. Comparisons of MIS-C patients to all COVID-19 patients revealed no significant differences in levels of troponin [SMD ( 95% CI ): 0.13 (−0.07, 0.32), p = 0.212] or AST [SMD ( 95% CI ): 0.10 (−0.11, 0.31), p = 0.336]. Compared to patients with non-severe MIS-C, those with severe MIS-C exhibited higher levels of BNP [SMD ( 95% CI ): 0.26 (0.04, 0.48), p < 0.05], but no differences in troponin [SMD ( 95% CI ): 0.05 (−0.06, 0.16) p = 0.387] or AST [SMD ( 95% CI ): 0.19 (−0.34, 0.71), p = 0.483] were observed. Moreover, there was no significant difference in BNP [SMD ( 95% CI ): −0.21 (−1.07, 0.64), p = 0.624] or troponin [SMD ( 95% CI ): −0.07 (−0.45, 0.31), p = 0.710] between MIS-C with and without coronary artery abnormality. Sensitivity analyses were performed to assess stability. No publication bias was detected based on Begg's test. Conclusions The key cardiac marker that showed differences between patients with MIS-C/non-severe COVID-19 and between patients with severe/non-severe MIS-C was BNP. Other markers, such as troponin and AST, did not exhibit notable differences in indicating cardiac injury between patients with MIS-C and COVID-19.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Fig.…”

Section: Resultsmentioning

confidence: 99%

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Cardiac markers of multisystem inflammatory syndrome in children (MIS-C) in COVID-19 patients: A meta-analysis

Zhao

Patel

Huang

et al. 2021

The American Journal of Emergency Medicine

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“…Gastrointestinal symptoms, such as vomiting, abdominal pain, and/or diarrhea, are more pronounced in children with MIS-C than the ones with KD [ 2 – 10 , 23 , 25 , 26 ]. According to the report of Abdel-Haqet et al the abdominal imaging findings of their MIS-C patients were lymphadenopathy, hepatosplenomegaly, mesenteric adenitis, calculous cholecystitis, pancreatitis, ascites, intestinal wall thickening, and inflammation [ 26 ]. Because some KD cases did not have abdominal ultrasound examination, the abovementioned gastrointestinal findings seem not common in KD [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

“…The standard recommended treatment for KD is a high dose of intravenous immunoglobulin (IVIG), i.e., 2 g/kg as a single infusion, along with a moderately high dose of acetylsalicylic acid (ASA). The infusion time is recommended to be over 10–12 h [ 26 ]. Nearly 10–20% of the KD cases are refractory.…”

Section: Introductionmentioning

confidence: 99%

Similarities and differences between multiple inflammatory syndrome in children associated with COVID-19 and Kawasaki disease: clinical presentations, diagnosis, and treatment

Zhang

2021

World J Pediatr

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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading rapidly around the world, while "multisystem inflammatory syndrome in children" (MIS-C) is a new type of syndrome that has now been reported in many countries. Similar and different characteristics between KD and MIS-C have been reported in a variety of literature. We aimed to focus on reviewing clinical presentations, diagnosis, and treatment of KD and MIS-C. Methods We searched articles in the electronic databases, including the Cochrane Library database, EMBASE, and MED-LINE with the keywords "multiple inflammatory syndrome" and/or "COVID-19" and/or "Kawasaki disease" and "children". Results Main presentations of MIS-C and KD include fever, rashes, mucous membrane involvement, conjunctivitis, hands and feet erythema/edema, and cervical lymphadenopathy. However, compared with the highest incidence of KD among some Asian countries, MIS-C is common among Black and Hispanic children. MIS-C is common in older children and teenagers, whereas classic KD is common in children under five years of age. Gastrointestinal symptoms, shock, and coagulopathy are common in MIS-C patients but are not common in classic KD. Cardiac manifestations are more common than KD, including myocarditis with cardiac dysfunction and coronary artery dilation or aneurysms. Severe cases in MIS-C present with vasodilated or cardiogenic shock that requires fluid resuscitation, muscular support, and even mechanical ventilation and extracorporeal membrane oxygenation (ECMO), whereas KD rarely presents with these manifestations and requires these treatments. Increased serum ferritin, leukopenia, lymphopenia and thrombocytopenia are common in MIS-C. However, thrombocytosis is a characteristic feature of KD. Intravenous immunoglobulin (IVIG) and moderate-high dose aspirin are still a standard recommended treatment for KD. In addition to the above-mentioned medications, steroids and biological drugs are frequently used in patients with MIS-C. Most of the children with KD have a good prognosis; however, the longterm clinical outcomes of MIS-C are not clear. Conclusions The overall presentation and treatment of MIS-C appear to overlap with KD. However, there are still great differences between the syndromes, and it is controversial to say whether MIS-C is a new entity or is a "severe type" of KD.

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American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS–CoV‐2 and Hyperinflammation in Pediatric COVID‐19: Version 3

Henderson

Canna

Friedman

et al. 2022

Arthritis & Rheumatology

164

201

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Objective To provide guidance on the management of Multisystem Inflammatory Syndrome in Children (MIS‐C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late in the course of SARS–CoV‐2 infection. Recommendations are also provided for children with hyperinflammation during COVID‐19, the acute, infectious phase of SARS–CoV‐2 infection. Methods The Task Force is composed of 9 pediatric rheumatologists and 2 adult rheumatologists, 2 pediatric cardiologists, 2 pediatric infectious disease specialists, and 1 pediatric critical care physician. Preliminary statements addressing clinical questions related to MIS‐C and hyperinflammation in COVID‐19 were developed based on evidence reports. Consensus was built through a modified Delphi process that involved anonymous voting and webinar discussion. A 9‐point scale was used to determine the appropriateness of each statement (median scores of 1–3 for inappropriate, 4–6 for uncertain, and 7–9 for appropriate). Consensus was rated as low, moderate, or high based on dispersion of the votes. Approved guidance statements were those that were classified as appropriate with moderate or high levels of consensus, which were prespecified before voting. Results The guidance was approved in June 2020 and updated in November 2020 and October 2021, and consists of 41 final guidance statements accompanied by flow diagrams depicting the diagnostic pathway for MIS‐C and recommendations for initial immunomodulatory treatment of MIS‐C. Conclusion Our understanding of SARS–CoV‐2–related syndromes in the pediatric population continues to evolve. This guidance document reflects currently available evidence coupled with expert opinion, and will be revised as further evidence becomes available.

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SARS-CoV-2-associated multisystem inflammatory syndrome in children: clinical manifestations and the role of infliximab treatment

Cited by 61 publications

References 30 publications

Cardiac markers of multisystem inflammatory syndrome in children (MIS-C) in COVID-19 patients: A meta-analysis

Cardiac markers of multisystem inflammatory syndrome in children (MIS-C) in COVID-19 patients: A meta-analysis

Similarities and differences between multiple inflammatory syndrome in children associated with COVID-19 and Kawasaki disease: clinical presentations, diagnosis, and treatment

American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS–CoV‐2 and Hyperinflammation in Pediatric COVID‐19: Version 3

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