Volume 10 - Special Issue                   J. Pediatr. Rev 2022, 10 - Special Issue: 367-388 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Kumar M, Swarnim S, Pallavi P. Clinical Characteristics of Multisystem Inflammatory Syndrome in Children and Young Adults With COVID-19: A Rapid Systematic Review. J. Pediatr. Rev. 2022; 10 :367-388
URL: http://jpr.mazums.ac.ir/article-1-432-en.html
1- Department of Pediatrics, All India Institute of Medical Sciences, Gorakhpur, India.
2- Department of Pediatrics, Maulana Azad Medical College, New Delhi, India.
3- Department of Pediatrics, Maulana Azad Medical College, New Delhi, India. , pallavi86.delhi@gmail.com
Full-Text [PDF 613 kb]   (541 Downloads)     |   Abstract (HTML)  (1370 Views)
Full-Text:   (212 Views)
1. Introduction
Several cases of a new kind of pneumonia were identified in Wuhan City, China, in 2019. This new disease is now a pandemic and a global health catastrophe. The World Health Organization (WHO) designated the disease as coronavirus disease (COVID-19), caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1). In initial reports, the morbidity of this disease was relatively mild in children and adolescents compared to the adult population (2). However, since late April 2020, several cases have been reported of children presenting with circulatory shock and systemic inflammation, with phenotypic similarity to Kawasaki disease (KD) and toxic shock syndrome (TSS). The first cases were reported from the United Kingdom as a series of eight previously healthy children presenting with hyperinflammation and cardiovascular shock (3), followed by similar reports from other parts of Europe and the United States of America. 
A case definition for this emerging hyperinflammatory disorder was formulated by The Royal College of Pediatrics and Child Health (RCPCH) in late April and was provisionally named pediatric inflammatory, multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) (4). Later, in May 2020, following a health alert issued by the New York State Department of Health, the Centers for Disease Control and Prevention (CDC) issued a clinical case definition and designated this syndrome as the multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 (5). WHO has also developed a preliminary case definition and case report form for this multisystem inflammatory disorder in children and adolescents (6). Case definitions of this pediatric inflammatory disorder, given by RCPCH, CDC, and WHO, have been summarized in supplementary Table 1.

There have been heterogeneous reports of MIS-C in the form of case reports or small case series. The lack of comprehensive clinical data describing the complete clinical spectrum, treatment options, and outcome of children and young adults under 21 years of age suffering from MIS-C has prompted this review.

2. Materials and Methods
This rapid review was initiated after registering the protocol in the International Prospective Register of Systematic Reviews (PROSPERO) database with registration No. CRD42020190751. This review was conducted following Cochrane guidance on Rapid Reviews (7) and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines (8) (Table 2).

Study objectives
The primary objective of this review was to systematically review the clinical characteristics, treatment options, and outcomes of MIS-C or KD-like hyperinflammatory states in children and young adults with COVID-19 infection.

Search strategy
Two authors independently searched PubMed and Embase databases from inception to July 3, 2020. The search was limited to publications in the English language. The search strategy consisted of CDC suggested COVID-19 search terms (9) along with a combination (using Boolean operator AND) of keywords and their corresponding Medical Subject Headings (MeSH). 

Novel coronavirus
Multisystem inflammatory syndrome in children

Kawasaki disease
Details of the search strategy used for PubMed and Embase databases are presented in supplementary Table 3.

Eligibility criteria
Search results were uploaded to Rayyan web applicationand no single method fulfills the principal requirements of speed with accuracy. Automation of systematic reviews is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making., We developed Rayyan (http://rayyan.qcri.org (10) for screening by two authors independently. We included all types of studies, including longitudinal studies, case series, case reports, or correspondences from all clinical settings reporting clinical-epidemiologic characteristics of MIS-C or KD-like illness in children and young adults up to the age of 21 years in the review. A third author screened all excluded records. Any disagreements regarding eligibility for inclusion were resolved by consensus.

Critical appraisal 
Critical appraisal and assessment of the risk bias in included studies were done by all authors independently using Joanna Briggs Institute Critical Appraisal Checklist for studies reporting prevalence data (11).

Data extraction 
Individual study data were extracted in a pre-designed format in Microsoft Excel by two authors independently. Study details included first author, location of study, study design, study period, demographic variables, clinical features, details of laboratory, radiological and other investigations, treatment details, and outcomes. Any disagreements related to collated data were resolved by consensus after discussion with the third author.

Data synthesis
Synthesis of included studies was performed through descriptive summaries (usually as a percentage) of demographic variables, clinical features, investigations performed, treatment details, and clinical outcomes.

3. Results 
Search results and critical appraisal
A total of 408 records were identified using the search mentioned above strategy. After excluding duplicate records, the title and abstracts of 301 articles were screened. In the initial screening of title and abstracts, 94 full-text articles were assessed for eligibility, and 55 articles were excluded. Of these rejected studies, 41 were reviews, correspondences, or editorials with no individual patient data; 13 studies did not meet the inclusion criteria for this review, and one study was excluded because it was in the Swedish language. Then, 39 remaining articles (3, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50) were subjected to critical appraisal using Joanna Briggs Institute Checklists and were included for qualitative synthesis after confirming their methodological rigor.

Included studies
Twenty out of 39 included studies were from Europe, 7 studies from the UK and 7 from France, and 16 studies from the USA. Three case reports from India and 1 case report from Israel were also included. Of the 39 included studies, 16 were case reports, 9 case series, 10 retrospective observational studies, and 4 prospective observational studies or surveillance studies. The study period of most of the included studies ranged from March to April 2020, with Verdoni et al. (38) reporting data from as early as February 2020 (Table 1). 

A total of 39 studies were included in this rapid review, constituting 799 participants with 446 males (55.8%). Feldstein et al. (44) and Belot et al. (26) studies were the largest studies in terms of participants, with 186 and 108 participants, respectively. The median age of participants in both studies was 8 years. Similar median age was reported by other included studies (3, 16, 23, 34). The youngest participant was a 4-month-old baby reported by Acharyya et al. (36), while in studies by Miller et al. (32) and Riollano-Cruz et al. (49), the maximum age of included participants was 20 years. Ancestry or racial characteristics were reported in 16 of 39 studies. Many studies from the USA and the UK documented an increased incidence of MIS-C in Black/Afro-American/Non-Hispanic races compared to other races or ethnicities (3, 13, 17, 24, 28, 34, 39, 44, 45).

Clinical features
Fever was a ubiquitous presenting feature in 96.4% (667/692) of patients. Respiratory symptoms were reported in 28 studies comprising 589 patients. Runny nose, sore throat, or cough was reported in 10% (59/589) of patients, while dyspnea was relatively more common and affected 33% of the patients (194/589). Gastrointestinal symptoms were the most common extra-pulmonary systemic feature of MIS-C. More than 50% of the participants in 25 of the 39 included studies presented with either abdominal pain, vomiting, or diarrhea. Neurocognitive features were present in 27.1 % of patients (162/597).
Amongst the symptoms characteristic of KD, rash and non-purulent conjunctivitis were most common, seen in 58.8% (374/635) and 59.9% (377/629), respectively. Other KD-like symptoms were lip/oral changes in 42.4% (242/570) of patients, extremity changes in 32.3% (135/417) of patients, and cervical lymphadenopathy in 17.95% (88/490) patients. More than half of the children in the hyperinflammatory state developed circulatory insufficiency, as 53% (358/668) of patients developed shock.
Comorbidities were reported in the participants of 12 of the 39 included studies. Obesity was the commonest comorbidity, seen in 113/581 (19.4%), asthma in 54/581 (9.2%), and various comorbidities in 49/581 (8.4%) patients.

Laboratory investigations
Table 3 summarizes the median values of laboratory investigations. Blood counts trends were non-specific. Out of 25 studies reporting median white cell counts, 14 showed trend towards leukocytosis (13, 14, 16, 17, 18, 19, 21, 23, 24, 34, 36, 39, 43, 46). All 22 studies reporting median lymphocyte count had lymphopenia except 3 studies (15, 30, 46). In 6 case reports, children with features of MIS-C were anemic (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 33, 36, 43) while median hemoglobin value was less than 11 g/dL in 3 other studies (24, 34, 46).
For documenting the underlying hyperinflammatory state, 35 studies reported median C-reactive protein (CRP) values raised in all except the French study by Leon et al. (15). The median value of other inflammatory markers was reported high in all reporting studies. These markers included procalcitonin (PCT) (19 studies), serum ferritin (28 studies), D-dimer (25 studies), and Interleukin (IL)- 6 (12 studies). 
Underlying cardiac dysfunction associated with MIS-C was documented through measurement of cardiac markers like troponin (25 studies) and pro-BNP (pro-brain natriuretic peptide) (21 studies). Median values of these cardiac markers were raised in all the reporting studies.
Underlying SARS-CoV-2 infection was more often documented through serology. Of all patients included in this review, 212 of 560 (37.8%) had positive nasopharyngeal reverse transcription-polymerase chain reaction (RT-PCR), while 79.15% (410/518) had antibodies against SARS-CoV-2.

Radiological investigations
Chest x-ray abnormality was found in 161 of 369 (43.6%) patients. Very few studies reported imaging findings of chest computed tomography (CT). Hameed et al. (48) performed a chest CT scan on 33 of 35 patients. The main findings were basal consolidation with the collapse in 39% and pleural effusion in 30% of the patients. Three children had bilateral diffuse ground-glass opacities along with patchy dense consolidation. Dufort et al. reported either abnormal chest x-ray or abnormal chest CT in 35% of the patients (35) (Table 4).

In echocardiography, ventricular dysfunction was the major abnormality found in 50.2% (284/565) of the patients, while coronary dilatation was seen in only 15% (87/577) of the cases. Other findings like valvular involvement and pericardial effusion were documented in around 33% (148/446) of the cases.

Treatment and outcomes
About 77% (571/741) of patients in this review required admission to the intensive care unit (ICU). Mechanical ventilation was required in 211 of 773 (27.2%) patients, while 56.35% (448/795) required inotropic support to maintain hemodynamic stability (Table 5).

Amongst treatment modalities used to manage MIS-C, intravenous immunoglobulins (IVIG) was the most common modality, which was used in 510 of 653 patients (78.1%), followed by steroids which were administered to 357 of 639 (55.8%) patients. In refractory cases, immunomodulators were used. Anti-IL-1 (anakinra and others) use was reported in 10.8% (54/500), anti-IL-6 (tocilizumab and others) in 10.2% (51/500), and infliximab in 2% (10/500) of patients. Very few studies reported the use of aspirin and anticoagulants. Aspirin was given in 80 of 108 (74%), while anticoagulants were used in 234 of 380 (61.5%) patients. The mortality rate of MIS-C documented in this review was 1.5%, with only 12 out of 797 participants succumbing to it. Median duration of hospital admission was 7-8 days in many studies (23, 31, 34, 41, 46, 49).

4. Discussion 
There is significant scope and need for studies defining the clinical characteristics of MIS-C in children and young adults because most of the 39 studies in this review were either case reports or case series with small sample sizes. However, their results provide a sneak peek into this previously unrecognized clinical syndrome associated with COVID-19 with KD-like presentation.
Although initial reports of MIS-C reported a phenotypic resemblance to KD, our review emphasizes specific important demographic differences. The median age of MIS-C presentation appears to be higher than that for KD. There is an increased incidence of this clinical entity in Black/Afro-American races than KD, which is more common in Asian ethnicities. Barring 3 case reports from India, none of the studies in this review hailed from Asia despite the COVID-19 pandemic having its origin in China. This racial predilection may emanate from genetic differences, mutations in the virus, or undetermined factors.
Certain manifestations of MIS-C are worth mentioning. As documented in this review, unlike KD, gastrointestinal symptoms are predominant in MIS-C. Similarly, circulatory insufficiency and myocardial dysfunction are distinctly more common than KD, affecting more than half of patients with MIS-C, as evident from clinical manifestations and increased cardiac markers reported by studies included in this review.
The hyperinflammatory state of MIS-C is well established through laboratory evidence synthesized in this review. This hyperinflammation is similar to cytokine storm syndrome associated with acute COVID-19 infection in adults, albeit delayed. Delay in interferon response and slow viral clearing has been putatively implicated in the pathogenesis of MIS-C (51).
Feldstein et al. have documented a temporal association between MIS-C and preceding SARS-CoV-2 infection (44). Also, based on the results of this review, the serological evidence of a preceding SARS-CoV-2 infection is more common than positive nasopharyngeal RT-PCR for viral nucleic acid, which probably suggests that these hyperinflammatory states are post-infectious phenomena brought about by a dysregulated immune response. However, given the lack of definitive data regarding causality other than the temporal association, an evolving body of evidence describing this clinical syndrome, and a myriad of clinical mimickers of its presentation, it is pertinent that the scientific community adopts a meticulous as well as the cautious approach in attributing these hyperinflammatory states to COVID-19.
The collated echocardiographic findings in this review show that ventricular dysfunction was more common than coronary changes in MIS-C. This pattern is distinct from KD, where coronary artery abnormalities are reported in about one-fourth of cases (52). Also, given the lack of follow-up data, the long-term cardiac sequel of MIS-C is still unknown.
Intravenous immunoglobulin (IVIG) was used as the primary treatment modality in 78.1% of participants included in this review. The indirect evidence for the use of IVIG in MIS-C stems from its use in other conditions with phenotypic similarities, such as KD or toxic shock syndrome (TSS). Adjunctive therapy has been used in the form of steroids and, in some studies, immunomodulators of IL-1 and IL-6. Their use, with a mostly favorable response, lends credence to the putative theory of MIS-C being a diffusely hyperinflammatory state of the dysregulated immune response. 
Another important finding of this review is that 77% of children required intensive care with a need for mechanical ventilation in about a quarter of included participants. Hence, early recognition and treatment in an appropriate setting are necessary to decrease mortality which in this review was 1.5%.

5. Conclusion
MIS-C is a clinical mimic of hyperinflammatory states such as KD and TSS. However, evidence collated in this review show notable clinical and epidemiological differences compared to KD, like an increased median age of presentation, a higher incidence in Afro-Americans, the preponderance of gastrointestinal manifestations, and ventricular dysfunction. More extensive epidemiological studies will help in better defining this entity and delineating its phenotypic subtypes
There are inherent limitations of our rapid review. Our search strategy had a selection bias as only articles in English were included. Despite the systematic search of two major databases of PubMed and Embase, the data from studies indexed in the Chinese database of China National Knowledge Infrastructure (CNKI) has not been included. In the absence of a consensus clinical definition, this review includes all studies which have reported a hyperinflammatory state resembling KD, which brings heterogeneity and inadequate generalizability to its findings. This rapid review lacks follow-up data to characterize squeal and reflect the evolving nature of both the pandemic and our understanding of it.

Ethical Considerations
Compliance with ethical guidelines

There were no ethical considerations to be considered in this research.

This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors. 

Authors' contributions
Conceptualized and Methodology: Manish Kumar; Data collection: Swarnim Swarnim and Pallavi Pallavi; Investigation: Manish Kumar; Writing – original draft, and Writing – review & editing: All authors.

Conflicts of interest
The authors declared no conflict of interest.

  1. World Health Organization (WHO). Coronavirus disease (COVID-19) pandemic [Internet]. 2020 [Updated 2022]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019
  2. Liguoro I, Pilotto Ch, Bonanni M, Ferrari ME, Pusiol A, Nocerino A, et al. SARS-COV-2 infection in children and newborns: A systematic review. European Journal of Pediatrics. 2020; 179(7):1029-46. [DOI:10.1007/s00431-020-03684-7] [PMID] [PMCID]
  3. Riphagen Sh, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. The Lancet. 2020; 395(10237):1607-8. [DOI:10.1016/S0140-6736(20)31094-1]
  4. Royal College of Paediatrics and Child Health. Guidance: Paediatric multisystem inflammatory syndrome temporally associated with COVID-19 [Internet]. 2020 [Updated 2020]. Available from: https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20.pdf
  5. Health Alert Network (HAN). HAN00432: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with coronavirus disease 2019 (COVID-19) [Internet]. 2020 [Updated 2020 May 14]. Available from: https://emergency.cdc.gov/han/2020/han00432.asp
  6. World Health Organization. Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19: Scientific brief [Internet]. 2020 [Updated 2020 May 15]. Available from: https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-COVID-19
  7. Garritty C, Gartlehner G, Kamel C, King VJ, Nussbaumer-Streit B, Stevens A, et al. Cochrane rapid reviews. Interim guidance from the cochrane rapid reviews methods group [Internet]. 2020 [Updated 2020 March]. Available from: https://methods.cochrane.org/rapidreviews/sites/methods.cochrane./cochrane_rr_-_guidance-23mar2020.pdf
  8. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Medicine. 2009; 6(7):e1000097. [DOI:10.1371/journal.pmed.1000097] [PMID] [PMCID]
  9. Centers for Disease Control and Prevention. COVID-19 PubMed search alert [Internet]. 2020 [Updated 2020 October 9]. Available from: https://www.cdc.gov/library/researchguides/2019novelcoronavirus/pubmedsearchalert.html
  10. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan - a web and mobile app for systematic reviews. Systematic Reviews. 2016; 5:210. [DOI:10.1186/s13643-016-0384-4] [PMID] [PMCID]
  11. Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C. Chapter 5: Systematic reviews of prevalence and incidence. In: Aromataris E, Munn Z, editors. JBI Manual for Evidence Synthesis. Adelaide: JBI; 2020. https://jbi-global-wiki.refined.site/space/MANUAL/3283910689
  12. Jones VG, Mills M, Suarez D, Hogan CA, Yeh D, Segal JB, et al. COVID-19 and Kawasaki disease: Novel virus and novel case. Hospital Pediatrics. 2020; 10(6):537-40. [DOI:10.1542/hpeds.2020-0123] [PMID]
  13. Chiotos K, Bassiri H, Behrens EM, Blatz AM, Chang J, Diorio C, et al. Multisystem inflammatory syndrome in children during the coronavirus 2019 pandemic: A case series. Journal of the Pediatric Infectious Diseases Society. 2020; 9(3):393-8. [DOI:10.1093/jpids/piaa069] [PMID] [PMCID]
  14. Labé P, Ly A, Sin C, Nasser M, Chapelon-Fromont E, Ben Saïd P, et al. Erythema multiforme and Kawasaki disease associated with COVID-19 infection in children. Journal of the European Academy of Dermatology and Venereology. 2020; 34(10):e539-41. [DOI:10.1111/jdv.16666] [PMID] [PMCID]
  15. Deza Leon MP, Redzepi A, McGrath E, Abdel-Haq N, Shawaqfeh A, Sethuraman U, et al. COVID-19-associated pediatric multisystem inflammatory syndrome. Journal of the Pediatric Infectious Diseases Society. 2020; 9(3):407-8. [DOI:10.1093/jpids/piaa061] [PMID] [PMCID]
  16. Balasubramanian S, Nagendran TM, Ramachandran B, Ramanan AV. Hyper-inflammatory syndrome in a child with COVID-19 treated successfully with intravenous immunoglobulin and tocilizumab. Indian Pediatrics. 2020; 57(7):681-3. [DOI:10.1007/s13312-020-1901-z] [PMID] [PMCID]
  17. Rivera-Figueroa EI, Santos R, Simpson S, Garg P. Incomplete Kawasaki disease in a child with COVID-19. Indian Pediatrics. 2020; 57(7):680-1. [DOI:10.1007/s13312-020-1900-0] [PMID] [PMCID]
  18. Belhadjer Z, Méot M, Bajolle F, Khraiche D, Legendre A, Abakka S, et al. Acute heart failure in multisystem inflammatory syndrome in children in the context of global SARS-CoV-2 pandemic. Circulation. 2020; 142(5):429-36. [DOI:10.1161/CIRCULATIONAHA.120.048360] [PMID]
  19. Chiu JS, Lahoud-Rahme M, Schaffer D, Cohen A, Samuels-Kalow M. Kawasaki disease features and myocarditis in a patient with COVID-19. Pediatric Cardiology. 2020; 41(7):1526-8. [DOI:10.1007/s00246-020-02393-0] [PMID] [PMCID]
  20. Schnapp A, Abulhija H, Maly A, Armoni-Weiss G, Levin Y, Faitatziadou SM, et al. Introductory histopathological findings may shed light on COVID-19 paediatric hyperinflammatory shock syndrome. Journal of the European Academy of Dermatology and Venereology. 2020; 34(11):e665-7. [DOI:10.1111/jdv.16749] [PMID] [PMCID]
  21. Greene AG, Saleh M, Roseman E, Sinert R. Toxic shock-like syndrome and COVID-19: Multisystem Inflammatory Syndrome in Children (MIS-C). The American Journal of Emergency Medicine. 2020; 38(11):2492.e5-6. [DOI:10.1016/j.ajem.2020.05.117] [PMID] [PMCID]
  22. Dolinger MT, Person H, Smith R, Jarchin L, Pittman N, Dubinsky MC, et al. Pediatric crohn disease and Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 treated with infliximab. Journal of Pediatric Gastroenterology and Nutrition. 2020; 71(2):153-5. [DOI:10.1097/MPG.0000000000002809] [PMID] [PMCID]
  23. Cheung EW, Zachariah Ph, Gorelik M, Boneparth A, Kernie SG, Orange JS, et al. Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York City. JAMA. 2020; 324(3):294-6. [DOI:10.1001/jama.2020.10374] [PMID] [PMCID]
  24. Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, et al. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA. 2020; 324(3):259-69. [DOI:10.1001/jama.2020.10369] [PMID] [PMCID]
  25. Blondiaux E, Parisot P, Redheuil A, Tzaroukian L, Levy Y, Sileo Ch, et al. Cardiac MRI in children with multisystem inflammatory syndrome associated with COVID-19. Radiology. 2020; 297(3):E283-8. [DOI:10.1148/radiol.2020202288] [PMID] [PMCID]
  26. Belot A, Antona D, Renolleau S, Javouhey E, Hentgen V, Angoulvant F, et al. SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020. Eurosurveillance. 2020; 25(22):pii=2001010. [DOI:10.2807/1560-7917.ES.2020.25.22.2001010] [PMID] [PMCID]
  27. Pouletty M, Borocco Ch, Ouldali N, Caseris M, Basmaci R, Lachaume N, et al. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): A multicentre cohort. Annals of the Rheumatic Diseases. 2020; 79(8):999-1006. [DOI:10.1136/annrheumdis-2020-217960] [PMID] [PMCID]
  28. Ramcharan T, Nolan O, Lai CY, Prabhu N, Krishnamurthy R, Richter AG, et al. Paediatric Inflammatory Multisystem Syndrome: Temporally associated with SARS-CoV-2 (PIMS-TS): Cardiac features, management and short-term outcomes at a UK tertiary paediatric hospital. Pediatric Cardiology. 2020; 41(7):1391-401. [DOI:10.1007/s00246-020-02391-2] [PMID] [PMCID]
  29. Waltuch T, Gill P, Zinns LE, Whitney R, Tokarski J, Tsung JW, et al. Features of COVID-19 post-infectious cytokine release syndrome in children presenting to the emergency department. The American Journal of Emergency Medicine. 2020; 38(10):2246.e3-6. [DOI:10.1016/j.ajem.2020.05.058] [PMID] [PMCID]
  30. Rauf A, Vijayan A, John ST, Krishnan R, Latheef A. Multisystem inflammatory syndrome with features of atypical Kawasaki disease during COVID-19 pandemic. The Indian Journal of Pediatrics. 2020; 87(9):745-7. [DOI:10.1007/s12098-020-03357-1]
  31. Kaushik Sh, Aydin SI, Derespina KR, Bansal PB, Kowalsky Sh, Trachtman R, et al. Multisystem Inflammatory Syndrome in Children associated with severe acute respiratory syndrome coronavirus 2 infection (MIS-C): A multi-institutional study from New York City. The Journal of Pediatrics. 2020; 224:24-9. [DOI:10.1016/j.jpeds.2020.06.045] [PMID] [PMCID]
  32. Miller J, Cantor A, Zachariah Ph, Ahn D, Martinez M, Margolis KG. Gastrointestinal symptoms as a major presentation component of a novel multisystem inflammatory syndrome in children that is related to coronavirus disease 2019: A single center experience of 44 cases. Gastroenterology. 2020; 159(4):1571-4.E2. [DOI:10.1053/j.gastro.2020.05.079] [PMID] [PMCID]
  33. Yozgat CY, Uzuner S, Bursal Duramaz B, Yozgat Y, Erenberk U, Iscan A, et al. Dermatological manifestation of pediatrics multisystem inflammatory syndrome associated with COVID-19 in a 3-year-old girl. Dermatologic Therapy. 2020; 33(4):e13770. [DOI:10.1111/dth.13770] [PMCID]
  34. Toubiana J, Poirault C, Corsia A, Bajolle F, Fourgeaud J, Angoulvant F, et al. Kawasaki-like multisystem inflammatory syndrome in children during the COVID-19 pandemic in Paris, France: Prospective observational study. BMJ. 2020; 369:m2094. [DOI:10.1136/bmj.m2094] [PMID] [PMCID]
  35. Grimaud M, Starck J, Levy M, Marais C, Chareyre J, Khraiche D, et al. Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children. Annals of Intensive Care. 2020; 10:69. [DOI:10.1186/s13613-020-00690-8] [PMID] [PMCID]
  36. Acharyya BC, Acharyya S, Das D. Novel coronavirus mimicking Kawasaki disease in an infant. Indian Pediatrics. 2020; 57(8):753-4. [DOI:10.1007/s13312-020-1924-5] [PMID] [PMCID]
  37. Licciardi F, Pruccoli G, Denina M, Parodi E, Taglietto M, Rosati S, et al. SARS-CoV-2-induced Kawasaki-like hyperinflammatory syndrome: A novel COVID phenotype in children. Pediatrics. 2020; 146(2):e20201711. [DOI:10.1542/peds.2020-1711] [PMID]
  38. Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: An observational cohort study. The Lancet. 2020; 395(10239):1771-8. [DOI:10.1016/S0140-6736(20)31103-X]
  39. Ng KF, Kothari T, Bandi S, Bird PW, Goyal K, Zoha M, et al. COVID-19 multisystem inflammatory syndrome in three teenagers with confirmed SARS-CoV-2 infection. Journal of Medical Virology. 2020; 92(11):2880-6. [DOI:10.1002/jmv.26206] [PMID] [PMCID]
  40. Capone CA, Subramony A, Sweberg T, Schneider J, Shah S, Rubin L, et al. Characteristics, cardiac involvement, and outcomes of multisystem inflammatory syndrome of childhood associated with severe acute respiratory syndrome coronavirus 2 infection. The Journal of Pediatrics. 2020; 224:141-5. [DOI:10.1016/j.jpeds.2020.06.044] [PMID] [PMCID]
  41. Abdel-Mannan O, Eyre M, Löbel U, Bamford A, Eltze Ch, Hameed B, et al. Neurologic and radiographic findings associated with COVID-19 Infection in children. JAMA Neurology. 2020; 77(11):1440-5. [DOI:10.1001/jamaneurol.2020.2687] [PMID] [PMCID]
  42. Bapst T, Romano F, Müller M, Rohr M. Special dermatological presentation of paediatric multisystem inflammatory syndrome related to COVID-19: Erythema multiforme. BMJ Case Reports CP. 2020; 13(6):e236986. [DOI:10.1136/bcr-2020-236986] [PMID] [PMCID]
  43. Rodriguez-Gonzalez M, Rodríguez-Campoy P, Sánchez-Códez M, Gutiérrez-Rosa I, Castellano-Martinez A, Rodríguez-Benítez A. New onset severe right ventricular failure associated with COVID-19 in a young infant without previous heart disease. Cardiology in the Young. 2020; 30(9):1346-9. [DOI:10.1017/S1047951120001857] [PMID] [PMCID]
  44. Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. The New England Journal of Medicine. 2020; 383(4):334-46. [DOI:10.1056/NEJMoa2021680]
  45. Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A, Rowlands J, et al. Multisystem inflammatory syndrome in children in New York State. The New England Journal of Medicine. 2020; 383(4):347-58. [DOI:10.1056/NEJMoa2021756] [PMID] [PMCID]
  46. Dasgupta K, Finch SE. A case of pediatric multisystem inflammatory syndrome temporally associated with COVID-19 in South Dakota. South Dakota Medicine. 2020; 73(6):246-51. [PMID]
  47. Perez-Toledo M, Faustini SE, Jossi SE, Shields AM, Kanthimathinathan HK, Allen JD, et al. Serology confirms SARS-CoV-2 infection in PCR-negative children presenting with paediatric inflammatory multi-system syndrome. medRxiv. 2020; June. [DOI:10.1101/2020.06.05.20123117]
  48. Hameed Sh, Elbaaly H, Reid CEL, Santos RMF, Shivamurthy V, Wong J, et al. Spectrum of imaging findings at chest radiography, US, CT, and MRI in multisystem inflammatory syndrome in children associated with COVID-19. Radiology. 2020; 298(1):E1-10. [DOI:10.1148/radiol.2020202543] [PMID] [PMCID]
  49. Riollano-Cruz M, Akkoyun E, Briceno-Brito E, Kowalsky Sh, Reed J, Posada R, et al. Multisystem inflammatory syndrome in children related to COVID-19: A New York City experience. Journal of Medical Virology. 2021; 93(1):424-33. [DOI:10.1002/jmv.26224] [PMID] [PMCID]
  50. Horne A, Nordenhäll L. Hyperinflammation hos barn kan ha samband med COVID-19. [Severe inflammation in children: Cause for awareness during the current pandemic (Swedish)]. Lakartidningen. 2020; 117:20094. [PMID]
  51. Rowley AH. Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children. Nature Reviews Immunology. 2020; 20(8):453-4. [DOI:10.1038/s41577-020-0367-5] [PMID] [PMCID]
  52. Dominguez SR, Anderson MS, El-Adawy M, Glodé MP. Preventing coronary artery abnormalities: A need for earlier diagnosis and treatment of Kawasaki disease. The Pediatric Infectious Disease Journal. 2012; 31(12):1217-20. [DOI:10.1097/INF.0b013e318266bcf9] [PMID]
Type of Study: Systematic Review | Subject: Pediatric Infectious Diseases
Received: 2021/09/2 | Accepted: 2021/11/27 | Published: 2022/01/1

Add your comments about this article : Your username or Email:

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2022 CC BY-NC 4.0 | Journal of Pediatrics Review

Designed & Developed by : Yektaweb