Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contact us Login 
  • Users Online:424
  • Home
  • Print this page
  • Email this page

 Table of Contents  
Year : 2021  |  Volume : 9  |  Issue : 1  |  Page : 101-106

Multisystem inflammatory syndrome in children associated with Coronavirus Disease-2019: An overview

1 Department of Pediatrics, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras al Khaimah, United Arab Emirates
2 Department of Obstetrics and Gynaecology, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras al Khaimah, United Arab Emirates

Date of Submission14-Oct-2020
Date of Decision28-Feb-2021
Date of Acceptance03-Mar-2021
Date of Web Publication26-Jun-2021

Correspondence Address:
Dr. Subhranshu Sekhar Kar
Department of Pediatrics, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras al Khaimah
United Arab Emirates
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/amhs.amhs_273_20

Rights and Permissions

Coronavirus disease-2019 has been ravaging the world since the past several months with devastating consequences. Although it is seen that specific categories of patients with comorbidities are especially vulnerable, the risks from the acute disease in pediatric population have been consistently lower. However, the alarming rise in pediatric admissions in intensive care units with varied clinical presentation during this pandemic gave an insight to a new hyperinflammatory response called as multisystem inflammatory syndrome in children. Although overlapping symptoms may mimic toxic shock syndrome, macrophage activation syndrome, secondary hemophagocytic lymphohistiocytosis, myocarditis, or Kawasaki-like illness, clinical findings are relatively consistent across geographically distinct regions. Diagnosis is essentially clinical, and laboratory investigations are suggestive of increased inflammatory markers. Early recognition and appropriate institution of inotropes, intravenous immunoglobulins, corticosteroids, and antibiotics apart from general supportive treatment are required for a favorable outcome.

Keywords: Coronavirus disease-2019, Kawasaki-like illness, multisystem inflammatory syndrome in children, pediatric multisystem inflammatory syndrome temporally associated with coronavirus disease-2019, severe acute respiratory syndrome coronavirus 2

How to cite this article:
Kar SS, Dube R. Multisystem inflammatory syndrome in children associated with Coronavirus Disease-2019: An overview. Arch Med Health Sci 2021;9:101-6

How to cite this URL:
Kar SS, Dube R. Multisystem inflammatory syndrome in children associated with Coronavirus Disease-2019: An overview. Arch Med Health Sci [serial online] 2021 [cited 2022 Jun 25];9:101-6. Available from: https://www.amhsjournal.org/text.asp?2021/9/1/101/319387

  Introduction Top

The major global challenges for public health in recent times have been the reemerging pathogens. Coronaviruses are positively stranded enveloped RNA viruses widely distributed in humans, other animals, and birds. In late 2019, in Wuhan city of the Hubei Province of China, the novel coronavirus was attributed as the cause in cluster of pneumonia patients. In no time, due to its extremely rapid spread, it reached to epidemic proportion in China, followed by spread to other neighboring countries and beyond. In February 2020, the World Health Organization designated the disease as coronavirus disease-2019 (COVID-19), which stands for coronavirus disease 2019.[1] The virus causing COVID-19 is designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was previously referred to as 2019-nCoV. These pathogens commonly cause respiratory, gastrointestinal, and neurologic diseases. Seven strains of the virus are known to cause diseases in humans. The four strains, namely, 229E9 (alphacoronavirus), NL 63 (alphacoronavirus), OC43 (betacoronavirus), and HKU1 (betacoronavirus) normally cause self-limiting upper respiratory tract infection in immunocompetent individuals. The rest three zoonotic coronavirus diseases have caused epidemics with fatal outcomes. They are Middle Eastern Respiratory Syndrome coronavirus causing Middle Eastern Respiratory Syndrome (betacoronavirus), SARS-CoV causing severe acute respiratory syndrome (SARS) (betacoronavirus), and SARS-CoV2 (the novel coronavirus that causes coronavirus disease-COVID-19). The worrisome fact is that a large number of SARS-related potentially mutagenic strains of coronaviruses have been discovered in their natural reservoir in bats and also SARS-CoV-2 isolates encoding a D614G mutation in the viral spike (S) protein predominate over time in locales where it is found, implying that this change enhances viral transmission.[2],[3]

Till date, COVID-19 has caused >22 million infections globally with over 795,000 deaths. However, there is less information about epidemiology and clinical impact of COVID-19 in children. Younger population under 18 years of age are less involved (attack rate 2.4%).[4],[5] Furthermore, the clinical manifestations are generally milder in infants and children compared to adults.[6],[7],[8] Multisystem inflammatory syndrome in children (MIS-C) was first recognized in late April 2020, where clinicians in the United Kingdom reported a cluster of eight previously healthy children presenting with cardiovascular shock, fever, and hyperinflammation similar to presentations of incomplete Kawasaki disease (KD) or toxic shock syndrome (TSS).[9] On May 14, 2020, the Centers for Disease Control and Prevention (CDC) issued a national health advisory to report on cases meeting the criteria for MIS-C.[10] Thereafter, many case series of MIS-C were reported requiring admissions in intensive care from across the globe, especially from the USA, Italy, France, United Kingdom, and Spain.[11],[12],[13] Alternatively, MIS-C is also referred as pediatric hyperinflammatory shock, pediatric multisystem inflammatory syndrome, or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). The true prevalence of this condition is difficult to estimate as the disease is still evolving at this point of time.

  Epidemiology Top

Like any other pandemic situation, the reported case counts hugely underestimate the overall burden of COVID-19, as only a minor fraction of acute infections are diagnosed and reported. Seroprevalence surveys in the United States and Europe did point to the fact that, after accounting for potential false positives or negatives, the rate of prior exposure to SARS-CoV-2, as reflected by seropositivity, exceeds the incidence of reported cases by approximately 10-fold or more.[14],[15],[16] While the incidence of MIS-C is uncertain, evidences suggest that this phenomenon appears to be relatively rare in COVID-19 in children. In one report, the estimated incidence of laboratory-confirmed SARS-CoV-2 infection in individuals <21 years old was 322/100,000 and the incidence of MIS-C was 2/100,000.[17] Like KD, where the cause is entirely not known, MIS-C is also a syndrome having wide range of clinical manifestations without any pathognomonic findings or specific diagnostic tests.[9],[12],[18],[19],[20],[21],[22],[23],[24] However, the predominant affection of children older than 5 years of age and adolescents with more frequent cardiovascular involvement are clinical differentiating features of MIS-C from KD.[9],[12],[20] With time, the epidemiologic association of MIS-C with COVID-19 is now well established. Regions heavily affected by SARS-CoV-2, all over the world, are reporting many cases of MIS-C. From these reports, it has been clearly shown that the clinical findings are relatively consistent across geographically distinct regions. The timing of MIS-C is also consistent with a mechanism related to host response and hyperinflammation. Prospective reporting of this condition has now been initiated by agencies worldwide to capture prevalence, early clinical course, and outcome.[25]

  Pathophysiology Top

The host receptor for SARS-CoV-2 cell entry is the same as for SARS-CoV, the angiotensin-converting enzyme 2 (ACE2).[26] ACE2 is a membrane-bound protein commonly found in vascular endothelia, cardiovascular tissue, renal, and small intestine. The cellular protease TMPRSS2 also appears important for SARS-CoV-2 cell entry.[27]

Immune response to SARS-CoV-2 seems to involve both cell-mediated immunity and antibody production. Invasion of the cardiac myocytes by virus or hypoxemia resulting from respiratory failure, results in oxidative stress and myocardial damage.[28] Sudden and excessive release of cytokines cause acute respiratory distress syndrome and rapid progress to multiorgan dysfunction. MIS-C is also a possible consequence of cytokine storm (CS) and interleukin-6 (IL-6) is the major cytokine implicated. Its level correlates well with disease severity. The exact pathophysiology of MIS-C is not yet fully understood. Negative polymerase chain reaction (PCR) testing for SARS-CoV-2 but positive serology has been documented in many affected children. This observation supports the hypothesis that MIS-C is related to immune dysregulation occurring after acute infection has passed, usually 2–4 weeks post-COVID-19 infection.[29] The low levels of antibodies in these children may prevent further spread of the SARS-CoV-2 infection, but antibody-dependent enhancement might be responsible for MIS-C.[30] However, some children do have positive PCR testing.[12],[13],[20] A postinfectious process is also postulated, based on the timing of the rise of these cases relative to the peak of COVID-19 cases in communities.[20]

  Clinical Presentation Top

Varied clinical presentation in the young is reported in many case series, encompassing the features of TSS, myocarditis, macrophage activation syndrome (MAS), and KD-like syndrome.[9],[31] The usual features are prolonged history of fever, gastrointestinal symptoms including abdominal pain, cardiovascular involvement, conjunctivitis, rash, irritability, peripheral edema, neurocognitive problems, lymphadenopathy, and generalized myalgia.[12],[13],[21],[32] Acutely, due to the development of pleural effusion, pericardial effusion, or ascites, they can have severe respiratory symptoms. More than half of these children present with significant gastrointestinal symptoms. In relation to the cardiovascular involvement, the patients may present with distinct yet overlapping features [Table 1] and [Table 2].[19],[32]
Table 1: Criteria for diagnosis of complete and incomplete Kawasaki disease[19]

Click here to view
Table 2: Clinical presentation of toxic shock syndrome[32]

Click here to view

However, the hallmark feature of MIS-C is the presence of high and persistent fever (≥3 days), unexplained by other causes. Fever together with laboratory evidence of marked systemic inflammation and temporal association with COVID-19 having been present in the community should raise the index of suspicion for MIS-C.[33] They can even experience KD shock syndrome (KDSS), which is defined by systemic hypotension and hypoperfusion, and/or MAS.[24],[34],[35],[36],[37] MAS is a potentially life-threatening complication that presents with persistent fever, rash, lymphadenopathy, hepatosplenomegaly, and occasionally with neurological complications. Affected individuals have characteristic laboratory features including marked increases in C-reactive protein, ferritin, lactate dehydrogenase (LDH), aspartate transaminase, alanine transaminase, triglycerides, and D-dimers, as well as progressive cytopenias.[24],[35]

  Spectrum of the Disease Top

Initially, MIS-C was reported mostly in severely affected children. Subsequently, it is found that the spectrum of disease ranges from mild to severe. Subphenotypes of the syndrome are also gradually evolving [Table 3].[13] The case definitions are likely to change with the availability of more information.
Table 3: Corona virus disease-19 spectrum[13]

Click here to view

  Case Definitions for Multisystem Inflammatory Syndrome in Children Top

MIS-C cases are defined differently by the US CDC,[10] the UK Royal College of Paediatrics and Child Health,[38] Canadian Pediatric Surveillance Program,[33] and also by the World Health Organization.[39] These case definitions include association with COVID-19 [Table 4], as defined by a positive test for SARS-CoV-2 or exposure to others with COVID-19 within 4 weeks before the onset of symptoms.
Table 4: Case definitions for multi-system inflammatory syndrome in children[10],[33],[38],[39]

Click here to view

  Laboratory Investigations Top

As MIS-C has only recently been recognized, evidence-based recommendations for laboratory testing is difficult at this moment. However, as children with MIS-C deteriorate quickly, certain principles must be kept in mind for successful management. Positive test for SARS-CoV-2 by reverse transcriptase PCR for viral RNA (RT-PCR), antigen, or antibody establishes the diagnosis of COVID-19. When a patient presents with otherwise unexplained, isolated high fever ≥3 days and a history of or potential exposure to COVID-19 based on local epidemiology, screening laboratory tests for hyperinflammation should be considered [Table 5].[33] When laboratory evidence of significant hyperinflammation is present, additional workup is needed for an evolving picture of CS (ferritin, LDH, fibrinogen, D-dimers, partial thromboplastin time, international normalized ratio, and triglycerides), and for myocarditis (troponin, N-terminal-pro-B-type natriuretic peptide [NT-proBNP], and electrocardiogram [ECG]).[33]
Table 5: Investigations for multi-system inflammatory syndrome in children[33]

Click here to view

The common laboratory abnormalities found in MIS-C are summarized in [Table 6].[33],[40]
Table 6: Laboratory abnormalities seen in multi-system inflammatory syndrome in children[33],[40]

Click here to view

  Management Top

As the spectrum of patients is highly variable, treatment mostly is supportive and includes maintenance of fluid and electrolyte balance. Urgent admission is indicated if the child appears sick and investigation parameters are suggestive of high inflammatory markers with abnormal values of troponin or NT-proBNP. Treatment in the line of KD should be instituted after doing a thorough cardiac evaluation. Pediatric rheumatology and pediatric cardiology consultation should be ought. In case of deferred admission in apparently well looking child with underlying hyper-inflammation, a close follow-up is warranted with repeat laboratory investigations in next 24–48 h. Children presenting with KD such as symptoms should be managed with Intravenous Immunoglobulin- IVIG-2 g/kg, to a maximum of 70 g/day and acetylsalicylic acid. ECG and echocardiogram are advised at admission and again repeated as needed. Pediatric rheumatology and if possible, pediatric infectious disease specialist consultation might be needed.[12],[19],[21] At diagnosis, corticosteroids are started along with IVIG in high-risk cases. Patients <1 year of age at presentation, fever for ≥10 days, KDSS, MAS, or coronary artery dilatations on baseline echocardiogram are considered as high-risk cases.[19],[41],[42] In case of nonresponders to IVIG, corticosteroids may be considered, either oral prednisolone at 2 mg/kg/day in 2–3 divided doses or pulse intravenous (IV) methylprednisolone infusion at a dose of 20–30 mg/kg/day (maximum 1 g) over 1–3 h.[19] In complicated cases, for patients with KD with refractory MAS or shock and with inadequate response to IV pulse methylprednisolone treatment, biologic therapy with anakinra is indicated. In these cases, it is better to consult with a pediatric rheumatologist before starting therapy. In serious cases, presenting severe myocardial dysfunction and cardiogenic shock (with abnormal ECG, elevated markers such as troponin, and NT-proBNP), urgent intensive care unit management is indicated as these subsets of patients can deteriorate very quickly and require judicious and controlled administration of fluid, inotropes, and ventilation. Broad-spectrum antibiotics are started at the beginning as its difficult to rule out severe bacterial sepsis based on only overlapping symptoms. Multispecialty consultation especially cardiology and critical care consultation are required before shifting the patient for tertiary care.[33] Use of hydroxychloroquine and azithromycin is purely based on the institutional guidelines. Heparin may be advised in mechanically ventilated patients or with thromboembolic phenomena.[12],[43] Anti-inflammatory agents such as tocilizumab (8 mg/kg IV over 2 h), an IL-6 receptor antagonist approved by US FDA for treating CS may be useful in selected cases.[31] Extracorporeal membranous oxygenation is generally reserved for the very severe cases with pulmonary involvement and hypotensive shock.

  Conclusion Top

Although COVID-19 affects children less commonly with milder symptoms than adults, MIS-C associated with SARS-CoV-2 has led to serious and life-threatening illness in previously healthy children and adolescents. It appears to be a late manifestation as a result of immune dysregulation to pathogen. This rare syndrome shares common features with other pediatric inflammatory conditions including KD, TSSs, bacterial sepsis, and MASs. Patients may have abdominal symptoms with excessive inflammatory markers. Early recognition and multidisciplinary specialist consultation including referral to critical care are essential. Treatment regimens are individualized depending on the clinical presentation.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020;382:727-33.  Back to cited text no. 1
Zimmermann P, Curtis N. Coronavirus infections in children including COVID-19: An overview of the epidemiology, clinical features, diagnosis, treatment and prevention options in children. Pediatr Infect Dis J 2020;39:355-68.  Back to cited text no. 2
Zhang L, Jackson CB, Mou H, Ojha A, Rangarajan ES, Izard T, et al. The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity. bioRxiv 2020. [doi: 10.1101/2020.06.12.148726].  Back to cited text no. 3
Castagnoli R, Votto M, Licari A, Brambilla I, Bruno R, Perlini S, et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: A systematic review. JAMA Pediatr 2020;174:882-9.  Back to cited text no. 4
Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 infection in children. N Engl J Med 2020;382:1663-5.  Back to cited text no. 5
Jiehao C, Jin X, Daojiong L, Zhi Y, Lei X, Zhenghai Q, et al. A case series of children with 2019 novel coronavirus infection: Clinical and epidemiological features. Clin Infect Dis 2020;71:1547-51.  Back to cited text no. 6
Xia W, Shao J, Guo Y, Peng X, Li Z, Hu D. Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults. Pediatr Pulmonol 2020;55:1169-74.  Back to cited text no. 7
Wei M, Yuan J, Liu Y, Fu T, Yu X, Zhang ZJ. Novel coronavirus infection in hospitalized infants under 1 year of age in China. JAMA 2020;323:1313-4.  Back to cited text no. 8
Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020;395:1607-8.  Back to cited text no. 9
Centers for Disease Control and Prevention. Emergency Preparedness and Response: Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19). Health Advisory. Available from: https://emergency.cdc.gov/han/2020/han00432.asp. [Last accessed on 14 Aug 2020].  Back to cited text no. 10
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:e20201711.  Back to cited text no. 11
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. Lancet 2020;395:1771-8.  Back to cited text no. 12
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;324:259-69.  Back to cited text no. 13
Stringhini S, Wisniak A, Piumatti G, Azman AS, Lauer SA, Baysson H, et al. Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): A population-based study. Lancet 2020;396:313-9.  Back to cited text no. 14
Centers for Disease Control and Prevention. Commercial Laboratory Seroprevalence Survey Data. Available from: https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/commercial-lab-surveys.html. [Last accessed on 2020 Aug 15].  Back to cited text no. 15
Havers FP, Reed C, Lim T, Montgomery JM, Klena JD, Hall AJ, et al. Seroprevalence of antibodies to SARS-CoV-2 in 10 sites in the United States, March 23-May 12, 2020. JAMA Intern Med 2020;180:1576-86. [doi: 10.1001/jamainternmed. 2020.4130].  Back to cited text no. 16
Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A, Rowlands J, et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med 2020;383:347-58.  Back to cited text no. 17
Shackelford PG, Strauss AW. Kawasaki syndrome. N Engl J Med 1991;324:1664-6.  Back to cited text no. 18
McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific statement for health professionals from the American Heart Association. Circulation 2017;135:e927-99.  Back to cited text no. 19
Belhadjer N, Méot M, Bajolle F, Khraiche D, Legendre A, Abakka A, et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation 2020;142:429-36. doi: 10.1161/ CIRCULATIONAHA.120.048360.  Back to cited text no. 20
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.  Back to cited text no. 21
MacDonald KL, Osterholm MT, Hedberg CW, Schrock CG, Peterson GF, Jentzen JM, et al. Toxic shock syndrome: A newly recognized complication of influenza and influenza like illness. J Am Med Assoc 1987;257:1053-8.  Back to cited text no. 22
Crayne C, Cron RQ. Pediatric macrophage activation syndrome, recognizing the tip of the Iceberg. Eur J Rheumatol 2019;7(Suppl 1):1-8. doi: 10.5152/eurjrheum.2019.19150.  Back to cited text no. 23
Wang W, Gong F, Zhu W, Fu S, Zhang Q. Macrophage activation syndrome in Kawasaki disease: More common than we thought? Semin Arthritis Rheum 2015;44:405-10.  Back to cited text no. 24
Royal College of Paediatrics and Child Health. BPSU Study: Multisystem Inflammatory Syndrome, Kawasaki Disease and Toxic Shock Syndrome; 2020. Available from: https://www.rcpch.ac.uk/work-we-do/bpsu/study-multisysteminflammatory-syndrome-kawasaki-disease-toxic-shock-syndrome. [Last accessed on 2020 Aug 15].  Back to cited text no. 25
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579:270-3.  Back to cited text no. 26
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271-80.  Back to cited text no. 27
Tan W, Aboulhosn J. The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease. Int J Cardiol 2020;309:70-7.  Back to cited text no. 28
Morand A, Urbina D, Fabre A. COVID-19 and Kawasaki like disease: The known-known, the unknown-known and the unknown-unknown. Preprints 2020. [doi: 10.20944/preprints202005.0160.v1].  Back to cited text no. 29
Ferguson NM, Laydon D, Nedjati-Gilani G, Imai N, Ainslie K, Baguelin M, et al. Impact of Non-Pharmaceutical Interventions (NPIs) to Reduce COVID-19 Mortality and Healthcare Demand. Imperial College London; 2020. [doi: 10.25561/77482].  Back to cited text no. 30
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 Pediatr 2020;57:681-3.  Back to cited text no. 31
Sharland M, Butler K, Cant A, Dagon R, Davies G, Groot RD, et al. editors. Manual of Childhood Infections: The Blue Book (Oxford Specialist Handbooks in Paediatrics). 4th ed. London, UK: Oxford University Press; 2016.  Back to cited text no. 32
Canadian Paediatric Surveillance Program. Paediatric Inflammatory Multisystem Syndrome Temporally Associated with COVID-19; July 6, 2020. Available from: https://www.cps.ca/en/documents/position/pims. [Last accessed on 2020 Aug 15].  Back to cited text no. 33
Kanegaye JT, Wilder MS, Molkara D, Frazer JR, Pancheri J, Tremoulet AH, et al. Recognition of a Kawasaki disease shock syndrome. Pediatrics 2009;123:e783-9.  Back to cited text no. 34
Natoli V, Rosina S, Ravelli A. Is macrophage activation syndrome in Kawasaki disease underrecognized? J Rheumatol 2021;48:162-4.  Back to cited text no. 35
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. Am J Emerg Med 2020;38:2246.e3-6.  Back to cited text no. 36
Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MB, et al. Multisystem inflammatory syndrome in U.S. Children and adolescents. N Engl J Med 2020;383:334-46.  Back to cited text no. 37
Royal College of Paediatric and Child Health. Guidance: Paediatric Multisystem Inflammatory Syndrome Temporally Associated with COVID-19; 2020. Available from: https://www.rcpch.ac.uk/resources/guidance-paediatric-multisysteminflammatory-syndrome-temporally-associated-covid-19. [Last accessed on 2020 Aug 15].  Back to cited text no. 38
World Health Organization. Multisystem Inflammatory Syndrome in Children and Adolescents with COVID-19. Available from: https://www.who.int/publicationsdetail/multisystem-inflammatory-syndrome-in-children-and-adolescentswith-covid-19. [Last accessed on 2020 Aug 15].  Back to cited text no. 39
Tullie L, Ford K, Bisharat M, Watson T, Thakkar H, Mullassery D, et al. Gastrointestinal features in children with COVID-19: An observation of varied presentation in eight children. Lancet Child Adolesc Health 2020;4:e19-20.  Back to cited text no. 40
Chen S, Dong Y, Yin Y, Krucoff MW. Intravenous immunoglobulin plus corticosteroid to prevent coronary artery abnormalities in Kawasaki disease: A meta-analysis. Heart 2013;99:76-82.  Back to cited text no. 41
de Graeff N, Groot N, Ozen S, Eleftheriou D, Avcin T, Bader-Meunier B, et al. European consensus-based recommendations for the diagnosis and treatment of Kawasaki disease - the SHARE initiative. Rheumatology (Oxford) 2019;58:672-82.  Back to cited text no. 42
Viner RM, Whittaker E. Kawasaki-like disease: Emerging complication during the COVID-19 pandemic. Lancet 2020;395:1741-3.  Back to cited text no. 43


  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Clinical Present...
Spectrum of the ...
Case Definitions...
Laboratory Inves...
Article Tables

 Article Access Statistics
    PDF Downloaded111    
    Comments [Add]    

Recommend this journal