Systematic review on the clinical presentation and management of the COVID-19 associated multisystem inflammatory syndrome in children (MIS-C)

Marah Shaikh Yousef; Nur Syazana Idris; Charles Yap; Abdulaziz Abdullah Alsubaie; Pramath Kakodkar; Marah Shaikh Yousef; Nur Syazana Idris; Charles Yap; Abdulaziz Abdullah Alsubaie; Pramath Kakodkar

doi:10.3934/Allergy.2021004

AIMS Allergy and Immunology

2021, Volume 5, Issue 1: 38-55. doi: 10.3934/Allergy.2021004

Previous Article Next Article

Review Topical Sections

Systematic review on the clinical presentation and management of the COVID-19 associated multisystem inflammatory syndrome in children (MIS-C)

School of Medicine, National University of Ireland Galway, Galway City, Republic of Ireland

Received: 22 November 2020 Accepted: 20 January 2021 Published: 25 January 2021

Firstly, we collated the vast repository of MIS-C cases and presented them in a simplified, condensed, and comprehensive format. Secondly, we explored the clinical presentation, and efficacy of the management options. Additionally, we briefly discussed the pathophysiology and addressed the variance in the jargon and criteria relating to this condition.
Methods
A systematic literature review was conducted on the 17th of October 2020 in accordance with PRISMA (2015) guidelines. The search terms: ‘MIS-C’, ‘Kawasaki-like Disease’, ‘PIMS-TS’, and ‘COVID-19’ were queried on Medline and Embase databases. Publications that fulfilled the inclusion criteria were included and were assessed for parameters pertaining to the clinical course and management.
Results
From December 2019 to October 2020, 131 publications were identified. Of these, 56 publications (n = 646 patients) fit the inclusion criteria. Median age was 10 years (range: 0.5–17 years), 52.2% (n = 337/646) were male, and 33.5% (n = 128/382) were of African ethnicity. SARS-CoV-2 reverse transcriptase PCR and serology were positive in 42% (n = 142/426), and 85.3% (n = 300/352) of cases respectively. Presenting complaint(s) were predominately gastrointestinal: 77.6% (n = 436/562) generalized abdominal pain, 76.4% (n = 386/505) vomiting, and 63.2% (n = 203/321) diarrhea. Hypotensive shock was also commonly observed at admission. Additionally, laboratory data revealed elevated neutrophils and inflammatory markers. Echocardiogram findings indicated reduced left ventricular ejection fraction and myocarditis in 22.6% (n = 85/376) and 22.3% (n = 84/376) of cases, respectively. Immunoglobulins and intravenous steroids were predominantly used in 76% (n = 433/571) and 51% (n = 317/618) of cases, respectively. Majority of the patients (97%, n = 418/431) were discharged home. A combination treatment of tocilizumab and IVIG had a mean length of stay of 7 ± 3 days and 95.5% (n = 21/22) discharge rate with low complications in comparison to either of the treatments alone.
Conclusion
MIC-S syndrome is a pediatric hyperinflammatory condition that has an association with COVID-19 background exposure. MIS-C has a heterogeneous multisystem presentation that can be associated with life threatening cardiac complications. There is a need to further explore its long-term morbidity.
- COVID-19,
- pediatrics,
- multisystem inflammatory syndrome in children (MIS-C),
- pediatric inflammatory multisystem syndrome (PIMS),
- Kawasaki like disease
Citation: Marah Shaikh Yousef, Nur Syazana Idris, Charles Yap, Abdulaziz Abdullah Alsubaie, Pramath Kakodkar. Systematic review on the clinical presentation and management of the COVID-19 associated multisystem inflammatory syndrome in children (MIS-C)[J]. AIMS Allergy and Immunology, 2021, 5(1): 38-55. doi: 10.3934/Allergy.2021004

Related Papers:

Abstract

Firstly, we collated the vast repository of MIS-C cases and presented them in a simplified, condensed, and comprehensive format. Secondly, we explored the clinical presentation, and efficacy of the management options. Additionally, we briefly discussed the pathophysiology and addressed the variance in the jargon and criteria relating to this condition.

Methods

A systematic literature review was conducted on the 17th of October 2020 in accordance with PRISMA (2015) guidelines. The search terms: ‘MIS-C’, ‘Kawasaki-like Disease’, ‘PIMS-TS’, and ‘COVID-19’ were queried on Medline and Embase databases. Publications that fulfilled the inclusion criteria were included and were assessed for parameters pertaining to the clinical course and management.

Results

From December 2019 to October 2020, 131 publications were identified. Of these, 56 publications (n = 646 patients) fit the inclusion criteria. Median age was 10 years (range: 0.5–17 years), 52.2% (n = 337/646) were male, and 33.5% (n = 128/382) were of African ethnicity. SARS-CoV-2 reverse transcriptase PCR and serology were positive in 42% (n = 142/426), and 85.3% (n = 300/352) of cases respectively. Presenting complaint(s) were predominately gastrointestinal: 77.6% (n = 436/562) generalized abdominal pain, 76.4% (n = 386/505) vomiting, and 63.2% (n = 203/321) diarrhea. Hypotensive shock was also commonly observed at admission. Additionally, laboratory data revealed elevated neutrophils and inflammatory markers. Echocardiogram findings indicated reduced left ventricular ejection fraction and myocarditis in 22.6% (n = 85/376) and 22.3% (n = 84/376) of cases, respectively. Immunoglobulins and intravenous steroids were predominantly used in 76% (n = 433/571) and 51% (n = 317/618) of cases, respectively. Majority of the patients (97%, n = 418/431) were discharged home. A combination treatment of tocilizumab and IVIG had a mean length of stay of 7 ± 3 days and 95.5% (n = 21/22) discharge rate with low complications in comparison to either of the treatments alone.

Conclusion

MIC-S syndrome is a pediatric hyperinflammatory condition that has an association with COVID-19 background exposure. MIS-C has a heterogeneous multisystem presentation that can be associated with life threatening cardiac complications. There is a need to further explore its long-term morbidity.

Abbreviations

CRP

C-reactive protein

gastrointestinal

PCR

polymerase chain reaction

interleukin

creatine kinase

LDH

lactate dehydrogenase

ECHO

echocardiogram

ECG

electrocardiogram

CXR

chest x-ray

Abdo U/S

abdominal ultrasound

computed tomography

ESR

erythrocyte sedimentation rate

pro-BNP

pro-b-type natriuretic peptide

BNP

b-type natriuretic peptide

IL-6

Interleukin-6

IL-8

Interleukin-8

TNF Alpha

tumor necrosis factor alpha

INR

international normalized ratio

BUN

blood urea nitrogen

AST

aspartate transaminase

ALT

alanine transaminase

length of stay

LOS

standard deviation

ICH

intracerebral hemorrhage

heart failure

MOF

multi-organ failure

respiratory failure

N/A

not available

HCQ

hydroxychloroquine

Conflict of interest

All authors declare no conflicts of interest in this paper.

References

[1]	Huang C, Wang Y, Li X, et al. (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395: 497-506. doi: 10.1016/S0140-6736(20)30183-5
[2]	Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Johns Hopkins Coronavirus Resource Center, 2020 Available from: https://coronavirus.jhu.edu/map.html.
[3]	Alqahtani JS, Oyelade T, Aldhahir AM, et al. (2020) Prevalence, severity and mortality associated with COPD and smoking in patients with COVID-19: a rapid systematic review and meta-analysis. PLoS One 15: e0233147. doi: 10.1371/journal.pone.0233147
[4]	Nguyen DC, Haydar H, Pace ER, et al. (2020) Pediatric case of severe COVID-19 with shock and multisystem inflammation. Cureus 12: e8915.
[5]	Consiglio CR, Cotugno N, Sardh F, et al. (2020) The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell 183: 968-981. doi: 10.1016/j.cell.2020.09.016
[6]	Riphagen S, Gomez X, Gonzalez-Martinez C, et al. (2020) Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 395: 1607-1608. doi: 10.1016/S0140-6736(20)31094-1
[7]	Tissières P, Teboul JL (2020) SARS-CoV-2 post-infective myocarditis: the tip of COVID-19 immune complications? Ann Intensive Care 10: 98. doi: 10.1186/s13613-020-00717-0
[8]	Walker PGT, Whittaker C, Watson OJ, et al. (2020) The impact of COVID-19 and strategies for mitigation and suppression in low- and middle-income countries. Science 369: 413.
[9]	Rowley AH, Shulman ST (2010) Pathogenesis and management of Kawasaki disease. Expert Rev Anti Infect Ther 8: 197-203. doi: 10.1586/eri.09.109
[10]	Nakra NA, Blumberg DA, Herrera-Guerra A, et al. (2020) Multi-system inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection: review of clinical presentation, hypothetical pathogenesis, and proposed management. Children 7: 69. doi: 10.3390/children7070069
[11]	Lee PY, Day-Lewis M, Henderson LA, et al. (2020) Distinct clinical and immunological features of SARS-CoV-2-induced multisystem inflammatory syndrome in children. J Clin Invest 130: 5942-5950. doi: 10.1172/JCI141113
[12]	Dufort EM, Koumans EH, Chow EJ, et al. (2020) Multisystem inflammatory syndrome in children in New York State. New Engl J Med 383: 347-358. doi: 10.1056/NEJMoa2021756
[13]	Kaushik S, Aydin SI, Derespina KR, et al. (2020) Multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2 infection (MIS-C): A multi-institutional study from New York City. J Pediatr 224: 24-29. doi: 10.1016/j.jpeds.2020.06.045
[14]	Toubiana J, Poirault C, Corsia A, et al. (2020) Outbreak of Kawasaki disease in children during COVID-19 pandemic: a prospective observational study in Paris, France. medRxiv In press.
[15]	Jain S, Sen S, Lakshmivenkateshiah S, et al. (2020) Multisystem inflammatory syndrome in children with COVID-19 in Mumbai, India. Indian Pediatr 57: 1015-1019. doi: 10.1007/s13312-020-2026-0
[16]	Belhadjer Z, Méot M, Bajolle F, et al. (2020) Acute heart failure in multisystem inflammatory syndrome in children in the context of global SARS-CoV-2 pandemic. Circulation 142: 429-436. doi: 10.1161/CIRCULATIONAHA.120.048360
[17]	Torres JP, Izquierdo G, Acuña M, et al. (2020) Multisystem inflammatory syndrome in children (MIS-C): Report of the clinical and epidemiological characteristics of cases in Santiago de Chile during the SARS-CoV-2 pandemic. Int J Infect Dis 100: 75-81. doi: 10.1016/j.ijid.2020.08.062
[18]	Moraleda C, Serna-Pascual M, Soriano-Arandes A, et al. (2020) Multi-Inflammatory Syndrome in Children related to SARS-CoV-2 in Spain. Clin Infect Dis 1–5.
[19]	Greene AG, Saleh M, Roseman E, et al. (2020) Toxic shock-like syndrome and COVID-19: A case report of multisystem inflammatory syndrome in children (MIS-C). Am J Emerg Med 38: 2492.e5-2492.e6. doi: 10.1016/j.ajem.2020.05.117
[20]	Dolinger MT, Person H, Smith R, et al. (2020) Pediatric Crohn disease and multisystem inflammatory syndrome in children (MIS-C) and COVID-19 treated with infliximab. J Pediatr Gastr Nutr In press.
[21]	Riollano-Cruz M, Akkoyun E, Briceno-Brito E, et al. (2021) Multisystem inflammatory syndrome in children related to COVID-19: A New York City experience. J Med Virol 93: 424-433. doi: 10.1002/jmv.26224
[22]	Kest H, Kaushik A, DeBruin W, et al. (2020) Multisystem inflammatory syndrome in children (MIS-C) associated with 2019 novel coronavirus (SARS-CoV-2) infection. Case Rep Pediatr 2020: 8875987.
[23]	Alnashri H, Aljohani N, Tayeb S, et al. (2020) A challenging case of multisystem inflammatory syndrome in children related to coronavirus disease-19 hospitalized under adult medical service. IDCases 22: e00957. doi: 10.1016/j.idcr.2020.e00957
[24]	Vari D, Miller JM, Rellosa N, et al. (2020) Severe cardiac dysfunction in a patient with multisystem inflammatory syndrome in children associated with COVID-19: Retrospective diagnosis of a puzzling presentation. A case report. Prog Pediatr Cardiol 58: 101270. doi: 10.1016/j.ppedcard.2020.101270
[25]	Okarska-Napierała M, Zalewska E, Kuchar E (2020) Fever and diarrhea as the only symptoms of multisystem inflammatory syndrome in children (MIS-C). Gastroenterology In press.
[26]	Giannattasio A, Maglione M, Zenzeri L, et al. (2020) A child with a severe multisystem inflammatory syndrome following an asymptomatic COVID-19 infection: A novel management for a new disease? J Med Virol In press.
[27]	Gupta A, Gill A, Sharma M, et al. (2020) Multi-System Inflammatory Syndrome in a Child Mimicking Kawasaki Disease. J Trop Pediatr In press.
[28]	Khesrani LS, Chana k, Sadar FZ, et al. (2020) Intestinal ischemia secondary to Covid-19. J Pediatr Surg Case Rep 61: 101604. doi: 10.1016/j.epsc.2020.101604
[29]	Feldstein LR, Rose EB, Horwitz SM, et al. (2020) Multisystem inflammatory syndrome in US children and adolescents. New Engl J Med 383: 334-346. doi: 10.1056/NEJMoa2021680
[30]	Gruber C, Patel R, Trachman R, et al. (2020) Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C). medRxiv In press.
[31]	Viner RM, Whittaker E (2020) Kawasaki-like disease: emerging complication during the COVID-19 pandemic. Lancet 395: 1741-1743. doi: 10.1016/S0140-6736(20)31129-6
[32]	Saeed A, Shorafa E (2020) Status epilepticus as a first presentation of COVID-19 infection in a 3 years old boy; Case report and review the literature. IDCases 22: e00942. doi: 10.1016/j.idcr.2020.e00942
[33]	Verdoni L, Mazza A, Gervasoni A, et al. (2020) An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet 395: 1771-1778. doi: 10.1016/S0140-6736(20)31103-X
[34]	Domico M, McCanta AC, Hunt JL, et al. (2020) High-grade heart block requiring transvenous pacing associated with multisystem inflammatory syndrome in children during the COVID-19 pandemic. HeartRhythm Case Rep 6: 811-814. doi: 10.1016/j.hrcr.2020.08.015
[35]	Farias ECF, Justino MCA, Mello M (2020) Multisystem inflammatory syndrome in a child associated with coronavirus disease 19 in the Brazilian Amazon: fatal outcome in an infant. Rev Paul Pediatr 38: e2020165. doi: 10.1590/1984-0462/2020/38/2020165
[36]	Akca UK, Kesici S, Ozsurekci Y, et al. (2020) Kawasaki-like disease in children with COVID-19. Rheumatol Int 40: 2105-2115. doi: 10.1007/s00296-020-04701-6
[37]	Balasubramanian S, Nagendran TM, Ramachandran B, et al. (2020) Hyper-inflammatory syndrome in a child with COVID-19 treated successfully with intravenous immunoglobulin and tocilizumab. Indian Pediatr 57: 681-683. doi: 10.1007/s13312-020-1901-z
[38]	Jones VG, Mills M, Suarez D, et al. (2020) COVID-19 and Kawasaki disease: novel virus and novel case. Hosp Pediatr 10: 537-540. doi: 10.1542/hpeds.2020-0123
[39]	Suratannon N, Dik WA, Chatchatee P, et al. (2020) COVID-19 in children: Heterogeneity within the disease and hypothetical pathogenesis. Asian Pac J Allergy Immunol 38: 170-177.
[40]	Theocharis P, Wong J, Pushparajah K, et al. (2020) Multimodality cardiac evaluation in children and young adults with multisystem inflammation associated with COVID-19. Eur Heart J Cardiovasc Imaging 1–8.
[41]	Swann OV, Holden KA, Turtle L, et al. (2020) Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicentre observational cohort study. BMJ 370: m3249. doi: 10.1136/bmj.m3249
[42]	Information for Healthcare Providers about Multisystem Inflammatory Syndrome in Children (MIS-C). Centers for Disease Control and Prevention, 2020 Available from: https://www.cdc.gov/mis-c/hcp/.
[43]	Wang C, Li W, Drabek D, et al. (2020) A human monoclonal antibody blocking SARS-CoV-2 infection. Nat Commun 11: 2251. doi: 10.1038/s41467-020-16256-y
[44]	Vuille-dit-Bille RN, Liechty KW, Verrey F, et al. (2020) SARS-CoV-2 receptor ACE2 gene expression in small intestine correlates with age. Amino Acids 52: 1063-1065. doi: 10.1007/s00726-020-02870-z
[45]	Brandtzaeg P, Johansen FE (2007) IgA and mucosal homeostasis. Mucosal Immune Defense: Immunoglobulin A Boston: Springer.
[46]	Hennon TR, Penque MD, Abdul-Aziz R, et al. (2020) COVID-19 associated multisystem inflammatory syndrome in children (MIS-C) guidelines; a western New York approach. Prog Pediatr Cardiol 23: 101232. doi: 10.1016/j.ppedcard.2020.101232
[47]	Nakra NA, Blumberg DA, Herrera-Guerra A, et al. (2020) Multi-system inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection: review of clinical presentation, hypothetical pathogenesis, and proposed management. Children 7: 69. doi: 10.3390/children7070069
[48]	Matsubara D, Kauffman HL, Wang Y, et al. (2020) Echocardiographic findings in pediatric multisystem inflammatory syndrome associated with COVID-19 in the United States. J Am Coll Cardiol 76: 1947-1961. doi: 10.1016/j.jacc.2020.08.056

allergy-05-01-004-s001.pdf

Reader Comments

Your name:*

Email:*
© 2021 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)