Clinical Characteristics and Outcomes in Children With Severe Multisystem Inflammatory Syndrome in Children in Malaysia: A Nationwide Cohort Study
Main Article Content
Abstract
Introduction: Early identification of patients at risk for severe multisystem inflammatory syndrome in children (MIS-C) is essential for favourable clinical outcomes. This study aims to identify the clinical characteristics, factors and outcomes associated with severe MIS-C. Materials and methods: In this retrospective cohort study involving 14 major hospitals in Malaysia, children <15 years who met the United States Centres for Disease Control and Prevention case definition for MIS-C were included. Severe MIS-C was defined as children who required inotropic support, ventilatory support (invasive or non-invasive ventilation), or left ventricular ejection fraction of <55%. The factors investigated for severe MIS-C were demographic characteristics, the presence of comorbidities, clinical characteristics, and laboratory measures. Multivariable logistic regression was used to compute the adjusted odds ratio (aORs) of factors associated with severe MIS-C. Results: Among the 155 patients, 91 (58.7%) presented with severe MIS-C. Severe MIS-C was more likely in patients aged ≥5 years old (aOR 2.13, 95% confidence interval [CI] 1.08-4.21), with dehydration (aOR 3.80, 95% CI 1.53-9.45), lethargy (aOR 2.02, 95% CI 0.97-4.18), tachycardia (aOR 8.33, 95% CI 3.27-21.22), albumin <30g/L (aOR 3.36, 95% CI 1.58-7.13), creatine kinase >200U/L (aOR 3.68, 95% CI 1.57-8.64), D-dimer >3.0μg/mL (aOR 2.11, 95% CI 1.08-4.13), ferritin >500ng/mL (aOR 3.77, 95% CI 1.88-7.55), prothrombin time >12.7 seconds (aOR 3.22, 95% CI 1.61-6.43), and urea >6mmol/L (aOR 5.09, 95% CI 2.04-12.71). Conclusion: Identification of these associated factors of severity in MIS-C could aid in early recognition and prompt escalation of care, leading to better outcomes.
Downloads
Article Details
References
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. https://doi.org/10.1136/bmj.m2094
DeBiasi RL, Song X, Delaney M, Bell M, Smith K, Pershad J, et al. Severe Coronavirus Disease-2019 in Children and Young Adults in the Washington, DC, Metropolitan Region. J Pediatr. 2020;223:199-203 e1. https://doi.org/10.1016/j.jpeds.2020.05.007
CDC. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 Infection 2023 Case Definition 2023. Available from: https://ndc.services.cdc.gov/case-definitions/multisystem-inflammatory-syndrome-in-children-mis-c/. Accessed April 4, 2024.
WHO. Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19. Scientific brief: May 15, 2020. 2020. Available from: https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19. Accessed April 10, 2024.
RCPCH. Paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS) - national consensus management pathway 2024. Available from: https://www.rcpch.ac.uk/resources/paediatric-multisystem-inflammatory-syndrome-temporally-associated-covid-19-pims-national. Accessed April 10, 2024.
Kabeerdoss J, Pilania RK, Karkhele R, Kumar TS, Danda D, Singh S. Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management. Rheumatol Int. 2021;41(1):19-32. https://doi.org/10.1007/s00296-020-04749-4
Li W, Tang Y, Shi Y, Chen Y, Liu E. Why multisystem inflammatory syndrome in children has been less commonly described in Asia? Transl Pediatr. 2020;9(6):873-5. https://doi.org/10.21037/tp-20-151
Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, et al. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med. 2020;383(4):334-46. https://doi.org/10.1056/NEJMoa2021680
Santos MO, Goncalves LC, Silva PAN, Moreira ALE, Ito CRM, Peixoto FAO, et al. Multisystem inflammatory syndrome (MIS-C): a systematic review and meta-analysis of clinical characteristics, treatment, and outcomes. J Pediatr (Rio J). 2022;98(4):338-49. https://doi.org/10.1016/j.jped.2021.08.006
Hospital YNHCs. Managment of Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19. 2020. Available from: https://lucid.app/documents/embeddedchart/e2fb545a-ac76-40b1-a11e-09bb6de8ec5b#. Accessed April 10, 2024.
WHO. Integrated Management of Childhood Illness (IMCI). Module 4 : Diarrhoea. 2014. Available from: https:// apps.who. int/iris/ bitstream /handle/ 10665/ 104772/ 978924 1506 823_ Module-4_eng.pdf;jsessionid=3FB42EE9 C05CD94 5EA45DB35 BD506623? sequence=6. Accessed April 10, 2024.
Keith Klienman LM, Matthew Molloy. The Harriet Lane Handbook, 22nd Edition: Elsevier; 2020.
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(17):e927-e99. https://doi.org/10.1161/CIR.0000000000000484
Choe YJ, Choi EH, Choi JW, Eun BW, Eun LY, Kim YJ, et al. Surveillance of COVID-19-Associated Multisystem Inflammatory Syndrome in Children, South Korea. Emerg Infect Dis. 2021;27(4):1196-200. https://doi.org/10.3201/eid2704.210026
Putri ND, Prawira Y, Tartila T, Jasin MR, Puspitasari HA, Puspaningtyas NW, et al. Clinical Features of Multisystem Inflammatory Syndrome in Children Associated with COVID-19 in Indonesia. J Trop Pediatr. 2022;68(3). https://doi.org/10.1093/tropej/fmac025
Mehra B, Pandey M, Gupta D, Oberoi T, Jerath N, Sharma R, et al. COVID-19-associated Multisystem Inflammatory Syndrome in Children: A Multicentric Retrospective Cohort Study. Indian J Crit Care Med. 2021;25(10):1176-82. https://doi.org/10.5005/jp-journals-10071-23996
Karunakar P, Ramamoorthy JG, Anantharaj A, Parameswaran N, Biswal N, Dhodapkar R, et al. Clinical profile and outcomes of multisystem inflammatory syndrome in children (MIS-C): Hospital-based prospective observational study from a tertiary care hospital in South India. J Paediatr Child Health. 2022. https://doi.org/10.1111/jpc.16129
Otar Yener G, Paç Kısaarslan A, Ulu K, Atalay E, Haşlak F, Özdel S, et al. Differences and similarities of multisystem inflammatory syndrome in children, Kawasaki disease and macrophage activating syndrome due to systemic juvenile idiopathic arthritis: a comparative study. Rheumatol Int. 2022;42(5):879-89. https://doi.org/10.1007/s00296-021-04980-7
Malaysia DoS. Current population estimates, Malaysia, 2021. 2021. Available from: https:// www.dosm.gov.my/ v1/index .php?r= column/ cthemeBy Cat&cat= 155&bul _idZjJOSn pJR21sQ WVUc Up6OD Rudm 5JZz09& menu_id= L0phe U43NWJ wRWVSZk lWdz Q4T lhU UT09. Accessed April 10, 2024.
DOSM. Department of Statistics Malaysia Official Portal: DOSM; 2022 [Available from: https://www.dosm.gov.my/v1/index.php.
Malaysia MoH. Github database, COVID-19 Malaysia. 2022. Available from: https://github.com/MoH-Malaysia/covid19-public/blob/main/epidemic/cases_malaysia.csv. Accessed April 10, 2024.
Lim L, Lim SJ, Loy JS, Ng DC. Multisystem inflammatory syndrome in children (MIS-C) occurring in temporal proximity between siblings. BMJ Case Rep. 2021;14(9). https://doi.org/10.1136/bcr-2021-246066
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(4):347-58. https://doi.org/10.1056/NEJMoa2021756
Kaushik S, Aydin SI, Derespina KR, Bansal PB, Kowalsky S, 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. J Pediatr. 2020;224:24-9. https://doi.org/10.1016/j.jpeds.2020.06.045
Rowley AH. Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children. Nat Rev Immunol. 2020;20(8):453-4. https://doi.org/10.1038/s41577-020-0367-5
Bautista-Rodriguez C, Sanchez-de-Toledo J, Clark BC, Herberg J, Bajolle F, Randanne PC, et al. Multisystem Inflammatory Syndrome in Children: An International Survey. Pediatrics. 2021;147(2). https://doi.org/10.1542/peds.2020-024554
Abrams JY, Oster ME, Godfred-Cato SE, Bryant B, Datta SD, Campbell AP, et al. Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study. Lancet Child Adolesc Health. 2021;5(5):323-31. https://doi.org/10.1016/S2352-4642(21)00050-X
Godfred-Cato S, Bryant B, Leung J, Oster ME, Conklin L, Abrams J, et al. COVID-19-Associated Multisystem Inflammatory Syndrome in Children - United States, March-July 2020. MMWR Morb Mortal Wkly Rep. 2020;69(32):1074-80. https://doi.org/10.15585/mmwr.mm6932e2
Feldstein LR, Tenforde MW, Friedman KG, Newhams M, Rose EB, Dapul H, et al. Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19. JAMA. 2021;325(11):1074-87. https://doi.org/10.1001/jama.2021.2091
Aydın F, Çelikel E, Ekici Tekin Z, Coşkun S, Sezer M, Karagöl C, et al. Comparison of baseline laboratory findings of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis and multisystem inflammatory syndrome in children. Int J Rheum Dis. 2021;24(4):542-7. https://doi.org/10.1111/1756-185x.14078
Lee PY, Day-Lewis M, Henderson LA, Friedman KG, Lo J, Roberts JE, et al. Distinct clinical and immunological features of SARS-CoV-2-induced multisystem inflammatory syndrome in children. J Clin Invest. 2020;130(11):5942-50. https://doi.org/10.1172/jci141113
Fernandes DM, Oliveira CR, Guerguis S, Eisenberg R, Choi J, Kim M, et al. Severe Acute Respiratory Syndrome Coronavirus 2 Clinical Syndromes and Predictors of Disease Severity in Hospitalized Children and Youth. J Pediatr. 2021;230:23-31 e10. https://doi.org/10.1016/j.jpeds.2020.11.016
Shabab J, Dubisky A, Singh A, Crippen M, Abulaban K, Aldrich A. A descriptive study on multisystem inflammatory syndrome in children in a single center in West Michigan. Pediatr Rheumatol Online J. 2021;19(1):172. https://doi.org/10.1186/s12969-021-00658-3
Flood J, Shingleton J, Bennett E, Walker B, Amin-Chowdhury Z, Oligbu G, et al. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): Prospective, national surveillance, United Kingdom and Ireland, 2020. Lancet Reg Health Eur. 2021;3:100075. https://doi.org/10.1016/j.lanepe.2021.100075
Chinniah K, Bhimma R, Naidoo KL, Archary M, Jeena P, Hoosen E, et al. Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 Infection in KwaZulu-Natal, South Africa. Pediatr Infect Dis J. 2023;42(1):e9-e14. https://doi.org/10.1097/inf.0000000000003759
Merckx J, Cooke S, El Tal T, Bitnun A, Morris SK, Yeh EA, et al. Predictors of severe illness in children with multisystem inflammatory syndrome after SARS-CoV-2 infection: a multicentre cohort study. CMAJ. 2022;194(14):E513-E23. https://doi.org/10.1503/cmaj.210873
Akhtar S, Anis I, Kumar NA, Ihsan MT, Raheem A, Bano S. Assessing pattern of the Pediatric Multisystem Inflammatory Syndrome (PMIS) in children during the COVID-19 pandemic: experience from the emergency department of tertiary care center of a low-middle-income country. BMC Pediatr. 2024;24(1):98. https://doi.org/10.1186/s12887-024-04572-x
Acevedo L, Pineres-Olave BE, Nino-Serna LF, Vega LM, Gomez IJA, Chacon S, et al. Mortality and clinical characteristics of multisystem inflammatory syndrome in children (MIS-C) associated with covid-19 in critically ill patients: an observational multicenter study (MISCO study). BMC Pediatr. 2021;21(1):516. https://doi.org/10.1186/s12887-021-02974-9