Abstract:Multisystem inflammatory syndrome in children (MIS-C) is a type of hyperinflammatory symptoms similar to Kawasaki disease after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is commonly observed in children aged 8-10 years. Primary therapeutic medications for MIS-C are intravenous immunoglobulins and glucocorticoids. It has been reported that biologics, such as IL-1 receptor antagonist anakinra, IL-6 receptor antagonist tocilizumab, and TNF-α receptor antagonist infliximab, can be used as an option for critically ill patients. This article elaborates on the mechanism of action of the above biologics and discusses the efficacy and safety biologics in the treatment of MIS-C after SARS-CoV-2 infection, in order to provide methods for the treatment of MIS-C with severe symptoms.
CUI Han-Yu,HU Chang-Ping. Recent research on the application of biologics in the treatment of multisystem inflammatory syndrome in children after SARS-CoV-2 infection[J]. CJCP, 2022, 24(2): 216-222.
3 World Health Organization. WHO coronavirus (COVID-19)dashboard [EB/OL]. (2021-11-01) [2021-11-01]. https://app.powerbi.com/.
4 Centers for Disease Control and Prevention. Health department-reported cases of multisystem inflammatory syndrome in children (MIS-C) in the United States[EB/OL]. (2021-11-01)[2021-11-01]. https://stacks.cdc.gov/view/cdc/104682.
Yasuhara J, Watanabe K, Takagi H, et al. COVID-19 and multisystem inflammatory syndrome in children: a systematic review and meta-analysis[J]. Pediatr Pulmonol, 2021, 56(5): 837-848. PMID: 33428826. PMCID: PMC8013394. DOI: 10.1002/ppul.25245.
McMurray JC, May JW, Cunningham MW, et al. Multisystem inflammatory syndrome in children (MIS-C), a post-viral myocarditis and systemic vasculitis-a critical review of its pathogenesis and treatment[J]. Front Pediatr, 2020, 8: 626182. PMID: 33425823. PMCID: PMC7793714. DOI: 10.3389/fped.2020.626182.
8 Centers for Disease Control and Prevention. Multisystem inflammatory syndrome (MIS)[EB/OL]. (2021-05-20)[2021-05-20]. https://www.cdc.gov/mis/.
Lima-Setta F, Magalh?es-Barbosa MCD, Rodrigues-Santos G, et al. Multisystem inflammatory syndrome in children (MIS-C) during SARS-CoV-2 pandemic in Brazil: a multicenter, prospective cohort study[J]. J Pediatr (Rio J), 2021, 97(3): 354-361. PMID: 33186512. PMCID: PMC7649656. DOI: 10.1016/j.jped.2020.10.008.
García-Salido A, de Carlos Vicente JC, Belda Hofheinz S, et al. Severe manifestations of SARS-CoV-2 in children and adolescents: from COVID-19 pneumonia to multisystem inflammatory syndrome: a multicentre study in pediatric intensive care units in Spain[J]. Crit Care, 2020, 24(1): 666. PMID: 33243303. PMCID: PMC7689392. DOI: 10.1186/s13054-020-03332-4.
McCormick DW, Richardson LC, Young PR, et al. Deaths in children and adolescents associated with COVID-19 and MIS-C in the United States[J]. Pediatrics, 2021, 148(5): e2021052273. PMID: 34385349. DOI: 10.1542/peds.2021-052273.
Whittaker E, Bamford A, Kenny J, et al. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2[J]. JAMA, 2020, 324(3): 259-269. PMID: 32511692. PMCID: PMC7281356. DOI: 10.1001/jama.2020.10369.
Lee PY, Day-Lewis M, Henderson LA, et al. Distinct clinical and immunological features of SARS-CoV-2-induced multisystem inflammatory syndrome in children[J]. J Clin Invest, 2020, 130(11): 5942-5950. PMID: 32701511. PMCID: PMC7598077. DOI: 10.1172/JCI141113.
Okarska-Napiera?a M, Mańdziuk J, Feleszko W, et al. Recurrent assessment of lymphocyte subsets in 32 patients with multisystem inflammatory syndrome in children (MIS-C)[J]. Pediatr Allergy Immunol, 2021, 32(8): 1857-1865. PMID: 34331778. DOI: 10.1111/pai.13611.
16 Karagol C, Tehci AK, Gungor A, et al. Delta neutrophil index and C-reactive protein: a potential diagnostic marker of multisystem inflammatory syndrome in children (MIS-C) with COVID-19[J]. Eur J Pediatr, 2021. PMID: 34647164. PMCID: PMC8514280. DOI: 10.1007/s00431-021-04281-y. Epub ahead of print.
Henderson LA, Canna SW, Friedman KG, et al. American college of rheumatology clinical guidance for multisystem inflammatory syndrome in children associated with SARS-CoV-2 and hyperinflammation in pediatric COVID-19: version2[J]. Arthritis Rheumatol, 2021, 73(4): e13-e29. PMID: 33277976. PMCID: PMC8559788. DOI: 10.1002/art.41616.
Felsenstein S, Willis E, Lythgoe H, et al. Presentation, treatment response and short-term outcomes in paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS)[J]. J Clin Med, 2020, 9(10): 3293. PMID: 33066459. PMCID: PMC7602286. DOI: 10.3390/jcm9103293.
Ouldali N, Toubiana J, Antona D, et al. Association of intravenous immunoglobulins plus methylprednisolone vs immunoglobulins alone with course of fever in multisystem inflammatory syndrome in children[J]. JAMA, 2021, 325(9): 855-864. PMID: 33523115. PMCID: PMC7851757. DOI: 10.1001/jama.2021.0694.
Kabeerdoss J, Pilania RK, Karkhele R, et al. Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management[J]. Rheumatol Int, 2021, 41(1): 19-32. PMID: 33219837. PMCID: PMC7680080. DOI: 10.1007/s00296-020-04749-4.
Fouriki A, Fougère Y, De Camaret C, et al. Case report: case series of children with multisystem inflammatory syndrome following SARS-CoV-2 infection in Switzerland[J]. Front Pediatr, 2020, 8: 594127. PMID: 33469522. PMCID: PMC7813982. DOI: 10.3389/fped.2020.594127.
Calò Carducci FI, De Ioris MA, Agrati C, et al. Hyperinflammation in two severe acute respiratory syndrome coronavirus 2-infected adolescents successfully treated with the interleukin-1 inhibitor anakinra and glucocorticoids[J]. Front Pediatr, 2020, 8: 576912. PMID: 33330276. PMCID: PMC7734022. DOI: 10.3389/fped.2020.576912.
Cirks BT, Geracht JC, Jones OY, et al. Multisystem inflammatory syndrome in children during the COVID-19 pandemic: a case report on managing the hyperinflammation[J]. Mil Med, 2021, 186(1-2): e270-e276. PMID: 33242097. PMCID: PMC7717316. DOI: 10.1093/milmed/usaa508.
Riollano-Cruz M, Akkoyun E, Briceno-Brito E, et al. Multisystem inflammatory syndrome in children related to COVID-19: a New York city experience[J]. J Med Virol, 2021, 93(1): 424-433. PMID: 32584487. PMCID: PMC7361761. DOI: 10.1002/jmv.26224.
Dolinger MT, Person H, Smith R, et al. Pediatric Crohn disease and multisystem inflammatory syndrome in children (MIS-C) and COVID-19 treated with infliximab[J]. J Pediatr Gastroenterol Nutr, 2020, 71(2): 153-155. PMID: 32452979. PMCID: PMC7268863. DOI: 10.1097/MPG.0000000000002809.
Pourmoghaddas Z, Sadeghizadeh A, Tara SZ, et al. Longitudinally extensive transverse myelitis as a sign of multisystem inflammatory syndrome following COVID-19 infection: a pediatric case report[J]. J Neuroimmunol, 2021, 360: 577704. PMID: 34517154. PMCID: PMC8397488. DOI: 10.1016/j.jneuroim.2021.577704.
Abdel-Haq N, Asmar BI, Deza Leon MP, et al. SARS-CoV-2-associated multisystem inflammatory syndrome in children: clinical manifestations and the role of infliximab treatment[J]. Eur J Pediatr, 2021, 180(5): 1581-1591. PMID: 33452570. PMCID: PMC7810600. DOI: 10.1007/s00431-021-03935-1.
Shikhare AR, Iqbal RM, Tariq R, et al. Diversity of cardiac and gastrointestinal presentations of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19: a case series[J]. Glob Pediatr Health, 2021, 8: 2333794X21996613. PMID: 33748343. PMCID: PMC7903818. DOI: 10.1177/2333794X21996613.
Navaeifar MR, Shahbaznejad L, Sadeghi Lotfabadi A, et al. COVID-19-associated multisystem inflammatory syndrome complicated with giant coronary artery aneurysm[J]. Case Rep Pediatr, 2021, 2021: 8836403. PMID: 33505752. PMCID: PMC7798113. DOI: 10.1155/2021/8836403.
Bautista-Rodriguez C, Sanchez-de-Toledo J, Clark BC, et al. Multisystem inflammatory syndrome in children: an international survey[J]. Pediatrics, 2021, 147(2): e2020024554. PMID: 33234669. DOI: 10.1542/peds.2020-024554.
Panigrahy N, Policarpio J, Ramanathan R. Multisystem inflammatory syndrome in children and SARS-CoV-2: a scoping review[J]. J Pediatr Rehabil Med, 2020, 13(3): 301-316. PMID: 33252101. DOI: 10.3233/PRM-200794.