Skip to main content
Top
Published in: World Journal of Pediatrics 4/2024

21-03-2024 | Post-COVID Syndrome | Review Article

Treatment of multisystem inflammatory syndrome in children

Authors: Tong Tong, Yi-Hua Jin, Min Wang, Fang-Qi Gong

Published in: World Journal of Pediatrics | Issue 4/2024

Login to get access

Abstract

Background

Multisystem inflammatory syndrome in children (MIS-C), a relatively uncommon but severe pediatric complication, is associated with coronavirus disease 2019 (COVID-19). A variety of treatment approaches, including intravenous immunoglobulins (IVIGs), glucocorticoids (GCs) and biologic agents, such as anakinra and infliximab, have been described for the management of COVID-19-related MIS-C. Anticoagulant therapy is also important. However, a well-developed treatment system has not been established, and many issues remain controversial. Several recently published articles related to the treatment of MIS-C have been released. Hence, in this review, we identified relevant articles published recently and summarized the treatment of MIS-C more comprehensively and systematically.

Data sources

We reviewed the literature on the treatment of MIS-C through 20 September 2023. The PubMed/Medline, Web of Science, EMBASE, and Cochrane Library databases were searched with the combination of the terms “multisystem inflammatory syndrome”, “MIS-C”, “PIMS-TS”, “therapy”, “treatment”, “drug”, “IVIG”, “GCs”, “intravenous immunoglobulin”, “corticosteroids”, “biological agent”, and “aspirin”.

Results

The severity of MIS-C varies, and different treatment schemes should be used according to the specific condition. Ongoing research and data collection are vital to better understand the pathophysiology and optimal management of MIS-C.

Conclusions

MIS-C is a disease involving multiple systems and has great heterogeneity. With the accumulation of additional experience, we have garnered fresh insights into its treatment strategies. However, there remains a critical need for greater standardization in treatment protocols, alongside the pressing necessity for more robust and meticulously conducted studies to deepen our understanding of these protocols.

Video abstract

Supplementary file1 (MP4 208044 kb)
Literature
1.
go back to reference Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395:1607–8.CrossRefPubMedPubMedCentral Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395:1607–8.CrossRefPubMedPubMedCentral
2.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
6.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
7.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
8.
go back to reference 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:e2020024554.CrossRefPubMed 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:e2020024554.CrossRefPubMed
9.
go back to reference Ahmed M, Advani S, Moreira A, Zoretic S, Martinez J, Chorath K, et al. Multisystem inflammatory syndrome in children: a systematic review. EClinicalMedicine. 2020;26:100527.CrossRefPubMedPubMedCentral Ahmed M, Advani S, Moreira A, Zoretic S, Martinez J, Chorath K, et al. Multisystem inflammatory syndrome in children: a systematic review. EClinicalMedicine. 2020;26:100527.CrossRefPubMedPubMedCentral
10.
go back to reference Kostik MM, Bregel LV, Avrusin IS, Dondurei EA, Matyunova AE, Efremova OS, et al. Distinguishing between multisystem inflammatory syndrome, associated with COVID-19 in children and the Kawasaki disease: development of preliminary criteria based on the data of the retrospective multicenter cohort study. Front Pediatr. 2021;9:787353.CrossRefPubMedPubMedCentral Kostik MM, Bregel LV, Avrusin IS, Dondurei EA, Matyunova AE, Efremova OS, et al. Distinguishing between multisystem inflammatory syndrome, associated with COVID-19 in children and the Kawasaki disease: development of preliminary criteria based on the data of the retrospective multicenter cohort study. Front Pediatr. 2021;9:787353.CrossRefPubMedPubMedCentral
11.
go back to reference Acevedo L, Piñeres-Olave BE, Niño-Serna LF, Vega LM, Gomez IJA, Chacón 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;21:516.CrossRefPubMedPubMedCentral Acevedo L, Piñeres-Olave BE, Niño-Serna LF, Vega LM, Gomez IJA, Chacón 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;21:516.CrossRefPubMedPubMedCentral
12.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
13.
go back to reference 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;383:334–46.CrossRefPubMed 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;383:334–46.CrossRefPubMed
14.
go back to reference Jiang L, Tang K, Levin M, Irfan O, Morris SK, Wilson K, et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect Dis. 2020;20:e276–88.CrossRefPubMedPubMedCentral Jiang L, Tang K, Levin M, Irfan O, Morris SK, Wilson K, et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect Dis. 2020;20:e276–88.CrossRefPubMedPubMedCentral
15.
go back to reference Schlapbach LJ, Andre MC, Grazioli S, Schöbi N, Ritz N, Aebi C, et al. Best practice recommendations for the diagnosis and management of children with pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS; multisystem inflammatory syndrome in children, MIS-C) in Switzerland. Front Pediatr. 2021;9:667507.CrossRefPubMedPubMedCentral Schlapbach LJ, Andre MC, Grazioli S, Schöbi N, Ritz N, Aebi C, et al. Best practice recommendations for the diagnosis and management of children with pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS; multisystem inflammatory syndrome in children, MIS-C) in Switzerland. Front Pediatr. 2021;9:667507.CrossRefPubMedPubMedCentral
16.
go back to reference Harwood R, Allin B, Jones CE, Whittaker E, Ramnarayan P, Ramanan AV, et al. A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): results of a national Delphi process. Lancet Child Adolesc Health. 2021;5:133–41.CrossRefPubMed Harwood R, Allin B, Jones CE, Whittaker E, Ramnarayan P, Ramanan AV, et al. A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): results of a national Delphi process. Lancet Child Adolesc Health. 2021;5:133–41.CrossRefPubMed
17.
go back to reference Henderson LA, Canna SW, Friedman KG, Gorelik M, Lapidus SK, Bassiri H, 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: version 3. Arthritis Rheumatol. 2022;74:e1–20.CrossRefPubMedPubMedCentral Henderson LA, Canna SW, Friedman KG, Gorelik M, Lapidus SK, Bassiri H, 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: version 3. Arthritis Rheumatol. 2022;74:e1–20.CrossRefPubMedPubMedCentral
18.
go back to reference Feleszko W, Okarska-Napierala M, Buddingh EP, Bloomfield M, Sediva A, Bautista-Rodriguez C, et al. Pathogenesis, immunology, and immune-targeted management of the multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome (PIMS): EAACI position paper. Pediatr Allergy Immunol. 2023;34:e13900.CrossRefPubMed Feleszko W, Okarska-Napierala M, Buddingh EP, Bloomfield M, Sediva A, Bautista-Rodriguez C, et al. Pathogenesis, immunology, and immune-targeted management of the multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome (PIMS): EAACI position paper. Pediatr Allergy Immunol. 2023;34:e13900.CrossRefPubMed
19.
go back to reference Algarni AS, Alamri NM, Khayat NZ, Alabdali RA, Alsubhi RS, Alghamdi SH. Clinical practice guidelines in multisystem inflammatory syndrome (MIS-C) related to COVID-19: a critical review and recommendations. World J Pediatr. 2022;18:83–90.CrossRefPubMedPubMedCentral Algarni AS, Alamri NM, Khayat NZ, Alabdali RA, Alsubhi RS, Alghamdi SH. Clinical practice guidelines in multisystem inflammatory syndrome (MIS-C) related to COVID-19: a critical review and recommendations. World J Pediatr. 2022;18:83–90.CrossRefPubMedPubMedCentral
20.
go back to reference Jonat B, Geneslaw AS, Capone CA, Shah S, Bartucca L, Sewell TB, et al. Early treatment of multisystem inflammatory syndrome in children. Pediatrics. 2023;152:e2023061297.CrossRefPubMed Jonat B, Geneslaw AS, Capone CA, Shah S, Bartucca L, Sewell TB, et al. Early treatment of multisystem inflammatory syndrome in children. Pediatrics. 2023;152:e2023061297.CrossRefPubMed
21.
go back to reference Cannon L, Campbell MJ, Wu EY. Multisystemic inflammatory syndrome in children and Kawasaki disease: parallels in pathogenesis and treatment. Curr Allergy Asthma Rep. 2023;23:341–50.CrossRefPubMed Cannon L, Campbell MJ, Wu EY. Multisystemic inflammatory syndrome in children and Kawasaki disease: parallels in pathogenesis and treatment. Curr Allergy Asthma Rep. 2023;23:341–50.CrossRefPubMed
22.
go back to reference Zhang QY, Xu BW, Du JB. Similarities and differences between multiple inflammatory syndrome in children associated with COVID-19 and Kawasaki disease: clinical presentations, diagnosis, and treatment. World J Pediatr. 2021;17:335–40.CrossRefPubMedPubMedCentral Zhang QY, Xu BW, Du JB. Similarities and differences between multiple inflammatory syndrome in children associated with COVID-19 and Kawasaki disease: clinical presentations, diagnosis, and treatment. World J Pediatr. 2021;17:335–40.CrossRefPubMedPubMedCentral
23.
go back to reference Furusho K, Kamiya T, Nakano H, Kiyosawa N, Shinomiya K, Hayashidera T, et al. High-dose intravenous gammaglobulin for Kawasaki disease. Lancet. 1984;2:1055–8.CrossRefPubMed Furusho K, Kamiya T, Nakano H, Kiyosawa N, Shinomiya K, Hayashidera T, et al. High-dose intravenous gammaglobulin for Kawasaki disease. Lancet. 1984;2:1055–8.CrossRefPubMed
24.
go back to reference Dove ML, Jaggi P, Kelleman M, Abuali M, Ang JY, Ballan W, et al. Multisystem inflammatory syndrome in children: survey of protocols for early hospital evaluation and management. J Pediatr. 2021;229:33–40.CrossRefPubMed Dove ML, Jaggi P, Kelleman M, Abuali M, Ang JY, Ballan W, et al. Multisystem inflammatory syndrome in children: survey of protocols for early hospital evaluation and management. J Pediatr. 2021;229:33–40.CrossRefPubMed
27.
go back to reference Ballow M. The IgG molecule as a biological immune response modifier: mechanisms of action of intravenous immune serum globulin in autoimmune and inflammatory disorders. J Allergy Clin Immunol. 2011;127:315–23 (quiz 324–5).CrossRefPubMed Ballow M. The IgG molecule as a biological immune response modifier: mechanisms of action of intravenous immune serum globulin in autoimmune and inflammatory disorders. J Allergy Clin Immunol. 2011;127:315–23 (quiz 324–5).CrossRefPubMed
28.
go back to reference Norris PAA, Kaur G, Lazarus AH. New insights into IVIg mechanisms and alternatives in autoimmune and inflammatory diseases. Curr Opin Hematol. 2020;27:392–8.CrossRefPubMed Norris PAA, Kaur G, Lazarus AH. New insights into IVIg mechanisms and alternatives in autoimmune and inflammatory diseases. Curr Opin Hematol. 2020;27:392–8.CrossRefPubMed
29.
go back to reference 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;142:429–36.CrossRefPubMed 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;142:429–36.CrossRefPubMed
30.
go back to reference Jone PN, Everitt MD. Management of multisystem inflammatory syndrome in children associated with COVID-19 infection. Curr Opin Pediatr. 2021;7:119–28. Jone PN, Everitt MD. Management of multisystem inflammatory syndrome in children associated with COVID-19 infection. Curr Opin Pediatr. 2021;7:119–28.
32.
go back to reference Ludwikowska KM, Okarska-Napierała M, Dudek N, Tracewski P, Kusa J, Piwoński KP, et al. Distinct characteristics of multisystem inflammatory syndrome in children in Poland. Sci Rep. 2021;11:23562.CrossRefPubMedPubMedCentral Ludwikowska KM, Okarska-Napierała M, Dudek N, Tracewski P, Kusa J, Piwoński KP, et al. Distinct characteristics of multisystem inflammatory syndrome in children in Poland. Sci Rep. 2021;11:23562.CrossRefPubMedPubMedCentral
33.
go back to reference Yilmaz Ciftdogan D, Ekemen Keles Y, Cetin BS, Dalgic Karabulut N, Emiroglu M, Bagci Z, et al. COVID-19 associated multisystemic inflammatory syndrome in 614 children with and without overlap with Kawasaki disease-Turk MIS-C study group. Eur J Pediatr. 2022;181:2031–43.CrossRefPubMedPubMedCentral Yilmaz Ciftdogan D, Ekemen Keles Y, Cetin BS, Dalgic Karabulut N, Emiroglu M, Bagci Z, et al. COVID-19 associated multisystemic inflammatory syndrome in 614 children with and without overlap with Kawasaki disease-Turk MIS-C study group. Eur J Pediatr. 2022;181:2031–43.CrossRefPubMedPubMedCentral
34.
go back to reference Belay ED, Abrams J, Oster ME, Giovanni J, Pierce T, Meng L, et al. Trends in geographic and temporal distribution of US children with multisystem inflammatory syndrome during the COVID-19 pandemic. JAMA Pediatr. 2021;175:837–45.CrossRefPubMed Belay ED, Abrams J, Oster ME, Giovanni J, Pierce T, Meng L, et al. Trends in geographic and temporal distribution of US children with multisystem inflammatory syndrome during the COVID-19 pandemic. JAMA Pediatr. 2021;175:837–45.CrossRefPubMed
35.
go back to reference Webb K, Abraham DR, Faleye A, McCulloch M, Rabie H, Scott C. Multisystem inflammatory syndrome in children in South Africa. Lancet Child Adolesc Health. 2020;4:e38.CrossRefPubMedPubMedCentral Webb K, Abraham DR, Faleye A, McCulloch M, Rabie H, Scott C. Multisystem inflammatory syndrome in children in South Africa. Lancet Child Adolesc Health. 2020;4:e38.CrossRefPubMedPubMedCentral
36.
go back to reference Bichali S, Bonnet M, Lampin ME, Baudelet JB, Reumaux H, Domanski O, et al. Impact of time to diagnosis on the occurrence of cardiogenic shock in MIS-C post-COVID-19 infection. World J Pediatr. 2023;19:595–604.CrossRefPubMedPubMedCentral Bichali S, Bonnet M, Lampin ME, Baudelet JB, Reumaux H, Domanski O, et al. Impact of time to diagnosis on the occurrence of cardiogenic shock in MIS-C post-COVID-19 infection. World J Pediatr. 2023;19:595–604.CrossRefPubMedPubMedCentral
37.
go back to reference Irfan O, Muttalib F, Tang K, Jiang L, Lassi ZS, Bhutta Z. Clinical characteristics, treatment and outcomes of paediatric COVID-19: a systematic review and meta-analysis. Arch Dis Child. 2021;106:440–8.CrossRefPubMed Irfan O, Muttalib F, Tang K, Jiang L, Lassi ZS, Bhutta Z. Clinical characteristics, treatment and outcomes of paediatric COVID-19: a systematic review and meta-analysis. Arch Dis Child. 2021;106:440–8.CrossRefPubMed
38.
go back to reference Sood M, Sharma S, Sood I, Sharma K, Kaushik A. Emerging evidence on multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection: a systematic review with meta-analysis. SN Compr Clin Med. 2021;3:38–47.CrossRefPubMedPubMedCentral Sood M, Sharma S, Sood I, Sharma K, Kaushik A. Emerging evidence on multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection: a systematic review with meta-analysis. SN Compr Clin Med. 2021;3:38–47.CrossRefPubMedPubMedCentral
39.
40.
go back to reference Villacis-Nunez DS, Jones K, Jabbar A, Fan L, Moore W, Peter AS, et al. Short-term outcomes of corticosteroid monotherapy in multisystem inflammatory syndrome in children. JAMA Pediatr. 2022;176:576–84.CrossRefPubMedPubMedCentral Villacis-Nunez DS, Jones K, Jabbar A, Fan L, Moore W, Peter AS, et al. Short-term outcomes of corticosteroid monotherapy in multisystem inflammatory syndrome in children. JAMA Pediatr. 2022;176:576–84.CrossRefPubMedPubMedCentral
42.
go back to reference Stahn C, Buttgereit F. Genomic and nongenomic effects of glucocorticoids. Nat Clin Pract Rheumatol. 2008;4:525–33.CrossRefPubMed Stahn C, Buttgereit F. Genomic and nongenomic effects of glucocorticoids. Nat Clin Pract Rheumatol. 2008;4:525–33.CrossRefPubMed
43.
go back to reference Son MBF, Murray N, Friedman K, Young CC, Newhams MM, Feldstein LR, et al. Multisystem inflammatory syndrome in children-initial therapy and outcomes. N Engl J Med. 2021;385:23–34.CrossRefPubMed Son MBF, Murray N, Friedman K, Young CC, Newhams MM, Feldstein LR, et al. Multisystem inflammatory syndrome in children-initial therapy and outcomes. N Engl J Med. 2021;385:23–34.CrossRefPubMed
44.
go back to reference Ouldali N, Toubiana J, Antona D, Javouhey E, Madhi F, Lorrot M, et al. Association of intravenous immunoglobulins plus methylprednisolone vs immunoglobulins alone with course of fever in multisystem inflammatory syndrome in children. JAMA. 2021;325:855–64.CrossRefPubMed Ouldali N, Toubiana J, Antona D, Javouhey E, Madhi F, Lorrot M, et al. Association of intravenous immunoglobulins plus methylprednisolone vs immunoglobulins alone with course of fever in multisystem inflammatory syndrome in children. JAMA. 2021;325:855–64.CrossRefPubMed
46.
go back to reference McArdle AJ, Vito O, Patel H, Seaby EG, Shah P, Wilson C, et al. Treatment of multisystem inflammatory syndrome in children. N Engl J Med. 2021;385:11–22.CrossRefPubMed McArdle AJ, Vito O, Patel H, Seaby EG, Shah P, Wilson C, et al. Treatment of multisystem inflammatory syndrome in children. N Engl J Med. 2021;385:11–22.CrossRefPubMed
47.
go back to reference Ouldali N, Son MBF, McArdle AJ, Vito O, Vaugon E, Belot A, et al. Immunomodulatory therapy for MIS-C. Pediatrics. 2023;152:e2022061173.CrossRefPubMed Ouldali N, Son MBF, McArdle AJ, Vito O, Vaugon E, Belot A, et al. Immunomodulatory therapy for MIS-C. Pediatrics. 2023;152:e2022061173.CrossRefPubMed
48.
go back to reference Welzel T, Atkinson A, Schobi N, Andre MC, Bailey DGN, Blanchard-Rohner G, et al. Methylprednisolone versus intravenous immunoglobulins in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): an open-label, multicentre, randomised trial. Lancet Child Adolesc Health. 2023;7:238–48.CrossRefPubMedPubMedCentral Welzel T, Atkinson A, Schobi N, Andre MC, Bailey DGN, Blanchard-Rohner G, et al. Methylprednisolone versus intravenous immunoglobulins in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): an open-label, multicentre, randomised trial. Lancet Child Adolesc Health. 2023;7:238–48.CrossRefPubMedPubMedCentral
50.
go back to reference Carter MJ, Fish M, Jennings A, Doores KJ, Wellman P, Seow J, et al. Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection. Nat Med. 2020;26:1701–7.CrossRefPubMed Carter MJ, Fish M, Jennings A, Doores KJ, Wellman P, Seow J, et al. Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection. Nat Med. 2020;26:1701–7.CrossRefPubMed
51.
go back to reference Gruber CN, Patel RS, Trachtman R, Lepow L, Amanat F, Krammer F, et al. Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C). Cell. 2020;183:982–95.e14.CrossRefPubMedPubMedCentral Gruber CN, Patel RS, Trachtman R, Lepow L, Amanat F, Krammer F, et al. Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C). Cell. 2020;183:982–95.e14.CrossRefPubMedPubMedCentral
52.
go back to reference Zhu YP, Shamie I, Lee JC, Nowell CJ, Peng W, Angulo S, et al. Immune response to intravenous immunoglobulin in patients with Kawasaki disease and MIS-C. J Clin Investig. 2021;131:e147076.CrossRefPubMedPubMedCentral Zhu YP, Shamie I, Lee JC, Nowell CJ, Peng W, Angulo S, et al. Immune response to intravenous immunoglobulin in patients with Kawasaki disease and MIS-C. J Clin Investig. 2021;131:e147076.CrossRefPubMedPubMedCentral
53.
go back to reference Toraih EA, Hussein MH, Elshazli RM, Kline A, Munshi R, Sultana N, et al. Multisystem inflammatory syndrome in pediatric COVID-19 patients: a meta-analysis. World J Pediatr. 2021;17:141–51.CrossRefPubMedPubMedCentral Toraih EA, Hussein MH, Elshazli RM, Kline A, Munshi R, Sultana N, et al. Multisystem inflammatory syndrome in pediatric COVID-19 patients: a meta-analysis. World J Pediatr. 2021;17:141–51.CrossRefPubMedPubMedCentral
54.
go back to reference Pouletty M, Borocco C, 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. Ann Rheum Dis. 2020;79:999–1006.CrossRefPubMed Pouletty M, Borocco C, 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. Ann Rheum Dis. 2020;79:999–1006.CrossRefPubMed
55.
go back to reference Diorio C, Henrickson SE, Vella LA, McNerney KO, Chase J, Burudpakdee C, et al. Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2. J Clin Investig. 2020;130:5967–75.CrossRefPubMedPubMedCentral Diorio C, Henrickson SE, Vella LA, McNerney KO, Chase J, Burudpakdee C, et al. Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2. J Clin Investig. 2020;130:5967–75.CrossRefPubMedPubMedCentral
56.
go back to reference Mori M, Hara T, Kikuchi M, Shimizu H, Miyamoto T, Iwashima S, et al. Infliximab versus intravenous immunoglobulin for refractory Kawasaki disease: a phase 3, randomized, open-label, active-controlled, parallel-group, multicenter trial. Sci Rep. 2018;8:1994.CrossRefPubMedPubMedCentral Mori M, Hara T, Kikuchi M, Shimizu H, Miyamoto T, Iwashima S, et al. Infliximab versus intravenous immunoglobulin for refractory Kawasaki disease: a phase 3, randomized, open-label, active-controlled, parallel-group, multicenter trial. Sci Rep. 2018;8:1994.CrossRefPubMedPubMedCentral
57.
go back to reference Abdel-Haq N, Asmar BI, Deza Leon MP, McGrath EJ, Arora HS, Cashen K, et al. SARS-CoV-2-associated multisystem inflammatory syndrome in children: clinical manifestations and the role of infliximab treatment. Eur J Pediatr. 2021;180:1581–91.CrossRefPubMedPubMedCentral Abdel-Haq N, Asmar BI, Deza Leon MP, McGrath EJ, Arora HS, Cashen K, et al. SARS-CoV-2-associated multisystem inflammatory syndrome in children: clinical manifestations and the role of infliximab treatment. Eur J Pediatr. 2021;180:1581–91.CrossRefPubMedPubMedCentral
58.
go back to reference Cole LD, Osborne CM, Silveira LJ, Rao S, Lockwood JM, Kunkel MJ, et al. IVIG compared with IVIG plus infliximab in multisystem inflammatory syndrome in children. Pediatrics. 2021;148:e2021052702.CrossRefPubMed Cole LD, Osborne CM, Silveira LJ, Rao S, Lockwood JM, Kunkel MJ, et al. IVIG compared with IVIG plus infliximab in multisystem inflammatory syndrome in children. Pediatrics. 2021;148:e2021052702.CrossRefPubMed
59.
go back to reference 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. J Pediatr Gastroenterol Nutr. 2020;71:153–5.CrossRefPubMed 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. J Pediatr Gastroenterol Nutr. 2020;71:153–5.CrossRefPubMed
60.
go back to reference Jain S, He F, Brown K, Burns JC, Tremoulet AH. Multisystem inflammatory syndrome therapies in children (MISTIC): a randomized trial. Contemp Clin Trials Commun. 2023;32:101060.CrossRefPubMedPubMedCentral Jain S, He F, Brown K, Burns JC, Tremoulet AH. Multisystem inflammatory syndrome therapies in children (MISTIC): a randomized trial. Contemp Clin Trials Commun. 2023;32:101060.CrossRefPubMedPubMedCentral
62.
go back to reference Stone JH, Frigault MJ, Serling-Boyd NJ, Fernandes AD, Harvey L, Foulkes AS, et al. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med. 2020;383:2333–44.CrossRefPubMed Stone JH, Frigault MJ, Serling-Boyd NJ, Fernandes AD, Harvey L, Foulkes AS, et al. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med. 2020;383:2333–44.CrossRefPubMed
63.
go back to reference Herold T, Jurinovic V, Arnreich C, Lipworth BJ, Hellmuth JC, von Bergwelt-Baildon M, et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020;146:128–36.e24.CrossRefPubMedPubMedCentral Herold T, Jurinovic V, Arnreich C, Lipworth BJ, Hellmuth JC, von Bergwelt-Baildon M, et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020;146:128–36.e24.CrossRefPubMedPubMedCentral
64.
go back to reference Del Valle DM, Kim-Schulze S, Huang HH, Beckmann ND, Nirenberg S, Wang B, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26:1636–43.CrossRefPubMedPubMedCentral Del Valle DM, Kim-Schulze S, Huang HH, Beckmann ND, Nirenberg S, Wang B, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26:1636–43.CrossRefPubMedPubMedCentral
65.
66.
go back to reference Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020;117:10970–5.CrossRefPubMedPubMedCentral Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020;117:10970–5.CrossRefPubMedPubMedCentral
67.
go back to reference Capra R, De Rossi N, Mattioli F, Romanelli G, Scarpazza C, Sormani MP, et al. Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia. Eur J Intern Med. 2020;76:31–5.CrossRefPubMedPubMedCentral Capra R, De Rossi N, Mattioli F, Romanelli G, Scarpazza C, Sormani MP, et al. Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia. Eur J Intern Med. 2020;76:31–5.CrossRefPubMedPubMedCentral
68.
go back to reference Albuquerque AM, Tramujas L, Sewanan LR, Williams DR, Brophy JM. Mortality rates among hospitalized patients with COVID-19 infection treated with tocilizumab and corticosteroids: a Bayesian reanalysis of a previous meta-analysis. JAMA Netw Open. 2022;5:e220548.CrossRefPubMedPubMedCentral Albuquerque AM, Tramujas L, Sewanan LR, Williams DR, Brophy JM. Mortality rates among hospitalized patients with COVID-19 infection treated with tocilizumab and corticosteroids: a Bayesian reanalysis of a previous meta-analysis. JAMA Netw Open. 2022;5:e220548.CrossRefPubMedPubMedCentral
69.
go back to reference Shankar-Hari M, Vale CL, Godolphin PJ, Fisher D, Higgins JPT, Spiga F, et al. Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19: a meta-analysis. JAMA. 2021;326:499–518.CrossRefPubMed Shankar-Hari M, Vale CL, Godolphin PJ, Fisher D, Higgins JPT, Spiga F, et al. Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19: a meta-analysis. JAMA. 2021;326:499–518.CrossRefPubMed
70.
go back to reference RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397:1637–45.CrossRef RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397:1637–45.CrossRef
71.
go back to reference Hermine O, Mariette X, Tharaux PL, Resche-Rigon M, Porcher R, Ravaud P. Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia: a randomized clinical trial. JAMA Intern Med. 2021;181:32–40.CrossRefPubMed Hermine O, Mariette X, Tharaux PL, Resche-Rigon M, Porcher R, Ravaud P. Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia: a randomized clinical trial. JAMA Intern Med. 2021;181:32–40.CrossRefPubMed
72.
go back to reference Somers EC, Eschenauer GA, Troost JP, Golob JL, Gandhi TN, Wang L, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clin Infect Dis. 2021;73:e445–54.CrossRefPubMed Somers EC, Eschenauer GA, Troost JP, Golob JL, Gandhi TN, Wang L, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clin Infect Dis. 2021;73:e445–54.CrossRefPubMed
73.
go back to reference Edinoff AN, Alpaugh ES, Newgaard O, Wajid I, Klapper RJ, Cornett EM, et al. Tocilizumab for severe COVID-19 infection and multisystem inflammatory syndrome in adults and children. Life (Basel). 2023;13:889.PubMed Edinoff AN, Alpaugh ES, Newgaard O, Wajid I, Klapper RJ, Cornett EM, et al. Tocilizumab for severe COVID-19 infection and multisystem inflammatory syndrome in adults and children. Life (Basel). 2023;13:889.PubMed
74.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
76.
go back to reference Yoshikawa T, Hill T, Li K, Peters CJ, Tseng CT. Severe acute respiratory syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells. J Virol. 2009;83:3039–48.CrossRefPubMed Yoshikawa T, Hill T, Li K, Peters CJ, Tseng CT. Severe acute respiratory syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells. J Virol. 2009;83:3039–48.CrossRefPubMed
77.
go back to reference Ghosh P, Katkar GD, Shimizu C, Kim J, Khandelwal S, Tremoulet AH, et al. An artificial intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease. Nat Commun. 2022;13:2687.CrossRefPubMedPubMedCentral Ghosh P, Katkar GD, Shimizu C, Kim J, Khandelwal S, Tremoulet AH, et al. An artificial intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease. Nat Commun. 2022;13:2687.CrossRefPubMedPubMedCentral
78.
go back to reference Bhat CS, Shetty R, Ramesh D, Banu A, Ramanan AV. Anakinra in refractory multisystem inflammatory syndrome in children (MIS-C). Indian Pediatr. 2021;58:994–6.CrossRefPubMedPubMedCentral Bhat CS, Shetty R, Ramesh D, Banu A, Ramanan AV. Anakinra in refractory multisystem inflammatory syndrome in children (MIS-C). Indian Pediatr. 2021;58:994–6.CrossRefPubMedPubMedCentral
79.
go back to reference Shakoory B, Carcillo JA, Chatham WW, Amdur RL, Zhao H, Dinarello CA, et al. Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of macrophage activation syndrome: reanalysis of a prior phase III trial. Crit Care Med. 2016;44:275–81.CrossRefPubMedPubMedCentral Shakoory B, Carcillo JA, Chatham WW, Amdur RL, Zhao H, Dinarello CA, et al. Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of macrophage activation syndrome: reanalysis of a prior phase III trial. Crit Care Med. 2016;44:275–81.CrossRefPubMedPubMedCentral
80.
go back to reference Caglayan S, Sonmez HE, Otar Yener G, Baglan E, Ozturk K, Ulu K, et al. Anakinra treatment in multisystemic inflammatory syndrome in children (MIS-C) associated with COVID-19. Front Pediatr. 2022;10:942455.CrossRefPubMedPubMedCentral Caglayan S, Sonmez HE, Otar Yener G, Baglan E, Ozturk K, Ulu K, et al. Anakinra treatment in multisystemic inflammatory syndrome in children (MIS-C) associated with COVID-19. Front Pediatr. 2022;10:942455.CrossRefPubMedPubMedCentral
81.
go back to reference Troisi A, Accomando F, Mambelli L, Marchetti F. Multi-system inflammatory syndrome in children (MIS-C) with retropharyngeal involvement mimicking abscess: the therapeutic role of anakinra. Arch Clin Med Case Rep. 2023;7:80–1.CrossRefPubMedPubMedCentral Troisi A, Accomando F, Mambelli L, Marchetti F. Multi-system inflammatory syndrome in children (MIS-C) with retropharyngeal involvement mimicking abscess: the therapeutic role of anakinra. Arch Clin Med Case Rep. 2023;7:80–1.CrossRefPubMedPubMedCentral
82.
go back to reference Dizon BLP, Redmond C, Gotschlich EC, Sule S, Ronis T, Vazzana KM, et al. Clinical outcomes and safety of anakinra in the treatment of multisystem inflammatory syndrome in children: a single center observational study. Pediatr Rheumatol Online J. 2023;21:76.CrossRefPubMedPubMedCentral Dizon BLP, Redmond C, Gotschlich EC, Sule S, Ronis T, Vazzana KM, et al. Clinical outcomes and safety of anakinra in the treatment of multisystem inflammatory syndrome in children: a single center observational study. Pediatr Rheumatol Online J. 2023;21:76.CrossRefPubMedPubMedCentral
83.
go back to reference Rajput RV, Sharron MP, Pavuluri P, Hansen H, Ansusinha E, DeBiasi R, et al. Clinical impact of a standardized risk-stratified thromboprophylaxis protocol for multisystem inflammatory syndrome in children. J Pediatr. 2023;262:113624.CrossRefPubMed Rajput RV, Sharron MP, Pavuluri P, Hansen H, Ansusinha E, DeBiasi R, et al. Clinical impact of a standardized risk-stratified thromboprophylaxis protocol for multisystem inflammatory syndrome in children. J Pediatr. 2023;262:113624.CrossRefPubMed
85.
go back to reference Cavalli G, De Luca G, Campochiaro C, Della-Torre E, Ripa M, Canetti D, et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol. 2020;2:e325–31.CrossRefPubMedPubMedCentral Cavalli G, De Luca G, Campochiaro C, Della-Torre E, Ripa M, Canetti D, et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol. 2020;2:e325–31.CrossRefPubMedPubMedCentral
86.
go back to reference Della Paolera S, Valencic E, Piscianz E, Moressa V, Tommasini A, Sagredini R, et al. Case report: use of anakinra in multisystem inflammatory syndrome during COVID-19 pandemic. Front Pediatr. 2020;8:624248.CrossRefPubMed Della Paolera S, Valencic E, Piscianz E, Moressa V, Tommasini A, Sagredini R, et al. Case report: use of anakinra in multisystem inflammatory syndrome during COVID-19 pandemic. Front Pediatr. 2020;8:624248.CrossRefPubMed
87.
go back to reference Jodele S, Dandoy CE, Lane A, Laskin BL, Teusink-Cross A, Myers KC, et al. Complement blockade for TA-TMA: lessons learned from a large pediatric cohort treated with eculizumab. Blood. 2020;135:1049–57.PubMedPubMedCentral Jodele S, Dandoy CE, Lane A, Laskin BL, Teusink-Cross A, Myers KC, et al. Complement blockade for TA-TMA: lessons learned from a large pediatric cohort treated with eculizumab. Blood. 2020;135:1049–57.PubMedPubMedCentral
88.
go back to reference Diorio C, McNerney KO, Lambert M, Paessler M, Anderson EM, Henrickson SE, et al. Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations. Blood Adv. 2020;4:6051–63.CrossRefPubMedPubMedCentral Diorio C, McNerney KO, Lambert M, Paessler M, Anderson EM, Henrickson SE, et al. Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations. Blood Adv. 2020;4:6051–63.CrossRefPubMedPubMedCentral
89.
go back to reference Diorio C, Shraim R, Vella LA, Giles JR, Baxter AE, Oldridge DA, et al. Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction. Nat Commun. 2021;12:7222.CrossRefPubMedPubMedCentral Diorio C, Shraim R, Vella LA, Giles JR, Baxter AE, Oldridge DA, et al. Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction. Nat Commun. 2021;12:7222.CrossRefPubMedPubMedCentral
90.
go back to reference Aurora T, Joseph N, Bhoopalan SV, Caniza MA, Flerlage T, Ghafoor S, et al. The successful use of eculizumab for treatment of thrombotic microangiopathy in pediatric acute SARSCoV2 infection and multisystem inflammatory syndrome in children. Haematologica. 2022;107:2517–22.CrossRefPubMedPubMedCentral Aurora T, Joseph N, Bhoopalan SV, Caniza MA, Flerlage T, Ghafoor S, et al. The successful use of eculizumab for treatment of thrombotic microangiopathy in pediatric acute SARSCoV2 infection and multisystem inflammatory syndrome in children. Haematologica. 2022;107:2517–22.CrossRefPubMedPubMedCentral
91.
go back to reference 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 Investig. 2020;130:5942–50.CrossRefPubMedPubMedCentral 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 Investig. 2020;130:5942–50.CrossRefPubMedPubMedCentral
92.
go back to reference Canna SW, Girard C, Malle L, de Jesus A, Romberg N, Kelsen J, et al. Life-threatening NLRC4-associated hyperinflammation successfully treated with IL-18 inhibition. J Allergy Clin Immunol. 2017;139:1698–701.CrossRefPubMed Canna SW, Girard C, Malle L, de Jesus A, Romberg N, Kelsen J, et al. Life-threatening NLRC4-associated hyperinflammation successfully treated with IL-18 inhibition. J Allergy Clin Immunol. 2017;139:1698–701.CrossRefPubMed
93.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
94.
go back to reference Nopp S, Moik F, Jilma B, Pabinger I, Ay C. Risk of venous thromboembolism in patients with COVID-19: a systematic review and meta-analysis. Res Pract Thromb Haemost. 2020;4:1178–91.CrossRefPubMedPubMedCentral Nopp S, Moik F, Jilma B, Pabinger I, Ay C. Risk of venous thromboembolism in patients with COVID-19: a systematic review and meta-analysis. Res Pract Thromb Haemost. 2020;4:1178–91.CrossRefPubMedPubMedCentral
95.
go back to reference Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children’s hospitals in the United States from 2001 to 2007. Pediatrics. 2009;124:1001–8.CrossRefPubMed Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children’s hospitals in the United States from 2001 to 2007. Pediatrics. 2009;124:1001–8.CrossRefPubMed
96.
go back to reference Whitworth H, Sartain SE, Kumar R, Armstrong K, Ballester L, Betensky M, et al. Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C. Blood. 2021;138:190–8.CrossRefPubMedPubMedCentral Whitworth H, Sartain SE, Kumar R, Armstrong K, Ballester L, Betensky M, et al. Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C. Blood. 2021;138:190–8.CrossRefPubMedPubMedCentral
97.
go back to reference Sharathkumar AA, Faustino EVS, Takemoto CM. How we approach thrombosis risk in children with COVID-19 infection and MIS-C. Pediatr Blood Cancer. 2021;68:e29049.CrossRefPubMedPubMedCentral Sharathkumar AA, Faustino EVS, Takemoto CM. How we approach thrombosis risk in children with COVID-19 infection and MIS-C. Pediatr Blood Cancer. 2021;68:e29049.CrossRefPubMedPubMedCentral
98.
go back to reference Morris T, Stables M, Hobbs A, de Souza P, Colville-Nash P, Warner T, et al. Effects of low-dose aspirin on acute inflammatory responses in humans. J Immunol. 2009;183:2089–96.CrossRefPubMed Morris T, Stables M, Hobbs A, de Souza P, Colville-Nash P, Warner T, et al. Effects of low-dose aspirin on acute inflammatory responses in humans. J Immunol. 2009;183:2089–96.CrossRefPubMed
99.
go back to reference Chiang N, Bermudez EA, Ridker PM, Hurwitz S, Serhan CN. Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial. Proc Natl Acad Sci U S A. 2004;101:15178–83.CrossRefPubMedPubMedCentral Chiang N, Bermudez EA, Ridker PM, Hurwitz S, Serhan CN. Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial. Proc Natl Acad Sci U S A. 2004;101:15178–83.CrossRefPubMedPubMedCentral
100.
go back to reference Meizlish ML, Goshua G, Liu Y, Fine R, Amin K, Chang E, et al. Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: a propensity score-matched analysis. Am J Hematol. 2021;96:471–9.CrossRefPubMedPubMedCentral Meizlish ML, Goshua G, Liu Y, Fine R, Amin K, Chang E, et al. Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: a propensity score-matched analysis. Am J Hematol. 2021;96:471–9.CrossRefPubMedPubMedCentral
101.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
102.
go back to reference Merzon E, Green I, Vinker S, Golan-Cohen A, Gorohovski A, Avramovich E, et al. The use of aspirin for primary prevention of cardiovascular disease is associated with a lower likelihood of COVID-19 infection. FEBS J. 2021;288:5179–89.CrossRefPubMedPubMedCentral Merzon E, Green I, Vinker S, Golan-Cohen A, Gorohovski A, Avramovich E, et al. The use of aspirin for primary prevention of cardiovascular disease is associated with a lower likelihood of COVID-19 infection. FEBS J. 2021;288:5179–89.CrossRefPubMedPubMedCentral
103.
go back to reference Consiglio CR, Cotugno N, Sardh F, Pou C, Amodio D, Rodriguez L, et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell. 2020;183:968–81.e67.CrossRefPubMedPubMedCentral Consiglio CR, Cotugno N, Sardh F, Pou C, Amodio D, Rodriguez L, et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell. 2020;183:968–81.e67.CrossRefPubMedPubMedCentral
105.
go back to reference Goldenberg NA, Sochet A, Albisetti M, Biss T, Bonduel M, Jaffray J, et al. Consensus-based clinical recommendations and research priorities for anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illness. J Thromb Haemost. 2020;18:3099–105.CrossRefPubMedPubMedCentral Goldenberg NA, Sochet A, Albisetti M, Biss T, Bonduel M, Jaffray J, et al. Consensus-based clinical recommendations and research priorities for anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illness. J Thromb Haemost. 2020;18:3099–105.CrossRefPubMedPubMedCentral
106.
go back to reference Bansal N, Azeka E, Neunert C, Kim JS, Murray J, May L, et al. Multisystem inflammatory syndrome associated with COVID-19 anti-thrombosis guideline of care for children by action. Pediatr Cardiol. 2021;42:1635–9.CrossRefPubMedPubMedCentral Bansal N, Azeka E, Neunert C, Kim JS, Murray J, May L, et al. Multisystem inflammatory syndrome associated with COVID-19 anti-thrombosis guideline of care for children by action. Pediatr Cardiol. 2021;42:1635–9.CrossRefPubMedPubMedCentral
107.
go back to reference Monagle P, Chan AKC, Goldenberg NA, Ichord RN, Journeycake JM, Nowak-Göttl U, et al. Antithrombotic therapy in neonates and children: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(Suppl 2):e737S–801S.CrossRefPubMedPubMedCentral Monagle P, Chan AKC, Goldenberg NA, Ichord RN, Journeycake JM, Nowak-Göttl U, et al. Antithrombotic therapy in neonates and children: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(Suppl 2):e737S–801S.CrossRefPubMedPubMedCentral
108.
go back to reference Malowany JI, Monagle P, Knoppert DC, Lee DS, Wu J, McCusker P, et al. Enoxaparin for neonatal thrombosis: a call for a higher dose for neonates. Thromb Res. 2008;122:826–30.CrossRefPubMed Malowany JI, Monagle P, Knoppert DC, Lee DS, Wu J, McCusker P, et al. Enoxaparin for neonatal thrombosis: a call for a higher dose for neonates. Thromb Res. 2008;122:826–30.CrossRefPubMed
109.
go back to reference Richard AA, Kim S, Moffett BS, Bomgaars L, Mahoney D Jr, Yee DL. Comparison of anti-Xa levels in obese and non-obese pediatric patients receiving treatment doses of enoxaparin. J Pediatr. 2013;162:293–6.CrossRefPubMed Richard AA, Kim S, Moffett BS, Bomgaars L, Mahoney D Jr, Yee DL. Comparison of anti-Xa levels in obese and non-obese pediatric patients receiving treatment doses of enoxaparin. J Pediatr. 2013;162:293–6.CrossRefPubMed
110.
go back to reference Mitchell WB, Davila J, Keenan J, Jackson J, Tal A, Morrone KA, et al. Children and young adults hospitalized for severe COVID-19 exhibit thrombotic coagulopathy. Pediatr Blood Cancer. 2021;68:e28975.CrossRefPubMedPubMedCentral Mitchell WB, Davila J, Keenan J, Jackson J, Tal A, Morrone KA, et al. Children and young adults hospitalized for severe COVID-19 exhibit thrombotic coagulopathy. Pediatr Blood Cancer. 2021;68:e28975.CrossRefPubMedPubMedCentral
111.
go back to reference Lawler PR, Goligher EC, Berger JS, Neal MD, McVerry BJ, Nicolau JC, et al. Therapeutic anticoagulation with heparin in noncritically ill patients with Covid-19. N Engl J Med. 2021;385:790–802.CrossRefPubMed Lawler PR, Goligher EC, Berger JS, Neal MD, McVerry BJ, Nicolau JC, et al. Therapeutic anticoagulation with heparin in noncritically ill patients with Covid-19. N Engl J Med. 2021;385:790–802.CrossRefPubMed
112.
go back to reference Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol. 2020;75:2950–73.CrossRefPubMedPubMedCentral Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol. 2020;75:2950–73.CrossRefPubMedPubMedCentral
113.
go back to reference Boehmer TK, Kompaniyets L, Lavery AM, Hsu J, Ko JY, Yusuf H, et al. Association between COVID-19 and myocarditis using hospital-based administrative data-United States, March 2020-January 2021. MMWR Morb Mortal Wkly Rep. 2021;70:1228–32.CrossRefPubMedPubMedCentral Boehmer TK, Kompaniyets L, Lavery AM, Hsu J, Ko JY, Yusuf H, et al. Association between COVID-19 and myocarditis using hospital-based administrative data-United States, March 2020-January 2021. MMWR Morb Mortal Wkly Rep. 2021;70:1228–32.CrossRefPubMedPubMedCentral
114.
go back to reference McCrindle BW, Harahsheh AS, Handoko R, Raghuveer G, Portman MA, Khoury M, et al. SARS-CoV-2 variants and multisystem inflammatory syndrome in children. N Engl J Med. 2023;388:1624–6.CrossRefPubMed McCrindle BW, Harahsheh AS, Handoko R, Raghuveer G, Portman MA, Khoury M, et al. SARS-CoV-2 variants and multisystem inflammatory syndrome in children. N Engl J Med. 2023;388:1624–6.CrossRefPubMed
115.
go back to reference Hoste L, Van Paemel R, Haerynck F. Multisystem inflammatory syndrome in children related to COVID-19: a systematic review. Eur J Pediatr. 2021;180:2019–34.CrossRefPubMedPubMedCentral Hoste L, Van Paemel R, Haerynck F. Multisystem inflammatory syndrome in children related to COVID-19: a systematic review. Eur J Pediatr. 2021;180:2019–34.CrossRefPubMedPubMedCentral
116.
go back to reference Kache S, Chisti MJ, Gumbo F, Mupere E, Zhi X, Nallasamy K, et al. COVID-19 PICU guidelines: for high- and limited-resource settings. Pediatr Res. 2020;88:705–16.CrossRefPubMedPubMedCentral Kache S, Chisti MJ, Gumbo F, Mupere E, Zhi X, Nallasamy K, et al. COVID-19 PICU guidelines: for high- and limited-resource settings. Pediatr Res. 2020;88:705–16.CrossRefPubMedPubMedCentral
117.
go back to reference Zimmerman D, Shwayder M, Souza A, Su JA, Votava-Smith J, Wagner-Lees S, et al. Cardiovascular follow-up of patients treated for MIS-C. Pediatrics. 2023;152:e2023063002.CrossRefPubMed Zimmerman D, Shwayder M, Souza A, Su JA, Votava-Smith J, Wagner-Lees S, et al. Cardiovascular follow-up of patients treated for MIS-C. Pediatrics. 2023;152:e2023063002.CrossRefPubMed
118.
go back to reference Blatz AM, Randolph AG. Severe COVID-19 and multisystem inflammatory syndrome in children in children and adolescents. Crit Care Clin. 2022;38:571–86.CrossRefPubMedPubMedCentral Blatz AM, Randolph AG. Severe COVID-19 and multisystem inflammatory syndrome in children in children and adolescents. Crit Care Clin. 2022;38:571–86.CrossRefPubMedPubMedCentral
119.
go back to reference Mainzer G, Zucker-Toledano M, Hanna M, Bar-Yoseph R, Kodesh E. Significant exercise limitations after recovery from MIS-C related myocarditis. World J Pediatr. 2023;19:1149–54.CrossRefPubMed Mainzer G, Zucker-Toledano M, Hanna M, Bar-Yoseph R, Kodesh E. Significant exercise limitations after recovery from MIS-C related myocarditis. World J Pediatr. 2023;19:1149–54.CrossRefPubMed
120.
Metadata
Title
Treatment of multisystem inflammatory syndrome in children
Authors
Tong Tong
Yi-Hua Jin
Min Wang
Fang-Qi Gong
Publication date
21-03-2024
Publisher
Springer Nature Singapore
Published in
World Journal of Pediatrics / Issue 4/2024
Print ISSN: 1708-8569
Electronic ISSN: 1867-0687
DOI
https://doi.org/10.1007/s12519-024-00798-y

Other articles of this Issue 4/2024

World Journal of Pediatrics 4/2024 Go to the issue