Clinical and immunological features in children with multisystem inflammatory syndrome associated with SARS-CoV-2: Clinical and immunological features in children with MIS-C

Clinical and immunological features in children with multisystem inflammatory syndrome associated with SARS-CoV-2

Clinical and immunological features in children with MIS-C

Authors

  • Indira Jaxybayeva Scientific Center of Pediatrics and Pediatric Surgery
  • Riza Boranbayeva Scientific Center of Pediatrics and Pediatric Surgery
  • Munira Bulegenova Scientific Center of Pediatrics and Pediatric Surgery
  • Nataliya Urazalieva Scientific Center of Pediatrics and Pediatric Surgery

Keywords:

Multisystem inflammatory syndrome, MIS-C, children, ICU.

Abstract

Background and aim: MIS-C is characterized by intense immune activation and increased production of cytokines. The aim of our study was to analyse the changes of cellular and humoral immune responses in children with MIS-C, depending on the severity of the disease.

Methods: To conduct the study, the results of clinical, hematological and immunological parameters in children with severe and extremely severe MIS-C were compared. A total of 50 patients participated in the study, which were divided into 3 groups, of which: 20 children with extremely severe MIS-C treated in the ICU (MIS-C ICU "+"); 15 children with severe MIS-C, but without the need for hospitalization in the ICU (MIS-C ICU "-"); 15 children who had COVID-19 and absence MIS-C (MIS-C "-") made up the control group.

Results: In patients with MIS-C hospitalized in the ICU, heart and liver damage, hematological changes, and the development of severe complications such as edematous syndrome, polyserositis, DIC, and cardiogenic shock were statistically more common.

Both groups of children with MIS-C had CD3+ T-cell lymphopenia and a decrease in CD95 expression. In the group of children with MIS-C hospitalized in the ICU, a significant increase in the relative number of B-lymphocytes, CD3-HLA-DR+ and CD25 and decrease of NK-cells was observed.

Conclusions: The risk of hospitalization in the ICU in children with MIS-C is associated with more profound immune dysregulation, as evidenced by our data. (www.actabiomedica.it)

 

References

Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem inflammatory syndrome in US children and adolescents. N Engl J Med. 2020 Jul 23;383(4):334-346.

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. JAMA. 2020 Jul 21;324(3):259-269.

Stasiak A, Perdas E, Smolewska E. Risk factors of a severe course of pediatric multi-system inflammatory syndrome temporally associated with COVID-19. Eur J Pediatr. 2022 Aug 10:1–6.

Rhedin S, Lundholm C, Horne A, et al. Risk factors for multisystem inflammatory syndrome in children - A population-based cohort study of over 2 million children. Lancet Reg Health Eur. 2022 Aug;19:100443.

Jaxybayeva I, Boranbayeva R, Abdrakhmanova S, et al. Comparative Analysis of Clinical and Laboratory Data in Children with Multisystem Inflammatory Syndrome Associated with SARS-CoV-2 in the Republic of Kazakhstan. Mediterr J Hematol Infect Dis 2022 Sep 1;14(1):e2022064.

Bukulmez H. Current Understanding of Multisystem Inflammatory Syndrome (MIS-C) Following COVID-19 and Its Distinction from Kawasaki Disease. Curr Rheumatol Rep. 2021 Jul 3;23(8):58.

Sood M, Sharma S, Sood I, et al. 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;7:1–10.

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 Clin Invest. 2020 Nov 2;130(11):5942-5950.

Beckmann ND, Comella PH, Cheng E et al. Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children. Nat Commun. 2021 Aug 11;12(1):4854.

Waggoner SN, Cornberg M, Selin LK, Welsh RM. Natural killer cells act as rheostats modulating antiviral T cells. Nature. 2011 Nov 20;481(7381):394-8.

Cook KD, Whitmire JK. The depletion of NK cells prevents T cell exhaustion to efficiently control disseminating virus infection. J Immunol. 2013 Jan 15;190(2):641-9.

Consiglio CR, Cotugno N, Sardh F, et al. The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19. Cell. 2020 Nov 12;183(4):968-981.e7.

Levacher M, Tallet S, Dazza MC, Dournon E, Rouveix B, Pocidalo JJ. T activation marker evaluation in ARC patients treated with AZT. Comparison with CD4+ lymphocyte count in non-progressors and progressors towards AIDS. Clin Exp Immunol. 1990 Aug;81(2):177-82.

Peter ME, Budd RC, Desbarats J, et al. The CD95 receptor: apoptosis revisited. Cell. 2007 May 4;129(3):447-50.

Yoshino T., Kondo E., Cao L., et al. Inverse expression of bcl-2 protein and Fas antigen in lymphoblasts in peripheral lymph nodes and activated peripheral blood T and B lymphocytes. Blood. 1994 Apr 1;83(7):1856-61.

Ramenghi U, Bonissoni S, Migliaretti G, et al. Deficiency of the Fas apoptosis pathway without Fas gene mutations is a familial trait predisposing to development of autoimmune diseases and cancer. Blood. 2000 May 15;95(10):3176-82.

Liu Y, Gao Y, Hao H, Hou T. CD279 mediates the homeostasis and survival of regulatory T cells by enhancing T cell and macrophage interactions. FEBS Open Bio. 2020 Jun;10(6):1162-1170.

Okarska-Napierała M, Mańdziuk J, Feleszko W, et al. Recurrent assessment of lymphocyte subsets in 32 patients with multisystem inflammatory syndrome in children (MIS-C). Pediatr Allergy Immunol. 2021 Nov;32(8):1857-1865.

Gowin E, Dworacki G, Siewert B, Wysocki J, Januszkiewicz-Lewandowska D. Immune profile of children diagnosed with multisystem inflammatory syndrome associated with SARS-CoV-2 infection (MIS-C). Central European Journal of Immunology. 2022;47(2):151-159.

Vella LA, Giles JR, Baxter AE, et al. Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19. Sci Immunol. 2021 Mar 2;6(57):eabf7570.

Moreews M, Le Gouge K, Khaldi-Plassart S. Polyclonal expansion of TCR Vbeta 21.3+ CD4+ and CD8+ T cells is a hallmark of Multisystem Inflammatory Syndrome in Children. Sci Immunol. 2021 May 25;6(59):eabh1516.

Carter MJ, Fish M, Jennings A, et al. Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection. Nat Med. 2020 Nov;26(11):1701-1707.

Abrams JY, Oster ME, Godfred-Cato SE, 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 May;5(5):323-331.

Miller AD, Zambrano LD, Yousaf AR, et al. Multisystem Inflammatory Syndrome in Children—United States, February 2020–July 2021, Clinical Infectious Diseases, 2021;ciab1007

Kıymet E, Böncüoğlu E, Şahinkaya Ş, et al. A Comparative Study of Children with MIS-C between Admitted to the Pediatric Intensive Care Unit and Pediatric Ward: A One-Year Retrospective Study. J Trop Pediatr. 2021 Dec 8;67(6):fmab104.

Esteve-Sole A, Anton J, Pino-Ramirez RM, at all. Similarities and differences between the immunopathogenesis of COVID-19-related pediatric multisystem inflammatory syndrome and Kawasaki disease. J Clin Invest. 2021 Mar 15;131(6):e144554.

Ramaswamy A, Brodsky NN, Sumida TS, et al. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity 2021; 54:1083–95.e7.

Peart Akindele N, Pieterse L, Suwanmanee S, Griffin DE. B cell responses in hospitalized SARS-CoV-2-infected children with and without Multisystem Inflammatory Syndrome. J Infect Dis. 2022 Apr 18:jiac119.

Sharpe AH, Pauken KE. The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol. 2018 Mar;18(3):153-167.

Bellesi S, Metafuni E, Hohaus S, et al. Increased CD95 (Fas) and PD-1 expression in peripheral blood T lymphocytes in COVID-19 patients. Br J Haematol. 2020 Oct;191(2):207-211.

Rieux-Laucat F, Le Deist F, Fischer A. Autoimmune lymphoproliferative syndromes: genetic defects of apoptosis pathways. Cell Death Differ. 2003 Jan;10(1):124-33.

Ross SH, Cantrell DA. Signaling and Function of Interleukin-2 in T Lymphocytes. Annu Rev Immunol. 2018 Apr 26;36:411-433.

Reddy M, Eirikis E, Davis C, Davis HM, Prabhakar U. Comparative analysis of lymphocyte activation marker expression and cytokine secretion profile in stimulated human peripheral blood mononuclear cell cultures: an in vitro model to monitor cellular immune function. J Immunol Methods. 2004 Oct;293(1-2):127-42.

Syrimi E, Fennell E, Richter A, et al. The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery. iScience. 2021 Nov 19;24(11):103215.

Lazova S, Dimitrova Y, Hristova D, Tzotcheva I, Velikova T. Cellular, Antibody and Cytokine Pathways in Children with Acute SARS-CoV-2 Infection and MIS-C—Can We Match the Puzzle? Antibodies. 2022; 11(2):25.

Sharma C, Ganigara M, Galeotti C, et al. Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison. Nat Rev Rheumatol. 2021 Dec;17(12):731-748.

Downloads

Published

24-04-2023

Issue

Section

PEDIATRICS AND ADOLESCENT MEDICINE

How to Cite

1.
Jaxybayeva I, Boranbayeva R, Bulegenova M, Urazalieva N. Clinical and immunological features in children with multisystem inflammatory syndrome associated with SARS-CoV-2: Clinical and immunological features in children with MIS-C. Acta Biomed. 2023;94(2):e2023016. doi:10.23750/abm.v94i2.13777