The difference of the inflammatory milieu in MIS-C and severe COVID-19.
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
23
10
2021
accepted:
26
02
2022
revised:
23
02
2022
pubmed:
31
3
2022
medline:
24
12
2022
entrez:
30
3
2022
Statut:
ppublish
Résumé
Coronavirus disease 19 (COVID-19) may have a severe course in children. Multisystem inflammatory syndrome in children (MIS-C) is the post-COVID complication characterized by an exaggerated inflammation, observed in children. However, data on the underlying pathophysiology are sparse. We therefore aimed to assess the cytokine and chemokine profiles of children with MIS-C and compare these to life-threatening severe SARS-CoV-2 and healthy controls (HCs) to shed light on disease pathophysiology. Samples of 31 children with MIS-C, 10 with severe/critical COVID-19 and 11 HCs were included. Cytokine and chemokine profiles were studied and compared in between groups. Most cytokines and chemokines related to IL-1 family and IFN-γ pathway (including IL-18 and MIG/CXCL9) and IL-17A were significantly higher in the MIS-C group when compared to the severe/critical COVID-19 group and HCs. IP-10/CXCL10 and IL-10 were higher in both MIS-C patients and severe/critical COVID-19 compared to HCs. Our results suggest that IL-1 and IFN-γ pathways play an important role in the pathophysiology of MIS-C. This study defines a pattern of distinctive immune responses in children with MIS-C and in patients with severe/critical COVID-19. As the COVID-19 pandemic continues, biomarkers to identify MIS-C risk are needed to guide our management that study results may shed light on it.
Sections du résumé
BACKGROUND
Coronavirus disease 19 (COVID-19) may have a severe course in children. Multisystem inflammatory syndrome in children (MIS-C) is the post-COVID complication characterized by an exaggerated inflammation, observed in children. However, data on the underlying pathophysiology are sparse. We therefore aimed to assess the cytokine and chemokine profiles of children with MIS-C and compare these to life-threatening severe SARS-CoV-2 and healthy controls (HCs) to shed light on disease pathophysiology.
METHODS
Samples of 31 children with MIS-C, 10 with severe/critical COVID-19 and 11 HCs were included. Cytokine and chemokine profiles were studied and compared in between groups.
RESULTS
Most cytokines and chemokines related to IL-1 family and IFN-γ pathway (including IL-18 and MIG/CXCL9) and IL-17A were significantly higher in the MIS-C group when compared to the severe/critical COVID-19 group and HCs. IP-10/CXCL10 and IL-10 were higher in both MIS-C patients and severe/critical COVID-19 compared to HCs.
CONCLUSION
Our results suggest that IL-1 and IFN-γ pathways play an important role in the pathophysiology of MIS-C.
IMPACT
This study defines a pattern of distinctive immune responses in children with MIS-C and in patients with severe/critical COVID-19. As the COVID-19 pandemic continues, biomarkers to identify MIS-C risk are needed to guide our management that study results may shed light on it.
Identifiants
pubmed: 35352005
doi: 10.1038/s41390-022-02029-4
pii: 10.1038/s41390-022-02029-4
pmc: PMC8963396
doi:
Substances chimiques
Cytokines
0
Interleukin-1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1805-1814Informations de copyright
© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
Références
Ludvigsson, J. F. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr. 109, 1088–1095 (2020).
doi: 10.1111/apa.15270
She, J., Liu, L. & Liu, W. COVID-19 epidemic: disease characteristics in children. J. Med. Virol. 92, 747–754 (2020).
doi: 10.1002/jmv.25807
Riphagen, S., Gomez, X., Gonzalez-Martinez, C., Wilkinson, N. & Theocharis, P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 395, 1607–1608 (2020).
doi: 10.1016/S0140-6736(20)31094-1
Verdoni, L. et al. 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 (2020).
doi: 10.1016/S0140-6736(20)31103-X
Jones, V. G. et al. COVID-19 and Kawasaki disease: novel virus and novel case. Hosp. Pediatr. 10, 537–540 (2020).
doi: 10.1542/hpeds.2020-0123
Feldstein, L. R. 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 325, 1074–1087 (2021).
doi: 10.1001/jama.2021.2091
Dong, Y. et al. Epidemiology of COVID-19 among children in China. Pediatrics 145, e20200702 (2020).
doi: 10.1542/peds.2020-0702
Liu, Y. et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect. Dis. 20, 656–657 (2020).
doi: 10.1016/S1473-3099(20)30232-2
Yang, J. et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int. J. Infect. Dis. 94, 91–95 (2020).
doi: 10.1016/j.ijid.2020.03.017
Reiff, D. D., Mannion, M. L., Samuy, N., Scalici, P. & Cron, R. Q. Distinguishing active pediatric COVID-19 pneumonia from MIS-C. Pediatr. Rheumatol. 19, 21 (2021).
doi: 10.1186/s12969-021-00508-2
Centers for Disease Control and Prevention. Multisystem Inflammatory Syndrome (MIS-C). https://www.cdc.gov/mis-c/cases/index.html . Accessed June 2021.
Henderson, L. A. 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 1. Arthritis Rheumatol. 72, 1791–1805 (2020).
doi: 10.1002/art.41454
Ravelli, A. et al. 2016 Classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Arthritis Rheumatol. (Hoboken, N. J.) 68, 566–576 (2016).
doi: 10.1002/art.39332
Diorio, C. et al. Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2. J. Clin. Investig. 130, 5967–5975 (2020).
doi: 10.1172/JCI140970
Pierce, C. A. et al. Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients. Sci. Transl. Med. 12, eabd5487 (2020).
doi: 10.1126/scitranslmed.abd5487
Carter, M. J. et al. Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection. Nat. Med. 26, 1701–1707 (2020).
doi: 10.1038/s41591-020-1054-6
Gruber, C. N. et al. Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C). Cell 183, 982–995.e14 (2020).
doi: 10.1016/j.cell.2020.09.034
Consiglio, C. R. et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell 183, 968–981.e7 (2020).
doi: 10.1016/j.cell.2020.09.016
Liang, Y., Ge, Y. & Sun, J. IL-33 in COVID-19: friend or foe? Cell. Mol. Immunol. 18, 1602–1604 (2021).
doi: 10.1038/s41423-021-00685-w
Tran, V. L., Parsons, S. & Nuibe, A. The trilogy of SARS-CoV-2 in pediatrics (Part 2): multisystem inflammatory syndrome in children. J. Pediatr. Pharmacol. Ther. 26, 318–338 (2021).
Zizzo, G. & Cohen, P. L. Imperfect storm: is interleukin-33 the Achilles heel of COVID-19? Lancet Rheumatol. 2, e779–e790 (2020).
doi: 10.1016/S2665-9913(20)30340-4
Liew, F. Y., Girard, J. P. & Turnquist, H. R. Interleukin-33 in health and disease. Nat. Rev. Immunol. 16, 676–689 (2016).
doi: 10.1038/nri.2016.95
Yazdi, A. S. & Ghoreschi, K. The interleukin-1 family. Adv. Exp. Med. Biol. 941, 21–29 (2016).
doi: 10.1007/978-94-024-0921-5_2
Mantovani, A., Dinarello, C. A., Molgora, M. & Garlanda, C. Interleukin-1 and related cytokines in the regulation of inflammation and immunity. Immunity 50, 778–795 (2019).
doi: 10.1016/j.immuni.2019.03.012
Migliorini, P., Italiani, P., Pratesi, F., Puxeddu, I. & Boraschi, D. The IL-1 family cytokines and receptors in autoimmune diseases. Autoimmun. Rev. 19, 102617 (2020).
doi: 10.1016/j.autrev.2020.102617
Put, K. et al. Cytokines in systemic juvenile idiopathic arthritis and haemophagocytic lymphohistiocytosis: tipping the balance between interleukin-18 and interferon-γ. Rheumatology 54, 1507–1517 (2015).
doi: 10.1093/rheumatology/keu524
Colafrancesco, S. et al. IL-18 serum level in adult onset Still’s disease: a marker of disease activity. Int. J. Inflamm. 2012, 156890 (2012).
doi: 10.1155/2012/156890
Kak, G., Raza, M. & Tiwari, B. K. Interferon-gamma (IFN-γ): exploring its implications in infectious diseases. Biomol. Concepts 9, 64–79 (2018).
doi: 10.1515/bmc-2018-0007
Caldarale, F. et al. Plasmacytoid dendritic cells depletion and elevation of IFN-γ dependent chemokines CXCL9 and CXCL10 in children with multisystem inflammatory syndrome. Front. Immunol. 12, 654587 (2021).
doi: 10.3389/fimmu.2021.654587
Bracaglia, C. et al. Elevated circulating levels of interferon-γ and interferon-γ-induced chemokines characterise patients with macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Ann. Rheum. Dis. 76, 166–172 (2017).
doi: 10.1136/annrheumdis-2015-209020
Di Cola, I., Ruscitti, P., Giacomelli, R. & Cipriani, P. The pathogenic role of interferons in the hyperinflammatory response on adult-onset Still’s disease and macrophage activation syndrome: paving the way towards new therapeutic targets. J. Clin. Med. 10 1164 (2021).
doi: 10.3390/jcm10061164
Rodriguez-Smith, J. J. et al. Inflammatory biomarkers in COVID-19-associated multisystem inflammatory syndrome in children, Kawasaki disease, and macrophage activation syndrome: a cohort study. Lancet Rheumatol. 3, e574–e584 (2021).
doi: 10.1016/S2665-9913(21)00139-9
Esteve-Sole, A. et al. Similarities and differences between the immunopathogenesis of COVID-19-related pediatric multisystem inflammatory syndrome and Kawasaki disease. J. Clin. Investig. 131, e144554 (2021).
doi: 10.1172/JCI144554
Lee, P. Y. et al. Distinct clinical and immunological features of SARS-CoV-2-induced multisystem inflammatory syndrome in children. J. Clin. Investig. 130, 5942–5950 (2020).
doi: 10.1172/JCI141113
Farooqi, K. M. et al. Longitudinal outcomes for multisystem inflammatory syndrome in children. Pediatrics 148, e2021051155 (2021).
doi: 10.1542/peds.2021-051155
Lev, S. et al. Observational cohort study of IP-10’s potential as a biomarker to aid in inflammation regulation within a clinical decision support protocol for patients with severe COVID-19. PloS One 16, e0245296 (2021).
doi: 10.1371/journal.pone.0245296
Yang, Y. et al. Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19. J. Allergy Clin. Immunol. 146, 119–127.e4 (2020).
doi: 10.1016/j.jaci.2020.04.027
Ozsurekci, Y. et al. Multisystem inflammatory syndrome in children during the COVID-19 pandemic in Turkey: first report from the Eastern Mediterranean. Clin. Rheumatol. 40, 3227–3237 (2021).
doi: 10.1007/s10067-021-05631-9
Dhar, S. K., K, V., Damodar, S., Gujar, S. & Das, M. IL-6 and IL-10 as predictors of disease severity in COVID-19 patients: results from meta-analysis and regression. Heliyon 7, e06155 (2021).
doi: 10.1016/j.heliyon.2021.e06155
Fenini, G., Contassot, E. & French, L. E. Potential of IL-1, IL-18 and Inflammasome Inhibition for the Treatment of Inflammatory Skin Diseases. Front. Pharmacol. 8, 278 (2017).
doi: 10.3389/fphar.2017.00278
Jesus, A. A. & Goldbach-Mansky, R. IL-1 blockade in autoinflammatory syndromes. Annu. Rev. Med. 65, 223–244 (2014).
doi: 10.1146/annurev-med-061512-150641