1. Home
  2. Vol 24, No 3
  3. Mustikawati

Multisystem inflammatory syndrome in children (mis-c) post infection sars-cov-2: a literature review

Rissa Mustikawati

Abstract


The number of COVID-19 instances involving children or adolescents is quite low. However, occurrences in children and adolescents are either not clinically identified or are modest due to silent infections. Multisystem Inflammatory Syndrome in Children (MIS-C) cases have been documented frequently throughout the past pandemic. MIS-C is an immune-mediated post-infectious process that develops autoantibodies and can be associated with many specificities. Increased levels of numerous plasma cytokines, such as IL-6, IL-8, IFN-γ, IL-17, TNF-α, and IL-10, as well as modifications to the interferon response pathway are present in patients with MIS-C. The majority of patients have a fever that lasts for more than 4 days, and typical symptoms include conjunctivitis, rash, and mucocutaneous symptoms like conjunctivitis, as well as neurologic abnormalities like headache, irritability, and encephalopathy. Management strategies based on particular symptoms, therapies for disorders with a similar presentation, such as Kawasaki disease, or recommendations for COVID-19 treatment in individuals over the age of 18. Patients who got corticosteroids together with IVIG recovered more quickly than patients who did not. Fewer MIS-C is self-limiting and may get better with just supportive treatment.

Keywords


Autoinflammation; Immunopathology; Multisystem Inflammatory Syndrome; SARS-CoV-2

References


Belhadjer, Z., Auriau, J., Méot, M., Oualha, M., Renolleau, S., Houyel, L., & Bonnet, D. (2020). Addition of Corticosteroids to Immunoglobulins Is Associated With Recovery of Cardiac Function in Multi-Inflammatory Syndrome in Children. Circulation, 142(23), 2282–2284. https://doi.org/10.1161/CIRCULATIONAHA.120.050147

Belhadjer, Z., Méot, M., Bajolle, F., Khraiche, D., Legendre, A., Abakka, S., Auriau, J., Grimaud, M., Oualha, M., Beghetti, M., Wacker, J., Ovaert, C., Hascoet, S., Selegny, M., Malekzadeh-Milani, S., Maltret, A., Bosser, G., Giroux, N., Bonnemains, L., … Bonnet, D. (2020). Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic. Circulation, 142(5), 429–436. https://doi.org/10.1161/CIRCULATIONAHA.120.048360

Cascella, M., Rajnik, M., Aleem, A., Dulebohn, S. C., & Di Napoli, R. (2023). Features, Evaluation, and Treatment of Coronavirus (COVID-19). StatPearls Publishing LLC.

Casciola-Rosen, L., Thiemann, D. R., Andrade, F., Trejo Zambrano, M. I., Hooper, J. E., Leonard, E., Spangler, J., Cox, A. L., Machamer, C., Sauer, L., Laeyendecker, O., Garibaldi, B. T., Ray, S. C., Mecoli, C., Christopher-Stine, L., Gutierrez-Alamillo, L., Yang, Q., Hines, D., Clarke, W., … Rosen, A. (2020). IgM autoantibodies recognizing ACE2 are associated with severe COVID-19. MedRxiv : The Preprint Server for Health Sciences. https://doi.org/10.1101/2020.10.13.20211664

Giamarellos-Bourboulis, E. J., Netea, M. G., Rovina, N., Akinosoglou, K., Antoniadou, A., Antonakos, N., Damoraki, G., Gkavogianni, T., Adami, M. E., Katsaounou, P., Ntaganou, M., Kyriakopoulou, M., Dimopoulos, G., Koutsodimitropoulos, I., Velissaris, D., Koufargyris, P., Karageorgos, A., Katrini, K., Lekakis, V., … Koutsoukou, A. (2020). Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure. Cell Host and Microbe, 27(6), 992-1000.e3. https://doi.org/10.1016/j.chom.2020.04.009

Grifoni, A., Weiskopf, D., Ramirez, S. I., Mateus, J., Dan, J. M., Moderbacher, C. R., Rawlings, S. A., Sutherland, A., Premkumar, L., Jadi, R. S., Marrama, D., de Silva, A. M., Frazier, A., Carlin, A. F., Greenbaum, J. A., Peters, B., Krammer, F., Smith, D. M., Crotty, S., & Sette, A. (2020). Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell, 181(7), 1489-1501.e15. https://doi.org/10.1016/j.cell.2020.05.015

Gruber, C. N., Patel, R. S., Trachtman, R., Lepow, L., Amanat, F., Krammer, F., Wilson, K. M., Onel, K., Geanon, D., Tuballes, K., Patel, M., Mouskas, K., O’Donnell, T., Merritt, E., Simons, N. W., Barcessat, V., Del Valle, D. M., Udondem, S., Kang, G., … Bogunovic, D. (2020). Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C). Cell, 183(4), 982-995.e14. https://doi.org/10.1016/j.cell.2020.09.034

Hsieh, L.-E., Song, J., Grifoni, A., Shimizu, C., Tremoulet, A. H., Dummer, K. B., Burns, J. C., Sette, A., & Franco, A. (2022). T Cells in Multisystem Inflammatory Syndrome in Children (MIS-C) Have a Predominant CD4+ T Helper Response to SARS-CoV-2 Peptides and Numerous Virus-Specific CD4− CD8− Double-Negative T Cells. International Journal of Molecular Sciences, 23(13), 7219. https://doi.org/10.3390/ijms23137219

Jiang, L., Tang, K., Levin, M., Irfan, O., Morris, S. K., Wilson, K., Klein, J. D., & Bhutta, Z. A. (2020). COVID-19 and multisystem inflammatory syndrome in children and adolescents. In The Lancet Infectious Diseases (Vol. 20, Issue 11, pp. e276–e288). Lancet Publishing Group. https://doi.org/10.1016/S1473-3099(20)30651-4

Lamers, M. M., Beumer, J., Vaart, J. Van Der, Knoops, K., Puschhof, J., Breugem, T. I., Ravelli, R. B. G., Schayck, J. P. Van, Mykytyn, A. Z., Duimel, H. Q., Donselaar, E. Van, Riesebosch, S., Kuijpers, H. J. H., Schipper, D., Wetering, W. J. V. De, Graaf, M. De, Koopmans, M., Cuppen, E., Peters, P. J., … Clevers, H. (2020). SARS-CoV-2 productively infects human gut enterocytes. Science, 369(6499), 50–54. https://doi.org/10.1126/science.abc1669

Lee, P. Y., Day-Lewis, M., Henderson, L. A., Friedman, K. G., Lo, J., Roberts, J. E., Lo, M. S., Platt, C. D., Chou, J., Hoyt, K. J., Baker, A. L., Banzon, T. M., Chang, M. H., Cohen, E., de Ferranti, S. D., Dionne, A., Habiballah, S., Halyabar, O., Hausmann, J. S., … Son, M. B. F. (2020). Distinct clinical and immunological features of SARS–CoV-2–induced multisystem inflammatory syndrome in children. Journal of Clinical Investigation, 130(11), 5942–5950. https://doi.org/10.1172/JCI141113

Lim, L., Lim, S. J., Loy, J. S., & Ng, D. C. (2021). Multisystem inflammatory syndrome in children (MIS-C) occurring in temporal proximity between siblings. BMJ Case Reports, 14(9), e246066. https://doi.org/10.1136/bcr-2021-246066

Morris, S. B., Schwartz, N. G., Patel, P., Abbo, L., Beauchamps, L., Balan, S., Lee, E. H., Paneth-Pollak, R., Geevarughese, A., Lash, M. K., Dorsinville, M. S., Vennus Ballen, ;, Eiras, D. P., Christopher Newton-Cheh, ;, Smith, E., Robinson, S., Stogsdill, P., Lim, S., Fox, S. E., … Godfred-Cato, S. (2020). Morbidity and Mortality Weekly Report Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection-United Kingdom and United States. https://www.cdc.gov/mis-c/pdfs/hcp/mis-c-form-fillable.pdf.

Nakazawa, D., & Ishizu, A. (2020). Immunothrombosis in severe COVID-19. In EBioMedicine (Vol. 59). Elsevier B.V. https://doi.org/10.1016/j.ebiom.2020.102942

Nakra, N. A., Blumberg, D. A., Herrera-Guerra, A., & Lakshminrusimha, S. (2020). Multi-system inflammatory syndrome in children (Mis-c) following sars-cov-2 infection: Review of clinical presentation, hypothetical pathogenesis, and proposed management. In Children (Vol. 7, Issue 7). MDPI. https://doi.org/10.3390/children7070069

Noris, M., Benigni, A., & Remuzzi, G. (2020). The case of complement activation in COVID-19 multiorgan impact. Kidney International, 98(2), 314–322. https://doi.org/10.1016/j.kint.2020.05.013

Ouldali, N., Toubiana, J., Antona, D., Javouhey, E., Madhi, F., Lorrot, M., Léger, P.-L., Galeotti, C., Claude, C., Wiedemann, A., Lachaume, N., Ovaert, C., Dumortier, M., Kahn, J.-E., Mandelcwajg, A., Percheron, L., Biot, B., Bordet, J., Girardin, M.-L., … Dalichoux, B. (2021). Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children. JAMA, 325(9), 855. https://doi.org/10.1001/jama.2021.0694

Park, A., & Iwasaki, A. (2020). Type I and Type III Interferons – Induction, Signaling, Evasion, and Application to Combat COVID-19. In Cell Host and Microbe (Vol. 27, Issue 6, pp. 870–878). Cell Press. https://doi.org/10.1016/j.chom.2020.05.008

Pierce, C. A., Preston-Hurlburt, P., Dai, Y., Burn Aschner, C., Cheshenko, N., Galen, B., Garforth, S. J., Herrera, N. G., Jangra, R. K., Morano, N. C., Orner, E., Sy, S., Chandran, K., Dziura, J., Almo, S. C., Ring, A., Keller, M. J., Herold, K. C., & Herold, B. C. (2020). Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients. In Sci. Transl. Med (Vol. 12). https://www.science.org

Prinz, N., Clemens, N., Strand, D., Pütz, I., Lorenz, M., Daiber, A., Stein, P., Degreif, A., Radsak, M., Schild, H., Bauer, S., Von Landenberg, P., & Lackner, K. J. (2011). Antiphospholipid antibodies induce translocation of TLR7 and TLR8 to the endosome in human monocytes and plasmacytoid dendritic cells. Blood, 118(8), 2322–2332. https://doi.org/10.1182/blood-2011-01-330639

Ramaswamy, A., Brodsky, N. N., Sumida, T. S., Comi, M., Asashima, H., Hoehn, K. B., Li, N., Liu, Y., Shah, A., Ravindra, N. G., Bishai, J., Khan, A., Lau, W., Sellers, B., Bansal, N., Guerrerio, P., Unterman, A., Habet, V., Rice, A. J., … Lucas, C. L. (2021). Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity, 54(5), 1083-1095.e7. https://doi.org/10.1016/j.immuni.2021.04.003

Rawat, M., Chandrasekharan, P., Hicar, M. D., & Lakshminrusimha, S. (2020). COVID-19 in Newborns and Infants-Low Risk of Severe Disease: Silver Lining or Dark Cloud? In American Journal of Perinatology (Vol. 37, Issue 8, pp. 845–849). Thieme Medical Publishers, Inc. https://doi.org/10.1055/s-0040-1710512

Reis, B. C. S. Dos, Soares Faccion, R., de Carvalho, F. A. A., Moore, D. C. B. C., Zuma, M. C. C., Plaça, D. R., Salerno Filgueiras, I., Leandro Mathias Fonseca, D., Cabral-Marques, O., Bonomo, A. C., Savino, W., Freitas, F. C. de P., Faoro, H., Passetti, F., Robaina, J. R., de Oliveira, F. R. C., Novaes Bellinat, A. P., Zeitel, R. de S., Salú, M. dos S., … Vasconcelos, Z. F. M. de. (2023). Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort study. Frontiers in Cellular and Infection Microbiology, 13. https://doi.org/10.3389/fcimb.2023.1182257

Rowley, A. H. (2020). Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children. In Nature Reviews Immunology (Vol. 20, Issue 8, pp. 453–454). Nature Research. https://doi.org/10.1038/s41577-020-0367-5

Royal College of Paediatrics and Child Health. (2020). Guidance: Paediatric multisystem inflammatory syndrome temporally associated with COVID-19. https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf

Sacco, K., Castagnoli, R., Vakkilainen, S., Liu, C., Delmonte, O. M., Oguz, C., Kaplan, I. M., Alehashemi, S., Burbelo, P. D., Bhuyan, F., de Jesus, A. A., Dobbs, K., Rosen, L. B., Cheng, A., Shaw, E., Vakkilainen, M. S., Pala, F., Lack, J., Zhang, Y., … Notarangelo, L. D. (2022). Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19. Nature Medicine, 28(5), 1050–1062. https://doi.org/10.1038/s41591-022-01724-3

Simpson, J. M., & Newburger, J. W. (2020). Multisystem Inflammatory Syndrome in Children in Association with COVID-19. In Circulation (Vol. 142, Issue 5, pp. 437–440). Lippincott Williams and Wilkins. https://doi.org/10.1161/CIRCULATIONAHA.120.048726

Son, M. B. F., Murray, N., Friedman, K., Young, C. C., Newhams, M. M., Feldstein, L. R., Loftis, L. L., Tarquinio, K. M., Singh, A. R., Heidemann, S. M., Soma, V. L., Riggs, B. J., Fitzgerald, J. C., Kong, M., Doymaz, S., Giuliano, J. S., Keenaghan, M. A., Hume, J. R., Hobbs, C. V., … Randolph, A. G. (2021). Multisystem Inflammatory Syndrome in Children — Initial Therapy and Outcomes. New England Journal of Medicine, 385(1), 23–34. https://doi.org/10.1056/nejmoa2102605

The Centers for Disease Control and Prevention. (2020). Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19) _ CDC Archive. https://archive.cdc.gov/emergency_cdc_gov/han/2020/han00432.asp

van Eijk, L. E., Binkhorst, M., Bourgonje, A. R., Offringa, A. K., Mulder, D. J., Bos, E. M., Kolundzic, N., Abdulle, A. E., van der Voort, P. H. J., Olde Rikkert, M. G. M., van der Hoeven, J. G., den Dunnen, W. F. A., Hillebrands, J. L., & van Goor, H. (2021). COVID-19: immunopathology, pathophysiological mechanisms, and treatment options. In Journal of Pathology (Vol. 254, Issue 4, pp. 307–331). John Wiley and Sons Ltd. https://doi.org/10.1002/path.5642

Vella, L. A., & Rowley, A. H. (2021). Current Insights Into the Pathophysiology of Multisystem Inflammatory Syndrome in Children. In Current Pediatrics Reports (Vol. 9, Issue 4, pp. 83–92). Springer Science and Business Media, LLC. https://doi.org/10.1007/s40124-021-00257-6

World Health Organization. (2020). Multisystem inflammatory syndrome in children and adolescents with COVID-19: Scientific brief .


Full Text: PDF

DOI: 10.24815/jks.v24i3.38618

Refbacks

  • There are currently no refbacks.