Research Article | | Peer-Reviewed

PIMS-TS Complicating SARS-CoV-2 Infection: A Report of 10 Pediatric Cases

Received: 18 May 2024     Accepted: 18 July 2024     Published: 20 August 2024
Views:       Downloads:
Abstract

SARS-CoV-2, or COVID-19, is a betacoronavirus identified by the WHO as the cause of the 2020 pandemic. Unlike most respiratory virus, children exhibit lower susceptibility to COVID-19 and generally develop milder disease courses, with reduced mortality rates. Recently, there have been reports of clustered cases characterized by shock states associated with elevated cardiac biomarkers and vasoplegia, necessitating treatment with inotropes, vasopressors, and fluid resuscitation. This clinical presentation has been linked to the emergence of Pediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS), also known as Kawasaki-like syndrome. This study is a retrospective analysis of 10 pediatric patients diagnosed with PIMS-TS secondary to COVID-19 infection, who were admitted to Mohammed VI International University Hospital in Casablanca, Morocco, from January 2021 to October 2023. The cohort's ages ranged from 2 to 13 years, with a mean age of 6 years, and demonstrated a male predominance (sex ratio 9M:1F). Clinical manifestations included prolonged fever, gastrointestinal disturbances, rash, conjunctivitis, and cheilitis. Laboratory findings revealed elevated levels of CRP, PCT, and ferritin, indicative of an atypical Kawasaki syndrome. These patients responded to intravenous immunoglobulin therapy, with adjunctive corticosteroids administered as needed. All patients experienced favorable outcomes, with resolution of systemic involvement and normalization of inflammatory markers, and no relapses or fatalities were recorded. The risk factors for PIMS-TS complicating COVID-19 infection remain unclear. However, there are noted parallels between PIMS-TS and Kawasaki syndrome diagnostic criteria, suggesting possible pathophysiological overlap. In conclusion, a novel multisystem inflammatory syndrome associated with COVID-19 infection, resembling Kawasaki syndrome, has been identified in pediatric patients. This emerging syndrome enhances our understanding of the complex pathophysiology associated with COVID-19 and underscores the need for continued research into its etiology and optimal management strategies.

Published in American Journal of Pediatrics (Volume 10, Issue 3)
DOI 10.11648/j.ajp.20241003.16
Page(s) 136-146
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

COVID-19, PIMS-TS, MIS-C, SRAS-COV-2, Kawasaki

References
[1] Cucinotta D, Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020 Mar 19; 91(1): 157-160.
[2] Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science. 2020; 368: 473–474.
[3] Lu X, Zhang L, Du H, et al. SARS-CoV-2 infection in children. N Engl J Med. 2020; 382: 1663–1665.
[4] Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020; 181(2): 281-292. e6.
[5] Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020; 367(6483): 1260-1263.
[6] Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020; 181(2): 271-280. e8.
[7] Ke Z, Oton J, Qu K, et al. Structures and distributions of SARS-CoV-2 spike proteins on intact virions. Nature. 2020; 588(7838): 498-502.
[8] Gao Y, Yan L, Huang Y, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020; 581(7807): 215-220.
[9] Zhu N, Wang W, Liu Z, et al. Morphogenesis and cytopathic effect of SARS-CoV-2 infection in human airway epithelial cells. Nature Communications. 2020; 11: 3910.
[10] Yan R, Zhang Y, Li Y, et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020; 367(6485): 1444-1448.
[11] Shang J, Ye G, Shi K, et al. Structural basis of receptor recognition by SARS-CoV-2. Nature. 2020; 581(7807): 221-224.
[12] Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798): 270-273.
[13] Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nature Microbiology. 2020; 5(4): 562-569.
[14] Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet. 2020; 395(10229): 1033-1034.
[15] Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. The cytokine release syndrome (CRS) of severe COVID-19 and interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality. International Journal of Antimicrobial Agents. 2020; 55(5): 105954.
[16] Rowley AH. Is Kawasaki disease an infectious disorder? Int J Rheum Dis. 2018; 21(1): 20-25.
[17] Shulman ST, Rowley AH. Kawasaki disease: insights into pathogenesis and approaches to treatment. Nat Rev Rheumatol. 2015; 11(8): 475-482.
[18] Burns JC, Glode MP. Kawasaki syndrome. Lancet. 2004; 364(9433): 533-544.
[19] Kuo HC, Chang WC. Genetic polymorphisms in Kawasaki disease. Acta Pharmacol Sin. 2011; 32(10): 1193-1198.
[20] Yeung RS. Kawasaki disease: update on pathogenesis. Curr Opin Rheumatol. 2010; 22(5): 551-560.
[21] Rowley AH. Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children. Nat Rev Immunol. 2020; 20(8): 453-454.
[22] Mercier, J.-C., Maroni, A. COVID-19 chez l’enfant: syndrome inflammatoire multi-systémique lié à SARS-CoV-2 mimant un syndrome de Kawasaki [COVID-19 in children: multisystem inflammatory syndrome associated with SARS-CoV-2 mimicking Kawasaki syndrome].
[23] Kanegaye JT, Wilder MS, Molkara D et al. Recognition of a Kawasaki disease shock syndrome. Pediatrics. 2009; 123: e783-e789.
[24] Gámez-González LB, Murata C, Muñoz-Ramírez M, Yamazaki-Nakashimada M Clinical manifestations associated with Kawasaki disease shock syndrome in Mexican children.
[25] Lin Y-J, Cheng M-C, Lo M-H, Chien S-J Early differentiation of Kawasaki disease shock syndrome and toxic shock syndrome in a pediatric intensive care unit. Pediatr Infect Dis J. 2015; 34: 1163-1167.
[26] Gamez-Gonzalez LB, Moribe-Quintero I, Cisneros-Castolo M, et al. Kawasaki disease shock syndrome: unique and severe subtype of Kawasaki disease.
[27] Fernández-Sarmiento J, De Souza D, Jabornisky R, Gonzalez GA, Arias López MDP, Palacio G. Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): a narrative review and the viewpoint of the Latin American Society of Pediatric Intensive Care (SLACIP) Sepsis Committee. BMJ Paediatr Open. 2021 Feb 4; 5(1): e000894.
[28] Kawasaki, T. Syndrome cutanéo-muqueux fébrile aigu avec atteinte lymphoïde avec desquamation spécifique des doigts et des orteils chez les enfants [Acute febrile mucocutaneous lymph node syndrome with specific desquamation of the fingers and toes in children]. Arerugi 1967, 16, 178-222.
[29] McCrindle, B. W.; Rowley, A. H.; Newburger, J. W.; Burns, J. C.; Bolger, A. F.; Gewitz, M.; Baker, A. L.; Jackson, M. A.; Takahashi, M.; Shah, P. B.; et al. Diagnostic, traitement et gestion à long terme de la maladie de Kawasaki: une déclaration scientifique pour les professionnels de la santé de l’American Heart Association [Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for healthcare professionals from the American Heart Association]. Diffusion 2017, 135, e927-e999.
[30] Ayusawa, M.; Sonobe, T.; Uemura, S.; Ogawa, S.; Nakamura, Y.; Kiyosawa, N.; Ishii, M.; Harada, K. Révision des directives diagnostiques pour la maladie de Kawasaki (la 5e édition révisée) [Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition)]. Pédiatre int. 2005, 47, 232 à 234.
[31] Gong, G. W.; McCrindle, B. W.; Ching, J. C.; Yeung, R. S. Arthrite se présentant pendant la phase aiguë de la maladie de Kawasaki [Arthritis presenting during the acute phase of Kawasaki disease]. J. Pédiatre. 2006, 148, 800 à 805.
[32] Kuo, H.-C. Diagnosis, Progress, and Treatment Update of Kawasaki Disease. Int. J. Mol. Sci. 2023, 24, 13948.
[33] Rife, E., Gedalia, A. Maladie de Kawasaki: une mise à jour [Kawasaki disease: an update]. Curr Rheumatol Rep 22, 75 (2020).
[34] Wessels PA, Bingler MA. Une comparaison de la maladie de Kawasaki et du syndrome inflammatoire multisystémique chez les enfants [A comparison of Kawasaki disease and multisystem inflammatory syndrome in children]. Prog Pediatr Cardiol. Juin 2022; 65: 101516.
[35] Consiglio CR, Cotugno N, Sardh F, et al. The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19. Nature Medicine. 2020; 26(10): 1664-1670.
[36] Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. New England Journal of Medicine. 2020; 383(4): 334-346.
[37] 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; 324(3): 259-269.
[38] Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. The Lancet. 2020; 395(10239): 1771-1778.
[39] Riphagen S, Gomez X, Gonzalez-Martinez C, et al. Hyperinflammatory shock in children during COVID-19 pandemic. The Lancet. 2020; 395(10237): 1607-1608.
[40] Toubiana J, Poirault C, Corsia A, et al. Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study. BMJ. 2020; 369.
[41] Cheung EW, Zachariah P, Gorelik M, et al. Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York City. JAMA. 2020; 324(3): 294-296.
[42] Ramaswamy A, Brodsky NN, Sumida TS, et al. Immune dysregulation and autoreactivity in autoimmune myocarditis induced by checkpoint inhibitors. Cancer Discovery. 2021; 11(4): 891-908.
Cite This Article
  • APA Style

    Ahchouch, S., Benechchehab, Y., Arrab, R., Ammari, I. A., Dini, N. (2024). PIMS-TS Complicating SARS-CoV-2 Infection: A Report of 10 Pediatric Cases. American Journal of Pediatrics, 10(3), 136-146. https://doi.org/10.11648/j.ajp.20241003.16

    Copy | Download

    ACS Style

    Ahchouch, S.; Benechchehab, Y.; Arrab, R.; Ammari, I. A.; Dini, N. PIMS-TS Complicating SARS-CoV-2 Infection: A Report of 10 Pediatric Cases. Am. J. Pediatr. 2024, 10(3), 136-146. doi: 10.11648/j.ajp.20241003.16

    Copy | Download

    AMA Style

    Ahchouch S, Benechchehab Y, Arrab R, Ammari IA, Dini N. PIMS-TS Complicating SARS-CoV-2 Infection: A Report of 10 Pediatric Cases. Am J Pediatr. 2024;10(3):136-146. doi: 10.11648/j.ajp.20241003.16

    Copy | Download

  • @article{10.11648/j.ajp.20241003.16,
      author = {Sanae Ahchouch and Youssef Benechchehab and Raja Arrab and Inssaf Al Ammari and Nouzha Dini},
      title = {PIMS-TS Complicating SARS-CoV-2 Infection: A Report of 10 Pediatric Cases
    },
      journal = {American Journal of Pediatrics},
      volume = {10},
      number = {3},
      pages = {136-146},
      doi = {10.11648/j.ajp.20241003.16},
      url = {https://doi.org/10.11648/j.ajp.20241003.16},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajp.20241003.16},
      abstract = {SARS-CoV-2, or COVID-19, is a betacoronavirus identified by the WHO as the cause of the 2020 pandemic. Unlike most respiratory virus, children exhibit lower susceptibility to COVID-19 and generally develop milder disease courses, with reduced mortality rates. Recently, there have been reports of clustered cases characterized by shock states associated with elevated cardiac biomarkers and vasoplegia, necessitating treatment with inotropes, vasopressors, and fluid resuscitation. This clinical presentation has been linked to the emergence of Pediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS), also known as Kawasaki-like syndrome. This study is a retrospective analysis of 10 pediatric patients diagnosed with PIMS-TS secondary to COVID-19 infection, who were admitted to Mohammed VI International University Hospital in Casablanca, Morocco, from January 2021 to October 2023. The cohort's ages ranged from 2 to 13 years, with a mean age of 6 years, and demonstrated a male predominance (sex ratio 9M:1F). Clinical manifestations included prolonged fever, gastrointestinal disturbances, rash, conjunctivitis, and cheilitis. Laboratory findings revealed elevated levels of CRP, PCT, and ferritin, indicative of an atypical Kawasaki syndrome. These patients responded to intravenous immunoglobulin therapy, with adjunctive corticosteroids administered as needed. All patients experienced favorable outcomes, with resolution of systemic involvement and normalization of inflammatory markers, and no relapses or fatalities were recorded. The risk factors for PIMS-TS complicating COVID-19 infection remain unclear. However, there are noted parallels between PIMS-TS and Kawasaki syndrome diagnostic criteria, suggesting possible pathophysiological overlap. In conclusion, a novel multisystem inflammatory syndrome associated with COVID-19 infection, resembling Kawasaki syndrome, has been identified in pediatric patients. This emerging syndrome enhances our understanding of the complex pathophysiology associated with COVID-19 and underscores the need for continued research into its etiology and optimal management strategies.
    },
     year = {2024}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - PIMS-TS Complicating SARS-CoV-2 Infection: A Report of 10 Pediatric Cases
    
    AU  - Sanae Ahchouch
    AU  - Youssef Benechchehab
    AU  - Raja Arrab
    AU  - Inssaf Al Ammari
    AU  - Nouzha Dini
    Y1  - 2024/08/20
    PY  - 2024
    N1  - https://doi.org/10.11648/j.ajp.20241003.16
    DO  - 10.11648/j.ajp.20241003.16
    T2  - American Journal of Pediatrics
    JF  - American Journal of Pediatrics
    JO  - American Journal of Pediatrics
    SP  - 136
    EP  - 146
    PB  - Science Publishing Group
    SN  - 2472-0909
    UR  - https://doi.org/10.11648/j.ajp.20241003.16
    AB  - SARS-CoV-2, or COVID-19, is a betacoronavirus identified by the WHO as the cause of the 2020 pandemic. Unlike most respiratory virus, children exhibit lower susceptibility to COVID-19 and generally develop milder disease courses, with reduced mortality rates. Recently, there have been reports of clustered cases characterized by shock states associated with elevated cardiac biomarkers and vasoplegia, necessitating treatment with inotropes, vasopressors, and fluid resuscitation. This clinical presentation has been linked to the emergence of Pediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS), also known as Kawasaki-like syndrome. This study is a retrospective analysis of 10 pediatric patients diagnosed with PIMS-TS secondary to COVID-19 infection, who were admitted to Mohammed VI International University Hospital in Casablanca, Morocco, from January 2021 to October 2023. The cohort's ages ranged from 2 to 13 years, with a mean age of 6 years, and demonstrated a male predominance (sex ratio 9M:1F). Clinical manifestations included prolonged fever, gastrointestinal disturbances, rash, conjunctivitis, and cheilitis. Laboratory findings revealed elevated levels of CRP, PCT, and ferritin, indicative of an atypical Kawasaki syndrome. These patients responded to intravenous immunoglobulin therapy, with adjunctive corticosteroids administered as needed. All patients experienced favorable outcomes, with resolution of systemic involvement and normalization of inflammatory markers, and no relapses or fatalities were recorded. The risk factors for PIMS-TS complicating COVID-19 infection remain unclear. However, there are noted parallels between PIMS-TS and Kawasaki syndrome diagnostic criteria, suggesting possible pathophysiological overlap. In conclusion, a novel multisystem inflammatory syndrome associated with COVID-19 infection, resembling Kawasaki syndrome, has been identified in pediatric patients. This emerging syndrome enhances our understanding of the complex pathophysiology associated with COVID-19 and underscores the need for continued research into its etiology and optimal management strategies.
    
    VL  - 10
    IS  - 3
    ER  - 

    Copy | Download

Author Information
  • The Department of Pediatrics, Mohammed VI International University Hospital, Casablanca, Morocco

  • The Department of Pediatrics, Mohammed VI International University Hospital, Casablanca, Morocco

  • The Department of Pediatrics, Mohammed VI International University Hospital, Casablanca, Morocco

  • The Department of Pediatrics, Mohammed VI International University Hospital, Casablanca, Morocco

  • The Department of Pediatrics, Mohammed VI International University Hospital, Casablanca, Morocco

  • Sections