Pathogenesis of COVID-19 and multi-system inflammatory syndrome in children

Arundhathi Shankaralingappa, Arun Babu Thirunavukkarasu


World health organization declared COVID-19 caused by SARS CoV-2 virus as a pandemic in early 2020. The target cells facilitating viral entry are ACE-2 receptor bearing cells like bronchial epithelial cells and pneumocytes.  Children pose a less risk compared to adults in acquiring this disease and mortality in them is low due to protective pathogenesis. Children with COVID-19 are also at risk of developing unique immunological phenomena, known as multi-system inflammatory syndrome in children. MIS-C is considered to be hyperimmune state resulting from cytokine storm and circulating immune complexes. This mini-review reflects the most recent understanding of the pathogenesis in children with special emphasis on MIS-C.


COVID-19, SARS CoV-2, Multi-system inflammatory syndrome in children, Pathogenesis, Children

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Guo Z-D, Wang Z-Y, Zhang S-F, Li X, Li L, Li C, et al. Aerosol and Surface Distribution of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospital Wards, Wuhan, China, 2020. Emerging Infect Dis. 2020;26:1583-91.

Hassan S. Presentation, management and pathogenesis of the SARS-CoV-2 in Children. Acta Sci Paediatr. 2020;3:13-31.

WHO Coronavirus Disease (COVID-19) Dashboard. Available at: Accessed on 20 October 2020.

Coronavirus in India: latest map and case count. Available at: Accessed on 20 October 2020.

Pandit K, Gupta S, Sharma AG. Clinico-Pathogenesis of COVID-19 in children. Indian J Biochem Biophysics. 2020;57:264-9.

Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, et al. Epidemiology of COVID-19 Among Children in China. Pediatr. 2020;145(6):e20200702.

Weiss SR, Leibowitz JL, Coronavirus Pathogenesis. Adv Virus Res. 2011;81:85-9.

Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270-3.

Hui DS, Azhar EI, Madani TA, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health-The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020;91:264-66.

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565-74.

Kampf G, Todt D, Pfaender S, Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. J Hosp Infect. 2020;104:246-51.

Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020;14:185-92.

Dhochak N, Singhal T, Kabra SK, Lodha R. Pathophysiology of COVID-19: why children fare better than adults?. Indian J Pediatr. 2020;1:10.

Ibrahim IM, Abdelmalek DH, Elshahat ME, Elfiky AA. COVID-19 spike-host cell receptor GRP78 binding site prediction. J Infect. 2020;80:554-62.

Wang F, Nie J, Wang H, Zhao Q, Xiong Y, Deng L, et al. Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia. J Infect Dis. 2020; 221:1762-69.

Chen YMA, Liang SY, Shih YP, Chen CY, Lee YM, Chang L. Epidemiological and genetic correlates of severe acute respiratory syndrome coronavirus infection in the hospital with the highest nosocomial infection rate in Taiwan in 2003. J Clin Microbiol. 2006;44:359-65.

Channappanavar R, Perlman S. Pathogenic human Coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39:529-39.

Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8:420-22.

Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18:844-7.

Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020;191: 145-7.

Lingappan K, Karmouty-Quintana H, Davies J, Akkanti B, Harting MT. Understanding the age divide in COVID-19: why are children overwhelmingly spared?. Am J Physiol Lung Cell Mol Physiol. 2020;319:L39-44.

Schouten LR, van Kaam AH, Kohse F, Veltkamp F, Bos LD, de Beer FM, et al. Age-dependent differences in pulmonary host responses in ARDS: a prospective observational cohort study. Ann Intensive Care. 2019;9:55.

Thome JJ, Bickham KL, Ohmura Y, Kubota M, Matsuoka N, Gordon C, et al. Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues. Nat Med. 2016;22:72-7.

Lawrence SM, Corriden R, Nizet V. Age-appropriate functions and dysfunctions of the neonatal neutrophil. Front Pediatr. 2017;5:23.

Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. Chinese pediatric novel coronavirus study team. SARS-CoV-2 infection in children. N Engl J Med. 2020;382:1663-5.

Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180:934-43.

Ying L, Alvira CM, Cornfield DN. Developmental differences in focal adhesion kinase expression modulate pulmonary endothelial barrier function in response to inflammation. Am J Physiol Lung Cell Mol Physiol. 2018;315:L66-77.

Sperotto F, Friedman KG, Son MBF, Vander PCJ, Newburger JW, Dionne A. Cardiac manifestations in SARS CoV-2-associated multisysteminflammatory syndrome in children: a comprehensive reviewand proposed clinical approach. Eur J Pediatr. 2020; 1:16.

Guidance: paediatricmultisystem inflammatory syndrome temporally associated with COVID-19. Available at: guidancepaediatric- multisystem-inflammatory-syndrome-temporally associated- covid-19. Accessed on 20 October 2020.

Emergency preparednessand response: health alert network. Available at: han/2020/han00432.asp. Accessed on 20 October 2020.

Multisystem inflammatory syndromein children and adolescents with COVID-19. Available at: detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19. Accessed on 20 October 2020.

Chiotos K, Bassiri H, Behrens EM, Blatz AM, Chang J, Diorio C, et al. Multisystem Inflammatory Syndrome in Children During the Coronavirus 2019 Pandemic: A Case Series. J Pediatric Infect Dis Soc. 2020;9:393-8.

Feldstein LR, Rose EB, Horwitz SM. Multisystem inflammatory syndrome in U.S. Children and Adolescents. N Engl J Med. 2020;383:334-9.

Balasubramanian S, Nagendran T, Ramachandran B, Ramanan A. Hyper-inflammatory syndrome in a child With COVID-19 treated successfully with intravenous immunoglobulin and tocilizumab. Indian Pediatr. 2020;57:681-3.

Mccrindle BW, Manlhiot C. SARS-CoV-2-related inflammatory multisystem syndrome in children: different or shared etiology and pathophysiology as Kawasaki disease?. JAMA. 2020;324:246-8.

Nakra NA, Blumberg DA, Herrera-Guerra A, Lakshminrusimha S. Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 infection: review of clinical presentation, hypothetical pathogenesis, and proposed management. Children (Basel). 2020;7:69.

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.

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;422:1884-9.

Gruber C, Patel R, Trachman R, Lepow L, Amanat F, Krammer F, et al. Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C). medRxiv. 2020.

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.

Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, et al. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020;5:e138999.