Multisystem Inflammatory Syndrome in Children (MIS-C) with COVID-19: A Single-Center Experience

Abstract

Objective Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory syndrome associated with multiorgan damage that occurs following coronavirus disease 2019 (COVID-19). Research on clinical and laboratory findings, and imaging studies, aiming to predict the progression to severe disease state is limited. This study recruited patients with MIS-C who presented with mild or severe symptoms from a single center in Turkey and evaluated factors related to their symptoms.

Methods This retrospective study included 25 pediatric patients with mild and severe presentations of MIS-C. We explored the differences in demographic and clinical data on clinical severity to understand their possible diagnostic and prognostic values.

Results Patients with MIS-C had cardiovascular symptoms (68%), gastrointestinal symptoms (64%), dermatologic/mucocutaneous findings (64%), lung involvement (36%), and neurological symptoms (16.0%). About 45.1% of patients with MIS-C had manifestations that overlapped with Kawasaki disease. Eleven patients (44%) were admitted to the intensive care unit, and one (4%) patient died. Grouping based on clinical severity did not differ statistically in terms of gender, age, height, weight, body mass index, and duration of hospital stay. Procalcitonin and ferritin levels correlated with disease severity. The receiver operating characteristic curve for D-dimer gave the highest value of area under the curve, among other biomarkers. The cutoff value for D-dimer was determined as more than 6780.

Conclusions Although COVID-19 is usually mild in children, some can be severely affected, and clinical severity in MIS-C can differ from mild to severe multisystem involvement. This study shows that procalcitonin, ferritin, and D-dimer levels may give us information about disease severity.

Keywords

COVID-19 - MIS-C - pediatrics - SARS-CoV-2

• References

• 1 Haslak F, Yıldız M, Adrovic A, Şahin S, Barut K, Kasapçopur Ö. A recently explored aspect of the iceberg named COVID-19: multisystem inflammatory syndrome in children (MIS-C). Turk Pediatri Ars 2021; 56 (01) 3-9
• 2 Tolunay O, Çelik Ü, Arslan İ. et al. Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19: a case series experience in a tertiary care hospital of Southern Turkey. J Trop Pediatr 2021; 67 (02) fmab050
• 3 Dong Y, Mo X, Hu Y. et al. Epidemiology of COVID-19 among children in China. Pediatrics 2020; 145 (06) e20200702
• 4 Dufort EM, Koumans EH, Chow EJ. et al; New York State and Centers for Disease Control and Prevention Multisystem Inflammatory Syndrome in Children Investigation Team. Multisystem inflammatory syndrome in children in New York State. N Engl J Med 2020; 383 (04) 347-358
• 5 Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020; 395 (10237): 1607-1608
• 6 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. Lancet 2020; 395 (10239): 1771-1778
• 7 Kavurt AV, Bağrul D, Gül AEK. et al. Echocardiographic findings and correlation with laboratory values in multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. [published online ahead of print, 2021] Pediatr Cardiol 2021: 1-13
• 8 Royal College of Paediatrics and Child Health. Guidance: paediatric multisystem inflammatory syndrome temporally associated with COVID19. Accessed May 16, 2022 at: https://www.rcpch.ac.uk/resources/paediatric-multisystem-inflammatory-syndrome-temporally-associated-covid-19-pims-guidance
• 9 World Health Organization. Multisystem inflammatory syndrome in children andadolescents temporally related to COVID-19. Published May 15, 2020. Accessed May 16, 2022 at: https://www.who.int/news-room/commentaries/detail/multisystemnn-inflammatory-syndrome-in-children-and-adolescents-with-covid-19
• 10 Centers for Disease Control and Prevention. Emergency preparedness and response: multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19). Published May 14, 2020. Accessed May 16, 2022 at: https://emergency.cdc.gov/han/2020/han00432.asp
• 11 Alkan G, Sert A, Oz SKT, Emiroglu M, Yılmaz R. Clinical features and outcome of MIS-C patients: an experience from Central Anatolia. Clin Rheumatol 2021; 40 (10) 4179-4189
• 12 Jonat B, Gorelik M, Boneparth A. et al. Multisystem inflammatory syndrome in children associated with coronavirus disease 2019 in a children's hospital in New York City: patient characteristics and an institutional protocol for evaluation, management, and follow-up. Pediatr Crit Care Med 2021; 22 (03) e178-e191
• 13 Godfred-Cato S, Bryant B, Leung J. et al; California MIS-C Response Team. COVID-19-associated multisystem inflammatory syndrome in children - United States, March-July 2020. Morb Mortal Wkly Rep 2020; 69 (32) 1074-1080
• 14 McCrindle BW, Rowley AH, Newburger JW. et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Epidemiology and Prevention. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. [published correction appears in Circulation. 2019;140(5):e181-e184] Circulation 2017; 135 (17) e927-e999
• 15 Rowley AH, Shulman ST, Arditi M. Immune pathogenesis of COVID-19-related multisystem inflammatory syndrome in children. J Clin Invest 2020; 130 (11) 5619-5621
• 16 Feldstein LR, Rose EB, Horwitz SM. et al; Overcoming COVID-19 Investigators, CDC COVID-19 Response Team. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med 2020; 383 (04) 334-346
• 17 Lima-Setta F, Magalhães-Barbosa MC, Rodrigues-Santos G. et al; Brazilian Research Network in Pediatric Intensive Care (BRnet-PIC). Multisystem inflammatory syndrome in children (MIS-C) during SARS-CoV-2 pandemic in Brazil: a multicenter, prospective cohort study. J Pediatr (Rio J) 2021; 97 (03) 354-361
• 18 Torres JP, Izquierdo G, Acuña M. et al. Multisystem inflammatory syndrome in children (MIS-C): report of the clinical and epidemiological characteristics of cases in Santiago de Chile during the SARS-CoV-2 pandemic. Int J Infect Dis 2020; 100: 75-81
• 19 Ozel A, Erol M, Onan SH. et al. Evaluation of clinical features of patients diagnosed with MIS-C. Bagcilar Medical Bulletin 2021; 6 (03) 295-302
• 20 Panigrahy N, Policarpio J, Ramanathan R. Multisystem inflammatory syndrome in children and SARS-CoV-2: a scoping review. [published correction appears in J Pediatr Rehabil Med. 2021;14(1):137] J Pediatr Rehabil Med 2020; 13 (03) 301-316
• 21 Belhadjer Z, Méot M, Bajolle F. et al. Acute heart failure in multisystem inflammatory syndrome in children in the context of global SARS-CoV-2 pandemic. Circulation 2020; 142 (05) 429-436
• 22 Radia T, Williams N, Agrawal P. et al. Multi-system inflammatory syndrome in children & adolescents (MIS-C): a systematic review of clinical features and presentation. Paediatr Respir Rev 2021; 38: 51-57
• 23 Yasuhara J, Watanabe K, Takagi H, Sumitomo N, Kuno T. COVID-19 and multisystem inflammatory syndrome in children: a systematic review and meta-analysis. Pediatr Pulmonol 2021; 56 (05) 837-848
• 24 Feldstein LR, Tenforde MW, Friedman KG. et al; Overcoming COVID-19 Investigators. Characteristics and outcomes of US children and adolescents with multisystem inflammatory syndrome in children (MIS-C) compared with severe acute COVID-19. JAMA 2021; 325 (11) 1074-1087
• 25 Bautista-Rodriguez C, Sanchez-de-Toledo J, Clark BC. et al. Multisystem inflammatory syndrome in children: an international survey. Pediatrics 2021; 147 (02) e2020024554
• 26 Levin M. Childhood multisystem inflammatory syndrome - a new challenge in the pandemic. N Engl J Med 2020; 383 (04) 393-395
• 27 Kaushik S, Aydin SI, Derespina KR. et al. Multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2 infection (MIS-C): a multi-institutional study from New York City. J Pediatr 2020; 224: 24-29
• 28 Valverde I, Singh Y, Sanchez-de-Toledo J. et al; AEPC COVID-19 Rapid Response Team*. Acute cardiovascular manifestations in 286 children with multisystem inflammatory syndrome associated with COVID-19 infection in Europe. Circulation 2021; 143 (01) 21-32
• 29 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: m2094
• 30 Jain S, Sen S, Lakshmivenkateshiah S. et al. Multisystem inflammatory syndrome in children with COVID-19 in Mumbai, India. Indian Pediatr 2020; 57 (11) 1015-1019
• 31 Whittaker E, Bamford A, Kenny J. et al; PIMS-TS Study Group and EUCLIDS and PERFORM Consortia. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA 2020; 324 (03) 259-269
• 32 Ciftdogan Y, Ekemen Keles D, Cetin Y. et al. COVID-19 associated multisystemic inflammatory syndrome in 614 children with and without overlap with Kawasaki disease-Turk MIS-C study group. Eur J Pediatr 2022; 181 (05) 2031-2043
• 33 Shabab J, Dubisky A, Singh A. et al. A descriptive study on multisystem inflammatory syndrome in children in a single center in West Michigan. Pediatr Rheumatol Online J. 2021;16;19(1):172
• 34 Al-Ghafry M, Vagrecha A, Malik M. et al. Multisystem inflammatory syndrome in children (MIS-C) and the prothrombotic state: Coagulation profiles and rotational thromboelastometry in a MIS-C cohort. J Thromb Haemost 2021; 19 (07) 1764-1770