Autoimmune status and subsequent rheumatologic outcomes in children diagnosed with multisystem inflammatory syndrome(MIS-C): a study in a tertiary hospital

Abstract

Background
Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of coronavirus disease 2019 (COVID-19), characterized by persistent fever, systemic inflammation, and organ failure. Its clinical features may overlap with hemophagocytic syndrome, Kawasaki disease, macrophage activation syndrome, and toxic shock syndrome.


Aim of work
An epidemiological study of MIS-C patients to assess the existence of autoantibodies and possible association with subsequent development of rheumatological autoimmune disorders.


Materials and methods
A prospective study conducted in a tertiary pediatric hospital on 98 children diagnosed with MIS-C according to World Health Organization (WHO) criteria 2020, for all patients; epidemiological data, laboratory and radiological investigations, comparative results according to management plan and prognosis were evaluated.


Results

The study included 98 MIS-C patients (mean age 5.97 years, 52% males), with 3.1% previously diagnosed with rheumatological disease and 10.2% other chronic conditions. Fever was universal, with 55.1% experiencing prolonged fever (> 2 weeks). Cardiac (80%), neurological (28%), and renal (50%) involvement were common, while autoimmune markers were positive in 36.7%. Leukocytosis (49%), anemia (83.7%), and elevated inflammatory markers were frequently noted. Management included intravenous immunoglobulin IVIG (96.9%), steroids (85.7%), and anticoagulation (17%), with biologic therapy in two cases. Prognosis was favorable in 74.5%, while 21.4% developed chronic complications including 12 patients (12.2%) who developed a heterogeneous combined group of chronic immune-mediated diseases, including 8 patients (8.1%) who developed autoimmune diseases. Four patients (4.1%) died. Autoimmune disease developed in 6/36 (16.7%) autoantibody-positive patients compared with 2/62 (3.2%) autoantibody-negative patients, corresponding to RR 5.17 (95% CI 1.10-24.26) and OR 5.16 (95% CI 1.13–23.63), with
p
 = 0.048.



Conclusion
Multisystem inflammatory syndrome in children involved stimulation of the innate immune system with a hyperinflammatory status, yet there is also involvement of the adaptive immune system, with production of autoantibodies in more than 30% of the patients. In our cohort, early autoantibody positivity was associated with a higher observed proportion of subsequent autoimmune disease during follow-up; however, this association was based on few events and should be considered exploratory, hypothesis-generating, and non-causal rather than definitive. More research is needed to investigate children with a previous diagnosis of rheumatological diseases regarding the occurrence of MIS-C.