COVID-19 İLİŞKİLİ MULTİSİSTEMİK ENFLAMATUVAR SENDROMLU ÇOCUKLARIN UZUN DÖNEM KOMORBİDİTE VE PROGNOZLARININ DEĞERLENDİRİLMESİ

Abstract

Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 is a condition characterized by high fever, multi-organ involvement and a significant increase in inflammatory markers, which usually requires hospitalization following a SARS-CoV-2 infection. MIS-C patients should be closely monitored for potential organ involvement, particularly cardiac, both at diagnosis and during follow-up. However, there are limited data in the literature regarding how frequently MIS-C patients should be followed or the complications that may develop during follow-up. Since MIS-C is a relatively new disease, long-term follow-up data for these patients are not yet available. Therefore, the aim of our study is to evaluate the demographic characteristics, clinical and laboratory findings (including autoantibodies), echocardiography and other imaging results, treatments received, treatment responses, the development of autoimmune diseases during follow-up, long-term comorbidities, and prognoses of patients diagnosed with Multisystem Inflammatory Syndrome (MIS-C) associated with COVID-19. This study includes 132 MIS-C patients aged 0-18 years who were diagnosed and followed up at our hospital between April 2020 and October 2023, as well as 13 patients diagnosed and followed up with severe COVID-19 pneumonia during this period. The findings of MIS-C patients were compared with those of COVID-19 pneumonia patients and according to the dominant variant periods, before and after December 2021. Before December 2021, 98 MIS-C patients (mostly associated with the Delta variant) were identified, and after December 2021, 34 MIS-C patients (associated with the Omicron variant) were identified. Of the patients, 65.9% were male, and the median age at diagnosis was 8.2 years. When MIS-C patients were divided according to their clinical phenotypes at presentation, 43 patients (32.6%) presented with shock, 36 patients (27.3%) with a KD phenotype, and 89 patients (67.4%) with a KD-like phenotype. The most common clinical findings in MIS-C patients were fever (100%), gastrointestinal system findings (84.8%), rash (72%), and conjunctivitis (72.7%). Almost all patients had lymphopenia (0.2-1.58) at diagnosis, with a platelet count of 180 x 10^3/μL (27-649) and a mean CRP of 18.5 mg/dL (0.5-144.7). Abnormal liver function tests were detected in 57 patients (43.2%). In severe COVID-19 pneumonia patients, the mean CRP was 5.8 mg/dL, significantly lower than in MIS-C patients (p<0.05). At diagnosis, 88 MIS-C patients (67.2%) had abnormal echocardiography findings, with a mean ejection fraction of 63.1%. The most common cardiac valve involvement was mitral insufficiency, observed in 60 patients (45.8%). In severe COVID-19 patients, there was no significant decrease in systolic function, and the mean ejection fraction was significantly higher compared to MIS-C patients (EF: 72%) (p<0.05). During treatment, all MIS-C patients received intravenous immunoglobulin (IVIG), steroids, and IV antibiotics. In addition, 123 patients (93.2%) received low molecular weight heparin, and 100 patients (75.8%) received aspirin. Anakinra therapy was administered to 82 patients (62.1%). The mean duration of treatment was 5 days (2-60 days) for steroids and 5 days (2-21 days) for anakinra. Intubation was required in 14 patients (10.6%), inotropic support in 44 patients (33.3%), therapeutic plasma exchange in 30 patients (22.7%), and extracorporeal membrane oxygenation (ECMO) in 4 patients (3%). Clinical remission was achieved in 129 patients (97.7%), while 3 patients (2.3%) died. It was observed that all the patients who died were MIS-C patients who presented with shock before December 2021. Of the 95 MIS-C patients evaluated after discharge, 49 (51.6%) had sequelae. Significant sequelae included abnormal echocardiography findings (29%), decreased school performance (32.5%), and neurological symptoms (13.7%). MIS-C patients before December 2021 were associated with more sequelae. At diagnosis, 75 patients (57.3%) had cardiac valve involvement, which decreased to 20 patients (29%) in the first year of follow-up. Neurological symptoms were present in 41 patients (31.1%) at diagnosis and in 13 patients (13.7%) in the first year of follow-up. Cognitive functions were evaluated in patients with neurological complaints, with abnormal findings in 44.4% of patients. Autoantibody positivity (especially ANA, lupus anticoagulant) was detected in 60 patients (63.2%), and thyroid autoantibody positivity was found in 29 patients (30.5%). Despite the high rate of autoantibodies, clinical manifestation was observed in only one patient (hypothyroidism). During follow-up, new diseases were detected in 25 patients (22.5%). Among these new diseases, obesity, hypertension, hyperglycemia, hyperlipidemia, hypogammaglobulinemia, immune deficiency, hypothyroidism, recurrent headaches, critical illness myopathy, and ocular myasthenia were noted, and patients were referred to the respective medical specialties. However, no comments can be made about the causal relationship between these diseases and COVID-19 and MIS-C. Considering the severe cytokine storm experienced by MIS-C patients, long-term follow-up with a multidisciplinary approach is very important in terms of possible future incidents.