COVID-19 temporally related multisystem inflammatory syndrome (MIS-C): an early window of opportunity is a good treatment strategy? The experience of the paediatric covid center in Palermo

Abstract

Introduction: Multi-system inflammatory syndrome in children (MISC) shows a presentation mimicking Kawasaki Disease (KD), Toxic Shock Syndrome (TSS), Macrophage Activation Syndrome (MAS). Furthermore, many children show respiratory or abdominal symptoms. Objectives: Intravenous immunoglobulin (IVIG) is recommended as first line treatment as in KD, followed by aspirin, steroids and, in IVIGresistant patients, IL-1 or IL-6 blocking agents. Methods: We describe a cohort of 16 Sicilian children (6M;10F; age:1.4-14 years), with MIS-C, with clinical features compatible with classical or incomplete KD, in some cases with MAS and/or TSS. Demographic, clinical, laboratory, echocardiographic and imaging findings, treatment strategy and outcome were collected. Results: Common presenting symptoms included: fever (94%), abdominal pain or vomiting (50%), mucocutaneous rash (50%), conjunctivitis (44%), latero-cervical lymphadenitis (63%), cheilitis/pharyngeal hyperaemia (81%), hands and feet oedema (13%). Symptoms started 1-8 days before the hospitalization. Nasopharyngeal swab for SARS-CoV-19 was positive in 12/16 patients, with positive serological IgG, negative or grey zone IgM-type antibodies. 2 patients with negative swab had a history of recent infection and positive IgG-type antibodies; 2 patients had parents with positive swab. All the patients showed significant increase of C-reactive protein (CRP). AST, ALT, gamma-GT were increased in 25%. Pancreatic amylase and lipase were increased in 13%, 19% showed lymphocytopenia. Pro-BNP was increased (129-3980pg/ml) in 44% and troponin was increased (27.3-246ng/ml) in 31%. In addition, hyponatraemia was found in 100% of cases. Furthermore, 31 % had proteinuria. 50% showed cardiac involvement (3 pericardial effusion; 5 mitral insufficiency; 2 mitral and aortic insufficiency; 1 coronaritis). Pleural, ascitic, pericardial effusion and abdominal adenitis were found in 19%, 25%, 19% and 31% of cases, respectively. IL-6 levels were evaluated in 9/16 patients and 8/9 showed a significant increase (30.2-285pg/ml) with a rapid normalization after steroids and IVIG treatment. Pro-BNP persisted increased for 7-10 days after IVG and steroids treatment. 25% of patients dramatically and rapidly evolved in a MAS-like form, fulfilling the classification criteria for the diagnosis of MAS (ACR/EULAR 2016). High doses of steroids and IVIG were promptly started with a significant improvement of the clinical course. In all the patients, treatment was started within 72 hours of admission, with IVIG (2 g/Kg/dose), methylprednisolone (2mg/Kg/day in 56% of patients; 30 mg/Kg/day for 3 days, followed by 2 mg/Kg/day in 38% of patients). 2 patients were treated with enoxaparin. TSS was described in 2 patients, who received additionally vasoactive drugs, albumin and diuretics. Conclusion: In our series, most of patients received a prompt treatment with IVIG and steroids. This approach could explain the good outcome in all the cases and the rapid restoring of cardiac function also in patients with MAS or TSS. Patients showed a wide spectrum of presenting signs and symptoms; evidence of inflammation with pathological values of CRP, ESR, D-dimer, ferritin, pro-BNP, troponin, transaminase, pancreatic amylase and albumin; a multi-organ involvement was documented in a high percentage of cases, inducing the clinician to perform a multi-specialistic approach.