Acute cardiovascular manifestations in children with multisystem inflammatory syndrome associated with COVID-19 infection in a Sicilian case series

ABSTRACT

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of COVID-19 infection, typically evidenced 4-6 weeks after the infection. The debated pathogenesis is a dysregulation of inflammatory response to SARS-CoV-2 infection ad a cytokine hyperexpression. Persistent fever, respiratory and gastrointestinal symptoms are the most common manifestations, associated with typical clinical signs described in Kawasaki Disease (KD). Furthermore, pleiomorphic cardiac manifestations are described, including ventricular dysfunction, coronary artery dilation and aneurysms, arrhythmia, conduction abnormalities and pericardial effusion. These manifestations are a strong link with KD, even if in MIS-C they are more frequently documented. Severe cases can present as Toxyc Shock Syndrome (TSS) with vasodilatory or cardiogenic shock, requiring treatment with plasma expanders, inotropic drugs, diuretics, albumin and -in the more severe patients- extracorporeal membrane oxygenation and mechanical ventilation. KD experience guided the clinicians to treat these children with intravenous immunoglobulin (IVIG), steroids, aspirin (ASA) and, in refractory cases, anti-IL-1 monoclonal antibodies. Objectives: Most patients recover within days to a couple of weeks and mortality is rare, although the medium- and long-term sequelae, particularly cardiovascular complications, are not yet known. Methods: We describe the short-term outcome in a case series of 12 Sicilian children (4M;8F;age 1.4-14 years) with MIS-C and a documented recent or actual infection by SARS-CoV-2 who showed cardiac involvement. Results: The cardiac features were 3 patients showed pericardial effusion;1 coronaritis;6 transient mitral valve regurgitation;1 Brugada pattern, evidenced when he was febrile;2 showed associated mitral and aortic valve regurgitation). 7/8 patients with valve regurgitation showed a significant increase of pro-BNP, normalized during the follow-up. TSS was described in 2 patients, showing a significant increase of troponin, promptly treated with high dose of methylprednisolone, IVIG, vasoactive drugs, albumin and diuretics. 3 patients (21%), after the resolution of the acute phase, showed bradycardia (heart rate < 50/min), persisting for 7-10 days. The bradycardia was not associated with first-degree AVB, or a pathological PR. 6 patients (42%) showed an altered ventricular repolarization phase, in association with an increase of pro-BNP (129-3980 pg/ml). 4/12 (33%) had increased troponin levels (27.3-246 ng/ml) in the acute phase, with the normalization of troponin after IVIG and steroids treatment. Pro-BNP persisted increased for a longer time, besides the clinical improvement and the normalization of blood chemistry parameters. Conclusion: Generally, pro-BNP and troponin levels in MIS-C are higher than in KD, reflecting vasculopathy and cardiomyocytes damage extent. Persistence of increased levels of pro-BNP, in patients with a normalization of inflammatory parameters, suggests a mechanism of myocardial oedema, persisting besides the intensive care approach useful, however, to limit effects on cardiac function and normalize inflammatory parameters. Patients admitted with MIS-C require close electrocardiogram monitoring during the acute phase and the recovery, even if they do not manifest dyselectroliteemia, coronary lesions, pericardial effusion, myocarditis, shock. This approach can avoid severe arrythmia.