Thrombotic Events in MIS-C Patients: A Single Case Report and Literature Review.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a systemic hyperinflammatory disorder that is associated with a hypercoagulable state and a higher risk of thrombotic events (TEs). We report the case of a 9-year-old MIS-C patient with a severe course who developed a massive pulmonary embolism that was successfully treated with heparin. A literature review of previous TEs in MIS-C patients was conducted (60 MIS-C cases from 37 studies). At least one risk factor for thrombosis was observed in 91.7% of patients. The most frequently observed risk factors were pediatric intensive care unit hospitalization (61.7%), central venous catheter (36.7%), age >12 years (36.7%), left ventricular ejection fraction <35% (28.3%), D-dimer >5 times the upper limit of normal values (71.9%), mechanical ventilation (23.3%), obesity (23.3%), and extracorporeal membrane oxygenation (15%). TEs may concurrently affect multiple vessels, including both arterial and venous. Arterial thrombosis was more frequent, mainly affecting the cerebral and pulmonary vascular systems. Despite antithrombotic prophylaxis, 40% of MIS-C patients developed TEs. Over one-third of patients presented persistent focal neurological signs, and ten patients died, half of whom died because of TEs. TEs are severe and life-threatening complications of MIS-C. In case with thrombosis risk factors, appropriate thromboprophylaxis should be promptly administered. Despite proper prophylactic therapy, TEs may occur, leading in some cases to permanent disability or death.

Neuro-PIMS-TS: a single case report and review of the literature.

Neurological manifestations related to SARS-CoV-2 infection in adults have been largely reported since the beginning of the pandemic. Subsequent large-scale studies involving children confirmed the occurrence of neurological symptoms associated with SARS-CoV-2 infection also among paediatric patients, especially in the context of paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS). At this regard, we report the challenging case of a 10-month-old baby with PIMS-TS complicated by acute cerebral oedema successfully treated with intravenous immunoglobulins, corticosteroids and anakinra. Our results, combined with the evidence of larger case series suggest that higher inflammatory burden is more frequent in patients with neuro PIMS-TS. As regards neuroimaging, neuroimmune disorders are found to be more common during acute COVID-19, MERS is more frequent during PIMS-TS. Distinct immune mechanisms may underlie these different types of neurological involvement, which are yet to be understood. Further studies are required to better define the physiopathology of neuro PIMS-TS and its possible therapeutical implications.

Cardiac MRI in midterm follow-up of MISC: a multicenter study.

In this multicenter retrospective study we aimed to evaluate the outcome of cardiac involvement in children affected by multisystem inflammatory syndrome (MIS-C), assessed through cardiac magnetic resonance (CMR). Children referring to three Italian tertiary pediatric centers between February 2020 and November 2021 with a diagnosis of MIS-C, who underwent CMR during a follow-up visit, were enrolled. Demographic, clinical, laboratory, treatment, and outcome data were collected. Twenty MIS-C patients (aged 9-17, median 12 years) were included in the study. Heart involvement at onset was testified by hypotension/shock (55%), laboratory evidence of myocardial involvement (100%), reduced LV ejection fraction (EF) on echocardiography (83%), and/or need for inotrope agents (40%); they all presented good clinical, laboratory, and echocardiographic response to treatment. CMR was performed after a median interval of 3 months from discharge. Pericardial effusion and myocardial edema were found in 5% of patients. Mild residual left ventricular (LV) dysfunction was found in 20% of patients, all showing normal echocardiographic LVEF at discharge. Minimal myocardial scars were found in 25% by late gadolinium enhancement (LGE). One patient was evaluated at two consecutive time points, showing partial resolution of a myocardial scar after 7 months from its first finding. CONCLUSION: Despite the severity of heart involvement in the acute MIS-C phase, the mid-term cardiac outcome is good. Direct cardiac tissue viral invasion may be involved in MIS-C pathogenesis. WHAT IS KNOWN: • Heart involvement is common in MIS-C, but conflicting findings have been shown regarding cardiac outcome when assessed through cardiac MRI. WHAT IS NEW: • Midterm cardiac MRI shows mild abnormalities in patients recovered from MIS-C with any grade of severity of cardiac involvement at presentation.

Early anti IL-1 treatment replaces steroids in refractory Kawasaki disease: clinical experience from two case reports.

Refractory Kawasaki disease (KD) is related to a major risk of coronary arteries abnormalities and its treatment is not standardized. In this regard, anakinra (ANA), an interleukin (IL)-1 receptor antagonist, represents an emerging therapeutic option. We report two cases of children, diagnosed with KD, nonresponsive to two doses of intravenous immunoglobulins, successfully treated with ANA, without a prior use of steroids. Patient 2 developed a coronary dilatation, that improved significantly after ANA therapy. Our experience highlights IL-1 blockade effectiveness in reducing KD inflammation and suggests ANA adoption as second-line therapy, with a timesaving and steroid-sparing strategy. Our results, combined with the evidence of the IL-1 key role in KD and coronary arteritis pathogenesis and to the recent clinical evidence reported by the KAWAKINRA trial, encourage an earlier recourse to ANA in patients with refractory KD, in order to fight inflammation, and to treat and prevent the development of coronary artery aneurysms. Further studies are needed to better define the place of IL-1 blockade in KD step-up treatment.