Assessing medium term cardiac outcomes in children with multi-system inflammatory syndrome

Background and Aim: Multi-system inflammatory syndrome in chil-dren (MIS-C) causes widespread systemic inflammation including a pancarditis in the weeks following a COVID infection. Further coronavirus surges appear inevitable and with vaccination rates lower in young people an understanding of the medium-term car-diac impacts of this condition is important for planning further treatment and understanding the impacts on their health. Method(s): A retrospective single-center study of 67 consecutive patients with MIS-C was performed. Three time points were determined as the point of worst cardiac dysfunction during the acute admission, then at intervals of 6-8 weeks and 6-8 months. Echocardiographic findings were used to evaluate both 2D and 3D measures of cardiac function. Coronary artery measurements were recorded. Corresponding serial ECG findings were evaluated. Result(s): The worst cardiac function arose 6.8 +/- 2.4 days after the onset of fever. The mean M mode-derived FS was 30.9 +/- 8.1% during the acute phase. The mean 3D left ventricle (LV) ejection fraction (EF) was borderline at 50.5 +/- 9.8%. A pancarditis was typ-ically present: 46.3% showed cardiac impairment;31.3% had some pericardial effusion;26.8% had moderate (or worse) valvar regur-gitation and;26.8% had coronary dilatation. Cardiac function returned to normal in all patients by 6-8 weeks (mean 3D LV EF 61.3 +/- 4.4%, plt;0.001 compared to admission). Coronary dila-tation normalized in all but one patient who initially developed large aneurysms at presentation;these continued 6 months later. ECG findings mainly featured T-wave changes resolving at fol-low-up. There were a small number of adverse events: need for ECMO (2), death as an ECMO-related complication (1), suben-docardial infarction (1), LV thrombus formation (1). Conclusion(s): MIS-C causes a pancarditis with decreased cardiac function and almost a quarter of patients showing coronary changes. In most, discharge from long-term follow-up can be con-sidered as full cardiac recovery is expected by 8 weeks. The excep-tion includes patients with medium sized aneurysms or greater or those with more of a Kawasaki disease phenotype as these require on-going surveillance for persistence of coronary changes.

Humoral cross-coronavirus responses against the S2 region in children with Kawasaki disease.

Multisystem Inflammatory Syndrome in Children (MIS-C), a post infectious complication of SARS CoV-2 infection, shares enough features with Kawasaki Disease (KD) that some have hypothesized cross-coronavirus (CoV) immunity may explain the shared pathology. Recent studies have shown that humoral cross-reactivity of the CoVs, particularly of OC43, is focused on the S2 region of the Spike protein. Due to efforts utilizing CoV S2 regions to produce a cross-CoV vaccine, we wished to assess SARS-CoV-2 S2 reactivity in children with KD and assess if cardiac involvement in KD correlated with S2 CoV antibody targeting. The presence of cross-reactivity does not distinguish KD from febrile controls and does not correlate with cardiac involvement in KD. These findings support that, in relation to cardiac vascular inflammation, vaccines targeting the S2 region appear to be a safe approach, but there is disparity in the ability of CoV species to raise cross-reactive S2 targeted antibodies.

Characteristics and Outcomes of Cases of Children and Adolescents With Pediatric Inflammatory Multisystem Syndrome in a Tertiary Care Center in Mexico City.

Background: Pediatric inflammatory multisystem syndrome (PIMS) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children that resembles Kawasaki syndrome and places them at high risk of cardiorespiratory instability and/or cardiac damage. This study aims to describe the clinical presentation and outcomes of patients with PIMS in Mexico City. Methods: This was an observational study of children hospitalized for PIMS based on the Centers for Disease Control and Prevention case definition criteria, in a single tertiary care pediatric center in Mexico City between May 1, 2020, and September 30, 2021. Demographic characteristics, epidemiological data, medical history, laboratory tests, cardiologic evaluations, treatment, and clinical outcomes were analyzed. Results: Seventy-five cases fulfilled the case definition criteria for PIMS [median age: 10.9 years, Interquartile range (IQR): 5.6-15.6]. Fifteen (20%) patients had a severe underlying disease, 48 (64%) were admitted to the intensive care unit, 33 (44%) required invasive mechanical ventilation and 39 (52%) received vasopressor support. The patients were clustered through latent class analysis based on identified symptoms: Cluster 1 had rash or gastrointestinal symptoms (n = 60) and cluster 2 were those with predominantly respiratory manifestations (n = 15). Two patients (2.7%) died, and both had severe underlying conditions. Five patients (6.7%), all from cluster 1, developed coronary aneurysms. Conclusion: There were a high proportion of patients with severe respiratory involvement and positive RT-PCR SARS-CoV-2 and very few cases of coronary aneurysms in our study which suggests that a high proportion of the children had severe acute COVID-19. The clinical manifestations and outcomes are comparable to previously reported international studies.

Myocardial Infarction in Children after COVID-19 and Risk Factors for Thrombosis.

Acute myocardial infarction (AMI) in children is rather anecdotic. However, following COVID-19, some conditions may develop which may favor thrombosis, myocardial infarction, and death. Such a condition is Kawasaki-like disease (K-lD). K-lD appears in children as a subgroup of the multisystem inflammatory syndrome (MIS-C). In some cases, K-lD patients may develop giant coronary aneurysms. The evolution and characteristics of coronary aneurysms from K-lD appear to be different from classical Kawasaki disease (KD) aneurysms. Differences include a lower percentage of aneurysm formation than in non-COVID-19 KD, a smaller number of giant forms, a tendency towards aneurysm regression, and fewer thrombotic events associated with AMI. We present here a review of the literature on the thrombotic risks of post-COVID-19 coronary aneurysms, starting from a unique clinical case of a 2-year-old boy who developed multiple coronary aneurysms, followed by AMI. In dehydration conditions, 6 months after COVID-19, the boy developed anterior descending artery occlusion and a slow favorable outcome of the AMI after thrombolysis. This review establishes severity criteria and risk factors that predispose to thrombosis and AMI in post-COVID-19 patients. These may include dehydration, thrombophilia, congenital malformations, chronic inflammatory conditions, chronic kidney impairment, acute cardiac failure, and others. All these possible complications should be monitored during acute illness. Ischemic heart disease prevalence in children may increase in the post-COVID-19 era, due to an association between coronary aneurysm formation, thrombophilia, and other risk factors whose presence will make a difference in long-term prognosis.

Giant Coronary Aneurysms in Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 Infection.

Multisystem inflammatory syndrome in children (MIS-C) can cause a myriad of cardiac manifestations, including coronary dilation and aneurysms; giant aneurysms are infrequent. We describe 3patients with giant coronary aneurysms associated with MIS-C, including the youngest case reported to date, treated with intravenous immunoglobulin, corticosteroids, and biologic agents. (Level of Difficulty: Intermediate.).

Regression of Coronary Aneurysms With Intravenous Immunoglobulins and Steroids for COVID-19 Adult Multisystem Inflammatory Syndrome.

A multisystem inflammatory syndrome mimicking Kawasaki disease has been increasingly reported, mainly in children, in the context of coronavirus disease-2019 (COVID-19). We report on the first case of coronary aneurysm resolution after treatment with steroids and intravenous immunoglobulins in an adult patient with multisystem inflammatory syndrome temporally associated with COVID-19. (Level of Difficulty: Beginner.).

Myocarditis and coronary aneurysms in a child with acute respiratory syndrome coronavirus 2.

A 6-year-old African boy with multi-viral infection including parvovirus B19 and severe acute respiratory syndrome coronavirus 2 was admitted for persistent fever associated with respiratory distress and myocarditis complicated by cardiogenic shock needing ventilatory and inotropic support. Coronary aneurysms were also documented in the acute phase. Blood tests were suggestive of macrophage activation syndrome. He was treated with intravenous immunoglobulins, aspirin, diuretics, dexamethasone, hydroxychloroquine, and prophylactic low molecular weight heparin. Normalization of cardiac performance and coronary diameters was noticed within the first days. Cardiac magnetic resonance imaging, performed 20 days after the hospitalization, evidenced mild myocardial interstitial oedema with no focal necrosis, suggesting a mechanism of cardiac stunning related to cytokines storm rather than direct viral injury of cardiomyocytes.

Coronary aneurysms, myocardial dysfunction, and shock in a COVID-19 child, role of ECMO, immunomodulation, and cardiac CT.

Coronary artery aneurysms in children were observed as a rare complication associated with coronavirus disease 2019 (COVID-19). This case report describes the severe end of the spectrum of the new multisystem inflammatory syndrome in a 12-year-old child with coronary aneurysms, myocardial dysfunction, and shock, managed successfully with extracorporeal membrane oxygenation support and immunomodulation therapy. This report also highlights the additional benefits of cardiac CT in the diagnosis and follow-up of coronary aneurysms.