Endothelial Dysfunction as a Component of Severe Acute Respiratory Syndrome Coronavirus 2-Related Multisystem Inflammatory Syndrome in Children With Shock.

TRIAL REGISTRATION: NCT04420468. OBJECTIVES: Severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children is frequently associated with shock; endothelial involvement may be one of the underlying mechanisms. We sought to describe endothelial dysfunction during multisystem inflammatory syndrome in children with shock and then assess the relationship between the degree of endothelial involvement and the severity of shock. DESIGN: Observational study. SETTING: A PICU in a tertiary hospital. PATIENTS: Patients aged under 18 (n = 28) with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children and shock, according to the Centers for Disease Control and Prevention criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between endothelial marker levels and shock severity were assessed using Spearman coefficient. The median (interquartile range) age was 9 years (7.5-11.2 yr). Sixteen children presented with cardiogenic and distributive shock, 10 presented with cardiogenic shock only, and two presented with distributive shock only. The median left ventricular ejection fraction, troponin level, and lactate level were, respectively, 40% (35-45%), 261 ng/mL (131-390 ng/mL), and 3.2 mmol/L (2-4.2 mmol/L). Twenty-five children received inotropes and/or vasopressors; the median Vasoactive and Inotropic Score was 8 (5-28). Plasma levels of angiopoietin-2 (6,426 pg/mL [2,814-11,836 pg/mL]), sE-selectin (130,405 pg/mL [92,987-192,499 pg/mL]), von Willebrand factor antigen (344% [288-378%]), and the angiopoietin-2/angiopoietin-1 ratio (1.111 [0.472-1.524]) were elevated and significantly correlated with the Vasoactive and Inotropic Score (r = 0.45, p = 0.016; r = 0.53, p = 0.04; r = 0.46, p = 0.013; and r = 0.46, p = 0.012, respectively). CONCLUSIONS: Endothelial dysfunction is associated with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children with shock and may constitute one of the underlying mechanisms.

Sudden cardiogenic shock mimicking fulminant myocarditis in a surviving teenager affected by severe acute respiratory syndrome coronavirus 2 infection.

In the context of the coronavirus disease 2019 pandemic, myocardial injury is a relatively frequent finding. Progression to cardiogenic shock has been rarely described, especially in healthy young patients. The underlying mechanisms are to date controversial. A previously healthy 18-year-old female teenager affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) developed fulminant cardiogenic shock requiring a prompt extracorporeal membrane oxygenation support. Cardiac involvement was predominant compared with the pulmonary one. Myocardial biopsies were performed; and in order to clarify the pathophysiology of the acute heart failure, optical and transmission electron microscopy study was realized. Two additional immunohistology techniques were developed in order to (i) detect a SARS-CoV-2 recombinant fusion nucleoprotein by using a specific antibody and (ii) study fractalkine expression induced by activated endothelium because this molecule is well known to be elevated in patients with severe cytokine release syndrome. SARS-CoV-2 genome was not detected in the myocardium. Even if the clinical presentation, laboratory markers, and cardiac imaging techniques strongly suggested fulminant myocarditis, histology and immunohistology were not fully consistent with this diagnosis according to the Dallas criteria. Although rare suspected coronavirus particles were found by transmission electron microscopy in the cardiac endothelium, neither significant immunoreactivity for the viral nucleocapsid protein nor image suggestive of endotheliitis was detected. Intense endothelial immunoreactivity pattern for fractalkine expression was observed. From a clinical point of view, the left ventricular systolic function gradually improved, and the patient survived after a long stay in the intensive care unit. Our observations suggest that a massive cytokine storm induced by SARS-CoV-2 infection was the main cause of the cardiogenic shock, making a direct viral injury pathway very unlikely.

Coronavirus disease-19 and cardiovascular disease: A risk factor or a risk marker?

Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to provide a succinct review about the pathophysiology and cardiac manifestations of COVID-19, as well as treatment considerations and the various adaptations made to the current healthcare structure as a result of the pandemic.

Myocardial localization of coronavirus in COVID-19 cardiogenic shock.

We describe the first case of acute cardiac injury directly linked to myocardial localization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a 69-year-old patient with flu-like symptoms rapidly degenerating into respiratory distress, hypotension, and cardiogenic shock. The patient was successfully treated with venous-arterial extracorporeal membrane oxygenation (ECMO) and mechanical ventilation. Cardiac function fully recovered in 5 days and ECMO was removed. Endomyocardial biopsy demonstrated low-grade myocardial inflammation and viral particles in the myocardium suggesting either a viraemic phase or, alternatively, infected macrophage migration from the lung.