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Case Report: Endothelial Glycocalyx Damage in Critically ill Patients With SARS-CoV-2-Related Multisystem Inflammatory Syndrome (MIS-C).

ABSTRACT: Endothelial insult and damage is one of the reported consequences of SARS-CoV-2 infection. It has been associated with severe inflammation, thrombotic phenomena and profound hypoxemia in critically ill patients. Endothelial activation leads to a loss of the endothelium's antithrombotic properties which, under normal conditions, are maintained by the endothelial glycocalyx, a carbohydrate-rich layer that covers the luminal surface of endothelial cells. In children, one of the serious forms of SARS-CoV-2 virus disease (COVID-19) is multisystem inflammatory syndrome (MIS-C). This new disease is characterized by a large inflammatory response and frequent cardiovascular, cutaneous and gastrointestinal disorders. We describe the first two cases of critically ill children with MIS-C who evidenced a large inflammatory response associated with elevated plasma and imaging biomarkers of endothelial activation and endothelial glycocalyx degradation. This microcirculation involvement in MIS-C could, at least partially, explain some of the clinical manifestations and laboratory and imaging alterations found in these patients. These findings contribute to a better understanding of this disease and suggest that medications to modulate the inflammatory response and protect or restore the endothelial glycocalyx should be considered in future studies.

SUBMITTER: Fernandez-Sarmiento J

PROVIDER: S-EPMC8451682 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Case Report: Endothelial Glycocalyx Damage in Critically ill Patients With SARS-CoV-2-Related Multisystem Inflammatory Syndrome (MIS-C).

Fernández-Sarmiento Jaime J Flórez Steffanie S Alarcón-Forero Laura C LC Salazar-Peláez Lina María LM Garcia-Casallas Julio J Mulett Hernando H Acevedo Lorena L Salamanca Carolina C

Frontiers in pediatrics 20210906

Endothelial insult and damage is one of the reported consequences of SARS-CoV-2 infection. It has been associated with severe inflammation, thrombotic phenomena and profound hypoxemia in critically ill patients. Endothelial activation leads to a loss of the endothelium's antithrombotic properties which, under normal conditions, are maintained by the endothelial glycocalyx, a carbohydrate-rich layer that covers the luminal surface of endothelial cells. In children, one of the serious forms of SAR ...[more]

PMID: 34552899

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Project description:BACKGROUND:A recent increase in children admitted with hypotensive shock and fever in the context of the COVID-19 outbreak requires an urgent characterization and assessment of the involvement of SARS-CoV-2 infection. This is a case series performed at 4 academic tertiary care centers in Paris of all the children admitted to the pediatric intensive care unit (PICU) with shock, fever and suspected SARS-CoV-2 infection between April 15th and April 27th, 2020. RESULTS:20 critically ill children admitted for shock had an acute myocarditis (left ventricular ejection fraction, 35% (25-55); troponin, 269 ng/mL (31-4607)), and arterial hypotension with mainly vasoplegic clinical presentation. The first symptoms before PICU admission were intense abdominal pain and fever for 6 days (1-10). All children had highly elevated C-reactive protein (> 94 mg/L) and procalcitonin (> 1.6 ng/mL) without microbial cause. At least one feature of Kawasaki disease was found in all children (fever, n = 20, skin rash, n = 10; conjunctivitis, n = 6; cheilitis, n = 5; adenitis, n = 2), but none had the typical form. SARS-CoV-2 PCR and serology were positive for 10 and 15 children, respectively. One child had both negative SARS-CoV-2 PCR and serology, but had a typical SARS-CoV-2 chest tomography scan. All children but one needed an inotropic/vasoactive drug support (epinephrine, n = 12; milrinone, n = 10; dobutamine, n = 6, norepinephrine, n = 4) and 8 were intubated. All children received intravenous immunoglobulin (2 g per kilogram) with adjuvant corticosteroids (n = 2), IL 1 receptor antagonist (n = 1) or a monoclonal antibody against IL-6 receptor (n = 1). All children survived and were afebrile with a full left ventricular function recovery at PICU discharge. CONCLUSIONS:Acute myocarditis with intense systemic inflammation and atypical Kawasaki disease is an emerging severe pediatric disease following SARS-CoV-2 infection. Early recognition of this disease is needed and referral to an expert center is recommended. A delayed and inappropriate host immunological response is suspected. While underlying mechanisms remain unclear, further investigations are required to target an optimal treatment.

Project description:BackgroundThe clinical presentation and severity of Multisystem Inflammatory Syndrome in Children associated with COVID-19 (MIS-C) is widespread and presents a very low mortality rate in high-income countries. This research describes the clinical characteristics of MIS-C in critically ill children in middle-income countries and the factors associated with the rate of mortality and patients with critical outcomes.MethodsAn observational cohort study was conducted in 14 pediatric intensive care units (PICUs) in Colombia between April 01, 2020, and January 31, 2021. Patient age ranged between one month and 18 years, and each patient met the requirements set forth by the World Health Organization (WHO) for MIS-C.ResultsThere were seventy-eight children in this study. The median age was seven years (IQR 1-11), 18 % (14/78) were under one year old, and 56 % were male. 35 % of patients (29/78) were obese or overweight. The PICU stay per individual was six days (IQR 4-7), and 100 % had a fever upon arrival to the clinic lasting at least five days (IQR 3.7-6). 70 % (55/78) of patients had diarrhea, and 87 % (68/78) had shock or systolic myocardial dysfunction (78 %). Coronary aneurysms were found in 35 % (27/78) of cases, and pericardial effusion was found in 36 %. When compared to existing data in high-income countries, there was a higher mortality rate observed (9 % vs. 1.8 %; p=0.001). When assessing the group of patients that did not survive, a higher frequency of ferritin levels was found, above 500 ngr/mL (100 % vs. 45 %; p=0.012), as well as more cardiovascular complications (100 % vs. 54 %; p = 0.019) when compared to the group that survived. The main treatments received were immunoglobulin (91 %), vasoactive support (76 %), steroids (70.5 %) and antiplatelets (44 %).ConclusionsMultisystem Inflammatory Syndrome in Children due to SARS-CoV-2 in critically ill children living in a middle-income country has some clinical, laboratory, and echocardiographic characteristics similar to those described in high-income countries. The observed inflammatory response and cardiovascular involvement were conditions that, added to the later presentation, may explain the higher mortality seen in these children.

Dataset Information

Case Report: Endothelial Glycocalyx Damage in Critically ill Patients With SARS-CoV-2-Related Multisystem Inflammatory Syndrome (MIS-C).

Publications

Case Report: Endothelial Glycocalyx Damage in Critically ill Patients With SARS-CoV-2-Related Multisystem Inflammatory Syndrome (MIS-C).

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