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.
Highlights
Since December 2019, when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was described, high morbidity and mortality have been seen worldwide
Endothelial injury has been widely described in COVID19, but we are unaware of reports in children showing endothelial glycocalyx damage in critically ill patients with Multisystem Inflammatory Syndrome in Children (MIS-C)
In adults, Fraser et al found biomarkers associated with endothelial glycocalyx damage, such as syndecan-1 and chondroitin sulfate, to be higher, which correlated with a prothrombotic state [16]
Summary
Since December 2019, when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was described, high morbidity and mortality have been seen worldwide. We recently encountered two patients with Centers for Disease Control and Prevention (CDC) criteria for MIS-C who had evidence of endothelial dysfunction, glycocalyx degradation, and altered microcirculation documented by plasma biomarkers and sublingual video microscopy (Table 1). The first patient with MIS-C is an 8-year-old male with a history of living donor liver transplantation due to hepatoblastoma, who was on outpatient immunosuppression with tacrolimus and prednisolone (Table 1) He was seen in the emergency room (11/30/2020) for COVID-19 pneumonia with a positive RT-PCR. The second patient is a 17-year-old adolescent whose father had had COVID-19 5 weeks prior, and who had no other significant medical history (Table 1) He presented to the emergency room due to 5 days of headache with diarrhea and fever, abdominal pain and musculoskeletal pain. The Supplementary Video 2 shows good microvascular flow, with good capillary recruitment and microcirculation perfusion, and a normal red blood cell velocity
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