Endothelial Injury and Glycocalyx Degradation in Critically Ill Coronavirus Disease 2019 Patients: Implications for Microvascular Platelet Aggregation

Fraser, Douglas D.; Patterson, Eric K.; Slessarev, Marat; Gill, Sean E.; Martin, Claudio M.; Daley, Mark; Miller, Michael R.; Patel, Maitray A.; Santos, Claudia C Dos; Bosma, Karen J.; O’Gorman, David B.; Cepinskas, Gediminas

doi:10.1097/cce.0000000000000194

Cited by 108 publications

(138 citation statements)

References 54 publications

(65 reference statements)

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“…This study was approved by the Human Subject Research Ethics Board at Western University [5][6][7]. Patients who were admitted to our academic ICU and suspected of having COVID19 based on standard hospital screening procedures and who had acute non-cardiogenic hypoxic respiratory failure requiring mechanical ventilation > 48 h were consecutively enrolled in the study.…”

Section: Study Participants and Clinical Datamentioning

confidence: 99%

“…Clinical interventions received in the ICU included use of antibiotics, anti-viral agents, systemic corticosteroids, vasoactive medications, renal replacement therapy, high-flow oxygen therapy, and mechanical ventilation (invasive and non-invasive). Final participant groups were constructed by identifying 7 COVID19 + patients and then matching to 7 COVID19− patients by age and sex only [5][6][7]. These patients have been included in previous studies performed by our group and this is a retrospective evaluation of the biological data from these patients [5][6][7].…”

Section: Study Participants and Clinical Datamentioning

confidence: 99%

“…Final participant groups were constructed by identifying 7 COVID19 + patients and then matching to 7 COVID19− patients by age and sex only [5][6][7]. These patients have been included in previous studies performed by our group and this is a retrospective evaluation of the biological data from these patients [5][6][7]. Further, given the exploratory nature of the study, no sample size calculation was performed.…”

Section: Study Participants and Clinical Datamentioning

confidence: 99%

“…However, these observations were made in comparison to healthy controls, and the increased circulating levels of pro-inflammatory cytokines observed in patients with COVID19 are also observed in other forms of sepsis and acute respiratory distress syndrome (ARDS) [4,10]. Our aim was to transcriptionally profile COVID19-positive (COVID19 +) ICU patients in comparison to COVID19-negative (COVID19-) ICU patients with severe acute respiratory diseases/conditions [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…Patients infected with SARS-CoV-2 exhibit a range of symptoms from mild hypoxemia with preserved lung compliance, and a mild inflammatory response, to severe hypoxemia associated with loss of lung function and a dysregulated inflammatory response with sustained tumour necrosis factor (TNF) and serine proteases that typically necessitates admission to an intensive care unit (ICU) [3][4][5][6]. The overall mortality rate of individuals with COVID19 has been reported to be approximately 3.4%; however, once COVID19 patients are admitted to the ICU, their mortality rate approximates 31-40% with a median of 9 days to ICU death [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional profiling of leukocytes in critically ill COVID19 patients: implications for interferon response and coagulation

Gill

Santos

O’Gorman

et al. 2020

ICMx

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Background COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19-associated host response. For these studies, all patients admitted to our tertiary care intensive care unit (ICU) suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Transcriptome profiling of leukocytes via ribonucleic acid sequencing (RNAseq) was then performed and differentially expressed genes as well as significantly enriched gene sets were identified. Results We enrolled seven COVID19 + (PCR positive, 2 SARS-CoV-2 genes) and seven age- and sex-matched COVID19- (PCR negative) control ICU patients. Cohorts were well-balanced with the exception that COVID19− patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19 + patients were more likely to suffer bilateral pneumonia. The mortality rate for this cohort of COVID19 + ICU patients was 29%. As indicated by both single-gene based and gene set (GSEA) approaches, the major disease-specific transcriptional responses of leukocytes in critically ill COVID19 + ICU patients were: (i) a robust overrepresentation of interferon-related gene expression; (ii) a marked decrease in the transcriptional level of genes contributing to general protein synthesis and bioenergy metabolism; and (iii) the dysregulated expression of genes associated with coagulation, platelet function, complement activation, and tumour necrosis factor/interleukin 6 signalling. Conclusions Our findings demonstrate that critically ill COVID19 + patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19− patients, providing guidance for future targeted studies exploring novel prognostic and therapeutic aspects of COVID19.

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Section: Study Participants and Clinical Datamentioning

confidence: 99%

Section: Study Participants and Clinical Datamentioning

confidence: 99%

Section: Study Participants and Clinical Datamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Transcriptional profiling of leukocytes in critically ill COVID19 patients: implications for interferon response and coagulation

Gill

Santos

O’Gorman

et al. 2020

ICMx

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Endothelial Function and Microcirculation

Dedda

2021

The Coagulation Labyrinth of Covid-19

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Endothelial glycocalyx degradation in multisystem inflammatory syndrome in children related to COVID-19

et al. 2022

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Multisystem inflammatory syndrome in children (MIS-C) represents a rare but severe complication of severe acute respiratory syndrome coronavirus 2 infection affecting children that can lead to myocardial injury and shock. Vascular endothelial dysfunction has been suggested to be a common complicating factor in patients with coronavirus disease 2019 (COVID-19). This study aims to characterize endothelial glycocalyx degradation in children admitted with MIS-C. We collected blood and urine samples and measured proinflammatory cytokines, myocardial injury markers, and endothelial glycocalyx markers in 17 children admitted with MIS-C, ten of which presented with inflammatory shock requiring intensive care admission and hemodynamic support with vasopressors. All MIS-C patients presented signs of glycocalyx deterioration with elevated levels of syndecan-1 in blood and both heparan sulfate and chondroitin sulfate in the urine. The degree of glycocalyx shedding correlated with tumor necrosis factor-α concentration. Five healthy age-matched children served as controls. Patients with MIS-C presented severe alteration of the endothelial glycocalyx that was associated with disease severity. Future studies should clarify if glycocalyx biomarkers could effectively be predictive indicators for the development of complications in adult patients with severe COVID-19 and children with MIS-C. Key messages Children admitted with MIS-C presented signs of endothelial glycocalyx injury with elevated syndecan-1 and heparan sulfate level. Syndecan-1 levels were associated with MIS-C severity and correlated TNF-α concentration. Syndecan-1 and heparan sulfate may represent potential biomarkers for patients with severe COVID-19 or MIS-C.

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Endothelial Injury and Glycocalyx Degradation in Critically Ill Coronavirus Disease 2019 Patients: Implications for Microvascular Platelet Aggregation

Abstract: Supplemental Digital Content is available in the text.

Cited by 108 publications

References 54 publications

Transcriptional profiling of leukocytes in critically ill COVID19 patients: implications for interferon response and coagulation

Transcriptional profiling of leukocytes in critically ill COVID19 patients: implications for interferon response and coagulation

Endothelial Function and Microcirculation

Endothelial glycocalyx degradation in multisystem inflammatory syndrome in children related to COVID-19

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