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SARS-CoV-2 Bound Human Serum Albumin and Systemic Septic Shock.

ABSTRACT: The emergence of the COVID-19 virus and the subsequent pandemic have driven a great deal of research activity. The effects of COVID-19 are caused by the severe respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is the underlying actions of SARs-CoV-2 virions on the endothelial glycocalyx that we consider here. One of the key factors in COVID-19 infection is its almost unique age-related profile, with a doubling in mortality every 10 years after the age of 50. The endothelial glycocalyx layer is essential in maintaining normal fluid homeostasis, but is fragile and prone to pathophysiological damage. It is physiologically significant in capillary microcirculation and in fluid distribution to the tissues. Human serum albumin (HSA), the most abundant protein in plasma, is created in the liver which also maintains its concentration, but this reduces by 10-15% after 50 years of age. HSA transports hormones, free fatty acids and maintains oncotic pressure, but SARS-CoV-2 virions bind competitively to HSA diminishing its normal transport function. Furthermore, hypoalbuminemia is frequently observed in patients with such conditions as diabetes, hypertension, and chronic heart failure, i.e., those most vulnerable to SARS-CoV-2 infection. Hypoalbuminemia, coagulopathy, and vascular disease have been linked in COVID-19 and have been shown to predict outcome independent of age and morbidity. Hypoalbuminemia is also known factor in sepsis and Acute respiratory distress syndrome (ARDS) occurs when fluids build-up in the alveoli and it is associated with sepsis, whose mechanism is systemic, being associated with the fluid and logistic mechanisms of the circulation. Glycocalyx damage is associated with changes plasma protein concentration, particularly HSA and blockage of albumin transport can produce the systemic symptoms seen in SARS-CoV-2 infection and sepsis. We therefore conclude that albumin binding to SARS-CoV-2 virions may inhibit the formation of the endothelial glycocalyx by inhibition of albumin transport binding sites. We postulate that albumin therapy to replace bound albumin might alleviate some of the symptoms leading to sepsis and that clinical trials to test this postulation should be initiated as a matter of urgency.

SUBMITTER: Johnson AS

PROVIDER: S-EPMC7498713 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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SARS-CoV-2 Bound Human Serum Albumin and Systemic Septic Shock.

Johnson Andrew S AS Fatemi Rouholah R Winlow William W

Frontiers in cardiovascular medicine 20200902

The emergence of the COVID-19 virus and the subsequent pandemic have driven a great deal of research activity. The effects of COVID-19 are caused by the severe respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is the underlying actions of SARs-CoV-2 virions on the endothelial glycocalyx that we consider here. One of the key factors in COVID-19 infection is its almost unique age-related profile, with a doubling in mortality every 10 years after the age of 50. The endothelial glycocalyx layer ...[more]

PMID: 33088822

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Project description:Goal of the experiment: To identify correlated genes, pathways and groups of patients with systemic inflammatory response syndrome and septic shock that is indicative of biologically important processes active in these patients. Background: We measured gene expression levels and profiles of children with systemic inflammatory response syndrome (SIRS) and septic shock as a means for discovering patient sub-groups and gene signatures that are active in disease-affected individuals and potentially in patients with poor outcomes. Methods: Microarray and bioinformatics analyses of 123 microarray chips representing whole blood derived RNA from controls, children with SIRS, and children with septic shock. Results: A discovery-based filtering approach was undertaken to identify genes whose expression levels were altered in patients with SIRS or septic shock. Clustering of these genes identified 3 Major and several minor sub-groups of patients with SIRS or septic shock. The three groups differed with respect to incidence of septic shock and trended toward differences in mortality. Statistical analyses demonstrated that 6,435 gene probes were differentially regulated between the three patient sub-groups (false discovery rate < 0.001%). Of these gene probes, 623 gene probes within 7 major gene ontologies accounted for the majority of group differentiation. Network analyses of these 623 gene probes demonstrated 5 major gene networks that were differentially expressed between the 3 groups. Statistical comparison of septic shock survivors and non-survivors identified one major gene network that was under expressed in a high fraction of the non-survivors and identified potential biomarkers for poor outcome. Conclusions: This is the first genome-level demonstration of pediatric patient sub-groups with SIRS and septic shock. The sub-groups differ clinically and differentially express 5 major gene networks. We have identified gene signatures and potential biomarkers associated with poor outcome in children with septic shock. These data represent a major advancement in our genome-level understanding of pediatric SIRS and septic shock. Keywords: Septic shock, SIRS, pediatrics, outcome, infection, inflammation

Project description:BackgroundTo determine the clinical significance of variations in serum sestrin2 protein levels in the development of septic cardiomyopathy in septic shock patients.MethodsThe serum sestrin2 concentrations of each sample were determined using ELISA in a total of 67 control persons and 188 patients with septic shock. Furthermore, using transthoracic echocardiography, septic shock patients were split into two groups based on whether or not cardiomyopathy had developed, and the differences in each index between the two groups were analyzed. We looked at the relationship between serum sestrin2 levels, norepinephrine dosage, and NTproBNP levels. The influencing variables for the prediction of septic cardiomyopathy linked with the development of septic cardiomyopathy and clinical prognosis in septic cardiomyopathy were determined using multivariate binary logistic regression.ResultsAssessment of left ventricular systolic function by measurement of LVEF revealed that 61/188 (32.4%) of the 188 patients with septic shock included in the research satisfied the diagnostic criteria for septic cardiomyopathy. (1) Sestrin2 protein levels showed a significant difference between septic shock and healthy controls (p < 0.01). (2) Compared to the group without septic cardiomyopathy, the group with combined septic cardiomyopathy had lower serum sestrin2 protein levels (p < 0.05), lower systolic blood pressure (p < 0.05), and higher plasma NTproBNP levels (p < 0.01) and used greater norepinephrine dosages (p < 0.01). The levels of serum sestrin2 protein revealed a little negative relationship with NTproBNP and norepinephrine dose. However, a binary logistic regression analysis revealed that none of these factors was an independent predictor of septic shock. (3) Age, lactate level, SOFA score, positive bacteremia, and sestrin2 protein were shown to be substantial discrepancies in clinical outcomes in patients with septic cardiomyopathy, becoming variables that impact clinical outcomes. Positive bacteremia (p = 0.031, OR = 5.084), SOFA score (p = 0.021, OR = 1.304), and sestrin2 protein (p = 0.039, OR = 0.897) were revealed to have independent influences in predicting clinical mortality outcome in septic cardiomyopathy using multivariate binary logistic regression.ConclusionHigh serum sestrin2 levels clearly distinguish septic shock patients from healthy controls, whereas low serum sestrin2 levels are related with cardiac dysfunction to some extent but are not an independent influence factor for septic cardiomyopathy. Low serum sestrin2 levels were shown to be useful in predicting clinical outcome in patients with septic cardiomyopathy.

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SARS-CoV-2 Bound Human Serum Albumin and Systemic Septic Shock.

Publications

SARS-CoV-2 Bound Human Serum Albumin and Systemic Septic Shock.

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