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.

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“…As infection continues, release of virions into the bloodstream prevents albumin from transporting nutrients into the cells, which results in unstable cells vulnerable to apoptosis. 25 …”

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“…An additional feature of COVID-19, which could be implicated in the multiplicity of organ targets and systemic symptoms, concerns a supposed interaction between SARS-CoV-2 virions and plasma albumin reflecting depletion of the endothelial glycocalyx layer [90]. Such alteration modifying endothelium integrity would undoubtedly refer to pathophysiological aspects of the blood circulation that manifest themselves in COVID-19 and complicate the clinical course of the disease.…”

“…The combination of endothelial-cell alteration and acute-phase hypoalbuminemia renal dysfunction [90] can lead to anasarca and capillary leak syndrome-a rare disorder characterised by a dysfunctional inflammatory response, endothelial dysfunction, extravasation of fluid, hypoalbuminemia, and subsequent organ failure [53]. [12].② These cells release xygen radicals, proteases, cytokines and products of arachidonic acid metabolism, damaging elial cells with increased vascular permeability.…”

“…⑨⑩ The combination of endothelial-cell alteration and acuteypoalbuminemia renal dysfunction [90] can lead to anasarca and capillary leak syndromedisorder characterised by a dysfunctional inflammatory response, endothelial dysfunction, sation of fluid, hypoalbuminemia, and subsequent organ failure [53]. ⑪ Hypoalbuminemia wn factor in ARDS [90], a clinical syndrome of non-cardiogenic pulmonary oedema that in dative stage is characterised by an increase in vascular permeability and alveolar oedema Cardiomyopathy causes hypoxia and hypoxemia. ⑬⑭⑮ Hypoxia activates macrophages utrophils that contribute to ARDS and pneumonia [32] and stabilise HIF-1α leading to e storm by activation of immune cells [40].…”

“…uring the pandemic, what is surprising and has put health management in an ency condition are the extent of the symptoms, which can easily progressively n and become complicated, and the high contagiousness of SARS-CoV-2. sually, coronaviruses interact with human biological systems in a transient and Hypoalbuminemia is a known factor in ARDS [90], a clinical syndrome of non-cardiogenic pulmonary oedema that in the exudative stage is characterised by an increase in vascular permeability and alveolar oedema [12]. [12].② These cells release toxic oxygen radicals, proteases, cytokines and products of arachidonic acid metabolism, damaging endothelial cells with increased vascular permeability.…”