COVID-19, Endothelium and the Cardiometabolic Patient: A Possible Role for Capillary Leak Syndrome

Abstract

Capillary leak syndrome is an under-diagnosed condition leading to serious hypoalbuminemia with diffuse edema, pulmonary edema, severe hypotension, and possibly death. Sepsis leading to hemophagocytic lymphohistiocytosis (HLH) is a major risk factor; however, capillary hyper-permeability is the core underlying pathophysiological mechanism. Endothelial dysfunction plays a major role in cardiometabolic disease through insulin resistance, lipotoxicity, and, eventually, oxidative stress and chronic inflammation. We review the literature concerning the aforementioned mechanisms as well-established risk factors for adverse COVID-19 outcomes. We especially focus on data regarding the underlying endothelial effects of SARS-CoV-2 infection, including direct damage and increased vascular leakage through a hyper-inflammatory cascade and diminished nitric oxide bioavailability. Interestingly, an increased incidence of hypoalbuminemia has been observed in patients with severe COVID-19, especially those with underlying cardiometabolic disease. Importantly, low albumin levels present a strong, positive association with poor disease outcomes. Therefore, in this review article, we highlight the important role of cardiovascular risk factors on endothelium integrity and the possible link of endothelial damage in the hypoalbuminemia-associated adverse prognosis of COVID-19 patients.

Serum Albumin as Prognostic Marker for Older Adults in Hospital and Community Settings

“…Studies have demonstrated that inflammation can increase capillary permeability, allowing serum albumin to escape into the interstitial space, thereby expanding the interstitial volume and increasing the distribution volume of albumin ( Dekker et al, 2018 ). This heightened capillary permeability serves as a key mechanism through which inflammation leads to the escape of serum albumin, ultimately resulting in hypoalbuminemia ( Lambadiari et al, 2022 ). Additionally, inflammation can induce hypoalbuminemia by promoting the catabolism of albumin in response to infection-related inflammation ( Arnau-Barrés et al, 2021 ).…”

COVID-19 Complications: Oxidative Stress, Inflammation, and Mitochondrial and Endothelial Dysfunction

“…Thrombosis and DIC are vascular events that are actively involved in the progression of COVID-19 and represent a coagulation/fibrinolytic abnormality manifested by macroand microthrombotic events. The likelihood of the occurrence of COVID-19 thrombosis increases with increased markers of coagulation and fibrinolysis [144,145].…”

The importance of microvascular inflammation in ageing and age-related diseases: a position paper from the ESH working group on small arteries, section of microvascular inflammation

“…Furthermore, oxidative stress is characterized by the production of peroxynitrite that down-regulates NO bioavailability and leads to vasoconstriction. Also, the accumulation of ROS promotes the apoptosis of ECs and augment the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin resulting in microvascular inflammation and hypercoagulability [180]. Chronic inflammation inhibits the production of endothelial eNOS and promotes the expression of ICAM-1, VCAM-1 and ET-1, further damaging endothelial integrity [181].…”