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

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.

Automated summary

Capillary leak syndrome is a condition that is often overlooked but can have serious consequences, including hypoalbuminemia and potential death. Endothelial dysfunction plays a key role in cardiovascular disease and chronic inflammation, and these factors are also associated with adverse outcomes in COVID-19. This review highlights the importance of cardiovascular risk factors in maintaining endothelial integrity and the potential link between endothelial damage and poor prognosis in COVID-19 patients with hypoalbuminemia.