Overcoming Barriers

Abstract

Objective: Coronavirus disease 2019 (COVID-19) is a global pandemic involving >5 500 000 cases worldwide as of May 26, 2020. The culprit is the severe acute respiratory syndrome coronavirus-2, which invades cells by binding to angiotensin-converting enzyme 2. While the majority of patients mount an appropriate antiviral response and recover at home, others progress to respiratory distress requiring hospital admission for supplemental oxygen. In severe cases, deterioration to acute respiratory distress syndrome necessitating mechanical ventilation, development of severe thrombotic events, or cardiac injury and dysfunction occurs. In this review, we highlight what is known to date about coronavirus disease 2019 and cardiovascular risk, focusing in on the putative role of the endothelium in disease susceptibility and pathogenesis. Approach and Results: Cytokine-driven vascular leak in the lung alveolar-endothelial interface facilitates acute lung injury in the setting of viral infection. Given that the virus affects multiple organs, including the heart, it likely gains access into systemic circulation by infecting or passing from the respiratory epithelium to the endothelium for viral dissemination. Indeed, cardiovascular complications of coronavirus disease 2019 are highly prevalent and include acute cardiac injury, myocarditis, and a hypercoagulable state, all of which may be influenced by altered endothelial function. Notably, the disease course is worse in individuals with preexisting comorbidities that involve endothelial dysfunction and may be linked to elevated ACE2 (angiotensin-converting enzyme 2) expression, such as diabetes mellitus, hypertension, and cardiovascular disease. Conclusions: Rapidly emerging data on coronavirus disease 2019, together with results from studies on severe acute respiratory syndrome coronavirus-1, are providing insight into how endothelial dysfunction may contribute to the pandemic that is paralyzing the globe. This may, in turn, inform the design of biomarkers predictive of disease course, as well as therapeutics targeting pathogenic endothelial responses.

ICU Admission Levels of Endothelial Biomarkers as Predictors of Mortality in Critically Ill COVID-19 Patients

“…Lung injury in COVID-19 is facilitated by cytokine-driven vascular leaks in the lung alveolar-endothelial interface; it seems possible that the virus gains access into systemic circulation by passing from the respiratory epithelium to the endothelium [ 1 ], turning the lung into a key organ target. Patients with COVID-19 exhibit problems in multiple organs.…”

COVID-19, host response treatment, and the need for political leadership

“…•prepare to communicate trial results to physicians, health officials, and the public abnormalities, cardiovascular involvement, and acute renal failure [6] These complications reflect underlying endothelial dysfunction.…”

Non-invasive assessment of endothelial dysfunction: A novel method to predict severe COVID-19?

“…Various treatment including antivirals, anti-inflammatory drugs, antimalarials have been tested, but the research and trials on treatment are continuously evolving [43] . Targeting endothelial function has also been proposed as a potential treatment option [44] . Currently, the management of severe COVID-19 patients includes respiratory support and intensive care.…”