Viewpoint: COVID-19 resembles endothelial disease, anti-inflammatory therapies may help
COVID-19 resembles an endothelial disease and treating it with anti-inflammatory agents, similarly to other endothelial diseases, may be appropriate, according to a viewpoint published in the European Heart Journal.
“Cytokines, protein pro-inflammatory mediators, serve as key danger signals that shift endothelial functions from the homeostatic into the defensive mode. The endgame of COVID-19 usually involves a cytokine storm, a phlogistic phenomenon fed by well-understood positive feedback loops that govern cytokine production and overwhelm counter-regulatory mechanisms,” Peter Libby, MD, cardiovascular specialist at Brigham and Women’s Hospital, Mallinckrodt Professor of Medicine at Harvard Medical School and Cardiology Today Vascular Medicine Section Editor, and Thomas Lüscher, MD, FRCP, director of research, education and development and consultant of cardiology at Royal Brompton & Harefield Hospital Trust and Imperial College in London and director of the Center for Molecular Cardiology at the University Zurich (Campus Schlieren), wrote in the viewpoint. “The concept of COVID-19 as an endothelial disease provides a unifying pathophysiological picture of this raging infection, and also provides a framework for a rational treatment strategy at a time when we possess an indeed modest evidence base to guide our therapeutic attempts to confront this novel pandemic.”
Cytokine storm
They wrote that cytokines such as interleukin (IL)-1-alpha, IL-1-beta, IL-6 and tissue necrosis factor-alpha normally perform host defenses, “but when produced inappropriately or in excess they can perturb all of the carefully orchestrated protective functions of the normal endothelium and potentiate pathological processes. The untrammelled production of proinflammatory cytokines contributes to a condition termed a cytokine storm.”
Crucially, Libby and Lüscher wrote, “The complications of COVID-19 follow very closely the consequences of excessive cytokine actions on endothelial cells.” These include thrombosis in the peripheral cerebral veins and arteries, which can cause strokes, “COVID toes” which likely result from microvascular dysfunction, thrombosis of the microvasculature of all arterial beds, venous thrombosis and pulmonary embolism.
Anti-inflammatory therapies
Therefore, they wrote, anti-inflammatory therapies can be considered as treatments for patients with COVID-19.
Glucocorticoids, colchicine and statins all have anti-inflammatory effects and appear to be beneficial in patients with COVID-19, and agents that inhibit the inflammasome–IL-1-beta–IL-6 pathway are under evaluation in some patients, but randomized controlled trials are necessary to determine the best approach, the authors wrote.
“We can envisage COVID-19 as a disease of the endothelium, certainly with respect to its complications,” Libby and Lüscher concluded. “This unifying hypothesis can help to understand the complex pathophysiology of this current plague and may also help to inform our therapeutic approaches to combatting the consequences of SARS-CoV-2 infection.”
Independent of the paper, many anti-inflammatory agents are under investigation as possible treatments for COVID-19. One being evaluated is a selective soluble tumor necrosis factor inhibitor (Quellor, Inmune Bio). The company recently announced it received permission from the FDA to conduct a phase 2 trial evaluating the agent for treatment of immune-mediated complications in patients with COVID-19. According to a press release from the company, the agent neutralizes soluble tumor necrosis factor without affecting transmembrane tumor necrosis factor or tumor necrosis factor receptors.
Reference:
- Inmune Bio. inmunebio.com/index.php/en/news-2/2020/364-muneioncnnouncescceptanceofpplicatio20200901. Sept. 1, 2020. Accessed Sept. 25, 2020.
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