The Angiogenesis Foundation reports today that new research published in the New England Journal of Medicine shows that the respiratory virus SARS-CoV-2, which causes COVID-19, causes severe damage to blood vessels, leading to widespread thrombosis, or blood clotting, in the lung1. The study was conducted by an international team of medical scientists who compared the lungs of patients who died from COVID-19 with lungs of patients who died from influenza as well as with healthy lungs donated for transplantation. These researchers discovered an unexpected disease pattern in COVID-19 lungs: The virus invaded the cells that line blood vessels, called endothelial cells, and this was accompanied by blood clots. Compared to the flu, COVID-19 lungs had 9-fold more blood clots and the blood vessels were injured by the virus causing an unusual reaction of blood vessel growth.
“One of the great mysteries of COVID-19 has been why blood clots, or thrombosis, form in some patients who are infected,” said Dr. William Li, President and Medical Director of the Angiogenesis Foundation. “These clots can become lethal because they severely compromise blood flow not only in the lungs, but also in other organs such as the brain and heart, among other tissues. Our research is the first to show that these clots are associated with damaged blood vessels. The damage causes a unique healing reaction called intussusceptive angiogenesis that was found in COVID-19 at levels 30-times above normal.” Scientists first described this phenomenon in the early 1990s as a way that blood vessels respond to injury by creating a new network of healing blood vessels2. In the NEJM study, the researchers found an association between the more intussusceptive angiogenesis present, the longer the hospital stay of the patient suggesting that severity of COVID-19 disease is linked to blood vessel damage. Intense inflammation was also found in all COVID-19 lungs.
“Although SARS-Cov-2 is a respiratory virus, we now see it can cause a vascular disease in COVID-19,” said Li. “The intussusceptive angiogenesis is how the body compensates when faced with thrombosis and blood vessel damage.” The injured blood vessel lining helps to explain the serious blood clotting observed in patients. This damage may also underlie other problems seen with COVID-19, such as stroke, deep vein thrombosis, COVID toe, and damage to the heart, and also explain why anticoagulation may be helpful in preventing serious complications. Separately, a May 6 report published in the Journal of the American College of Cardiology described how using blood thinners in patients hospitalized with COVID-19 appeared to be protective and associated with better outcomes3.
The current study highlights the need for additional research on angiogenesis and the vascular effects of COVID-19. “Our blood vessels are the lifelines for all of our organs,” said Li. “If COVID-19 damages our vessels, the long-term effects could be devastating even after the virus is cleared. Finding ways to protect our blood vessels and helping them heal could be an important dimension to COVID-19 treatment. These interventions could involve not only medications, but importantly, dietary factors and lifestyle.”
In addition to the Angiogenesis Foundation, the following institutions were involved in this research: Harvard Medical School (Boston); University Hospital Basel (Basel, Switzerland); KU Leuven (Leuven, Belgium), German Center for Lung Research and Hanover Medical School (Hannover, Germany); Helios University, University of Witten-Herdecke, and Johannes Gutenberg University of Mainz (Mainz, Germany).
1. Ackermann M, et. al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. New Engl J Med 2020 (May 21, 2020)
2. Burri PH. Intussusceptive microvascular growth, a new mechanism of capillary network formation. EXS 1992;61:32-9.
3. Paranjpe I, et. al. Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19. J Am Coll Cardiol 2020 May 5;S0735-1097(20)35218-9.