SARS-CoV-2 and influenza A (H1N1) are in the same category of virus and both infect the respiratory tract. However, research has shown distinctive vascular changes in the lungs of patients with COVID-19 compared to those with H1N1.
A new study published in the New England Journal of Medicine (NEJM) examined seven lungs obtained during autopsy from patients who died of COVID-19. Researchers compared this group to seven autopsied lungs obtained from patients who died of acute respiratory distress syndrome (ARDS) secondary to H1N1 infection, as well as to 10 age-matched uninfected control lungs.
“COVID-19 seems to involve the vascular system to a much greater extent than H1N1,” says Steven Mentzer, MD, senior author of the study and a thoracic surgeon in The Lung Center at Brigham and Women’s Hospital. “That vascular involvement may explain some of the systemic organ dysfunction that we see in patients with COVID-19.”
COVID-19 Lungs Show Distinctive Vascular Features
For this study, Dr. Mentzer’s team at the Brigham worked with researchers in Germany, Switzerland, Belgium and the U.S. The international research team described three distinctive angiocentric features in the lungs of patients with COVID-19. These include: severe endothelial injury, widespread blood clotting with diseased capillaries and significant new vessel growth.
The severe endothelial injury is caused by damage to the endothelial cells, while the significant new vessel growth is likely a result of the body’s response to the virus. This response, known as intussusceptive angiogenesis (IA), reflects the body’s attempt to compensate for the clotting and blood vessel damage.
“While both COVID-19 and H1N1 lead to destruction of the lungs, COVID-19 shows selective and systemic injury of the blood vessels—in contrast to what you see with influenza,” explains Dr. Mentzer.
Studies have shown that COVID-19 patients face increased risk of thrombosis. This means the vascular features in the lungs of deceased COVID-19 patients are consistent with this distinctive pattern of pulmonary vascular disease progression that has been observed in some cases of COVID-19.
It’s possible that these damaged blood vessels could connect other problems observed in patients with COVID-19, such as ‘COVID toe,’ children with Kawasaki disease, stroke and other unusual presentations of the disease.
Vascular Phase of COVID-19 is “Potentially Lethal”
The COVID-19 disease is known to progress in phases. An initial phase may involve the upper respiratory tract, while a more advanced phase of the disease involves the lower respiratory tract. The systemic, or vascular, phase may follow in some patients.
“The vascular phase seems to involve multiple organs,” says Dr. Mentzer. Accordingly, a patient’s risk of mortality tends to increase as the phases progress.
For the study, researchers used a forensic pathology approach. That is, by looking at the lungs of deceased COVID-19 patients, they hoped to identify the phase of the disease associated with the death of the patient.
“This study shows that the vascular phase is a potentially lethal phase of the disease,” says Dr. Mentzer. “This suggests that we need to broaden our focus on COVID-19 as being only a respiratory disease.”
Collaborating Towards Clinical Implications
Throughout the pandemic, Brigham researchers have been collaborating on a global scale to better understand this novel virus. “Our attitude at the Brigham has been one of collective effort,” says Dr. Mentzer. “We share a mutual commitment to solving this worldwide crisis.”
Going forward, these vascular findings could have important practical implications in terms of treatment. That being said, Dr. Mentzer notes that the NEJM study was limited by its small size, and more research on the vascular effects of COVID-19 will be needed to translate this work into the clinical treatment of COVID-19 patients.
Research on the vascular phase of COVID-19 could also have implications for vaccine development. “I think the development of the circulating antibodies with a vaccine would be a promising way to prevent this vascular phase,” says Dr. Mentzer.