In a study released this week in the New England Journal of Medicine (NEJM) researchers in Europe examined 7 lungs from patients who died of COVID-19, 7 lungs of patients with acute respiratory distress syndrome from influenza A (H1N1) and 10 age-matched non-infected control lungs. They examined the lungs using a variety of tools including immunohistochemical analysis, computed tomographic (CT) imaging, and electron microscopy, and measurements of genetic expression among other modalities.
Patients with COVID-19 and influenza can develop a condition known as acute respiratory distress syndrome (ARDS). ARDS is a very severe pulmonary condition that generally leads to worsening blood oxygenation (hypoxemia) that doesn’t respond well to oxygen and often results in patients requiring mechanical ventilation to survive. On x-ray, patients with ARDS can have a ground glass appearance and lung fields can show increasing consolidation to the point of near complete opacification of the x-ray. Histologically, the alveoli (air sacks in the lungs) are diffusely damaged and edematous (filled with protein containing fluid) often with hemorrhage (bleeding) and fibrin deposition (a marker for inflammation and coagulation).
The researchers set out to compare the lungs of patients with ARDS from influenza A to those with ARDS from COVID-19. There were some similarities. In general patients with ARDS from COVID-19 and influenza A had diffuse alveolar damage and edema but the edema in the influenza patients was more massive and correlated with the lungs of deceased patients with influenza weighing more than those who died of COVID-19. Both sets of patients had immune cells though there was some difference in the types of T-cells. With respect to measures of inflammation-related gene expression, COVID-19 patients had a total of 79 inflammation-related genes expressed but only 2 genes were uniquely differentially regulated in patients with influenza. The two groups shared an expression pattern for 7 genes.
Significant differences started to arise when the researchers looked at thrombosis and blood vessel pathology. The alveolar capillaries (very small blood vessels where gas exchange of oxygen and carbon dioxide occurs) were 9 times more likely to have microthrombi (small blood clots) and occluded small blood vessels in COVID-19. Additionally, the endothelium (cells that make up the walls of the blood vessels) and endothelial cell membranes of the COVID-19 patients showed significantly more damage from virus present within the cells than similar cells in influenza infected lungs. Finally and most surprisingly, from all of this vascular damage done by SARS-CoV-2 to the lungs of patients with COVID-19, there was significant angiogenesis (development of new blood vessels) in COVID-19 lungs. The combination of increased blood vessel cell damage and microclotting in patients with COVID-19 may be responsible for the lungs working overtime to create new blood vessels to compensate.
This study is small and because of that there could be other reasons for the differences seen between the two groups and the authors concede this. But these findings fit with the experiences of clinicians and researchers who report much higher frequency of clotting abnormalities and dramatic levels of inflammatory response in COVID-19 patients. It’s unknown if the angiogenesis has any effect on survivability either way–further studies may help to elucidate this question.
CHRIS DAEL 