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A close look at the body after death from COVID-19 turned up some potentially novel differences in the lungs.

Histology showed the same diffuse alveolar damage with perivascular T-cell infiltration in the lungs of seven people who died with acute respiratory distress syndrome (ARDS) from COVID-19 as in those from seven decedents with ARDS from influenza A (H1N1).

However, the vascular damage was different, Steven Mentzer, MD, of Brigham and Women's Hospital in Boston, and colleagues .

For one, COVID-19 lungs showed "severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes."

This evidence of virus in endothelial cells "suggests there is a direct cause and effect for the virus in this very profound inflammatory response and thrombosis response," commented Richard Becker, MD, director of the University of Cincinnati Heart, Lung and Vascular Institute, who recently published a in the Journal of Thrombosis and Thrombolysis.

Pulmonary vessels in the COVID-19 autopsies also showed widespread thrombosis with microangiopathy: Capillaries in lung alveoli had nine times more microthrombi as in patients with influenza (P<0.001).

As well, COVID-19 lungs showed 2.7-fold more new vessel growth as seen in the influenza cases (P<0.001). These new vessels were predominantly intussusceptive angiogenesis, defined by an endothelial-lined pillar or post spanning the lumen of the vessel rather than sprouting of new vessels, which the researchers called unexpected.

That finding and corresponding differential up-regulation of angiogenesis-associated genes were "intriguing, and it is tempting to ascribe this difference as being specific to SARS-CoV-2," wrote Lida Hariri, MD, PhD, and C. Corey Hardin, MD, PhD, both of Massachusetts General Hospital in Boston, in an .

Direct comparison was complicated by heavier, and thus more advanced stage of diffuse alveolar damage, in the influenza cases, they cautioned.

However, there were differences even when the angiogenesis was plotted as a function of the length of hospital stay, with a degree of intussusceptive angiogenesis that increased significantly with duration of admission in COVID-19 but not influenza.

While there's still a lot to learn about what this means in the natural history of COVID-19, Becker speculated that the angiogenesis could be stimulated by the profound amount of injury, inflammation, and blood clotting from the virus.

"There are growth factors that are produced in the body and really require a lot of stimulation for those to be released by white blood cells and macrophages and other things that are there to protect us against offenders but occasionally our own immune response is not well regulated," Becker told MedPage Today. "And I believe in all likelihood that is what those new blood vessels reflect."

There may be implications from the growth of these blood vessels for distribution of the virus or harmful byproducts of the body's fight against it around to other organs, he said. Or, it's possible that these new vessels act simply as a marker of disease severity.

"Regardless, the finding of a novel pathological process opens up the possibility of developing sorely needed new treatments and should spur further research," the editorialists noted.

The study included seven autopsies from patients with COVID-19 and the same number of historical samples from the 2009 H1N1 influenza outbreak. The researchers used immunohistochemical assay, microcomputed tomographic imaging, scanning electron microscopy, corrosion casting, and direct multiplexed measurements of gene expression.

Additional limitations included that none of the COVID-19 cases had been intubated (two had received noninvasive ventilation), whereas five with influenza had been intubated "and treated with ventilator settings that we would now consider not to be lung protective," the editorialists noted. "The sample size of the study was also small, which is particularly problematic in a heterogeneous condition such as ARDS."

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