Long-term neurological symptoms such as “brain fog” experienced by some patients with COVID-19 may be caused by a single pathology: the occlusion of brain capillaries by large megakaryocytic cells, a new report suggests.
The authors report five separate post-mortem cases of patients who died with COVID-19 in which large cells resembling megakaryocytes in cortical capillaries were identified. Subsequently, immunohistochemistry confirmed their megakaryocyte identity.
They point out that the finding is of interest because, as far as they know, no megakaryocytes had been found in the brain before.
The observations are described in a research letter published online on February 12 a JAMA Neurology.
Bone marrow cells in the brain
Lead author David Nauen, MD, a neuropathologist at Johns Hopkins University in Baltimore, Maryland, said Medscape Medical News identified these cells in the first post-mortem brain tissue analysis of a patient who had COVID-19.
“Some other viruses cause changes in the brain, such as encephalopathy, and because neurological symptoms often present with COVID-19, I was curious to see if similar effects were seen in brain post-mortem samples from patients who had died of the infection. , “Nauen said.
In his first analysis of the brain tissue of a patient who had COVID-19, Nauen saw no evidence of viral encephalitis, but observed some “unusually large” cells in the brain capillaries.
“I was surprised; I couldn’t figure out what they were. Then I realized that these cells were megakaryocytes from the bone marrow. I’ve never seen these cells in the brain. I asked several colleagues and none I didn’t have any of them. After doing a lot of bibliographic research, I couldn’t find any evidence that there are megakaryocytes in the brain, “Nauen said.
Megakaryocytes, he explained, are “very large cells and the brain capillaries are very small, large enough to let red blood cells and lymphocytes through. Seeing such large cells in these vessels is extremely unusual. It seems that they are causing occlusions “.
If they block the flow through individual capillaries, these large cells could cause ischemic alterations with a different pattern, which could lead to an atypical form of neurological impairment, the authors suggest.
“This could alter hemodynamics and put pressure on other vessels, possibly contributing to the increased risk of stroke that has been reported in COVID-19,” Nauen said. Although, she reported, none of the samples she examined came from patients with COVID-19 who had had a stroke.
Aside from the presence of megakaryocytes in the capillaries, the brain looked normal, he said. He has now examined samples from the brains of 15 patients who had COVID-19 and found megakaryocytes in brain capillaries in five cases.
New neurological complication
Classical encephalitis found with other viruses has not been reported in brain post-mortem examinations of patients who had COVID-19, Nauen noted.
“Cognitive issues such as the discomfort associated with COVID-19 would indicate problems with the cortex, but this has not been documented. This occlusion of a multitude of small vessels by megalocaryocytes may offer some explanation for the cognitive problems. This is a new type of cognitive impairment. ‘vascular insult seen in pathology, and suggests a new type of neurological complication,’ he added.
The big question is what do these megakaryocytes do to the brain.
“Megakaryocytes are bone marrow cells. They are not immune cells. Their job is to produce platelets to help the blood clot. They are not normally found outside the bone marrow, but have been reported. in other organs in patients with COVID-19 “.
“But the big puzzle associated with finding them in the brain is how they pass through the thin network of blood vessels in the lungs. Geometry just doesn’t work. We don’t know what part of the COVID inflammatory response makes that happen,” he said. Nauen.
The authors suggest that one possibility is that the alteration of endothelial or other signaling is the recruitment of megakaryocytes into the circulation and somehow allows them to pass through the lungs.
“We need to try to understand if there is anything distinctive about these megakaryocytes, what proteins they are expressing, and that can explain why they behave in such an unusual way,” Nauen said.
Noting that many patients with severe COVID-19 have clotting problems and that megakaryocytes are part of the clotting system, he speculated that some kind of aberrant message is being sent to these cells.
“It is noteworthy that we found megakaryocytes in the cortical capillaries in 33% of the cases examined. Because standard brain autopsy sections were taken at random [are] only a minimal portion of the cortical volume, finding these cells suggests that the total load could be considerable, ”the authors write.
Nauen added that to the best of his knowledge, this is the first report of these observations and the next step is to look for similar results in larger sample sizes.
JAMA Neurol. Published online February 12, 2021. Research letter
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