Long-term neurological symptoms, such as “brain fog,” experienced by some patients with COVID-19 may be caused by a unique pathology – the occlusion of brain capillaries by large megakaryocyte cells, suggests a new report.
The authors report five separate post-mortem cases of patients who died of COVID-19 in which large megakaryocyte-like cells were identified in the cortical capillaries. Immunohistochemistry later confirmed their megakaryocytic identity.
They point out that the discovery is of interest because – to their knowledge – megakaryocytes have not been found in the brain before.
The comments are described in a research letter published online on February 12 in JAMA Neurology.
Bone marrow cells in the brain
Lead author David Nauen, MD, PhD, neuropathologist at Johns Hopkins University, Baltimore, Maryland, said Medscape medical news he identified these cells in the first post-mortem brain tissue analysis from a patient who had COVID-19.
“Some other viruses cause changes in the brain, such as encephalopathy, and because neurological symptoms are often reported in COVID-19, I was curious to see if similar effects were observed in post-mortem brain samples from patients who had died of the infection, ”Nauen said.
At his first analysis of the brain tissue of a patient with COVID-19, Nauen saw no evidence of viral encephalitis, but observed several “unusually large” cells in the capillaries of the brain.
“I was amazed; I couldn’t figure out what they were. Then I realized that these cells were megakaryocytes in the bone marrow. I haven’t seen these cells in the brain before. I’ve asked several colleagues and none of them “He didn’t have any. After extensive research in the literature, we couldn’t find any evidence that megakaryocytes were in the brain,” Nauen said.
Megakaryocytes, he explained, are “very large cells, and the capillaries in the brain are very small – large enough to allow red blood cells and lymphocytes to pass through. Seeing these very large cells in such vessels is extremely unusual. Looks like they’re causing occlusions. ”
By occluding the flow through individual capillaries, these large cells could cause ischemic changes in a distinct pattern, leading 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, he reported, none of the samples he examined came from patients with COVID-19 who had had a stroke.
In addition to the presence of megakaryocytes in the capillaries, the brain looked normal, he said. He now examined samples from 15 brains of patients who had COVID-19 and megakaryocytes were found in the capillaries of the brain in five cases.
New neurological complication
Classical encephalitis found with other viruses was not reported in post-mortem brain examinations in patients who had COVID-19, Nauen noted.
“Cognitive problems, such as damage 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 megalokaryocytes can provide an explanation for cognitive problems. This is a new type of vascular insult observed on the pathology and suggests a new type of neurological complication, “he added.
The big question is what do these megakaryocytes do in the brain.
“Megakaryocytes are bone marrow cells. They are not immune cells. Their job is to produce platelets to help form blood clots. They are not normally found outside the bone marrow, but have been reported in other organs in patients with bone marrow. COVID-19. “
“But the big puzzle associated with finding them in the brain is how they go through the very fine network of blood vessels in the lungs. Geometry just doesn’t work. We don’t know what part of the COVID inflammatory response makes this happen,” he said. Nauen.
The authors suggest that one possibility is that altered or other endothelial signaling recruits circulating megakaryocytes and somehow allows them to pass through the lungs.
“We need to try and understand if there is anything distinctive about these megakaryocytes – what proteins they express that could explain why they behave in such an unusual way,” Nauen said.
Noting that many patients with severe COVID-19 have problems with clotting, and megakaryocytes are part of the clotting system, he speculated that such an aberrant message is being sent to these cells.
“It is remarkable that we found megakaryocytes in the cortical capillaries in 33% of the cases examined. Because the standard brain autopsy sections taken were sampled at random. [are] only a small portion of the cortical volume, finding these cells suggests that the total burden could be considerable, “the authors write.
Nauen added that, to his knowledge, this is the first report of such observations, and the next step is to look for similar results in larger samples.
JAMA Neurol. Published online February 12, 2021. Research letter
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