Long-term neurological symptoms, such as “brain fog” experienced by some patients with COVID-19, can be caused by a unique pathology – the occlusion of brain capillaries by large megakaryocyte cells, a new report suggests.
The authors report five separate postmortem cases of patients who died with COVID-19 in which large megakaryocyte-like cells were identified in the cortical capillaries. Immunohistochemistry subsequently confirmed its megakaryocyte identity.
They point out that the discovery is interesting, since – as far as they know – megakaryocytes have not been found in the brain before.
The observations 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, a neuropathologist at Johns Hopkins University, Baltimore, Maryland, said Medscape Medical News he 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, like encephalopathy, and because neurological symptoms are often reported in COVID-19, I was curious to see if similar effects were seen in postmortem samples from the brain of patients who died from the infection, “Nauen said.
In his first analysis of the brain tissue of a patient with COVID-19, Nauen saw no evidence of viral encephalitis, but noted some “exceptionally large” cells in the capillaries of the brain.
“I was surprised; I couldn’t find out what they were. Then I realized that these cells were bone marrow megakaryocytes. I had never seen these cells in the brain before. I asked several colleagues and none of them either. After extensive research in the literature, I couldn’t find any evidence. of megakaryocytes in the brain, “noted Nauen.
Megakaryocytes, he explained, are “very large cells and brain capillaries are very small – large enough to allow red blood cells and lymphocytes to pass through. Seeing these very large cells in these vessels is extremely unusual. It seems so. Causing occlusions. ”
By occluding the flow through individual capillaries, these large cells can cause ischemic changes in a distinct pattern, potentially resulting in an atypical form of neurological impairment, suggest the authors.
“This can alter hemodynamics and put pressure on other vessels, possibly contributing to the increased risk of stroke that was reported in COVID-19,” said Nauen. Although, he reported, none of the samples he examined came from patients with COVID-19 who had a stroke.
In addition to the presence of megakaryocytes in capillaries, the brain looked normal, he said. He now examined samples from 15 brains from patients who had COVID-19 and megakaryocytes were found in brain capillaries in five cases.
New Neurological Complication
Classical encephalitis found with other viruses has not been reported in postmortem brain scans of patients who had COVID-19, noted Nauen.
“Cognitive problems, like torpor associated with COVID-19, indicate problems with the cortex, but this has not been documented. This occlusion of a multitude of small vessels by megalocarocytes may offer some explanation for cognitive problems. This is a new type of vascular insult seen in pathology and suggests a new type of neurological complication “, he added.
The big question is what these megakaryocytes are doing in the brain.
“Megakaryocytes are bone marrow cells. They are not immune cells. Their job is to produce platelets to help clot the blood. 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 very thin network of blood vessels in the lungs. The geometry just doesn’t work. We don’t know which part of the COVID inflammatory response makes this happen,” said Nauen.
The authors suggest that one possibility is that endothelial alteration or other signaling is recruiting megakaryocytes into the circulation and, in some way, allowing them to pass through the lungs.
“We need to try to understand if there is anything different about these megakaryocytes – what proteins they are expressing that may explain why they are behaving so uncommonly,” said Nauen.
Noting that many patients with severe COVID-19 have clotting problems and megakaryocytes are part of the clotting system, he speculated that some kind of aberrant message is being sent to these cells.
“It is notable that we found megakaryocytes in cortical capillaries in 33% of the cases examined. Because the autopsy sections of the standard brain collected at random [are] just a small portion of the cortical volume, finding these cells suggests that the total load may be considerable “, write the authors.
Nauen added that, to his knowledge, this is the first report of such observations, and the next step is to look for similar findings in larger samples.
JAMA Neurol. Published online February 12, 2021. Research Letter
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