The 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 vessels by large megakaryocytes, reads a new report.
The authors report five separate post-mortem cases of patients who died with COVID-19, in which large cells such as megakaryocytes in cortical capillaries were identified. Immunohistochemistry subsequently confirmed their megakaryocyte identity.
They point out that the finding is important, as megakaryocytes to their knowledge have not been previously found in the brain.
The observations are described in a research letter published online on 12 February 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 analysis of postmortem brain tissue of a patient with COVID-19.
“Some other viruses cause changes in the brain, such as encephalopathy, and since neurological symptoms are often reported in COVID-19, I was curious to see if similar effects were seen in brain post-mortem examinations of patients who died with the infection,” Said Nauen.
With his first analysis of the brain tissue of a patient with COVID-19, Nauen saw no evidence of viral encephalitis, but he did see some “extraordinarily large” cells in the brain vessels.
“I was surprised; I could not figure out what it was. Then I realized that these cells are megakaryocytes from the bone marrow. I have never seen these cells in the brain. I asked several colleagues and neither of them. “After extensive literature searches, I could not find any evidence that megakaryocytes were in the brain,” Nauen noted.
Megakaryocytes, he explained, are “very large cells, and the brain capillaries are very small – just large enough to let red blood cells and lymphocytes through. It is extremely uncommon to see these very large cells in such vessels. cause occlusions. ”
By blocking the flow through individual capillaries, these large cells can cause ischemic changes in a clear pattern, possibly resulting in an atypical form of neurological impairment.
“It can alter hemodynamics and put pressure on other vessels, potentially contributing to the increased risk of stroke reported in COVID-19,” Nauen said. Although, according to him, none of the samples he examined came from patients with COVID-19 who had a stroke.
Except for the presence of megakaryocytes in the capillaries, the brain looked normal, he said. He now found samples from 15 brains of patients who had COVID-19 and megakaryocytes in five brains.
New neurological complication
Classical encephalitis found with other viruses has not been reported in post-mortem examinations of patients with COVID-19, Nauen noted.
“The cognitive issues such as grogginess associated with COVID-19 indicate problems with the cortex, but this has not been documented. This occlusion of a multitude of small vessels by megalokaryocytes may provide an explanation for the cognitive problems. a new kind of vascular insult seen on pathology, and indicates a new kind of neurological complications, ” 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 the blood clot. They are not normally found outside the bone marrow, but they have been reported in other organs in COVID-19 patients.”
“But the big mystery of finding them in the brain is how they get through the fine network of blood vessels in the lungs. The geometry just does not work. We do not know what part of the COVID inflammatory response it causes. Said Nauen.
According to the authors, the possibility is that altered endothelial or other signal recruits megakaryocytes into the circulation and may somehow move through the lungs.
“We need to try to understand if there is something characteristic about these megakaryocytes – what proteins do they express that could explain why they behave in such an unusual way,” Nauen said.
He noted that many patients with severe COVID-19 have problems with coagulation, and that megakaryocytes are part of the coagulation system. He speculates that some kind of deviant message is being sent to these cells.
“It is noteworthy that in 33% of cases we found megakaryocytes in cortical capillaries, because the standard sections of the brain autopsy were randomly sampled. [are] only a small part of the cortical volume, and the finding of these cells indicates that the total load can 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 findings in larger sample sizes.
JAMA Neurol. Published online on February 12, 2021. Research letter
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