The long-term neurologic signs resembling “mind fog” skilled by some sufferers with COVID-19 could also be brought on by a novel pathology — the occlusion of mind capillaries by massive megakaryocyte cells, a brand new report suggests.
The authors report 5 separate autopsy instances from sufferers who died with COVID-19 through which massive cells resembling megakaryocytes had been recognized in cortical capillaries. Immunohistochemistry subsequently confirmed their megakaryocyte identification.
They level out that the discovering is of curiosity as — to their information — megakaryocytes haven’t been discovered within the mind earlier than.
The observations are described in a analysis letter published online February 12 in JAMA Neurology.
Bone Marrow Cells within the Mind
Lead creator David Nauen, MD, PhD, a neuropathologist from Johns Hopkins College, Baltimore, Maryland, informed Medscape Medical Information he recognized these cells within the first evaluation of autopsy mind tissue from a affected person who had COVID-19.
“Another viruses trigger modifications within the mind resembling encephalopathy, and as neurologic signs are sometimes reported in COVID-19, I used to be curious to see if related results had been seen in mind autopsy samples from sufferers who had died with the an infection,” Nauen mentioned.
On his first evaluation of the mind tissue of a affected person who had COVID-19, Nauen noticed no proof of viral encephalitis, however he noticed some “unusually massive” cells within the mind capillaries.
“I used to be greatly surprised; I could not work out what they had been. Then I spotted these cells had been megakaryocytes from the bone marrow. I’ve by no means seen these cells within the mind earlier than. I requested a number of colleagues and none of them had both. After intensive literature searches, I might discover no proof of megakaryocytes being within the mind,” Nauen famous.
Megakaryocytes, he defined, are “very massive cells, and the mind capillaries are very small — simply massive sufficient to let red blood cells and lymphocytes move by. To see these very massive cells in such vessels is extraordinarily uncommon. It appears like they’re inflicting occlusions.”
By occluding movement by particular person capillaries, these massive cells might trigger ischemic alteration in a definite sample, probably leading to an atypical type of neurologic impairment, the authors counsel.
“This may alter the hemodynamics and put strain on different vessels, probably contributing to the elevated danger of stroke that has been reported in COVID-19,” Nauen mentioned. Though, he reported, not one of the samples he examined got here from sufferers with COVID-19 who had had a stroke.
Apart from the presence of megakaryocytes within the capillaries, the mind seemed regular, he mentioned. He has now examined samples from 15 brains of sufferers who had COVID-19 and megakaryocytes have been discovered within the mind capillaries in 5 instances.
New Neurologic Complication
Basic encephalitis discovered with different viruses has not been reported in mind autopsy examinations from sufferers who had COVID-19, Nauen famous.
“The cognitive points resembling grogginess related to COVID-19 would point out issues with the cortex however that hasn’t been documented. This occlusion of a mess of tiny vessels by megalokaryocytes could provide some clarification of the cognitive points. This can be a new type of vascular insult seen on pathology, and suggests a brand new type of neurologic complication,” he added.
The large query is what these megakaryocytes are doing within the mind.
“Megakaryocytes are bone marrow cells. They aren’t immune cells. Their job is to supply platelets to assist the blood clot. They aren’t usually discovered exterior the bone marrow, however they’ve been reported in different organs in COVID-19 sufferers.”
“However the huge puzzle related to discovering them within the mind is how they get by the very wonderful community of blood vessels within the lungs. The geometry simply does not work. We do not know which a part of the COVID inflammatory response makes this occur,” mentioned Nauen.
The authors counsel one chance is that altered endothelial or different signaling is recruiting megakaryocytes into the circulation and in some way letting them move by the lungs.
“We have to try to perceive if there may be something distinctive about these megakaryocytes — which proteins are they expressing which will clarify why they’re behaving in such an uncommon manner,” mentioned Nauen.
Noting that many sufferers with extreme COVID-19 have issues with clotting, and megakaryocytes are a part of the clotting system, he speculated that some kind of aberrant message is being despatched to those cells.
“It’s notable that we discovered megakaryocytes in cortical capillaries in 33% of instances examined. As a result of the usual mind post-mortem sections taken sampled at random [are] solely a minute portion of the cortical quantity, discovering these cells suggests the whole burden may very well be appreciable,” the authors write.
Nauen added that to his information, that is the primary report of such observations, and the following step is to search for related findings in bigger pattern sizes.
JAMA Neurol. Printed on-line February 12, 2021. Research Letter