Surprise Find in COVID-19 Brain Capillaries

Large cell nuclei that appeared to be megakaryocytes were found in cortical capillaries of five people who died with severe COVID-19, neuropathologists reported.

“To further characterize these cells, we performed immunohistochemistry for CD61 and CD42b, markers of platelets and megakaryocytes,” wrote David Nauen, MD, PhD, of Johns Hopkins University in Baltimore, and colleagues, in a JAMA Neurology research letter. “CD61 labels these cells, as does CD42b, confirming their megakaryocyte identity.” The cells were distinct from platelet clusters, which were found in postmortem intravascular precipitates.

This is the first known report of megakaryocytes in brain vessels in COVID-19 or any other disease, Nauen noted.

“These are cells that normally live in the bone marrow,” he said. “They’ve been seen in the lung and other places, but not in brain capillaries,” Nauen told MedPage Today. “How they got there is a mystery.”

This atypical finding is “extremely unanticipated and thought-evoking,” observed Gerald Soff, MD, a hematologist with Memorial Sloan Kettering Cancer Center in New York City, who wasn’t involved with the research.

“It’s well known that COVID-19 is associated with activation of the clotting system, and this is part of the clotting system, although not the part that’s typically targeted with anticoagulants,” Soff said in an interview with MedPage Today. “The clinical impact is to be determined, but it suggests we should be looking more aggressively for circulating megakaryocyte fragments, which may indicate an additional target for intervention.”

In their study, Nauen and colleagues assessed brain tissue from autopsies of 15 patients with nucleic acid-proven SARS-CoV-2 infection and confirmed pulmonary pathology, plus two control patients without COVID-19. In some cases, only fragments of brain were available. The first five cases were from Johns Hopkins; the remaining were randomly selected from autopsies of people who were stroke-free and who died with COVID-19 in April and May 2020 at Brigham and Women’s Hospital in Boston.

Megakaryocytes in brain capillaries were seen in tissues from COVID-19 patients who died in their 40s as well as patients in their 70s. Four of five were men. “It is notable that we found megakaryocytes in cortical capillaries in 33% of cases examined,” the researchers pointed out. “Because the standard brain autopsy sections taken sampled at random only a minute portion of the cortical volume, finding these cells suggests the total burden could be considerable.”

It’s hard to say what the presence of megakaryocytes in brain capillaries means, Nauen said. Megakaryocytes are big cells: “It’s like taking a football and shoving it into a pipe with the diameter of a golf ball,” he noted. “It’s going to occlude things. It’s possible the fogginess or less sharp mentation that people with COVID-19 are reporting could be connected to that.”

But other factors could contribute to COVID brain fog, too, said Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, who wasn’t involved with the study. While the significance of megakaryocytes in cortical capillaries is unclear, “I am not sure that this can explain brain fog,” Nath told MedPage Today. “That would be a big stretch. All the patients in this paper had other comorbidities, so I’m not sure if that may have contributed to the process.”

What SARS-CoV-2 does in the brain is “still a big mystery,” Nauen said. “If you don’t have viral encephalitis and you don’t have inflammation in a conventional sense in the cortex, why are people with coronavirus experiencing symptoms we would associate with cortical disturbance in thought?”

“Without the virus being present in the brain, without classic inflammation being present, maybe it’s the oxygen delivery,” he suggested. “So then the question is, what else has changed in the brain?”