Detection of COVID-19 brain capillaries

Large cell nuclei resembling megakaryocytes were found in the cortical capillaries of five people who died of severe COVID-19 damage, neuropathologists reported.

“To further characterize these cells, we performed immunohistochemistry for CD61 and CD42b, platelet markers and megakaryocytes,” wrote David Nauen, MD, PhD, of Johns Hopkins University in Baltimore, and colleagues, in a Neurology JAMA research letter. “CD61 labels these cells, as does CD42b, confirming their megakaryocyte identity.” The cells were differentiated from platelet aggregates, which were detected in intravascular postmortem 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 bone marrow,” he said. “They have been seen in the lungs and elsewhere, but not in brain capillaries,” Nauen said MedPage today. “How they got there is a mystery.”

This unusual finding is “extremely unexpected and thoughtful,” saw Gerald Soff, MD, a hematologist with the Sloan Memorial Kettering Cancer Center in New York City, who was not involved in the research.

“COVID-19 is known to be linked to the activation of the clotting system, and this is part of the clotting system, although it is not the part that is usually targeted by antipsychotic drugs,” he said. Soff in an interview with MedPage today. “The clinical impact is yet to be determined, but it suggests that we should look more aggressively for the circulation of megakaryocyte particles, which may be an additional target for intervention.”

In their study, Nauen and colleagues evaluated brain tension from autopsies of 15 patients with SARS-CoV-2 infection diagnosed with nuclear acid and confirmed lung pathology, as well as two controlled patients without COVID- 19. In some cases, only brain fragments were available. The first five cases came from Johns Hopkins; the remainder were randomly selected from autopsies of stroke-free people who died from COVID-19 in April and May 2020 at Brigham and Women’s Hospital in Boston.

Megakaryocytes in brain capillaries have been observed in interferons from COVID-19 patients who died in their 40s as well as patients in their 70s. Four of the five were men. “Interestingly, we found megakaryocytes in cortical capillaries in 33% of cases studied,” the researchers noted. “Because the randomly sampled normal brain autopsy segments contain only a minute fraction of the cortical measurement, the detection of these cells indicates that the total burden may be quite large.”

It’s hard to say what the presence of megakaryocytes in brain capillaries means, Nauen said. Megakaryocytes are large cells: “It’s like taking a football and moving it into a tube with the diameter of a golf ball,” he noted. “It’s going to keep things out. It’s possible that the fog or the sharp reference that people with COVID-19 report could be linked to that.”

But other factors could contribute to COVID ‘s brain fog, too, said Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, who was not involved in the study. While the importance of megakaryocytes in cortical capillaries is unclear, “I’m not sure if this can explain brain fog,” Nath said. MedPage today. “That would be a huge stretch. Every patient in this paper had other comorbidities, so I’m not sure if that contributed to the process.”

What SARS-CoV-2 does in the brain “remains a great mystery,” Nauen said. “If you don’t have viral encephalitis and you don’t have inflammation in the normal way in the cortex, why are people with coronavirus getting symptoms that we would associate with cortical anxiety in thinking?”

“Without the virus present in the brain, in the absence of classic inflammation, it may be the delivery of oxygen,” he suggested. “So the question is, what else has changed in the brain?”