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COVID-19 May Invade, Damage Blood Vessels – Not Nerve Cells

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COVID-19 symptoms such as headaches and "fuzziness" or brain fog that linger following recovery may be caused by damage to the brain's small blood vessels, not nerve cells, according to a study by the Uniformed Services University and the National Institutes of Health.

The study, "Microvascular Injury in the Brain of Patients with COVID-19," was published Dec. 30, 2020, in the New England Journal of Medicine.

Syringes filled with COVID-19 vaccines are on a table.
Moderna Vaccine
Doses of the Moderna COVID-19 vaccine are ready to be administered to airmen of the 163d Attack Wing, California Air National Guard, at March Air Reserve Base, Calif., Jan. 9, 2021. Military members can receive the vaccine voluntarily, and the initial doses have been prioritized for airmen on the front lines of the COVID-19 pandemic response.
Credit: Air Force Master Sgt. Julianne M. Showalter
VIRIN: 210109-Z-RZ465-2044


Persistent symptoms lasting beyond recovery from the acute respiratory symptoms have baffled scientists, but until now were believed to be a result of direct damage to nerve cells.

Knowing COVID-19 could potentially cause inflammation in and around blood vessels elsewhere in the body, according to other studies, the researchers took a closer look at the brains of 13 patients who died from COVID-19. With high-resolution MRI scanning of brain tissues obtained from these patients, the researchers identified focal hyperintensities, which corresponded to small blood vessels showing evidence of inflammation and damage to their walls. Damage to these vessels included leakage of a protein, fibrinogen, from the blood into adjacent brain regions. Despite using very sensitive techniques, the researchers were not able to detect significant levels of SARS-CoV-2, the virus that causes COVID-19, in the brains of the cases they studied — and they found very little evidence of damage to nerve cells.

An airman loads a syringe with the Moderna COVID-19 vaccine.
Vaccination Preparation
A 133rd Medical Group member prepares a syringe with the Moderna COVID-19 vaccine in St. Paul, Minn., Jan. 8, 2021. Airmen from the 133rd Airlift Wing received their first dose of the Moderna COVID-19 vaccine.
Credit: Air Force Tech. Sgt. Amy M. Lovgren
VIRIN: 210108-Z-LY731-1023C

Also of significance, the brains of the patients studied were mostly from people who died without being hospitalized for the disease. Prior studies have mostly looked at patients who endured lengthy hospitalization, including being on ventilators. Such factors could make it difficult to interpret the direct effects the virus has on the brain and the consequences that lengthy hospital stays can have on the body, explained Dr. Dan Perl, a professor of pathology at USU and director of the USU Brain Tissue Repository.     

"COVID-19 seems to have a propensity to damage small blood vessels in the brain, rather than the nerve cells themselves," Perl said. "While it was tempting to connect our findings of specific brain locations of involvement to specific clinical manifestations, the cases examined had very little associated clinical information. So this could not be done."

An airman vaccinates a fellow airman.
First Dose
Air Force Airman 1st Class Helyena Schmite, a medical technician with the 116th Medical Group Detachment 1, administers the first of two doses of the new COVID-19 vaccine at Robins Air Force Base, Ga., January 10, 2021. Airmen from the 116th Air Control Wing volunteered to receive the COVID-19 vaccination to safeguard Georgia National Guardsmen and to maintain the highest standards of readiness to ensure rapid response to the needs of the state and nation.
Credit: Air Force 1st Lt. Dustin Cole
VIRIN: 210110-Z-WH753-1006A

"These findings address important concepts for understanding the acute and persistent neurologic manifestations of COVID-19. The pandemic is raging in both civilian and military populations and producing considerable mortality and long-term effects among those who have recovered from the infection. The results are of interest and importance to both communities," Perl added.

The study was a collaboration between USU, the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, the University of Auckland in New Zealand, the University of Michigan, the Joint Pathology Center, the New York University School of Medicine and the University of Iowa. To read the full study, visit: https://www.nejm.org/doi/full/10.1056/NEJMc2033369.

(Sarah Marshall is assigned to the Uniformed Services University.)

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