“For healthcare workers, there are two issues,” he says. “One is the impact of [the] SARS-CoV-2 virus itself [on the] brain. The other is the stress of the COVID-19 pandemic, seeing patients die before their eyes. That causes post-traumatic stress disorder (PTSD). I think we need to monitor frontline healthcare workers even more closely [than patients], because the stress response in our body can actually harm the brain significantly.”

Loss of sense of smell (anosmia), “stroke, paralysis, cranial nerve deficits, encephalopathy, delirium, meningitis, and seizures are some of the neurological complications in patients with COVID-19,” Fotuhi and co-authors note. “There remains a challenge to determine the extent to which neurological abnormalities in COVID-19 are caused by SARS-Cov-2 itself, the exaggerated cytokine response it triggers, and/or the resulting hypercoagulapathy and formation of blood clots in blood vessels throughout the body and the brain.”

The article reviews neurological problems reported in COVID-19 patients and proposes a basic “NeuroCovid” classification scheme.

“Keeping accurate registries of COVID-19 patients with neurological deficits may enable us to establish plausible connections with aging-associated and neurodegenerative disorders, such as Parkinson’s disease, in the future,” the authors conclude. “Standardized evaluations, such as quantitative EEG (electroencephalogram), fluid biomarkers, cognitive evaluations, and multimodal neuroimaging can also lend insight to possible long-term neurological sequalae in COVID-19, such as depression, memory loss, mild cognitive impairment, or Alzheimer’s disease.”

Fotuhi is medical director of  NeuroGrow Brain Fitness Center in McLean, VA, and an affiliate staff member at Johns Hopkins Medicine in Baltimore. The paper identifies three distinct NeuroCovid neurological categories or stages.

In Stage I, the virus damage is limited to epithelial cells of nose and mouth. “The majority — 95% — recover without any problem,” he says. “These are the patients who are least likely to have long-term neurological problems.”

In NeuroCovid Stage II, patients may experience blood clots in their brain caused in part by an inflammatory immune response called the “cytokine storm.” This can result in mini-strokes that can cause cumulative neural damage.

“We can talk of large strokes the same way we do in patients that do not have COVID-19,” he says. “But when they have small strokes, the patient may have no symptoms, an MRI (magnetic resonance imaging) is not done, and no one knows what this patient has suffered. These patients, long-term, are likely to have depression, memory loss, and other neurological [problems].”

In NeuroCovid Stage III, there is damage to the blood-brain barrier, which protects the blood vessels of the brain, causing seizures or encephalopathy.

“The cytokine storm is so huge that it ruptures and damages the blood-brain barrier, such that the virus particles get inside the brain, along with the inflammatory markers,” Fotuhi says.

“When that happens, there is significant damage to the brain cells, and these are the patients that I think will have the highest degree of neurological issues in the future,” he adds.

There are blood tests to measure the intensity of the inflammatory immune response, which may be responsible for the relatively rare severe infections in younger people.

“It is the body’s own immune systems that harms the patient,” he says.

In healthcare workers, the neurological effects of COVID-19 could be compounded by the stress of fighting the pandemic.

“The more stressed you are, the more the part of your brain for memory — the hippocampus — shrinks,” Fotuhi says. “Frontline healthcare workers dealing with patients in dire situations experience an extreme amount of stress. The cortisol that is produced in response to stress indirectly harms the hippocampus. We need to monitor our healthcare workers dealing with COVID-19 patients closely. They may have secondary harm due to PTSD even if they don’t have the virus [itself].”

PTSD can harm areas of the brain affecting regulation of emotion, memory, and executive functions, he adds.

Overall, the basic measures to boost brain performance, regardless of patient history, include vigorous exercise, stress reduction, and eight hours of sleep nightly, he recommends.

REFERENCE

1. Fotuhi M, Mian A, Meysami S, Raji CA. Neurobiology of COVID-19. J Alzheimers Dis 2020;76:3-19.