Public Health

Long COVID and the brain: Neurological symptoms may persist

Jennifer Lubell , Contributing News Writer

Neurological effects of post-acute sequelae SARS-CoV-2 infection (PASC)—or long COVID—poses a conundrum for physicians. How it manifests is unclear and finding effective treatments may be an exercise of trial and error.

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Symptoms may never go completely away, but studies suggest that a patient’s health should improve over time, noted John Vasudevan, MD, associate professor of clinical physical medicine and rehabilitation at Penn Medicine in Philadelphia. Dr. Vasudevan spoke on neurological sequelae in long COVID during an education session at the 2022 AMA Interim Meeting in Honolulu.

“We don't have all the answers, but the more you consider the emerging evidence, the more we can help our patients,” Dr. Vasudevan said.

Origins of neurological symptoms may occur when the virus finds its way to the ACE2 receptor, inhibiting mitochondrial function and nitric oxide synthesis.

“These receptors are less dense in neural tissues, so a majority of neurologic injury may be a  consequence of damage to other systems,” such as the cardiovascular system, said Dr. Vasudevan, adding that some experts posit that viral fragments could potentially linger within the neuron like a herpes infection, causing dysfunction to the neuron.

Fatigue, headache, and brain fog are the most common neurologic symptoms of long COVID. In fact, according to a study from the University of California, San Diego (UCSD), at six months, 68.8% of patients experienced memory impairment. Meanwhile, 61.5% experienced decreased concentration.

“There can also be persistent loss of taste and smell lasting well after the infection,” said Dr. Vasudevan. Skin biopsies may be considered to identify autonomic dysfunction or signs of small fiber neuropathy.

Risk factors include age, comorbidities, hypertension, nonwhite race, preexisting neurologic disorders, female sex, and severity of the initial infection.

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At baseline, physicians should exclude other potential causes for symptoms that would cause fatigue, or some other easily measurable and correctable problem. Treatment is often targeted toward the patient’s symptoms.

“We're physicians, so we understand how to appropriately use medications on a trial and error basis,” monitoring regularly for regression.  Treatment should be focused simultaneously on physical and psychological aspects of the disease, Dr. Vasudevan said, emphasizing that “you're missing half the picture if you're not talking about both.”

Forty percent of patients will screen positive for anxiety or depression, which may be a chicken-egg situation—whether this is a direct effect of the syndrome or people are just frustrated with how it's interfering with their life.

“You must address it. Don't forget to incorporate neuropsychology, speech, and language pathology,” he said.

Patients wanting to return to sports or fitness should be treated in a similar manner to those with post-concussive syndrome.

Physicians will likely have to try several medications until something works, said Dr. Vasudevan. But “just like anything, start low, and go slow. Don't forget non-pharmacologic treatment such as compression garments for patients with dysautonomia, or olfactory training for those with loss of smell.”

Experimental trials are taking place on low dose naltrexone, “but there's not enough to conclude anything on that right now,” said Dr. Vasudevan.

He also noted that vaccinations don’t prevent you from getting COVID, but there is evidence suggesting it may reduce PASC incidence by 8.8% and prevalence at three months by 12.8%.

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It is important for physicians to try to ease their patients’ suffering the best they can, Dr. Vasudevan said. “You have to be honest with your patients while working through it with them.”

UCSD researchers determined that 80% of patients with long COVID reported only mild to moderate initial disease, with only 9% being hospitalized. However, many sufferers experienced improvement by six months from symptoms onset.

Based on these findings, physicians may counsel such patients to reassess for changes by the six-month mark, said Dr. Vasudevan.

“We need to establish many more multidisciplinary, multi-centered consensus on the diagnostic criteria for this neurologic component,” he said, noting “a lot of the data is just emerging and requires constant vigilance and collaboration.”