Ann Hui Ching

In a recent study, Yale researchers ruled out potential causes for neurological and psychiatric symptoms of long COVID, offering more clarity on an opaque field. 

According to Hailey Reister, a postgraduate researcher associated with the study, a significant proportion of people who suffer from long COVID endure neuropsychiatric symptoms, such as the loss of the senses, memory loss and brain fog. In their study, the researchers investigated two potential causes of these symptoms: neuroinflammation, the brain’s immune response, which leads to the inflammation of nervous tissue, and dysfunction of the blood-brain barrier, a layer of blood cells that keeps harmful substances from entering the brain.

By comparing patients who suffered from neuropsychiatric symptoms of long COVID and those who were never infected with COVID-19, the researchers found that neuroinflammation and blood-brain barrier dysfunction are not the causes of neuropsychiatric symptoms.

“I think [our research] really suggests that strategies aimed at reducing brain inflammation are really unlikely to work for people who are suffering from these types of symptoms,” said Sheli Farhadian, lead author of the study and a professor of infectious diseases at the School of Medicine.

Long COVID refers to the variety of new or returning symptoms that people experience after their initial COVID-19 infection. According to Reister, the research team knew that many patients struggled with neuropsychiatric symptoms, though their precise causes were unclear.

So, the team sought to examine why these symptoms occurred, starting with neuroinflammation.

“We knew that [people with] other infectious diseases, who have similar symptoms to what people experience with long COVID, do have neuroinflammation,” Reister told the News. “We were wondering if long COVID’s neuropsychiatric symptoms were similar to people who have these symptoms with other infectious diseases.”

For Farhadian, the cerebrospinal fluid, or CSF, is the best place in the body to determine the presence of dysfunction and inflammation because it can travel across the central nervous system. By tracking CSF, the team analyzed its immunoglobulin production and white blood cell ratio, which indicate the amount of brain-blood barrier dysfunction and neuroinflammation, respectively. 

The team obtained the CSF from two groups. The first group included samples of patients with long COVID. The second group was the control group, which had samples from patients who volunteered to participate in other studies before the initial outbreak of COVID-19. 

“Both of the groups consented to a lumbar puncture [near the bottom of the back] to draw blood for analysis … and their blood samples were stored in freezers [for further analysis],” said Lindsay McAlpine, a lead investigator of the study and an Instructor in the Division of Neurological Infections and Global Neurology.

Then, the researchers compared the levels of the different markers for infection. 

Both groups’ white blood cell ratio and immunoglobulin production did not significantly increase, indicating a small infection of the nervous system.

“If there was an infection in the nervous system, it can get in there by blood-barrier breakdown. And inflammation is another way to say that the body is fighting an infection.” Reister said. 

Nevertheless, Riester said that the study had its limitations. Many patients in the experiment group were young white women, while there was a higher proportion of older men of color in the control group. 

Still, with little difference between the two groups’ results, Farhadian, and his team concluded that inflammation and dysfunction aren’t causes of neuropsychiatric symptoms of long COVID.

“Negative results in science are underpublished. But this is still pretty important in the field of Long Covid because we won’t be going down a pathway where there are no answers,” McAlpine said. 

McAlpine said that she hopes that their study will help guide other researchers to study other causes that are actual contributors to these neuropsychiatric symptoms.

As of September 2023, 6.9 percent of Americans have long COVID, according to the CDC.