While many people think of Covid-19 as a disease that primarily affects patients' respiratory systems, research suggests many Covid-19 patients experience some form of neurological symptoms, as well—with one recent study finding nearly a third of hospitalized Covid-19 patients experienced altered mental function.

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How Covid-19 affects the brain

For the recent study, published this month in the Annals of Clinical and Translational Neurology, researchers examined the neurologic functions of 509 Covid-19 patients hospitalized at Northwestern Medicine's hospital network and found that 82.3% experienced neurological symptoms at some point while ill. According to the researchers, the most common neurological symptom was muscle pain, which was present in 44.8% of the patients, followed by headaches, present in 37.7% of the patients.

The researchers also found that 31.8% of the patients experienced altered mental function, or encephalopathy. Igor Koralnik, a senior author of the study and chief of neuro-infectious disease and global neurology at Northwestern, explained that encephalopathy "is a generic term meaning something's wrong with the brain," and it can include attention or concentration problems, short-term memory loss, disorientation, stupor, and "profound unresponsiveness."

Koralnik added that "[e]ncephalopathy was associated with the worst clinical outcomes in terms of [patients'] ability to take care of their own affairs after leaving the hospital, and we also see it's associated with higher mortality, independent of severity of their respiratory disease."

Patients with encephalopathy in the study were more likely to be older, male, and have underlying medical conditions, according to the study. But in general, younger patients in the study were more likely to develop neurological symptoms aside from encephalopathy than older patients, the researchers found.

Avindra Nath, a senior investigator of nervous system infections at NIH's National Institute of Neurological Disorders and Stroke, said that finding was surprising. "While it is not unexpected that the sickest patients would have the most neurological complications, it is surprising that these manifestations occur more commonly in younger individuals and is independent of the severity of respiratory involvement," Nath said.

Other reports have highlighted similar neurological complications in Covid-19 patients, including one recent study from France, which involved 120 patients hospitalized with Covid-19. According to that study, 34% of the patients experienced memory loss and 27% had problems concentrating months after they had initially developed Covid-19.

In addition, the New York Times reports that a separate survey of 3,930 members of Survivor Corps, a group of Covid-19 survivors, that will be released soon found more than half of the respondents reported having difficulty concentrating or focusing since they had developing Covid-19, according to Natalie Lambert, an associate research professor at Indiana University School of Medicine who helped lead the survey.

Rick Sullivan, a Covid-19 survivor, told the Times that the neurological symptoms he faces are "debilitating."

"I become almost catatonic," he said. "It feels as though I am under anesthesia."

Similarly, Lisa Mizelle, an NP who was diagnosed with Covid-19 in July, told the Times that she sometimes forgets routine treatments and lab tests, and she frequently has to ask her coworkers about terms she used to easily remember.

"I leave the room and I can't remember what the patient just said," Mizelle said. "It scares me to think I'm working," she added. "I feel like I have dementia."

What causes neurological symptoms in Covid-19 patients?

Experts aren't entirely certain what causes neurological symptoms in Covid-19 patients, but leading theories suggest the effects could be related to the body's immune response to the novel coronavirus, which cause Covid-19.

"The simplest answer is people still have persistent immune activation after the initial infection subsided," Nath said.

Serena Spudich, chief of neurological infections and global neurology at Yale School of Medicine, explained that molecules released during an immune response "can also be sort of toxins, particularly to the brain."

Blood vessel inflammation also could be a culprit for Covid-19 patients' neurological symptoms, Spudich said.

For instance, inflammation elsewhere in the body, such as the lungs, might release molecules that make a patient's blood stickier and clog blood vessels, which could lead to strokes, the Times reports.

Michael Zandi, a consultant neurologist at the National Hospital for Neurology and Neurosurgery in Britain, explained, "There's no need for the brain cells themselves to be infected for that to occur."

And Dona Kim Murphey, a neurologist and neuroscientist, said small strokes could cause some of the neurological symptoms in Covid-19 patients. Murphey, herself, has experienced neurological symptoms from Covid-19, including so-called "alien hand syndrome." Murphey said she felt a "super-bizarre sense of [her] left hand, like [she] didn't understand why it was positioned the way it was and [she] was really captivated by it."

A recent study that has yet to be peer-reviewed also may offer some insight. For the study, researchers looked at infection from the novel coronavirus in the brain tissue of a deceased Covid-19 patient, in a mouse model, and in organoids (or brain-cell clusters in a lab dish). The researchers found that the virus invaded brain cells so it could multiply, but the pathogen didn't destroy the cells. Instead, it used up oxygen in nearby cells, which in turn killed those cells and could lead to strokes.

The researchers did not, however, find evidence of an immune response to this infection.

"It's kind of a silent infection," Akiko Iwasaki, an immunologist at Yale University and the leader of the study, said. "This virus has a lot of evasion mechanisms."

According to Alysson Muotri, a neuroscientist at the University of California-San Diego, the novel coronavirus also appears to quickly decrease the number of synapses—which are the connections between neurons—in the brain.

"Days after infection, and we already see a dramatic reduction in the amount of synapses," Muotri said. "We don't know yet if that is reversible or not."

But overall, Iwasaki said that infections of the novel coronavirus in the brain appear to be even more deadly than respiratory infections of the virus. "If the brain does become infected, it could have a lethal consequence" (Belluck, New York Times, 10/11; Ortiz, USA Today, 10/6; George, MedPage Today, 10/6; Belluck, New York Times, 10/5; Mandavilli, New York Times, 9/9).