Study: A Third of COVID Patients Develop Neuropsychiatric Symptoms

Some COVID-19 patients have reported experiencing psychotic symptoms weeks after their initial infection. And now researchers say the development of these symptoms may be more common than previously thought.

According to new research published in JAMA Psychiatry, as many as one-third of COVID-19 patients have long-term neuropsychiatric symptoms, including psychosis and anxiety. Researchers believe that the symptoms could be the result of how the virus itself damages the brain, rather than of a lack of oxygen related to COVID-19's impact on the lungs.

COVID-19-Related Psychosis

Researchers were especially concerned about the development of psychosis—a mental disorder characterized by a disconnection from reality—in some patients. “Some [patients] are saying, 'I’m having paranoid feelings or I’m noticing my mind playing tricks on me' or 'I think I’m seeing things or I’m hearing things that aren’t there,'” Roger McIntyre, MD, a professor of psychiatry and pharmacology at the University of Toronto and CEO of AltMed, tells Verywell. “This is definitely coming out, and I’m not surprised given the magnitude of the effect that [COVID-19] is having on people’s brains.”

A retrospective study recently published in The Lancet Psychiatry looked at the electronic health records of more than 200,000 patients with confirmed COVID-19.

The researchers found that in the six months after a COVID-19 diagnosis:

• 34% of patients received a neurological or psychiatric diagnosis
• 17% received a diagnosis for anxiety disorder
• 1.4% were diagnosed with a psychotic disorder

How COVID-19 Harms the Brain

Neuropsychiatric symptoms can appear before, during, and after the respiratory symptoms of COVID-19, which has led researchers to believe that SARS-CoV-2, the virus that causes COVID-19, can cause brain damage that is unrelated to oxygen deprivation.

Direct Damage to Cells

Researchers are still trying to figure out how SARS-CoV-2 enters the brain, after having discovered the virus in various brain spaces and regions. 

“The COVID-19 virus is now established as being capable of entering the human brain,” McIntyre says. “It’s an RNA virus that has a very robust capability of penetrating brain tissue."

Other viruses, like HIV, can also cause direct brain damage. "We have a long history, in a large amount of literature, that has shown that viruses when they enter the brain, can cause significant problems to brain function," McIntyre says.

Once it's in the brain, the SARS-CoV-2 virus enters endothelial cells through angiotensin-converting enzyme 2 receptors and damaging them, driving inflammation and other brain-damaging processes in the body.

Cytokines

Damage to the brain could also be related to the immune response developed by the body in response to the virus.

“We know that cytokines, which are molecules produced by your immune cells, do good things. They get rid of viruses," McIntyre says. "But the problem is they can do some collateral damage. They can actually jeopardize the brain cell function and the brain cell structure. And what happens then is you begin to see neuropsychiatric symptoms.”

According to the JAMA article, once the cytokines cross the blood-brain barrier, they activate glial cells, which then secrete inflammatory mediators that boost receptor sensitivity and potentially induce cognitive issues—even hallucinations.

Inflammation can also lead to diminished neurotransmitter release and stunted neurotransmission, which could cause changes in mood.

Blood Clots

When the SARS-CoV-2 virus enters the brain’s endothelial cells and drives inflammation, it also encourages the production of thrombin, an enzyme in blood plasma that can cause blood clotting. McIntyre says that this is a "direct toxic effect of the virus."

Cytokines can also increase blood clots in your brain. "Then, what the inflammation can do is cause a lot of swelling because the blood vessels get very leaky," McIntyre says. "All that taken together can cause a lot of problems.”

Drug-Induced Psychosis

While it's not related to direct brain damage, there are some treatments used in some people with COVID-19 that can cause neurological symptoms—even psychosis.

“Steroids have been benefiting people with COVID, reducing, for example, mortality, or reducing the need for them to be intubated going to the ICU. This is all good news,” McIntyre says. "[But] there are side effects. And one of the side effects of steroids in some people is that they can cause psychosis.”

McIntyre adds that steroid-induced psychosis usually resolves once someone is no longer on the medication.

Worsening Existing Mental Illness

The COVID-19 virus can not only bring on new neuropsychiatric symptoms (such as anxiety, depression, or psychosis) but also has the potential to worsen existing mental health symptoms.

“People who already have a preexisting or previously declared mental illness are at greater risk of decompensation—[or the failure to generate effective psychological coping mechanisms]—during this time,” McIntyre says. “To make matters more complicated and concerning, if you have a diagnosis of depression or bipolar, not only are you at greater risk of decompensation during this time but also you are at a greater risk of contracting, being hospitalized with, and dying from COVID-19.”

What to Watch For

McIntyre says there are some warning signs to watch for. Some symptoms like fatigue, insomnia, and changes in appetite are common when a person is sick with COVID-19 as well as during their recovery. However, other symptoms are red flags—such as suicidal thoughts or feelings of apathy toward life.

You should also watch for signs of paranoia—which might feel like your mind is playing tricks on you. 

“What is also important, is when somebody is finding that the symptoms that we’re describing are really beginning to interfere with their day-to-day function," McIntyre says. "That is an indication to me that that person should probably speak to a care provider.”

How Symptoms Can Manifest

Wilfred van Gorp, PhD, a past president of the American Academy of Clinical Neuropsychology and a practicing psychologist in New York and Chicago, tells Verywell that he’s seeing patients with a variety of post-COVID-19 neuropsychiatric symptoms. 

One example van Gorp describes is a patient who developed personality changes. “All of a sudden with COVID, he was having flying-off-the-handle arguments with his spouse—a short fuse,” van Gorp says. 

Another of van Gorp’s patients is a physician who is experiencing slow-processing speeds and memory impairment. “She said—'You know, I have to make split-second life-and-death decisions in the operating room. Now I can’t decide between a ham and a corn beef sandwich,’” van Gorp says.

Neither of these two patients required hospitalization for their COVID-19 symptoms. “It can happen to people who are not, by some yardsticks, with severe illness,” van Gorp adds.

He believes that his patient's symptoms are related to either direct brain damage or damage from inflammation by the COVID-19 virus.

For his patient who is a physician, van Gorp says that “if there’s an interruption of oxygen to the brain, that obviously causes impairment, but she’s not had that. She’s not had a known stroke. She’s not had cardiac arrest where she would have hypoxia. She had none of the other things that could cause brain impairment."

In the absence of any clear cause, van Gorp says what he's left with is a "diagnosis of exclusion.”

What Will Treatment Look Like?

Although treating neuropsychiatric symptoms resulting from COVID-19 is a relatively new frontier, van Gorp says that the terrain feels somewhat familiar.

“People with concussions have similar manifestations,” van Gorp says. "They have neuropsychiatric changes where they’re short-tempered, they’re kind of overly emotional, they have slow speed of processing. It reminds me a lot of these long-term post-COVID patients.”

Right now, treatment for some post-COVID-19 neuropsychiatric issues consists of treating the symptoms. Someone who is experiencing fluctuations in mood might benefit from a mood stabilizer, for example.

“We’re dealing with a biologically-related phenomenon,” van Gorp says. “It’s not that he’s an irrational person by nature. This is an acute change in his personality based upon a brain illness.”

For now, van Gorp is treating his patient's symptoms and taking a wait-and-see approach with ongoing monitoring. In other instances, he's seen neuronal damage occur and repair itself; therefore, he's optimistic that his patients will improve. 

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