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Long COVID Brings Focus to Mental-Physical Connection

Scientists and providers seek to understand increased psychiatric health issues post-infection

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Written by Debra Melani on May 23, 2024
What You Need To Know

In recognition of Mental Health Awareness Month, the CU Anschutz newsroom is highlighting some of the ways our campus faculty conduct research, provide patient care and extend support around mental health.

While the pandemic left millions of people worldwide with lasting COVID-19 effects, it also fueled a research and healthcare focus that Thida Thant, MD, and colleagues have long promoted – the overlap of physical and mental illness.

Some surveys suggest as many as a quarter of the 775 million-plus people infected with SARS-CoV-2 had lingering symptoms at three months out, a phenomenon coined long COVID and now ranked a top research priority in the country. Many of those cases (some studies suggest a majority) included neurological and/or mental health issues.

“I was glad to see a stronger focus on that mind-body connection, the understanding that you could have a psychiatric symptom or illness develop as the result of a physical illness,” said Thant, a psychiatrist who specializes in the intersection between chronic disease and mental illness. “And not just in the coping sort of a way, but directly, as a physiologic result.”

The link between mental illness and long COVID is not novel, said Thant, an assistant professor of psychiatry at the University of Colorado School of Medicine. There are mental health connections between heart disease and other respiratory viral illness.

“But historically, there’s always been this sort of divide, and long COVID has really taught us all that that overlap is there,” said Thant, who works with patients at the UCHealth Post-COVID clinic and is the director of the Psychiatric Consultation for the Medically Complex Program at the CU Anschutz Medical Campus.

Thant, who recently joined colleagues in publishing guidance on treating long COVID mental health disorders for the American Psychiatric Association, shared more about the issues she sees in practice in the Q&A below.

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The data appear clear that people are more likely to develop mental health disorders in the months following a COVID infection. Is that correct, and if so, what have we learned about why?

Yes, that definitely happens. The why is still more complicated. There are different hypotheses. A major one involves the inflammatory process and that relationship with viruses and mental illness. There have been lots of folks who have gone for years dealing with other post-viral issues, whether mental- or physical-health related (from flu, Epstein-Barr, measles, etc.). We know that inflammation is also associated with mental health in general.

(Inflammation of the brain can cause confusion, difficulty concentrating and memory problems along with potentially more severe issues, such as depression, anxiety and even psychosis, causing people to see and hear things that aren't there and to believe things that aren't true.)

The mechanism can depend a bit on your illness. They’ve been talking a lot about serotonin recently and serotonin deficiencies. They have been testing things like residual serotonin in the gut, and so there’s a question about the gut-brain connection. There’s likely an association there.

(Scientists suspect COVID-19 could compromise the diversity of bacteria and microbes in the gut, which have been shown to produce such neurotransmitters as serotonin and dopamine. Disruption of these mood-regulating neurotransmitters, therefore, could be a basis of some neuropsychiatric issues.)

For ICU patients, there are other players that we know contribute to these symptoms: things like all the medications they get while in the ICU, delirium, being intubated – we know that these can cause things like PTSD symptoms, depression, physical debilitation, cognitive problems. So folks who were in the ICU with COVID, it’s sort of a double hit for them.

What mental health conditions can COVID trigger?

We see a wide range. I see a lot of depression and anxiety after COVID. And that can be either folks who already had it and it got worse after they had a COVID infection or folks who never had depression or anxiety, and it’s brand new. I’ve seen both, where I wonder if it’s a direct neurologic kind of impact, or neuropsychiatric kind of depression or anxiety.

And there’s trauma, which we’re working on a paper about now. We do see PTSD in patients with long COVID. Especially in the early waves with a lot of those folks who thought they might die in the hospital. And I see people who had problems breathing, so any time they are feeling short of breath, they are re-triggered by that.

Then there are the symptoms that cross multiple specialties (neurology, psychiatry), such as brain fog, or cognitive impact. They can look very different, too. For some people, it’s memory issues. Some people, they just can’t focus. Some folks, it’s all of the above. Sleep problems are common.

Suddenly being hurled into a dark depression or other psychiatric disorder, which we know can happen with any COVID infection, must be confusing, even terrifying for some patients.

Yes, that’s probably a lot of people who come to see me. I’ve had some folks where it didn’t last long, but it was really scary. Or some people who say yeah, I’ve had long-term depression, but it had been controlled for many years before I got COVID. So it does seem to trigger something. There is some aspect of the infection that has this connection with the mental health symptoms.

And, yes, studies are saying that it doesn’t have to be tied to severity of your COVID infection. We don’t fully understand why you can have someone with a mild infection develop long COVID symptoms.

That’s why people are looking again at the serotonin connection, the pathways of tryptophan and what does it mean to have residual serotonin. I have sometimes used SSRIs (selective serotonin reuptake inhibitors, such as Prozac) in long COVID patients. So the question is: Am I treating a major depressive episode? Or am I treating some serotonin deficiency with long COVID?

What’s the longest long COVID patient you’ve seen?

There are some folks from the early days (four years ago) who are still having some symptoms. They are definitely better than when they first came to our program, but they are not back to where they were pre-infection. But most of my patients are about six months.

Does having a past mental health issue increase the risk of problems with a COVID infection?

Yes, if you already had a mental health history like depression or anxiety, that puts you at higher risk. And in some of my folks, this is anecdotal, but I tend to see that associated with longer recovery times, too, if they already had pre-existing history vs. folks who truly had nothing.

But then with a lot of people who come in and talk to me, we discover that it’s not that you didn’t have anything. It was just manageable and subclinical. You may have had mood changes or anxiety before your COVID infection, but it wasn’t causing problems. But with your COVID infection, it tipped over now to something that’s impairing and causing problems in your life.

Is there any association between substance use and long COVID?

It’s been flagged as a potential risk factor. I’m part of a research grant where we’re evaluating this, primarily in ICU patients, but we’re looking at those who had a history of alcohol use and whether that affected their outcome respiratory-wise (previous studies have suggested a link between alcohol use disorder and increased death rate from COVID infection). That’s a big question.

Does long COVID increase suicidal thoughts?

I don’t actually see it a lot in my clinic, but something that got a lot of media attention was new-onset psychosis after COVID infection. Psychosis and suicidal ideation do happen, and it’s really scary, but they are pretty rare. A lot of those patients get treated in an in-patient psychiatric setting or in ER settings. It’s not as common as people who have depression, anxiety and trauma without suicidal thoughts.

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Thida Thant, MD