1 in 3 Covid-19 patients are diagnosed with a neuropsychiatric condition in the next six months, large study finds

Six months after being diagnosed with Covid-19, 1 in 3 patients also had experienced a psychiatric or neurological illness, mostly mood disorders but also strokes or dementia, a large new study shows.

About 1 in 8 of the patients (12.8%) were diagnosed for the first time with such an illness, most commonly anxiety or depression. Compared to control groups of people who had the flu or other non-Covid respiratory infections, first-ever neuropsychiatric diagnoses were almost twice as high.

The study, published Tuesday in The Lancet Psychiatry, used real-world health data on millions of people to gauge the incidence of 13 brain disorders. Anxiety, mood, and substance use disorders were most common, but the researchers also found worrying, if lower, rates of serious neurological complications, especially in patients who had been severely ill with Covid-19. In all Covid-19 patients, 0.6% developed a  brain hemorrhage, 2.1% an ischemic stroke, and 0.7% dementia. 

“We need urgent research to better understand how and why does this occur in patients with Covid-19 and how they can be treated and [how to] prevent it,” Max Taquet, a clinical fellow in psychiatry at the University of Oxford and a study co-author, said on a call with reporters on Tuesday. “But we think that regardless of the explanation, health services need to be prepared for the increased demand that this data is showing.” 

The size of the study lends confidence to its findings, which confirm what has been hinted in smaller studies, including earlier work from the Oxford group. The researchers analyzed electronic health records of 81 million U.S. patients (both insured and uninsured), finding 236,379 people who had been diagnosed with Covid-19 and comparing them to three cohorts of similar people: one cohort had the flu, another had another respiratory illness such as sinusitis or pneumonia, and one cohort included people who were hospitalized for unrelated conditions such as bone fractures or gallstones. The researchers hoped that comparing the Covid group to the others would help isolate Covid-19 as a cause and tease out its effects on the brain. 

After accounting for patients’ age, sex, ethnicity, and existing health conditions, patients overall had a 44% higher risk of neurological and mental health diagnoses after Covid-19 than after flu, and a 16% higher risk after Covid-19 than after other respiratory tract infections. 

There were two exceptions: The researchers did not see increased risk of Parkinson’s disease, a movement disorder, or Guillain-Barré syndrome, which is a rare disorder that shows up after some viral infections as tingling and weakness when the immune system attacks nerves.

Allison Navis, assistant professor in the division of neuro-infectious diseases at the Icahn School of Medicine at Mount Sinai, sounded a note of caution. The lead clinical neurologist at Mount Sinai’s post-Covid clinic, she was not involved in the Lancet study.  

“It does highlight that there is something unique going on with Covid,” she told STAT. “And the 12.8% who have a new diagnosis of something neuropsychiatric can sound very sensational. That 12.8% encompasses depression and anxiety, so it’s extremely important to not minimize that and not make that sound like a lesser diagnosis at all, but the more severe things like strokes are still fairly uncommon. I don’t want people thinking that 1 in 10 people get a stroke with Covid.”

The new study reinforces previous research that showed some brain disorders increased with the severity of illness, going up in people who needed to be hospitalized and rising further in people who needed intensive care. While 33.6% of people developed a neuropsychiatric illness overall, that risk grew to 46.4% among Covid patients treated in an ICU.

What’s new is the distinction between neurological and psychiatric complications. People with very severe Covid-19 had a higher risk of complications like stroke or dementia, but people who developed anxiety or depression spanned the spectrum of illness severity. 

While the study did not examine the mechanisms that might explain neuropsychiatric disorders associated with the virus, the authors did speculate in the call with reporters that if patients know that they have Covid-19, that and other stressors might contribute to a psychiatric illness. “It could be psychological factors and biological factors and psychosocial factors, such as, for instance, the need to isolate and the loss of income as a result of that,” Taquet said. 

It’s easier to tie neurological disorders to the virus’ effects on the brain. Scientists believe the virus can enter the brain through the olfactory bulb, where taste and smell are decoded. Inflammation throughout the body also harms blood vessels in the brain, and can lead to stroke-causing blood clots, delirium, or dementia.

While the medical records could tell the researchers whether someone had previously suffered a stroke or been diagnosed with dementia, they couldn’t surmise whether someone was going to have a recurrence anyway or whether Covid-19 caused it, Masud Husain, professor of neurology and cognitive neuroscience at Oxford and a study co-author, warned. Longer follow-up will be needed to answer that question, but the signal was too strong to ignore, he said. 

Husain also cautioned that the numbers they reported could be an underestimate if they don’t include people who were infected with Covid but did not test positive for it, or if people had no symptoms that drove them to seek medical care. On the flip side, patients with Covid-19 might be more likely to have a neurological and psychiatric disorder diagnosed simply because they were receiving more medical attention compared to patients with the flu or other respiratory infections, Taquet pointed out.

This was not a study of long-Covid, said Paul Harrison, professor of psychiatry at the University of Oxford and a study co-author, referring to the constellation of lingering symptoms that overlap with some problems caused by the neuropsychiatric illnesses described in the current paper. But the need for more research and continued clinical care is the same.

“Sadly, many of the disorders identified in this study tend to be chronic or recurrent, so we can anticipate that the impact of Covid-19 could be with us for many years,” Jonathan Rogers and Anthony David of University College London wrote in a commentary appearing with the Lancet study.