Study sheds new light on severe COVID's long-term brain impacts

Brain fog and more

Lisa Schnirring

More than a year after COVID-19 hospitalization, many patients have worse cognitive function than those who weren't hospitalized, a symptom that comes with reduced brain volume and brain injury markers on blood tests, according to a new study, the largest of its kind in the United Kingdom.

The multicenter study from the COVID-CNS Consortium included 351 patients who were hospitalized for COVID and 2,927 matched controls. The researchers, led by a team at the University of Liverpool and King's College London, published their findings in Nature Medicine.

Looking for brain-fog markers

Study goals included understanding biological causes and long-term outcomes of neurologic and neuropsychiatric complications following COVID hospitalization. Researchers tested participants' cognitive skills and examined findings from brain scans and blood tests 12 to 18 months after hospitalization. 

Greta Wood, MBBS, first author of the study and an academic clinical fellow in infectious diseases at the University of Liverpool, said in university press release that many patients hospitalized with COVID report persistent symptoms, often called "brain fog."

"However, it has been unclear as to whether there is objective evidence of cognitive impairment and, if so, is there any biological evidence of brain injury; and most importantly if patients recover over time," she said.

Cognitive deficits resembled 2 decades of aging

Of the patients hospitalized for COVID, some did and some didn't have new neurologic complications. The researchers found that both groups had worse cognition than expected for their age, sex, and level of education.

One of the most striking findings was that post-COVID deficits in hospitalized patients look similar to 20 years of normal aging. The team also found that people who had been hospitalized with COVID had reduced brain volume in key areas and abnormally high levels of brain injury proteins in their blood.

The team saw the greatest deficits in people who had the most severe infections, had post-acute psychiatric symptoms, and had a history of encephalopathy. 

In a promising finding, longer-term follow-up of 106 patients pointed to a trend toward recovery.

Could other severe infections cause similar problems?

Benedict Michael, MBChB, PhD, the study's corresponding author and professor of neuroscience at the University of Liverpool, said COVID isn't just a lung condition, and some of the most severely affected patients are those who have brain complications. 

That the cognitive impairments occurred alongside brain-cell injury markers and reduced brain volume on magnetic resonance imaging suggest there may be measurable biomechanisms, he said. "Now our group is working to understand whether the mechanisms that we have identified in COVID-19 may also be responsible for similar findings in other severe infections, such as influenza."

Gerome Breen, PhD, a study author and psychiatric geneticist with King's College London, said the work might be helpful for guiding similar studies of patients with long COVID who had milder respiratory symptoms who also report brain fog and for the development of treatment strategies.