Long COVID 'Brain Fog' Confounds Doctors, but New Research Offers Hope

Sara Novak

July 03, 2023

Editor's note: Find the latest long COVID news and guidance in Medscape's Long COVID Resource Center.

Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.

She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can't remember basic aspects of her job. She can't tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.

Whitley doesn't like the term "brain fog" because it doesn't begin to describe the dramatic disruption to her life over the past 7 months.

"I just can't think anymore," she said. "It makes you realize that you're nothing without your brain. Sometimes I feel like a shell of my former self."

Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn't truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.

"There's not a lot of imprecision in the term because it might mean different things to different patients," said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University School of Medicine and author of a new book, Clearing the Fog: From Surviving to Thriving With Long COVID ― A Practical Guide.

Jackson, who began treating Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn't occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.

Even among those with milder cases of acute COVID, there's some evidence that persistent neuro-inflammation in the brain caused by an activated immune system may also cause damage.

In both cases, the results can be debilitating. Whitley also has dysautonomia — a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.

She said that she's so forgetful that when she sees people socially, she's nervous of what she'll say. "I feel like I'm constantly sticking my foot in my mouth because I can't remember details of other people's lives," she said.

Although brain disorders such as Alzheimer's disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.

"With a brain injury, you're doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different," said Jackson.

Additionally, ABI is an actual diagnosis, whereas brain fog is not.

"With a brain injury, there's a treatment pathway for cognitive rehabilitation," said Jackson.

Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Jackson said that while many patients aren't functioning cognitively or physically at 100%, they can make enough strides that they don't have to give up things such as driving and, in some cases, their jobs.

Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.

Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.

Calling it a "fog" makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the Department of Psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.

"The COVID virus is very invasive to the brain," Bell said.

Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina School of Medicine's COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it's reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.

Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.

Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.

Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.

"It will make a big difference once we have some consistency among clinicians in diagnosing the condition," said McComsey.

Whitley is thankful for the treatment that she's received thus far. She's seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don't feel overwhelming. She's back behind the wheel and back to work.

But perhaps most importantly, Whitley joined a support group, led by Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.

"Talking to other survivors has been the only solace in all this," Whitley said. "Together, we grieve all that's been lost."


Kate Whitley, long COVID patient

JAMA Network, "Prevalence and Correlates of Long COVID Symptoms Among US Adults," October 2022.

James C. Jackson, PsyD, director of Long-Term Outcomes at the Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center at Vanderbilt University Medical Center.

Oxford Open Immunology, "Long Covid brain fog: a neuroinflammation phenomenon?" September 2022.

Nature, "SARS-CoV-2 is associated with changes in brain structure in UK Biobank," April 2022.

SN Comprehensive Clinical Medicine, "Brain fog as a Long-term Sequela of COVID-19," November 2022.

Tyler Reed Bell, PhD, a fellow in the Department of Psychiatry at the University of California, San Diego.

Karla L. Thompson, PhD, lead neuropsychologist at University of North Carolina School of Medicine COVID Recovery Clinic.

Grace McComsey, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio.

Stanford News Center, "Researchers identify biomarkers associated with chronic fatigue syndrome severity, " July 2017.


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