Brain Fog and Chronic Fatigue Syndrome

June 15, 2021

Written by: Marissa Maroni

According to the Center for Disease Control and Prevention, up to 2.5 million Americans are struggling with Chronic Fatigue Syndrome (CFS)1. CFS can be caused by infection, physical or emotional trauma, and genetic or environmental factors1. The definition of CFS can vary, but it is generally defined as six months or more of fatigue that causes various impairments in cognition including difficulty concentrating and memory problems. Cognitive impairments are often described as “brain fog” but what exactly is brain fog? And what changes are occurring in your brain to cause this foggy feeling? Here, we’ll review the literature characterizing brain fog experienced by patients with CFS and the potential risk of CFS occurring after infection with COVID-19.

What is brain fog and what brain functions are impaired?

            Brain fog is the perception of mental fatigue that include various cognitive impairments such as slower thought processes, trouble concentrating, confusion, and forgetting2. Despite the wide variety of symptoms experienced by patients with CFS, up to 85% have reported cognitive impairment often described as brain fog2. Scientists were interested in understanding what specific brain functions were impacted that could be leading patients to feel “foggy”. To measure brain function, scientists use various cognitive tests aimed at characterizing specific mental tasks. The Digit Span Test, for example, measures attention and working memory by asking individuals to read a sequence of numbers and recite the numbers in the order given or in reverse3. Forward recitation measures attention whereas reverse recitation evaluates working memory, which holds temporary information such as remembering directions given by a friend3. Using this test and others, researchers found that both attention and working memory were impaired in individuals with CFS2,4. Further, CFS patients had impairments in information processing and their reaction times were slower than control subjects2. Although the reaction times were slower, some cognitive tests have shown that individuals with CFS still had similar accuracy to controls, suggesting that they are cognitively accurate but slower to process information4. Overall, there are measurable cognitive impairments in individuals with CFS that impact various brain functions such as working memory and reaction time.

What changes are occurring in the brain to cause cognitive impairments?

Brain Activity

Scientists then questioned what underlying changes in brain function could explain these cognitive impairments. Using neuroimaging to visualize brain activity, studies found an increase in brain activity in specific brain regions, such as sub-cortical and cortical areas4. Further, there was an overall increase in the number of activated brain regions during cognitive tests in CFS patients in comparison to control2. This could suggest that individuals with CFS require more brain activity to complete cognitive tasks. Further, scientists found altered connectivity during cognitive tasks which suggests these individuals have a less efficient way of processing information, which could explain cognitive fatigue4.

Cerebral Blood Flow

Cerebral blood flow is another measurement used to characterize changes in brain function. Blood delivers oxygen to the brain, which is needed to perform normal functions. Overall, studies have suggested that CFS patients may have decreased cerebral blood flow2. Scientists were interested to see if decreased cerebral blood flow could be tied to impaired cognitive performance. They measured cerebral blood flow before and during a cognitive test and found that CFS patients had decreased cerebral blood flow prior to the test but increased cerebral blood flow during the test compared to control subjects2. Interestingly, CFS patients had similar cognitive performance to the control subjects, suggesting that CFS patients may have an increased need for cerebral blood flow to perform the same tasks. Consistent with their condition, patients with CFS reported that they felt mentally fatigued after performing the cognitive test2. These findings indicate that CFS patients have altered cerebral blood flow regulation that could contribute to the experience of brain fog.


            Brain function can also be altered by neuroinflammation, an immune response that can be caused by various external factors such as infection or injury. One study found that neuroinflammation was correlated to cognitive impairments reported by subjects with CFS4. Further, natural killer cells, part of the innate immune system that help fight infections and tumors, are low functioning in CFS patients and correlate with the severity of CFS and cognitive impairment5. Cumulatively, brain activity, cerebral blood flow, and neuroinflammation are still being investigated in relation to cognitive impairments in CFS patients but all have the potential to explain the fatigue and brain fog experienced by individuals with CFS.

Could CFS occur in individuals infected with COVID-19?

Brain fog is not restricted to individuals with CFS. This cognitive impairment, or fuzzy feeling, can occur in a variety of conditions including individuals undergoing chemotherapy referred to as chemo-brain. Recently, brain fog in individuals who had been infected with COVID-19 has become a growing concern. In a survey of over 3,000 patients, more than 50% of individuals reported cognitive impairments such as attention difficulties and slowed thinking 7 months post-infection6. These lasting post-infection effects are being referred to as “long-COVID syndrome” or “post-COVID syndrome”6. There is currently no conclusive evidence that patients previously infected with COVID-19 are at risk for developing CFS however, the similarities in symptoms in patients with CFS and long-COVID syndrome are leading scientists to speculate this could be the case. It is important to keep in mind that this data is new and not yet fully understood, but it may indicate that CFS could be a lasting condition in a subset of COVID-infected patients.

Image Credits:

Photo by Cristian Newman on Unsplash


1. Centers for Disease Control and Prevention. (2018). Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. U.S. Department of Health and Human Services

2. Ocon, A. J. (2013). Caught in the thickness of brain fog: exploring the cognitive symptoms of Chronic Fatigue Syndrome. Frontiers in physiology4, 63.

3. Fink, H. A., Hemmy, L. S., MacDonald, R., Carlyle, M. H., Olson, C. M., Dysken, M. W., … & Wilt, T. J. (2014). Cognitive Outcomes After Cardiovascular Procedures in Older Adults: A Systematic Review [Internet].

4. Cvejic, E., Birch, R. C., & Vollmer-Conna, U. (2016). Cognitive dysfunction in chronic fatigue syndrome: a review of recent evidence. Current rheumatology reports18(5), 24.

5. Bested, A. C., & Marshall, L. M. (2015). Review of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: an evidence-based approach to diagnosis and management by clinicians. Reviews on environmental health30(4), 223-249.

6. Komaroff, A. L., & Bateman, L. (2021). Will COVID-19 lead to myalgic encephalomyelitis/chronic fatigue syndrome?. Frontiers in Medicine7, 1132.

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