By Laura Budurlean

Are you a victim of “brain fog”? You can blame the pandemic. Individuals previously infected with SARS-CoV-2, resulting in COVID-19, sometimes experience lingering brain fog, one of the symptoms of post-acute COVID-19 syndrome (PACS or “long-COVID”). Brain fog is characterized by a general confusion, an inability to focus, and decreased mental clarity lasting for several weeks or months.  While not exclusive to PACS, brain fog can develop from a variety of conditions and a recent study showed that 67% of 156 patients attending Mount Sinai’s post-acute COVID-19 clinic reported brain fog after COVID-19 infection (Figure 1).¹ Patients also reported exhaustion, difficulty thinking, and trouble remembering for months after the initial infectious period. In the early months of the pandemic medical professionals and scientists did not understand the effects COVID-19 had on the brain, however new preliminary studies reveal clues about how the immune system response to COVID-19 can affect the brain.¹

While cognitive impairment due to immune system activation in the brain and body arising from infections, such as human immunodeficiency virus (HIV), is not a new concept, the wide breadth and impact of COVID-19 makes PACS a potential public health crisis.² Our daily activities, whether personal or related to work, require us to pay attention, to organize, and to problem-solve, and brain fog can interfere with our ability to carry out life’s daily challenges and necessities.

New studies aimed at understanding COVID-19’s effects on the central nervous system (CNS) build on immune activation patterns seen in patients living with HIV and displaying cognitive problems. A small study from UCSF conducted on patients who were previously infected with COVID-19 showed that the cerebrospinal fluid of over 70% of patients who experienced brain fog symptoms contained SARS-CoV-2, unlike the individuals that did not experience brain fog symptoms. Cognitive impairment in the former individuals persisted anywhere from 71-120 days.⁵ While it is widely known that COVID-19 affects respiratory tissues, few studies examine the effects on CNS pathways. Several hypotheses have emerged recently including a direct effect of viral damage such as neuroinflammation, chronic immune activation, microvascular injuries, and aberrant host immunological responses among others (Figure 2).⁴

Despite patient-reported symptoms, two common cognitive screening tests did not detect the cognitive effects in patients recovering from COVID-19, suggesting that current testing may be inadequate at diagnosing minor cognitive conditions.³ The authors hypothesized that since not all patients with brain fog had SARS-CoV-2 in the cerebrospinal fluid that direct and indirect viral mechanisms may be contributing to this cognitive disfunction. One possible suspect is anti-neuronal antibodies that aberrantly attack self-proteins and cause inflammation in the brain. Spinal IgG production was seen in one patient displaying cognitive impairment following COVID-19 infection, supporting central nervous system adaptive immune activation. At present the targets of these antibodies is unknown but could reflect anti-SARS-CoV-2 antibodies residing in the CNS. Presently, more research in larger-scale studies is needed to interpret the findings in the context of CNS immunological response.⁵

Identifying the source of these neurological impairments can reveal treatments for patients experiencing PACS. Treatment possibilities include therapies that quench the overactivation of the immune system, and the basis of these therapies can aid us in understanding other neurological conditions such as chronic fatigue syndrome.

In the meantime, anyone experiencing similar symptoms can pursue activities that are known to help with thinking and memory. These include aerobic exercise, Mediterranean style meals, participating actively in social activities, avoiding alcohol, and engaging in brain stimulating activities, (chess, sudoku, Wordle, crosswords, and practicing mindfulness).⁶ To improve your general memory, Harvard nutritionist Dr. Uma Naidoo recommends limiting foods that weaken memory and focus, including additional added sugars, fried foods, high-carbohydrate foods such as bread or pasta, and nitrates frequently used in deli and cured meats.¹¹ Tracking activities that trigger or make brain fog worse can also be helpful as well as taking a daily multivitamin with omega-3 fatty acids⁷. While no one specific activity has been shown to be more beneficial in resolving PACS related brain fog, many brain stimulating activities may ameliorate brain fog symptoms.^6-10

TL:DR

• COVID-19 causes brain fog in some individuals that lasts many months post-infection. Several proposed mechanisms, including immune activation, need to be explored.
• The good news is there are several steps we can take to lessen the effect of brain fog.

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References

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2. McArthur JC, Steiner J, Sacktor N, Nath A. Human immunodeficiency virus-associated neurocognitive disorders: Mind the gap. Ann Neurol. 2010;67(6):699-714.
3. Hellmuth J, Barnett TA, Asken BM, et al. Persistent COVID-19-associated neurocognitive symptoms in non-hospitalized patients. J Neurovirol. 2021;27(1):191-195.
4. Damiano RF, Guedes BF, de Rocca CC, et al. Cognitive decline following acute viral infections: literature review and projections for post-COVID-19. Eur Arch Psychiatry Clin Neurosci. 2022;272(1):139-154.
5. Apple AC, Oddi A, Peluso MJ, et al. Risk factors and abnormal cerebrospinal fluid associate with cognitive symptoms after mild COVID ‐19. Ann Clin Transl Neurol. 2022;9(2):221-226.
6. Al-Thaqib A, Al-Sultan F, Al-Zahrani A, et al. Brain training games enhance cognitive function in healthy subjects. Med Sci Monit Basic Res. 2018;24:63-69.
7. Naidoo U. A Harvard nutritionist and brain expert says she avoids these 5 foods that ‘weaken memory and focus’. CNBC. https://www.cnbc.com/2021/11/28/a-harvard-nutritionist-and-brain-expert-avoids-these-5-foods-that-weaken-memory-and-focus.html. Published November 28, 2021.
8. Valls-Pedret, Cinta – JAMA Intern Med (2015) Mediterranean diet and age-related cognitive decline a randomized clinical trial.pdf
9. Morris MC, Tangney CC, Wang Y, et al. MIND diet slows cognitive decline with aging. Alzheimer’s & dementia : the journal of the Alzheimer’s Association. 2015;11(9):1015.
10. Cassilhas RC, Tufik S, de Mello MT. Physical exercise, neuroplasticity, spatial learning and memory. Cell Mol Life Sci. 2016;73(5):975-983.
11. Memory inhibition and energy regulation. Physiology & Behavior. 2005;86(5):731-746.