The Causes of Long COVID Cognitive Dysfunction (“Brain Fog”) and Nutritional Supplementation That May Help
We recently published an article on long COVID (found by clicking here), where we addressed some basic questions about it: what is it, who gets it, what are its symptoms, and initial things we can do about it. An important takeaway from research to-date is that long COVID particularly affects the brain and cognitive function, resulting in symptoms such as trouble remembering things, concentration difficulties, depression/anxiety, and insomnia. In fact, doctors increasingly view long COVID as a neurological disease. William Pittman, MD, who treats long COVID at UCLA Health reflects this perspective in a recent quote, “I now think of COVID as a neurological disease as much as I think of it as a pulmonary disease, and that’s definitely true in long COVID.”1
Here, we’ll introduce three suspected causes of long COVID and “COVID brain.” Armed with that knowledge, we’ll consider which nutrients or nutritional supplements researchers are investigating to address those causes.
Suspected Causes of Long COVID: the Triad of Microclots, Lingering Virus, and Haywire Inflammation.
1. Microclots. Blood flow is essential, especially for brain function. Researchers and case studies are revealing that microclots in certain organs, such as the lungs and brain, may be inducing long COVID symptoms through restricted blood flow and oxygen deprivation.2 In the lungs, microclots may drive fatigue and breathlessness. In the brain, microclots may lead to ministrokes, resulting in damaging or destroying nerve cells. How do these microclots arise? Scientists find that SARS-CoV-2 (the COVID virus) attacks endothelial cells, which are the cells that make-up blood vessels. Blood clots may form to help heal the damaged blood vessels, but sometimes they don’t adequately dissolve, and they are swept to other organs where they can block flow.
2. Lingering Virus. Scientists are finding that the COVID virus is more persistent than we expected. Long after the acute phase of COVID, small amounts of the virus can “hide out” in isolated pockets in the brain, muscle, gut, and lungs and continue to replicate.3 A very recent research publication found that SARS-CoV-2 viral RNA was detected in the brain as long as 230 days after infection.1 Other studies indicate that the virus gains access to the brain through mucosal cells deep in the nose, where they then damage neurons and astrocytes (which are brain cells that support neurons in the brain).4
3. Haywire Inflammation. What happens when your immune system goes into attack mode and can’t turn off? Haywire inflammation. People with “COVID brain” appear to have an immune system that is chronically activated in or near the central nervous system. In particular, macrophages are a type of immune cell that assaults invaders (like viruses) by “carpet bombing” them with damaging free radicals and cytokines (molecules that generate inflammation).1,5 The problem with macrophages is that they produce significant collateral damage and they are slow to shut down. Lingering virus in the brain may then lead to persistent inflammation in that organ, leading to neuroimmune disorder.
Nutrients Researchers Are Investigating That May Help
Given the potential causes mentioned above, researchers can now consider specific nutritional interventions to address long COVID. Here we list a few under investigation and how they could address one more of the causes:
- Vitamin B3: Known as niacin, nicotinamide, niacinamide, and nicotinamide riboside, this vitamin is essential to maintaining levels of NAD+, which reduce the inflammatory response.6,7
- Vitamin D3: Not only is vitamin D important for calcium metabolism and bone health, but also its receptors are found on several immune cell types, including macrophages, lymphocytes, and monocytes; in addition, it possesses antithrombotic effects. Given that vitamin D deficiency affects much of the population, vitamin D is widely researched as a potential prophylactic and treatment for both acute and long COVID.8
- Omega-3 fats, such as DHA and EPA: Well-known for their anti-inflammatory properties these omega-3’s are also being clinically tested for their effect on long COVID.9 In addition, DHA and EPA have potent antithrombotic (anti-clotting) properties.10
- Plant-based flavonoids, like quercetin, kaempferol, luteolin, epigallocatechin: Found in colorful vegetables, these bioactive nutrients provide unique antioxidant and anti-inflammatory properties. In addition, they can interfere with the coronavirus replication cycle, making them antivirals as well.6,11
- Probiotics and prebiotics: Probiotics and the compounds that they release (metabolites) can increase mucosal immune defense in the gut, resulting in anti-inflammatory, antioxidant, and antiviral activity. Certain strains, such as S. thermophilus, L. acidophilus, L. helveticus, L. paracasei, L. plantarum, L. brevis, and B. lactis are being evaluated through clinical study and observational studies.7,8
- Melatonin: Typically known as a hormone that promotes sleep, melatonin is also recently found to be an activator of a molecule called NRF2, which promotes antioxidant activity and preventing macrophages from going into an inflammatory state.12
- Zinc and selenium: In addition to its important immune roles as an antioxidant and anti-inflammatory, zinc also may reduce viral replication. Selenium is also essential for antioxidant processes, and low levels of selenium are correlated with increased tissue damage from COVID, leading to long COVID symptoms.8
There are many other nutrients under investigation, including vitamin C, amino acids, iron, magnesium, and herbal extracts.8 In addition, there are a variety of drugs under investigation, such as anticoagulants and anti-inflammatories/antihistamines.
A potent way to deliver antioxidant, anti-inflammatory, and antiviral nutrients against long COVID is to adopt the Mediterranean (MeDi) or MIND diets. In fact, the MeDi is being investigated for its effects on health outcomes during the COVID pandemic.10 Not only are these diets well-known to promote a long life, but also recent evidence indicates that they are very brain protective. The MeDi and MIND are primarily plant-based, rich in unsaturated fats, and include some healthy meats like fish and poultry. You can learn more about these diets by clicking here.
Keep in-mind, if you suspect you are struggling with long COVID, see your doctor. Everyone’s circumstances are unique, and long COVID presents in many ways, which may require a team effort among your primary care physician and specialists. Nutrition could be a potent tool to manage and ultimately prevail over long COVID, along with a regimen of good sleep, physical activity, stress management, and possible medication.
Keywords: post-acute COVID syndrome (PCS), post-acute sequelae of SARS-CoV-2 infection (PASC), post-COVID condition (PCC), post-acute COVID-19, long-haul COVID, long COVID syndrome, long COVID, COVID brain, brain fog
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1. Sutherland, S. Long COVID Now Looks like a Neurological Disease, Helping Doctors to Focus Treatments. Scientific American (2023).
2. Pretorius, E. et al. Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin. Cardiovasc Diabetol 20, 172 (2021).
3. Couzin-Frankel, J. Clues to Long COVID. Science (1979) 376, 1261–1265 (2022).
4. Huang, S. & Fishell, G. In SARS-CoV-2, astrocytes are in it for the long haul. Proceedings of the National Academy of Sciences 119, e2209130119 (2022).
5. Phetsouphanh, C. et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol 23, 210–216 (2022).
6. Picone, P. et al. Neurological Consequences, Mental Health, Physical Care, and Appropriate Nutrition in Long-COVID-19. Cell Mol Neurobiol (2022) doi:10.1007/s10571-022-01281-w.
7. Crook, H., Raza, S., Nowell, J., Young, M. & Edison, P. Long covid - Mechanisms, risk factors, and management. The BMJ vol. 374 Preprint at https://doi.org/10.1136/bmj.n1648 (2021).
8. Tosato, M. et al. Nutraceuticals and Dietary Supplements for Older Adults with Long COVID-19. Clinics in Geriatric Medicine vol. 38 565–591 Preprint at https://doi.org/10.1016/j.cger.2022.04.004 (2022).
9. Koc, H. C., Xiao, J., Liu, W., Li, Y. & Chen, G. Long COVID and its Management. International Journal of Biological Sciences vol. 18 4768–4780 Preprint at https://doi.org/10.7150/ijbs.75056 (2022).
10. Tsoupras, A., Lordan, R. & Zabetakis, I. Thrombosis and COVID-19: The Potential Role of Nutrition. Front Nutr 7, (2020).
11. Russo, M., Moccia, S., Spagnuolo, C., Tedesco, I. & Russo, G. L. Roles of flavonoids against coronavirus infection. Chem Biol Interact 328, 109211 (2020).
12. Jarrott, B., Head, R., Pringle, K. G., Lumbers, E. R. & Martin, J. H. “LONG COVID”—A hypothesis for understanding the biological basis and pharmacological treatment strategy. Pharmacology Research and Perspectives vol. 10 Preprint at https://doi.org/10.1002/prp2.911 (2022).