COVID-19 and the Brain (Part 2 of 2) The Immune Response and How to Strengthen It

June 09, 2020
(a 5 min read)

Today, we bring you the 2nd installment in our series on COVID-19's typical (and severe) effects on the brain and nervous system.  If you missed the first installment, click on the button below to learn more.

COVID-19 and the Brain: Part 1 - the Symptoms

Today in Part 2, we will share:

  • How neurological symptoms of COVID-19 compare with common colds and flu
  • How the immune system and inflammation get involved
  • How your diet could help: nutrients to fortify your immune system and your brain health

Neurological Symptoms: COVID-19 vs. Common Colds or Flu

While the thought of neurological symptoms with coronavirus can be startling and even a bit scary, these symptoms are observed in many different viruses.  Neurological symptoms with common colds and flu can be mild, such as a headache or blurry vision, or they can be more severe, like those seen in some COVID-19 cases.

The table below puts neurological symptoms associated with COVID-19 and the flu/common cold side-by-side - to help you compare.

* For more information, see references 1, 2, and 3 below.

While reports suggest that a significant number of people diagnosed with COVID-19 experience some “typical” neurological symptoms, it is important to keep in-mind that a large percentage of patients with common colds or flu also experience neurological symptoms (3). Additionally, the neurological symptoms of COVID-19 and the flu/common cold tend to be very similar - with one exception: a loss of smell and taste appears to be more prevalent and distinctive in COVID-19.

Symptoms should improve with time, but if you or someone you know has specific concerns, you should always seek assistance from your physician.

What's Driving These Brain and Neurological Symptoms?

Oftentimes, our immune response and inflammation can drive brain symptoms. Although, to be clear, brain symptoms don’t always mean that there’s something directly wrong with the brain. For example, sometimes when you’re dehydrated you may get a headache or experience dizziness. Dehydration is a systemic condition that results from more water exiting the body than entering it. Thus, the condition is not directly related to the brain. However, dehydration can still result in numerous neurological symptoms.

This brings us to inflammation. When the immune system responds to an infection, it often initiates an inflammatory response that can cause symptoms throughout the body (4). People typically think of inflammation as the pain from a joint ache or headache, and a simple solution may be treatment with over-the-counter drugs, such as ibuprofen. In reality, the body's inflammatory response to infection or other stresses is a very complex system involving many moving parts.

So, What Exactly Is an Inflammatory Response?

Have you ever wondered what's really going on when your immune system is responding to a viral infection?  What is it that the virus (whether coronavirus or flu) is doing that affects our bodies and brains?  We've broken it down into five basic steps (4).

1. Detection: We have immune cells called macrophages, and if you're infected with a virus, the macrophages detect virus-infected cells (5, 6).

Expert notes:

  • When a cell becomes infected by a virus, there are structures on the surface of the infected cell called antigens that binds to receptors on a macrophage (5).
  • Helper T cells (not shown) can also detect infected cells and signal the presence of an infection to the rest of the immune system (6).

 

2. Raising the alarm: Not only do they detect, macrophages also "eat" (or engulf, known in science as phagocytosis) infected cells and release inflammatory "signaling" molecules, called cytokines, to alert other immune cells of the infection (5).

Expert notes:

  • In addition, macrophages release cellular material from the infected cells to cytotoxic T cells, so that they can recognize and destroy the specific virus (5).

 

3. The cavalry arrives: Other immune cells, including "natural killer" (NK) cells and cytotoxic T cells arrive to fight the infection (7).

Expert notes:

  • NK cells are responsible for killing infected cells in the body by releasing molecules that harm and kill the cell.
  • Cytotoxic T cells recognize molecules specific to the particular virus on the surface of an infected cell and then release their own toxic chemicals to kill infected cells.
  • The cytotoxic molecules are stored in vesicles that release (or secrete) the cytotoxic molecules once an infected cell is identified.
  • Macrophages contribute by continuing to destroy infected cells by "eating" them (7).

 

4. The battle ensues: NK and cytotoxic T cells kill virus-infected cells by releasing molecules that harm and kill such cells.  This creates other harmful compounds called reactive oxygen species (ROS) that can affect not only the infected cells, but healthy ones also (8, 9).

Expert notes:

  • What are ROS? ROS are highly reactive molecules containing oxygen that go through a series of chemical chain reactions. When they are released by immune cells, they react with nearby molecules, which can damage important proteins, lipids, and even DNA in our cells.
  • ROS are produced as a by-product when a macrophage engulfs an infected cell (8). Cytotoxic T cells produce ROS during the process of generating energy so that they can effectively destroy infected cells and create more immune cells (9).

 

5. It can spread: As more and more inflammatory signaling molecules (called cytokines) make their way into systemic circulation, the inflammatory response can affect every part of the body, including the brain.  This results in symptoms like runny nose, sore throat, headaches, and fevers (4, 8, 10, 11, 12, 13).

Expert notes:

  • As mentioned, ROS can damage cells by causing harm to the plasma membrane, proteins, and our DNA (8).
  • In addition to recruiting immune cells to fight an infection, the circulation of certain inflammatory cytokines in the blood, including ones called TNF, IFN-g, and IL-2, can cause headaches (10). In addition, high levels of inflammatory cytokines called TNF and MIF have been shown to cause headache, dizziness, and fatigue (11). The cytokines TNF, IFN-g, and IL-2 are all associated with an immune response to an infection (12).
  • Cytokines also increase brain levels of prostaglandin E2 (PGE2), which is a hormone involved in regulating inflammatory responses.  It is believed that PGE2 is involved in headaches, as current headache treatments (such as ibuprofen) serve to inhibit the synthesis of prostaglandins (13).

A similar response occurs when the infection impacts the brain. The brain, however, has its own immune cells, called microglia. The brain is a very sensitive part of the body, so the immune system reacts strongly and quickly to fight an infection in the brain (12). Therefore, symptoms involving an immune response in the brain are often more disruptive. In fact, the immune response to both an infection in the brain and a brain injury, such as a head impact injury or stroke, can be similar and often involves a severe inflammatory response (12).

When an immune response in the brain gets out of hand, it can be associated with a wide range of symptoms, including confusion, seizures, and psychosis – similar to the symptoms reported with severe cases of COVID-19 (14). This begs the question: Can coronavirus enter the brain? We looked at the most recent reports, and evidence has not conclusively suggested that COVID-19 has infiltrated the brains of patients. As more research is conducted into this novel virus, the full extent of its impacts may be revealed.

We will delve further into the complex immune system of the brain in a later article to shed more light on how the brain's immune responses contribute to overall brain health and functioning during aging.

What Can You Do to Promote a Healthy Immune System and Brain Health?

The great news is that there are things you can do to strengthen your own immune system and protect yourself from a bad infection. In fact, the daily choices you make about the foods you eat have a major impact on your health in many ways, including how well the immune system functions.

Keep in-mind: immune system function tends to decrease with age. For example, total white blood cell counts decrease with age, as do levels of certain types of T cells. However, consuming a diet high in antioxidants can counteract some of these effects (8).

What are antioxidants? Antioxidants are compounds that can stop chain reactions involving reactive oxygen species (ROS), which can damage cells. "Oxidative stress" occurs when there is an imbalance of ROS and antioxidants. As we covered earlier, inflammation contributes to oxidative stress, and therefore can tip the balance towards cell damage. Antioxidants help combat inflammation and oxidative stress to maintain the functionality of cells in the body, particularly immune cells (15).

Fortunately, antioxidants are found in many common foods, and increasing your consumption of such foods can help your body be prepared to fight a virus like coronavirus, if need be.

Some foods that are high in antioxidants include berries, leafy green vegetables, nuts, fish, and green tea. You are probably familiar with antioxidants, such as vitamin C or vitamin E, but there are many more antioxidant compounds found in food. For example, anthocyanins, a group of pigments in berries and grapes, are potent antioxidants.

Antioxidants, Brain Health, and Parting Thoughts

Antioxidant consumption is also associated with brain health. A pleasant mix of antioxidants are found in the Mediterranean diet, and researchers have begun investigating its effect on brain health outcomes (16). Also, studies have found a significantly reduced risk of developing Alzheimer’s disease with people who consume a high amount of antioxidants over time, versus those who do not (17). In some studies, just 1 serving/day of spinach or kale, or 2-3 servings of berries are linked to a significant positive impact (18, 19). This suggests that a diet high in antioxidants can not only help your immune system during this stressful period, but also maintain brain health – a win-win.

While consuming antioxidants is important in supporting the immune system and brain health, it is important not to overdo it. Too much of anything may be unhelpful and may be even harmful, and that includes antioxidants. A proper balance needs to be maintained between antioxidants and ROS. As mentioned, some ROS are necessary to carry out the immune response, so stopping ROS production entirely is not ideal (20)! All good things in moderation!

As the world continues to navigate this pandemic, we will return to this topic again and keep you updated with the latest research findings. There is much more we will learn!

In good health,
The NeuroReserve Research Team

Article keywords: coronavirus, COVID-19, brain, symptoms, immune system, inflammation, what food is good for the brain, brain health diet, antioxidants, Mediterranean diet

References:

  1. Yan, C. H., Faraji, F., Prajapati Bs, D. P., Boone, C. E. & Deconde, A. S. Association of Chemosensory Dysfunction and Covid-19 in Patients Presenting with Influenza-like Symptoms. doi:10.1111/alr.22579
  2. Mao, L. et al. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: A Retrospective Case Series Study JAMA Neurol (accepted manuscript). (2020). doi:10.1001/jamaneurol.2020.1127
  3. Yang, J. H. et al. Predictive Symptoms and Signs of Laboratory-confirmed Influenza. Med. (United States) 94, e1952 (2015). doi:10.1097/MD.0000000000001952
  4. Eccles, R. Understanding the symptoms of the common cold and influenza. Lancet Infectious Diseases 5, 718–725 (2005). https://doi.org/10.1016/S1473-3099(05)70270-X
  5. Hirayama, D., Iida, T. & Nakase, H. The phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis. International Journal of Molecular Sciences 19, (2018). https://doi.org/10.3390/ijms19010092
  6. Klimpel, G. R. Immune Defenses. in Medical Microbiology (1996). https://www.ncbi.nlm.nih.gov/books/NBK8423/
  7. Laing, K. & Hutchinson, F. Immune Responses to Viruses. https://www.immunology.org/public-information/bitesized-immunology/pathogens-and-disease/immune-responses-viruses
  8. Knight, J. A. Review: Free Radicals, Antioxidants, and the Immune System. Ann. Clin. Lab. Sci. 30, 145–158 (2000). http://www.annclinlabsci.org/content/30/2/145.short
  9. Yarosz, E. L. & Chang, C. H. Role of reactive oxygen species in regulating T cell-mediated immunity and disease. Immune Network 18, (2018). https://doi.org/10.4110/in.2018.18.e14
  10. Smith, R. S. The cytokine theory of headache. Med. Hypotheses 39, 168–174 (1992). https://doi.org/10.1016/0306-9877(92)90181-B
  11. Christian, L. M., Porter, K., Karlsson, E. & Schultz-Cherry, S. Proinflammatory cytokine responses correspond with subjective side effects after influenza virus vaccination. Vaccine 33, 3360–3366 (2015). https://doi.org/10.1016/j.vaccine.2015.05.008
  12. Chen, L. et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 9, 7204–7218 (2018) https://doi.org/10.18632/oncotarget.23208
  13. Eccles, R. Mechanisms of symptoms of common cold and flu. Br. J. Hosp. Med. 68, 71–75 (2009). https://doi.org/10.12968/hmed.2007.68.2.22824
  14. Klein, R. S., Garber, C., Howard, N. & Author, N. I. Infectious immunity in the central nervous system and brain function HHS Public Access Author manuscript. Nat Immunol 18, 132–141 (2017). https://doi.org/10.1038/ni.3656
  15. Amir Aslani, B. & Ghobadi, S. Studies on oxidants and antioxidants with a brief glance at their relevance to the immune system. Life Sci. 146, 163–173 (2016). https://doi.org/10.1016/j.lfs.2016.01.014
  16. Martínez-Lapiscina, E. H. et al. Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial. J. Neurol. Neurosurg. & Psychiatry. 84, 1318 LP – 1325 (2013). http://dx.doi.org/10.1136/jnnp-2012-304792
  17. Engelhart, M. J. et al. Dietary intake of antioxidants and risk of Alzheimer disease: Food for thought. J. Am. Med. Assoc. 287, 3261–3263 (2002). doi:10.1001/jama.287.24.3261
  18. Morris, M. C. et al. Nutrients and bioactives in green leafy vegetables and cognitive decline: Prospective study. Neurology 90, E214–E222 (2018). https://doi.org/10.1212/WNL.0000000000004815
  19. Devore, E. E., Kang, J. H., Breteler, M. M. B. & Grodstein, F. Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann. Neurol. 72, 135–143 (2012). https://doi.org/10.1002/ana.23594
  20. Halliwell, B. Free radicals and antioxidants: Updating a personal view. Nutr. Rev. 70, 257–265 (2012). https://doi.org/10.1111/j.1753-4887.2012.00476.x
Back to Blog