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Feeling Fatigued and Burned Out? Inflammation May Be Playing a Role

Are you wondering why you feel fatigued all the time?

Key points

  • A recent study showed that fatigue associated with the COVID-19 pandemic may be due to brain inflammation.
  • The inflammation was probably attributable to immune mechanisms that were activated because of social isolation.
  • Seeing your doctor is foremost, but other tips to reduce inflammation and improve cognition include socializing and exercise.
Brain inflammation.
Source: peopleimages/iStockphoto

Nearly three in five U.S. adult workers surveyed in 20211 by the American Psychological Association reported negative impacts of work-related stress, including a lack of interest, motivation, energy, and effort. Employees also reported experiencing cognitive weariness (36 percent), emotional exhaustion (32 percent), and physical fatigue (44 percent). Somehow, the pandemic-related burnout has felt different,2 and people can’t quite account for why they feel this way. A doctor even wrote about how it might have permanently changed him.3 And, until recently, there was no information clear enough to point to a possible reason, until this study from Massachusetts General Hospital in collaboration with King’s College London, The Maudsley NIHR Maudsley Biomedical Research Centre, and other collaborators.4

Study Comparing Brains Before and During Pandemic Lockdowns

This study compared 57 pre-pandemic and 15 pandemic data sets from individuals originally enrolled as control subjects for various completed or ongoing research studies available, with a confirmed negative test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. The investigators used a combination of brain-imaging modalities as well as blood samples to investigate whether there were any differences in the brains of healthy people before and during the pandemic after the lockdowns.

The study found that healthy individuals examined after the enforcement of the lockdown had elevated brain levels of two independent neuroinflammatory markers (the 18 kDa translocator protein, TSPO, and myoinositol) compared to pre-lockdown participants. And participants endorsing higher symptom burden showed higher TSPO signal in the hippocampus (mood alteration, mental fatigue), intraparietal sulcus, and precuneus (physical fatigue), compared to those reporting little or no symptoms. This implied that inflammation in these regions may have accounted for their mental and physical fatigue and mood alterations. This study provided preliminary signals that the lockdown had the effect of increasing brain inflammation, and this was probably due to immune mechanisms that were activated because of social isolation.

Prior studies would support this hypothesis. One study illustrated that adverse social experiences (social isolation, perceived social threat) may induce inflammatory responses while suppressing antiviral immunity, whereas positive experiences of social connection may reduce inflammation and bolster antiviral responses.5 Social isolation has also been associated with impaired memory6 and immune dysfunction in other studies.7 And studies have also demonstrated that social isolation could increase immune markers such as IL-6,8 and it could also increase microglial cell activity in the brain as part of this inflammatory response.9,10 Called sterile neuroinflammation, these changes resemble changes caused by infections, and they are correlated with fatigue and anxiety.11,12

What You Can Do

Aside from checking in with your primary care physician to clarify what is happening, there are a few things that you may try to help to get yourself out of his fatigued state:

  1. Socializing: The pandemic might have left you feeling somewhat isolated, but also perhaps pleased that you don’t have to interact with people. This may have left you smugly on your own, and you may even think you prefer this. However, to the extent that you can safely socialize, it could help to be around other people. A large number of studies have shown that social isolation impacts your life negatively in a variety of ways.13
  2. Diet: In her book, This Is Your Brain on Food,14 Harvard psychiatrist Dr. Uma Naidoo explains that neuroinflammation is a real thing. She recommends anti-inflammatory and fiber-rich foods. Spices like turmeric with black pepper can help, and she refers to how helpful it can be to eat vegetables that are the colors of the rainbow, such as peppers, tomatoes, and leafy greens. Take this idea to your doctor to personalize your diet for you.
  3. Nature-based imagery: Studies have shown that viewing nature15,16 can have beneficial effects on the brain. We have demonstrated17 that people can feel clearer and focus better with less anxiety and emotional distress just 10 minutes after viewing nature in virtual reality, and we have also found that people are less fixated on worry.18 Both studies have been accepted by peer-reviewed journals and will be published soon.
  4. Physical exercise: Physical exercise can improve the neuroimmune response19 and can be anti-inflammatory.20 Work with your doctor to determine what routine is best for you.

Social isolation could lead to brain inflammation. But there are things that you can start doing today about this, so why not begin now?


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(9) Stein, D. J.; Vasconcelos, M. F.; Albrechet-Souza, L.; Ceresér, K. M. M.; de Almeida, R. M. M. Microglial Over-Activation by Social Defeat Stress Contributes to Anxiety- and Depressive-Like Behaviors. Front. Behav. Neurosci. 2017, 11.

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(13) CORNWELL, E. Y.; WAITE, L. J. Social Disconnectedness, Perceived Isolation, and Health among Older Adults. J. Health Soc. Behav. 2009, 50 (1), 31–48.

(14) MD, U. N. This Is Your Brain on Food: An Indispensable Guide to the Surprising Foods That Fight Depression, Anxiety, PTSD, OCD, ADHD, and More; Little, Brown Spark: New York, 2020.

(15) Franco, L. S.; Shanahan, D. F.; Fuller, R. A. A Review of the Benefits of Nature Experiences: More Than Meets the Eye. Int. J. Environ. Res. Public. Health 2017, 14 (8).

(16) Jo, H.; Song, C.; Miyazaki, Y. Physiological Benefits of Viewing Nature: A Systematic Review of Indoor Experiments. Int. J. Environ. Res. Public. Health 2019, 16 (23).

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(18) Reulay Announces Results From Study of Virtual Reality Interventions for Workplace Stress and Anxiety… (accessed 2022 -03 -01).

(19) Seo, D.-Y.; Heo, J.-W.; Ko, J. R.; Kwak, H.-B. Exercise and Neuroinflammation in Health and Disease. Int. Neurourol. J. 2019, 23 (Suppl 2), S82-92.

(20) Scheffer, D. da L.; Latini, A. Exercise-Induced Immune System Response: Anti-Inflammatory Status on Peripheral and Central Organs. Biochim. Biophys. Acta Mol. Basis Dis. 2020, 1866 (10), 165823.

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