Author: Dr. Chad Prusmack, MD

The International Lyme and Associated Diseases Society (ILADS) is a nonprofit, international, multidisciplinary medical society dedicated to the diagnosis and treatment of Lyme and other complex inflammatory diseases. With these educational blog posts from experts and members of our board, ILADS aims to promote awareness and understanding of health and wellness, especially as it relates to complex inflammatory diseases, so that we can all learn and grow together. If you have any questions or want more information, you can email us at contact@ilads.org. 

Disclaimer: Every patient is an individual with unique characteristics. This blog article is not medical advice. It does not constitute a physician-patient relationship. It is for educational purposes only. Do not try out what is in this article without medical advice, working with your licensed physician and licensed healthcare providers

As we continue to learn more about COVID-19 infections, one area of increasing concern is the long-term impact on brain health. Emerging evidence suggests that COVID-19 not only affects the lungs but can also have profound neurological consequences. For many, these effects are not short-lived. One in five adults who have had COVID-19 report persistent symptoms, with neurocognitive issues being some of the most concerning.

Even a year after infection, many COVID-19 survivors continue to experience a range of neurocognitive symptoms. Some of the most prevalent symptoms include olfactory dysfunction, taste impairment, anxiety, depression, fatigue, sleep difficulties, memory impairment, headaches and dizziness. Other neurological sequelae can also be seizures, stroke, neuralgia, bell’s palsy, and neuropathy.

COVID-19 and Those With a History of Mild Traumatic Brain Injury (mTBI)

Both brain trauma and the COVID-19 infection can cause neuronal injury, or damage to cells in the brain, including neurons. This damage can cause inflammation, both in the brain and in the body. Inflammation is part of the innate immune system and is initiated when the innate immune system recognizes invading pathogens (such as SARS-CoV-2) or mechanical damage (such as traumatic brain injury) through pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and inflammasomes of the innate immune system. 

Although inflammation is a protective response to eliminate harmful stimuli, initiate tissue repair, and restore health, if not properly regulated or resolved, it can also contribute to the development of autoimmune diseases, cardiovascular diseases, and neurodegenerative diseases. The innate immune system constitutes the first line of defense against invading microbial pathogens. It relies on a large family of pattern recognition receptors (PRRs), which detect distinct evolutionarily conserved structures on pathogens, termed pathogen-associated molecular patterns (PAMPs), or on damaged tissue from trauma termed, Damage associated molecular Patterns. 

We have found that patients with a history of both COVID-19 and traumatic brain injury have worsened long-term symptoms and outcomes, increased inflammation, increased risk of neurodegenerative disease, and Astrocyte-derived exosomes (ADEs) that display an increased propensity to induce an inflammatory phenotype in astrocytes in vitro.

The Role of Inflammation and Immune Activation

During the past decade, scientists have found that extracellular vesicles (EVs) “EXOSOMES” play important roles in both short and long-distance communications between cells, within and out of the brain. Astrocyte-derived EVs are enriched with various biological molecules including genes, microRNAs (miRNA), and proteins. Interestingly, astrocytes-derived EVs that are secreted in normal conditions are known to be enriched with neuroprotective and neurotrophic elements. On the contrary, EVs released by astrocytes under abnormal conditions such as oxidative stress, nutrient deficiency, and inflammation have been witnessed to exert a neuroprotective effect, and promote neurite regeneration and outgrowth. 

Exploring Preventive and Therapeutic Strategies

We are exploring new ways to mitigate the impact of SARS-CoV-2 on brain health. One area of study is the potential of blocking toll-like receptors 3 and 9, which appear to block the activating properties of inflammatory exosomes. 

Healthcare providers can support the cognitive and mental health needs of COVID-19 patients by referring them to both a concussion specialist and a long COVID specialist who can help rehab the hardware (TBI) and treat the software (post-COVID) problems of the brain simultaneously.
Listen to Dr. Chad Prusmack, MD speak at the 2024 ILADS Annual Conference in San Antonio on: “Probing the Long-Term Consequences of SARS-CoV-2 Infection on Brain Health in Patients With and Without a History of Mild Traumatic Brain Injury”