By Parmida Pajouhesh, Neurobiology, Physiology & Behavior ‘23

Author’s Note: The Coronavirus Disease has undoubtedly affected us in many sectors of our lives. There has been a lot of discussion surrounding the respiratory symptoms induced by the disease but less focus on how contracting the disease can result in long-term suffering. As someone who is fascinated by the brain, I wanted to investigate how COVID-19 survivors have been neurologically impacted post-recovery and what insight it can provide on more severe neurological disorders. 

The Coronavirus Disease (COVID-19) has drastically changed our lives over the past fifteen months. The viral disease produces mild to severe symptoms, including fever, chills, and nausea. There are individual differences in the length of recovery, typically ranging from 1-2 weeks after contraction [1]. Once recovered, those infected are assumed to be healthy and “back to normal,” but data shows that this is not the case for some COVID-19 survivors. COVID-19 has resulted in more severe long-term effects for patients, greatly affecting their ability to perform daily tasks. Taking a deeper look into the neuroimmunological side effects of COVID-19 can help explain the long-term symptoms experienced by survivors. 

Developing our knowledge of long-term neurological effects on COVID-19 survivors is crucial in understanding the risk of cognitive impairments, including dementia and Alzheimer’s disease [2].

A team led by Dr. Alessandro Padovani at the University of Brescia recruited COVID-19 survivors with no previous neurological disease or cognitive impairment for check-ins six months after infection [3]. The exam assessed motor and sensory cranial nerves and global cognitive function. The results showed that the most prominent symptoms were fatigue, memory complaints, and sleep disorder.  Notably, these symptoms were reported much more frequently in patients who were older in age and hospitalized for a longer period of time [3]. 

Other symptoms reported include “brain fog,” a loss of taste or smell, and brain inflammation [2]. Researchers hypothesize that the virus does not necessarily need to make its way inside neurons to result in “brain fog” but instead claim that it is an attack on the sensory neurons, the nerves that extend from the spinal cord throughout the body to gather information from the external environment. When the virus hijacks nociceptors, neurons that are specifically responsible for sensing pain, symptoms like brain fog can follow [4].

Theodore Price, a neuroscientist at the University of Texas at Dallas, investigated the relationship between nociceptors and angiotensin-converting enzyme 2 (ACE2), a protein embedded in cell membranes that allows for viral entry when the spike protein of SARS-CoV-2 binds to it [4, 5]. The nociceptors live in clusters around the spinal cord, which are called dorsal root ganglia (DRG). Price determined that a set of DRG neurons did contain ACE2, enabling the virus to enter the cells. The DRG neurons that contained ACE2 had messenger RNA for the sensory protein MRGPRD, which marks neurons with axons concentrated at the skin, inner organs and lungs. If sensory neurons are infected with the virus, it can result in long-term consequences. It might not be the case that the virus is directly entering the brain and infecting the sensory neurons. Alternatively, it is the immune response triggering an effect on the brain, which leads to the breakdown of the blood-brain barrier surrounding the brain [6]. While this area of research is still under investigation, studies have shown that the breakdown of the blood-brain barrier and lack of oxygen to the brain are hallmarks of Alzheimer’s disease and dementia. Scientists are tracking global function to further understand the impact of COVID-19 treatments and vaccines on these neurological disorders. 

Understanding whether the cause of neurological symptoms is viral brain infection or immune activity is important to clinicians who provide intensive care and prescribe treatments [2, 6]. With future studies, researchers plan to further examine the causes of these symptoms. This knowledge will hopefully provide COVID-19 survivors with adequate support to combat these difficulties and reduce their risk of developing a more severe neurological disorder in the future.

References :

1. Sissons, Beth. 2021. “What to Know about Long COVID.” Medical News Today. www.medicalnewstoday.com/articles/long-covid#diagnosis
2. Rocheleau, Jackie. 2021. “Researchers Are Tracking Covid-19’s Long-Term Effects On Brain Health.” Forbes. www.forbes.com/sites/jackierocheleau/2021/01/29/researchers-are-tracking-covid-19s-long-term-effects-on-brain-health/?sh=59a0bb284303
3. George, Judy. 2021. “Long-Term Neurologic Symptoms Emerge in COVID-19.” MedPage Today. www.medpagetoday.com/infectiousdisease/covid19/90587
4. Sutherland, Stephani. 2020. “What We Know So Far about How COVID Affects the Nervous System.” Scientific American. www.scientificamerican.com/article/what-we-know-so-far-about-how-covid-affects-the-nervous-system
5. Erausquin, Gabriel A et al. 2021. “The Chronic Neuropsychiatric Sequelae of COVID‐19: The Need for a Prospective Study of Viral Impact on Brain Functioning.” Alzheimer’s & Dementia. Crossref, doi:10.1002/alz.12255  
6. Marshall, Michael. 2020. “How COVID-19 Can Damage the Brain.” Nature. www.nature.com/articles/d41586-020-02599-5?error=cookies_not_supported&code=5b856480-d7e8-4a22-9353-9000e12a8962