SARS-CoV-2—causing COVID-19, is a very contagious respiratory virus that was first discovered in China (CDC, 2020). Infections spread quickly throughout the world—causing the start of a global pandemic in early 2020. In the U.S. alone, there have been 44,311,292 COVID-19 cases reported as of October 2021, and over 700,000 deaths (Centers for Disease Control and Prevention, 2021a). As the virus spread, day-to-day life changed dramatically. Many people began working remotely, others lost their jobs. The pandemic has had far-reaching consequences including feelings of isolation as well as worsening mental health outcomes due to loneliness, unemployment, and loss of loved ones (Kamal et al., 2021).
To better comprehend the impact of COVID-19, one needs a better understanding of the disease causing it. SARS-CoV-2 belongs to the family of coronaviruses, which include the common cold, severe acute respiratory syndrome (SARS) (WHO, 2021). SARS is caused by SARS-associated coronavirus (SARS-CoV), while MERS is caused by Middle East respiratory syndrome coronavirus (MERS-CoV). Diseases in the coronavirus family share similar characteristics. Namely, “Corona” means “crown” and refers to the way the virus looks under a microscope, with spike proteins surrounding the edges like a crown. Like other coronavirus infections, symptoms of COVID-19 include fever, cough, and tiredness. The more serious symptoms include difficulty breathing or shortness of breath, loss of mobility, chest pain, and even death. However, unlike other coronaviruses, SARS-CoV-2 seems to be impacting the whole body including the central nervous system.
Researchers have noted that infections with SARS-CoV-2 are associated with a wide range of symptoms which vary from continued difficulty breathing, to mood swings, and to changes in menstrual period cycles (CDC, 2021b). These COVID-19 symptoms can unfortunately hang around for weeks or months after a patient has recovered from the infection and individuals experience long term effects, known as post-COVID conditions (PCC) or long COVID. Some individuals have reported that these symptoms have simply not gone away, but rather seem to be permanent (Chung et al., 2021). The term “long-haulers” has become a frequently used term for those individuals suffering from the long-term effects of COVID-19. There seems to be no correlation between certain risk factors such as high blood pressure or smoking, and long-term problems from the virus. Research focusing on long-haulers remains a very active and relevant line of study impacting 27-33% of individuals who had COVID-19 (Null, 2021).
SARS-CoV-2 also affects the brain, more severely for some individuals than others. These developments include disturbances in a person’s ability to smell and taste and in some cases even cause anosmia, the loss of smell, and ageusia, the loss of taste (Johansson et al., 2021). Some neurological problems that may develop after the infection of COVID-19 can include headaches, dizziness, brain fog, and fatigue. Other symptoms caused by effects to the brain and central nervous system have been reported to include hallucinations and even strokes (Jacobs, 2020). These neurological complications can range from mild to severe.
Impact on Gray Matter
Grey matter is composed of neuronal cell bodies and unmyelinated axons. Gray matter processes information in the brain and can be found in the surface of the cerebral hemispheres, surface of the cerebellum, the hypothalamus, the thalamus, and structures that make up the basal ganglia (Robertson, 2018). It can also be found in the red nucleus, substantia nigra, and cranial nerve nuclei. Any alteration or loss in gray matter can have large implications for overall brain function.
Regardless of severity, COVID-19 seems to reduce gray matter in the brain. In a preliminary, large-scale study (of over 40,000 participants), gray matter tissue was found to be reduced in scans of participants who had contracted COVID-19 in comparison to those who had not (Douaud et al., 2021). The results were the same for individuals who had mild or serve COVID.
Some COVID-19 survivors face symptoms long after recovery since the disease reaches all the body’s organs (Jetelina, 2021). Angiotensin-converting enzyme-2 (ACE2) receptors can be found all over the body and are the gateway for COVID-19 to enter and start to wreak havoc. The virus can enter the body through the olfactory bulb or the oral cavity and from there reach the brain. As the virus spreads, it kills cells and leads to tissue damage in brain areas related to smell, taste, memory, and emotion. This causes not only initial inflammation but a loss of brain tissue in the long run. The brain areas that seem to be affected are directly involved in an individual’s sense of smell and taste. This is one hypothesis to explain the long-term neurological symptoms of COVID-19. SARS-CoV-2 creates a loss of gray matter in the brain to a certain extent in every individual who contracts it, and this loss of gray matter may potentially lead to higher risks of dementia as individuals grow older (Douaud et al., 2021). Since researchers do not yet know why SARS-CoV-2 behaves differently on different brains, further study is required.
Impact on Olfaction
Olfaction is the sense that allows us to detect the presence of odorants in our surroundings. There are six million olfactory cells in the nose, each sending a single axon to the olfactory bulbs (Carlson, 2014). From there, axons project to the amygdala as well as the limbic cortex including the piriform cortex and entorhinal cortex. These brain regions interact with several other parts of the brain to process olfactory information, including the hippocampus, hypothalamus, and orbitofrontal cortex.
The effects of COVID-19 on our sense of smell occur when the virus enters a cell through a receptor (ACE2) that supports neurons in the nose (Brann et al., 2020). These cells are known as sustentacular cells and when the SARS-CoV-2 disease enters through a receptor, the sensory neurons become vulnerable, then leading to infection. Neurologically, the infection activates microglia adjacent to neurons, suggesting neuronophagia in parts of the brain such as the olfactory bulb, substantia nigra, dorsal motor nucleus of the vagal nerve, and the pre-Bötzinger complex in the medulla. Neuronophagia is when damaged neurons are removed by phagocytic cells. When enough neurons have died from the virus and are removed, this causes neurological issues throughout the brain. This then affects our day-to-day lives through our sense of smell. In this same study data showed the SARS-CoV-2 disease damaging support and vascular cells, leading to inflammation. This was thought to produce “leaky” blood vessels in the olfactory bulbs which could affect both the sense of smell as well as taste.
A study at Northeast Ohio Medical University found that olfaction issues were seen more commonly in females than in males (Suresh Kumar et al., 2021). The study was searching for gender-based differences in COVID-19 symptoms and found that women reported a loss of smell and taste slightly more frequently than men. While there was no hypothesis as to why this gender-based difference exists, the study does call for future research on this topic. Another study found similar results, noting that impaired smell and taste were seen more frequently in both younger patients as well as women (Whitcroft & Hummel, 2020). Olfactory dysfunction was found in 64 percent of 202 patients with the virus, with most patients reporting a loss of smell and taste interchangeably.
Impact on Gustation
Gustation is the sense that allows us to detect the presence of tastants in the food we consume. Receptor cells for taste are located on the tongue and send messages to the primary gustatory cortex in the brain (Wein, 2016). The gustatory pathway is from the taste receptors on the tongue through the seventh, ninth, and tenth cranial nerves (Carlson, 2014). This information enters the nucleus of the solitary tract (in the medulla) and is sent by the ventral posteromedial thalamus to the primary gustatory cortex. The primary gustatory cortex is in the basal frontal and insular areas of the brain.
A study on the prevalence of dysfunction in gustation, as well as olfaction, determined that 53% of individuals who contracted COVID-19 had problems with taste and smell (Tong et al., 2020). A full recovery can take up to 6 months, while some individuals have still not regained these senses. Some participants of a study reported a lack of appetite, altered eating habits, and loss of pleasure in food because of this change in gustation (Burges Watson et al., 2021). These disruptions impact a person’s psychological well-being, physical health, and sense of self.
This neurological manifestation seems to relate to the loss of gray matter in limbic cortical areas of the brain, thus affecting the gustatory system (Douaud et al., 2021). The spread of the virus through the olfactory bulb has a direct effect on the gustatory pathway. Since olfaction is intertwined with the experience of taste, the effects of COVID-19 on a person’s sense of smell would affect the sense of taste as well. Another study suggests that since there are a higher number of epithelial cells in the oral cavity, that when ACE2 receptors are targeted by SARS-CoV-2 this might contribute more heavily to the taste disturbances some individuals experience (Harikrishnan, 2020). There is a higher concentration of epithelial cells in this area, making the oral cavity a high-risk route for the virus’ entry into the body.
Conclusion
In conclusion, the COVID-19 pandemic has left its mark on individuals in several ways, including neurologically. A reduction in gray matter in several brain areas, as well as issues of anosmia and ageusia, are common long-term effects found in individuals who contract COVID-19. This reduction occurs through the way that the virus enters cells and eventually tissue in the brain. These infections also lead to a loss of smell and taste, found slightly more often in females and younger patients. These symptoms clear up within a few weeks or months for most individuals who contract COVID-19, but for others, they are experienced long-term. Longitudinal studies are looking at brain scans of these patients and will provide further data in the future. Neurological effects of COVID-19 are being noticed and studied, and the results of further investigations will offer more evidence of how exactly these symptoms are occurring. One thing is for certain, COVID-19 has and will continue to neurologically impact every individual who contracts the virus.