top of page

More Than a Respiratory Infection

By Allison Lee

Art by Melody Fang

Phone, keys, wallet, mask—the list of items that runs through the minds of most as we rush out of the door in the morning. It used to be just “phone, keys, and wallet,” but since March of 2020, masks have been a crucial new addition to the list. It is no secret that COVID-19 has transformed society in previously unimaginable ways. From babies who have never known a world without COVID-19, to older individuals who have never before experienced something like the pandemic, we have all felt the lasting impacts of this global health crisis.

While remembering a mask in the morning is a minuscule change in comparison to the larger-scale effects of the pandemic on politics, the economy, and cultural norms, it is a common example of how we still feel the effects of the virus in our day-to-day lives. The virus has not only impacted our everyday life; it has also had significant health consequences for people across the globe, with 445 million cases of COVID-19 and upwards of 5.6 million deaths reported worldwide as of February 2022 [1]. However, the virus’s health effects do not always end after the initial infection; many of those diagnosed with COVID-19 experience persistent long-term symptoms beyond short-term respiratory infection, including general fatigue, brain fog, and other neurological conditions [2].

Typical COVID-19 infections present themselves as severe acute respiratory illnesses characterized by symptoms such as cough, shortness of breath, and fever [3]. However, recent research suggests the continuation of long-term neuropsychiatric symptoms in some individuals past the initial acute infection. This is known as “long COVID” [2,4,5]. These lasting symptoms resulting from previous COVID-19 infection are known as sequelae and commonly include cognitive symptoms such as brain fog, impaired mental functioning syndrome, psychosis, newly-onset anxiety, depression, and panic [4,6,7]. Cognitive symptoms in particular, have been seen to persist beyond acute infection, suggesting that neurological damage due to COVID-19 infection may be independent of the respiratory and gastrointestinal symptoms caused by the virus [6,8].

The experience of a 55-year-old woman, who will be referred to as Katherine for the purposes of this article, provides an example of the possible neurological consequences thought to be due to previous COVID-19 infection [9]. Gary Price and associates at the National Hospital for Neurology and Neurosurgery in London found that prior to infection, Katherine had no previous medical conditions [9]. Her case initially presented routine symptoms of COVID-19, defined by the Centers for Disease Control and Prevention (CDC) as fever, cough, loss of smell and taste, and headache [10]. She received typical treatments for COVID-19, including intravenous fluids and increased oxygen via nasal intervention, and she was discharged after two days in good health [9].

The day after her release, however, Katherine started to present more severe neurological symptoms similar to those of long COVID. She reported visual hallucinations of her cat as a lion and was readmitted to the hospital [9]. Upon readmission, she began acting irrationally and exhibiting newly impulsive behavior—spitting, swearing, and throwing items of clothing at the hospital staff. While Katherine presented no abnormal physical symptoms, she showed general confusion about the date and time and anxiety about her surroundings. In addition, she exhibited peculiar behaviors, such as washing her phone in the sink and brushing her teeth with soapy water. She also began associating the color red with people trying to kill her and started believing the hospital staff to be “devils” intent on harming her [9].

Katherine was then treated with haloperidol, an antipsychotic drug commonly used to lessen symptoms of hallucinations and delusions [9,11]. Following treatment with this drug, Katherine’s cognitive state improved [9]. While she still experienced fluctuating periods of paranoia and agitation, her overall awareness of reality and her surroundings bettered drastically. At times, she even expressed remorse about her violent behavior towards hospital staff. On day 52 of her readmittance to the hospital, she finally reported no psychotic symptoms. While the paranoia, delusions, and hallucinations Katherine experienced continue to confound researchers, her responsiveness to traditional antipsychotic treatment suggests that psychosis was indeed an element of her post-COVID health. The close onset of these cognitive symptoms to her infection with COVID-19 further suggests that an element of Katherine’s psychosis was linked to her infection with the virus [9].

As we are still in the midst of the pandemic, it is hard to paint a complete picture of the impact that COVID-19 infection can have on the brain. Knowledge of the virus changes by the day, but we may be able to better understand the effects of the virus by analyzing similar conditions. Some of the long-term psychological COVID-19 symptoms Katherine experienced mirror those of more thoroughly researched conditions such as traumatic brain injuries and various chronic brain disorders [9]. Katherine displayed symptoms of disorientation, delusions, and confusion that are similar to those of neurodegenerative conditions such as Alzheimer’s and other forms of dementia [12]. Changes in psychological and neurological function—as in such neurodegenerative disorders—can often be destabilizing, changing an individual’s emotional reactions, sense of understanding, and ability to communicate [13]. Thus, changes in brain function may cause extreme changes in the way a person presents themselves to others [14].

Neurological symptoms of COVID-19 show strong similarities to those of Alzheimer’s disease including disorientation, mood and behavior change, memory loss, and unfounded suspicions about family, friends, and professional caregivers [12,15]. In fact, the antipsychotic drug haloperidol used in Katherine’s treatment is also used in Alzheimer’s treatments to ease psychosis and related symptoms [16]. While these conditions initially seemed linked only by their similar symptoms, a recent study suggests that there may be strong neural parallels between COVID-19 and Alzheimer’s disease [17]. Through a review analysis of current COVID-19 knowledge and previous knowledge about Alzheimer’s disease, the study found that many of the symptoms characteristic of both conditions arise from damage to the central nervous system (CNS) [17].

The onset of both conditions is due partly to increased interactions between the COVID-19 viral particle and the ACE2 receptor, a protein found to facilitate the entry of the virus into body cells [18]. Post-mortem studies of Alzheimer’s patients’ brains revealed ACE2 gene activity to be associated with development of the neurodegenerative disease [17]. Similarly, in COVID-19, neurological symptoms have been found to present as a result of interaction between the COVID-19 spike protein and the ACE2 protein [17]. Researchers hypothesize that when interacting with the ACE2 protein, COVID-19 infection may cause damage to the CNS directly through neurotoxicity—the disruption of neural activity by toxins, including viruses—or indirectly through the activation of the body’s natural immune response to fight against the virus [19]. Prolonged interactions with the virus can lead to neurodegeneration, or the progressive loss of neurons, which could accelerate brain aging and the development of diseases like Alzheimer’s [17]. The implications of interactions with the ACE2 gene in both Alzheimer’s disease and COVID-19 infection suggest that the cognitive impairment frequently experienced by patients of COVID-19 could represent a critical repercussion of COVID-19 infection [17].

Some COVID-19 symptoms also closely resemble the symptoms commonly associated with dementia, such as memory loss, poor judgment, confusion, paranoia, impulsive actions, hallucinations, and delusions [20]. Although dementia shares symptoms with Alzheimer’s, it is a separately defined condition. Unlike Alzheimer’s, which is classified as a neurodegenerative disease, dementia describes the larger group of symptoms associated with a decline in memory and reasoning [12]. The relationship between patients with Alzheimer’s disease or dementia and COVID-19 patients has been further explored using neuroimaging techniques. A 2021 study by Praveen Sharma et al. found brain abnormalities in patients infected with COVID-19 such as large vessel occlusion (strokes due to insufficient oxygen), cerebral venous thrombosis (clotting), and damage to the arteries supplying the brain with blood [21]. These findings are in accordance with the typical neuroimaging results of the brains of individuals with Alzheimer’s disease and dementia [22].

In addition to offering insight into COVID-19’s possible connection to Alzheimer’s and dementia, cases like Katherine’s have prompted further investigation into the heightened neurological effects following infection with COVID-19. Jennifer Frontera et al. sought to explore this phenomenon in greater depth through examining the symptomatic manifestations of post-COVID neurological conditions. They conducted a study examining the differences in cognitive processes of patients hospitalized for COVID-19 infection across four New York City area hospitals [23]. Over the course of six months, observational interviews were performed to assess the long-term outcomes of COVID-19 infection among these hospitalized patients.

Researchers found that 13.49 percent of patients experienced the onset of neurological disorders. Impaired cognition, which is often characterized by forgetting events or difficulty remembering words, occurred in 50 percent of these patients with new-onset neurological complications. Additionally, 46 percent experienced worsened anxiety, 38 percent experienced worsened fatigue, and 25 percent experienced worsened depression. These patients also experienced significantly worse physical and mental outcomes, with 47 percent of patients unable to return to work during the six-month period following infection. Furthermore, abnormalities in functional and cognitive processes were present in more than 90 percent of patients within the six months following hospitalization [20,23].

Considering this evidence suggesting the existence and severity of neurological conditions following COVID-19 infection, Maxime Taquet et al. further sought to profile the probability of neurological and psychiatric disorder diagnoses in the sixth months following COVID-19 infection through a retrospective study [24]. Using data from TriNetX, an extensive health record network boasting data from over 81 million patients, researchers conducted a statistical analysis to determine the likelihood of diagnosis with neurological or psychiatric disorders in the six months following an individual’s infection with COVID-19. Investigators examined data from three cohorts—patients with a COVID-19 diagnosis, patients diagnosed with influenza and not COVID-19, and a control cohort of patients diagnosed with other respiratory tract infections. The incidence of neurological and psychiatric diagnoses was assessed via determination of the diagnosis rates of 14 conditions, including stroke, Parkinson’s disease, dementia, and psychosis. Researchers found that the likelihood of diagnosis with a neurological or psychiatric disorder in the six-month period following infection was significantly higher for patients who had COVID-19 than for patients who were previously diagnosed with influenza or other respiratory tract infections. Of the 236,379 patients diagnosed with COVID-19, the incidence rate of neurological or psychiatric disorders within six months was 33.62 percent, whereas incidence rates were only 1.44 percent and 1.16 percent following infection with influenza or other respiratory tract infections, respectively [24].

Researchers in this same study also performed a Hazard Ratio (HR) analysis to assess the likelihood of a patient contracting a defined “hazard,” with a value over one indicating increased probability [24]. In this study, HR analysis was conducted for a multitude of neurological disorders, or “hazards,” including mood, anxiety, and psychotic disorders. HR analyses revealed that the likelihood of these neurological “hazards” developing was much higher for patients infected with COVID-19 than for patients with any other respiratory tract infections: COVID-19 positive patients had an HR value of 1.44 for any neurological diagnosis, while other respiratory tract infections yielded an HR value of only 1.16 [24]. This analysis further supports the hypothesis that COVID-19 patients are more likely to develop symptoms associated with neurological disorders after infection.

Katherine’s story has shown us the effects that COVID-19 may have on typical brain function. While her experience with the virus is unique, Katherine faced an incredibly disorienting and unsettling period of life. To better understand how these perturbing psychological symptoms develop, an understanding of the mechanisms by which COVID-19 enters the brain is crucial. COVID-19 viral particles have been detected in the medulla, the brain region responsible for heartbeat and respiration, and the cerebellum, which is implicated in balance and kinesthetic movement [25,26]. Although there are not yet any clear explanations as to how COVID-19 enters the brain, there are a multitude of theories surrounding the topic [8]. One theory suggests that since the virus is known to penetrate the olfactory mucosa, the mucus-secreting membrane in the upper region of the nose, viral particles may enter the brain through the olfactory tract and subsequently infect the olfactory bulb [8]. The olfactory bulb, which is located in the most anterior, or frontal, part of the forebrain, is responsible for receiving information concerning scent and transferring it to other regions of the brain [27,28]. Infection of this region could explain why one of the hallmark symptoms of COVID-19 is anosmia, the loss of one’s sense of smell [8].

Furthermore, researchers believe that infection of the olfactory bulb leads to the activation of non-neuronal cells, such as glial and mast cells, which act as support for the neural system [19]. Unlike neurons, non-neuronal cells are not actually responsible for transmitting and processing information [19]. When activated, non-neuronal cells promote an inflammatory response. The non-neuronal cells increase the release of cytokines—small proteins responsible for triggering an immune response [29]. This release ultimately disrupts the body’s ideal chemical and physical state, known as homeostasis, and causes an increase in overall bodily inflammation. Specifically, the sudden change in internal homeostasis can also result in uncontrollable inflammation in the brain and is thought to have the potential to induce changes in overall brain function, as well as increase the likelihood of neurodegeneration disorders, such as Alzheimer’s disease [29].

Another theory suggests that the neural and psychological symptoms such as those displayed by Katherine could be the result of other types of immune malfunction [30]. A study conducted by Prüss et al. posited that some people’s immune systems overreact and can misfire in response to any infection, including COVID-19. In this case, the body can be its own worst enemy, as this misfiring can result in the creation of anti-neuronal auto-antibodies, or antibodies specifically targeting one’s own neural tissue [31]. Researchers collaborating on the Prüss et al. study collected and examined the blood and cerebrospinal fluid of 11 individuals who were deemed critically ill due to COVID-19 infection and were experiencing severe neurological symptoms such as delirium, epileptic seizures, and vision-related disturbances [31]. From an analysis of these fluids via antibody detecting techniques, researchers found that all examined individuals produced auto-antibodies capable of binding to neurons and potentially disrupting brain function [31]. While these findings do not provide a comprehensive explanation for the viral impact of COVID-19 on neurological function, they do suggest that autoimmune responses triggered by viruses may play a role in the onset of later neurological symptoms.

A final theory surrounding the harmful effects of COVID-19 on the neural system suggests that the impairment of neurological function is a result of restricted blood flow due to viral infection [32]. A study conducted by David Atwell et al. found that COVID-19 can affect the behavior of pericytes, cells found on capillaries throughout the brain [33]. Pericytes play an important role in controlling blood flow to the brain that supplies neurons with the oxygen and glucose needed to function [33]. Neurons are responsible for practically all bodily functions, so their impairment by pericytes has the potential to drastically alter brain function.

Atwell and associates concluded that COVID-19 affects pericyte behavior by analyzing the brains of golden hamsters infected with the virus [32]. Following infection, the researchers used live imaging of infected hamsters’ brains to quantify the response of pericytes to COVID-19. They found that COVID-19 viral particles can block the ACE2 receptor on the surface of pericyte cells, a receptor not only responsible for regulating capillary action but also implicated in enhancing COVID-19 infection development, as mentioned earlier [32]. The blocking of ACE2 causes capillaries to constrict and rapidly reduce blood flow to the brain, resulting in symptoms akin to those seen in stroke patients, such as confusion and numbness [34]. Their study demonstrated that prolonged restricted blood flow to the brain undoubtedly had adverse effects on overall brain function and may play an important role in the onset of psychological and neurological symptoms [33]. Thus it can be interpreted that these symptoms could be remedied by blood pressure medications, easing the stress on the neuronal capillaries.

While it is clear that COVID-19 infection has profound effects on the overall health of presently infected individuals, it is also important to consider the more generational repercussions of the virus. To this end, recent research has explored the effects of COVID-19 infection in pregnant individuals. A study conducted by Kaisenberg and associates found that maternal infection with COVID-19 can also lead to severe brain damage in developing fetuses [35]. The study, focusing on a 36-year-old woman who contracted COVID-19 in her 25th week of pregnancy, found that infection with the virus, causing severe respiratory decline, had devastating effects on fetal development [35]. While the fetus’s development appeared typical initially, viral infection eventually caused the mother’s lung function to drastically deteriorate and deprive the fetus of adequate oxygen [35]. Following two weeks of treatment for infection, ultrasound analysis revealed severe fetal brain bleeding which progressed into overall deterioration of the fetal brain [35]. This included the irreversible decline of the basal ganglia—the brain region largely responsible for emotion regulation and motor control—leading to the pregnancy’s ultimate termination [35,36]. While this individual’s experience represents an extreme of the possible pre-birth effects of COVID-19, it is likely that the virus has at least some level of effect on pregnancy.

Such tragic effects of COVID-19 on fetal development contribute to a larger conversation on the social impact of the virus. The pressure COVID-19 puts on hospitals inevitably trickles down to others hoping to receive care, regardless of whether it is for the virus. In the case of pregnancy specifically, new mothers often feel this strain through limitations in resources needed for prenatal care as well as in the anxiety and restlessness associated with fear for the health of their child and themselves [37]. While the social impacts of COVID-19 continue well beyond the scope of this article, the virus has undoubtedly had an impact greater than just its immediate infection. COVID-19 research is ongoing, and we learn new information about the virus every day. Thus, it is important to remember that despite our greatest efforts, it is impossible for this article to touch upon all aspects of current COVID-19 research. Our pursuit of knowledge is continuous, and it will take time before we know the true extent of the virus’s repercussions. However, one thing is certain: the effects of COVID-19 are here to stay, and it is imperative that we continue to take the virus seriously. Whether you feel its impact both physically and psychologically, through yourself or your children, or even more subtly through differences in out-the-door routines, the impression COVID-19 has left on the human race is long lasting. As the virus continues to develop, so must we. While we do not know what the future of COVID-19 holds, it is becoming increasingly important that we have the strength to face what it might bring.


12. Alzheimer’s Association. (2021). Dementia vs. Alzheimer’s Disease: What is the Difference? (n.d.). Alzheimer’s Disease and Dementia. Retrieved February 4, 2022, from

13. Guynup, S. (2021). Can COVID-19 alter your personality? Here's what brain research shows. National Geographic. Retrieved January 26, 2022, from

14. Chow, T. W. (2000). Personality in frontal lobe disorders. Current Psychiatry Reports, 2(5), 446–451.

15. Smith, C. M., Gilbert, E. B., Riordan, P. A., Helmke, N., von Isenburg, M., Kincaid, B. R., & Shirey, K. G. (2021). COVID-19-associated psychosis: A systematic review of case reports. General Hospital Psychiatry, 73, 84–100.

19. NIH. (2019). Brain basics: The life and death of a neuron. National Institute of Neurological Disorders and Stroke. Retrieved April 8, 2022, from

20. NIH. (2021). What is dementia? Symptoms, types, and diagnosis. National Institute on Aging. Retrieved April 8, 2022, from

22. Hakim, A. M. (2019). Small vessel disease. Frontiers in Neurology, 10.

23. Frontera, J. A., Yang, D., Lewis, A., Patel, P., Medicherla, C., Arena, V., Fang, T., Andino, A., Snyder, T., Madhavan, M., Gratch, D., Fuchs, B., Dessy, A., Canizares, M., Jauregui, R., Thomas, B., Bauman, K., Olivera, A., Bhagat, D., Sonson, M., … Galetta, S. (2021). A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications. Journal of the Neurological Sciences, 426, 117486.

24. Taquet, M., Geddes, J. R., Husain, M., Luciano, S., & Harrison, P. J. (2021). 6-month neurological and psychiatric outcomes in 236379 survivors of COVID-19: A retrospective cohort study using electronic health records. The Lancet Psychiatry, 8(5), 416–427.

25. Later Development of Embryonic Central Nervous System. (2014). In Reference Module in Biomedical Sciences. Elsevier.

26. Halvorson, K. G., Lober, R. M., & Grant, G. A. (2017). Cerebellar astrocytomas. In Youmans and Winn Neurological Surgery (Seventh Edition.). Elsevier.

27. ​​NCI Dictionary of Cancer Terms. (2011) Definition of olfactory bulb. National Cancer Institute. Retrieved April 4, 2022, from

29. Zhang, J. M., & An, J. (2007). Cytokines, inflammation, and pain. International anesthesiology clinics, 45(2), 27–37.

30. Marshall, M. (2021). Covid and the brain: Researchers zero in on how damage occurs. Nature News. Retrieved April 4, 2022, from

31. Franke, C., Ferse, C., Kreye, J., Reincke, S. M., Sanchez-Sendin, E., Rocco, A., Steinbrenner, M., Angermair, S., Treskatsch, S., Zickler, D., Eckardt, K. U., Dersch, R., Hosp, J., Audebert, H. J., Endres, M., Ploner, J. C., & Prüss, H. (2021). High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms. Brain, behavior, and immunity, 93, 415–419.

32. Hirunpattarasilp, C., James, G., Freitas, F., Sethi, H., Kittler, J. T., Huo, J., Owens, R. J., & Attwell, D. (2021). SARS-COV-2 binding to ACE2 triggers pericyte-mediated angiotensin-evoked cerebral capillary constriction.

33. Attwell, D., Mishra, A., Hall, C. N., O'Farrell, F. M., & Dalkara, T. (2016). What is a pericyte?. Journal of Cerebral Blood Fflow and Mmetabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 36(2), 451–455.

35. Düppers, A. L., Bohnhorst, B., Bültmann, E., Schulz, T., Higgins‐Wood, L., & Kaisenberg, C. S. (2021). Severe fetal brain damage subsequent to acute maternal hypoxemic deterioration in COVID ‐19. Ultrasound in Obstetrics & Gynecology, 58(3), 490–491.

36. Lanciego, J. L., Luquin, N., & Obeso, J. A. (2012). Functional neuroanatomy of the basal ganglia. Cold Spring Harbor Perspectives in Medicine, 2(12), a009621.

63 views0 comments

Recent Posts

See All


bottom of page