Long-Haul COVID-19: What We Know, and What We Don’t

Written by: Delia Silva, PsyD, ABPP-CN

What is Long-Haul COVID?

“Long-Haul COVID” is a term that has been used extensively in the media to describe people who have experienced persisting physical, cognitive, or emotional symptoms for months following recovery from the acute phase of the SARS-CoV-2 (COVID-19) infection. The reported symptoms have included: “brain fog,” sleep problems, temperature dysregulation, gastrointestinal problems, tachycardia with mild exercise or standing (Vanderlind et al., 2021) dizziness, headache, generalized aches or pain, and loss of smell or taste (Broche-Perez & Medina-Navarro, 2021).  While we may hear about “long-haulers” a lot in the news or may even know people who have experienced these symptoms, there continues to be very little scientific research about this phenomenon. The purpose of this blog article is to summarize what we do know, so far (as of August 2021), about the scientific underpinnings of long-haul COVID-19, particularly with brain functioning.

How Might COVID-19 Affect the Brain?

The way in which the SARS-CoV-2 virus might actually affect the brain is still largely unknown, but there are three main theories:

Cerebrovascular Ischemia:

What appears to be prominent in the scientific studies that have found neurological changes in COVID-19 patients is that these particular patients have had severe respiratory symptoms during the acute infection that required hospitalization, and in most cases, intubation. Additionally, people who are at risk for experiencing severe COVID-19-related symptoms tend to be older in age or have medical co-morbidities, such as high blood pressure or diabetes, which also increases their risk of having a stroke. People who require medical ventilation are at higher risk of experiencing hypoxia, or a lack of oxygen to the brain. There is insufficient research to state that the SARS-CoV-2 virus itself causes strokes or hypoxia. There are hypotheses that require further research about the virus leading to constricting of small blood vessels that could potentially lead to cerebrovascular events.

Secondary Neuroinflammatory Response:

There continues to be a lack of research with this theory, but the hypothesis is that the body’s immune system goes into overdrive to fight off the COVID-19 virus and produces a maladaptive inflammatory response cause more harm to the body’s tissue and organs, maybe more so than the virus itself. Essentially, the immune system may go into overdrive and attack the healthy body tissue. We know this happens with autoimmune disorders such as multiple sclerosis and lupus.

Direct Viral Infection of the Brain:

The evidence for this is still sparse, but there is a theory that the virus may enter the brain through the olfactory pathways in the brain. Loss of smell is a very common symptom reported by patients experiencing a COVID-19 infection, regardless of the severity of other symptoms (deMaria et al., 2020; Voruz et al., 2021). Some mainstream magazines have recently mentioned that the COVID-19 virus appears to specifically attack astrocytes (a specific type of brain cell involved in many “worker” functions), particularly within the limbic system (Douaud et al., 2021). However, those studies have not yet gone through the peer-review process required for publication into scientific journals, and therefore should be looked at with extra scrutiny.

Cognitive Functioning

There are very limited neuropsychological studies examining the neuropsychological profiles for COVID-19 patients at the present time, and the few studies that are available inconsistently exclude people from the sample that might have pre-existing cognitive impairment.

However, what does appear to be emerging from the research is that persisting cognitive symptoms appears to be most prevalent in COVID-19 survivors who have had severe symptoms that required hospitalization. This group of people was at higher risk for experiencing delirium, strokes, and hypoxia. People who experienced delirium during their hospitalization appear to be at highest risk for having persisting cognitive impairment (Burdick & Millett., 2021).

One meta-analytic study (Vanderlind et al., 2021) combined the results of 26 studies and determined that approximately 15-40% of the total participants who underwent formal neuropsychological testing were documented as having abnormal cognitive performance, 10-105 days following hospital discharge. Compared to matched controls, there were significant differences in performance on measures of sustained attention, executive functioning, visuospatial processing, attention, memory, and language. All of these participants had been hospitalized with severe COVID-19 symptoms. Patients who were treated in the ICU and required oxygen therapy were found to have lower scores across most cognitive domains.

On studies that solely looked at self-reported or observer-reported questionnaires that were collected 4-15 weeks after hospital discharge or recovery from the acute phase of COVID-19, approximately 25% reported cognitive complaints (de Graaf et. Al, 2021). People who had medical co-morbidities tended to report problems with concentration and memory loss more often (Mannan et al., 2021).

One study showed that poor cognitive performance was correlated with increased inflammatory markers (Zhou et. Al, 2020).

Psychiatric Symptoms

Psychiatric symptoms are commonly seen in COVID-19 survivors, regardless of the severity of the COVID-19 illness or if they were hospitalized. In some studies, people who had mild COVID-19 infections actually reported having higher levels of depression, stress, anxiety, and reported more cognitive complaints that people who had more severe COVID-19 symptoms (Vanderlind et al., 2021).


Approximately 10-42% of patients who were previously hospitalized due to COVID-19 reported moderate to severe depression, two to three months following discharge. Survivors reporting the most severe levels of depressive symptoms tended to have a prior psychiatric history (Vanderlind et al., 2021).

Similarly, in COVID-19 survivors who were not hospitalized, depression ranged from 15-68%. Risk factors for depression in those groups included female gender, older age, and decreased sense of smell (Vanderlind et al., 2021).


Across 25 studies, clinically significant anxiety symptoms ranged anywhere from 5 to 55.2% of COVID-19 patients. Risk factors for anxiety included: COVID-19 illness severity, co-morbid medical conditions, reduced quality of life, persistent shortness of breath, younger age, having close relatives with COVID-19, having a decreased sense of smell, and having a prior psychiatric history (Vanderlind et al., 2021).

Anxiety related to COVID-19 may be related to the unknowns of the disease process, as we simply still don’t know what to expect. This lack of information about the virus leading to frequent changes in public policies and the emergence of conspiracy theories and “alternative facts” certainly do not help the collective mental health for our society! More in-depth discussion about the day-to-day impact of the pandemic on our mental health can be seen in other articles in our blog series.

Stress most definitely has an impact on the brain and body. The stress response is mediated by the pathways between the hypothalamus, the pituitary gland, and the adrenal gland (“HPA axis”) which sends signals to the body to activate our primitive “fight-or-flight response” while inhibiting our ability to activate our higher-order thinking skills. The high rate of stress in individuals who have experienced COVID-19 infections may be a factor in the cognitive difficulties reported in the long-haulers.


Fatigue following severe COVID-19 infection appears to be the most common finding, with 40-69% of COVID-19 survivors endorsing ongoing fatigue that interfered with their quality of life, two to three months after hospital discharge (Vanderlind et al., 2021).


On one study, about 26% of COVID-19 survivors reported persisting sleep difficulties, six months after being discharged from the hospital (Huang et al., 2021).

What Can We Do Now?

Overall, there’s still a lot more to learn about the long-term effects of COVID-19, particularly on people who have experienced mild cases of COVID-19 without severe respiratory distress. While the medical science is still figuring out the biological effects of the virus on the body and the brain, it appears that reducing inflammation may be a goal in treating long-haul COVID-19 symptoms. Nutrition should certainly not be ignored, as it is known that specific foods can lead to inflammation and others can help to reduce it. Meeting with a registered dietitian to determine an optimal diet is something to consider. Likewise, depression, anxiety, and chronic stress is known to have a physical impact on the body by mechanism of increased production of stress hormones and neurotransmitters (Vogelzangs et al., 2013; Salim et al., 2012). Therefore, psychological treatment for anxiety or depression should be considered as an essential part of a multi-disciplinary approach to treatment of persisting COVID-19 symptoms. Of course, following up with your primary care physician and recommended medical specialists while you continue to experience physical symptoms is recommended to obtain the latest treatment as the science develops.



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