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December 7, 2022

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The Long COVID Series Part 3: Neurologic Consideration

COVID-19 Resources

During the pandemic, the SARS-Co-V-2 virus has been associated with a number of acute neurological problems. Because of this, it should be no surprise that lasting outcomes have also been identified as part of Long COVID. In this segment, we will briefly cover some of the most commonly reported neurologic issues associated with the nervous system and Long COVID.

Neurologic Problems Following COVID-19

Scientific reports of long-term neurologic symptoms following COVID-19 vary. The prevalence of specific neurological complaints six months following COVID-19 infection range from approximately 10 to 34%. The rate of long-term symptoms can approach 50% in those admitted to an ICU. Patients report both central nervous system (CNS) and peripheral nervous system (PNS) symptoms months to years following the initial infection. The most common and important findings associated with the neurologic impacts of Long COVID include high fatigue levels, memory impairment, prolonged cognitive response times, dysnomia, short-term and long-term memory issues, dizziness and an overall decline in general cognitive function.

The Causes of Neurologic Impacts in Long COVID

An overview of COVID-19 pathophysiology is covered in part one of this series. Even though the SARS-CoV-2 virus has an affinity for nerve tissue, the neurologic features of Long COVID do not necessarily result from direct infection of the CNS or PNS. Many symptoms seem to arise because of an aggressive systemic inflammatory and immune response to COVID-19 infection outside of the neurological system. For example, this is supported by evidence that non-neurologic systemic mediators seem to cluster in patients with Long COVID cognitive problems.

At the same time, it is clear that SARS-Co-V-2 can and does directly infect the nervous system. This is particularly true of the CNS where viral encephalitis and meningitis have been reported due to SARS-CoV-2. The pathophysiology associated with these disorders is not well understood, though several reasonable hypotheses have been advanced. Most researchers anticipate multiple factors given the complexity of COVID-19 infection and the immunologic-inflammatory responses.

Specific Neurologic Long COVID Complications

The neurologic symptoms linked to COVID-19 infections are vast. Disorders such as acute stroke, seizures, Bell’s palsy, Guillain-Barre syndrome, sensory dysfunction, transverse myelitis, depression, mood disorders, sleep cycle disturbances, post-traumatic stress disorder (PTSD), dysexecutive syndrome and others have been reported. Exactly how these symptoms and syndromes mesh with Long COVID is not always clear and can differ depending on the definitions and diagnostic criteria used. We will discuss a few of the most common and serious Long COVID neurologic symptoms.

Cognitive Disorders

A particularly concerning aspect of Long COVID is a reported disruption in cognitive function. Although there is no strict scientific definition, various descriptions exist including “Brain Fog.” One group reported a 22% prevalence of cognitive dysfunction (brain fog) after COVID-19 in a sample of patients. In the overall context of Long COVID, fatigue and the neurocognitive impacts have the potential to be the most debilitating.

Researchers have, with varying success measured the levels of these Long COVID-induced mental impacts through cognitive tests. All of the descriptions typically have a decline in global cognitive ability in common. The reported duration of these problems is from six months to greater than two years. The patient often experiences periodic exacerbations and remissions of symptoms. In some patients, the impairments are likely permanent.

Fatigue and Fatigue Syndromes

Fatigue is a commonly reported post-viral syndrome and has been one of the most commonly reported and significant neurologic manifestations of Long COVID. Fatigue also seems to be more prevalent post-COVID-19 than with most other viral diseases, although this may correlate with the larger number of COVID-19 cases.

The fatigue is usually pervasive and debilitating. It may or may not be associated with significant muscle pain and cognitive symptoms. As with the cognitive symptoms, the patient frequently experiences periodic exacerbations and remissions. The mean duration of post-COVID-19 fatigue seems to be about six months; however, reports suggest that up to 33% of patients express continued symptoms from mild to severe for greater than two years.

A number of potential treatments for Long COVID fatigue have been suggested including antivirals, anti-inflammatories, antihistamines and antidepressants. Such agents are either under or have been suggested for investigation. Although well-designed and populated trials are being initiated, none are complete. As such, no specific recommendations can be made at this time. However, one negative therapeutic point does merit mention: Graded Exercise Therapy (GET) is highly controversial. Several large existing studies indicate that GET is not effective. In fact, GET may be harmful in viral-related fatigue syndromes.

Sensory Dysfunction (Anosmia, Dysgeusia, Paresthesia)

Sensory dysfunctions are one of the more common and annoying neurologic symptoms of Long COVID. In fact, loss of smell (anosmia) is so frequent it has often been used as one of the initial clinical manifestations of COVID-19. Most experts are of the opinion that these sensory dysfunctions are probably due to direct SARS-CoV-2 viral infection. In most cases, both anosmia and taste disorders (dysgeusia) tend to resolve after six months but may persist for years.

Zinc preparations, steroids, mucolytics and decongestants have been touted as a potentially helpful treatments for anosmia and dysgeusia, but this is mostly without supporting clinical trial evidence. Feelings of “pins and needles” (paresthesia) is less common but can be somewhat more debilitating depending on the location and severity.


Around three to ten percent of post-COVID-19 patients report persistent headaches (cephalgia) four to six months after infection. Although it is not well characterized in reports, it seems to range from migraines to muscle tension. The headaches are usually periodic and often associated with fatigue. The results of standard treatment approaches are not sufficiently reported as of yet.

Peripheral Neuropathy

Up to 56.3% of COVID-19 patients developed acute peripheral neurologic conditions in one prospective study of 400 cases. Although the authors attempted to decrease bias, it is difficult to sort out complications as all the patients in the study were admitted. Other reports that include outpatients have lower case counts for this disorder. The important issue is to differentiate peripheral or radicular pathology due to COVID-19 from other causes, particularly those that respond to surgical interventions.

Summary: Long COVID Neurologic Considerations

Neurologic conditions in Long COVID are likely the most common and impactful symptoms. The potential for disability and quality of life disruption from these symptoms are considerable. Clinicians must differentiate Long COVID-induced neurologic symptoms from other causes. This often leaves Long COVID neurologic manifestations as “diagnoses of exclusion.”

The most likely causes of Long COVID neurologic symptoms will likely be a combination of infectious, inflammatory/immune and thrombotic mechanisms. Therefore, the development of treatments will likely target these mechanisms; however, for now, most management of Long COVID symptoms remains supportive. While the initiation of trials aimed at learning more has been slow, this will likely change as new studies demonstrate more effective approaches.

Access more COVID-19 resources and see a full list of references.