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What Is the Newest Guidance for Neurologic Complications of Long COVID?

  • Authors: News Author: Alicia Ault; CME Author: Charles P. Vega, MD
  • CME / ABIM MOC / CE Released: 6/23/2023
  • Valid for credit through: 6/23/2024, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for primary care clinicians, neurologists, nurses, pharmacists, physician assistants, and other clinicians who care for patients with post-acute sequelae of COVID-19 (PASC).

The goal of this activity is for learners to be better able to evaluate the management of patients with neurologic symptoms of PASC.

Upon completion of this activity, participants will:

  • Assess health conditions that might predispose patients to PASC
  • Evaluate the management of patients with neurologic symptoms of PASC
  • Outline implications for the healthcare team


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News Author

  • Alicia Ault

    Freelance writer, Medscape


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CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine


    Charles P. Vega, MD, has the following relevant financial relationships:
    Consultant or advisor for: Boehringer Ingelheim Pharmaceuticals, Inc.; GlaxoSmithKline; Johnson & Johnson Research & Development, L.L.C.

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  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC


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  • Stephanie Corder, ND, RN, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC


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What Is the Newest Guidance for Neurologic Complications of Long COVID?

Authors: News Author: Alicia Ault; CME Author: Charles P. Vega, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 6/23/2023

Valid for credit through: 6/23/2024, 11:59 PM EST


Clinical Context

Post-acute sequelae of COVID-19 (PASC) is one of the most consequential outcomes of COVID-19. A study by Fritsche and colleagues, which was published in the February 2023 issue of the Journal of Clinical Medicine, analyzed the prevalence and symptoms of PASC in a cohort of more than 60,000 patients with a history of COVID-19.[1] The retrospective analysis was conducted using health records at one large US academic health center.

A small percentage (2.7%) of patients with COVID-19 had a diagnosis of PASC. The most common symptoms of PASC were shortness of breath, anxiety, fatigue, depression, and sleep disorders. Researchers also found multiple pre--COVID-19 conditions associated with a higher risk for PASC, including irritable bowel syndrome, concussion, nausea and vomiting, respiratory conditions, food allergies, and circulatory conditions; however, the presence of these conditions was still a poor predictor of PASC after COVID-19.

Neurologic symptoms are also a prominent feature of many cases of PASC. The current review by Melamed and colleagues highlights these symptoms and their management.

Study Synopsis and Perspective

The American Academy of Physical Medicine and Rehabilitation (AAPM&R) has issued new consensus guidance on the assessment and treatment of neurologic sequelae in patients with long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC).

The new recommendations, which were published online May 16 in Physical Medicine & Rehabilitation,[2] are the result of a collaboration among experts from a variety of medical specialties at 41 long COVID clinics across the United States.

Because physical medicine specialists treat individuals with disability and functional impairments, the AAPM&R was among the first organizations to initiate guidance for the assessment and treatment of long COVID and issued its first consensus statement that addressed long COVID-related fatigue in 2021.[3]

Even though the number of COVID-19 cases and hospitalizations has declined from the peak, long COVID continues to be a major public health issue, Steven Flanagan, MD, AAPM&R president-elect and Howard A. Rusk Professor of Rehabilitation Medicine at NYU Grossman School of Medicine, New York, New York, told reporters attending a press briefing.

"There is some evidence that some of the antivirals may actually help reduce the incidence but not everybody gets them," said Flanagan, in a briefing with reporters.

"In our own clinic here, we continue to see many, many people with problems associated with long COVID," he added.

According to the consensus guidelines, about 80% of patients hospitalized with acute COVID-19 have neurologic symptoms, but these symptoms are not just limited to people who had severe illness, said Leslie Rydberg, MD, co-author of the neurology long COVID guidance statement.

"What we know is that many people with mild or moderate COVID[-19] infection end up with neurologic sequelae that last longer than 4 weeks," said Rydberg, the Henry and Monika Betts Medical Student Education Chair and assistant residency program director at Shirley Ryan AbilityLab, Chicago, Illinois.

Rydberg added that patients who have symptoms for longer than a month after the initial infection should be evaluated. Although the definition of what constitutes PASC is evolving, the guidance states that the literature indicates that it should be defined as the persistence of symptoms 4 weeks beyond the initial infection.

The most common neurologic symptoms are headache, weakness, muscular pain, nerve pain, tremors, peripheral nerve issues, sleep issues, and cognitive effects, Rydberg told reporters.

She added that "identifying patients with progressive or ominous 'red flag' neurologic symptoms is essential for emergent triaging."

Among the red flags are sudden or progressive weakness or sudden or progressive sensory changes because those could indicate an acute neurologic condition -- either due to long COVID or other illnesses -- such as a stroke or a problem with the spinal cord, Guillain-Barre syndrome (GBS), or myopathy.

Although those signs and symptoms would likely be flagged by most clinicians, some of the emergent or urgent signs -- such as upper motor neuron changes on physical exam -- are more subtle, said Rydberg.

The new guidance spells out steps for initial evaluation, including identification of red flag symptoms, and also provides treatment recommendations.

Experts also recommend clinicians do the following:

  • Treat underlying medical conditions, such as pain, psychiatric, cardiovascular, respiratory, and other conditions that may be contributing to neurologic symptoms
  • Consider polypharmacy reduction, looking especially closely at medications with a known impact on neurologic symptoms
  • Urge patients to get regular physical activity, as tolerated, while avoiding overuse syndrome
  • Work with physical, occupational, and speech therapists to increase function and independence
  • Refer patients to counseling and community resources for risk factor modification

The treatment recommendations are more in-depth for specific long COVID conditions, including headache, cranial neuropathies, sleep disturbances, and neuropathies.

The guidance also includes a special statement on the importance of ensuring equitable access to care.

Underserved, marginalized, and socioeconomically disadvantaged communities had notably higher rates of infection, hospitalization, and death with less access to rehabilitation services before the pandemic, said Monica Verduzco-Gutierrez, MD, chair of the department of rehabilitation medicine at the Long School of Medicine at The University of Texas Health Center at San Antonio and a guideline co-author.

"We know that these communities have been historically underserved, that there's already access issues, and that they're disproportionately impacted by the pandemic," said Verduzco-Gutierrez. "This continues as patients develop PASC, or long COVID," she said, adding that these individuals are still less likely to receive rehabilitation services. "This can lead to poorer outcomes and widened disparities."

The AAPM&R PASC Multi-Disciplinary Collaborative has previously issued consensus guidance on fatigue, breathing discomfort and respiratory distress, cognitive symptoms, cardiovascular complications, pediatrics, and autonomic dysfunction and will be publishing guidance on mental health soon.

The collaborative is also putting together a compilation of all the guidance: a 'greatest hits' if you like," said Verduzco-Gutierrez.

For clinicians who are unaccustomed to caring for patients with long COVID, the hope is that this new guidance will help them manage the condition, Rydberg said.

The guidance was written with the support of the AAPM&R. Melamed and 2 co-authors have disclosed grants, contracts, or honoraria from various funding sources, some paid to their institutions and some personal reimbursement for activities related to PASC and broader areas of research and expertise; however, none of the authors have any conflicts relative to the work on the guidance.

Study Highlights

  • There are now different definitions of PASC, but symptoms extending ≥ 4 weeks after acute COVID-19 remains widely accepted as part of the definition.
  • Neurologic symptoms affect ~ 80% of patients after hospital discharge for COVID-19. The most prominent symptoms include brain fog, headache, numbness/tingling, dysgeusia, anosmia, and myalgias.
  • The risk for cognitive disorders and epilepsy remains increased at 2 years after the diagnosis of COVID-19, but the risk for mood and anxiety disorders was not long-lasting after the resolution of acute COVID-19.
  • ≤ 10% of patients with COVID-19 critical illness have a cranial nerve involvement.
  • PASC symptoms do not fully correlate with the severity of acute COVID-19 symptoms. Patients with mild COVID-19 can still develop PASC.
  • Red flag symptoms that deserve immediate attention in PASC include progressive weakness, hallucinations, severe headache, and unexplained upper motor neuron findings, such as clonus, spasticity, or impaired bladder or bowel function.
  • GBS/Miller Fisher syndrome (MFS) has also been reported after COVID-19.
  • The routine laboratory assessment of neurologic symptoms of PASC should include a complete blood count with differential; chemistries, including renal and hepatic function tests, thyroid stimulating hormone, C-reactive protein, erythrocyte sedimentation rate, vitamins B1, B6, B12, and D, magnesium, and glycated hemoglobin.
  • Multiple cranial neuropathies may prompt a lumbar puncture for evaluation of cytoalbuminologic dissociation toward a diagnosis of GBS/MFS. Clinicians can consider testing for antinuclear antibodies, antimyelin oligodendrocyte antibodies, and antibodies to gangliosides GM1, GD1b, and GQ1b in cases of neuropathy.
  • Isolated cranial neuropathies may respond to corticosteroids, and antiherpetic drugs should be applied in cases of suspected latent neuronal herpes virus infection.
  • One study found that the prevalence of headache during the first 6 months after COVID-19 was 8% to 15%. Clinicians should be aware medication overuse is a common cause of headache in the post--COVID-19 period. Magnetic resonance imaging of the brain may be used if there are particularly dangerous features of headache.
  • Over one-third of patients with COVID-19 have sleep disturbance. Cognitive behavioral therapy remains the first-line treatment for insomnia generally and in PASC specifically.
  • The prevalence of muscle pain and weakness in PASC is widely variable. Clinicians should consider workup with creatine kinase levels and electromyography for these patients.

Implications for the Healthcare Team

  • In a previous study by Fritsche and colleagues, health conditions that were significantly associated with a higher risk for PASC included irritable bowel syndrome, concussion, nausea and vomiting, respiratory conditions, food allergies, and circulatory conditions.
  • The routine laboratory assessment of neurologic symptoms of PASC should include a complete blood count with differential and chemistries including renal and hepatic function tests; thyroid stimulating hormone; c-reactive protein; erythrocyte sedimentation rate; vitamins B1, B6, B12, and D; magnesium; and hemoglobin A1c.
  • The healthcare team should be aware of red flag symptoms following COVID-19 and initiate a workup and treatment when possible for neurologic symptoms of PASC.


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