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This COVID-19 Practice: Hundreds of ‘Long Haulers’ Presenting with Neurologic Complaints at Post-COVID-19 Clinics

Hundreds of COVID-19 "long haulers," whose symptoms persist for months, are presenting with neurologic complaints at post-COVID outpatient clinics that have opened in hard-hit areas of the country.

Most of the patients report non-specific symptoms, which nonetheless require a thorough workup: headache, fatigue, dizziness, myalgia, sleep disorders, difficulty concentrating and disorders of taste or smell, according to neurologists who consult with the clinics.

At the Mount Sinai Center for Post-COVID Care in Manhattan, for instance, one-third of the 300 or so outpatients seen in its first three months of operation required referral to neurology, a neurologist who receives those referrals said.

"The clinic is booked out till January—there's quite the demand," said Allison P. Navis, MD, assistant professor in the division of neuro-infectious diseases at the Icahn School of Medicine at Mount Sinai. "Neurology is one of the top referrals, along with pulmonology and cardiology."

The need for neurologic care was highlighted by a paper published online in Annals of Clinical and Translational Neurology ahead of print on October 5, involving 509 consecutive patients admitted to Northwestern Medicine hospitals in Chicago with COVID-19.  Neurologic manifestations were present at hospitalization in 319 (62.7 percent) patients and at any time during the disease course in 419 patients (82.3 percent).

Strikingly, however, many of the patients presenting with neurologic symptoms at the COVID-19 outpatient clinics never required hospitalization.

"The patients we've been seeing have largely been individuals who were not hospitalized, had a relatively mild version of COVID-19, but have had ongoing neurologic issues," said Felicia Chow, MD, associate professor of neurology and medicine at the University of California, San Francisco.

Apart from the patients who present specific neurologic syndromes such as stroke or Guillain- Barré syndrome, Dr. Navis said, "I don't think there's much evidence of widespread damage to or inflammation of the central nervous system from COVID-19. For a lot of the patients, the symptoms seem more consistent with chronic fatigue syndrome. I don't think this is like with HIV, where we saw AIDS dementia."

At the same time, she and other clinicians emphasized, too little is known about the neurologic sequelae of COVID-19 after less than a year of experience to be certain of prognosis or best treatments.

"This is a complicated entity that we knew nothing about in January," said Ross Zafonte, DO, chair of the Harvard Medical School department of physical medicine and rehabilitation at Spaulding, where he has long specialized in the treatment of brain injuries. "A lot of progress has already been made in reducing the mortality, but it's going to take us maybe a couple of years to learn how to combat the morbidity."

His group has developed a long-term outcome study to evaluate all of the biological, psychological and social manifestations of COVID-19.

The Workup

Fourteen post-COVID care centers have now opened in 10 states: California, Colorado, Connecticut, Illinois, Maryland, Massachusetts, Michigan, New Jersey, New York, and Pennsylvania. However, only one of them focuses solely on the neurologic sequelae of the disease: the Neuro COVID-19 Clinic at Northwestern Memorial Hospital in Chicago.

"We do a full clinical exam that lasts an hour," said the program's founder and director, Igor J. Koralnik, MD, FAAN, FANA, the Archibald Church Professor of Neurology and section chief of neuro-infectious diseases & global neurology at Northwestern Memorial Hospital. 

"We take blood to look at T cells and other factors in patients who are interested to participate to our immunological studies. Those who complain of brain fog can take a tablet-based cognitive test. And the differential diagnosis can lead us to do additional investigations if necessary. That may include a CT scan or MRI, a spinal tap, EMG nerve conduction studies, or EEG."

Dr. Koralnik was the senior author of the paper, analyzing the frequency of neurologic symptoms in COVID patients. The most frequent neurologic symptoms found in the study were myalgias (44.8 percent), headaches (37.7 percent), encephalopathy (31.8 percent), dizziness (29.7 percent), dysgeusia (15.9 percent), and anosmia (11.4 percent). Strokes, movement disorders, motor and sensory deficits, ataxia, and seizures were uncommon (0.2 to 1.4 percent of patients in each). Although 71.1 percent of patients had a favorable functional outcome at discharge, with a modified Rankin Scale of 0-2, "encephalopathy was independently associated with worse functional outcome (OR 0.22; 95% CI 0.11-0.42; p<0.001) and higher mortality within 30 days of hospitalization (35 [21.7%] vs. 11 [3.2%] patients; p<0.001)," the paper reported.

Dr. Navis at Mount Sinai agreed that a thorough workup is essential, especially for patients whose illness required hospitalization. But for the majority of patients who remained ambulatory during their illness, she said, too many tests can cause needless worry.

"When I started seeing these patients in the summer, I did a very broad workup," Dr. Navis said. "But unless a patient has unique or very concerning symptoms, I now think it's important to do a more focused workup. I've had patients who saw other neurologists previously, had million-dollar workups, and got some slightly abnormal results. That can trigger their anxiety. Going overboard with tests that aren't clinically indicated can lead to more issues."

Her basic workup now consists of a neurological exam, a mental status exam, a basic blood panel, as well as tests for B12, thyroid hormone, HIV, and syphilis.

"If the patient has positional headaches, or if they're acute in onset, I might consider getting an MRI or vessel imaging," Dr. Navis said.  

Her primary role, as Dr. Navis sees it, is to rule out serious neurologic issues, "and then to provide a lot of reassurance. That's the most important thing. There's a lot of fear of the unknown. Letting them know that there's nothing really abnormal, nothing to worry about and that hopefully with time, their symptoms will improve."

Gaining the patients' trust, however, takes more than the standard 20-minute exam, she said.

"One thing that's important with this patient population is to spend time, which can be hard for neurologists, to go over tests and explain why the results are not concerning," Dr. Navis said. "A lot of the patients who come to me feel that prior tests results were inadequately explained to them by their previous doctors."  


As is often the case with post- or para-infectious syndromes, especially when viral, "There aren't any specific treatments we have for post-COVID neurologic symptoms," said Dr. Chow. "It's symptomatic management of the issues they're having, whether that's headache or dizziness or cognitive complaints."

Dr. Chow provides neurology consulting to UCSF's post-COVID clinic and is also participating in the university's Long-term Impact of Infection with Novel Coronavirus study.  

Dr. Chow sees post-COVID patients in her neuro-infectious diseases clinic at UCSF and is also involved in developing a study of neurologic complications of COVID led by neurology and internal medicine colleagues as part of UCSF's Long-term Impact of Infection with Novel Coronavirus study.  

"I've seen patients with what seems like postural orthostatic tachycardia syndrome," Dr. Chow said. "They've had COVID with a couple weeks of typical symptoms including fatigue, malaise, cough, and loss of smell and taste. Then they started to feel better, but now they're having this dizziness. We're trying the usual symptomatic treatments. If it weren't for the fact that we're in the middle of a pandemic and these patients had documented COVID-19, there isn't necessarily anything unique or distinct about the complaints or the treatments."      

Dr. Koralnik agreed: "It's not one-size-fits-all," he said. "We treat patients symptomatically."  But, he added, it's important not to assume that all the symptoms of a patient recovering from COVID-19 are due to COVID-19

"You may have a headache because you had a viral illness," he said, "but in addition, you could have a brain tumor or some other disease. Just because you were exposed to a virus doesn't mean you can't have something else going on."

Rather than being directly caused by COVID-19, some of the symptoms may be unmasked by the illness, Dr. Navis said.

"For people who had milder illness, where they're older, and the cognitive tests show mild cognitive impairment, those deficits were probably there before COVID-19," she said. "That's something that I've seen, and other neurologists at Mount Sinai have commented on, that COVID seems to do a lot of unmasking of pre-existing conditions, sometimes even a genetic disorder."

Treatment should not ignore the emotional or psychological impact of patients' experience of surviving a potentially life-threatening illness, clinicians said.   

"A lot of these patients have depression, anxiety or PTSD from their experience with COVID," said Dr. Navis. "I try to address the mental health aspects, to let patients know it's okay if they're dealing with that."

Dr. Zafonte said: "Some of these patients can have an affective issue that could be making things worse. Depression or PTSD can have a real impact on their other symptoms. What I've noticed is that these post-COVID symptoms are really, really multi-factorial."

Dismissing a patient's symptoms as being merely psychological, however, can be destructive, particularly if their COVID antibody test comes back negative, Dr. Koralnik said.

"Some of these patients feel rejected by the medical establishment due to a lack of understanding of what's going on with them," he said. "The Abbott antibody test has been calibrated to detect immunity in patients who were severely sick, with pneumonia, not patients who were ambulatory or did not have severe disease."

Disclosures: Dr. Koralnik has received royalities from UpToDate for chapters on neuro-AIDS and progressive multifocal leukoencephalopathy. Drs. Chow and Navis reported no disclosures. Dr. Zafonte receives royalties from Oakstone for an educational CD- Physical Medicine and Rehabilitation a Comprehensive Review and Demos publishing for serving as co-editor of the textbook, Brain Injury Medicine. Dr. Zafonte serves on the scientific advisory board of Oxeia Biopharma, Biodirection, ElMINDA, and Myomo.

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