Neurologic Symptoms Frequent in COVID Long-Haulers

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Cognitive dysfunction tops the list of neurologic complaints in long-haul COVID-19 patients whose illness wasn’t severe enough for them to be hospitalized, but it isn’t the only problem, new research shows.

Researchers who tracked 100 COVID-19 long-haul, nonhospitalized patients from May to November found 85% reported four or more neurologic symptoms.

“It’s the first of its kind study on neurological symptoms appearing in patients nonhospitalized,” senior author Igor Koralnik, MD, professor of neurology at Northwestern University, Chicago, Illinois, told Medscape Medical News.

“Most of what we know today [about long-haulers] is what is happening in patients severely sick in the hospital,” Koralnik, who is also chief of neuro-infectious disease and global neurology, added.

The study was published online today in Annals of Clinical and Translational Neurology.

Persistent, Debilitating Symptoms

The patients tracked had clinical symptoms consistent with COVID-19, said Koralnik, but only mild and fleeting respiratory symptoms. None developed pneumonia or low oxygen levels that would have required hospitalization.

Long COVID-19 was defined as symptoms persisting for more than 6 weeks, with the consensus that most patients fully recover from COVID-19 in 4 to 6 weeks.

What was surprising, said Koralnik, was that the patients, despite not needing hospitalization, had persistent and debilitating symptoms for months after symptom onset.

The investigators also found recovery from the symptoms seemed to vary greatly from patient to patient, so it was difficult to predict whether a specific symptom would likely resolve within a certain timeframe.

To track patients’ progress, researchers used the Patient-Reported Outcomes Measurement Information System (PROMIS) quality of life and National Institutes of Health (NIH) toolbox cognitive assessments, among other measures.

The 10 most common complaints among study participants (70% women, average age 43) were:

• Cognitive dysfunction, reported by 81%

• Headache, 68%

• Numbness or tingling, 60%

• Disorder of taste, 59%

• Disorder of smell, 55%

• Muscle pain, 55%

• Dizziness, 47%

• Pain, 43%

• Blurred vision, 30%

• Tinnitus (ringing in the ears), 29%

In addition, many reported non-neurologic symptoms, including:

• Fatigue, 85%

• Depression or anxiety, 47%

• Shortness of breath, 46%

• Chest pain, 37%

• Insomnia, 33%

• Variation of heart rate and blood pressure, 30%

• Gastrointestinal complaints, 29%

The researchers tracked 50 long-haulers who had laboratory-positive tests and 50 with lab-negative tests, although all met the definition of COVID-19 by criteria set by the Infectious Diseases Society of America, said Koralnik.

This reflects the limitations of early testing, he added. Early in the pandemic, people often could not get a test, could not get a test in the timeframe that would accurately detect infection, or had a test that wasn’t sensitive enough to detect infection accurately, he noted.

Patients resided in 21 states; 52 were seen in-person and 48 by telehealth at a neuro COVID-19 clinic. They had either limited or comprehensive cognitive testing; memory and attention deficit problems were common.  

Many patients (42%) reported depression or anxiety prior to COVID diagnosis, said Koralnik, suggesting a “neuropsychiatric vulnerability” to developing long-haul COVID-19.

Approximately 70% of long-haul patients were women and 16% had preexisting autoimmune disorders. This profile, said Koralnik, resembles the female to male ratio of autoimmune diseases such as multiple sclerosis or rheumatoid arthritis.

Although the study did not aim to explain why some patients develop long-haul COVID-19, it suggests post-infectious autoimmune mechanisms may be at play, the investigators note.

The range of symptoms varied widely, with some patients experiencing cognitive impairment and dizziness, with no smell or taste issues, or vice versa, said Koralnik.   

Predicting recovery from specific symptoms is not yet possible, he noted. “People tend to improve over time, but they do it at their own pace.”

“We were hoping the further away from the disease onset, the better the patient would feel recovered. In fact that was not the case,” said Koralnik.

Some reported they were 95% recovered after 2 months, while in 10% it took 9 months. That means it is impossible to tell a patient with specific symptoms to expect recovery after a specific period of time, he noted.

Accurate Reflection of Clinical Practice

Commenting on the findings for Medscape Medical News, Allison Navis, MD, assistant professor of neuro-infectious diseases at the Icahn School of Medicine at Mount Sinai in New York City and lead clinical neurologist at the Post-COVID Center at Mount Sinai, said they reflect clinical practice and noted that she has seen at least 200 long-haul patients.

She welcomed the study’s focus on neurologic symptoms and noted ”we don’t fully understand what is going on” with the long-haul patients.

“We are seeing improvement for a lot of people, but it is taking some time. For some of the more debilitating symptoms, we have treatments,” such as effective headache medications.

One promising clue from the study, said Navis, who was not involved in the research, is the idea that the long-haul symptoms might be an autoimmune response, maybe similar to some other post-infection syndromes. 

The study shows that that it’s important not to be dismissive of patients’ persistent symptoms. “ ’Just get over it’ is not the correct approach,” she said.

No funding source was listed. The study authors have disclosed no relevant financial relationships.

Ann Clin Transl Neurol. Published online March 23, 2021.

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