Most common neurologic symptoms in COVID-19 ‘long-haulers’ include ‘brain fog,’ headache

Non-hospitalized ‘long hauler’ patients with COVID-19 experienced “prominent and persistent” neurological symptoms, including brain fog and fatigue, according to results published in Annals of Clinical and Translational Neurology.

The researchers, who defined “long COVID-19” as symptoms lasting for more than 6 weeks, called long COVID-19 “an important emerging entity” that requires a multidisciplinary approach to care.

“There are many patients who have long term neurological effects of COVID-19 despite a relatively mild illness,” Edith L. Graham, MD, an instructor of neurology (MS/neuroimmunology) at Northwestern University’s Feinberg School of Medicine, told Healio Neurology. “Igor J. Koralnik, MD, FAAN, FANA, chief of neuroinfectious diseases and global neurology and Archibald Church professor of neurology at Northwestern University’s Feinberg School of Medicine, started the Neuro COVID-19 clinic in May 2020 to meet this need.”

Neurologic findings

Graham and colleagues conducted a prospective study of the first 100 consecutive patients presenting to the Neuro COVID-19 clinic between May and November 2020, including 50 individuals who were SARS-CoV-2 lab-positive and 50 who were lab-negative. Because of “early pandemic testing limitations,” researchers used the Infectious Diseases Society of America symptoms of COVID-19 and the presence of neurologic symptoms for more than 6 weeks to include patients and used hospitalizations for pneumonia or hypoxemia as exclusion criteria. They recorded the rate of neurologic symptoms and examined patient-reported quality of life measures as well as standardized cognitive tests, including the Patient Reported Outcome Measurement Information System tool.

The mean age of patients was 43.2 years (±11.3 years; n = 100)) in the study population; 70% were women and 48% were evaluated using telemedicine. The most common comorbidities included depression/anxiety (42%) and autoimmune disease (16%).

“We were surprised to find that a higher proportion of our patients had a pre-existing autoimmune disorder or depression/anxiety compared with the general population,” Graham said. “This may suggest an autoimmune or neuropsychiatric predisposition to long COVID-19.”

The primary neurologic symptoms reported in the study results included “brain fog” (81%), headache (68%), numbness/tingling (60%), dysgeusia (59%), anosmia (55%) and myalgias (55%). Most patients (85%) also reported fatigue. Only anosmia was more common in patients positive for SARS-CoV-2 vs. negative (74% vs. 36%; P < .001). The researchers observed no relationship between time from disease onset and subjective impression of recovery, according to the study results.

Next steps

Both patient groups demonstrated impaired quality of life in cognitive and fatigue domains. Specifically, patients positive for SARS-CoV-2 did poorer on attention and working memory cognitive tasks compared with a demographic-matched U.S. population (T-score, 41.5 vs. 43; both P < .01).

“Patients have a large range of ‘brain fog’ symptoms, from minor impairment in everyday tasks such as ‘Why did I come in this room?’ to much more severe impairment, including inability to return to work and/or being at risk for layoffs due to significant errors at work,” Graham said.

The researchers noted that both patients hospitalized with COVID-19 and non-hospitalized patients have reported symptoms beyond the initial disease onset, ranging from 60 days after to a mean of 4 months. As a result, “several million people in the world” may already be experiencing long COVID-19.

“Many neurologic symptoms such as headaches and anosmia present during the acute infection and never go away. Other symptoms like ‘brain fog’ tend to become more prevalent over time,” Graham said. “Perhaps this is a delayed secondary phenomenon, or it may have been masked by other symptoms early in the disease.”

Graham also said researchers “are still working” to determine the underlying cause of, and the best treatments for, long COVID-19.

“We do not yet have any clinical trials to suggest that one treatment is better than another, so we are treating these patients symptomatically,” she said. “More than 85% of patients had four or more neurologic symptoms, so we typically ask the patient what their biggest complaint is (ie, headaches, pain, anosmia, brain fog, fatigue) and start there. We have a great team of providers in neurology, neuropsychiatry, neuropsychology, sleep medicine and rehabilitation who help address our patients’ needs. Dr. Koralnik and I, along with the medical student Jeffrey R. Clark, BA, and the rest of our research team, are conducting a 6-to-9-month follow-up study to understand the trajectory of recovery in these patients.”