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Novel Study Finds Mild COVID-19 Associated with Prominent, Persistent Neurologic Symptoms


Brain fog topped the list of neurological symptoms in patients with long-haul COVID-19 whose illness was not severe enough to warrant hospitalization, according to a novel study.



Non-hospitalized coronavirus disease 2019 (COVID-19) “long haulers” experience prominent and persistent neurologic symptoms that affect cognition and quality of life, according to a new study published March 23, 2021 in the Annals of Clinical and Translational Neurology.

“Our study is the first to report neurologic findings in non-hospitalized COVID-19 long-haulers, including detailed neurologic exam, diagnostic testing, and validated measures of patient quality of life, as well as cognitive function test results,” said corresponding author Igor Koralnik, MD, chief of Neuro-infectious Diseases and Global Neurology, Ken & Ruth Davee Department of Neurology, Northwestern Medicine, in a press release.

Koralnik and colleagues sought to characterize the range of neurologic manifestations in the first 100 consecutive patients presenting to the Nuero-COVID-19 Clinic, part of the Comprehensive COVID-19 Center at Northwestern Memorial Hospital, between May and November 2020. Patients came from 21 states.

“At the beginning of the pandemic, patients with mild disease often didn’t qualify for nasal swab or serology testing. Because of this, we included 50 long-haulers with laboratory-positive tests and 50 with laboratory-negative tests,” said Koralnik in the press release. “All patients in this study had clinical symptoms consistent with COVID-19, but only had mild and transient respiratory symptoms (sore throat, cough, mild fever) and never developed pneumonia or low oxygen levels requiring hospitalization.”

For the purposes of the study, researchers defined “long COVID-19” as symptoms lasting >6 weeks, given that most patients fully recover within 4-6 weeks.

"Our study is the first to report neurologic findings in non-hospitalized COVID-19 long-haulers, including detailed neurologic exam, diagnostic testing, and validated measures of patient quality of life, as well as cognitive function test results."

Out of the 100 non-hospitalized COVID-19 long-haulers included in the study, the average age was 43 years, 70% were women, and 85% reported experiencing ≥4 neurologic symptoms.

The main neurologic symptoms reported by participants were brain fog (81%), headache (68%), numbness/tingling (60%), dysgeusia (59%), anosmia (55%), and myalgias (55%).

Fatigue was the most common non-neurological symptom reported by participants (85%), followed by depression/anxiety (47%), shortness of breath (46%), chest pain (37%), insomnia (33%), variation of heart rate and blood pressure (30%), and gastrointestinal symptoms (29%).

In addition, the most common comorbidities prior to COVID-19 diagnosis were:

  • Depression/anxiety (42%)
  • Autoimmune disease (16%)
  • Insomnia (16%)
  • Lung disease (16%)
  • Headache (14%)

“We were surprised by the number of patients who were suffering from depression/anxiety before their COVID-19 diagnosis, and this suggests a possible neuropsychiatric vulnerability to developing long COVID,” added Koralnik in the press release.

Long-haulers who were COVID-19-negative came into the clinic on average 1 month later vs those who were COVID-19-positive. “This may have been caused by the difficulty for these patients to find medical providers, since they do not fit into classical diagnostic criteria of COVID-19,” explained Koralnik. He pointed to a parallel with the stigma experienced by patients with fibromyalgia and chronic fatigue syndrome that underscores the need for diagnostic “gold standards” for COVID-19 infection.

Also, participants reported fluctuating symptoms that lasted for months. For example, when asked to estimate their percentage of recovery compared to their pre-COVID-19 baseline, participants reported to feel 64% recovered on average after 5 months.

“We are already performing cognitive rehab in some patients and are considering a variety of therapeutic interventions,” concluded Koralnik in the press release. “We are also evaluating long-lasting neurologic symptoms across larger groups of COVID-19 patients including those with a history of hospitalization for severe illness. Future extended studies are needed to evaluate the cognitive impacts on long-haulers and devise appropriate treatment options.”

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