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Northwestern Medicine Releases First-of-its-kind Study on the Neurologic Symptoms in Non-Hospitalized COVID-19 Long-Haulers

Includes 100 patients from 21 states; 85% of patients experienced four or more neurologic symptoms with the most frequent being brain fog

A new Northwestern Medicine study published in the Annals of Clinical and Translational Neurology analyzed 100 non-hospitalized COVID-19 long-haulers and discovered 85% of patients experienced four or more neurologic symptoms which impacted their quality of life, and in some patients, their cognitive abilities. The study sought to characterize the range of neurologic manifestations in the first 100 non-hospitalized COVID-19 long-haulers from 21 states who were seen in-person or via telehealth at the Neuro COVID-19 Clinic, part of the Comprehensive COVID-19 Center at Northwestern Memorial Hospital, from May to November 2020.

“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,” says Igor Koralnik, MD, chief of Neuro-infectious Diseases and Global Neurology in the Ken & Ruth Davee Department of Neurology at Northwestern Medicine, who also oversees the Neuro COVID-19 Clinic. “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. 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, the Northwestern Medicine Neuro COVID-19 research group defined long COVID-19 as symptoms lasting more than six weeks, given the majority of patients fully recover by four to six weeks.

Of the 100 non-hospitalized COVID-19 long-haulers who participated in the study:
- Average age was 43
- 70% were female
- 85% reported at least four neurologic symptoms

Most frequent neurologic symptoms:
- Brain fog (81%)
- Headache (68%)
- Numbness/tingling (60%)
- Disorder of taste (59%)
- Disorder of smell (55%)
- Muscle pain (55%)
- Dizziness (47%)
- Pain (43%)
- Blurred vision (30%)
- Tinnitus (29%)

Most frequent non-neurologic symptoms:
- Fatigue (85%)
- Depression/anxiety (47%)
- Shortness of breath (46%)
- Chest pain (37%)
- Insomnia (33%)
- Variation of heart rate and blood pressure (30%)
- Gastrointestinal symptoms (29%)

Most common comorbidities prior to COVID-19 diagnosis:
- 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,” says Dr. Koralnik.

With 70% of patients being women and 16% having a pre-existing autoimmune disorder, Dr. Koralnik notes that it resembles the female to male ratio of autoimmune diseases such as multiple sclerosis (2:1) and rheumatoid arthritis (3:1). Compared to those with positive test results of COVID-19, long-haulers with negative test results came in on average one month later to the clinic.

“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,” adds Dr. Koralnik. “This is reminiscent of the stigma experienced by women with fibromyalgia and chronic fatigue syndrome, highlighting the need for improved diagnostic ‘gold standards’ for COVID-19 infection, which our group hopes to address by elucidating the T cell response of long-haulers against COVID-19 proteins.”

Many patients reported fluctuating symptoms lasting for months; for example, when asked to estimate their percentage of recovery compared to their pre-COVID-19 baseline, patients reported to feel only 64% recovered on average after five months. While most patients tend to improve over time, there are still long-haulers who continue to experience symptoms more than nine months later.

“We are already performing cognitive rehab in some patients and are considering a variety of therapeutic interventions,” says Dr. Koralnik. “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.”

In October 2020, the Northwestern Medicine Neuro COVID-19 research group also published a study in the Annals of Clinical and Translational Neurology that analyzed 509 hospitalized COVID-19 patients and discovered neurologic manifestations happened 82% at any time during the course of the disease.

To learn more about the Neuro COVID-19 Clinic, part of the Comprehensive COVID-19 Center at Northwestern Memorial Hospital, visit nm.org.

Full study published here: https://onlinelibrary.wiley.com/doi/10.1002/acn3.51350.