Clinical Phenotyping of Long COVID Patients Evaluated in a Specialized Neuro-COVID Clinic

Abstract

Objective: To report Long COVID characteristics and longitudinal courses of patients evaluated between 4/14/21-4/14/22 at the University of Pennsylvania Neurological COVID Clinic (PNCC), including clinical symptoms, neurological examination findings, and neurocognitive screening tests from a standardized PNCC neurological evaluation approach.

Methods: This is a retrospective cross-sectional and longitudinal study in a single-center tertiary care academic center. Participants include 240 patients with documented evidence of a positive SARS-CoV-2 PCR or antibody test who underwent initial evaluation and 182 patients with longitudinal follow-up. Main outcomes evaluated are patient demographics, duration of illness prior to self-reported improvement, and cognitive testing results-including the Montreal Cognitive Assessment (version 8.2) (MoCA) and Oral Trail Making Test-B (OTMT-B).

Results: The majority (73%) of patients did not require hospitalization for their acute COVID-19 symptoms. Frequent Long COVID complaints included headache (60%), dizziness/vertigo (40%), and disturbance of taste/smell (40%). Almost all (94%) patients reported cognitive symptoms, and over 30% of patients had abnormal scores on cognitive testing. Severe infection, fewer years of education level, and non-White race were found to be statistically associated with an increased likelihood of having abnormal scores on cognitive testing. Neuroimaging and clinical laboratory testing were largely not informative for patient care. Sixty-two percent of patients with follow-up visits self-reported improvement in their primary neurological complaint within 1 year of evaluation.

Interpretation: Performance on standardized cognitive screening tests may not be consistent with frequently reported cognitive complaints in Long COVID patients. The most common clinical trajectory was self-reported improvement in the primary neurological symptom.

Keywords: MoCA; brain fog; cognitive; long COVID; post‐COVID.

FIGURE 1

Bar chart depicting the percentage of patients (x‐axis) reporting each neurological symptom domain (y‐axis) during acute and Long COVID phases of illness. “Other” symptoms refer to pain, tremor, hearing loss, or restless legs syndrome. Left panel refers to the entire cohort (n: 240). Middle panel depicts patients with non‐severe infection (i.e., not‐hospitalized or treated at outpatient settings including ED) (n: 176). Right panel depicts patients with severe infection (i.e., hospitalization) (n: 64). Key: Acute infection (blue), Long COVID (red).

FIGURE 2

Heat map chart showing the percentage of abnormal testing outcomes by age, severity of acute infection, sex, BMI, race, level of education, and previous history of neuropsychiatric diagnoses. The left panel includes the percentage of patients who missed > 4 points on the MoCA, with a 1 point adjustment for education. The middle panel includes patients who scored < 25th percentile on the OTMT‐B. The right panel includes patients who received abnormal scores in both tests.