Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 "long haulers"

Abstract

Objective: Most SARS-CoV-2-infected individuals never require hospitalization. However, some develop prolonged symptoms. We sought to characterize the spectrum of neurologic manifestations in non-hospitalized Covid-19 "long haulers".

Methods: This is a prospective study of the first 100 consecutive patients (50 SARS-CoV-2 laboratory-positive (SARS-CoV-2⁺ ) and 50 laboratory-negative (SARS-CoV-2^- ) individuals) presenting to our Neuro-Covid-19 clinic between May and November 2020. Due to early pandemic testing limitations, patients were included if they met Infectious Diseases Society of America symptoms of Covid-19, were never hospitalized for pneumonia or hypoxemia, and had neurologic symptoms lasting over 6 weeks. We recorded the frequency of neurologic symptoms and analyzed patient-reported quality of life measures and standardized cognitive assessments.

Results: Mean age was 43.2 ± 11.3 years, 70% were female, and 48% were evaluated in televisits. The most frequent comorbidities were depression/anxiety (42%) and autoimmune disease (16%). The main neurologic manifestations were: "brain fog" (81%), headache (68%), numbness/tingling (60%), dysgeusia (59%), anosmia (55%), and myalgias (55%), with only anosmia being more frequent in SARS-CoV-2⁺ than SARS-CoV-2^- patients (37/50 [74%] vs. 18/50 [36%]; p < 0.001). Moreover, 85% also experienced fatigue. There was no correlation between time from disease onset and subjective impression of recovery. Both groups exhibited impaired quality of life in cognitive and fatigue domains. SARS-CoV-2⁺ patients performed worse in attention and working memory cognitive tasks compared to a demographic-matched US population (T-score 41.5 [37, 48.25] and 43 [37.5, 48.75], respectively; both p < 0.01).

Interpretation: Non-hospitalized Covid-19 "long haulers" experience prominent and persistent "brain fog" and fatigue that affect their cognition and quality of life.

Figure 1

Patient‐reported outcomes measurement information system (PROMIS®) quality of life and NIH Toolbox cognitive assessments demographic‐matched T‐scores in SARS‐CoV‐2⁺ (circles) and SARS‐CoV‐2^‐ (squares) individuals. A T‐score of 50 is the mean/median for the demographic‐matched United States normative population with a standard deviation of 10. (A) PROMIS® cognitive function (C, filled symbols) and fatigue (F, empty symbols) assessments. Lower cognition scores indicate worse cognition quality of life and higher fatigue scores correspond to worse fatigue quality of life. Patient group median values are represented by horizontal bars. (B) NIH Toolbox assessments for processing speed (PS), attention (A), executive function (EF), and working memory (WM). Median values are represented by horizontal bars. One‐sample Wilcoxon signed‐rank test p‐values between patient group T‐scores and the demographic‐matched normative US population median of 50 are provided in the figure table.

Figure 2

Subjective impression of recovery compared to pre‐Covid‐19 baseline for SARS‐CoV‐2⁺ (A) and SARS‐CoV‐2^‐ individuals (B). The patients were asked to grade their recovery at the time of their visit, assuming a pre‐Covid‐19 baseline of 100%. Each person is represented by a single time point, and r values demonstrate no meaningful relationship between time from onset and percentage of recovery.