Research Letter | Neurology

Assessment of Cognitive Function in Patients After COVID-19 Infection

Jacqueline H. Becker, PhD; Jenny J. Lin, MD, MPH; Molly Doernberg, MPH; Kimberly Stone, MPH; Allison Navis, MD; Joanne R. Festa, PhD; Juan P. Wisnivesky, MD, DrPH

Introduction Author affiliations and article information are

listed at the end of this article.
People who have survived COVID-19 frequently complain of cognitive dysfunction, which has been
described as brain fog. The prevalence of post–COVID-19 cognitive impairment and the association
with disease severity are not well characterized. Previous studies on the topic have been limited by
small sample sizes and suboptimal measurement of cognitive functioning.1 We investigated rates of
cognitive impairment in survivors of COVID-19 who were treated in outpatient, emergency
department (ED), or inpatient hospital settings.

Methods
We analyzed data in this cross-sectional study from April 2020 through May 2021 from a cohort of
patients with COVID-19 followed up through a Mount Sinai Health System registry. Study participants
were 18 years or older, spoke English or Spanish, tested positive for SARS-CoV-2 or had serum
antibody positivity, and had no history of dementia. Participant demographic characteristics (eg, age,
race, and ethnicity) were collected via self-report. Cognitive functioning was assessed using well-
validated neuropsychological measures: Number Span forward (attention) and backward (working
memory), Trail Making Test Part A and Part B (processing speed and executive functioning,
respectively), phonemic and category fluency (language), and the Hopkins Verbal Learning Test–
Revised (memory encoding, recall, and recognition). The Mount Sinai Health System Institutional
Review Board approved this study, and informed consent was obtained from study participants. The
study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)
reporting guideline.
We calculated the frequency of impairment on each measure, defined as a z score of less than
or equal to 1.5 SDs below measure-specific age-, educational level–, and sex-adjusted norms.2,3
Logistic regression assessed the association between cognitive impairment and COVID-19 care site
(outpatient, ED, or hospital), adjusting for race and ethnicity, smoking, body mass index,
comorbidities, and depression. The threshold for statistical significance was α = .05, and the tests
were 2-tailed. Analyses were performed using SAS, version 9.4 (SAS Institute).

Results
The mean (IQR) age of 740 participants was 49 (38-59) years, 63% (n = 464) were women, and the
mean (SD) time from COVID-19 diagnosis was 7.6 (2.7) months (Table 1). Participants self-identified
as Black (15%), Hispanic (20%), or White (54%) or selected multiracial or other race and ethnicity
(11%; other race included Asian [4.5%, n = 33)] and those who selected “other” as race). The most
prominent deficits were in processing speed (18%, n = 133), executive functioning (16%, n = 118),
phonemic fluency (15%, n = 111) and category fluency (20%, n = 148), memory encoding (24%,
n = 178), and memory recall (23%, n = 170; Table 2).
In adjusted analyses, hospitalized patients were more likely to have impairments in attention
(odds ratio [OR]: 2.8; 95% CI: 1.3-5.9), executive functioning (OR: 1.8; 95% CI: 1.0-3.4), category
fluency (OR: 3.0; 95% CI: 1.7-5.2), memory encoding (OR: 2.3; 95% CI: 1.3-4.1), and memory recall

Open Access. This is an open access article distributed under the terms of the CC-BY License.

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 JAMA Network Open | Neurology Assessment of Cognitive Function in Patients After COVID-19 Infection

Table 1. Characteristics of Patients Who Had COVID-19

Characteristic No. of Patients (%) (N = 740)

Time from diagnosis to baseline visit, mo, mean (SD) 7.6 (2.7)
Age, y, mean (SD) 49.0 (14.2)
Sex
Female 464 (63)
Male 276 (37)
Race/ethnicity
Black 112 (15)
Hispanic 149 (20)
White 397 (54)
Multiracial or othera 75 (11)
Educational level, y
≤12 103 (14)
>12 636 (86)
Income
<$25 000 109 (15)b
$25 000-$60 000 113 (15)
$60 000-$150 000 244 (33)
>$150 000 206 (28)
Former smoker 226 (31)
Comorbidities
Hypertension 191 (26)
Diabetes 74 (10)
Asthma 179 (24)
Cancer 72 (10)
Body mass indexc
Normal weight 273 (37)b a
Other included Asian (33 [4.5%]), and the remainder
Overweight 212 (29) included those who reported other as race.
Obese 249 (34) b
The sum of the subcategories is less than 100 due to
Site of COVID-19 care missing data.
c
Outpatient 379 (51) Calculated as weight in kilograms divided by height
Emergency department 165 (22) in meters squared. Normal weight is a body mass
index of 18.5 to 24.9, overweight is 25.0 to 30.0, and
Hospital 196 (27)
obese is greater than 30.0.

Table 2. Prevalence of Cognitive Impairment After COVID-19 Infection

Impaired (z score ≤1.5), No. (%) Adjusted odds ratio (95% CI)a
Total Outpatient ED Hospitalized
Cognitive domain (N = 740) (n = 379) (n = 165) (n = 196) ED vs outpatient Hospital vs outpatient
Attention 74 (10) 19 (5) 10 (6) 29 (15) 0.8 (0.3-2.0) 2.8 (1.3-5.9)
Working memory 74 (10) 30 (8) 17 (10) 29 (15) 1.0 (0.5-2.2) 1.7 (0.8-3.3)
Processing speed 133 (18) 57 (15) 21 (13) 55 (28) 0.7 (0.4-1.3) 1.4 (0.8-2.5)
Executive functioning 118 (16) 45 (12) 23 (14) 53 (27) 1.0 (0.5-1.8) 1.8 (1.0-3.4)
Phonemic fluency 111 (15) 42 (11) 25 (15) 39 (20) 0.9 (0.5-1.8) 1.5 (0.8-2.8)
Category fluency 148 (20) 49 (13) 35 (21) 69 (35) 1.8 (1.1-3.1) 3.0 (1.7-5.2)
Memory encoding 178 (24) 61 (16) 43 (26) 73 (37) 1.7 (1.0-3.0) 2.3 (1.3-4.1)
Memory recall 170 (23) 45 (12) 38 (23) 76 (39) 1.5 (0.9-2.6) 2.2 (1.3-3.8)
Memory recognition 74 (10) 34 (9) 20 (12) 25 (13) 1.5 (0.8-3.0) 1.1 (0.5-2.4)

Abbreviation: ED, emergency department.

a
Adjusted for race and ethnicity, smoking history, body mass index (calculated as weight in kilograms divided by height in meters squared), comorbidities, and depressive symptoms.

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 JAMA Network Open | Neurology Assessment of Cognitive Function in Patients After COVID-19 Infection

(OR: 2.2; 95% CI: 1.3-3.8) than those in the outpatient group. Patients treated in the ED were more
likely to have impaired category fluency (OR: 1.8; 95% CI: 1.1-3.1) and memory encoding (OR: 1.7; 95%
CI: 1.0-3.0) than those treated in the outpatient setting. No significant differences in impairments in
other domains were observed between groups.

Discussion
In this study, we found a relatively high frequency of cognitive impairment several months after
patients contracted COVID-19. Impairments in executive functioning, processing speed, category
fluency, memory encoding, and recall were predominant among hospitalized patients. The relative
sparing of memory recognition in the context of impaired encoding and recall suggests an executive
pattern. This pattern is consistent with early reports describing a dysexecutive syndrome after
COVID-194 and has considerable implications for occupational, psychological, and functional
outcomes. It is well known that certain populations (eg, older adults) may be particularly susceptible
to cognitive impairment after critical illness5; however, in the relatively young cohort in the present
study, a substantial proportion exhibited cognitive dysfunction several months after recovering from
COVID-19. The findings of this study are generally consistent with those of research on other viruses
(eg, influenza).6
Limitations of this study include a potential sampling bias, as some participants may have
presented to Mount Sinai Health System because of health concerns. Future studies should
investigate long-term post–COVID-19 cognitive trajectories and the association with neuroimaging
findings to assess potential mechanisms.

Conclusions
The association of COVID-19 with executive functioning raises key questions regarding patients’ long-
term treatment. Future studies are needed to identify the risk factors and mechanisms underlying
cognitive dysfunction as well as options for rehabilitation.

ARTICLE INFORMATION
Accepted for Publication: August 17, 2021.
Published: October 22, 2021. doi:10.1001/jamanetworkopen.2021.30645
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Becker JH
et al. JAMA Network Open.
Corresponding Author: Jacqueline H. Becker, PhD, Division of General Internal Medicine, Icahn School of
Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 ([email protected]).
Author Affiliations: Division of General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York,
New York (Becker, Lin, Doernberg, Stone, Wisnivesky); Department of Neurology, Icahn School of Medicine at
Mount Sinai, New York, New York (Navis, Festa); The Catherine and Henry J. Gaisman Division of Pulmonary,
Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Wisnivesky).
Author Contributions: Drs Becker and Wisnivesky had full access to all of the data in the study and take
responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Becker, Lin, Wisnivesky.
Acquisition, analysis, or interpretation of data: Becker, Doernberg, Stone, Navis, Festa, Wisnivesky.
Drafting of the manuscript: Becker, Stone, Wisnivesky.
Critical revision of the manuscript for important intellectual content: Becker, Lin, Doernberg, Navis, Festa,
Wisnivesky.
Statistical analysis: Becker, Stone, Wisnivesky.
Obtained funding: Wisnivesky.

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 JAMA Network Open | Neurology Assessment of Cognitive Function in Patients After COVID-19 Infection

Administrative, technical, or material support: Becker, Lin, Doernberg, Wisnivesky.

Supervision: Becker, Lin, Doernberg, Navis, Wisnivesky.
Conflict of Interest Disclosures: Dr Wisnivesky reported receiving personal fees from Sanofi, Atea
Pharmaceuticals, and Banook Group and grants from Sanofi, Regeneron Pharmaceuticals, and Arnold Consulting
outside the submitted work. No other disclosures were reported.

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