Characterizing long-COVID brain fog: a retrospective cohort study

Grace Y Lam; Ronald W Damant; Giovanni Ferrara; Rachel K Lim; Michael K Stickland; Natacha S Ogando; Christopher Power; Maeve P Smith

doi:10.1007/s00415-023-11913-w

Characterizing long-COVID brain fog: a retrospective cohort study

J Neurol. 2023 Oct;270(10):4640-4646. doi: 10.1007/s00415-023-11913-w. Epub 2023 Aug 9.

Authors

Grace Y Lam^{1

2}, Ronald W Damant^{3

4}, Giovanni Ferrara^{3

4}, Rachel K Lim⁵, Michael K Stickland^{3

4}, Natacha S Ogando⁶, Christopher Power⁶, Maeve P Smith^{3

4}

Affiliations

¹ Division of Pulmonary Medicine, Department of Medicine, University of Alberta and Alberta Health Services, 3-111C Clinical Sciences Building, 11302 83 Ave NW, Edmonton, AB, T6G 2G3, Canada. glam@ualberta.ca.
² Alberta Respiratory Centre, University of Alberta, Edmonton, AB, Canada. glam@ualberta.ca.
³ Division of Pulmonary Medicine, Department of Medicine, University of Alberta and Alberta Health Services, 3-111C Clinical Sciences Building, 11302 83 Ave NW, Edmonton, AB, T6G 2G3, Canada.
⁴ Alberta Respiratory Centre, University of Alberta, Edmonton, AB, Canada.
⁵ Division of Respiratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada.
⁶ Division of Neurology, Department of Medicine, University of Alberta and Alberta Health Services, Edmonton, AB, Canada.

PMID: 37555926
DOI: 10.1007/s00415-023-11913-w

Abstract

Background: Long COVID or post-COVID condition (PCC) is a common complication following acute COVID-19 infection. PCC is a multi-systems disease with neurocognitive impairment frequently reported regardless of age. Little is known about the risk factors, associated biomarkers and clinical trajectory of patients with this symptom.

Objective: To determine differences in clinical risk factors, associated biochemical markers and longitudinal clinical trajectories between patients with PCC with subjective neurocognitive symptoms (NC+) or without (NC-).

Methods: A retrospective longitudinal cohort study was performed using a well-characterized provincial database of patients with clinically confirmed PCC separated into NC+ and NC- cohorts. Demographical, clinical and biochemical differences at initial consultation between the two patient cohorts were analyzed in cross-section. Multivariate regression analyses were conducted to identify independent risk factors for neurocognitive impairment. Determination of the recovery trajectory was performed using serial assessments of the patient-reported health-related quality of life (HR-QoL) metric Eq-5D-5L-vas score.

Findings: Women, milder acute infection and pre-existing mental health diagnoses were independently associated with subjective neurocognitive impairment at 8 months post-infection. NC + patients demonstrated lower levels of IgG, IgG1 and IgG3 compared to NC- patients. The NC + cohort had poorer HR-QoL at initial consultation 8 months post-infection with gradual improvement over 20 months post-infection.

Conclusions: Neurocognitive impairment represents a severe phenotype of PCC, associated with unique risk factors, aberrancy in immune response and a delayed recovery trajectory. Those with risk factors for neurocognitive impairment can be identified early in the disease trajectory for more intense medical follow-up.

Keywords: Neurocognitive impairment; Post-COVID condition; Recovery trajectory.

MeSH terms

Brain
COVID-19* / complications
Female
Humans
Longitudinal Studies
Post-Acute COVID-19 Syndrome
Quality of Life*
Retrospective Studies