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Characterizing long-COVID brain fog: a retrospective cohort study

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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.

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Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request in accordance with the regulations of Alberta Health Services.

Abbreviations

PCC:

Post-COVID condition

BMI:

Body mass index

PCFS:

Post-COVID functional scale

PHQ-9:

Patient health questionnaire

GAD-7:

General anxiety disorder-7

HR-QOL:

Health-related quality of life

CI:

Confidence interval

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Acknowledgements

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Authors and 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

    Grace Y. Lam, Ronald W. Damant, Giovanni Ferrara, Michael K. Stickland & Maeve P. Smith

  2. Alberta Respiratory Centre, University of Alberta, Edmonton, AB, Canada

    Grace Y. Lam, Ronald W. Damant, Giovanni Ferrara, Michael K. Stickland & Maeve P. Smith

  3. Division of Respiratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada

    Rachel K. Lim

  4. Division of Neurology, Department of Medicine, University of Alberta and Alberta Health Services, Edmonton, AB, Canada

    Natacha S. Ogando & Christopher Power

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  1. Grace Y. Lam
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  2. Ronald W. Damant
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  3. Giovanni Ferrara
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  4. Rachel K. Lim
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Contributions

GYL was responsible for conceptualization, data acquisition, data analysis and manuscript writing; RWD, RKL and GFS were responsible for data acquisition, manuscript editing and review; MKS, NSO and CP were responsible for manuscript editing and review; and MPS was responsible for data acquisition, manuscript editing and review. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Grace Y. Lam.

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Conflicts of interest

GYL has received research funding from Roche Diagnostics, Alberta Lung and the Canadian Institutes for Health Research and has received honoraria for educational activities from Boehringer Ingelheim, Alberta Lung, and Canadian Thoracics Society/Respiplus. GF has received honoraria for lectures or presentations from Boehringer Ingelheim, AstraZeneca and Roche and is on an advisory board for Boehringer Ingelheim and Roche. MKS has received funding from the Canadian Institutes for Health Research, Natural Sciences and Engineering Council and the University of Alberta Hospital. The remaining authors declare that they have no competing interests.

Ethics approval and consent to participate

The study was approved by the University of Alberta Research Ethics Board (Pro00104564) and conducted in full accordance with the ethics board guidelines.

Consent for publications

A waiver of consent was granted by the Research Ethics Board given that the study involved anonymized, de-identified and unidentifiable patient data.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplemental Table 1

. Baseline Demographics of the Study Population. p-values determined using non-parametric test for continuous variables or Fisher’s Exact test for categorical variables. BMI = body mass index; ED = emergency department; ICU = intensitve care unit; COPD = chronic obstructive pulmonary disease; CAD = coronary artery disease; CHF = congestive heart failure; CKD = chronic kidney disease; PCC = post-COVID condition; GI = gastrointestinal (DOCX 23 KB)

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Lam, G.Y., Damant, R.W., Ferrara, G. et al. Characterizing long-COVID brain fog: a retrospective cohort study. J Neurol 270, 4640–4646 (2023). https://doi.org/10.1007/s00415-023-11913-w

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  • DOI: https://doi.org/10.1007/s00415-023-11913-w

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