Brain hypoxia, neurocognitive impairment, and quality of life in people post-COVID-19

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Abstract

Objective

Systemic hypoxia occurs in COVID-19 infection; however, it is unknown if cerebral hypoxia occurs in convalescent individuals. We have evidence from other conditions associated with central nervous system inflammation that hypoxia may occur in the brain. If so, hypoxia could reduce the quality of life and brain function. This study was undertaken to assess if brain hypoxia occurs in individuals after recovery from acute COVID-19 infection and if this hypoxia is associated with neurocognitive impairment and reduced quality of life.

Methods

Using frequency-domain near-infrared spectroscopy (fdNIRS), we measured cerebral tissue oxygen saturation (S _tO ₂) (a measure of hypoxia) in participants who had contracted COVID-19 at least 8 weeks prior to the study visit and healthy controls. We also conducted neuropsychological assessments and health-related quality of life assessments, fatigue, and depression.

Results

Fifty-six percent of the post-COVID-19 participants self-reported having persistent symptoms (from a list of 18), with the most reported symptom being fatigue and brain fog. There was a gradation in the decrease of oxyhemoglobin between controls, and normoxic and hypoxic post-COVID-19 groups (31.7 ± 8.3 μM, 27.8 ± 7.0 μM and 21.1 ± 7.2 μM, respectively, p = 0.028, p = 0.005, and p = 0.081). We detected that 24% of convalescent individuals’ post-COVID-19 infection had reduced S _tO ₂ in the brain and that this relates to reduced neurological function and quality of life.

Interpretation

We believe that the hypoxia reported here will have health consequences for these individuals, and this is reflected in the correlation of hypoxia with greater symptomology. With the fdNIRS technology, combined with neuropsychological assessment, we may be able to identify individuals at risk of hypoxia-related symptomology and target individuals that are likely to respond to treatments aimed at improving cerebral oxygenation.

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Most cited references 54

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6-month consequences of COVID-19 in patients discharged from hospital: a cohort study

Chaolin Huang, Lixue Huang, Yeming Wang … (2021)

Background The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. Methods We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5–6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. Findings In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0–65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0–199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5–6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5–6, and median CT scores were 3·0 (IQR 2·0–5·0) for severity scale 3, 4·0 (3·0–5·0) for scale 4, and 5·0 (4·0–6·0) for scale 5–6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80–3·25) for scale 4 versus scale 3 and 4·60 (1·85–11·48) for scale 5–6 versus scale 3 for diffusion impairment; OR 0·88 (0·66–1·17) for scale 4 versus scale 3 and OR 1·77 (1·05–2·97) for scale 5–6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58–0·96) for scale 4 versus scale 3 and 2·69 (1·46–4·96) for scale 5–6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up. Interpretation At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. Funding National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

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Persistent Symptoms in Patients After Acute COVID-19

Angelo Carfì, Roberto Bernabei, Francesco Landi (2020)

This case series describes COVID-19 symptoms persisting a mean of 60 days after onset among Italian patients previously discharged from COVID-19 hospitalization.

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Neuroinflammation in Alzheimer's disease.

Michael T Heneka, Monica Carson, Joseph El Khoury … (2015)

Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

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Author and article information

Contributors

Damilola D. Adingupu:

ORCID: http://orcid.org/0000-0002-0312-2359

Deborah.adingupu@ucalgary.ca

Jeff F. Dunn: Dunnj@ucalgary.ca

Journal

Journal ID (nlm-ta): J Neurol

Journal ID (iso-abbrev): J Neurol

Title: Journal of Neurology

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0340-5354

ISSN (Electronic): 1432-1459

Publication date (Electronic): 21 May 2023

Publication date PMC-release: 21 May 2023

Pages: 1-12

Affiliations

[1 ]GRID grid.22072.35, ISNI 0000 0004 1936 7697, Department of Radiology, , University of Calgary, ; Calgary, Canada

[2 ]GRID grid.22072.35, ISNI 0000 0004 1936 7697, Hotchkiss Brain Institute (HBI), , University of Calgary, ; Calgary, Canada

[3 ]GRID grid.22072.35, ISNI 0000 0004 1936 7697, Department Of Clinical Neurosciences, , University of Calgary, ; Calgary, Canada

[4 ]GRID grid.22072.35, ISNI 0000 0004 1936 7697, Faculty of Kinesiology, , University of Calgary, ; Calgary, Canada

Author information

Damilola D. Adingupu http://orcid.org/0000-0002-0312-2359

Article

Publisher ID: 11767

DOI: 10.1007/s00415-023-11767-2

PMC ID: 10200033

PubMed ID: 37210689

SO-VID: ccc25b48-232e-4a95-ab9e-6a4f168f76ff

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 25 March 2023

Date revision received : 4 May 2023

Date accepted : 5 May 2023

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Brain hypoxia, neurocognitive impairment, and quality of life in people post-COVID-19

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Abstract

Objective

Methods

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Interpretation

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Novel Coronavirus Disease COVID-19

Most cited references 54

6-month consequences of COVID-19 in patients discharged from hospital: a cohort study

Persistent Symptoms in Patients After Acute COVID-19

Neuroinflammation in Alzheimer's disease.

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Cited by 12

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