Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization

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Abstract

Post-COVID cognitive deficits, including ‘brain fog’, are clinically complex, with both objective and subjective components. They are common and debilitating, and can affect the ability to work, yet their biological underpinnings remain unknown. In this prospective cohort study of 1,837 adults hospitalized with COVID-19, we identified two distinct biomarker profiles measured during the acute admission, which predict cognitive outcomes 6 and 12 months after COVID-19. A first profile links elevated fibrinogen relative to C-reactive protein with both objective and subjective cognitive deficits. A second profile links elevated D-dimer relative to C-reactive protein with subjective cognitive deficits and occupational impact. This second profile was mediated by fatigue and shortness of breath. Neither profile was significantly mediated by depression or anxiety. Results were robust across secondary analyses. They were replicated, and their specificity to COVID-19 tested, in a large-scale electronic health records dataset. These findings provide insights into the heterogeneous biology of post-COVID cognitive deficits.

Abstract

Longitudinal proteomic profiling of over 1,800 patients revealed two distinct profiles of blood biomarkers measured on admission to hospital for COVID-19, which predict cognitive deficits 6 and 12 months later.

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Most cited references 58

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Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Nanshan Chen, Min Zhou, Xuan Dong … (2022)

Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.

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The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.

Ziad S Nasreddine, Natalie Phillips, ValÃ©rie BÃ©dirian … (2005)

To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. Validation study. A community clinic and an academic center. Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.

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OpenSAFELY: factors associated with COVID-19 death in 17 million patients

Elizabeth J Williamson, Alex J Walker, Krishnan Bhaskaran … (2020)

COVID-19 has rapidly impacted on mortality worldwide. 1 There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets. Working on behalf of NHS England we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19 related deaths. COVID-19 related death was associated with: being male (hazard ratio 1.59, 95%CI 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared to people with white ethnicity, black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.29-1.69 and 1.45, 1.32-1.58 respectively). We have quantified a range of clinical risk factors for COVID-19 related death in the largest cohort study conducted by any country to date. OpenSAFELY is rapidly adding further patients’ records; we will update and extend results regularly.

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Author and article information

Contributors

Maxime Taquet:

ORCID: http://orcid.org/0000-0002-8987-952X

maxime.taquet@psych.ox.ac.uk

Paul J. Harrison:

ORCID: http://orcid.org/0000-0002-6719-1126

paul.harrison@psych.ox.ac.uk

Journal

Journal ID (nlm-ta): Nat Med

Journal ID (iso-abbrev): Nat Med

Title: Nature Medicine

Publisher: Nature Publishing Group US (New York )

ISSN (Print): 1078-8956

ISSN (Electronic): 1546-170X

Publication date (Electronic): 31 August 2023

Publication date PMC-release: 31 August 2023

Publication date (Print): 2023

Volume: 29

Issue: 10

Pages: 2498-2508

Affiliations

[1 ]Department of Psychiatry, University of Oxford, ( https://ror.org/052gg0110) Oxford, UK

[2 ]Oxford Health NHS Foundation Trust, ( https://ror.org/04c8bjx39) Oxford, UK

[3 ]Department of Brain Sciences, Imperial College London, ( https://ror.org/041kmwe10) London, UK

[4 ]GRID grid.416266.1, ISNI 0000 0000 9009 9462, University of Dundee, Ninewells Hospital and Medical School, ; Dundee, UK

[5 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, MRC Human Immunology Unit, , University of Oxford, ; Oxford, UK

[6 ]Division of Infection, Immunity & Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, ( https://ror.org/027m9bs27) Manchester, UK

[7 ]GRID grid.498924.a, ISNI 0000 0004 0430 9101, Manchester University NHS Foundation Trust, ; Manchester, UK

[8 ]Department of Clinical Research, London School of Hygiene & Tropical Medicine, ( https://ror.org/00a0jsq62) London, UK

[9 ]GRID grid.439749.4, ISNI 0000 0004 0612 2754, Hospital for Tropical Diseases, , University College London Hospital, ; London, UK

[10 ]Division of Infection and Immunity, University College London, ( https://ror.org/02jx3x895) London, UK

[11 ]GRID grid.512915.b, ISNI 0000 0000 8744 7921, Asthma and Lung UK, ; London, UK

[12 ]Radcliffe Department of Medicine, University of Oxford, ( https://ror.org/052gg0110) Oxford, UK

[13 ]GRID grid.410556.3, ISNI 0000 0001 0440 1440, Oxford University Hospitals NHS Foundation Trust, ; Oxford, UK

[14 ]Department of Population Health Sciences, University of Leicester, ( https://ror.org/04h699437) Leicester, UK

[15 ]GRID grid.9918.9, ISNI 0000 0004 1936 8411, The institute for Lung Health, NIHR Leicester Biomedical Research Centre, , University of Leicester, ; Leicester, UK

[16 ]GRID grid.9918.9, ISNI 0000 0004 1936 8411, NIHR Leicester Biomedical Research Centre, , University of Leicester, ; Leicester, UK

[17 ]University Hospitals of Leicester NHS Trust, ( https://ror.org/02fha3693) Leicester, UK

[18 ]Centre for Exercise and Rehabilitation Science, NIHR Leicester Biomedical Research Centre-Respiratory, University of Leicester, ( https://ror.org/04h699437) Leicester, UK

[19 ]Department of Respiratory Sciences, University of Leicester, ( https://ror.org/04h699437) Leicester, UK

[20 ]Therapy Department, University Hospitals of Leicester, NHS Trust, ( https://ror.org/02fha3693) Leicester, UK

[21 ]MQ: Transforming Mental Health, ( https://ror.org/04g6r1b21) London, UK

[22 ]Centre for Medical Informatics, The Usher Institute, University of Edinburgh, ( https://ror.org/01nrxwf90) Edinburgh, UK

[23 ]Usher Institute, University of Edinburgh, ( https://ror.org/01nrxwf90) Edinburgh, UK

[24 ]GRID grid.418716.d, ISNI 0000 0001 0709 1919, Royal Infirmary of Edinburgh, NHS Lothian, ; Edinburgh, UK

[25 ]NHLI, Imperial College London, ( https://ror.org/041kmwe10) London, UK

[26 ]School of Cardiovascular and Metabolic Health, University of Glasgow, ( https://ror.org/00vtgdb53) Glasgow, UK

Author information

Maxime Taquet http://orcid.org/0000-0002-8987-952X

Alex Horsley http://orcid.org/0000-0003-1828-0058

Amisha Singapuri http://orcid.org/0009-0002-4711-7516

Marco Sereno http://orcid.org/0000-0003-4573-9303

Linzy Houchen-Wolloff http://orcid.org/0000-0003-4940-8835

Neil J. Greening http://orcid.org/0000-0003-0453-7529

Ewen M. Harrison http://orcid.org/0000-0002-5018-3066

Annemarie B. Docherty http://orcid.org/0000-0001-8277-420X

Nazir I. Lone http://orcid.org/0000-0003-2707-2779

Naveed Sattar http://orcid.org/0000-0002-1604-2593

Rachael E. Evans http://orcid.org/0000-0002-1667-868X

Paul J. Harrison http://orcid.org/0000-0002-6719-1126

Article

Publisher ID: 2525

DOI: 10.1038/s41591-023-02525-y

PMC ID: 10579097

PubMed ID: 37653345

SO-VID: 429ded81-b4bc-4c6a-8866-0b64e11988b5

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 5 April 2023

Date accepted : 31 July 2023

Funding

Funded by: FundRef https://doi.org/10.13039/501100001320, Wolfson Foundation;

Award ID: C-Fog

Award Recipient : Maxime Taquet Paul J. Harrison

Funded by: FundRef https://doi.org/10.13039/501100000272, DH | National Institute for Health Research (NIHR);

Award ID: COV0319

Award Recipient : Christopher E. Brightling Louise V. Wain Rachael E. Evans

Custom metadata

ScienceOpen disciplines: Medicine

Keywords: viral infection,neurological manifestations

Data availability:

ScienceOpen disciplines: Medicine

Keywords: viral infection, neurological manifestations

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Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization

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UCL: Covid-19 Research

Most cited references 58

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.

OpenSAFELY: factors associated with COVID-19 death in 17 million patients

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