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Cited by 20Long-Term Effects of COVID-19SARS-CoV-2 and COVID-19 ResearchSingle-cell and spatial transcriptomics

Brain-wide alterations revealed by spatial transcriptomics and proteomics in COVID-19 infection

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Zhang, Ting, Li, Yunfeng, Pan, Liuliu, Sha, Jihui, Bailey, Michael, Faure-Kumar, Emmanuelle, Williams, Christopher Kazu, Wohlschlegel, James +7 more·2024·Nature Aging
DOI 10.1038/s43587-024-00730-zPMC PMC11867587

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Abstract

Understanding the pathophysiology of neurological symptoms observed after severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is essential to optimizing outcomes and therapeutics. To date, small sample sizes and narrow molecular profiling have limited the generalizability of findings. In this study, we profiled multiple cortical and subcortical regions in postmortem brains of patients with coronavirus disease 2019 (COVID-19) and controls with matched pulmonary pathology (total n = 42) using spatial transcriptomics, bulk gene expression and proteomics. We observed a multi-regional antiviral response without direct active SARS-CoV2 infection. We identified dysregulation of mitochondrial and synaptic pathways in deep-layer excitatory neurons and upregulation of neuroinflammation in glia, consistent across both mRNA and protein. Remarkably, these alterations overlapped substantially with changes in age-related neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Our work, combining multiple experimental and analytical methods, demonstrates the brain-wide impact of severe acute/subacute COVID-19, involving both cortical and subcortical regions, shedding light on potential therapeutic targets within pathways typically associated with pathological aging and neurodegeneration.

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  • COVID-19 is very rarely neuroinvasive, but its impact on the brain might be immune-mediated and cause glial neuroinflammation.

    “Indeed, while COVID-19 is very rarely neuroinvasive [127], its impact on the brain might be immune-mediated [126] and cause glial neuroinflammation [128,129,130].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [130]

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Authors
Zhang, T., Li, Y., Pan, L., Sha, J., Bailey, M., Faure-Kumar, E., Williams, C. K., Wohlschlegel, J., Magaki, S., Niu, C., Lee, Y., Su, Y.-C., Li, X., Vinters, H. V., & Geschwind, D. H.
Affiliations
  • University of California, Los Angeles (US)
  • Duality Biotherapeutics, Inc. (China) (CN)
  • Bruker (United States) (US)
Corresponding author
  • Vinters, Harry V.
  • Geschwind, Daniel H.
ORCID
Venue
Nature Aging
Publisher
Springer Science and Business Media LLC
Published
2024-11-14
Volume
4
Issue
11
Pages
1598-1618
ISSN
2662-8465 (ISSN-L)
DOI
10.1038/s43587-024-00730-z
PMC
PMC11867587
OpenAlex
W4404347532
Cited by
20
References
159
Citations by year
2026: 11 · 2025: 9
FWCI
5.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Aging (publishedVersion)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (20231126)
  • University of California, Los Angeles (OCRC #20-70)
  • National Institute of General Medical Sciences (T32GM008243)
  • Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles
  • David Geffen School of Medicine, University of California, Los Angeles
Topics
  • Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Keywords
COVID-19 pandemic, postmortem brain, neuroinflammation, mitochondrial dysfunction, synaptic dysfunction, excitatory neurons, glial inflammation, Parkinson's disease, Alzheimer's disease, age-related neurodegeneration, antiviral response, cortical and subcortical regions, proteomics
MeSH terms
COVID-19, SARS-CoV-2, Aged, Aged, 80 and over, Brain, Female, Humans, Male, Middle Aged, Gene Expression Profiling, Proteomics, Transcriptome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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