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

Ting Zhang^1,2,3,4, Yunfeng Li⁵, Liuliu Pan^6,7

¹Section of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

|November 15, 2024

Summary

Neurological symptoms after coronavirus disease 2019 (COVID-19) involve brain-wide antiviral responses and neuroinflammation. These changes in the brain overlap with pathways seen in neurodegenerative diseases like Parkinson's and Alzheimer's.

Area of Science:

Neuroscience
Immunology
Pathology

Background:

Neurological symptoms are common after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Previous studies had small sample sizes and limited molecular profiling, hindering generalizability.

Purpose of the Study:

To investigate the pathophysiology of neurological symptoms post-COVID-19.
To identify molecular and cellular changes in the brain following SARS-CoV-2 infection.

Main Methods:

Utilized spatial transcriptomics, bulk gene expression, and proteomics on postmortem brains from COVID-19 patients and controls (n=42).
Analyzed multiple cortical and subcortical brain regions.

Main Results:

Observed a multi-regional antiviral response in the brain without direct SARS-CoV-2 infection.
Identified dysregulation of mitochondrial and synaptic pathways in neurons and increased neuroinflammation in glia.
Found significant overlap between COVID-19-related brain alterations and those in age-related neurodegenerative diseases (e.g., Parkinson's, Alzheimer's).

Conclusions:

Severe acute/subacute COVID-19 has a widespread impact on the brain, affecting both cortical and subcortical regions.
The findings suggest potential therapeutic targets within pathways common to pathological aging and neurodegeneration.

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