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

Ting Zhang, Yunfeng Li, Liuliu Pan, Jihui Sha, Michael Bailey, Emmanuelle Faure-Kumar, Christopher Kazu Williams, James Wohlschlegel, Shino Magaki, Chao Niu, Yoojin Lee, Yu-Chyuan Su, Xinmin Li, Harry V Vinters, Daniel H Geschwind

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

Paper

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.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper investigates the neurological effects of COVID-19, highlighting alterations in brain pathways that overlap with age-related neurodegenerative diseases. While it does not directly address the root causes of aging or lifespan extension, it provides insights into mechanisms that could be relevant for understanding neurodegeneration in the context of aging. The findings are solid and contribute to the field, but they are not groundbreaking enough to warrant a higher impact score.

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