# Cerebrospinal Fluid Immune Cell Alterations in Women With Neuropsychiatric Long COVID

## TL;DR

Women with neuropsychiatric Long COVID show unique gene expression patterns in cerebrospinal fluid, indicating central nervous system-specific immune and stress responses.

## Contribution

Identifies CSF-specific gene expression changes in women with neuropsychiatric Long COVID, revealing compartmentalized molecular mechanisms.

## Key findings

- CSF samples from women with Long COVID show differential gene expression related to oxidative stress and P53 response.
- Androgen response and lipid metabolism pathways are dysregulated in both CSF and PBMC of Long COVID patients.
- Transcriptional profiles in CSF highlight central nervous system-specific alterations not seen in peripheral blood.

## Abstract

Women are disproportionately affected by neuropsychiatric symptoms following recovery from acute COVID-19. However, whether there are central nervous system-specific changes in gene expression in women with neuropsychiatric Long COVID (NP-Long COVID) remains unknown.

Twenty-two women with and 10 women without NP-Long COVID were enrolled from New Haven, Connecticut, and the surrounding region and consented to a blood draw and large volume lumbar puncture. Total RNA was extracted from cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMC). Polyadenylated RNA was sequenced, and differential expression analyses were performed.

Both CSF and PBMC samples showed differential gene expression associated with Long COVID status. There were CSF-specific differentially expressed genes in people with Long COVID, including in genes related to oxidative stress, reactive oxygen species, and P53 response, indicating compartment-specific immune responses. Some pathways were dysregulated in both the CSF and PBMC of Long COVID compared with controls, including those related to androgen response, MTORC1 signaling, and lipid metabolism.

Women with NP-long COVID show compartment-specific, transcriptional profiles in the CSF with evidence of enrichment in cellular stress pathways. These results underscore the importance of examining CSF-specific molecular profiles to better understand post-viral neurological syndromes.

Women with neuropsychiatric Long COVID exhibit unique cerebrospinal fluid transcriptional profiles, revealing central nervous system-specific immune, metabolic, and stress pathway alterations not observed in peripheral blood, highlighting compartmentalized molecular mechanisms underlying persistent post-infectious neurological symptoms.