CSF immune cell alterations in women with neuropsychiatric Long COVID

Background: Women are disproportionately affected by neuropsychiatric symptoms following recovery from acute COVID-19, commonly termed neuropsychiatric long COVID (NP-long COVID). However, whether there are central nervous system-specific changes in gene expression in women with NP-long COVID remains unknown. Methods: Twenty-two women with and ten women without NP-long COVID were enrolled from New Haven, CT, 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 then sequenced, and differential expression analyses were performed using DESeq2. Results: Both CSF and PBMC samples showed differential gene expression associated with long COVID status. While some pathways were dysregulated in both the CSF and PBMC of long COVID compared to controls, including those related to androgen response, MTORC1 signaling, and lipid metabolism, these are likely driven by different suites of genes. Moreover, there were also CSF-specific differentially expressed genes in people with long COVID, indicating compartment-specific immune responses. Notably, oxidative stress, reactive oxygen species, and P53 response were all enriched in the CSF of women with long COVID but not PBMC. Conclusions: Women with NP-long COVID show distinct, compartment-specific, transcriptional profiles in the CSF.