Long COVID’s Cognitive Effects Depend on Sex, MRI Study Finds
A new MRI study published in Frontiers in Psychiatry in October 2025 found that long COVID may alter brain structure in ways that differ by sex. Researchers compared gray matter volume (GMV) in people with cognitive impairment following a COVID-19 infection to both healthy controls and long-COVID patients without cognitive issues.
These findings add to a growing body of research on how immune, hormonal, and structural factors shape recovery from infection:
- Long-COVID patients showed significant gray-matter alterations across multiple regions
Echoing findings in a Nature study showing that even mild COVID-19 can cause gray matter loss and structural changes linked to smell, memory, and emotion.
- Women exhibited more localized changes in frontal and limbic regions tied to mood and emotion
Consistent with studies showing that women experience longer-lasting inflammation and greater cardiovascular stiffness and inflammatory markers.
- Men showed more widespread gray-matter alterations across parietal, occipital, and motor cortices
Aligning with wearable sensor data showing stronger stress responses in men and autoantibody studies finding broader immune activation compared to women.
- These patterns may arise from hormonal and chromosomal influences on immune signaling
As explored in research on hormones and sex chromosomes that shape autoimmune risk and findings suggesting estrogen may influence Long COVID vulnerability.
- Understanding sex-specific mechanisms could improve personalized rehabilitation and mental-health support
Supporting the need for targeted care, as discussed in genetic and hormonal studies of autoimmunity and recent analyses linking Long COVID to anxiety, depression, and financial hardship.
Citation
Toepffer, A., et al. (2025). Cognition-associated gray matter volume alterations in long-COVID show sex-specific patterns. Frontiers in Psychiatry, 16. https://doi.org/10.3389/fpsyt.2025.1653295