Cell reports. MedicineNov 8, 2025

Sex-specific immune, hormone, and gene activity differences in long COVID patients with chronic fatigue syndrome

Updated Jun 28, 2026

Abstract

Essence

Long COVID with ME/CFS was linked to sex-specific immune, hormonal, and transcriptomic changes, with women showing stronger inflammatory disruption.

Evidence

This multimodal profiling study of long-COVID patients with ME/CFS compared females and males and found in females a myelopoiesis shift, fewer lymphocytes and regulatory T cells, higher neutrophils/monocytes, altered erythropoiesis, stronger pro-inflammatory cytokine signals, gut-barrier dysfunction markers, lower testosterone, and neuroinflammatory transcriptomic signatures.

Caveat

The abstract does not state the study size or an interventional design, so these sex-specific biomarkers are associative and their clinical utility remains preliminary.

Simplified

Long COVID (LC) manifests with sex-specific differences, particularly in those with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Our study reveals that female LC patients (LCF) with ME/CFS show a shift toward myelopoiesis, reduced lymphocytes, increased neutrophils/monocytes, and depleted regulatory T cells-suggesting persistent immune activation. Elevated CD71erythroid cells and disrupted erythropoiesis contribute to fatigue and tissue damage in LCF. Cytokine profiling indicates a stronger pro-inflammatory response in LCF compared to males (LCM), along with markers of gut barrier dysfunction. Hormonal analysis shows reduced testosterone in LCF and estradiol in LCM. Transcriptomic data reveal neuroinflammatory signatures in LCF, potentially explaining cognitive symptoms. We also identify biomarkers that distinguish LCF from LCM and correlate with sex-specific clinical symptoms. Overall, LC with ME/CFS is characterized by sex-specific immune, hormonal, and transcriptional alterations, with females exhibiting more severe inflammation. These insights underscore the need for sex-tailored interventions, including consideration of hormone replacement therapy. +