Thomas et al. (2026)
- Authors: Natalie Thomas, Katherine Huang, Elena K. Schneider-Futschik, Tracey Chau, Darcy Tantanis, Christopher W. Armstrong
- Institutes: Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, Australia
- Publisher: npj Women’s Health
- Link: DOI
Summary
This protocol addresses a major gap in ME/CFS and Long COVID research by accounting for biological rhythms that have historically been ignored. By synchronizing multi-omic sampling with menstrual and diurnal cycles, the MELLOW study aims to resolve inconsistent biomarker findings and clarify the role of hormonal dysregulation in female patients. This approach could lead to more accurate diagnostic tools and a better understanding of why these conditions disproportionately affect women.
What was researched?
The researchers developed a comprehensive protocol for the MELLOW study to investigate how biological rhythms influence molecular and physiological markers in women with ME/CFS and Long COVID. The study focuses on mapping the interactions between the menstrual cycle, daily (diurnal) rhythms, and various biological signatures.
Why was it researched?
Female sex is a primary risk factor for these conditions, yet most studies fail to account for fluctuating sex hormones and biorhythms, leading to inconsistent results. Understanding these temporal dynamics is essential for identifying reliable biomarkers and clarifying the underlying endocrine and immune disruptions.
How was it researched?
The MELLOW study is a prospective longitudinal study involving reproductive-aged women with ME/CFS, Long COVID, and healthy controls. It uses a ‘multi-omics’ approach—including genomics, proteomics, metabolomics, and steroidomics—combined with wearable devices for physiological monitoring and symptom tracking across the menstrual cycle.
What has been found?
As a protocol paper, the primary finding is the design of a specialized research framework that integrates chronobiology into complex molecular analysis. The protocol establishes standardized methods for timing blood and saliva sampling to capture hormonal peaks and troughs, ensuring that data reflects natural biological fluctuations.
Discussion
The study’s strength lies in its ability to improve biomarker reproducibility by controlling for the ‘noise’ of natural biorhythms. A potential limitation is the specific focus on reproductive-aged women, which may limit the direct applicability of findings to post-menopausal or male populations.
Conclusion & Future Work
The implementation of chronobiology-based protocols is expected to clarify the relationship between hormonal shifts and symptom exacerbations. Future results from the MELLOW study may provide a definitive map of the endocrine network disruptions in ME/CFS and Long COVID.