Protocol A chronobiology-based protocol for multi-omic mapping of menstrual cycle and diurnal rhythms in ME/CFS and long COVID, 2026, Thomas et al.

[Chandelier]

A chronobiology-based protocol for multi-omic mapping of menstrual cycle and diurnal rhythms in ME/CFS and long COVID

Spoiler: Authors

Thomas, Natalie; Huang, Katherine; Schneider-Futschik, Elena K.; Pollack, Beth; Tal, Michal Caspi; Fineberg, David; Gurvich, Caroline; Pretorius, Resia; Bergquist, Jonas; Armstrong, Christopher W.

Abstract​

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID are debilitating multisystem illnesses with overlapping symptoms and poorly understood mechanisms.
Female sex is a major risk factor, and preliminary evidence links sex hormones and other fluctuating endocrine hormones, including cortisol, aldosterone, and DHEA, to these conditions.
However, existing studies have not comprehensively captured diurnal, infradian, and circadian biorhythms, leaving critical gaps in understanding.

The MELLOW study (ME/CFS + Long COVID Longitudinal Omics and Women’s Health) is a prospective, chronobiology-based study of reproductive-aged women with ME/CFS, long COVID, and healthy controls.
It integrates menstrual-phase and diurnal sampling with multi-omics profiling (genomics, proteomics, metabolomics, lipidomics, steroidomics), physiological monitoring, and symptom tracking.
By accounting for natural and disrupted biorhythms, MELLOW will map temporal links between hormonal, molecular, physiological, and symptom dynamics, improving biomarker reproducibility and clarifying endocrine network disruption underlying ME/CFS, long COVID, and women’s health more broadly.

Web | DOI | PDF | npj Women's Health

 

[ME/CFS Science Blog]

Wrote a summary of this protocol on social media:

1)

The protocol for the MELLOW study (ME/CFS + Long COVID Longitudinal Omics and Women’s Health) has been published.
It will look in-depth at the influence of hormones and the menstrual cycle in both diseases using home sampling.

2) The rationale are:
- that these illnesses are much more common in women
- that pregnancy seems to reduce the female-associated risk of Long Covid
- that hormones such as cortisol (but also aldosterone, DHEA, vasopressin) have been reported to abnormal in several studies.

3) MELLOW is a well-controlled study that accounts for reproductive status, menstrual cycle dynamics, and diurnal variation. It will include 20 ME/CFS patients, 20 Long Covid patients and 20 controls who will provide repeated measurements using home testing kits.

4) Participants will get
- a wearable device for physiological data (heart rate variability, temperature, oxygen saturation levels, etc.)
- a Mira® digital device for point-of-care hormone monitoring
- urine and micro-blood collection tools.

5) If I understand correctly, participants will self-collect dried blood and urine samples daily to monitor hormone levels (and store them in their -20 degree freezer). Sampling will then be based on the hormonal cycle the person is in.

6) The paper explains: "The MELLOW protocol is explicitly biology-driven and cycle-specific. Each participant’s sampling schedule is determined from their own real-time hormonal data captured by the Mira device rather than fixed calendar days."

7) Participants will also be asked to conduct sample collection and fill in questionnaires during a ‘crash’—periods of significant PEM or a generalised worsening of symptoms.

8 ) The researchers will apply multiple biological analyses on the samples including:
- Metabolomics and proteomics
- Cytokine measurements
- Steroid concentrations
- RNA sequencing
- Flow cytometry + fluorescence microscopy to study clotting and endothelial homeostasis.
- etc

9) Looks like an interesting and well-conducted study.

Link:
A chronobiology-based protocol for multiomic mapping of menstrual cycle and diurnal rhythms in ME/CFS and long COVID.
https://www.nature.com/articles/s44294-025-00120-9