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

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.