The study found that people with Q fever fatigue syndrome, chronic fatigue syndrome, and even those who had been exposed to Q fever but feel fine have lower levels of the mitochondrial peptides humanin and MOTS‑c in their blood. This suggests these tiny proteins might be part of why they feel constantly tired, but the research didn’t test any treatments.

Q fever fatigue syndrome (QFS) is a well-documented state of prolonged fatigue following around 20% of acute Q fever infections. It has been hypothesized that low grade inflammation plays a role in its aetiology. In this study, we aimed to identify transcriptome profiles that could aid to better understand the pathophysiology of QFS. RNA of monocytes was collected from QFS patients (n = 10), chronic fatigue syndrome patients (CFS, n = 10), Q fever seropositive controls (n = 10), and healthy controls (n = 10) who were age- (± 5 years) and sex-matched. Transcriptome analysis was performed using RNA sequencing. Mitochondrial-derived peptide (MDP)-coding genes MT-RNR2 (humanin) and MT-RNR1 (MOTS-c) were differentially expressed when comparing QFS (- 4.8 log2-fold-change P = 2.19 × 10^-9 and - 4.9 log2-fold-change P = 4.69 × 10^-8), CFS (- 5.2 log2-fold-change, P = 3.49 × 10^-11 - 4.4 log2-fold-change, P = 2.71 × 10^-9), and Q fever seropositive control (- 3.7 log2-fold-change P = 1.78 × 10^-6 and - 3.2 log2-fold-change P = 1.12 × 10^-5) groups with healthy controls, resulting in a decreased median production of humanin in QFS patients (371 pg/mL; Interquartile range, IQR, 325-384), CFS patients (364 pg/mL; IQR 316-387), and asymptomatic Q fever seropositive controls (354 pg/mL; 292-393). Expression of MDP-coding genes MT-RNR1 (MOTS-c) and MT-RNR2 (humanin) is decreased in CFS, QFS, and, to a lesser extent, in Q fever seropositive controls, resulting in a decreased production of humanin. These novel peptides might indeed be important in the pathophysiology of both QFS and CFS.