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Frontiers | Bipolar spectrum, hypothyroidism, and their association with chronic fatigue/myalgic encephalomyelitis-like syndrome in long COVID: could they be identified as early determinants?
BackgroundLong COVID has been increasingly linked to persistent clinical manifestations, including chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME...
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ORIGINAL RESEARCH article
Front. Psychiatry, 28 August 2025
Sec. Mood Disorders
Volume 16 - 2025 | https://doi.org/10.3389/fpsyt.2025.1623288
Bipolar spectrum, hypothyroidism, and their association with chronic fatigue/myalgic encephalomyelitis-like syndrome in long COVID: could they be identified as early determinants?
Massimo Tusconi1Serdar M. Dursun2Francesco Pegreffi3Cesar Ivan Aviles Gonzalez3*Vanessa Barrui4Michele Fornaro5
Felice Curcio7Mauro Giovanni Carta6,8Giulia Cossu8- 1University Hospital of Cagliari, Cagliari, Italy
- 2Neurochemical Research Unit, Department of Psychiatry University of Alberta, Edmonton, AB, Canada
- 3Department of Medicine and Surgery, University of Enna “Kore”, Enna, Italy
- 4Department of Mental Health and Addiction, ASL Ogliastra, Lanusei, Italy
- 5Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy
- 6Faculty of Health Sciences, Universidad Popular del Cesar, Valledupar, Colombia
- 7Faculty of Medicine and Surgery, University of Sassari (UNISS), Sassari, Italy
- 8Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
Objectives: This study investigates the prevalence of hypothyroidism and bipolar spectrum disorders in patients with CFS/ME associated with long-term COVID-19. It compares it with pre-pandemic population data to determine whether these conditions may be predisposing factors.
Methods: A case–control design was used to select cases from a clinical trial on CFS/ME in long COVID, while controls were extracted from pre-COVID epidemiological databases. Comparative statistical analyses, including chi-square tests and analysis of variance (ANOVA), were performed to assess significant differences in the frequency of these conditions between both groups.
Results: The clinical sample showed significantly higher prevalence rates of hypothyroidism [27.78% vs. 1.14%; odds ratio (OR) = 33.07; 95% confidence interval (CI): 7.10–153.70] and bipolar spectrum disorders (16.67% vs. 0.2%; OR = 138.4; 95% CI: 36.40–526.43) compared to control populations (p < 0.0001 for both). Similarly, individuals screening positive for depressive symptoms (PHQ9 > 9) showed markedly increased odds (55.5% vs. 4.16%; OR = 28.75; 95% CI: 6.52–126.73).
Conclusion: The findings suggest that hypothyroidism and bipolar spectrum disorders may act as predisposing factors in the development of CFS/ME in long-term COVID-19. Identifying these clinical antecedents could facilitate early detection and the development of targeted intervention strategies in at-risk populations.
