Bipolar spectrum, hypothyroidism, and their association with chronic fatigue/myalgic encephalomyelitis-like syndrome in long COVID: could they be identified as early determinants?

Massimo Tusconi; Serdar M Dursun; Francesco Pegreffi; Cesar Ivan Aviles Gonzalez; Vanessa Barrui; Michele Fornaro; Luz Alba Hurtado Lujan; Lina Patricia Camacho Nunez; Arley Denisse Vega Ochoa; Felice Curcio; Mauro Giovanni Carta; Giulia Cossu

doi: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?

Front Psychiatry. 2025 Aug 28:16:1623288. doi: 10.3389/fpsyt.2025.1623288. eCollection 2025.

Affiliations

¹ University Hospital of Cagliari, Cagliari, Italy.
² Neurochemical Research Unit, Department of Psychiatry University of Alberta, Edmonton, AB, Canada.
³ Department of Medicine and Surgery, University of Enna "Kore", Enna, Italy.
⁴ Department of Mental Health and Addiction, ASL Ogliastra, Lanusei, Italy.
⁵ Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy.
⁶ Faculty of Health Sciences, Universidad Popular del Cesar, Valledupar, Colombia.
⁷ Faculty of Medicine and Surgery, University of Sassari (UNISS), Sassari, Italy.
⁸ Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.

Abstract

Background: Long COVID has been increasingly linked to persistent clinical manifestations, including chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). However, the relationship between this syndrome and pre-existing conditions such as bipolar spectrum disorders and hypothyroidism is not yet clearly established. These disorders may influence the regulation of biorhythms and immune function, suggesting a possible role in the predisposition to the development of CFS/ME in the context of long-term COVID-19.

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.

Keywords: bipolar disorder; chronic fatigue syndrome; hypothyroidism; long COVID; myalgic encephalomyelitis; psychiatric comorbidities.