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 Dursun²Cesar Ivan Aviles Gonzalez^3*Francesco Pegreffi³Vanessa Barrui⁴Michele Fornaro⁵Luz Alba Hurtado Lujan⁶Lina Patricia Camacho Nunez⁶Arley Denisse Vega Ochoa⁶Felice Curcio⁷Mauro Giovanni Carta¹Giulia Cossu⁸

• ¹University Hospital of Cagliari, Cagliari, Italy
• ²Neurochemical Research Unit, Department of Psychiatry University of Alberta, Edmonton, Canada, Edmonton, Canada
• ³Kore University of Enna, Enna, Italy
• ⁴ASL Ogliastra Via is Piscinas 5 08045 Lanusei, Lanusei, Italy
• ⁵Department of Neuroscience, Reproductive Science and Odontostomatology Federico II University of Naples, 80131 Naples, Italy, Naples, Italy
• ⁶Universidad Popular del Cesar, Valledupar 200002, Colombia, Valledupar, Colombia
• ⁷Faculty of Medicine and Surgery, University of Sassari (UNISS), Viale San Pietro 43/B, 07100 Sassari, Italy, Sassari, Italy
• ⁸Department of Medical Sciences and Public Health, University of Cagliari, 09042 Cagliari, Italy, Cagliari, Italy

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.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.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 ANOVA, were performed to assess significant differences in the frequency of these conditions between both groups.The clinical sample showed significantly higher prevalence rates of hypothyroidism (27.78% vs. 1.14%; OR = 33.07; 95% 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 (PHQ-9 > 9) showed markedly increased odds (55.5% vs. 4.16%; OR = 28.75; 95% CI: 6.52-126.73).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.