The clinical characteristics and thyroid hormone levels of neuro-long COVID among Hong Kong adults

Abstract

According to the US Centre for Disease Control and Prevention, Long COVID is defined by unexplained persistent symptoms lasting for 4 weeks or more upon the onset of acute infection. Over 30% of COVID-19 survivors experience persistent neurological, neuropsychological or neuropsychiatric symptoms, i.e. Neuro-Long COVID, which is debilitating and causes immense healthcare burden. At present, there is no consensus on Neuro-Long COVID management simply because of a lack of pathophysiological knowledge. The thyroid gland is a known target of COVID-19 infections. Thyroid hormones are important in regulating brain function, yet the association between thyroid hormone imbalance and Neuro-Long COVID remains unclear. We aim to better understand Neuro-Long COVID by describing 1) the epidemiology in Hong Kong adults; 2) the predictors and protective factors; 3) the association with thyroid hormone level; 4) the association with clinical assessment results and 5) a proposed definition for this novel syndrome.

A two-part cross-sectional study was conducted. First, a population-based online survey was performed among Hong Kong residents from April 2023 to May 2024. Demographics and information on COVID-19 infection(s) were collected. Further in-person assessments were conducted on a subset of participants to evaluate their neurological functioning. Serum samples were then collected to assess thyroid hormone levels. The Chi-square or Fisher’s exact test was used to compare group differences between demographic variables, as appropriate. Student’s t-test or one-way ANOVA was used to compare thyroid hormone levels between groups, as appropriate. Univariate and multivariate analyses were conducted to determine predictors of Neuro-Long COVID. Statistical significance was inferred when p <.05.

Among 5007 survey respondents, most general symptoms resolved within 4 weeks; fatigue (34.8%) was the most reported persistent symptom. Attention/concentration loss (34.4%) and memory disturbances (31.1%) are the most prevalent neurological persistent symptoms among COVID-19 survivors. Female sex, older age, community treatment facilities admission, pre-existing medical conditions, and repeated COVID-19 infections were significantly associated with an increased risk of developing Neuro-Long COVID; while reduced risk was observed in participants who were fully vaccinated. Pre-existing thyroid disorders were an independent risk factor of cognitive Neuro-Long COVID subtype. Among 378 subjects who participated in further assessments, individuals who scored lower in the MoCA memory subsection were more likely to develop Neuro-Long COVID. No significant differences between serum levels of free triiodothyronine (fT3) and thyroid stimulating hormone (TSH) were observed in the presence of Neuro-Long COVID and persistent fatigue, independently.

In summary, this thesis provided evidence regarding the epidemiology of Neuro-Long COVID in Hong Kong adults; the predictive value of pre-existing comorbidities, acute severe illness, and repeated infections; and the protective value of a full vaccination regimen for Neuro-Long COVID. Furthermore, thyroid function does not play an important role in the pathogenesis of Neuro-Long COVID. Based on our findings, the presence of ≥ 3 persistent neurological symptoms may serve as useful criteria for defining this novel syndrome. Future treatment guidelines for COVID-19 should reflect corresponding care for managing neurological symptoms among these high-risk populations.