Objective COVID-19 is a new coronavirus infectious disease. We aimed to study the characteristics of thyroid hormone levels in patients with COVID-19 and to explore whether thyroid hormone predicts all-cause mortality of severely or critically ill patients. Methods The clinical data of 100 patients with COVID-19, who were admitted to Wuhan Tongji Hospital from February 8 to March 8, 2020, were analyzed in this retrospective study. The patients were followed up for 6–41 days. Patients were grouped into non-severe illness and severe or critical illness, which included survivors and non-survivors. Multivariate Cox proportional hazards analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality in association with continuous and the lower two quartiles of thyroid hormone concentrations in severely or critically ill patients. Results The means of free T3 (FT3) were 4.40, 3.73 and 2.76 pmol/L in non-severely ill patients, survivors and non-survivors, respectively. The lower (versus upper) two quartiles of FT3 was associated with all-cause mortality HR (95% CI) of 9.23 (2.01, 42.28). The HR (95% CI) for all-cause mortality in association with continuous FT3 concentration was 0.41 (0.21, 0.81). In the multivariate-adjusted models, free T4 (FT4), TSH and FT3/FT4 were not significantly related to all-cause mortality. Patients with FT3 less than 3.10 pmol/L had increased all-cause mortality. Conclusion FT3 concentration was significantly lower in patients with severe COVID-19 than in non-severely ill patients. Reduced FT3 independently predicted all-cause mortality of patients with severe COVID-19.

ObjectiveTo investigate the independent associations of social isolation and loneliness with incident dementia and to explore the potential neurobiological mechanisms.MethodsWe utilized the UK Biobank cohort to establish Cox proportional hazard models with social isolation and loneliness as separate exposures. Demographic (sex, age and ethnicity), socioeconomic (education level, household income and Townsend deprivation index), biological (BMI, APOE genotype, diabetes, cancer, cardiovascular disease and other disabilities), cognitive (speed of processing and visual memory), behavioral (current smoker, alcohol intake and physical activity), and psychological (social isolation or loneliness, depressive symptoms and neuroticism) factors measured at baseline were adjusted. Then, voxel-wise brain-wide association analyses were used to identify gray matter volumes (GMV) associated with social isolation and with loneliness. Partial least squares regression was performed to test the spatial correlation of GMV differences and gene expression using the Allen Human Brain Atlas.ResultsWe included 462,619 participants (mean age at baseline 57.0 years [SD 8.1]). With a mean follow-up of 11.7 years (SD 1.7), 4,998 developed all-cause dementia. Social isolation was associated with a 1.26-fold increased risk of dementia (95% CI, 1.15-1.37) independently of various risk factors including loneliness and depression (i.e., full adjustment). However, the fully adjusted hazard ratio for dementia related to loneliness was 1.04 (95% CI, 0.94-1.16); and 75% of this relationship was attributable to depressive symptoms. Structural MRI data were obtained from 32,263 participants (mean age 63.5 years [SD 7.5]). Socially isolated individuals had lower GMVs in temporal, frontal and other (e.g., hippocampal) regions. Mediation analysis showed that the identified GMVs partly mediated the association between social isolation at baseline and cognitive function at follow-up. Social isolation-related lower GMVs were related to under-expression of genes that are down-regulated in Alzheimer’s disease and to genes that are involved in mitochondrial dysfunction and oxidative phosphorylation.ConclusionSocial isolation is a risk factor for dementia that is independent of loneliness and many other covariates. Social isolation-related brain structural differences coupled with different molecular functions also support the associations of social isolation with cognition and dementia. Social isolation may thus be an early indicator of an increased risk of dementia.