Long-term antibody responses and neutralizing activities in response to SARS-CoV-2 infection are not yet clear. Here we quantify immunoglobulin M (IgM) and G (IgG) antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein, and neutralizing antibodies during a period of 6 months from COVID-19 disease onset in 349 symptomatic COVID-19 patients who were among the first be infected world-wide. The positivity rate and magnitude of IgM-S and IgG-N responses increase rapidly. High levels of IgM-S/N and IgG-S/N at 2-3 weeks after disease onset are associated with virus control and IgG-S titers correlate closely with the capacity to neutralize SARS-CoV-2. Although specific IgM-S/N become undetectable 12 weeks after disease onset in most patients, IgG-S/N titers have an intermediate contraction phase, but stabilize at relatively high levels over the 6 month observation period. At late time points, the positivity rates for binding and neutralizing SARS-CoV-2-specific antibodies are still >70%. These data indicate sustained humoral immunity in recovered patients who had symptomatic COVID-19, suggesting prolonged immunity.

OBJECTIVE: To investigate whether serum uric acid (SUA) level is associated with all-cause and cardiovascular disease (CVD) mortality among individuals with diabetes. RESEARCH DESIGN AND METHODS: In this prospective cohort study, we included patients with diabetes from the U.S. National Health and Nutritional Examination Survey (NHANES) 1999–2018. Mortality and underlying causes of death were ascertained by linkage to national death records through 31 December 2019. Weighted Cox proportional hazards regression models were used to evaluate hazard ratios (HRs) and 95% CIs for all-cause and CVD mortality. We also performed a meta-analysis of available cohort studies to combine the association between SUA level and mortality in diabetes. RESULTS: Among the 7,101 patients with diabetes from NHANES 1999–2018, the weighted mean of SUA level was 5.7 mg/dL. During 57,926 person-years of follow-up, 1,900 deaths (n = 674 deaths from CVD) occurred. In the fully adjusted model, when compared with patients with diabetes in the lowest SUA quintile, those in the highest SUA quintile had the HRs (95% CIs) of 1.28 (1.03, 1.58) for all-cause mortality and 1.41 (1.03, 1.94) for CVD mortality. We included 13 cohort studies in the meta-analysis and found that the pooled HRs (95% CIs) were 1.08 (1.05, 1.11) for all-cause mortality and 1.05 (1.03, 1.06) for CVD mortality per 1 mg/dL increment of SUA level in patients with diabetes. CONCLUSIONS: This study indicated that higher SUA levels were associated with increased risks of all-cause and CVD mortality in diabetes. Interventional studies are needed to elucidate the health effect of treatments to lower SUA levels.

Background: Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. Methods: Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. Results: A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2–31.6%) and 26.2% (23.9–28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. Conclusions: The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.

Parkinson disease (PD) is the second most prevalent neurodegenerative disease with manifestations of resting tremor, bradykinesia, rigidity, and postural gait disturbance and has the fastest increase in prevalence, death, and disability-adjusted life-years among neurological disorders, according to The Global Burden of Diseases, Injuries, and Risk Factors Study.¹ The prevalence of PD in 2016 was 2.4 times higher than the prevalence in 1990.² The pathophysiology of PD is thought to be neuronal death of dopaminergic neurons and accumulation of Lewy body in neuronal cytoplasm, and the course of PD is considered as irreversible, which emphasizes the importance of prevention. However, few risk factors of PD have been recognized so far.

Circulating uric acid levels were associated with insulin resistance, but the causality is unclear. We aimed to investigate the association between plasma uric acid and insulin resistance in newly diagnosed type 2 diabetes (T2D). We enrolled 1,938 patients who underwent a 75-g oral glucose tolerance test. Insulin resistance was estimated based on the homeostatic model assessment index (HOMA2-IR) and the Matsuda index. Uric acid was measured in fasting plasma by uricase-peroxidase method. We genotyped single nucleotide polymorphisms (SNPs) that were recently identified as top hits in genome-wide association studies of uric acid levels. A weighted genetic risk score (wGRS) was calculated based on the associations between selected SNPs and uric acid levels. The adjusted β coefficients for Ln-transformed Matsuda index and HOMA2-IR per 1 mg/dL uric acid increment were -0.070 (95%CI: -0.089, -0.052) and 0.057 (95%CI: 0.039, 0.075). These associations were more pronounced among women than men. In Mendelian randomization analysis, the wGRS raised uric acid by 0.225 mg/dL (95%CI: 0.138, 0.312) per SD increase of the score. However, no association was observed between the wGRS and insulin resistance indices whether in men or women. Elevated plasma uric acid was associated with higher risk of insulin resistance, along with observation of gender difference in such association. However, our study does not support a causal role of plasma uric acid on insulin resistance among newly diagnosed T2D patients.

Background: longitudinal evidence concerning frailty phenotype and the risk of cardiovascular disease (CVD) remained insufficient, and whether CVD preventive strategies exert low CVD risk on frail adults is unclear. Objectives: we aimed to prospectively evaluate the association of frailty phenotype, adherence to ideal cardiovascular health (CVH) and their joint associations with the risk of CVD. Methods: a total of 314,093 participants from the UK Biobank were included. Frailty phenotype was assessed according to the five criteria of Fried et al.: weight loss, exhaustion, low physical activity, slow gait speed and low grip strength. CVH included four core health behaviours (smoking, physical activity and diet) and three health factors (weight, cholesterol, blood pressure and glycaemic control). The outcome of interest was incident CVD, including coronary heart disease, heart failure and stroke. Results: compared with the non-frail people whose incident rate of overall CVD was 6.54 per 1,000 person-years, the absolute rate difference per 1,000 person-years was 1.67 (95% confidence interval, CI: 1.33, 2.02) for pre-frail and 5.00 (95% CI: 4.03, 5.97) for frail. The ideal CVH was significantly associated with a lower risk of all CVD outcomes. For the joint association of frailty and CVH level with incident CVD, the highest risk was observed among frailty accompanied by poor CVH with an HR of 2.92 (95% CI: 2.68, 3.18). Conclusions: our findings indicate that physical frailty is associated with CVD incidence. Improving CVH was significantly associated with a considerable decrease in CVD risk, and such cardiovascular benefits remain for the frailty population.