Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mimics the influenza A (H1N1) virus in terms of clinical presentation, transmission mechanism, and seasonal coincidence. Comprehensive data for the clinical severity of adult patients co-infected by both H1N1 and SARS-CoV-2, and, particularly, the relationship with PCR cycle threshold (Ct) values are not yet available. All participants in this study were tested for H1N1 and SARS-CoV-2 simultaneously at admission. Demographic, clinical, treatment, and laboratory data were extracted from electronic medical records and compared among adults hospitalized for H1N1 infection, SARS-CoV-2 infection and co-infection with both viruses. Ct values for viral RNA detection were further compared within SARS-CoV-2 and co-infection groups. Score on seven-category ordinal scale of clinical status at day 7 and day 14 were assessed. Among patients with monoinfection, H1N1 infection had higher frequency of onset symptoms but lower incidence of adverse events during hospitalization than SAR-CoV-2 infection (P < 0.05). Co-infection had an increased odds of acute kidney injury, acute heart failure, secondary bacterial infections, multilobar infiltrates and admittance to ICU than monoinfection. Score on seven-category scale at day 7 and day 14 was higher in patients with coinfection than patients with SAR-CoV-2 monoinfection (P<0.05). Co-infected patients had lower initial Ct values (referring to higher viral load) (median 32) than patients with SAR-CoV-2 monoinfection (median 36). Among co-infected patients, low Ct values were significantly and positively correlated with acute kidney injury and ARDS (P = 0.03 and 0.02, respectively). Co-infection by SARS-CoV-2 and H1N1 caused more severe disease than monoinfection by either virus in adult inpatients. Early Ct value could provide clues for the later trajectory of the co-infection. Multiplex molecular diagnostics for both viruses and early assessment of SAR-CoV-2 Ct values are recommended to achieve optimal treatment for improved clinical outcome.

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Background Emerging data suggests the neuroprotective and anti-neuroinflammatory effects of glucosamine. We aimed to examine the association between regular glucosamine use and risk of incident dementia, including dementia subtypes. Methods We conducted large-scale observational and two-sample Mendelian randomization (MR) analyses. Participants in UK Biobank having accessible data for dementia incidence and who did not have dementia at baseline were included in the prospective cohort. Through the Cox proportional hazard model, we examined the risks of incident all-cause dementia, Alzheimer’s disease (AD), and vascular dementia among glucosamine users and non-users. To further test the causal association between glucosamine use and dementia, we conducted a 2-sample MR utilizing summary statistics from genome-wide association studies (GWAS). The GWAS data were obtained from observational cohort participants of mostly European ancestry. Results During a median follow-up of 8.9 years, there were 2458 cases of all-cause dementia, 924 cases of AD, and 491 cases of vascular dementia. In multivariable analysis, the hazard ratios (HR) of glucosamine users for all-cause dementia, AD, and vascular dementia were 0.84 (95% CI 0.75–0.93), 0.83 (95% CI 0.71–0.98), and 0.74 (95% CI 0.58–0.95), respectively. The inverse associations between glucosamine use and AD appeared to be stronger among participants aged below 60 years than those aged above 60 years (p = 0.04 for interaction). The APOE genotype did not modify this association (p > 0.05 for interaction). Single-variable MR suggested a causal relationship between glucosamine use and lower dementia risk. Multivariable MR showed that taking glucosamine continued to protect against dementia after controlling for vitamin, chondroitin supplement use and osteoarthritis (all-cause dementia HR 0.88, 95% CI 0.81–0.95; AD HR 0.78, 95% CI 0.72–0.85; vascular dementia HR 0.73, 95% CI 0.57–0.94). Single and multivariable inverse variance weighted (MV-IVW) and MR-Egger sensitivity analyses produced similar results for these estimations. Conclusions The findings of this large-scale cohort and MR analysis provide evidence for potential causal associations between the glucosamine use and lower risk for dementia. These findings require further validation through randomized controlled trials.

Objective. Emerging evidence indicates that hyperglycemia has an adverse impact on the knee joint which, in turn, may increase the risk of knee osteoarthritis (OA), but evidence from the real-life settings of large-scale cohort studies remains unclear. We sought to evaluate the association of glycemic control and the risk of symptomatic knee OA in a community-based cohort of older adults.Methods. We conducted a prospective analysis of 10,730 participants without knee OA. Comprehensive blood biomarker data were obtained. Diabetes mellitus (DM) was defined mainly using a glycosylated hemoglobin (HbA 1c ) level of ≥6.5%; poor glycemic control in individuals with DM was defined as an HbA 1c level of ≥7%. We fit Cox regression models, stratified according to DM status. We evaluated the hazards associated with HbA 1c and fasting blood glucose levels using a spline model.Results. During a median follow-up of 5 years, knee OA developed in 1,089 participants (108 with DM and 971 without). Knee OA was related to DM (hazard ratio [HR] 1.29 [95% confidence interval (95% CI) 1.02-1.78]), bad glycemic regulation in DM patients (HR 1.41 [95% CI 1.05-2.09]), and long-term DM (≥5 versus <5 years; HR 1.49 [95% CI 1.02-2.17]). High levels of HbA 1c (>7.7% and 61 mmoles/mole) and fasting blood glucose (>186 mg/dl) were significantly associated with higher risk of incident knee OA.Conclusion. DM, bad glycemic management, and long-term DM are potential risk factors of symptomatic knee OA independent of age and body mass index. Targeting blood glucose, in addition to bodyweight, may be an important avenue for prevention of knee OA.