Lin Xu

OBJECTIVE Patients with obesity are at increased risk of exacerbations from viral respiratory infections. However, the association of obesity with the severity of coronavirus disease 2019 (COVID-19) is unclear. We examined this association using data from the only referral hospital in Shenzhen, China. RESEARCH DESIGN AND METHODS A total of 383 consecutively hospitalized patients with COVID-19 admitted from 11 January 2020 to 16 February 2020 and followed until 26 March 2020 at the Third People’s Hospital of Shenzhen were included. Underweight was defined as a BMI <18.5 kg/m2, normal weight as 18.5–23.9 kg/m2, overweight as 24.0–27.9 kg/m2, and obesity as ≥28 kg/m2. RESULTS Of the 383 patients, 53.1% were normal weight, 4.2% were underweight, 32.0% were overweight, and 10.7% were obese at admission. Obese patients tended to have symptoms of cough (P = 0.03) and fever (P = 0.06) compared with patients who were not obese. Compared with normal weight patients, those who were overweight had 1.84-fold odds of developing severe COVID-19 (odds ratio [OR] 1.84, 95% CI 0.99–3.43, P = 0.05), while those who were obese were at 3.40-fold odds of developing severe disease (OR 3.40, 95% CI 1.40–2.86, P = 0.007), after adjusting for age, sex, epidemiological characteristics, days from disease onset to hospitalization, presence of hypertension, diabetes, cardiovascular disease, chronic obstructive pulmonary disease, liver disease, and cancer, and drug used for treatment. Additionally, after similar adjustment, men who were obese versus those who were normal weight were at increased odds of developing severe COVID-19 (OR 5.66, 95% CI 1.80–17.75, P = 0.003). CONCLUSIONS In this study, obese patients had increased odds of progressing to severe COVID-19. As the severe acute respiratory syndrome coronavirus 2 may continue to spread worldwide, clinicians should pay close attention to obese patients, who should be carefully managed with prompt and aggressive treatment.

BACKGROUND: Testosterone therapy is increasingly promoted. No randomized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events, although very high levels of androgens are thought to promote cardiovascular disease. METHODS: A systematic review and meta-analysis was conducted of placebo-controlled randomized trials of testosterone therapy among men lasting 12+ weeks reporting cardiovascular-related events. We searched PubMed through the end of 2012 using "("testosterone" or "androgen") and trial and ("random*")" with the selection limited to studies of men in English, supplemented by a bibliographic search of the World Health Organization trial registry. Two reviewers independently searched, selected and assessed study quality with differences resolved by consensus. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting. RESULTS: Of 1,882 studies identified 27 trials were eligible including 2,994, mainly older, men who experienced 180 cardiovascular-related events. Testosterone therapy increased the risk of a cardiovascular-related event (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.09 to 2.18). The effect of testosterone therapy varied with source of funding (P-value for interaction 0.03), but not with baseline testosterone level (P-value for interaction 0.70). In trials not funded by the pharmaceutical industry the risk of a cardiovascular-related event on testosterone therapy was greater (OR 2.06, 95% CI 1.34 to 3.17) than in pharmaceutical industry funded trials (OR 0.89, 95% CI 0.50 to 1.60). CONCLUSIONS: The effects of testosterone on cardiovascular-related events varied with source of funding. Nevertheless, overall and particularly in trials not funded by the pharmaceutical industry, exogenous testosterone increased the risk of cardiovascular-related events, with corresponding implications for the use of testosterone therapy.

Inheritance of the apoE4 allele (epsilon4) increases the risk of developing Alzheimer's disease; however, the mechanisms underlying this association remain elusive. Recent data suggest that inheritance of epsilon4 may lead to reduced apoE protein levels in the CNS. We therefore examined apoE protein levels in the brains, CSF and plasma of epsilon2/2, epsilon3/3, and epsilon4/4 targeted replacement mice. These apoE mice showed a genotype-dependent decrease in apoE levels; epsilon2/2 >epsilon3/3 >epsilon4/4. Next, we sought to examine the relative contributions of apoE4 and apoE3 in the epsilon3/4 mouse brains. ApoE4 represented 30-40% of the total apoE. Moreover, the absolute amount of apoE3 per allele was similar between epsilon3/3 and epsilon3/4 mice, implying that the reduced levels of total apoE in epsilon3/4 mice can be explained by the reduction in apoE4 levels. In culture medium from epsilon3/4 human astrocytoma or epsilon3/3, epsilon4/4 and epsilon3/4 primary astrocytes, apoE4 levels were consistently lower than apoE3. Secreted cholesterol levels were also lower from epsilon4/4 astrocytes. Pulse-chase experiments showed an enhanced degradation and reduced half-life of newly synthesized apoE4 compared with apoE3. Together, these data suggest that astrocytes preferentially degrade apoE4, leading to reduced apoE4 secretion and ultimately to reduced brain apoE levels. Moreover, the genotype-dependent decrease in CNS apoE levels, mirror the relative risk of developing AD, and suggest that low levels of total apoE exhibited by epsilon4 carriers may directly contribute to the disease progression, perhaps by reducing the capacity of apoE to promote synaptic repair and/or Abeta clearance.