Pathogenic human coronaviruses (CoVs), such as the severe acute respiratory syndrome (SARS)-CoV and the Middle East respiratory syndrome–CoV, cause acute respiratory illness. Epidemiological data from the 2002–2003 SARS epidemic and recent Middle East respiratory syndrome outbreak indicate that there may be sex-dependent differences in disease outcomes. To investigate these differences, we infected male and female mice of different age groups with SARS-CoV and analyzed their susceptibility to the infection. Our results showed that male mice were more susceptible to SARS-CoV infection compared with age-matched females. The degree of sex bias to SARS-CoV infection increased with advancing age, such that middle-aged mice showed much more pronounced differences compared with young mice. Enhanced susceptibility of male mice to SARS-CoV was associated with elevated virus titers, enhanced vascular leakage, and alveolar edema. These changes were accompanied by increased accumulation of inflammatory monocyte macrophages and neutrophils in the lungs of male mice, and depletion of inflammatory monocyte macrophages partially protected these mice from lethal SARS. Moreover, the sex-specific differences were independent of T and B cell responses. Furthermore, ovariectomy or treating female mice with an estrogen receptor antagonist increased mortality, indicating a protective effect for estrogen receptor signaling in mice infected with SARS-CoV. Together, these data suggest that sex differences in the susceptibility to SARS-CoV in mice parallel those observed in patients and also identify estrogen receptor signaling as critical for protection in females.

The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pneumonia. MERS was recently identified as a candidate for vaccine development, but most efforts focus on antibody responses, which are often transient after CoV infections. CoV-specific T cells are generally long-lived, but the virus-specific T cell response has not been addressed in MERS patients. We obtained peripheral blood mononuclear cells and/or sera from 21 MERS survivors. We detected MERS-CoV–specific CD4⁺ and CD8⁺ T cell responses in all MERS survivors and demonstrated functionality by measuring cytokine expression after peptide stimulation. Neutralizing (PRNT₅₀) antibody titers measured in vitro predicted serum protective ability in infected mice and correlated with CD4⁺ but not CD8⁺ T cell responses; patients with higher PRNT₅₀ and CD4⁺ T cell responses had longer intensive care unit stays and prolonged virus shedding and required ventilation. Survivors with undetectable MERS-CoV–specific antibody responses mounted CD8⁺ T cell responses comparable with those of the whole cohort. There were no correlations between age, disease severity, comorbidities, and virus-specific CD8⁺ T cell responses. In conclusion, measurements of MERS-CoV–specific T cell responses may be useful for predicting prognosis, monitoring vaccine efficacy, and identifying MERS patients with mild disease in epidemiological studies and will complement virus-specific antibody measurements.

Purpose: Clinicians anecdotally noted that elderly patients who suffered from traumatic injuries (falls or other injuries) often re-present and are readmitted with fall injuries. Herein, we hypothesized that fall injuries and fall-related deaths and readmissions are increasing over time, and assessed whether the overall rates of death, hospital admission, and 30-day readmission due to falls increased from 2010 to 2014 in the elderly population (≥65) in the US. Patients and methods: The WHO mortality database and the National Readmission Database (NRD) were queried to assess rates of deaths and hospital admissions and 30-day readmissions associated with fall injuries in the elderly population that presented with trauma. Descriptive statistics were obtained. The generalized linear mixed modeling (GLMM) framework was utilized to examine the relationship between fixed-effect predictor variables and the dichotomous outcome, indicating readmission within 30 days of previous discharge while accounting for hospital clustering with a random intercept. Results: Fall-related death increased by 1.4% from 2010 to 2014. Similarly, the hospital admission rate increased by 2% and was mainly associated with increased admission of elderly 65–74 years old. Approximately 55% of the fall patients were placed in nursing facilities in 2010, and this rate increased by 3% from 2010 to 2014. Thirty-day readmission rates for fall and trauma patients remained stable from 2010 to 2014. However, the rate of fall patients readmitted within 30 days for a subsequent fall increased from 15.6% to 17.4% between 2010 and 2014. Conclusion: Our data indicate a steady increase in deaths and admissions for fall injuries in the elderly population. Strikingly, the incidence of readmission for a subsequent fall is increasing. With the aging population, this trend is likely to continue and highlights the need for elderly social support systems and fall prevention programs.

The Beam F3 and 5.5 cm methods are the two most common targeting strategies for localizing the left dorsolateral prefrontal cortex (DLPFC) treatment site in repetitive transcranial magnetic stimulation (rTMS) protocols. This prospective, randomized, double-blind comparative effectiveness trial assesses the clinical outcomes for these two methods in a naturalistic sample of patients with major depressive disorder (MDD) undergoing clinical rTMS treatment. 105 adult patients with MDD (mean age = 43.2; range = 18-73; 66% female) were randomized to receive rTMS to the Beam F3 (n = 58) or 5.5 cm (n = 47) target. Between group differences from pre-to post-treatment were evaluated with the Patient Health Questionnaire-9 (PHQ-9) [primary outcome measure], Generalized Anxiety Disorder-7 (GAD-7), and clinician-administered Montgomery-Åsberg Depression Scale (MADRS). Primary treatment endpoint was completion of daily treatment series. Per-protocol analyses showed no statistically significant differences on any measure between the 5.5 cm and F3 groups (all p ≥ 0.50), including percent improvement (PHQ-9: 39% vs. 39%; GAD-7: 34% vs. 27%; MADRS: 40% vs. 38%), response rate (PHQ-9: 37% vs. 43%; GAD-7: 27% vs. 30%; MADRS: 43% vs. 43%), and remission rate (PHQ-9: 22% vs. 21%; MADRS: 20% vs. 19%). Post hoc analysis of anxiety symptom change while controlling for depression severity suggested more favorable anxiolytic effects with 5.5 cm targeting (p = 0.03). Similar antidepressant effects were observed with DLFPC rTMS using either the Beam F3 or 5.5 cm targeting method, supporting clinical equipoise in MDD patients with head circumference ≤ 60 cm. Comparison to MRI-based targeting and differential effects on anxiety symptoms require further investigation. ClinicalTrials.gov identifier: NCT03378570.

Background: Patients with CKD and diabetes are at higher risk of developing cardiovascular disease, in part, because of impaired endothelial function. Cardioprotective compounds such as resveratrol could improve endothelial function and attenuate the cardiovascular burden in patients with CKD and diabetes. We hypothesized that resveratrol supplementation would improve endothelial function in patients with CKD and diabetes. Methods: Twenty-eight adults aged 68±7 years (84% men) with stage 3 CKD and diabetes were enrolled in a randomized, double-blind, placebo-controlled, crossover study to investigate the effects of 6-week resveratrol supplementation (400 mg/d) on endothelial function. Endothelial function was determined through brachial artery flow-mediated dilation. Results: The mean values for eGFR and hemoglobin A_1c were 40±9 ml/min per 1.73 m² and 7.36%±0.72%, respectively. Compared with placebo, resveratrol supplementation increased flow-mediated dilation (ratio of geometric mean changes and 95% confidence interval for between-group comparisons, 1.43 (1.15 to 1.77); P value = 0.001). eGFR, hemoglobin A_1c, BP, and nitroglycerin-mediated dilation were unchanged with resveratrol or placebo (P = 0.15), suggesting the observed change in flow-mediated dilation was likely independent of changes in traditional cardiovascular risk factors. Conclusions: Resveratrol supplementation improved endothelial function in patients with CKD and diabetes. Clinical Trial registry name and registration number: Resveratrol and Vascular Function in CKD, NCT03597568. Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_20_CJN0000000000000337.mp3