Throughout the world, including the United States, men have worse outcomes from COVID-19 than women. SARS-CoV-2, the causative virus of the COVID-19 pandemic, uses angiotensin-converting-enzyme-2 (ACE2) to gain cellular entry. ACE2 is a member of the renin-angiotensin-system (RAS) and plays an important role in counteracting the harmful effects mediated by the angiotensin-type-1-receptor. Therefore, we conducted Ovid MEDLINE and Embase database searches of basic science studies investigating the impact of the biological variable of sex on ACE2 expression and regulation from 2000, the year ACE2 was discovered, through December 31, 2020. Out of 2131 publications, we identified 853 original research articles on ACE2 conducted in primary cells, tissues and/or whole mammals excluding humans. The majority (68.7%) of these studies that cited the sex of the animal were conducted in males, while 11.2% were conducted solely in females; 9.26% compared ACE2 between the sexes, while 10.8% did not report the sex of the animals used. General findings are that sex-differences are tissue-specific and when present, are dependent-upon gonadal state. Renal, cardiac and adipose ACE2 is increased in both sexes under experimental conditions that model co-morbidities associated with worse COVID-19 outcomes including hypertension, obesity, and renal and cardiovascular diseases; however, ACE2 protein was generally higher in the males. Studies in Ace2- knockout-mice indicate ACE2 plays a greater role protecting the female from developing hypertension than the male. Studying the biological variable of sex in ACE2 research provides an opportunity for discovery in conditions involving RAS-dysfunction and will shed light on sex-differences in COVID-19-severity.

In primary hyperparathyroidism, an increased risk of developing the cardiovascular disease may exist due to increased activity of the renin-angiotensin-aldosterone system. The aim of this study was to evaluate the relationship between parathyroid hormone and aldosterone in patients with primary hyperparathyroidism. The study included 48 patients with primary hyperparathyroidism and 30 healthy subjects who matched age and gender to the study group. This study was conducted at the Center for Laboratory medicine, Clinical center of Vojvodina, Novi Sad, Serbia. In addition to clinical data and laboratory determination of the concentration of total and ionized calcium, phosphorus, measurements of parathyroid hormone, vitamin D, direct renin, and aldosterone were performed by the method of chemiluminescent technology. Compared to the controls, the study group had statistically significantly higher values of aldosterone ( p = 0.028 ), total calcium ( p = 0.01 ), ionized calcium ( p = 0.003 ) and parathyroid hormone ( P ≤ 0.001 ) Serum aldosterone and parathyroid hormone levels were correlated positively in patients with primary hyperparathyroidism ( r = 0.509 , p < 0.05 ). A statistically significant positive correlation between renin and parathyroid hormone ( r = 0.688 , p < 0.05 ) and renin and calcium ( r = 0.673 , p < 0.05 ) was determined in hyperparathyroid patients. In multivariate regression analysis, the strongest predictive variable of aldosterone secretion was parathyroid hormone ( p = 0.011 ). An independent relationship between parathyroid hormone and aldosterone in patients with primary hyperparathyroidism and the correlation between renin and parathyroid hormone as well as with calcium indicate not only the direct but also the indirect associations between parathyroid hormone and aldosterone in primary hyperparathyroidism. These findings may represent another possible model of renin-angiotensin-aldosterone-induced organ damage.

Backgrounds and Objectives: Obstructive sleep apnea (OSA) is associated with increased morbidity and mortality. OSA is an independent risk factor for many different conditions, especially cardiovascular diseases. The purpose of this study was to ascertain the comorbidity profile of non-obese patients with newly diagnosed OSA and evaluate the risk for cardiovascular disease and mortality. The present study also aimed to establish predictors for OSA severity. Materials and Methods: This study included 138 newly diagnosed patients who underwent polysomnographic analysis. The 10-year risk for cardiovascular disease was assessed using a newly validated prediction model: Systematic Coronary Risk Evaluation (SCORE-2). In addition, the Charlson Comorbidity Index (CCI) was assessed as a widely-used example of a mortality comorbidity index. Results: The study population included 138 patients: 86 males and 52 females. Patients were stratified, according to AHI (apnea/hypopnea index), into four groups: 33 patients had mild OSA (5 ≤ AHI < 15), 33 patients had moderate OSA (15 ≤ AHI < 30), 31 patients had severe OSA (AHI ≥ 30), and 41 individuals had AHI < 5, which were a part of the control group. SCORE-2 increased in line with OSA severity and was higher in OSA groups compared to the control group (H = 29.913; DF = 3; p < 0.001). Charlson Index was significantly higher in OSA patients compared to controls (p = 0.001), with a higher prevalence of total comorbidities in the OSA group of patients. Furthermore, CCI 10-year survival score was significantly lower in the OSA group, suggesting a shorter survival of those patients with a more severe form of OSA. We also examined the prediction model for OSA severity. Conclusions: Determining the comorbidity profile and estimation of the 10-year risk score of OSA patients could be used to classify these patients into various mortality risk categories and, according to that, provide them with adequate treatment.