Could Lower Testosterone in Older Men Explain Higher COVID-19 Morbidity and Mortalities?

The health scourge imposed on humanity by the COVID-19 pandemic seems not to recede. This fact warrants refined and novel ideas analyzing different aspects of the illness. One such aspect is related to the observation that most COVID-19 casualties were older males, a tendency also noticed in the epidemics of SARS-CoV in 2003 and the Middle East respiratory syndrome in 2012. This gender-related difference in the COVID-19 death toll might be directly involved with testosterone (TEST) and its plasmatic concentration in men. TEST has been demonstrated to provide men with anti-inflammatory and immunological advantages. As the plasmatic concentration of this androgen decreases with age, the health benefit it confers also diminishes. Low plasmatic levels of TEST can be determinant in the infection’s outcome and might be related to a dysfunctional cell Ca2+ homeostasis. Not only does TEST modulate the activity of diverse proteins that regulate cellular calcium concentrations, but these proteins have also been proven to be necessary for the replication of many viruses. Therefore, we discuss herein how TEST regulates different Ca2+-handling proteins in healthy tissues and propose how low TEST concentrations might facilitate the replication of the SARS-CoV-2 virus through the lack of modulation of the mechanisms that regulate intracellular Ca2+ concentrations.

Reduced older male presence linked to increased rates of aggression to non-conspecific targets in male elephants

Males in many large mammal species spend a considerable portion of their lives in all-male groups segregated from females. In long-lived species, these all-male groups may contain individuals of vastly different ages, providing the possibility that behaviours such as aggression vary with the age demographic of the social environment, as well as an individual's own age. Here, we explore social factors affecting aggression and fear behaviours in non-musth male African elephants ( Loxodonta africana ) aggregating in an all-male area. Adolescent males had greater probabilities of directing aggressive and fearful behaviours to non-elephant targets when alone compared to when with other males. All males, regardless of age, were less aggressive towards non-elephant targets (e.g. vehicles and non-elephant animals) when larger numbers of males from the oldest age cohort were present. The presence of older males did not influence the probability that other males were aggressive to conspecifics or expressed fearful behaviours towards non-elephant targets. Older bulls may police aggression directed towards non-elephant targets or may lower elephants’ perception of their current threat level. Our results suggest male elephants may pose an enhanced threat to humans and livestock when adolescents are socially isolated, and when fewer older bulls are nearby.

Clinical Characteristics of COVID-19 Infection

The typical clinical symptoms of the patients who suffered from the novel viral pneumonia were fever, cough, and myalgia or fatigue with abnormal chest CT, and the less common symptoms were sputum production, headache, hemoptysis, and diarrhea. This new infectious agent is more likely to affect older males to cause severe respiratory diseases. Major risk factors for severe illness and mortality from COVID-19 are age, comorbidities such as: heart disease, hypertension, prior stroke, diabetes, chronic lung disease, and chronic kidney disease and associated with adverse outcomes. Loss of taste and smell preceding the onset of respiratory symptoms has been reported.

Berberine ameliorates testosterone-induced benign prostate hyperplasia in rats

Introduction Benign prostatic hyperplasia (BPH) is a major urologic problem that mostly develops in older males. Oxidative stress and inflammation influence the occurrence of BPH. Berberine (BBR) is a natural ingredient that has antioxidant and anti-inflammatory properties. The current research aims at examining the effects of BBR on testosterone-stimulated BPH in rats. Methods Animals were randomly categorized to six groups. In the control group, normal saline and olive oil were injected as the vehicle. BPH group: received testosterone (3 mg/kg, subcutaneous, 28 days), BPH + BBR groups; received BBR (25 and 50 mg/kg, p.o, 28 days), BPH + finasteride groups: received finasteride (1 mg/kg, p.o, 28 days), BBR (50 mg/kg, p.o, alone) was administered for subjects in the BBR group. On the 29th day, after anesthesia, cervical dislocation was used to kill the subjects. Serum concentration of testosterone and dihydrotestosterone was measured and prostate tissues were excised and used for biochemical, inflammation, and histological analysis. Results BBR prevented increased serum concentrations of testosterone and dihydrotestosterone. BBR considerably reduced BPH-stimulated oxidative stress and inflammation through preventing the rise in lipid peroxidation and nitrite concentration and declined the accumulations of pro-inflammatory cytokines (e.g. interleukin 1β and tumor necrosis factor α) and declining the depletion rate of GSH and the function of catalase and superoxide dismutase. Histopathological investigations reported that administration of BBR could suppress testosterone-stimulated BPH. Conclusion This study demonstrated that BBR could significantly prevent the development of BPH in rats.

A genome-wide association study of COVID-19 related hospitalization in Spain reveals genetic disparities among sexes

We describe the results of the Spanish Coalition to Unlock Research on Host Genetics on COVID-19 (SCOURGE). In sex-disaggregated genome-wide studies of COVID-19 hospitalization, we found two known loci associated among males (SLC6A20-LZTFL1 and IFNAR2), and a novel one among females (TLE1). Meta-analyses with independent studies revealed two novel associations (AQP3 and ARHGAP33) and replicated ELF5. A genetic risk score predicted COVID-19 severity, especially among younger males. We found less SNP-heritability and larger heritability differences by age (<60/≥60 years) among males than females. Inbreeding depression was associated with COVID-19 hospitalization and severity, and the effect was stronger among older males.

Transcriptional and mutational signatures of the aging germline

Aging is a complex biological process which is accompanied by changes in gene expression and mutational load. In many species including humans, old fathers pass on more paternally-derived de novo mutations, however, the cellular basis and cell types driving this pattern are still unclear. To understand the root causes of this phenomenon, we performed single-cell RNA-sequencing (scRNA-seq) on testes from young and old male Drosophila, as well as genomic sequencing (DNA-seq) on somatic tissue from the same flies. We found that early germ cells from old and young flies have similar mutational loads, but older flies are less able to remove mutations during spermatogenesis. This indicates that germline mutations arise from primarily non-replicative factors, and that the increased mutational load of older males is due to differences in genome maintenance activities such as repairs to DNA damage. We also found that T>A mutations are enriched in older flies, and transcription-related enrichment terms are depleted in older males. Early spermatogenesis-enriched genes have lower dN/dS than late spermatogenesis-enriched genes, supporting the hypothesis that late spermatogenesis is the source of evolutionary innovation. This transcriptional disruption is reflected in the decreased expression of genome maintenance genes in early germ cells of older flies, as well as potentially aberrant transcription of transposable elements in the aging germline. Our results provide novel insights into the transcriptional and mutational signatures of the male germline.

Occurrence, Trends, Management and Outcomes of Patients Hospitalized with Clinically Suspected Myocarditis—Ten-Year Perspectives from the MYO-PL Nationwide Database

The epidemiology of myocarditis is unknown and based mainly on small single-centre studies. The study aimed to evaluate the current incidence, clinical characteristics, management and outcomes of patients hospitalized due to myocarditis in a general population. The study was registered in ClinicalTrials.gov (NCT04827706). The nationwide MYO-PL (the occurrence, trends, management and outcomes of patients with myocarditis in Poland) database (years 2009–2020) was created to identify hospitalization records with a primary diagnosis of myocarditis according to the International Classification of Diseases and Related Health Problems, 10th Revision (ICD 10), derived from the database of the national healthcare insurer. We identified 19,978 patients who were hospitalized with suspected myocarditis for the first time, of whom 74% were male. The standardized incidence rate of myocarditis ranged from 1.15 to 14 per 100,000 people depending on the age group and was the highest in patients aged 16–20 years. The overall incidence increased with time. The performance of the recommended diagnostic tests (in particular, endomyocardial biopsy) was low. Relative five-year survival ranged from 0.99 to 0.56—worse in younger females and older males. During a five-year follow-up, 6% of patients (3.7% and 6.9% in females and males, respectively) were re-hospitalized for myocarditis. Surprisingly, females more frequently required hospitalization due to heart failure/cardiomyopathy (10.5%) and atrial fibrillation (5%) than compared to males (7.3% and 2.2%, respectively) in the five-year follow up. In the last ten years, the incidence of suspected myocarditis increased, particularly in males. Survival rates for patients with myocarditis were worse than in the general population. Management of myocarditis requires significant improvement.