Worse progression of COVID‐19 in men: Is testosterone a key factor?

Giagulli, Vito Angelo; Guastamacchia, Edoardo; Magrone, Thea; Jirillo, Emilio; Lisco, Giuseppe; Pergola, Giovanni De; Triggiani, Vincenzo

doi:10.1111/andr.12836

Cited by 130 publications

(132 citation statements)

References 183 publications

(275 reference statements)

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“…The measurement of testosterone levels is not routinely undertaken and therefore there is little empirical evidence of its impact, with currently only one smallscale study of 31 patients demonstrating an increased risk [108]. Such that this link remains mostly a hypothesis based on the already recognized negative effect of low testosterone on recognized preexisting morbidity such as epithelial dysfunction and cardiovascular disease, the risk of obesity; and the metabolic syndrome [109,112,113114]. There may also be an association with the immune response to the virus, through an association with increased pro-inflammatory cytokines [115].…”

Section: Reproductive Healthmentioning

confidence: 99%

Men and COVID-19: the aftermath

White

2020

Postgraduate Medicine

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The global pandemic as a result of the SARS-CoV2 virus has seen over 16 m people infected and over 650,000 deaths, with men at double the risk of both developing the severe form of the disease and mortality. There are both biological (sex) and socio-cultural (gender) factors, compounded by socioeconomic factors and ethnicity, that impact on the aftermath of what has occurred over the short time that this novel coronavirus has been circulating the world. The potential lifelong morbidity as a result of the infection and as a consequence of highly invasive critical care treatment needs to be factored into the rehabilitation of survivors. There are also many men whose lives will have been severely affected both physically and emotionally by the pandemic without ever contracting the disease, with the widespread disruption to normal existence and its impact on their social world and the economy. The implications of the closure of many healthcare services over the initial lockdown will also have both a shorter-and longer-term impact on other diseases due to missed early diagnosis and disrupted treatment regimes. Getting effective public health messages out to the population is critical and this current pandemic is demonstrating that there needs to be a more focused view on men's health behavior. Without effective public support for preventative action, the more likely the disease will continue its path unabated. This review explores the wider ramifications of the disease both for those men who have survived the disease and those that have been affected by the wider social effects of the pandemic. The pandemic should be a wake-up call for all involved in the planning and delivery of health and social care for the greater attention to the central role of sex and gender.

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Section: Reproductive Healthmentioning

confidence: 99%

Men and COVID-19: the aftermath

White

2020

Postgraduate Medicine

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“…2(c)], which is the only steroid for which a structure of a complex with albumin has been determined (Czub et al, 2019). Testosterone is suspected of playing a critical role in driving the pronounced excess of COVID-19 lethality in male patients (Pozzilli & Lenzi, 2020), and low testosterone levels predict adverse clinical outcomes (Giagulli et al, 2020). Critically ill male COVID-19 patients suffer from severe testosterone deficiency, which may or may not be caused by the disease.…”

Section: Competing Compounds and Albumin Glycation May Impair Dexametmentioning

confidence: 99%

Molecular determinants of vascular transport of dexamethasone in COVID-19 therapy

Shabalin

Czub

Majorek

et al. 2020

Int Union Crystallogr J

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Dexamethasone, a widely used corticosteroid, has recently been reported as the first drug to increase the survival chances of patients with severe COVID-19. Therapeutic agents, including dexamethasone, are mostly transported through the body by binding to serum albumin. Here, the first structure of serum albumin in complex with dexamethasone is reported. Dexamethasone binds to drug site 7, which is also the binding site for commonly used nonsteroidal anti-inflammatory drugs and testosterone, suggesting potentially problematic binding competition. This study bridges structural findings with an analysis of publicly available clinical data from Wuhan and suggests that an adjustment of the dexamethasone regimen should be further investigated as a strategy for patients affected by two major COVID-19 risk factors: low albumin levels and diabetes.

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“…For example, testosterone was top-ranked by XGboost, with higher levels associated with increased risk. Studies have suggested elevated or reduced testosterone levels may be both associated with a more severe clinical course 31 . Higher IGF-1 appeared to be associated with greater mortality in cohort B.…”

Section: Highlights Of Potential Risk Factorsmentioning

confidence: 99%

Uncovering clinical risk factors and prediction of severe COVID-19: A machine learning approach based on UK Biobank data

Wong

Xiang

2020

Preprint

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Background: COVID-19 is a major public health concern. Given the extent of the pandemic, it is urgent to identify risk factors associated with severe disease. Accurate prediction of those at risk of developing severe infections is also important clinically. Methods: Based on the UK Biobank (UKBB data), we built machine learning(ML) models to predict the risk of developing severe or fatal infections, and to evaluate the major risk factors involved. We first restricted the analysis to infected subjects, then performed analysis at a population level, considering those with no known infections as controls. Hospitalization was used as a proxy for severity. Totally 93 clinical variables (collected prior to the COVID-19 outbreak) covering demographic variables, comorbidities, blood measurements (e.g. hematological/liver and renal function/metabolic parameters etc.), anthropometric measures and other risk factors (e.g. smoking/drinking habits) were included as predictors. XGboost (gradient boosted trees) was used for prediction and predictive performance was assessed by cross-validation. Variable importance was quantified by Shapley values and accuracy gain. Shapley dependency and interaction plots were used to evaluate the pattern of relationship between risk factors and outcomes. Results: A total of 1191 severe and 358 fatal cases were identified. For the analysis among infected individuals (N=1747), our prediction model achieved AUCs of 0.668 and 0.712 for severe and fatal infections respectively. Since only pre-diagnostic clinical data were available, the main objective of this analysis was to identify baseline risk factors. The top five contributing factors for severity were age, waist-hip ratio(WHR), HbA1c, number of drugs taken(cnt_tx) and gamma-glutamyl transferase levels. For prediction of mortality, the top features were age, systolic blood pressure, waist circumference (WC), urea and WHR. In subsequent analyses involving the whole UKBB population (N for controls=489987), the corresponding AUCs for severity and fatality were 0.669 and 0.749. The same top five risk factors were identified for both outcomes, namely age, cnt_tx, WC, WHR and cystatin C. We also uncovered other features of potential relevance, including testosterone, IGF-1 levels, red cell distribution width (RDW) and lymphocyte percentage. Conclusions: We identified a number of baseline clinical risk factors for severe/fatal infection by an ML approach. For example, age, central obesity, impaired renal function, multi-comorbidities and cardiometabolic abnormalities may predispose to poorer outcomes. The presented prediction models may be useful at a population level to help identify those susceptible to developing severe/fatal infections, hence facilitating targeted prevention strategies. Further replications in independent cohorts are required to verify our findings.

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Worse progression of COVID‐19 in men: Is testosterone a key factor?

Cited by 130 publications

References 183 publications

Men and COVID-19: the aftermath

Men and COVID-19: the aftermath

Molecular determinants of vascular transport of dexamethasone in COVID-19 therapy

Uncovering clinical risk factors and prediction of severe COVID-19: A machine learning approach based on UK Biobank data

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