Low testosterone levels predict clinical adverse outcomes in SARS‐CoV‐2 pneumonia patients

Abstract

Background: The pandemic of new severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) has stressed the importance of effective diagnostic and prognostic biomarkers of clinical worsening and mortality. Epidemiological data showing a differential impact of SARS-CoV-2 infection on women and men have suggested a potential role for testosterone (T) in determining gender disparity in the SARS-CoV-2 clinical outcomes. Objectives: To estimate the association between T level and SARS-CoV-2 clinical outcomes (defined as conditions requiring transfer to higher or lower intensity of care or death) in a cohort of patients admitted in the respiratory intensive care unit (RICU). Materials and methods: A consecutive series of 31 male patients affected by SARS-CoV-2 pneumonia and recovered in the respiratory intensive care unit (RICU) of the "Carlo Poma" Hospital in Mantua were analyzed. Several biochemical risk factors (ie, blood count and leukocyte formula, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), ferritin, D-dimer, fibrinogen, interleukin 6 (IL-6)) as well as total testosterone (TT), calculated free T (cFT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were determined. Results: Lower TT and cFT were found in the transferred to ICU/deceased in RICU group vs groups of patients transferred to IM or maintained in the RICU in stable condition. Both TT and cFT showed a negative significant correlation with biochemical risk factors (ie, the neutrophil count, LDH, and PCT) but a positive association with the lymphocyte count. Likewise, TT was also negatively associated with CRP and ferritin levels. A steep increase in both ICU transfer and mortality risk was observed in men with TT < 5 nmol/L or cFT < 100 pmol/L. How to cite this article: RastrelliG, Di Stasi V, Inglese F, et al. Low testosterone levels predict clinical adverse outcomes in SARS-CoV-2 pneumonia patients.

Effect of serum total testosterone and its relationship with other laboratory parameters on the prognosis of coronavirus disease 2019 (COVID-19) in SARS-CoV-2 infected male patients: a cohort study

“…Rastrelli et al [12] included 31 consecutive male patients with COVID-19 who recovered in the ICU of a hospital in Italy. They demonstrated that lower baseline levels of total testosterone and calculated free testosterone levels predicted poor prognosis and mortality in the SARS-CoV-2 infected patients who admitted to intensive care unit.…”

“…The prevalence of hypogonadism in age hospitalized male patients has been reported as 53.3% [7]. Low levels of testosterone have been found as an association with higher rates of infection-related hospitalization and allcause mortality in male hemodialysis and intensive care unit patients [6,7,11,12]. In a double blind, placebo controlled, randomized study, testosterone replacement therapy provided improvement in peak oxygen consumption in elderly patients with chronic heart failure [13].…”

“…Therefore, viral binding to the ACE2 receptor may decrease its expression causing deterioration in a lung protective pathway, and might affect testosterone production, leading to increases in pro-inflammatory cytokines in SARS-CoV-2 infected patients [16]. Very few studies have investigated the relationship between testosterone and mortality with the contradictory results in patients with COVID-19 with a small sample size and short follow-up period [12,17].…”

Understanding the Complex Relationship Between Androgens and SARS-CoV2

“…Lower testosterone on admission was associated with a higher likelihood of mortality or escalation of care. 5 Similarly, a cohort from Germany identified low testosterone and dihydrotestosterone (DHT) levels in 67% and 49% of SARS-CoV-2 infected men on admission to the ICU, respectively. 15 These studies suggest a relationship between testosterone and SARS-CoV-2 infection, however these observational data must be interpreted with caution for several reasons.…”

“…It is possible that an androgen-dependent process may help account for these epidemiological findings, which is a topic of intense focus currently. [4][5][6] An androgen-mediated protein (transmembrane serine protease 2: TMPRSS2) plays a critical role in priming the virus' spike proteins for entry into the host cell as one of the first steps involved in infection. 7 To enter the cell, the SARS-CoV-2 virus uses primed spike proteins to bind cellular angiotensin converting enzyme receptor 2, which leads to cell entry and infection.…”