Testosterone as a Biomarker of Adverse Clinical Outcomes in SARS-CoV-2 Pneumonia

Abstract

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect testicles. Lower testosterone levels have been associated with worse clinical outcomes and higher mortality. Our objective was to evaluate the hypothalamic–pituitary–gonadal axis of men admitted with SARS-CoV-2 pneumonia and its link with the pneumonia-treatment intensification. Short-term changes in hormonal parameters were also assessed. Methods: Men admitted with SARS-CoV-2 pneumonia were recruited in two different hospitals in Piedmont, Italy. In all patients, the assessment of total testosterone (TT), calculated free testosterone (cFT), gonadotropins, inhibin B (InhB), and other biochemical evaluations were performed at admission (T0) and before discharge (T1). Through a review of medical records, clinical history was recorded, including data on pneumonia severity. Results: Thirty-five men (median age 64 [58–74] years) were recruited. Lower TT and cFT levels at T0 were associated with CPAP therapy (p = 0.045 and 0.028, respectively), even after adjusting for age and PaO2/FIO2 ratio in a multivariable analysis. In those discharged alive, lower TT and cFT levels were associated with longer hospital stay (p < 0.01). TT, cFT, and InhB were below the normal range at T0 and significantly increased at T1 (TT 1.98 [1.30–2.72] vs. 2.53 [1.28–3.37] ng/mL, p = 0.038; cFT (0.0441 [0.0256–0.0742] vs. 0.0702 [0.0314–0.0778] ng/mL, p = 0.046; InhB 60.75 [25.35–88.02] vs. 77.05 [51.15–134.50], p < 0.01). Conclusions: Both TT and cFT levels are associated with adverse clinical outcomes in men admitted with SARS-CoV-2 pneumonia. As TT, cFT and InhB levels increase before discharge, short-term functional recovery of steroidogenesis and an indirect improvement of spermatozoa functional status could be hypothesized.

Androgens’ Role in Severity and Mortality Rates of COVID-19

“…According to data noted in the previous section of the present study, direct probable effects of SARS-CoV-2 on testis and subsequently reduction in testosterone production, which may lead to cytokine storm as well as hyper catabolic states, contribute to the severe complications of COVID-19. SARS-CoV-2 has high tropism for Leydig cells and levels of testosterone substantially decreases following viral infection by SARS-CoV-2 116 . A study proved that men with a severe COVID-19 infection had lower serum total testosterone levels compared to healthy ones 117 .…”

Testosterone in males with COVID‐19: a 12‐month cohort study

“…Here, we may discuss at least a few of our original biopathology hypotheses dealing with the potential importance of low T levels in terms of differences in COVID‐19 severity and clinical outcomes between sexes 6 . Indeed, on the one hand, current findings support the concept that tT levels may be a marker of illness severity, with a progressive notwithstanding slow recovery of circulating tT levels, also recapitulating a progressive recovery from COVID‐19‐associated severe multisystem impairment 6,21 . On the other hand, although probably still incomplete, this further recovery of circulating tT levels may only partially exclude a chronic low T pre‐existing condition in those men, which could have somehow facilitated the overall greater incidence, higher severity and greater probability of fatal events in males than in females 22 .…”

“… 6 Indeed, on the one hand, current findings support the concept that tT levels may be a marker of illness severity, with a progressive notwithstanding slow recovery of circulating tT levels, also recapitulating a progressive recovery from COVID‐19‐associated severe multisystem impairment. 6 , 21 On the other hand, although probably still incomplete, this further recovery of circulating tT levels may only partially exclude a chronic low T pre‐existing condition in those men, which could have somehow facilitated the overall greater incidence, higher severity and greater probability of fatal events in males than in females. 22 In fact, even current findings can neither corroborate nor rebut the possible role of pre‐infection tT levels in terms of subsequent worse clinical outcomes in men with COVID‐19, as already previously extensively argued.…”

Testosterone and Covid‐19: An update

“… 49 Lower TT and cFT also correlated with longer hospital stays (rho = −0.51, p < 0.01 and rho = −0.55, p < 0.01, respectively), and TT levels were an independent predictive factor for the length of hospitalisation. 49 A similar observation was reported by Camici et al. (2021) who observed that low TT and low cFT were associated with longer hospital stay following Covid‐19 infection ( p = 0.052 and p = 0.041 respectively) and the increased occurrence of hyperinflammatory syndrome determined by lymphocyte count, and levels of ferritin, lactate dehydrogenase, d‐dimer and c‐reactive proteins ( p = 0.018 and p = 0.048 respectively).…”

“…The requirement for continuous positive airway pressure therapy, a measure of adverse clinical outcome, was associated with lower levels of TT and cFT at time of hospitalisation in a multicenter observational study of 35 men 49 . Lower TT and cFT also correlated with longer hospital stays (rho = −0.51, p < 0.01 and rho = −0.55, p < 0.01, respectively), and TT levels were an independent predictive factor for the length of hospitalisation 49 . A similar observation was reported by Camici et al.…”