Understanding the Complex Relationship Between Androgens and SARS-CoV2

Ory, Jesse; Lima, Thiago Fernandes; Towe, Maxwell; Frech, Fabio Stefano; Best, Jordan C.; Kava, Bruce R.; Ramasamy, Ranjith

doi:10.1016/j.urology.2020.06.048

Cited by 10 publications

(15 citation statements)

References 24 publications

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“…27 Based on our results, at least five hypotheses might be considered to explain the potential importance of low T levels in terms of sex differences in COVID-19 severity. 6,32,33 First, low T levels may simply be a marker of illness severity, thus recapitulating what has been reported for many other severe illnesses, thus potentially including severe viral infections. 34,35 Second, androgens per se are poorly protective over the immune response in males, whereas estrogens (and progesterone) can provide adequate protection to females, stimulating the humoral response to viral infections 2,3,36 ; as a consequence, T levels could not elicit an effective counteracting response to the inflammatory and immunological outcome COVID-19 induces respiratory-predominant multiorgan dysfunction, including myocardial, renal, enteric and hepatic dysfunction, which coincides with the tissue expression of ACE2.…”

Section: Detection Of Covid-19 In the Male Reproductive Tractmentioning

confidence: 60%

“…However, the results are controversial. For example, some researchers have reported that SARS-CoV-2 was not detected in the male reproductive tract, [25][26][27][28][29][30][31][32][33][34] while others reported that SARS-CoV-2 RNA was found in the semen or testes of COVID-19 patients. 35,36 There are also unknown factors regarding COVID-19 and male reproduction.…”

Section: Introductionmentioning

confidence: 99%

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Severely low testosterone in males with COVID‐19: A case‐control study

et al. 2021

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Background Circulating androgens could have a relevant pathobiological role in clinical outcomes in men with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection (COVID‐19). Objectives We aimed to assess: (a) circulating sex steroids levels in a cohort of 286 symptomatic men with laboratory‐confirmed COVID‐19 at hospital admission compared to a cohort of 281 healthy men; and (b) the association between serum testosterone levels (tT), COVID‐19, and clinical outcomes. Materials and Methods Demographic, clinical, and hormonal values were collected for all patients. Hypogonadism was defined as tT ≤9.2 nmol/l. The Charlson Comorbidity Index (CCI) was used to score health‐significant comorbidities. Severe clinical outcomes were defined as patients either transferred to intensive care unit (ICU) or death. Descriptive statistics and multivariable linear and logistic regression models tested the association between clinical and laboratory variables and tT levels. Univariable and multivariable logistic regression models tested the association between tT and severe clinical outcomes. Results Overall, a significantly lower levels of LH and tT were found in patients with COVID‐19 compared to healthy controls (all p < 0.0001); conversely, healthy controls depicted lower values of circulating E 2 ( p < 0.001). Testosterone levels suggestive for hypogonadism were observed in 257 (89.8%) patients at hospital admission. In as many as 243 (85%) cases, hypogonadism was secondary. SARS‐CoV‐2 infection status was independently associated with lower tT levels ( p < 0.0001) and greater risk of hypogonadism ( p < 0.0001), after accounting for age, BMI, CCI, and IL‐6 values. Lower tT levels were associated with higher risk of ICU admission and death outcomes (all p ≤ 0.05), after accounting for clinical and laboratory parameters. Conclusions We unveil an independent association between SARS‐CoV‐2 infection status and secondary hypogonadism already at hospital admission, with lower testosterone levels predicting the most severe clinical outcomes.

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Section: Detection Of Covid-19 In the Male Reproductive Tractmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Severely low testosterone in males with COVID‐19: A case‐control study

et al. 2021

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“…Conversely, testosterone may favour resistance to COVID‐19 by maintaining respiratory muscle activity and suppressing immune and inflammatory responses 57,58 . In summary, the relationship between testosterone and COVID‐19 is multifactorial and needs further research 59 . The research also reported that 3 of 12 enrolled patients experienced a loss of libido, and 1 experienced the loss of morning erections after having COVID‐19 30 .…”

Section: Resultsmentioning

confidence: 98%

“…57,58 In summary, the relationship between testosterone and COVID-19 is multifactorial and needs further research. 59 The research also reported that 3 of 12 enrolled patients experienced a loss of libido, and 1 experienced the loss of morning erections after having COVID-19. 30 It was suspected that COVID-19 might affect male sexual health.…”

Section: Association Of Covid-19 and Semen Qualitymentioning

confidence: 93%

COVID‐19 and male reproduction: Current research and unknown factors

Yao

Yuan

et al. 2021

Andrology

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Background The testes are suspected target organs of SARS‐CoV‐2. However, the results of studies on the effect of COVID‐19 on male reproduction are controversial. Objective To summarize current research on the effects of COVID‐19 on male reproduction. Methods A systematic review of English literature was performed using PubMed and Ovid Embase up to 18 August 2020. Research articles on the presence of SARS‐CoV‐2 in semen, the effects of the virus on semen parameters and any pathological changes in the testes were evaluated. Results Fourteen studies were included in this review. Six of 176 survivors (3.4%) and 1 of 13 decedents (7.7%) in 2 of 12 studies were positive for viral RNA in semen and testicular tissue, respectively. After stratification of patient groups, we found that the virus was detected in the relatively early stage of infection, 6–16 days after disease onset, in semen from survivors. Two of 3 studies reported that some participants had substandard semen quality after COVID‐19, and 1 study found that COVID‐19 may impair semen quality in a severity‐related manner. Pathological analyses showed that injuries to the seminiferous tubule occurred in all decedents (N = 11). Another study found that orchitic and testis fibrin microthrombi occurred in patients with fatal disease (100%, N = 2). Scrotal discomfort of orchiepididymitis or spermatic cord inflammation has also been reported in COVID‐19 patients. Conclusion Current studies suggest that semen is rarely considered a carrier of SARS‐CoV‐2 genetic material during the infection period but not in the semen of recovered patients. Fatal COVID‐19 may cause testicular structure damage without the presence of virus.

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“… 115 Although the study had shortcomings, such as its observational nature, the use of a tumor registry as a comparison group, and the small samples of SARS-CoV-2-positive patients without ADT ( n = 114) and with ADT ( n = 4), the findings support the hypothesis of a protective role of androgen deprivation in COVID-19. 116 In vivo studies in TMPRSS2-knockout (KO) would give more clarity on whether TMPRSS2 is dispensable for SARS-CoV-2 infection and pathogenesis.…”

Section: Tmprss2mentioning

confidence: 99%

Targeting Crucial Host Factors of SARS-CoV-2

et al. 2020

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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide since its first incidence in Wuhan, China, in December 2019. Although the case fatality rate of COVID-19 appears to be lower than that of SARS and Middle East respiratory syndrome (MERS), the higher transmissibility of SARS-CoV-2 has caused the total fatality to surpass other viral diseases, reaching more than 1 million globally as of October 6, 2020. The rate at which the disease is spreading calls for a therapy that is useful for treating a large population. Multiple intersecting viral and host factor targets involved in the life cycle of the virus are being explored. Because of the frequent mutations, many coronaviruses gain zoonotic potential, which is dependent on the presence of cell receptors and proteases, and therefore the targeting of the viral proteins has some drawbacks, as strain-specific drug resistance can occur. Moreover, the limited number of proteins in a virus makes the number of available targets small. Although SARS-CoV and SARS-CoV-2 share common mechanisms of entry and replication, there are substantial differences in viral proteins such as the spike (S) protein. In contrast, targeting cellular factors may result in a broader range of therapies, reducing the chances of developing drug resistance. In this Review, we discuss the role of primary host factors such as the cell receptor angiotensin-converting enzyme 2 (ACE2), cellular proteases of S protein priming, post-translational modifiers, kinases, inflammatory cells, and their pharmacological intervention in the infection of SARS-CoV-2 and related viruses.

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Understanding the Complex Relationship Between Androgens and SARS-CoV2

Cited by 10 publications

References 24 publications

Severely low testosterone in males with COVID‐19: A case‐control study

Severely low testosterone in males with COVID‐19: A case‐control study

COVID‐19 and male reproduction: Current research and unknown factors

Targeting Crucial Host Factors of SARS-CoV-2

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