Semen Analysis Changes in Covid-19 Positivepatients

Covid19 Clinical Trial

Official title: Semen Analysis Changes in Covid-19 Positive Patients

Status Completed

Clinical Trial Summary

The viral pandemic of the coronavirus disease 2019 (COVID-19), generated by a novel mutated severe acute respiratory syndrome coronavirus (SARS-CoV-2), has become a serious worldwide public health emergency, evolving exponentially. While the main organ targeted in this disease is the lungs, other vital organs, such as the heart and kidney, may be implicated. The main host receptor of the SARS-CoV-2 is angiotensin converting enzyme 2 (ACE2), a major component of the renin-angiotensin-aldosterone system (RAAS). The ACE2 is also involved in testicular male regulation of steroidogenesis and spermatogenesis. As the SARS-CoV-2 may have the potential to infect the testis via ACE2 and adversely affect male reproductive system.

Clinical Trial Description

A recent report published in JAMA Network Open revealed that in an analysis 38 semen samples from COVID-19 patients, 6 (four at the acute stage of infection and, alarmingly, two who were recovering) tested positive for the virus by RT-PCR.

Importantly, at this point, the investigators have no idea whether the actual virus was viable and infectious. Nevertheless, the possibility that this coronavirus could have a pathophysiological impact on the testes was suggested by additional data indicating that active COVID-19 infection dramatically reduced the testosterone-to-LH ratio, suggesting a significant impact on the responsiveness of Leydig cells to LH stimulation In many ways, the investigators should not be surprised by these observations because the blood-testes barrier is known to offer little defense against viral invasion, given the wide range of pathogenic viruses (HIV, hepatitis, mumps, papilloma) that are known to be capable of damaging the testes and rendering the host infertile.

The angiotensin system plays a critical role in the survival and functionality of human spermatozoa but also creates a vulnerability to COVID-19 attack. Angiotensin 1 is a biologically inactive decapeptide that is cleaved by ACE1 to create angiotensin II, which in turn activates the AT1R and AG2R receptors, both of which are present in these cells. Angiotensin II is further processed by ACE2 to generate angiotensin 1-7 which binds the MAS receptor activating PI3K. The latter then phosphorylates AKT, which maintains cell viability by phosphorylating key regulators of sperm apoptosis such as BAD. As long as BAD is phosphorylated, it is held in abeyance by a 14-3-3 keeper protein. However, if the PI3/AKT pathway becomes compromised, BAD dephosphorylates, is released from its association with 14-3-3, and moves to the mitochondria where it inactivates anti-apoptotic factors and promotes the intrinsic apoptotic cascade. The spike protein on COVID-19 specifically targets ACE2 and in so doing removes an important stimulus for PI3K/AKT, thereby compromising sperm viability. Subsequent to COVID-19 binding, the ectodomain of ACE2 may be removed by ADAM proteases and shed from the sperm surface. Alternatively proteases from the TMPRSS-family, either as intrinsic components of the sperm plasma membrane or delivered by seminal prostasomes, can facilitate fusion between the virus and the sperm surface by cleaving ACE2 and the viral spike proteins (S1 and S2) at the sites indicated by dashed lines, thereby completing the transformation of this cell from procreating gamete to viral vector.

An additional concern of the COVID-19 pandemic that might impact male fertility is fever. Particularly high and sustained elevation in body temperature is a major manifestation of the COVID-19 pandemic, which complicates more than 80% of patients. The concept that fever and elevation of testicular temperature result in impairment of spermatogenesis is widely accepted.

More importantly, emerging evidence indicates that a subgroup of patients with severe COVID-19 might have a secondary cytokine storm syndrome (hemophagocytic lymphohistiocytosis). This is an underrecognized, hyperinflammatory syndrome characterized by sustained fever, with fulminant and fatal hypercytokinemia with multiorgan failure. These patients have a particular serum blood cytokine profile with cytopenia and hyperferritinemia. These findings also suggest that immunomodulatory therapy (IL-6 antagonist) may improve mortality rate considerably in these patients.

As cytokines contribute to testicular function and maintenance of male reproductive health, and to the pathologies associated with their abnormal activity in this organ, COVID-19-induced changes in cytokines profile may have further implications to male fertility. In addition, immunomodulatory therapies may provoke potential long-term effects on male fertility and are a matter of concern. Furthermore, cytokine microenvironment deviations within the testis may have tumorigenic adverse effects on the cellular level, leading eventually to testicular cancer, a second long-term matter of concern.

Aim of the study :

Know the Effect of covid-19 on spermatogenesis ;

Related Conditions & MeSH terms

• Covid19

• NCT number: NCT04595240
• Study type: Observational
• Source: Assiut University
• Status: Completed
• Start date: May 1, 2020
• Completion date: October 15, 2020