Impaired spermatogenesis in COVID-19 patients

Abstract

Background The current study aimed to determine the impact of SARS-CoV-2 infection on male fertility. Methods This is a single-center, hospital-based observational study that included autopsied testicular and epididymal specimens of deceased COVID-19 male patients ( n =6) and recruited recovering COVID-19 inpatients ( n =23) with an equal number of age-matched controls, respectively. We performed histopathological examinations on testicular and epididymal specimens, and also performed TUNEL assay and immunohistochemistry. Whereas, we investigated the semen specimen for sperm parameters and immune factors. Findings Autopsied testicular and epididymal specimens of COVID-19 showed the presence of interstitial edema, congestion, red blood cell exudation in testes, and epididymides. Thinning of seminiferous tubules was observed. The number of apoptotic cells within seminiferous tubules was significantly higher in COVID-19 compared to control cases. It also showed an increased concentration of CD3+ and CD68+ in the interstitial cells of testicular tissue and the presence of IgG within seminiferous tubules. Semen from COVID-19 inpatients showed that 39.1% ( n =9) of them have oligozoospermia, and 60.9% ( n =14) showed a significant increase in leucocytes in semen. Decreased sperm concentration, and increased seminal levels of IL-6, TNF-α, and MCP-1 compared to control males were observed. Interpretation Impairment of spermatogenesis was observed in COVID-19 patients, which could be partially explained as a result of an elevated immune response in testis. Additionally, autoimmune orchitis occurred in some COVID-19 patients. Further research on the reversibility of impairment and developing treatment are warranted. Funding This study was supported by Ministry of Science and Technology of China Plan, Hubei Science and Technology Plan, National Key Research and Development Program of China, HUST COVID-19 Rapid Response Call, China and National Natural Science Foundation of China; these funding bodies are public institutions, and they had no role in study conception, design, interpretation of results, and manuscript preparation.

Potential impacts of COVID-19 on reproductive health: Scientific findings and social dimension

“…Infection may also take place after touching an infected surface followed by touching the mouth, nose, or eyes ( Stadnytskyi et al, 2020 ). Moreover, clinical research has reported that other routes of contagion may occur, such as via contact with the blood ( Yu et al, 2020 ), feces ( Cheung et al, 2020 ), or semen ( Li et al, 2020a , Li et al, 2020b , Li et al, 2020c ) of an infected person.…”

“…In males, COVID-19 virus can affect male fertility through increasing the body temperature and subsequently the incidence of fever ( Fan et al, 2020 ). Around 80% of COVID-19 patients were reported to exhibit sustained increases in body temperature ( Li et al, 2020a , Li et al, 2020b , Li et al, 2020c ). It has also been suggested that fever and the increase of patients’ testicular temperature can damage spermatogenesis and thus male fertility ( Younis et al, 2020 ).…”

“…A series of studies have provided the negative influence of COVID-19 infection in spermatogenesis through impairment the immune responses ( Li et al, 2020a , Li et al, 2020b , Li et al, 2020c ), abnormal sex hormone secretions ( Ma et al, 2020 ). Additionally, autoimmune orchitis occurred in some COVID-19 patients ( Li et al, 2020a , Li et al, 2020b , Li et al, 2020c ). From the pathological screening, it was observed that testes from COVID-19 patients displayed significant seminiferous tubular injury, mild lymphocytic inflammation and reduced Leydig cells ( Yang et al, 2020 ).…”

“…Concerns were thus raised about whether COVID‐19 can affect male reproductive health. In a cohort study by Li et al, 2020a , Li et al, 2020b , Li et al, 2020c , it was observed that COVID-19 can appear in the semen of infected individuals and may even be present in the semen of recovering patients. Because of the deficient epididymis barrier/deferens/blood-testes barrier, COVID-19 might be scattered throughout the male reproductive system, mainly in the form of systemic local infection.…”

“…Surveys on viral recognition and semen perseverance would be valuable for clinical practice and public health, especially regarding viruses that could trigger high morbidity or mortality, such as COVID-19. It has been reported that 24% of 38 patients infected with COVID-19 were incapable of providing a semen specimen because of erectile dysfunction, dying prior to recruitment, or being in a comatose state ( Li et al, 2020a , Li et al, 2020b , Li et al, 2020c ).…”