Bioinformatic and mouse model reveal the potential high vulnerability of Leydig cells on SARS-CoV-2

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in China and spread rapidly since the end of 2019. Previous studies have confirmed that SARS-CoV-2 infects host cells via binding to angiotensin converting enzyme II (ACE2). METHODS: To explore the expression of ACE2 and the potential risk of infection in testis, we performed a bioinformatic analysis based on public databases, and conducted a pilot study using a mouse model. We also collected clinical follow-up date on male patients who had recovered from COVID-19 for 6 months. RESULTS: The results showed that the RNA expression of ACE2 was higher in testis compared with other organs. Single-cell analysis and immunocytochemistry further indicated that Leydig cells were at risk of SARS-CoV-2 infection. Green fluorescence was only detected in the Leydig cells after intratesticular injection of pseudovirus SARS-CoV-2 in the mouse model. In the clinical follow-up, serum total testosterone level was statistically lower in patients who had recovered from COVID-19 compared with healthy men (P=0.010). CONCLUSIONS: The findings of the present study indicate the potential vulnerability of Leydig cells. It is important to monitor the reproductive system and its complications in male COVID-19 patients. Further studies are still needed on SARS-CoV-2-associated reproductive complications.