SARS-CoV-2 replicates in the human testis with slow kinetics and has no major deleterious effects ex vivo .

SARS-CoV-2, the etiological agent of the ongoing Covid-19 pandemic, is a respiratory virus that infects several organs beyond the lungs. The alterations of semen parameters, testicular morphology, and testosteronemia reported in Covid-19 patients, along with the high expression of SARS-CoV-2 main receptor ACE2 in the testis, raise questions about the underlying mechanisms. Using a previously validated ex vivo model of human testis, we show that SARS-CoV-2 infects ACE2-positive Leydig and Sertoli cells. Slow virus replication kinetics were observed, with a peak of infection at day 6 post-infection and a decline of infectious virions at day 9. The infection had no major impact on testicular morphology or main hormonal functions, but some steroidogenic enzymes were decreased at day 9. While antiviral effectors were upregulated, there was no transcriptional induction of key pro-inflammatory cytokines. Altogether, these data indicate that SARS-CoV-2 replication in the human testis ex vivo is limited and suggest that testicular damages in infected individuals are unlikely to result from direct deleterious effects of SARS-CoV-2 on this organ. IMPORTANCE SARS-CoV-2 is a new virus responsible for the Covid-19 pandemic. Although SARS-CoV-2 primarily affects the lungs, other organs are infected. Alterations of testosteronemia and spermatozoa motility in infected men have raised questions about testicular infection, along with high level in the testis of ACE2, the main receptor used by SARS-CoV-2 to enter host cells. Using an organotypic culture of human testis, we found that SARS-CoV-2 replicated with slow kinetics in the testis. The virus first targeted testosterone-producing Leydig cells and then germ-cell nursing Sertoli cells. After a peak followed by the upregulation of antiviral effectors, viral replication in the testis decreased and did not induce any major damage to the tissue. Altogether, our data show that SARS-CoV-2 replicates in the human testis to a limited extent and suggest that testicular damages in infected patients are more likely to result from systemic infection and inflammation than from viral replication in the testis.