SARS-CoV-2 infects, replicates, elevates angiotensin II and activates immune cells in human testes (Costa et al., 2022) (pre-print)
- The coronavirus infects sperm stem cells in the testicles more often than previously thought.
- Detecting viral RNA in the testicles requires a specific laboratory methodology, which may not be well-known.
- This finding raises the possibility of viral persistence in the testicles for two reasons:
- Sperm stem cells are very long-lived cells that replicate continuously to form new sperm.
- The testicles are considered an "immune-privileged" tissue, out of the reach of the blood-borne immune system. (However, in acute infection of critically ill patients, this tissue barrier may be breached, allowing monocytes to enter the testicles.)
- If the virus persists in the testicles, then the coronavirus may become a sexually transmitted disease.
(emphasis and spacing added)Costa et al. 2022 said:Although much has been published since the first cases of COVID-19, there remain unanswered questions regarding SARS-CoV-2 impact on testes and the potential consequences for reproductive health. We investigated testicular alterations in deceased COVID-19-patients, the precise location of the virus, its replicative activity, and the molecules involved in the pathogenesis.
We found that SARS-CoV-2 testicular tropism is higher than previously thought and that reliable viral detection in the testis requires sensitive nanosensoring or RT-qPCR using a specific methodology. Macrophages and spermatogonial cells are the main SARS-CoV-2 lodging sites and where new virions form inside the Endoplasmic Reticulum Golgi Intermediate Complex. Moreover, we showed infiltrative infected monocytes migrating into the testicular parenchyma.
SARS-CoV-2 maintains its replicative and infective abilities long after the patient’s infection, suggesting that the testes may serve as a viral sanctuary. Further, infected testes show thickening of the tunica propria, germ cell apoptosis, Sertoli cell barrier loss, evident hemorrhage, angiogenesis, Leydig cell inhibition, inflammation, and fibrosis.
Finally, our findings indicate that high angiotensin II levels and activation of mast cells and macrophages may be critical for testicular pathogenesis. Importantly, our data suggest that patients who become critically ill exhibit severe damages and may harbor the active virus in testes.