ArticleBMC biology2023
High SARS-CoV-2 tropism and activation of immune cells in the testes of non-vaccinated deceased COVID-19 patients.
Article in BMC biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- SARS-CoV-2 infection reduces the number of spermatogonial stem cells and dysregulates the transcriptional landscape of the human testis.Research square · 2026Article
- Ultrastructural Features, Immune Response, and Junctional Proteins in the Seminiferous Epithelium of SARS-CoV-2-Infected Mice.International journal of molecular sciences · 2026Article
- Advances in immune-inflammatory interactions within the testicular-penile microenvironment of varicocele patients: molecular mechanisms underlying erectile dysfunction and spermatogenic impairment.Frontiers in endocrinology · 2026Review
- Has the Number of Pediatric Testicular Torsion Cases Abated After the Height of the COVID-19 Pandemic?Cureus · 2026Article
- A survey of SARS-CoV-2 tropism.Infectious diseases & immunity · 2025Review
- Review
- Advanced Computational Techniques for Plasmonic Metasurfaces in the Detection of Neglected Infectious Diseases.Analytical chemistry · 2025Review
- Effect of SARS-CoV-2 infection on sperm telomere length.Journal of assisted reproduction and genetics · 2025Article
- Immune Regulation in the Testis and Epididymis.Advances in experimental medicine and biology · 2025Review
- SARS-CoV-2 exploits steroidogenic machinery, triggers lipid metabolism for viral replication and induces immune response in Leydig cells of K18-hACE2 mice.Frontiers in cellular and infection microbiology · 2025Article
- SARS-CoV-2 in semen: a multicenter prospective study and literature review.Basic and clinical andrology · 2024Article
- COVID-19: a multi-organ perspective.Frontiers in cellular and infection microbiology · 2024Review
- Article
- In vitro evidence against productive SARS-CoV-2 infection of human testicular cells: Bystander effects of infection mediate testicular injury.PLoS pathogens · 2023Article
- High SARS-CoV-2 tropism and activation of immune cells in the testes of non-vaccinated deceased COVID-19 patients.BMC biology · 2023Article
- Testicular pathological alterations associated with SARS-CoV-2 infection.Frontiers in reproductive health · 2023Review
Corrections and comments
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Authors and funding
35 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundCellular entry of SARS-CoV-2 has been shown to rely on angiotensin-converting enzyme 2 (ACE2) receptors, whose expression in the testis is among the highest in the body. Additionally, the risk of mortality seems higher among male COVID-19 patients, and though much has been published since the first cases of COVID-19, there remain unanswered questions regarding SARS-CoV-2 impact on testes and potential consequences for reproductive health. We investigated testicular alterations in non-vaccinated deceased COVID-19-patients, the precise location of the virus, its replicative activity, and the immune, vascular, and molecular fluctuations involved in the pathogenesis.
resultsWe found that SARS-CoV-2 testicular tropism is higher than previously thought and that reliable viral detection in the testis requires sensitive nanosensors or RT-qPCR using a specific methodology. Through an in vitro experiment exposing VERO cells to testicular macerates, we observed viral content in all samples, and the subgenomic RNA's presence reinforced the replicative activity of SARS-CoV-2 in testes of the severe COVID-19 patients. The cellular structures and viral particles, observed by transmission electron microscopy, indicated that macrophages and spermatogonial cells are the main SARS-CoV-2 lodging sites, 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. Further, we demonstrated high levels of angiotensin II and activated immune cells in the testes of deceased patients. The infected testes show thickening of the tunica propria, germ cell apoptosis, Sertoli cell barrier loss, evident hemorrhage, angiogenesis, Leydig cell inhibition, inflammation, and fibrosis.
conclusionsOur findings indicate that high angiotensin II levels and activation of mast cells and macrophages may be critical for testicular pathogenesis. Importantly, our findings suggest that patients who become critically ill may exhibit severe alterations and harbor the active virus in the testes.
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