Departamento de Cirurgia, Disciplina de Urologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Androscience, Science & Innovation Center in Andrology and High-Complex Clinical and Research Andrology Laboratory., Androscience Institute, Sao Paulo, Brasil.
Andrology. 2024 Nov;12(8):1799-1807. doi: 10.1111/andr.13612. Epub 2024 Mar 12.
Severe acute syndrome coronavirus 2 can invade a variety of tissues, including the testis. Even though this virus is scarcely found in human semen polymerase chain reaction tests, autopsy studies confirm the viral presence in all testicular cell types, including spermatozoa and spermatids.
To investigate whether the severe acute syndrome coronavirus 2 is present inside the spermatozoa of negative polymerase chain reaction-infected men up to 3 months after hospital discharge.
This cross-sectional study included 13 confirmed moderate-to-severe COVID-19 patients enrolled 30-90 days after the diagnosis. Semen samples were obtained and examined with real-time polymerase chain reaction for RNA detection and by transmission electron microscopy.
In moderate-to-severe clinical scenarios, we identified the severe acute syndrome coronavirus 2 inside spermatozoa in nine of 13 patients up to 90 days after discharge from the hospital. Moreover, some DNA-based extracellular traps were reported in all studied specimens.
Although severe acute syndrome coronavirus 2 was not present in the infected men's semen, it was intracellularly present in the spermatozoa till 3 months after hospital discharge. The Electron microscopy (EM) findings also suggest that spermatozoa produce nuclear DNA-based extracellular traps, probably in a cell-free DNA-dependent manner, similar to those previously described in the systemic inflammatory response to COVID-19. In moderate-to-severe cases, the blood-testes barrier grants little defence against different pathogenic viruses, including the severe acute syndrome coronavirus 2. The virus could also use the epididymis as a post-testicular route to bind and fuse to the mature spermatozoon and possibly accomplish the reverse transcription of the single-stranded viral RNA into proviral DNA. These mechanisms can elicit extracellular cell-free DNA formation. The potential implications of our findings for assisted conception must be addressed, and the evolutionary history of DNA-based extracellular traps as preserved ammunition in animals' innate defence might improve our understanding of the severe acute syndrome coronavirus 2 pathophysiology in the testis and spermatozoa.
严重急性综合征冠状病毒 2 可侵犯多种组织，包括睾丸。尽管该病毒在人类精液聚合酶链反应检测中很少发现，但尸检研究证实，该病毒存在于睾丸的所有细胞类型中，包括精子和精原细胞。
研究严重急性综合征冠状病毒 2 是否存在于聚合酶链反应感染阴性的男性精子中，这些男性在出院后 3 个月内。
本横断面研究纳入了 13 名确诊为中度至重度 COVID-19 的患者，在诊断后 30-90 天入组。采集精液样本，用实时聚合酶链反应检测 RNA，用电镜观察。
在中重度临床情况下，我们在 13 名患者中的 9 名患者的精子中发现了严重急性综合征冠状病毒 2，这些患者在出院后 90 天内。此外，在所有研究标本中均报告了一些基于 DNA 的细胞外陷阱。
虽然严重急性综合征冠状病毒 2 未存在于感染男性的精液中，但它在出院后 3 个月内在精子内仍呈细胞内存在。电子显微镜（EM）发现还表明，精子产生基于核 DNA 的细胞外陷阱，可能以无细胞游离 DNA 依赖的方式，类似于 COVID-19 全身炎症反应中先前描述的方式。在中重度情况下，血睾屏障对不同的致病病毒，包括严重急性综合征冠状病毒 2 的防御能力较弱。病毒也可以将附睾用作睾丸后的途径，与成熟精子结合并融合，并可能将单链病毒 RNA 逆转录为前病毒 DNA。这些机制可以引发细胞外游离 DNA 的形成。我们的发现对辅助受孕的潜在影响必须加以解决，并且作为动物先天防御中保存的弹药的 DNA 细胞外陷阱的进化历史可能会提高我们对睾丸和精子中严重急性综合征冠状病毒 2 病理生理学的理解。
