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Main Claims & Relevance:

This preprint investigates the impact of SARS-CoV-2 infection on the testes of males who died of the infection. Of the 11 non vaccinated male patients who were included in the study, RT-qPCR revealed the presence of the virus in 10 patients' testicles. Notably, COVID was detected in the testes up to 26 days after symptoms began, which suggests that the testes may act as a viral sanctuary harboring the virus for some time after patients may test negative by nasal swab. Upon further investigation, several virus infected macrophages were detected in blood vessels, parenchyma, and the seminiferous tubules. Additionally, spermatogonial cells displayed intense spike protein labeling. The authors claim that this suggests a "trojan horse" like mechanism where macrophages can bring the virus into the immune privileged area of the testicles and infect the tissue within. Longer duration of severe disease was correlated with a loss of germ cells, as well as fibrosis of the parenchyma and tubules. The authors claim that this may suggest that severe COVID may be associated with an increased risk of infertility.

Are the findings strong, reliable, potentially informative, not informative, or misleading?

The findings are reliable, although certain claims are not substantiated by the evidence presented in the preprint. The histological findings are well powered and controlled against a group of healthy individuals. However, the sample size is not adequate to support the claim that germ cell loss and the progression of the pathogeny is weakly or not correlated with age. The authors also comment that the claims that COVID may cause infertility in these patients are not substantiated, as it is possible that recovery may occur. In order to adequately assess this claim, further studies must be made.

How might these ideas presented by the main claims further knowledge of the COVID-19 Pandemic?

The findings of this preprint are not novel, as previous literature has revealed similar findings (1, 2). Despite this, the ideas presented by this preprint contribute to the body of knowledge of SARS-CoV-2 and thus are valuable to use inform future care of patients. As well, this preprint highlights the need for a study to be performed to illuminate the possible infertility resulting from COVID infection.

References

1. Ma, X., Guan, C., Chen, R. et al. Pathological and molecular examinations of postmortem testis biopsies reveal SARS-CoV-2 infection in the testis and spermatogenesis damage in COVID-19 patients. Cell Mol Immunol 18, 487–489 (2021). https://doi.org/10.1038/s41423-020-00604-5
2. Duarte-Neto, AN, Teixeira, TA, Caldini, EG, et al. Testicular pathology in fatal COVID-19: A descriptive autopsy study. Andrology. 2022; 10: 13– 23. https://doi.org/10.1111/andr.13073