Pathological Findings in the Testes of COVID-19 Patients: Clinical Implications

Abstract

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), involves multiple organs. Testicular involvement is largely unknown.

Objective: To determine the pathological changes and whether SARS-CoV-2 can be detected in the testes of deceased COVID-19 patients.

Design, setting, and participants: Postmortem examination of the testes from 12 COVID-19 patients was performed using light and electron microscopy, and immunohistochemistry for lymphocytic and histiocytic markers. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the virus in testicular tissue.

Outcome measurements and statistical analysis: Seminiferous tubular injury was assessed as none, mild, moderate, or severe according to the extent of tubular damage. Leydig cells in the interstitium were counted in ten 400× microscopy fields.

Results and limitations: Microscopically, Sertoli cells showed swelling, vacuolation and cytoplasmic rarefaction, detachment from tubular basement membranes, and loss and sloughing into lumens of the intratubular cell mass. Two, five, and four of 11 cases showed mild, moderate, and severe injury, respectively. The mean number of Leydig cells in COVID-19 testes was significantly lower than in the control group (2.2 vs 7.8, p < 0.001). In the interstitium there was edema and mild inflammatory infiltrates composed of T lymphocytes and histiocytes. Transmission EM did not identify viral particles in three cases. RT-PCR detected the virus in one of 12 cases.

Conclusions: Testes from COVID-19 patients exhibited significant seminiferous tubular injury, reduced Leydig cells, and mild lymphocytic inflammation. We found no evidence of SARS-CoV-2 virus in the testes in the majority (90%) of the cases by RT-PCR, and in none by electron microscopy. These findings can provide evidence-based guidance for sperm donation and inform management strategies to mitigate the risk of testicular injury during the COVID-19 disease course.

Patient summary: We examined the testes of deceased COVID-19 patients. We found significant damage to the testicular parenchyma. However, virus was not detected in testes in the majority of cases.

Keywords: COVID-19; Fertility; Postmortem needle autopsy; SARS-CoV-2; Testis.

Fig. 1

Pathology in testes from COVID-19 patients. (A) Sertoli cells shows swelling, vacuolation, and cytoplasmic rarefaction, and detachment from the tubular basement membranes. Spermatogenesis is present but reduced. (B) A case with severe tubular injury shows cytoplasmic vacuolation and detachment of Sertoli cells from the basement membranes. Spermatogenesis is present. Scattered Leydig cells are present (arrow). (C) A case with moderate tubular injury shows loss and sloughing of intratubular cells into the lumens (asterisks). There is marked interstitial edema. Note the normal spermatogenesis. (D) Testis from a non-COVID patient with protracted disease shows normal spermatogenesis. In the interstitium there is edema and mild inflammatory infiltrates composed predominantly of (E) CD3-positive T lymphocytes and (F) CD68-positive histiocytes according to immunohistochemistry. COVID-19 = coronavirus disease 2019.

Fig. 2

ACE2 is diffusely expressed in Sertoli cells and strongly expressed in Leydig cells (long arrows) according to immunohistochemistry. Spermatogonia are negative (short arrows). Spermatocytes of later stages are surrounded by the Sertoli cell cytoplasm (open arrows).