World J Mens Health.  2021 Jan;39(1):65-74. 10.5534/wjmh.200170.

Histopathology and Ultrastructural Findings of Fatal COVID-19 Infections on Testis

Affiliations
  • 1Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA.
  • 2Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL, USA.
  • 3The Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL, USA.
  • 4John P Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.

Abstract

Purpose
To evaluate the presence and analyze the pathological changes within the testes of patients who died or recovered from severe acute respiratory syndrome coronavirus 2 (COVID-19) complications.
Materials and Methods
Testis tissue was collected from autopsies of COVID-19 positive (n=6) and negative men (n=3).Formalin-fixed paraffin-embedded tissues were stained with hematoxylin and eosin (H&E) and subjected to immunofluorescence for angiotensin-converting enzyme 2 (ACE-2) expression. Fluorescent-labeled tissue slides were imaged on a quantitative pathology scope with various zoom levels allowing for qualitative and quantitative interpretation. Tissue from four COVID-19 positive autopsy cases and a live seroconverted patient was imaged with transmission electron microscopy (TEM).
Results
H&E histomorphology showed three of the six COVID-19 biopsies had normal spermatogenesis while the remaining three had impaired spermatogenesis. TEM showed the COVID-19 virus in testis tissue of one COVID-19 positive autopsy case and the live biopsy, H&E stain on the same autopsy case demonstrated interstitial macrophage and leukocyte infiltration.Immunofluorescent stained slides from six COVID-19 positive men demonstrated a direct association between increased quantitative ACE-2 levels and impairment of spermatogenesis.
Conclusions
The novel COVID-19 has an affinity for ACE-2 receptors. Since ACE-2 receptor expression is high in the testes, we hypothesized that COVID-19 is prevalent in testes tissue of infected patients. This study suggests the male reproductive tract, specifically the testes, may be targets of COVID-19 infection. We found an inverse association between ACE-2 receptor levels and spermatogenesis, suggesting a possible mechanism of how COVID-19 can cause infertility.

Keyword

Autopsy; Coronavirus; COVID-19; Infertility; Testis
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