Case series - COVID-19 is unlikely to affect male fertility: Results of histopathological and reverse transcriptase polymerase chain reaction analysis.

INTRODUCTION: We aimed to analyze the testicular histopathology of men who died with active COVID-19 infection. METHODS: We performed autopsy of eight consecutive men who died of COVID-19 pneumonia. Lung and testis tissue of all men were stained for SARS-CoV-2 nucleocapsid, angiotensin-converting enzyme 2 (ACE-2) receptor immunohistochemistry (IHC). H&E was performed to assess for spermatogenesis and evidence of testicle tissue damage. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis for SARS-CoV-2 was performed on matched lung and bilateral testicular tissue samples from all men. RESULTS: Patient age ranged from 50-79 years. SARS-CoV-2 viral RNA was detected by RTPCR in testis tissue in one man. All eight testicle specimens that underwent IHC for ACE2 receptor showed uniformly strong immunoreactivity against all testicle cell populations. By H&E, all testis specimens showed no inflammation, vascular thrombosis, vasculitis, or morphological evidence of viral changes. One case showed diminished but not absent spermatogenesis, consistent with patient age. CONCLUSIONS: Our results suggest that SARS-CoV-2 is unlikely to affect male fertility. Contrary to all prior histological studies, our results showed no evidence of damage to reproductive tissues that might impair fertility.

Feminising hormone therapy reduces testicular ACE-2 receptor expression: Implications for treatment or prevention of COVID-19 infection in men.

It has been proposed that men hospitalised with COVID-19 be treated with oestrogen or progesterone to improve COVID-19 outcomes. Transgender women (male-to-female) are routinely treated with oestrogen or oestrogen +progesterone for feminisation which provides a model for the effect of feminising hormones on testicular tissue. Our goal was to analyse differences in ACE-2 expression in testicles of trans-women taking oestrogen or oestrogen +progesterone. Orchiectomy specimens were collected from trans-women undergoing gender-affirming surgery, who were taking oestrogen or oestrogen+progesterone preoperatively. For controls, we used benign orchiectomy specimens from cis-gender men. All specimens were stained with H&E, Trichrome (fibrosis), insulin-like 3 antibody (Leydig cell) and ACE-2 IHC. Cells per high-powered field were counted by cell type (Leydig, Sertoli and Germ). Stain intensity was rated on a 0-2 scale. On immunohistochemistry staining for Leydig cells and ACE-2 staining, the oestrogen+progesterone cohort had fewer Leydig cells compared with controls. The oestrogen+progesterone cohort also had greater degree of tissue fibrosis compared with controls and the oestrogen cohort. This work supports the hopeful possibility that a short course of progesterone (or oestrogen+progesterone) could downregulate ACE-2 to protect men from COVID-19 infection.

Deleterious Effects of SARS-CoV-2 Infection on Human Pancreatic Cells.

COVID-19 pandemic has infected more than 154 million people worldwide and caused more than 3.2 million deaths. It is transmitted by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and affects the respiratory tract as well as extra-pulmonary systems, including the pancreas, that express the virus entry receptor, Angiotensin-Converting Enzyme 2 (ACE2) receptor. Importantly, the endocrine and exocrine pancreas, the latter composed of ductal and acinar cells, express high levels of ACE2, which correlates to impaired functionality characterized as acute pancreatitis observed in some cases presenting with COVID-19. Since acute pancreatitis is already one of the most frequent gastrointestinal causes of hospitalization in the U.S. and the majority of studies investigating the effects of SARS-CoV-2 on the pancreas are clinical and observational, we utilized human iPSC technology to investigate the potential deleterious effects of SARS-CoV-2 infection on iPSC-derived pancreatic cultures containing endocrine and exocrine cells. Interestingly, iPSC-derived pancreatic cultures allow SARS-CoV-2 entry and establish infection, thus perturbing their normal molecular and cellular phenotypes. The infection increased a key cytokine, CXCL12, known to be involved in inflammatory responses in the pancreas. Transcriptome analysis of infected pancreatic cultures confirmed that SARS-CoV-2 hijacks the ribosomal machinery in these cells. Notably, the SARS-CoV-2 infectivity of the pancreas was confirmed in post-mortem tissues from COVID-19 patients, which showed co-localization of SARS-CoV-2 in pancreatic endocrine and exocrine cells and increased the expression of some pancreatic ductal stress response genes. Thus, we demonstrate that SARS-CoV-2 can directly infect human iPSC-derived pancreatic cells with strong supporting evidence of presence of the virus in post-mortem pancreatic tissue of confirmed COVID-19 human cases. This novel model of iPSC-derived pancreatic cultures will open new avenues for the comprehension of the SARS-CoV-2 infection and potentially establish a platform for endocrine and exocrine pancreas-specific antiviral drug screening.