High SARS-CoV-2 tropism and activation of immune cells in the testes of non-vaccinated deceased COVID-19 patients.

Autor: Costa GMJ; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. costagmj@gmail.com., Lacerda SMSN; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Figueiredo AFA; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Wnuk NT; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Brener MRG; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Andrade LM; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Campolina-Silva GH; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Kauffmann-Zeh A; Clínica MF Fertilidade Masculina, Belo Horizonte, MG, Brazil., Pacifico LGG; Clínica MF Fertilidade Masculina, Belo Horizonte, MG, Brazil., Versiani AF; Faculdade de Medicina de São Jose do Rio Preto, São Jose do Rio Preto, SP, Brazil.; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA., Antunes MM; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Souza FR; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Cassali GD; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Caldeira-Brant AL; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.; Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Women's Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, USA., Chiarini-Garcia H; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., de Souza FG; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Costa VV; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., da Fonseca FG; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Nogueira ML; Faculdade de Medicina de São Jose do Rio Preto, São Jose do Rio Preto, SP, Brazil.; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA., Campos GRF; Faculdade de Medicina de São Jose do Rio Preto, São Jose do Rio Preto, SP, Brazil., Kangussu LM; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Martins EMN; Centro de Desenvolvimento da Tecnologia Nuclear-CDTN/CNEN, Belo Horizonte, MG, Brazil., Antonio LM; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Bittar C; Universidade Estadual Paulista, São José do Rio Preto, SP, Brazil., Rahal P; Universidade Estadual Paulista, São José do Rio Preto, SP, Brazil., Aguiar RS; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Mendes BP; Clínica MF Fertilidade Masculina, Belo Horizonte, MG, Brazil., Procópio MS; Clínica MF Fertilidade Masculina, Belo Horizonte, MG, Brazil., Furtado TP; Clínica MF Fertilidade Masculina, Belo Horizonte, MG, Brazil., Guimaraes YL; Clínica MF Fertilidade Masculina, Belo Horizonte, MG, Brazil.; Departamentos de Urologia e de Reprodução Humana da Rede Mater Dei de Saúde, Belo Horizonte, MG, Brazil., Menezes GB; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Martinez-Marchal A; Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Women's Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, USA., Orwig KE; Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Women's Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, USA., Brieño-Enríquez M; Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Women's Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, USA. brienoenriquezma@mwri.magee.edu., Furtado MH; Clínica MF Fertilidade Masculina, Belo Horizonte, MG, Brazil.; Departamentos de Urologia e de Reprodução Humana da Rede Mater Dei de Saúde, Belo Horizonte, MG, Brazil.
Jazyk: angličtina
Zdroj: BMC biology [BMC Biol] 2023 Feb 16; Vol. 21 (1), pp. 36. Date of Electronic Publication: 2023 Feb 16.
DOI: 10.1186/s12915-022-01497-8
Abstrakt: Background: Cellular entry of SARS-CoV-2 has been shown to rely on angiotensin-converting enzyme 2 (ACE2) receptors, whose expression in the testis is among the highest in the body. Additionally, the risk of mortality seems higher among male COVID-19 patients, and though much has been published since the first cases of COVID-19, there remain unanswered questions regarding SARS-CoV-2 impact on testes and potential consequences for reproductive health. We investigated testicular alterations in non-vaccinated deceased COVID-19-patients, the precise location of the virus, its replicative activity, and the immune, vascular, and molecular fluctuations involved in the pathogenesis.
Results: We found that SARS-CoV-2 testicular tropism is higher than previously thought and that reliable viral detection in the testis requires sensitive nanosensors or RT-qPCR using a specific methodology. Through an in vitro experiment exposing VERO cells to testicular macerates, we observed viral content in all samples, and the subgenomic RNA's presence reinforced the replicative activity of SARS-CoV-2 in testes of the severe COVID-19 patients. The cellular structures and viral particles, observed by transmission electron microscopy, indicated that macrophages and spermatogonial cells are the main SARS-CoV-2 lodging sites, where new virions form inside the endoplasmic reticulum Golgi intermediate complex. Moreover, we showed infiltrative infected monocytes migrating into the testicular parenchyma. SARS-CoV-2 maintains its replicative and infective abilities long after the patient's infection. Further, we demonstrated high levels of angiotensin II and activated immune cells in the testes of deceased patients. The infected testes show thickening of the tunica propria, germ cell apoptosis, Sertoli cell barrier loss, evident hemorrhage, angiogenesis, Leydig cell inhibition, inflammation, and fibrosis.
Conclusions: Our findings indicate that high angiotensin II levels and activation of mast cells and macrophages may be critical for testicular pathogenesis. Importantly, our findings suggest that patients who become critically ill may exhibit severe alterations and harbor the active virus in the testes.
(© 2023. The Author(s).)
Databáze: MEDLINE
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