International Journal of Reproductive BioMedicine
ISSN: 2476-3772
The latest discoveries in all areas of reproduction and reproductive technology.
Vimentin as a contributing factor in SARS-CoV-2-induced orchitis on postmortem testicular autopsy of COVID-19 cases: A case-control study
Published date: Jan 01 2025
Journal Title: International Journal of Reproductive BioMedicine
Issue title: International Journal of Reproductive BioMedicine (IJRM): Volume 22, Issue No. 11
Pages: 895 – 906
Authors:
Abstract:
Background: Coronavirus disease 2019 (COVID-19) was identified in China in late December 2019 and led to a pandemic that resulted in millions of confirmed cases and deaths. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uses distinct receptors and co-receptors to enter host cells. Vimentin has emerged as a potential co-receptor for SARS-CoV-2 due to the high level of vimentin expression in testis tissue.
Objective: The present study investigated the link between vimentin expression level and SARS-CoV-2-induced orchitis.
Materials and Methods: In this case-control study, testis autopsy samples were collected immediately after the death of both COVID-19 cases and a control group that included individuals who died due to accidental causes. Gene expression and immunohistochemical assays were conducted to evaluate the level of vimentin expression, cell proliferation, and leukocyte infiltration.
Results: A significant expression of vimentin and infiltration of immune cells (CD68+, CD38+, and CD138+) in the testicular tissue of COVID-19 cases, along with extensive immunoglobulin G precipitation and reduced inhibin expression (p = 0.001) were observed. Additionally, gene expression analysis revealed increased expression of vimentin and decreased expression of the proliferation markers Ki67 and proliferating cell nuclear antigen, suggesting that SARS-CoV-2 may disrupt spermatogenesis through immune responses and the arrest of cell proliferation.
Conclusion: There may be a strong link between vimentin expression and COVID-19-induced orchitis. Further studies are needed to confirm these findings. Considering some limitations, vimentin can be used as a biomarker option for testicular damage following COVID-19-induced orchitis.
Keywords: Autopsy, COVID-19, Orchitis, SARS-CoV-2, Vimentin.
References:
[1] Hsu AL, Finlinson A, Warncke K. Mechanisms by which SARS-CoV-2 may impact male fertility. Reprod Sci 2021; 28: 332–333.
[2] Moghimi N, Eslami Farsani B, Ghadipasha M, Mahmoudiasl GhR, Piryaei A, Aliaghaei A, et al. COVID-19 disrupts spermatogenesis through the oxidative stress pathway following induction of apoptosis. Apoptosis 2021; 26: 415–430.
[3] Peirouvi T, Aliaghaei A, Eslami Farsani B, Ziaeipour S, Ebrahimi V, Forozesh M, et al. COVID-19 disrupts the blood-testis barrier through the induction of inflammatory cytokines and disruption of junctional proteins. Inflamm Res 2021; 70: 1165–1175.
[4] Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181: 271–280.
[5] Pan F, Xiao X, Guo J, Song Y, Li H, Patel DP, et al. No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil Steril 2020; 113: 1135–1139.
[6] Stanley KE, Thomas E, Leaver M, Wells D. Coronavirus disease-19 and fertility: Viral host entry protein expression in male and female reproductive tissues. Fertil Steril 2020; 114: 33–43.
[7] Duarte-Neto AN, Teixeira TA, Caldini EG, Kanamura CT, Gomes-Gouvêa MS, Dos Santos ABG, et al. Testicular pathology in fatal COVID-19: A descriptive autopsy study. Andrology 2022; 10: 13–23.
[8] Yu YTC, Chien SC, Chen IY, Lai CT, Tsay YG, Chang SC, et al. Surface vimentin is critical for the cell entry of SARS-CoV. J Biomed Sci 2016; 23: 14.
[9] Zhao S, Miao C, Gao X, Li Z, Eriksson JE, Jiu Y. Vimentin cage - a double-edged sword in host anti-infection defense. Curr Opin Cell Biol 2024; 86: 102317.
[10] Beileke S, Claassen H, Wagner W, Matthies C, Ruf C, Hartmann A, et al. Expression and localization of lung surfactant proteins in human testis. PLoS One 2015; 10: e0143058.
[11] Zomer HD, Reddi PP. Characterization of rodent Sertoli cell primary cultures. Mol Reprod Dev 2020; 87: 857–870.
[12] Zhao W-P, Wang H-W, Liu J, Tan P-P, Luo X-L, Zhu Sh-Q, et al. Positive PCNA and Ki-67 expression in the testis correlates with spermatogenesis dysfunction in fluoride-treated rats. Biol Trace Elem Res 2018; 186: 489–497.
[13] Li Zh, Paulin D, Lacolley P, Coletti D, Agbulut O. Vimentin as a target for the treatment of COVID-19. BMJ Open Respir Res 2020; 7: e000623.
[14] Suprewicz Ł, Swoger M, Gupta S, Piktel E, Byfield FJ, Iwamoto DV, et al. Extracellular vimentin as a target against SARS-CoV-2 host cell invasion. Small 2022; 18: 2105640.
[15] Dos Santos G, Rogel MR, Baker MA, Troken JR, Urich D, Morales-Nebreda L, et al. Vimentin regulates activation of the NLRP3 inflammasome. Nat Commun 2015; 6: 6574.
[16] Liu Y, Yan LM, Wan L, Xiang TX, Le A, Liu JM, et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis 2020; 20: 656–657.
[17] Li H, Xiao X, Zhang J, Zafar MI, Wu C, Long Y, et al. Impaired spermatogenesis in COVID-19 patients. EClinicalMedicine 2020; 28: 100604.
[18] Ma X, Guan C, Chen R, Wang Y, Feng S, Wang 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 2021; 18: 487–489.
[19] Shigyo M, Kuboyama T, Sawai Y, Tada-Umezaki M, Tohda C. Extracellular vimentin interacts with insulin-like growth factor 1 receptor to promote axonal growth. Sci Rep 2015; 5: 12055.
[20] Shigyo M, Tohda C. Extracellular vimentin is a novel axonal growth facilitator for functional recovery in spinal cord-injured mice. Sci Rep 2016; 6: 28293.
[21] Mak T, Brüggemann H. Vimentin in bacterial infections. Cells 2016; 5: 18.
[22] Yang J, Zou L, Yang Y, Yuan J, Hu Z, Liu H, et al. Superficial vimentin mediates DENV-2 infection of vascular endothelial cells. Sci Rep 2016; 6: 38372.
[23] Schäfer G, Graham LM, Lang DM, Blumenthal MJ, Bergant Marušič M, Katz AA. Vimentin modulates infectious internalization of human papillomavirus 16 pseudovirions. J Virol 2017; 91: e00307.
[24] Thalla DG, Jung P, Bischoff M, Lautenschläger F. Role of extracellular vimentin in cancer-cell functionality and its influence on cell monolayer permeability changes induced by SARS-CoV-2 receptor binding domain. Int J Mol Sci 2021; 22: 7469.
[25] Ramos I, Stamatakis K, Oeste CL, Pérez-Sala D. Vimentin as a multifaceted player and potential therapeutic target in viral infections. Int J Mol Sci 2020; 21: 4675.
[26] Parvanian S, Coelho-Rato LS, Patteson AE, Eriksson JE. Vimentin takes a hike-emerging roles of extracellular vimentin in cancer and wound healing. Curr Opin Cell Biol 2023; 85: 102246.
[27] Arrindell J, Desnues B. Vimentin: From a cytoskeletal protein to a critical modulator of immune response and a target for infection. Front Immunol 2023; 14: 1224352.
[28] Yang M, Chen S, Huang B, Zhong JM, Su H, Chen YJ, et al. Pathological findings in the testes of COVID-19 patients: Clinical implications. Eur Urol Focus 2020; 6: 1124–1129.
[29] Xu J, Qi L, Chi X, Yang J, Wei X, Gong E, et al. Orchitis: A complication of severe acute respiratory syndrome (SARS)1. Biol Reprod 2006; 74: 410–416.
