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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2020  |  Volume : 31  |  Issue : 6  |  Page : 1443-1444
Can transmembrane protease serine 2 be attributed to coronavirus disease-2019 related acute kidney injury predominance in males?

1 GlaxoSmithKline Pharmaceutical Company, Riyadh, Saudi Arabia
2 Mylan Pharmaceutical Company, Riyadh, Saudi Arabia

Click here for correspondence address and email

Date of Web Publication29-Jan-2021

How to cite this article:
AlDkhil LM, Alenazi AA. Can transmembrane protease serine 2 be attributed to coronavirus disease-2019 related acute kidney injury predominance in males?. Saudi J Kidney Dis Transpl 2020;31:1443-4

How to cite this URL:
AlDkhil LM, Alenazi AA. Can transmembrane protease serine 2 be attributed to coronavirus disease-2019 related acute kidney injury predominance in males?. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2022 Dec 8];31:1443-4. Available from: https://www.sjkdt.org/text.asp?2020/31/6/1443/308368

To the Editor,

It has recently been discovered that apart from angiotensin converting enzyme 2 (ACE2), the transmembrane protease serine 2 (TMPRSS2) is also critical for successful entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells.[1],[2] ACE2 serves as the spike (S) protein’s target receptor for SARS-CoV-2, allowing viral affinity to host cells, whereas S protein cleavage by TMPRSS2 furthers viral fusion to host cell membrane.[2] Both ACE2 and TMPRSS2 genes have been respectively identified to play key role in SARS-CoV and H1N1 infection, and intriguingly in SARS-CoV-2 lately.[3],[4]

Epidemiologic studies from advanced nations such as China, Italy, and the United States report that incidence and severity of coronavirus disease-2019 (COVID-19) may be more frequent in males than females. In this regard, cigarette smoking has been linked with gender differences in susceptibility and severity of COVID-19. No significant gender-specific differences with reference to tobacco consumption have been established as yet. However, the catch here is that both ACE2 and TMPRSS2 genes regulate gender-associated differences in susceptibility of COVID-19. ACE2 gene is positioned on the X chromosome. On the other hand, TMPRSS2 gene is expressed in response to trigger from androgens.[5] This latter gene directs us towards the male predominance of COVID-19-related multiorgan injuries, including acute kidney injury (AKI). In fact, research literature also cites the predominance of non-COVID AKI predominance in male gender.

Most importantly, the presence of TMPRSS2 in several tissues lungs, heart, and kidneys in particular has been acknowledged in literature. Recently, co-expression of ACE2 and TMPRSS2 genes have been demonstrated in podocytes.[6] This evidently explains the extra-respiratory manifestations observed in COVID-19 like AKI or laboratory results of raised serum creatinine. In addition to that, endo-thelial cells of microvasculature also possess TMPRSS2 which can cause endothelial injury or dysfunction and may subsequently precipitate glomerular injury and chronic complications of COVID-19.[7] Of late, a study from Italy linked TMPRSS2 variants and expression levels with COVID-19 severity.[5] Moreover, TMPRSS2 involvement in prostate cancer also suggest its strong relationship with gender-specific difference in COVID-19.[8] It is, therefore, quite reasonable to hypothesize that besides gender differences to develop COVID-19 and AKI due to SARS-CoV-2 invasion of podocytes through the presence of TMPRSS2, male individuals with existent comorbidities might have severe form of COVID-19 owing to TMPRSS2-triggered lung and kidney damage. Perhaps molecular studies would be of significance in emphasizing the gender differences, if any, of COVID-19-related AKI.

Conflict of interest: None declared.

   References Top

Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579:270-3.  Back to cited text no. 1
Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271-80.  Back to cited text no. 2
Hofmann H, Pyrc K, van der Hoek L, Geier M, Berkhout B, Pöhlmann S. Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry. Proc Natl Acad Sci 2005;102:7988-93.  Back to cited text no. 3
Cheng Z, Zhou J, To KK, et al. Identification of TMPRSS2 as a susceptibility gene for severe 2009 pandemic A(H1N1) influenza and A(H7N9) influenza. J Infect Dis 2015;212: 1214-21.  Back to cited text no. 4
Asselta R, Paraboschi EM, Mantovani A, Duga S. ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy. Aging (Albany NY) 2020;12:10087-98.  Back to cited text no. 5
Pan XW, Xu D, Zhang H, Zhou W, Wang LH, Cui XG. Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: A study based on single-cell transcriptome analysis. Intensive Care Med 2020;46:1114-6.  Back to cited text no. 6
Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020;395:1417-8.  Back to cited text no. 7
Stopsack KH, Mucci LA, Antonarakis ES, Nelson PS, Kantoff PW. TMPRSS2 and COVID-19: Serendipity or opportunity for intervention? Cancer Discov 2020;10:779-82.  Back to cited text no. 8

Correspondence Address:
Abeer Ageel Alenazi
Mylan Pharmaceutical Company, Riyadh
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.308368

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