Saudi Journal of Kidney Diseases and Transplantation

: 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?

Lujain Mohammad Dkhil AlDkhil1, Abeer Ageel Alenazi2,  
1 GlaxoSmithKline Pharmaceutical Company, Riyadh, Saudi Arabia
2 Mylan Pharmaceutical Company, Riyadh, Saudi Arabia

Correspondence Address:
Abeer Ageel Alenazi
Mylan Pharmaceutical Company, Riyadh
Saudi Arabia

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;31:1443-1444

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 2021 Aug 6 ];31:1443-1444
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Full Text

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.


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