Racial/Ethnic Variation in Nasal Gene Expression of Transmembrane Serine Protease 2 (TMPRSS2)

Abstract

Discussion | This study of nasal epithelial gene expression in a racially/ethnically diverse cohort showed significantly higher expression of TMPRSS2 in Black individuals compared with other self-identified races/ethnicities. Given the essential role of TMPRSS2 in SARS-CoV-2 entry, 3 higher nasal expression of TMPRSS2 may contribute to the higher burden of COVID-19 among Black individuals. TMPRSS2 inhibitors such as camostat mesylate 3 are undergoing clinical trials to test their utility for COVID-19 treatment. The finding of racial/ethnic variation in TMPRSS2 expression emphasizes that inclusion of diverse participants and analyses stratified by race/ethnicity should be incorporated into such trials.The limitations of this study include its modest cohort size, constraint to 1 metropolitan region, and participant age range of 4 to 60 years. Although this study suggests one factor that may partially contribute to COVID-19 risk among New York-area Black individuals, many additional factors are likely, especially because gene expression and race/ ethnicity reflect multiple social, environmental, and geographic factors.

ACE2/ADAM17/TMPRSS2 Interplay May Be the Main Risk Factor for COVID-19

“…Moreover, using public gene expression datasets, a differential expression was found not only for ACE2 but also for the TMPRSS2 gene in the nasal and bronchial airways in relation to age ( 41 ). Interestingly, it was found a higher TMPRSS2 expression on nasal epithelial cells from Black individuals than Asian, Latino, and White individuals ( 42 ). These finding could explain the 2–3 times higher incidence of COVID-19 among Black individuals ( 43 ).…”

“…However, it is still unknown whether ACE2 cleavage by both proteases is mutually exclusive or not, and the relevance of the interplay of these mechanisms on the pathophysiology of COVID-19. In this scenario, it can be expected that increased expression of TMPRSS2 induced by androgen hormones or the occurrence of specific genetic variants ( 5 , 42 , 121 ), or both factors together, may lead to exacerbate, even more, the ACE2 cleavage—mediated harmful effects, by decreasing the membrane-bound or soluble biologically active ACE2 forms.…”

“…This hypothesis may explain the higher incidence in men than in women or in certain races ( 5 , 42 , 121 ). More recently, a specific SARS-CoV-2 A2a subtype—mediated TMPRSS2 and MX1 genes up-regulation has been described in European and North American populations ( 22 ).…”

COVID-19—Lessons Learned and Questions Remaining

“…Lowering the excess prevalence of comorbid conditions such as obesity, diabetes and hypertension in minority populations [ 37 ] should be a public health priority. Higher rates of SARS-CoV-2 infection seen across all age groups rather than differences in age-adjusted case-fatality rates suggest that a primary cause of racial disparity in COVID-19 may be differences in household, community and workplace exposure [ 37 , 38 ], although biological factors may also be contributory [ 39 ].…”

New Horizons: Does Mineralocorticoid Receptor Activation by Cortisol Cause ATP Release and COVID-19 Complications?

“…A serine protease TMPRSS2 on nasal and bronchial epithelium is important in coronavirus infection ( 47 ). Bunyavanich and colleagues showed that TMPRS22 expression was significantly higher in Black compared to Asian, Latino, mixed race, and White individuals ( 48 ).…”