key: cord-0854593-jb3x827r authors: Vinciguerra, Mattia; Greco, Ernesto title: Sars-CoV-2 and black population: ACE2 as shield or blade? date: 2020-05-13 journal: Infect Genet Evol DOI: 10.1016/j.meegid.2020.104361 sha: 4d2eef58b48aa6a8fe4ac8c7a3d3de55948ac74d doc_id: 854593 cord_uid: jb3x827r nan Moreover, the different molecular expression of ACE2, limiting the ingress of Sars-CoV-2 into the cells, seems to be crucial to track the incidence of COVID-19 in different populations and to explain their dissimilar susceptibility. Regarding the potential racial heterogeneous molecular expression of ACE2, first Zhao et al. [6] have analyzed lung cells through single-cell RNA sequencing (scRNA-Seq) and have interestingly found higher ACE2 pulmonary levels in Asian than white and African American donors. Additional studies in literature, analyzing big datasets such as the cancer genome atlas (TCGA), have not confirmed this evidence, indicating a similar molecular expression of ACE2 in the lung cells, without difference of race [7, 8] . Evidences result controversial, although recently has been documented the highest expression of ACE2 in the upper respiratory tract, particularly in the nasal epithelial cells, explaining a possible lack in the previous studies limited only to analysis of lung tissue [9] . However, focusing on black population, a reduced molecular expression of ACE2 is documented and represents the key to explain the higher predisposition to develop essential arterial hypertension and an early end organ damage than in others races [10] . Physiologically, ACE2 enzymatic activity is involved in the pathway counter to Angiotensin Converting Enzyme (ACE) leading to the formation of Angiotensin II (Ang II); in fact, ACE2 represents a modulator of the Renin Angiotensin Aldosterone System (RAAS) able to mitigate the largely known deleterious effects. The peptides produced by ACE2, Angiotensin 1-7 (Ang 1-7) and Angiotensin 1-9 (Ang 1-9), have demonstrated to exert a protective role for cardiovascular system among others, reducing the availability of substrate for ACE action, being Ang II associated to cardiac remodeling, hypertrophy and fibrosis leading to heart failure (HF). ACE-inhibitors (ACEi) and Angiotensin II Receptor Blockers (ARBs) use this mechanism to treat Heart Failure and prevent cardiac remodeling, reducing circulating Ang II [11] . Pathogenesis of hypertension is strongly associated to RAAS system dysfunction and recent evidences suggest that an unbalanced symmetry of ACE/ACE2 pathways play a crucial role leading high level of blood pressure, vascular disease and organ damage [12, 13] . In this context, as discussed by Patel et al [13] , patients with risk factors or known evidence of cardiovascular disease (CVD) have documented elevation of plasma ACE2 activity; conversely, a deficiency of ACE2 may lead to primary hypertension. Paradoxically, African descendent populations such as African Americans and particularly subjects affected by pre-hypertensive status, diabetes and renal disease have shown a reduced plasma ACE2 activity [12, 13] . The molecular response to CVD risk factors is completely specular in these J o u r n a l P r e -p r o o f Journal Pre-proof subjects, depressing ACE2 pathway, than in the normal population, in which as previous described it has been documented high levels of ACE2 to balance activation of RAAS. This biological variability is probably correlated to environmental genetic selection for renal sodium-retainers affecting RAAS [16] . Moreover, hypertension profile in black race is characterized by low circulating plasma renin resulting in the documented resistance to RAAS inhibitors, explained by deficit of ACE2 pathway. In fact, lacking the biological counterbalance represented by ACE2 axis, normal or low level of RAAS components exposing constantly to Ang II, leading to long-standing vasoconstriction, hypertrophy and fibrosis [10, 16] . Therefore, taking these evidences our hypothesis consists in the potential COVID-19 less incidence in the black race, if only biological factors are considered. Available online data and statistics to support this hypothesis are not manifest due to mostly missing or unspecified race and ethnicity data on reports in Europe and United States (U.S. The high prevalence of risk factors for CVD in black population may give a determinant contribution, offering to viral replication a pathogenetic substrate characterized by chronic inflammation of endothelium, to develop more frequently the severe disease leading potentially to death; as also confirmed analyzing retrospectively predisposing risk factors in affected patients [1, 19, 20 ]. In conclusion, as summarized in the Figure 1 we think that black race may be less subject to COVID-19 but, once infection is acquired, due to the same reason of potential 'immunity', clinical manifestation may be worse leading definitely to adverse outcome. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Angiotensin -converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor COVID-19 and the cardiovascular system COVID-19: gastrointestinal manifestations and potential fecal-oral transmission Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov Asians and other races express similar levels of and share the same genetic polymorphisms of the SARS-CoV-2 cell-entry receptor Bulk and single-cell transcriptomics identify tobacco-use disparity in lung gene expression of ACE2, the receptor of 2019-nCov SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes Is hypertension in Africandescent populations contributed to by an imbalance in the activities of the ACE2/Ang -(1-7)/Mas and the ACE/Ang II/AT1 axes? Role of the ACE2/angiotensin 1-7 axis of the renin-angiotensin system in heart failure Circulating ACE2 activity is increased in patients with type 1 diabetes and vascular complications From gene to