Figure 1.

Simplified schematic diagram of the renin-angiotensinogen system (RAS). (A) Typical balanced RAS system. Renin claves angiotensinogen to angiotensin-I (Ang-I (1-10)) which is then converted to angiotensin-II (Ang-II (1-8)) by angiotensin-converting enzyme (ACE), the Ang-I is also converted to Ang (1-9) by angiotensin-converting enzyme-2 (ACE2), this enzyme also balances the excessive concentration of Ang-II by converting it to Ang (1-7). (B) The imbalanced RAS system caused by the chronic malaria exposure, and the subsequent polymorphism selection of the ACE-1 D allele that increases the enzyme levels and ACE-2 T allele (rs2106809) which results in the decreased expression of ACE2. This will increase Ang-II concentration which leads to an increase in the proinflammatory response, and the decrease of Ang (1-7) and subsequently the decrease in anti-inflammatory response. (C) SARS-CoV-2 infection in the malaria-endemic region where D and/or T alleles are fixed in the population due to malaria, is characterized by decreased concentrations of ACE and ACE2 respectively. This result in a reduced number of ACE-2 receptors required for viral entry, and also an increased pro-inflammatory response due to the increased concentrations of Ang-II (1-8).