The RAS disorder and ineffective immune responses are related to the severity of COVID-19: The RAS inhibitor and the antiviral drugs can be useful

Abstract

Author(s): Sepideh Abbaszadeh, Pejman Molaei, Saeid Afshar and Fatemeh Bahrami Banan*

SARS-CoV2 utilizes the Angiotensin-Converting Enzyme (ACE2) transmembrane receptor to infect the cell. ACE2 plays a pivotal role as one of the primary enzymes within the Renin-Angiotensin System (RAS), responsible for regulating the homeostasis of different organs. RAS hyperactivity, accompanied by an increase in the ACE/ACE2 ratio, leads disorders such as cardiovascular, pulmonary, and renal problems and uncontrolled inflammatory responses having been similarly observed in patients with COVID-19 too. Probably using the ACE2 as the receptor by SARS-CoV2 leads disturbance in RAS, which may be the cause of the destructive effects of the virus. On the other hand, humoral immunity plays a considerable role in the recovery of patients by producing antibodies against the viral particles, while inflammation response inducing cellular and innate immunity, has a negative effect. Therefore, what seems to affect the severity of the disease is the kind of the response of the immune system and the different ACE / ACE2 ratio in individuals. If during viral infection, before effective elimination of the virus by humoral immunity, the ACE/ACE2 ratio surpasses the usual amount, the deregulation of the system will be ineffective, and the destructive effects of RAS hyperactivity on the target organs will occur, the patient will experience the severe type of the disease, but if the virus is removed on time, a mild form will happen. Probably combination therapy with RAS inhibitors and the antiviral drugs that prevent viral proliferation can be useful.