Background:: The Coronavirus Disease 2019 (COVID-19) is becoming the major health issue in recent human history with thousands of deaths and millions of cases worldwide. Newer research and old experience with other corona-viruses highlighted a probable underlying mechanism of disturbance of the renin-angiotensin system (RAS) that is associ-ated with intrinsic effects of SARS-CoV-2 infection Objective:: In this review, we aimed to describe the intimate connections between the RAS components, the immune system and COVID-19 pathophysiology. Methods:: This non-systematic review article summarizes recent evidence on the relationship between COVID-19 and the RAS. Results:: Several studies have indicated that the downregulation of membrane-bound ACE2 may exert a key role for the impairment of immune functions and for COVID-19 patients’ outcome. The downregulation may occur by distinct mecha-nisms, particularly: (1) the shedding process induced by SARS-CoV-2 fusion pathway, which reduces the amount of mem-brane-bound ACE2, stimulating more shedding by the high levels of Angiotensin II; (2) the endocytosis of ACE2 receptor with the virus itself and (3) by the interferon inhibition caused by SARS-CoV-2 effects on immune system, which leads to reduction of ACE2 receptor expression. Conclusion:: Recent research provides evidence of a reduction of the components of the alternative RAS axis, including ACE2 and Angiotensin-(1-7). In contrast, increased levels of Angiotensin II can activate the AT1 receptor in several organs. Consequently, increased inflammation, thrombosis and angiogenesis occur in patients infected with SARS-COV-2. Atten-tion should be paid to the interactions of the RAS and COVID-19, mainly in the context of novel vaccines and proposed medications.

Background: The identification of vulnerable subgroups and risk factors associated with the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) are of utmost importance in a pandemic scenario. Potential interactions between renin-angiotensin system (RAS), immune markers and COVID-19 play a role in disease outcome in specific groups of patients. Objective: This review aimed to describe the particularities of the RAS and the immune system profile of particular subgroups of patients. Methods: This non-systematic review summarizes evidence on SARS-CoV-2 infection in specific subgroups of patients and possible relationships between immune system, RAS and the pathophysiology of COVID-19. Results: The RAS and the immune system exert a role in the pathogenesis and prognosis of COVID-19, mainly in cases of hypertension, diabetes, obesity and other chronic diseases. The overactivation of the ACE/Ang II/AT1R axis and the enhancement of inflammation contribute to deleterious effects of COVID-19. Likewise, pregnant women and elderly patients usually display immune responses that are less effective in withstanding exposition to viruses, while children are relatively protected against severe complications of COVID-19. Women, conversely, exhibit stronger antiviral responses and are less sensitive to the effects of increased Ang II. Future Perspectives: The recognition of vulnerable subgroups and risk factors for disease severity are essential to better understand the pandemic. Precision medicine tools, including proteomics and metabolomics approaches, identified metabolic patterns of the severe form of disease and might be the alternative to diagnose, evaluate and predict the prognosis and the efficiency of therapies.