Discussion
In this study, we have shown that patients with COVID-19 who use ACEIs as antihypertensive have less multilobar involvement compared to patients who use drugs other than ACEIs as antihypertensive treatment and have a diagnosis of COVID-19. That multilobar involvement was less common in patients using ACEIs in our study suggests that viral replication is limited and viral load decreases in these patients. The significance of multilobar involvement and ACEIs in predicting mortality in the univariate regression analysis supports these results.
ACEIs treatment has been shown to reduce viral load and inhibit viral replication in previous studies 13, 14. The renin-angiotensin system (RAAS) is critical in maintaining electrolyte balance and regulating blood pressure 8. Therefore, blockade of the RAAS pathway with ACEIs is considered among the leading treatment options in the treatment of hypertension 8. When the literature is examined, there are different views about the results of ACEIs use in COVID 19 cases. It has been reported that ACE2 receptors act as binding sites for virions of betacoronaviruses1, and the RAAS pathway is considered to play a critical role in acute lung injury caused by viruses besides blood pressure regulation 1, 14, 15. Therefore, a view has been proposed that patients using ACEIs may be at higher risk for SARS-CoV-2 infections, given that the number of ACE2 receptors will increase 1. However, sufficient evidence was not obtained to support or reject this view. The reason for this uncertainty is that there are not enough studies showing the ACE2 receptor levels in patients using ACEIs 16. When the previous studies were examined, it is seen that no significant difference was found concerning ACE2 activity between the patient groups who were using ACEIs and were not using ACEIs for the treatment of heart failure, atrial fibrillation, and coronary artery disease 16-19.
Angiotensin 2 has been shown to have pro-inflammatory properties, cause endothelial and microvascular dysfunctions, and play a role in maintaining vascular tone 14, 20, 21 . Therefore, the RAAS blockade will also likely to decrease inflammatory cytokine release14. Through this mechanism, the RAAS blockade can contribute to hemodynamic stabilization in the case of inflammation and will play a critical role in preventing sepsis-related adverse clinical outcomes 14, 22. However, it is still unclear whether angiotensin II blockade that arises from ACEIs is associated with an improved clinical outcome in patients with COVID-19. In previous studies, it was reported that mostly bilateral or multilobar lung involvement was detected during the admission of COVID-19 cases23. In a study conducted with 102 patients with a confirmed diagnosis of COVID-19, the findings showed that the number of lung lobes affected by COVID-19 was associated with mortality24. Lung injury has been shown to correlate with viral load in patients infected with COVID-19 13, 14.
In previous studies, it was reported that mortality rates in patients using ACEIs were lower than the patients who did not. In a cohort study in which 52 727 patients with a diagnosis of sepsis were included, it was shown that mortality rates were lower in patients using ACEIs or ARBs compared to the patients who did not use them regardless of the infectious agent and underlying comorbid diseases 22. Consistent with this study, other studies have also found an association between ACEIs use and reduced mortality rates in patients hospitalized with a diagnosis of community-acquired pneumonia 22, 25, 26.
In our study, the mortality rate was statistically different between the two groups. This difference may arise from the decreased viral load and multilobar involvement in patients using ACEIs. The small sample size and being single-centred are the major limitations of our study. Prospective studies that would be conducted with a higher number of patients may reflect the effects of ACEIs use on the mortality more accurately.