ABSTRACT
Background: Obesity is a strong risk factor for more severe Covid-19 infection as adipocytes play an important role in intermediating the spreading, replication, and release of SARS-COV-2. An increase in pro-coagulation factors (tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1)) was observed in Covid-19 patients with moderate to severe symptoms and is reported to be associated with Angiotensin-converting enzyme 2 (ACE2) overexpression. Cardiovascular medications affecting ACE2, such as Perindopril and Losartan, are hypothesized to have an effect on Covid-19 infection-related coagulopathy. This study aims to identify and compare the effect of perindopril and losartan on TF and PAI-1 levels in adipocytes exposed to SARS-COV-2 spike protein. Method(s): Adipocytes were isolated enzymatically from adipose tissue obtained from an obese male donor. Adipocytes were then exposed to SARS-COV-2 S1 spike protein for 24 hours. After exposure, perindopril and losartan were added to the culture medium. ACE2, TF, and PAI-1expression were measured 2 hours later using ELISA. Result(s): SARS-CoV-2 spike protein exposure increased ACE2, TF, and PAI-1 expression. Perindopril addition discernible reduced the tissue factor (TF) expression (4.843 +/- 0.396) compared to a positive control (6.857 +/- 0.228) (p=0.005) but not losartan (5.624 +/- 0.606) (p=0.111). Perindopril was also able to lower PAI-1 expressions (3.484 +/- 0.252) compared to a positive control (4.865 +/- 0.115) (p=0.001), but the losartan did so more effectively (2.633 +/- 0.269) (p=0.000). Conclusion(s): Losartan and perindopril both have the ability to lower pro-coagulation factors, proving the value of ACEIs/ARBs in preventing thrombotic complications in Covid-19 patients.Copyright © 2023
ABSTRACT
Background and Aims: The SARS-CoV-2 virus can infect adipocyte cells via ACE2 Receptor thus triggering ACE2 overexpression and cytokine storms which cause lethal complications. Hence, we explore the effect of Perindopril on the expression of ACE2, IL-6, IL-1B TNF-alpha in adipocyte cultures infected by SARS-CoV-2 spike protein and identify the possible mechanism involved. Material(s) and Method(s): Adipocyte culture obtained from a healthy and obese donor was divided into 4 triplicate groups (P0: negative control without treatment;P1: positive control (SARS-CoV-2 spike protein);P2: SARS-CoV-2 spike protein + exposure to Perindopril 0.5 muM);P3: SARS-CoV-2 spike protein + anti-ACE2 antibody 100 mug/mL;and evaluated at 24 and 48 hours. ACE2 expression was evaluated using immunofluorescence. IL-6, TNFalpha, and IL-1B were evaluated using ELISA. SARS-COV-2 Spike-ACE2 Binding was evaluated using Competitive ELISA. Data analysis was performed using SPSS 25.0 software. Result(s): At first 24 hours of incubation, perindopril treatment has the highest ACE2 expression compared to negative control, positive control and anti-ACE2 antibody (113.52+/-0.34 ng/mL vs 13.3+/-0.87 ng/mL, 90.2+/-2.73 ng/mL, 17.3+/-0.11 ng/mL, p<0.01), lower ACE-ACE2R binding compared to anti-ACE2 antibody group (169.52+/-4.07 ng/mL vs 290.71+/-6.22 ng/mL, p<0.01) and higher IL-6 expression compared to positive control group (64.65+/-0.12 ng/mL vs 60.08+/-0.77 ng/mL p<0.01). Interestingly, after 48 hours, perindopril treatment was shown to prevent further increase of ACE2 expression compared to a positive control (47.37+/-0.76 ng/mL vs 80.31+/-5.37 ng/mL, p<0.01), higher SARS-COV-2 Spike-ACE2 binding compared to anti-ACE2 antibody group (143.68+/-3.68 ng/mL vs 103.1+/-9.49 ng/mL, p<0.01), and lower IL-6 expression compared to the positive control group (42.66+/-1.94 ng/mL vs 90.93+/-2.48 ng/mL p<0.01). However, no significant difference in TNFalpha and IL-1B expression between perindopril treatment and positive control in both 24 and 48 hours. Conclusion(s): This study showed that perindopril reduces cytokine storm by preventing ACE-2 and IL-6 overexpression via an increasing number of SARS-COV-2 Spike-ACE2 competitive binding in adipocyte culture infected with SARS-COV-2 spike protein. A further clinical trial is needed to prove the benefit of perindopril in obese patients with COVID-19.
ABSTRACT
Introduction: This study aimed to compare the clinical effects between UFH and fondaparinux in COVID-19 patients with hypercoagulation. Material(s) and Method(s): This was a prospective cohort study. Samples were taken consecutively from hospitalized COVID-19 patients with hypercoagulation who received UFH or fondaparinux based on the standardized guidelines. A total of 71 patients met the inclusion criteria. Patients were evaluated for platelet and D-dimer values before and after administration of UFH or fondaparinux. Result(s): Although there was no difference in D-dimer reduction between the two groups (p = 0.44), fondaparinux showed a greater reduction, 26% against 22% for UFH. While on platelets, there was a significant difference (p = 0.04) between fondaparinux and UFH. Fondaparinux showed a reduced thrombocytopenia impact, as seen by an increase in pre-and post-therapy platelets of up to 50%, compared to 16% in UFH. In regard to the incidence of Heparin-Induced Thrombocytopenia (HIT), there was no significant difference between post-UFH therapy and post-fondaparinux therapy (p = 0.361). Conclusion(s): Fondaparinux did not reduce platelet levels as much as UFH, but there was no difference between the fondaparinux group compared to the UFH group in the effect of decreasing D-dimer levels and the sign of HIT. Copyright © 2022 Via Medica.
ABSTRACT
Background. One of the efforts to reduce hypertension rates in the community is through dietary changes that refer to the Dietary Approach to Stop Hypertension guidelines or abbreviated as DASH. However, in the COVID-19 pandemic, there is a significant obstacle regarding the most effective way to transfer knowledge, skill, and attitude towards society. Aims. Department of Cardiology and Vascular Medicine created a virtual education series about dietary guideline that refers to DASH by adapting the local wisdom of the Surabaya community. We aimed to evaluate the impact of Airlangga Comprehensive Anti-Hypertensive Diets Virtual Education Series towards knowledge, attitude, practice, and reduction of blood pressure in the primary care setting during COVID- 19 pandemic. Methods. This type of online action research is quantitative with a quasi-experimental design that designs using one group pretest-posttest, when this study was conducted in October-December 2020. The population in this study were all patients with hypertension who were treated in Mojo primary health care setting. A purposive sampling technique were done to receive 110 participants using online questionnaire. Results. A total of 110 participants were included in the analysis, 55 in the intervention group and 55 in the control group. Following the Airlangga Comprehensive Anti-Hypertensive Diets Virtual Education Series implementation, the only parameter that showed significant improvement were knowledge and attitude (p < 0 .001). There is no significant change in the skill parameters (p = 0.131) and blood pressure parameters (p = 0.433) . Conclusion. Airlangga Comprehensive Anti-Hypertensive Diets Virtual Education Series implementation in our study population seems to be effective to improve knowledge and attitude of participants, however, this program seems to be ineffective to improve skill and blood pressure reduction in participants. Future study with longer durations and more comprehensive programme needs to be done to scrutinize the clinical impact of this program nationwide.