The Impact of COVID-19 On Comorbidities: A Review Of Recent Updates For Combating It.

Coronavirus disease is caused by the SARS-CoV-2 virus. The virus first appeared in Wuhan (China) in December 2019 and has spread globally. Till now, it affected 269 million people with 5.3 million deaths in 224 countries and territories. With the emergence of variants like Omicron, the COVID-19 cases grew exponentially, with thousands of deaths. The general symptoms of COVID-19 include fever, sore throat, cough, lung infections, and, in severe cases, acute respiratory distress syndrome, sepsis, and death. SARS-CoV-2 predominantly affects the lung, but it can also affect other organs such as the brain, heart, and gastrointestinal system. It is observed that 75 % of hospitalized COVID-19 patients have at least one COVID-19 associated comorbidity. The most common reported comorbidities are hypertension, NDs, diabetes, cancer, endothelial dysfunction, and CVDs. Moreover, older and pre-existing polypharmacy patients have worsened COVID-19 associated complications. SARS-CoV-2 also results in the hypercoagulability issues like gangrene, stroke, pulmonary embolism, and other associated complications. This review aims to provide the latest information on the impact of the COVID-19 on pre-existing comorbidities such as CVDs, NDs, COPD, and other complications. This review will help us to understand the current scenario of COVID-19 and comorbidities; thus, it will play an important role in the management and decision-making efforts to tackle such complications.

The role of angiotensin-converting enzyme 2 in the pathogenesis of COVID-19: the villain or the hero?

Angiotensin-converting enzyme 2 (ACE 2) is the entry receptor for the novel coronavirus SARS-CoV-2, the aetiological agent of COVID-19. At the same time, ACE 2 expression decreases during COVID-19. Two seemingly contradictory relationships between the expression of ACE 2 and COVID-19 have been reported. Increased level of expression of ACE 2 may be a risk factor for the development of COVID-19 infection, while reduced ACE 2 expression during COVID-19 leads to acute respiratory distress syndrome. This article provides a comprehensive overview of available scientific knowledge about the role of ACE 2 in the pathogenesis of COVID-19, which is available up to current day. Also, it discusses unknown factors that we will have to reveal in order to understand the whole role of ACE 2 in the pathogenesis of COVID-19.

Renin Angiotensin Blockers and Cardiac Protection: From Basis to Clinical Trials.

Despite a similar beneficial effect on blood pressure lowering observed with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor (AT1R) blocker (ARBs), several clinical trials and meta-analyses have reported higher cardiovascular mortality and lower protection against myocardial infarction with ARBs when compared with ACEIs. The European guidelines for the management of coronary syndromes and European guidelines on diabetes recommend using ARBs in patients who are intolerant to ACEIs. We reviewed the main pharmacological differences between ACEIs and ARBs, which could provide insights into the differences in the cardiac protection offered by these 2 drug classes. The effect of ACEIs on the tissue and plasma levels of bradykinin and on nitric oxide production and bioavailability is specific to the mechanism of action of ACEIs; it could account for the different effects of ACEIs and ARBs on endothelial function, atherogenesis, and fibrinolysis. Moreover, chronic blockade of AT1 receptors by ARBs induces a significant and permanent increase in plasma angiotensin II and an overstimulation of its still available receptors. In animal models, AT4 receptors have vasoconstrictive, proliferative, and inflammatory effects. Moreover, in models with kidney damage, atherosclerosis, and/or senescence, activation of AT2 receptors could have deleterious fibrotic, vasoconstrictive, and hypertrophic effects and seems prudent and reasonable to reserve the use of ARBs for patients who have presented intolerance to ACE inhibitors.

Treatment with renin-angiotensin system inhibitors and prognosis of heart failure with preserved ejection fraction: A propensity-matched study in the community.

AIMS: There is currently no consensus on the effect of treatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), on the prognosis of patients with heart failure and preserved ejection fraction (HFpEF). Therefore, we have analysed the relationship of commencing treatment with ACEIs or ARBs and the prognosis of patients with incident HFpEF. METHODS: Retrospective study over 15 years on 3864 patients with HFpEF (GAMIC cohort). Main outcomes were mortality (all-cause and cardiovascular) and hospitalisations for HF. The independent relationship between CT-RASIs and the prognosis, stratifying patients for cardiovascular comorbidity after propensity score-matching was analysed. RESULTS: During a median follow-up of 7.94 years, 2960 died (76.6%) and 3138 were hospitalised (81.2%). Therapy with RASIs was associated with a lower mortality, all-cause (RR [95% CI] for ACEIs: 0.76 [0.66-0.86], and RR for ARBs: 0.88 [0.80-0.96]; P < 0.001 in both cases), and cardiovascular (RR for ACEIs: 0.72 [0.66-0.78], and RR for ARBs: 0.87 [0.80-0.94]; P < 0.001), a lower hospitalisation rate (RR for ACEIs: 0.82 [0.74-0.90], and RR for ARBs: 0.90 [0.82-0.98]; P < 0.001), and a lower 30-day readmission rate (RR for ACEIs: 0.66 [0.60-0.73], and RR for ARBs: 0.86 [0.75-0.97]; P < 0.001), after adjustment for the propensity to take RASIs or other medications, comorbidities and other potential confounders. Results on the effect of ARBs are compromised by the small number of patients. Analyses of recurrent hospitalisations gave larger treatment benefits than time-to-first-event analyses. CONCLUSION: In this propensity-matched study, commencing treatment with ACEIs is associated with an improved prognosis of patients newly diagnosed with incident HFpEF.

The impact of age and sex on the reporting of cough and angioedema with renin-angiotensin system inhibitors: a case/noncase study in VigiBase.

The purpose of this study was to assess the impact of age and sex on the reporting of cough and angioedema related to renin-angiotensin system (RAS) inhibitors. A case/noncase study was performed in VigiBase. Two case groups were identified, reports of cough and reports of angioedema, and noncases were all reports of all other adverse events. Logistic regression analysis was used to assess the association between reporting of cough and angioedema with each class of RAS inhibitors stratified by age/sex and to control for confounding. The reporting of cough with angiotensin-converting enzyme (ACE) inhibitors was significantly higher in women than in men [adjusted reporting odds ratio (ROR): 44.0, 95% CI (43.2-44.8) for women vs. 29.2, 95% CI (28.5-29.9) for men]. There was no difference in reporting of cough linked to angiotensin receptor blockers (ARBs) and aliskiren between men and women. In contrast, the reporting of angioedema with ACE inhibitors and ARBs was significantly higher in men than in women, but for aliskiren, women had a significantly higher ROR than men [adjusted ROR: 5.20, 95% CI (4.18-6.46) for women vs. 3.04, 95% CI (2.30-4.02) for men]. The reporting of cough with ACE inhibitors was increased with age until reaching a plateau at middle adulthood (40-59 years) and the reporting of angioedema with ACE inhibitors was increased with age until elderly (60-79 years). Age had only a slight effect on the reporting of cough and angioedema with ARBs and aliskiren. Both age and sex have substantial effects on the reporting of cough and angioedema with RAS inhibitors and in particular ACE inhibitors. Further study is needed to determine whether these differences mainly express different adverse drug reaction risks in subgroups or also can be explained by factors influencing reporting.

Renin-Angiotensin System Inhibitors Might Help to Reduce the Development of Symptomatic Radiation Pneumonitis After Stereotactic Body Radiotherapy for Lung Cancer.

INTRODUCTION: The purpose of the present study was to evaluate the role of renin-angiotensin system (RAS) inhibitors in preventing symptomatic radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: The data from 158 patients with a solitary lung lesion treated with 1 to 3 fractions of SBRT from December 2008 to July 2014 were retrospectively analyzed. The incidence of RP was evaluated according to the Common Toxicity Criteria for Adverse Events, version 4. The use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) was analyzed to assess for possible correlations with the development of grade ≥ 2 RP. The patient and dosimetric variables were also assessed. RESULTS: After a median follow-up period of 13.8 months (range, 3.2-55.0 months), 22 patients had developed grade ≥ 2 RP. Patients with peripheral lesions, favorable dosimetric data, and ACEI and/or ARB use had a reduced risk of symptomatic RP. In unadjusted and adjusted multivariate analyses, ACEI and/or ARB intake and the dosimetric variables were statistically significant factors. In a secondary analysis, the use of ACEIs and ARBs among patients with a greater planning target volume and higher dosimetric values correlated with a reduced risk of symptomatic RP. CONCLUSION: The use of a RAS inhibitor was associated with a decreased incidence of symptomatic RP among patients undergoing SBRT for lung lesions. Patients with higher dosimetric values had a reduced risk of grade ≥ 2 RP with ACEI and ARB use.

Pharmacological perspectives in sarcopenia: a potential role for renin-angiotensin system blockers?

Sarcopenia represents a major health problem highly prevalent in elderly and age-related chronic diseases. Current pharmacological strategies available to prevent and reverse sarcopenia are largely unsatisfactory thus raising the need to identify novel targets for pharmacological intervention and possibly more effective and safe drugs. This review highlights the current knowledge of the potential benefits of renin-angiotensin system blockade in sarcopenia and discuss the main mechanisms underlying the effects.

Treatment with angiotensin II receptor blockers is associated with prolonged relapse-free survival, lower relapse rate, and corticosteroid-sparing effect in patients with giant cell arteritis.

OBJECTIVE: To determine whether concomitant treatment with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) is associated with changes in the outcome of patients with giant cell arteritis (GCA). METHODS: A study cohort of 106 patients with biopsy-proven GCA was longitudinally followed up for 7.8 ± 3.3 years. Patients were stratified according to their treatment with ACEI, ARB, or no ACEI/ARB. Time to first relapse, number of flares, time to achieve a stable prednisone dose <10mg/day and <5mg/day with no relapses, time required to completely discontinue prednisone, cumulative dose of prednisone received during the first year, and concentrations of acute-phase reactants at pre-defined time points (baseline, 6, 12, 18, and 24 months) were compared among the 3 groups. Cox proportional hazards models were performed to adjust for potential confounders. RESULTS: Patients receiving ARB presented a significantly longer relapse-free survival than patients treated with ACEI or patients not receiving ACEI/ARB (p = 0.02). The adjusted hazard ratio for relapses in patients treated with ARB was 0.32 (95% CI: 0.12-0.81, p = 0.017). In addition, patients who received ARB achieved a prednisone maintenance dose <10mg/day faster than all other patients (p = 0.0002). No significant differences were observed among groups in acute-phase reactant levels during follow-up. However, patients not receiving ACEI/ARB had significantly higher C-reactive protein and haptoglobin concentrations than those receiving ACEI or ARB at various time points. CONCLUSIONS: Addition of ARB to glucocorticoids is associated with lower relapse rate and more prolonged disease-free survival in patients with GCA.

Effect of conversion from CCB to ARB in treatment of hypertension and proteinuria in kidney transplant recipients / 中华器官移植杂志

Objective To compare the efficacy and safety of conversion from CCB to ARB in the treatment of hypertension and proteinuria in kidney transplant recipients.Methods 127 long-term recipients who used CCB as their anti-hypertensive drug were enrolled.All recipients had stable renal function and no diabetes.Recipients were randomly assigned to experimental group (65 cases) which received ARB (Losartan,50～ 100 mg/day) instead of CCB,or control group (62 cases) which received routine CCB.All recipients were followed up for 2 years.Blood count,urinalysis,liver and kidney chemistry,blood lipid,serum electrolytes,24-h urine protein,blood concentration of CNI drugs and other biochemical indexes were observed.Results During the 2-year follow-up,the blood pressure of the two groups was maintained within normal level.The 24-h urine protein was decreased in the experimental group ( 176.32 ± 54.54 to 155.69 ± 62.25,P＜0.05),but increased slightly in the control group (P＞0.05).Although the blood lipid of the experimental group was not different before and after the follow-up,the high density lipoprotein (HDL) was increased statistically (2.25 ± 0.26 to 2.46 ±0.31,P＜0.05).The blood count,liver and kidney chemistry,serum potassium,blood concentration of CNI drugs in both groups showed no significant differences.Conclusion Both CCB and ARB could be effectively and safely used for the treatment of hypertension and proteinuria in kidney transplant recipients.ARB would be more effective in reducing cardiovascular disease (CVD)rate and decreasing proteinuria.