Drugs acting on the renin-angiotensin-aldosterone system (RAAS) and deaths of COVID-19 patients: a systematic review and meta-analysis of observational studies.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are two of the most commonly used antihypertensive drugs acting on the renin-angiotensin-aldosterone system (RAAS). Previous research has shown that RAAS inhibitors increase the expression of angiotensin-converting enzyme, a cellular receptor for the severe acute respiratory syndrome coronavirus 2, raising concerns that the use of ACEi and ARBs in hypertensive patients may increase COVID-19 patient mortality. Therefore, the main aim of the current study was to find out the role of drugs acting on RAAS, particularly ACEi/ARBs in the deaths of COVID-19 patients. RESULTS: In total, 68 studies were found to be appropriate, reporting a total of 128,078 subjects. The odds ratio was found to be 1.14 [0.95, 1.36], which indicates the non-significant association of ACEi/ARBs with mortality of COVID-19 patients. Further, the association of individual ACEi/ARBs with mortality of COVID-19 patients was also found non-significant. The sensitivity analysis results have shown no significant effect of outliers on the outcome. CONCLUSIONS: Based on available evidence, ACEi/ARB were not significantly associated with deaths of COVID-19 patients.

Overcoming the Pandemic: Analysing the Ongoing Challenges in the Prevention of COVID-19 in India

World Health Organization (WHO) has declared the recent outbreak of coronavirus disease (COVID-19) a Pandemic and a global public health emergency. The eventual scope and consequences of this outbreak are uncertain at present as the condition is swiftly evolving. The purpose of this article is to cumulate existing published data and researches, identify the challenges with reference to India and develop a comprehensive preventive plan to prevent the spread of this deadly pandemic. The authors explored WHO situation dashboards, the web portal of Ministry of Health and Family Welfare of India and press reports of different countries, published literature on coronavirus transmission, textbooks, scientific and medical journals and several other sources to identify ongoing challenges in the fight against COVID-19 in India. After an exhaustive literature search, 15 ongoing challenges in the fight against novel COVID-19 especially with reference to India have been identified. After a thorough analysis of all these challenges along with the lessons from the International community, a preventive plan has been established to be devised by different agencies from our personal perspectives to overcome the challenges which may assist decision-makers in the prevention and control of COVID-19 in India.

Therapeutic opportunities of edible antiviral plants for COVID-19.

The pandemic of Serious Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) that produces corona virus disease (COVID-19) has challenged the entire mankind by rapidly spreading globally in 210 countries affecting over 25 million people and about 1 million deaths worldwide. It continues to spread, afflicting the health system globally. So far there is no remedy for the ailment and the available antiviral regimens have been unsatisfactory for the clinical outcomes and the mode of treatment has been mainly supportive for the prevention of COVID-19-induced morbidity and mortality. From the time immortal the traditional plant-based ethno-medicines have provided the leads for the treatment of infectious diseases. Phytopharmaceuticals have provided potential and less toxic antiviral drugs as compared to conventional modern therapeutics which are associated with severe toxicities. The ethnopharmacological knowledge about plants has provided food supplements and nutraceuticals as a promise for prevention and treatment of the current pandemic. In this review article, we have attempted to comprehend the information about the edible medicinal plant materials with potential antiviral activity specifically against RNA virus which additionally possess property to improve immunity along with external and internal respiration and exhibit anti-inflammatory properties for the prevention and treatment of the disease. This will open an arena for the development of novel nutraceutical herbal formulations as an alternative therapy that can be used for the prevention and treatment of COVID-19.

Current targets and drug candidates for prevention and treatment of SARS-CoV-2 (COVID-19) infection.

Angiotensin-converting enzyme 2 (ACE2), the host cell-binding site for SAR-CoV-2, poses two-fold drug development problems. First, the role of ACE2 itself is still a matter of investigation, and no specific drugs are available targeting ACE2. Second, as a consequence of SARS-CoV-2 interaction with ACE2, there is an impairment of the renin-angiotensin system (RAS) involved in the functioning of vital organs like the heart, kidney, brain, and lungs. In developing antiviral drugs for COVID-19, ACE2, RNA-dependent RNA polymerase (RdRp), and the specific enzymes involved in the viral and cellular gene expression have been the primary targets. SARS-CoV-2 being a new virus with unusually high mortality, there has been a need to get medicines in an emergency, and the drug repurposing has been a primary strategy. Considering extensive mortality and morbidity throughout the world, we have made a maiden attempt to discover the drugs interacting with RAS and identify the lead compounds from herbal plants using molecular docking. Both host ACE2 and viral RNA-dependent RNA polymerase (RdRp) and ORF8 appear to be the primary targets for the treatment of COVID-19. While the drug repurposing of currently approved drugs seems to be one strategy for the treatment of COVID-19, purposing phytochemicals may be another essential strategy for discovering lead compounds. Using in silico molecular docking, we have identified a few phytochemicals that may provide insights into designing herbal and synthetic therapeutics to treat COVID-19.

Delineating clinical characteristics and comorbidities among 206 COVID-19 deceased patients in India: Emerging significance of renin angiotensin system derangement.

AIM: While there are rampant deaths reported worldwide due to novel corona virus (COVID-19) on one side, hypertension, diabetes and renal failure are emerging comorbidities with mortality risk due to respiratory failure on the other side. The link of these morbidities with renin angiotensin system (RAS) and angiotensin converting enzyme-2 (ACE2) as the site of the multiplication of COVID-19 has widely been accepted. The objective of this research report was to delineate the clinical characteristics with COVID-19 infection with RAS and to consider its significance not just for the search of novel antiviral drugs, but for the management and prevention of death of patients with COVID-19. METHODS: It was a retrospective case series analysis of demographic and clinical data with associated comorbidities of 206 deaths reported in India up to 10th April 2020. The data were available from the official release from Ministry of Health and Family welfare, Government of India. This was followed by a literature search to correlate the available evidence for their possible relationship with RAS. RESULTS: The demographic data were consistent with those reported from other countries. The death (53.4%) was more common in patients with age above 60 years and men (69.3%) were more susceptible as compared to women (30.68%).We found that 50.5% of the deceased patients had pre-existing comorbidities. Diabetes and hypertension were the major comorbidities in 27.8% and 22.1% of the deceased cases respectively. Although respiratory and cardiac problems were prevalent at the time of death, the pre-existing pulmonary disease was comparatively less prevalent. Only 13.6% of the deceased were having pre-existing respiratory problems and 6.2% had cardiac ailments. We could correlate the reports that RAS plays a significant role in the prognosis of the disease. CONCLUSIONS: Patients with cardiovascular diseases, diabetes mellitus and hypertension are at greater risk for developing COVID-19 infection. There may be massive derangement of the entire RAS after the attack of COVID-19 and hence, patients with these pre-existing comorbidities and on ACE inhibitors or angiotensin receptor blockers should be monitored carefully considering the role of RAS in the prognosis of COVID-19 infections.