Influence of inhibitors of the renin–angiotensin system on risk of acute respiratory distress syndrome in Danish hospitalized COVID-19 patients

Holt, Anders; Mizrak, I; Lamberts, Morten; Madsen, Per

doi:10.1097/hjh.0000000000002515

Cited by 8 publications

(4 citation statements)

References 6 publications

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“…There is a correlation between these two parameters and higher ACE-2 expression in tissues, which, in turn, enhances viral absorption and raises the risk of life-threatening infection in type 2 diabetics. 16 Multiple studies have shown that adults with proven SARSCOV-2 infection are more likely to die if they are older and have health problems like high blood pressure, diabetes, and heart disease. 17,18 According to the data, hypertension, diabetes, and COVID-19 were found to be prevalent in persons at rates of 21, 11, and 7%, respectively.…”

Section: Demographic and Clinical Characteristics Of Participantsmentioning

confidence: 99%

Genetic Association of Angiotensin-converting enzyme 2 ACE-2 (rs2285666) Polymorphism with the Susceptibility of COVID-19 Disease in Iraqi Patients

2023

TJNPR

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Significant risks to human health are posed by the 2019 coronavirus illness (COVID-19). SARS coronavirus type 2 receptor, also known as the major enzyme in the renin-angiotensin system (RAS), angiotensin-converting enzyme 2 (ACE-2), connects COVID-19 and RAS. This study was conducted with the intention of determining whether or not RAS gene polymorphisms and ACE-2 (G8790A) play a part in the process of predicting susceptibility to infection with COVID-19. In this study 127 participants, 67 of whom were deemed by a physician to be in a severe state of illness, and 60 of whom were categorized as "healthy controls" .The genetic study included an extraction of genomic DNA from blood samples of each covid 19 patients and healthy controls, then amplification the site of SNP (rs2285666) Within the ACE2 gene by using specific primers, sequencing PCR products, and genotyping to detect the role of the ACE-2 gene (rs2285666) in the incidence of COVID-19. ACE-2 (rs2285666) is statistically associated to COVID-19. The COVID-19 group had 65.67 %of individuals with the wild-type homozygous genotype (GG) and 20% in the control group, while the control group had 63.33% of individuals with the mutant genotype (AA). Consequently, the wild-type homozygous (GG) and allele (G) may be considered a risk factor (etiological fraction E. F) for COVID-19 in Iraqi patients, whereas the mutant homozygous (AA) and allele (A) may be considered a protective factor (preventive fraction). The findings of the present study reveal that carriers of the GG genotype of ACE2 (rs2285666) are substantially more susceptible to COVID-19.

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Section: Demographic and Clinical Characteristics Of Participantsmentioning

confidence: 99%

Genetic Association of Angiotensin-converting enzyme 2 ACE-2 (rs2285666) Polymorphism with the Susceptibility of COVID-19 Disease in Iraqi Patients

2023

TJNPR

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“…inhibitors and angiotensin-receptor blockers (ARBs) do not adversely affect the COVID-19 progression or may even be beneficial [22][23][24][25][26][27][28]. In general, studies showed that polypharmacy increases the risk for severe COVID-19 [29,30].…”

Section: Study Populationmentioning

confidence: 99%

“…Some researchers analyzed the influence of anti-hypertensive drugs acting on the renin-angiotensin-aldosterone-system (RAAS)-system [23,24]. The majority of these studies provided evidence that angiotensin converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) do not adversely affect the COVID-19 progression or may even be beneficial [22][23][24][25][26][27][28]. In general, studies showed that polypharmacy increases the risk for severe COVID-19 [29,30].…”

Section: Introductionmentioning

confidence: 99%

Drug-Disease Severity and Target-Disease Severity Interaction Networks in COVID-19 Patients

Schöning

Hammann

2022

Pharmaceutics

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Drug interactions with other drugs are a well-known phenomenon. Similarly, however, pre-existing drug therapy can alter the course of diseases for which it has not been prescribed. We performed network analysis on drugs and their respective targets to investigate whether there are drugs or targets with protective effects in COVID-19, making them candidates for repurposing. These networks of drug-disease interactions (DDSIs) and target-disease interactions (TDSIs) revealed a greater share of patients with diabetes and cardiac co-morbidities in the non-severe cohort treated with dipeptidyl peptidase-4 (DPP4) inhibitors. A possible protective effect of DPP4 inhibitors is also plausible on pathophysiological grounds, and our results support repositioning efforts of DPP4 inhibitors against SARS-CoV-2. At target level, we observed that the target location might have an influence on disease progression. This could potentially be attributed to disruption of functional membrane micro-domains (lipid rafts), which in turn could decrease viral entry and thus disease severity.

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“…Most studies were conducted in hospitalized patients. Some had norestriction on hypertension and analyzed the association between RAASblockers and outcome in unselected inpatients with COVID-19 ( Bean et al, 2020 ; Holt et al, 2020 ; Iaccarino et al, 2020 ; Lahens et al, 2020 ; Liabeuf et al, 2020 ; Shah et al, 2020 ). Except for onestudy which showed an increased risk of severe disease despite – potentially insufficient – adjustment ( Liabeuf et al, 2020 ), and anotherstudy which found a negative association between RAAS blockerexposure and the composite of death or transfer to ICU( Bean et al, 2020 ), all other studies, and in particular all thosewhich analyzed mortality as an outcome, found no association betweenexposure and outcome after adjustment, although an increased risk was frequent in crude analyses.…”

Section: Evidence From Clinical Studiesmentioning

confidence: 99%

Controversial Roles of the Renin Angiotensin System and Its Modulators During the COVID-19 Pandemic

et al. 2021

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Since December 2019, the coronavirus 2019 (COVID-19) pandemic has rapidly spread and overwhelmed healthcare systems worldwide, urging physicians to understand how to manage this novel infection. Early in the pandemic, more severe forms of COVID-19 have been observed in patients with cardiovascular comorbidities, who are often treated with renin-angiotensin aldosterone system (RAAS)-blockers, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), but whether these are indeed independent risk factors is unknown. The cellular receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the membrane-bound angiotensin converting enzyme 2 (ACE2), as for SARS-CoV(-1). Experimental data suggest that expression of ACE2 may be increased by RAAS-blockers, raising concerns that these drugs may facilitate viral cell entry. On the other hand, ACE2 is a key counter-regulator of the RAAS, by degrading angiotensin II into angiotensin (1-7), and may thereby mediate beneficial effects in COVID-19. These considerations have raised concerns about the management of these drugs, and early comments shed vivid controversy among physicians. This review will describe the homeostatic balance between ACE-angiotensin II and ACE2-angiotensin (1-7) and summarize the pathophysiological rationale underlying the debated role of the RAAS and its modulators in the context of the pandemic. In addition, we will review available evidence investigating the impact of RAAS blockers on the course and prognosis of COVID-19 and discuss why retrospective observational studies should be interpreted with caution. These considerations highlight the importance of solid evidence-based data in order to guide physicians in the management of RAAS-interfering drugs in the general population as well as in patients with more or less severe forms of SARS-CoV-2 infection.

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Influence of inhibitors of the renin–angiotensin system on risk of acute respiratory distress syndrome in Danish hospitalized COVID-19 patients

Cited by 8 publications

References 6 publications

Genetic Association of Angiotensin-converting enzyme 2 ACE-2 (rs2285666) Polymorphism with the Susceptibility of COVID-19 Disease in Iraqi Patients

Genetic Association of Angiotensin-converting enzyme 2 ACE-2 (rs2285666) Polymorphism with the Susceptibility of COVID-19 Disease in Iraqi Patients

Drug-Disease Severity and Target-Disease Severity Interaction Networks in COVID-19 Patients

Controversial Roles of the Renin Angiotensin System and Its Modulators During the COVID-19 Pandemic

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