ACE-inhibitors and Angiotensin-2 Receptor Blockers are not associated with severe SARS-COVID19 infection in a multi-site UK acute Hospital Trust

Bean, Daniel; Kraljević, Željko; Searle, Thomas; Bendayan, Rebecca; Pickles, Andrew; Folarin, Amos; Roguski, Łukasz; Noor, Kawsar; Shek, Anthony; Zakeri, Rosita; Shah, Ajay M.; Teo, James; Dobson, Richard

doi:10.1101/2020.04.07.20056788

Cited by 112 publications

(138 citation statements)

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“…et al found a slightly lower rate of severe outcomes which included admission to the intensive care unit, the use of noninvasive or invasive mechanical ventilation, or death in patients on ACEI/ARB (24.8%) versus no ACEI/ARB (24.9%). [12,13,15,16,19,20,[23][24][25][26][27]. (Table 2) On the contrary, Guo [13,23].…”

Section: Resultsmentioning

confidence: 99%

“…Further, abstracts of 98 articles were read and subsequently, the full text of 41 articles were reviewed. Of these, sixteen articles were shortlisted which compared the clinical and/or mortality outcomes of COVID-19 patients on ACEI or ARB with non-users [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Finally, these sixteen studies were included for review and out of these, nine and five studies were included in the meta-analysis of mortality and severity outcomes in COVID-19 patients on ACEI/ARB, respectively.…”

Section: Resultsmentioning

confidence: 99%

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A systematic review and meta-analysis to evaluate the clinical outcomes in COVID -19 patients on angiotensin converting enzyme inhibitors or angiotensin receptor blockers

Grover

Oberoi

2020

Preprint

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Introduction: Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor upregulation which raised concerns regarding ACEI and ARB use in COVID-19 patients. However, many medical professional societies recommended their continued use given the paucity of clinical evidence but there is need for an updated systematic review of latest clinical studies. Methods:A search was conducted on PubMed, Google Scholar, EMBASE and various preprint servers for studies comparing clinical outcomes and mortality in COVID-19 patients on ACEI and/or ARB and a meta-analysis was performed. Results: A total of sixteen studies were included for review and meta-analysis. There were conflicting findings reported in several studies as Meng J. et al, Liu Y. et al, Feng Y. et al, Zhang P. et al, Mancia G. et al and Reynolds H.R. et al reported that patients on ACE inhibitors/ARB had lower rates of severe outcomes whereas Richardson S. et al reported higher rates of invasive ventilation and intensive care unit (ICU) admissions in patients on ACE inhibitors/ARB as compared to non-users. Similarly, there were conflicting results in the rate of mortality reported in the various studies. Meng J. et al, Li J. et al, Zhang P. et al, Yang G. et al, Zeng Z. et al and Andrew Ip et al reported lower rates of mortality in ACE inhibitors/ARB users versus non-users whereas Richardson S. et al and Guo T. et al reported higher rates of mortality.In a pooled analysis of 9 studies, there was a statistically significant reduction (OR = 0.86, 95% CI = 0.75-0.99, I 2 = 53.25, p value = 0.03) in the odds of death in those on ACEI/ARB as compared to patients not on ACEI/ARB. In a pooled analysis of five studies, there was a statistically nonsignificant reduction (OR = 0.90, 95% CI: 0.63-1.23, I 2 =70.36) in the odds of developing severe disease in patients on ACEI/ARB versus non-users.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A systematic review and meta-analysis to evaluate the clinical outcomes in COVID -19 patients on angiotensin converting enzyme inhibitors or angiotensin receptor blockers

Grover

Oberoi

2020

Preprint

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“…Side effects of RAAS manipulation are understandably a cause for concern, specifically hypotension and acute kidney injury in the setting of acute illness. The most severe risks of ARBs [111,112] Finally, in addition to the inhibitory effects on AT1R, a pre-print publication from Iran [113] identified losartan as a potential candidate treatment based on molecular docking and dynamic simulation. In addition to the effects on angiotensin homeostasis, therefore, losartan may directly inhibit the viral macrodomain and cell cycle.…”

Section: Ace2 Binding Viral Infection Sars-covmentioning

confidence: 99%

Understanding the renin–angiotensin–aldosterone–SARS-CoV axis: a comprehensive review

et al. 2020

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ImportanceCoronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic with significant morbidity and mortality since first appearing in Wuhan, China, in late 2019. As many countries are grappling with the onset of their epidemics, pharmacotherapeutics remain lacking. The window of opportunity to mitigate downstream morbidity and mortality is narrow but remains open. The renin–angiotensin–aldosterone system (RAAS) is crucial to the homeostasis of both the cardiovascular and respiratory systems. Importantly, SARS-CoV-2 utilises and interrupts this pathway directly, which could be described as the renin–angiotensin–aldosterone–SARS-CoV (RAAS–SCoV) axis. There exists significant controversy and confusion surrounding how anti-hypertensive agents might function along this pathway. This review explores the current state of knowledge regarding the RAAS–SCoV axis (informed by prior studies of SARS-CoV), how this relates to our currently evolving pandemic, and how these insights might guide our next steps in an evidence-based manner.ObservationsThis review discusses the role of the RAAS–SCoV axis in acute lung injury and the effects, risks and benefits of pharmacological modification of this axis. There may be an opportunity to leverage the different aspects of RAAS inhibitors to mitigate indirect viral-induced lung injury. Concerns have been raised that such modulation might exacerbate the disease. While relevant preclinical, experimental models to date favour a protective effect of RAAS–SCoV axis inhibition on both lung injury and survival, clinical data related to the role of RAAS modulation in the setting of SARS-CoV-2 remain limited.ConclusionProposed interventions for SARS-CoV-2 predominantly focus on viral microbiology and aim to inhibit viral cellular injury. While these therapies are promising, immediate use may not be feasible, and the time window of their efficacy remains a major unanswered question. An alternative approach is the modulation of the specific downstream pathophysiological effects caused by the virus that lead to morbidity and mortality. We propose a preponderance of evidence that supports clinical equipoise regarding the efficacy of RAAS-based interventions, and the imminent need for a multisite randomised controlled clinical trial to evaluate the inhibition of the RAAS–SCoV axis on acute lung injury in COVID-19.

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“…The study cohort was defined as all adult inpatients testing positive for SARS-Cov2 by reverse transcription polymerase chain reaction (RT-PCR) between 1 st March to 5 st April 2020 at a multi-site acute NHS hospital in South East London (UK Starting from our previous model 26 , further supervised training improved detection of annotations and meta-annotations such as experiencer (is the concept annotated experienced by the patient or other), negation (is the concept annotated negated or not) and temporality (is the concept annotated in the past or present) with MedCATTrainer. Meta-annotations for hypothetical, historical and experiencer were merged into "Irrelevant" allowing us to exclude any mentions of a concept that do not directly relate to the patient currently.…”

Section: Patientsmentioning

confidence: 99%

Evaluation and Improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study

Carr

Bendayan

Bean

et al. 2020

Preprint

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ACE-inhibitors and Angiotensin-2 Receptor Blockers are not associated with severe SARS-COVID19 infection in a multi-site UK acute Hospital Trust

Cited by 112 publications

References 25 publications

A systematic review and meta-analysis to evaluate the clinical outcomes in COVID -19 patients on angiotensin converting enzyme inhibitors or angiotensin receptor blockers

A systematic review and meta-analysis to evaluate the clinical outcomes in COVID -19 patients on angiotensin converting enzyme inhibitors or angiotensin receptor blockers

Understanding the renin–angiotensin–aldosterone–SARS-CoV axis: a comprehensive review

Evaluation and Improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study

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