Angiotensin‐converting enzyme 2 in severe acute respiratory syndrome coronavirus and SARS‐CoV‐2: A double‐edged sword?

Yan, Tiantian; Xiao, Rong; Lin, Guoan

doi:10.1096/fj.202000782

Cited by 94 publications

(118 citation statements)

References 51 publications

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“…On the other hand, several studies suggest that ACE2 has an anti-inflammatory and protective effect, especially on the respiratory system, by changing angiotensin II to angiotensin (1-7). In this view, the administration of ACEIs/ARBs could help the respiratory system to respond more efficiently to the infection with SARS-CoV2 [19].…”

Section: Discussionmentioning

confidence: 99%

Angiotensin enzyme inhibitors and angiotensin receptor blockers as protective factors in COVID-19 mortality: a retrospective cohort study

et al. 2020

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Targeting the renin-angiotensin system is proposed to affect mortality due to coronavirus disease 2019 (COVID-19). We aimed to compare the mortality rates in COVID-19 patients who received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) and those who did not. In this retrospective cohort study, mortality was considered as the main outcome measure. All underlying diseases were assessed by the chronic use of medications related to each condition. We defined two main groups based on the ACEIs/ARBs administration. A logistic regression model was designed to define independent predictors of mortality as well as a Cox regression analysis. In total, 2553 patients were included in this study. The mortality frequency was higher in patients with a history of underlying diseases (22.4% vs 12.7%, P value < 0.001). The mortality rate in patients who received ACEIs/ARBs were higher than non-receivers (29.3% vs. 19.5%, P value = 0.013, OR = 1.3, 95% CI 1.1, 1.7) in the univariate analysis. However, the use of ACEIs/ARBs was a protective factor against mortality in the model when adjusted for underlying conditions, length of stay, age, gender, and ICU admission (P value < 0.001, OR = 0.5, 95% CI 0.3, 0.7). The Kaplan-Meier curve showed an overall survival of approximately 85.7% after a 120-day follow-up. ACEIs/ARBs are protective factors against mortality in COVID-19 patients with HTN, and these agents can be considered potential therapeutic options in this disease. The survival probability is higher in ACEIs/ ARBs receivers than non-receivers.

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Section: Discussionmentioning

confidence: 99%

Angiotensin enzyme inhibitors and angiotensin receptor blockers as protective factors in COVID-19 mortality: a retrospective cohort study

et al. 2020

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“…The ACE2 receptor is expressed in the type II pneumocytes of the lungs and also in other tissues, including the heart, tubular epithelial cells in kidneys, testis, adipose tissue, and the enterocytes in the gastrointestinal tract and vascular endothelial cells ( 119 ). A recent study evaluated ACE2 expression in older men and women with heart failure and found in two independent cohorts that circulating plasma concentrations of ACE2 were higher in men than in women ( 120 ).…”

Section: Immune Responsementioning

confidence: 99%

What’s Sex Got to Do With COVID-19? Gender-Based Differences in the Host Immune Response to Coronaviruses

et al. 2020

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The novel severe acute respiratory syndrome coronavirus 2, the cause of the coronavirus disease 2019 (COVID-19) pandemic, has ravaged the world, with over 22 million total cases and over 770,000 deaths worldwide as of August 18, 2020. While the elderly are most severely affected, implicating an age bias, a striking factor in the demographics of this deadly disease is the gender bias, with higher numbers of cases, greater disease severity, and higher death rates among men than women across the lifespan. While pre-existing comorbidities and social, behavioral, and lifestyle factors contribute to this bias, biological factors underlying the host immune response may be crucial contributors. Women mount stronger immune responses to infections and vaccinations and outlive men. Sex-based biological factors underlying the immune response are therefore important determinants of susceptibility to infections, disease outcomes, and mortality. Despite this, gender is a profoundly understudied and often overlooked variable in research related to the immune response and infectious diseases, and it is largely ignored in drug and vaccine clinical trials. Understanding these factors will not only help better understand the pathogenesis of COVID-19, but it will also guide the design of effective therapies and vaccine strategies for gender-based personalized medicine. This review focuses on sex-based differences in genes, sex hormones, and the microbiome underlying the host immune response and their relevance to infections with a focus on coronaviruses.

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“…The unique SARS-CoV-2 characteristics and its unprecedented mechanisms of actions challenge the precise description of its mechanisms of actions and pathogenicity [10][11][12][13][14][15]. The only aspect of SARS-CoV-2 that has demonstrated undisputed characterization is its cell entry, which has shown to be dependent on angiotensinconverting enzyme-2 (ACE2) receptor and transmembrane serine protease 2 (TMPRSS2).…”

Section: Introductionmentioning

confidence: 99%

Repurposing existing drugs for COVID-19: an endocrinology perspective

Cadegiani

2020

BMC Endocr Disord

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Background Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. Main text While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. Conclusion While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.

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Angiotensin‐converting enzyme 2 in severe acute respiratory syndrome coronavirus and SARS‐CoV‐2: A double‐edged sword?

Cited by 94 publications

References 51 publications

Angiotensin enzyme inhibitors and angiotensin receptor blockers as protective factors in COVID-19 mortality: a retrospective cohort study

Angiotensin enzyme inhibitors and angiotensin receptor blockers as protective factors in COVID-19 mortality: a retrospective cohort study

What’s Sex Got to Do With COVID-19? Gender-Based Differences in the Host Immune Response to Coronaviruses

Repurposing existing drugs for COVID-19: an endocrinology perspective

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