COVID‐19 and renin‐angiotensin system inhibition: role of angiotensin converting enzyme 2 (ACE2) ‐ Is there any scientific evidence for controversy?

Aleksova, Aneta; Ferro, Federico; Gagno, Giulia; Cappelletto, Chiara; Santon, Daniela; Rossi, Maddalena; Ippolito, Giuseppe; Zumla, Alimuddin; Beltrami, Antonio Paolo; Sinagra, Gianfranco

doi:10.1111/joim.13101

Cited by 42 publications

(41 citation statements)

References 120 publications

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“…Patients with pre-existing vascular risk factor burden such as hypertension and diabetes were likely to be treated with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Both ACEI and ARB can upregulate ACE2, facilitating the SARS-CoV-2 entry into pneumocytes, and might cause exacerbation of the underlying disease [24]. However, available clinical evidence does not confirm an association between the use of ACEI or ARB and the poor outcomes of COVID-19 [7,25,26].…”

Section: Discussionmentioning

confidence: 99%

The effect of vascular risk factor burden on the severity of COVID-19 illness, a retrospective cohort study

Pan

Liu

et al. 2020

Respir Res

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Background Patients with cardiovascular comorbidities are at high risk of poor outcome from COVID-19. However, how the burden (number) of vascular risk factors influences the risk of severe COVID-19 disease remains unresolved. Our aim was to investigate the association of severe COVID-19 illness with vascular risk factor burden. Methods We included 164 (61.8 ± 13.6 years) patients with COVID-19 in this retrospective study. We compared the difference in clinical characteristics, laboratory findings and chest computed tomography (CT) findings between patients with severe and non-severe COVID-19 illness. We evaluated the association between the number of vascular risk factors and the development of severe COVID-19 disease, using a Cox regression model. Results Sixteen (9.8%) patients had no vascular risk factors; 38 (23.2%) had 1; 58 (35.4%) had 2; 34 (20.7%) had 3; and 18 (10.9%) had ≥4 risk factors. Twenty-nine patients (17.7%) experienced severe COVID-19 disease with a median (14 [7–27] days) duration between onset to developing severe COVID-19 disease, an event rate of 4.47 per 1000-patient days (95%CI 3.10–6.43). Kaplan-Meier curves showed a gradual increase in the risk of severe COVID-19 illness (log-rank P < 0.001) stratified by the number of vascular risk factors. After adjustment for age, sex, and comorbidities as potential confounders, vascular risk factor burden remained associated with an increasing risk of severe COVID-19 illness. Conclusions Patients with increasing vascular risk factor burden have an increasing risk of severe COVID-19 disease, and this population might benefit from specific COVID-19 prevention (e.g., self-isolation) and early hospital treatment measures.

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Section: Discussionmentioning

confidence: 99%

The effect of vascular risk factor burden on the severity of COVID-19 illness, a retrospective cohort study

Pan

Liu

et al. 2020

Respir Res

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“…There are some contradictory results in such reports about the effect of such drugs on predisposition to COVID-19. 75 , 76 Many of the HPB suppressors affect ACE2 gene expression in a tissue-specific manner. 77 − 79 To the best of our knowledge, no experimental result has been published about the effect of ACE2-specific drugs on the affinity of ACE2 for S1 of SARS-CoV-2.…”

Section: Resultsmentioning

confidence: 99%

Studying the Effects of ACE2 Mutations on the Stability, Dynamics, and Dissociation Process of SARS-CoV-2 S1/hACE2 Complexes

Hadi-Alijanvand

Rouhani

2020

J. Proteome Res.

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A highly infectious coronavirus, SARS-CoV-2, has spread in many countries. This virus recognizes its receptor, angiotensin-converting enzyme 2 (ACE2), using the receptor binding domain of its spike protein subunit S1. Many missense mutations are reported in various human populations for the ACE2 gene. In the current study, we predict the affinity of many ACE2 variants for binding to S1 protein using different computational approaches. The dissociation process of S1 from some variants of ACE2 is studied in the current work by molecular dynamics approaches. We study the relation between structural dynamics of ACE2 in closed and open states and its affinity for S1 protein of SARS-CoV-2.

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“…It has been reported that the Spike (S) protein of SARS-CoV-2 binds with high a nity to human ACE2, and before SARS-CoV-2's entry into the cells [18][19][20], the S protein is subjected to a priming process via serine protease TMPRSS2 in order to permit the attachment of viral particles to ACE2 and thus on cell surface [21,22]. Therefore, SARS-CoV-2 can directly attack cardiac muscle cells through this pathway [23][24][25]. This entry mechanism is con rmed by the fact that TMPRSS2 inhibition or TMPRSS2-KO mice show both decreased, though not abolished, S protein priming, and reduced viral entry, spread, as well as, in ammatory chemokine and cytokine release [21].…”

Section: Discussionmentioning

confidence: 99%

A nomogramic model based on clinical and laboratory parameters at admission for predicting the survival of COVID-19 patients

Wang

Huang

et al. 2020

Preprint

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Background and AimCOVID-19 has become a major global threat. The present study aimed to develop a nomogram model to predict the survival of COVID-19 patients based on their clinical and laboratory data at admission.MethodsCOVID-19 patients who were admitted at Hankou Hospital and Huoshenshan Hospital in Wuhan, China from January 12, 2020 to March 20, 2020, whose outcome during the hospitalization was known, were retrospectively reviewed. The categorical variables were compared using Pearson’s χ2-test or Fisher’s exact test, and continuous variables were analyzed using Student’s t-test or Mann Whitney U-test, as appropriate. Then, variables with a P-value of ≤0.1 were included in the log-binomial model, and merely these independent risk factors were used to establish the nomogram model. The discrimination of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), and internally verified using the Bootstrap method.ResultsA total of 262 patients (134 surviving and 128 non-surviving patients) were included in the analysis. Seven variables, which included age (relative risk [RR]: 0.905, 95% confidence interval [CI]: 0.868-0.944; P<0.001), chronic heart disease (CHD, RR: 0.045, 95% CI: 0.0097-0.205; P<0.001, the percentage of lymphocytes (Lym%, RR: 1.125, 95% CI: 1.041-1.216; P=0.0029), platelets (RR: 1.008, 95% CI: 1.003-1.012; P=0.001), C-reaction protein (RR: 0.982, 95% CI: 0.973-0.991; P<0.001), lactate dehydrogenase (LDH, RR: 0.993, 95% CI: 0.990-0.997; P<0.001) and D-dimer (RR: 0.734, 95% CI: 0.617-0.879; P<0.001), were identified as the independent risk factors. The nomogram model based on these factors exhibited a good discrimination, with an AUC of 0.948 (95% CI: 0.923-0.973).ConclusionA nomogram based on age, CHD, Lym%, platelets, C-reaction protein, LDH and D-dimer was established to accurately predict the prognosis of COVID-19 patients. This can be used as an alerting tool for clinicians to take early intervention measures, when necessary.

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COVID‐19 and renin‐angiotensin system inhibition: role of angiotensin converting enzyme 2 (ACE2) ‐ Is there any scientific evidence for controversy?

Cited by 42 publications

References 120 publications

The effect of vascular risk factor burden on the severity of COVID-19 illness, a retrospective cohort study

The effect of vascular risk factor burden on the severity of COVID-19 illness, a retrospective cohort study

Studying the Effects of ACE2 Mutations on the Stability, Dynamics, and Dissociation Process of SARS-CoV-2 S1/hACE2 Complexes

A nomogramic model based on clinical and laboratory parameters at admission for predicting the survival of COVID-19 patients

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