Dataset Information

Angiotensin converting enzyme genotypes and mortality from COVID-19: An ecological study.

ABSTRACT:

Background

Angiotensin converting enzyme (ACE) genotypes are known to be associated with development of acute respiratory distress syndrome (ARDS) and resultant mortality. In the present study, we examined the association between distribution frequency of ACE genotypes and COVID-19 mortality.

Methods

We undertook an ecological study to examine the association between ACE genotypes and COVID-19 mortality across 25 countries to represent different geographical regions of the world. The population frequencies of ACE genotypes were drawn from previously published reports and data on COVID-19-related mortality were extracted from 'Worldometer'. Multivariable analyses were also undertaken adjusting for age (median age), sex (percentage of females) and the number of COVID-19 tests undertaken. Associations between genotypes deletion/deletion (DD) and insertion/insertion (II) prevalence and COVID-19-related mortality (per million people per day since the first diagnosed case) were evaluated.

Results

The frequency of II genotype is highest in east Asian countries and lower among the European and African countries. An inverse geographical distribution frequency was noted for DD genotype. Increasing II genotype frequency was significantly associated with decreased COVID-19 mortality rates (adjusted incident rate ratio [IRR] 0.3, 95% confidence interval [CI]: 0.002-0.7, p?=?0.03). However, no association was found between DD genotype frequency and COVID-19 mortality rates (adjusted IRR 4.3, 95% CI: 0.5-41.2, p?=?0.2).

Conclusions

Distribution frequency of ACE insertion/insertion (II) genotype may have a significant influence on COVID-19 mortality. This information has potential utility for resource planning at a systemic level, as well as for clinical management.

SUBMITTER: Aung AK

PROVIDER: S-EPMC7666537 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Angiotensin converting enzyme genotypes and mortality from COVID-19: An ecological study.

Aung Ar K AK Aitken Tess T Teh Bing M BM Yu Christiaan C Ofori-Asenso Richard R Chin Ken L KL Liew Danny D

The Journal of infection 20201114 6

<h4>Background</h4>Angiotensin converting enzyme (ACE) genotypes are known to be associated with development of acute respiratory distress syndrome (ARDS) and resultant mortality. In the present study, we examined the association between distribution frequency of ACE genotypes and COVID-19 mortality.<h4>Methods</h4>We undertook an ecological study to examine the association between ACE genotypes and COVID-19 mortality across 25 countries to represent different geographical regions of the world. ...[more]

PMID: 33197472

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Project description:ImportanceIt has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 (COVID-19) and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2.ObjectiveTo examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19.Design, setting, and participantsTo examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020.ExposuresACEI/ARB use was defined as prescription fillings 6 months prior to the index date.Main outcomes and measuresIn the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis.ResultsIn the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age- and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]).Conclusions and relevancePrior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.

Project description:The ongoing COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Age, smoking, obesity, and chronic diseases such as cardiovascular disease and diabetes have been described as risk factors for severe complications and mortality in COVID-19. Obesity and diabetes are usually associated with dysregulated lipid synthesis and clearance, which can initiate or aggravate pulmonary inflammation and injury. It has been shown that for viral entry into the host cell, SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptors present on the cells. We aimed to characterize how SARS-CoV-2 dysregulates lipid metabolism pathways in the host and the effect of dysregulated lipogenesis on the regulation of ACE2, specifically in obesity. In our study, through the re-analysis of publicly available transcriptomic data, we first found that lung epithelial cells infected with SARS-CoV-2 showed upregulation of genes associated with lipid metabolism, including the SOC3 gene, which is involved in the regulation of inflammation and inhibition of leptin signaling. This is of interest as viruses may hijack host lipid metabolism to allow the completion of their viral replication cycles. Furthermore, a dataset using a mouse model of diet-induced obesity showed a significant increase in Ace2 expression in the lungs, which negatively correlated with the expression of genes that code for sterol response element-binding proteins 1 and 2 (SREBP). Suppression of Srebp1 showed a significant increase in Ace2 expression in the lung. Moreover, ACE2 expression in human subcutaneous adipose tissue can be regulated through changes in diet. Validation of the in silico data revealed a higher expression of ACE2, TMPRSS2 and SREBP1 in vitro in lung epithelial cells from obese subjects compared to non-obese subjects. To our knowledge this is the first study to show upregulation of ACE2 and TMPRSS2 in obesity. In silico and in vitro results suggest that the dysregulated lipogenesis and the subsequently high ACE2 expression in obese patients might be the mechanism underlying the increased risk for severe complications in those patients when infected by SARS-CoV-2.

Dataset Information

Angiotensin converting enzyme genotypes and mortality from COVID-19: An ecological study.

Background

Methods

Results

Conclusions

Publications

Angiotensin converting enzyme genotypes and mortality from COVID-19: An ecological study.

Similar Datasets

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