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Open accessJournal ArticleDOI: 10.1016/J.MEEGID.2021.104801

Impact of I/D polymorphism of angiotensin-converting enzyme 1 (ACE1) gene on the severity of COVID-19 patients.

04 Mar 2021-Infection, Genetics and Evolution (Elsevier)-Vol. 91, pp 104801-104801
Abstract: Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has first emerged from China in December 2019 and causes coronavirus induced disease 19 (COVID-19). Since then researchers worldwide have been struggling to detect the possible pathogenesis of this disease. COVID-19 showed a wide range of clinical behavior from asymptomatic to severe acute respiratory disease syndrome. However, the etiology of susceptibility to severe lung injury is not yet fully understood. Angiotensin-converting enzyme1 (ACE1) convert angiotensin I into Angiotensin II that was further metabolized by ACE 2 (ACE2). The binding ACE2 receptor to SARS-CoV-2 facilitate its enter into the host cell. The interaction and imbalance between ACE1 and ACE2 play a crucial role in the pathogenesis of lung injury. Thus, the aim of this study was to investigate the association of ACE1 I/D polymorphism with severity of Covid-19. The study included RT-PCR confirmed 269 cases of Covid-19. All cases were genotyped for ACE1 I/D polymorphism using polymerase chain reaction and followed by statistical analysis (SPSS, version 15.0). We found that ACE1 DD genotype, frequency of D allele, older age (≥46 years), unmarried status, and presence of diabetes and hypertension were significantly higher in severe COVID-19 patient. ACE1 ID genotype was significantly independently associated with high socio-economic COVID-19 patients (OR: 2.48, 95% CI: 1.331-4.609). These data suggest that the ACE1 genotype may impact the incidence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.

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Topics: Angiotensin II (62%), Lung injury (57%), Angiotensin-converting enzyme (54%) ... read more
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11 results found


Open accessJournal ArticleDOI: 10.1186/S40246-021-00356-X
25 Aug 2021-Human Genomics
Abstract: Over the past year and a half, SARS-CoV-2, the etiological agent of the COVID-19 pandemic, led to a total of almost 200 million cases, causing more than 4 million of deaths globally (Johns Hopkins University, CSSE) [1]. While we are facing rising daily hospitalizations (https://ourworldindata.org/covid-hospitalizations, accessed on July 31, 2021) [2], attributable to novel emerging variants of the virus [3, 4], we also observe a decrease in both hospitalizations due to severe forms of the disease and deaths in several parts of the world, thanks to the launch of massive vaccination campaigns [2]. To date, 4 billion vaccine doses have been administered [1]. Despite of the efforts of global organizations to face this health emergency, including the COVAX plan which aims to achieve the vaccination coverage in developing countries [5], we are still far from reaching the desired results and the end of this pandemic especially in emerging countries. As we discussed in our recent review on “COVID-19 one year into the pandemic: from genetics and genomics to therapy, vaccination, and policy” [6], vaccines represent one of the most valuable aid to halt the SARS-CoV-2 spread. The emergence of novel variants of concern (VOC) aroused concern among the scientific community, since they are associated with a rise of viral transmissibility [7], and with a reduction in the therapeutic response to both monoclonal antibodies and antibody activity in vaccinated individuals [8]. Nevertheless, results arising from the analysis of vaccine coverage against the emerging Delta variant are promising [9]. It is known that the mRNA vaccines, both BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna), can potentially be implemented to match the need of a response against SARS-CoV-2 mutations. For this reason, it is crucial to increase the genomic surveillance in the different departments of public health systems all over the world [10]. In the same publication [6], we arrive at the conclusion that not only the virus, but significantly also the synergic relationship with the host represents the core of the understanding of mechanisms underpinning the infectious cycle, transmission, resistance and susceptibility to SARS-CoV-2. In addition, we also expressed concern about effects that environmental pollution may exert on susceptibility to SARS-CoV-2 by diminishing immune responses. We are aware that increased knowledge of this aspects is fundamental to unveil the clinical course and a more targeted therapeutical approach for patients affected by COVID-19. In this editorial, we focus on genetic and genomics susceptibility factors to COVID-19, and we aim to summarize the current knowledge in the literature providing an updated, easy to consult and constantly revised tool, through an update of Table 2 from our recent review [6].

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Topics: Environmental pollution (53%)

4 Citations


Open accessJournal ArticleDOI: 10.1016/J.CCA.2021.04.024
Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread from China in 2019/2020 to all continents. Significant geographical and ethnic differences were described, and host genetic background seems to be important for the resistance to and mortality of COVID-19. Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism (rs4646994) is one of the candidates with the potential to affect infection symptoms and mortality. Methods In our study, we successfully genotyped 408 SARS-CoV-2-positive COVID-19 survivors (163 asymptomatic and 245 symptomatic) and compared them with a population-based DNA bank of 2,559 subjects. Results The frequency of ACE I/I homozygotes was significantly increased in COVID-19 patients compared with that in controls (26.2% vs. 21.2%; P = 0.02; OR [95% CI] = 1.55 [1.17–2.05]. Importantly, however, the difference was driven just by the symptomatic subjects (29.0% vs. 21.2% of the I/I homozygotes; P = 0.002; OR [95% CI] = 1.78 [1.22–2.60]). The genotype distribution of the ACE genotypes was almost identical in population controls and asymptomatic SARS-CoV-2-positive patients (P = 0.76). Conclusions We conclude that ACE I/D polymorphism could have the potential to predict the severity of COVID-19, with I/I homozygotes being at increased risk of symptomatic COVID-19.

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Topics: Population (53%), Asymptomatic (50%)

2 Citations


Open accessJournal ArticleDOI: 10.1016/J.JAIM.2021.06.003
Abstract: Recent reports on COVID-19 suggest, the susceptibility to COVID-19 and its progression have a genetic predisposition. Majorly associated genetic variants are found in human leukocyte antigen (HLA), angiotensin convertase enzyme (ACE; rs1799752: ACE2; rs73635825), transmembrane protease serine 2 (TMPRSS-2; rs12329760) genes. Identifying highly prone population having these variants is imperative for determining COVID-19 therapeutic strategy. Ayurveda (Indian traditional system of medicine) concept of Prakriti holds potential to predict genomic and phenotypic variations. Reported work on Prakriti correlates HLA-DR alleles with three broad phenotypes (Tridosha) described in Ayurveda (AyuGenomics). This is suggestive of differences in immune responses in individuals with specific constitutions. Therefore, the reported studies provide clues for clinically relevant hypotheses to be tested in systematic studies. The proposed approach of Ayurveda based phenotype screening may offer a way ahead to design customized strategies for management of COVID-19 based on differences in Prakriti, immune response and drug response. However, this needs clinical evaluation of the relation between Prakriti and genetic or phenotypic variants in COVID-19 prone and resistant populations.

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Topics: Genetic predisposition (55%), Population (51%)

2 Citations



Open accessJournal ArticleDOI: 10.1016/J.IMBIO.2021.152130
17 Aug 2021-Immunobiology
Abstract: In this review, we highlight the interaction of SARS-CoV-2 virus and host genomes, reporting the current studies on the sequence analysis of SARS-CoV-2 isolates and host genomes from diverse world populations. The main genetic variants that are present in both the virus and host genomes were particularly focused on the ACE2 and TMPRSS2 genes, and their impact on the patients' susceptibility to the virus infection and severity of the disease. Finally, the interaction of the virus and host non-coding RNAs is described in relation to their regulatory roles in target genes and/or signaling pathways critically associated with SARS-CoV-2 infection. Altogether, these studies provide a significant contribution to the knowledge of SARS-CoV-2 mechanisms of infection and COVID-19 pathogenesis. The described genetic variants and molecular factors involved in host/virus genome interactions have significantly contributed to defining patient risk groups, beyond those based on patients' age and comorbidities, and they are promising candidates to be potentially targeted in treatment strategies for COVID-19 and other viral infectious diseases.

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Topics: Virus (55%), Genome (54%), Gene (51%)

1 Citations


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35 results found


Open accessJournal ArticleDOI: 10.1001/JAMA.2020.2648
Zunyou Wu1, Jennifer M. McGoogan1Institutions (1)
07 Apr 2020-JAMA
Abstract: Background: Hospitalised COVID-19 patients are frequently elderly subjects with co-morbidities receiving polypharmacy, all of which are known risk factors for d

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Topics: Outbreak (56%)

10,464 Citations


Open accessJournal ArticleDOI: 10.1001/JAMA.2020.6775
26 May 2020-JAMA
Abstract: Importance There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19). Objective To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system. Design, Setting, and Participants Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates. Exposures Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission. Main Outcomes and Measures Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected. Results A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/min, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. As of April 4, 2020, for patients requiring mechanical ventilation (n = 1151, 20.2%), 38 (3.3%) were discharged alive, 282 (24.5%) died, and 831 (72.2%) remained in hospital. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1). Conclusions and Relevance This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.

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Topics: Interquartile range (55%), Respiratory virus (51%)

5,140 Citations


Open accessJournal ArticleDOI: 10.1172/JCI114844
Abstract: A polymorphism consisting of the presence or absence of a 250-bp DNA fragment was detected within the angiotensin I-converting enzyme gene (ACE) using the endothelial ACE cDNA probe. This polymorphism was used as a marker genotype in a study involving 80 healthy subjects, whose serum ACE levels were concomitantly measured. Allele frequencies were 0.6 for the shorter allele and 0.4 for the longer allele. A marked difference in serum ACE levels was observed between subjects in each of the three ACE genotype classes. Serum immunoreactive ACE concentrations were, respectively, 299.3 +/- 49, 392.6 +/- 66.8, and 494.1 +/- 88.3 micrograms/liter, for homozygotes with the longer allele (n = 14), and heterozygotes (n = 37) and homozygotes (n = 29) with the shorter allele. The insertion/deletion polymorphism accounted for 47% of the total phenotypic variance of serum ACE, showing that the ACE gene locus is the major locus that determines serum ACE concentration. Concomitant determination of the ACE genotype will improve discrimination between normal and abnormal serum ACE values by allowing comparison with a more appropriate reference interval.

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Topics: Angiotensin-converting enzyme (62%), Allele frequency (56%), Genotype (53%) ... read more

3,641 Citations


Open accessJournal ArticleDOI: 10.1016/J.IJID.2020.03.017
Jing Yang1, Ya Zheng1, Xi Gou1, Ke Pu1  +6 moreInstitutions (1)
Abstract: Background: An outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan, China; the epidemic is more widespread than initially estimated, with cases now confirmed in multiple countries.

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Topics: Outbreak (55%), Betacoronavirus (55%)

2,149 Citations


Open accessJournal ArticleDOI: 10.1002/JMV.25678
Abstract: Since December 2019, a total of 41 cases of pneumonia of unknown etiology have been confirmed in Wuhan city, Hubei Province, China. Wuhan city is a major transportation hub with a population of more than 11 million people. Most of the patients visited a local fish and wild animal market last month. At a national press conference held today, Dr. Jianguo Xu, an academician of the Chinese Academy of Engineering, who led a scientific team announced that a new-type coronavirus, tentatively named by World Health Organization as the 2019-new coronavirus (2019-nCoV), had caused this outbreak (1).

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1,836 Citations


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202111