SARS-CoV-2 Infections: An ACE in the Hole and Systems Biology Studies—a Research Agenda

Bass, Jessica; Goldstein, Mark R.

doi:10.1016/j.mayocp.2020.06.044

Cited by 3 publications

(3 citation statements)

References 10 publications

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“…The explanation behind this controversy arises from the very fact that it shares the target receptor site with ACEIs and ARBs, which can cause the upregulation of ACE2 receptors ( 21 ). ACE2 is additionally the notable cellular surface receptor and a necessary entry point for SARS-CoV-2 into the target cell ( 22 , 23 ). As cardiovascular diseases and their therapy affects ACE2 levels, it plays an integral part in consideration of infectivity and outcomes of SARS-CoV-2 ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

Mortality and Severity in COVID-19 Patients on ACEIs and ARBs—A Systematic Review, Meta-Analysis, and Meta-Regression Analysis

Singh

Rathore²,

Khan³

et al. 2022

Front. Med.

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Purpose: The primary objective of this systematic review is to assess association of mortality in COVID-19 patients on Angiotensin-converting-enzyme inhibitors (ACEIs) and Angiotensin-II receptor blockers (ARBs). A secondary objective is to assess associations with higher severity of the disease in COVID-19 patients.Materials and Methods: We searched multiple COVID-19 databases (WHO, CDC, LIT-COVID) for longitudinal studies globally reporting mortality and severity published before January 18th, 2021. Meta-analyses were performed using 53 studies for mortality outcome and 43 for the severity outcome. Mantel-Haenszel odds ratios were generated to describe overall effect size using random effect models. To account for between study results variations, multivariate meta-regression was performed with preselected covariates using maximum likelihood method for both the mortality and severity models.Result: Our findings showed that the use of ACEIs/ARBs did not significantly influence either mortality (OR = 1.16 95% CI 0.94–1.44, p = 0.15, I2 = 93.2%) or severity (OR = 1.18, 95% CI 0.94–1.48, p = 0.15, I2 = 91.1%) in comparison to not being on ACEIs/ARBs in COVID-19 positive patients. Multivariate meta-regression for the mortality model demonstrated that 36% of between study variations could be explained by differences in age, gender, and proportion of heart diseases in the study samples. Multivariate meta-regression for the severity model demonstrated that 8% of between study variations could be explained by differences in age, proportion of diabetes, heart disease and study country in the study samples.Conclusion: We found no association of mortality or severity in COVID-19 patients taking ACEIs/ARBs.

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Section: Introductionmentioning

confidence: 99%

Mortality and Severity in COVID-19 Patients on ACEIs and ARBs—A Systematic Review, Meta-Analysis, and Meta-Regression Analysis

Singh

Rathore²,

Khan³

et al. 2022

Front. Med.

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“…The S protein contains two functional subunits, S1 and S2, cleaved by furin protease at the host cell [4]. The S1 subunit contains the receptor binding domain and facilitates the interactions with the host cell surface receptor, Angiotensin-converting enzyme 2 (ACE2) [5,6]. The S2 subunit, activated by the host Transmembrane Serine Protease 2, harbors necessary elements for membrane fusion [7].…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2: Possible recombination and emergence of potentially more virulent strains

et al. 2021

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COVID-19 is challenging healthcare preparedness, world economies, and livelihoods. The infection and death rates associated with this pandemic are strikingly variable in different countries. To elucidate this discrepancy, we analyzed 2431 early spread SARS-CoV-2 sequences from GISAID. We estimated continental-wise admixture proportions, assessed haplotype block estimation, and tested for the presence or absence of strains’ recombination. Herein, we identified 1010 unique missense mutations and seven different SARS-CoV-2 clusters. In samples from Asia, a small haplotype block was identified, whereas samples from Europe and North America harbored large and different haplotype blocks with nonsynonymous variants. Variant frequency and linkage disequilibrium varied among continents, especially in North America. Recombination between different strains was only observed in North American and European sequences. In addition, we structurally modelled the two most common mutations, Spike_D614G and Nsp12_P314L, which suggested that these linked mutations may enhance viral entry and replication, respectively. Overall, we propose that genomic recombination between different strains may contribute to SARS-CoV-2 virulence and COVID-19 severity and may present additional challenges for current treatment regimens and countermeasures. Furthermore, our study provides a possible explanation for the substantial second wave of COVID-19 presented with higher infection and death rates in many countries.

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“…The S protein contains two functional subunits S1 and S2 cleaved by FURIN protease at the host cell [4]. The S1 subunit contains the receptor binding domain and facilitates interactions with the host cell surface receptor, Angiotensin-converting enzyme 2 (ACE2) [5,6]. The S2 subunit, activated by the host Transmembrane Serine Protease 2, harbors necessary elements for membrane fusion [7].…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2: Proof of recombination between strains and emergence of possibly more virulent ones

Haddad

John

Mohammad

et al. 2020

Preprint

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COVID-19 is challenging healthcare preparedness, world economies, and livelihoods. The infection and death rates associated with this pandemic are strikingly variable in different countries. To elucidate this discrepancy, we analyzed 2431 early spread SARS-CoV-2 sequences from GISAID. We estimated continental-wise admixture proportions, assessed haplotype block estimation, and tested for the presence or absence of strains recombination. Herein, we identified 1010 unique missense mutations and seven different SARS-CoV-2 clusters. In samples from Asia, a small haplotype block was identified; whereas, samples from Europe and North America harbored large and different haplotype blocks with nonsynonymous variants. Variant frequency and linkage disequilibrium varied among continents, especially in North America. Recombination between different strains was only observed in North American and European sequences. Additionally, we structurally modeled the two most common mutations D614G and P314L which suggested that these linked mutations may enhance viral entry and stability. Overall, we propose that COVID-19 virulence may be more severe in Europe and North America due to coinfection with different SARS-CoV-2 strains leading to genomic recombination which might be challenging for current treatment regimens and vaccine development. Furthermore, our study provides a possible explanation for the more severe second wave of COVID-19 that many countries are currently experiencing presented as higher rates of infection and death.

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SARS-CoV-2 Infections: An ACE in the Hole and Systems Biology Studies—a Research Agenda

Cited by 3 publications

References 10 publications

Mortality and Severity in COVID-19 Patients on ACEIs and ARBs—A Systematic Review, Meta-Analysis, and Meta-Regression Analysis

Mortality and Severity in COVID-19 Patients on ACEIs and ARBs—A Systematic Review, Meta-Analysis, and Meta-Regression Analysis

SARS-CoV-2: Possible recombination and emergence of potentially more virulent strains

SARS-CoV-2: Proof of recombination between strains and emergence of possibly more virulent ones

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