Evidence map›Paper›PMID 34708878›Full record

ArticleJournal of medical virology2022

Angiotensin-converting-enzyme insertion/deletion polymorphism, ACE activity, and COVID-19: A rather controversial hypothesis. A case-control study.

Anna Papadopoulou, Paraskevi C Fragkou, Eirini Maratou, Dimitra Dimopoulou, Antonis Kominakis, Ioanna Kokkinopoulou, Christos Kroupis, Athina Nikolaidou, Georgios Antonakos, Vasiliki Papaevangelou and 6 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medical virology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 4 pooled it
1.2field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 4 syntheses or guidelines pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Frontiers in genetics · 2022
    Pooled it
  5. Article
  6. Review
  7. Article
  8. Article
  9. Correlation ofPharmacogenomics · 2024
    Observational
  10. ACE2, ACE, DPPIV, PREP and CAT L enzymatic activities in COVID-19: imbalance of ACE2/ACE ratio and potential RAAS dysregulation in severe cases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Article
  11. Article
  12. The association ofEXCLI journal · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Anna PapadopoulouDepartment of Clinical Biochemistry, University General Hospital "ATTIKO," National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Paraskevi C FragkouFourth Department of Internal Medicine, University General Hospital "ATTIKO," National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Eirini MaratouDepartment of Clinical Biochemistry, University General Hospital "ATTIKO," National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Dimitra DimopoulouThird Department of Pediatrics, University General Hospital "ATTIKO," National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Antonis KominakisDepartment of Animal Science and Aquaculture, Agricultural University of Athens, Athens, Greece.
Ioanna KokkinopoulouDepartment of Clinical Biochemistry, University General Hospital "ATTIKO," National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Christos KroupisDepartment of Clinical Biochemistry, University General Hospital "ATTIKO," National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Athina NikolaidouDepartment of Clinical Biochemistry, University General Hospital "ATTIKO," National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Georgios AntonakosDepartment of Clinical Biochemistry, University General Hospital "ATTIKO," National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Vasiliki PapaevangelouThird Department of Pediatrics, University General Hospital "ATTIKO," National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Apostolos ArmaganidisSecond Department of Critical Care, "Attikon" University Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Argirios TsantesLaboratory of Haematology and Blood Bank Unit, "Attiko" Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
Eftychia PolyzogopoulouDepartment of Emergency Medicine, "Attiko" Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
Sotirios TsiodrasFourth Department of Internal Medicine, University General Hospital "ATTIKO," National and Kapodistrian University of Athens, Medical School, Athens, Greece.ORCID 0000-0002-0463-4321
Anastasia AntoniadouFourth Department of Internal Medicine, University General Hospital "ATTIKO," National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Paraskevi MoutsatsouDepartment of Clinical Biochemistry, University General Hospital "ATTIKO," National and Kapodistrian University of Athens, Medical School, Athens, Greece.
National and Kapodistrian University of Athens · GRAgricultural University of Athens · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Accumulating data has shown a contribution of the renin-angiotensin system in COVID-19 pathogenesis. The role of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism as a risk factor in developing COVID-19 disease comes from epidemiological data and is controversially discussed. We conducted a retrospective case-control study and assessed the impact of ACE I/D genotype in COVID-19 disease prevalence and severity. In 81 COVID-19 patients explicitly characterized and 316 controls, recruited during the first wave of COVID-19 pandemic, ACE I/D genotype, and ACE activity were determined. A generalized linear model was used and Poisson regression analysis estimated the risk ratios (RRs) of alleles and genotypes for disease severity. DD patients had almost 2.0-fold increased risk (RR: 1.886, confidence limit [CL] 95%: 1.266-2.810, p = 0.0018) of developing a more severe disease when contrasted to ID and II individuals, as did D allele carriers compared to I carriers (RR: 1.372; CL 95%: 1.051-1.791; p = 0.0201). ACE activity (expressed as arbitrary units, AU/L) was lower in patients (3.62 ± 0.26) than in controls (4.65 ± 0.13) (p < 0.0001), and this reduction was observed mainly among DD patients compared to DD controls (3.97 ± 0.29 vs. 5.38 ± 0.21; p = 0.0014). Our results demonstrate that ACE DD genotype may predispose to COVID-19 increased disease severity via a mechanism associated, at least in part, with the significant fall in their ACE activity. Our findings suggest a more complex pattern of synergy between this polymorphism and ACE activity in COVID-19 patients compared to healthy individuals and set the grounds for large-scale studies assessing ACE genotype-based optimized therapies with ACE inhibitors and angiotensin receptor blockers.

Indexed as

COVID-19AllelesCase-Control StudiesHumansINDEL MutationPandemicsPeptidyl-Dipeptidase APolymorphism, GeneticRetrospective StudiesSeverity of Illness IndexACE protein, humanPeptidyl-Dipeptidase AACEACE activityACE polymorphismangiotensin converting enzymeCOVID-19SARS-CoV-2

Identifiers

PMID34708878
PMCPMC8661574
OpenAlexW3208471204

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.