Evidence map›Paper›PMID 32708430›Full record

ReviewAntioxidants (Basel, Switzerland)2020

Genetic Polymorphisms Complicate COVID-19 Therapy: Pivotal Role of HO-1 in Cytokine Storm.

Eddie W Fakhouri, Stephen J Peterson, Janish Kothari, Ragin Alex, Joseph I Shapiro, Nader G Abraham

Open access · goldAbstract readReview
In one paragraph

Review in Antioxidants (Basel, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 7% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Role of Cytochrome P450 2C9 in COVID-19 Treatment: Current Status and Future Directions.European journal of drug metabolism and pharmacokinetics · 2023
    Review
  7. Article
  8. Heme, Heme Oxygenase-1, Statins, and SARS-CoV-2.Antioxidants (Basel, Switzerland) · 2023
    Article
  9. Effects of PM2.5 Exposure on the ACE/ACE2 Pathway: Possible Implication in COVID-19 Pandemic.International journal of environmental research and public health · 2023
    Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. The spike protein of SARS-CoV-2 induces heme oxygenase-1: Pathophysiologic implications.Biochimica et biophysica acta. Molecular basis of disease · 2022
    Article
  17. Review
  18. Article
  19. Review
  20. Article
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

6 authors at 3 institutions in 1 country.

Eddie W FakhouriNew York Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY 11215, USA.ORCID 0000-0002-2066-3632
Stephen J PetersonNew York Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY 11215, USA.
Janish KothariNew York Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY 11215, USA.
Ragin AlexDepartment of Pharmacology, New York Medical College, Valhalla, NY 10595, USA.
Joseph I ShapiroJoan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA.
Nader G AbrahamDepartment of Pharmacology, New York Medical College, Valhalla, NY 10595, USA.
NewYork–Presbyterian Brooklyn Methodist Hospital · USNew York Medical College · USMarshall University · US

Funding

Adipocyte EET-PGC1alpha-HO-1 in Obesity-driven HypertensionR56HL139561 · NHLBI · NEW YORK MEDICAL COLLEGE · PI ABRAHAM, NADER G. · 2018 to 2018
$503k
NHLBI NIH HHS R56 HL139561
6 · The paper itself

Abstract

Coronaviruses are very large RNA viruses that originate in animal reservoirs and include severe acute respiratory distress syndrome (SARS) and Middle East respiratory syndrome (MERS) and other inconsequential coronaviruses from human reservoirs like the common cold. SARS-CoV-2, the virus that causes COVID-19 and is believed to originate from bat, quickly spread into a global pandemic. This RNA virus has a special affinity for porphyrins. It invades the cell at the angiotensin converting enzyme-2 (ACE-2) receptor and binds to hemoproteins, resulting in a severe systemic inflammatory response, particularly in high ACE-2 organs like the lungs, heart, and kidney, resulting in systemic disease. The inflammatory response manifested by increased cytokine levels and reactive oxygen species results in inhibition of heme oxygenase (HO-1), with a subsequent loss of cytoprotection. This has been seen in other viral illness like human immunodeficiency virus (HIV), Ebola, and SARS/MERS. There are a number of medications that have been tried with some showing early clinical promise. This illness disproportionately affects patients with obesity, a chronic inflammatory disease with a baseline excess of cytokines. The majority of the medications used in the treatment of COVID-19 are metabolized by cytochrome P450 (CYP) enzymes, primarily CYP2D6. This is further complicated by genetic polymorphisms of CYP2D6, HO-1, ACE, and ACE-2. There is a potential role for HO-1 upregulation to treat/prevent cytokine storm. Current therapy must focus on antivirals and heme oxygenase upregulation. Vaccine development will be the only magic bullet.

Indexed as

ACE-2ACE-2RCOVID-19CYP2D6Cytochrome P450cytokine stormGenetic polymorphismsHO-1mitochondrial dysfunctionSARS-CoV-2white adipose tissue

Identifiers

PMID32708430
PMCPMC7402116
OpenAlexW3042268828

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.