Researchers at the University of Georgia in the United States have highlighted the underlying pathological mechanisms between the 3p21. 31 genetic locus and severe coronavirus disease 2019 (COVID-19).
Although 3p21. 31 is known to be a primary genetic locus involved in severe COVID-19, so far, the underlying pathological mechanisms and target genes affected have remained unknown.
Now, Kaixiong Ye and his colleagues have demonstrated that this COVID-19 threat variant is related to changed mobile blood characteristics involving monocytes, eosinophils and neutrophils, and degrees of expression of their target genes candidates CCR1 (CC 1 chemokine receptor), CCR2 and CCR3.
Researchers claim that the multiple blood characteristics known in this study, as well as their candidate genes, are intriguing and proven hypotheses to be followed in long-term studies on the role they play in COVID-19.
You must have a preprinted edition of the article on the medRxiv server, while the article is peer-reviewed.
The clinical manifestations of COVID-19 vary significantly from one individual to another, from an asymptomatic illness to flu-like symptoms, loss of smell, pneumonia, and respiratory failure.
In addition to underlying fitness problems and demographic points, such as complex age and male gender, genetic variation also influences how other people respond to the infection differently.
The first pangenomic disposition examination (GWAS) to compare COVID-19 in patients who evolved with respiratory failure in known genetic arrangements with locus 3p21. 31.
“However, the underlying causal variant, target gene, and pathological procedure are unknown,” Ye and his colleagues said.
The Phenome Scale Association Study (PheWAS) is a technique that can be used to compare associations between a genetic variant related to the disease and a wide variety of phenotypes, identifying intermediate characteristics or biomarkers involved in the causal pathway, from the genetic variant to the disease of interest.
Now, Ye and his colleagues have performed a PheWAS to the intermediate characteristics underlying the link between locus 3p21. 31 and severe COVID-19.
The team leveraged deep phenotyping data from 310,999 US Europeans in the UK Biobank and performed a PheWAS for a COVID-19 threat allele with 923 disease phenotypes, biomarkers and blood mobility traits. Candidate associations were then replicated to some other dataset.
Second, for candidate genes regulated through the COVID-19 threat variant, associations between their degrees of expression and polygenic scores (PGS) of 1,263 characteristics were evaluated in a meta-analysis of 31,684 blood samples.
PheWAS in the British biobank for the severe risk variant of COVID-19, as well as known replications in an additional knowledge set, revealed that the variant is related to altered blood characteristics.
Specifically, the variant related to a minimization in the number and percentage of monocytes, a minimization in the number and percentage of eosinophils, and an accumulation in the percentage of neutrophils.
PGS research for possible target genes of the variant yielded consistent evidence and pathways involving globular monocyte and eosinophil counts and weaker evidence of a pathway involving neutrophil counts.
Evidence also suggests basophils as a candidate pathway: the threat allele downregulates CCR3 expression, reduces its stimulation of basophil production, and thus decreases the number of basophils.
The cell-type specificity of their expression patterns also demonstrated the prospective importance of these candidate genes. CCR3 was strongly expressed and particularly in eosinophils and basophils, although it was only expressed in neutrophils; CCR2 was expressed in maximum degrees in basophils and moderate degrees in monocytes, while CCR1 was expressed in medium to high degrees in all types of granulocytes and monocytes.
The team says its haematological processes prioritized as a downstream physiopathology of a severe COVID-19 primary genetic locus.
“Our phenome-scale arrangement for the severe threat variant of COVID-19 to locus 3p21. 31 and its known candidate target genes changed the characteristics of blood cells, namely the number of monocytes, eosinophils and neutrophils, such as the likely mechanical links between the locus and severe COVID-19 genes,” the researchers write.
“These motile blood traits, together with their candidate genes, CCR1, CCR2, and CCR3, constitute compelling and testable hypotheses that require follow-up studies on their role in the pathogenesis of COVID-19,” they conclude.
medRxiv publishes initial clinical reports that are not peer-reviewed and therefore should not be considered conclusive, the consultant’s clinical practice/health-related habit or treated as established information.
Written by
Sally holds a bachelor’s degree in biomedical sciences (B. Sc. ). He specializes in reviewing and synthesizing the latest discoveries in all medical spaces covered in world-renowned, high-impact foreign medical journals, foreign press conferences, and newsletters from government agencies and regulators. At News-Medical, Sally generates news, life science articles, and interview coverage.
Use one of the following to cite this article in your essay, job, or report:
Apa
Robertson, Sally. (2020, 13 September). To eliminate changed blood cell characteristics in severe cases of COVID-19. News-Medical. Recovered on September 27, 2020 in https://www. news-medical. net/news/20200913/Shedding-gentle-on-altered-blood-cell-tracts-in-serious-COVID-19. aspx.
Mla
Robertson, Sally. ” To eliminate changes in blood cell characteristics in severe cases of COVID-19 News-Medical. September 27, 2020.
Chicago
Robertson, Sally. ” To eliminate changes in blood cell characteristics in severe cases of COVID-19. News-Medical. Https://www. news-medical. net/news/20200913/Shedding-gentle-on-altered-blood -cell-traits – in-serio-COVID-19. aspx. (accessed 27 September 2020).
Harvard
Robertson, Sally. 2020. Beware of the changed characteristics of blood cells in severe COVID-19 cases. News-Medical, see September 27, 2020, https://www. news-medical. net/news/20200913/Shedding-gentle -in-traits-of-blood cells-altered – en-serio-COVID-19. aspxArray
News-Medical. net – An AZoNetwork site
Ownership and operation through AZoNetwork, © 2000-2020