Genetic mechanisms of critical illness in Covid-19 - Nature Magazine

In summary, the study found that ACE2 and TMPRSS2 are both abundant in human organoids, and that innate immune pathways are upregulated in ACE2+ cells. Innate immune pathways are also highly enriched in ACE2+ cells in intestinal, lung, and retinal organoids. Together, these findings suggest that organoids can be used as an experimental platform to explore the virus disease mechanism and for drug development.
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Tom.G
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Genetic mechanisms of critical illness in Covid-19
33 pages.
Free PDF download at:
https://www.nature.com/articles/s41586-020-03065-y_reference.pdf

"...we found evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease; transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms, and mediators of inflammatory organ damage in Covid-19. Both mechanisms may be amenable to targeted treatment with existing drugs."

Cheers,
Tom
 
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A somewhat related paper.

Single‐cell RNA sequencing analysis of SARS‐CoV‐2 entry receptors in human organoids
https://onlinelibrary.wiley.com/doi/10.1002/jcp.30054
Abstract: Coronavirus disease‐2019 (COVID‐19) is a global pandemic and caused by severe acute respiratory syndrome Coronavirus 2 (SARS‐CoV‐2), which has resulted in millions of deaths worldwide. Reports denote SARS‐CoV‐2 uses angiotensin‐converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) as its primary entry point into the host cell. However, understanding the biology behind this viral replication, disease mechanism and drug discovery efforts are limited due to the lack of a suitable experimental model. Here, we used single‐cell RNA sequencing data of human organoids to analyze expressions of ACE2 and TMPRSS2, in addition to an array of RNA receptors to examine their role in SARS‐CoV‐2 pathogenesis. ACE2 is abundant in all organoids, except the prostate and brain, and TMPRSS2 is omnipresent. Innate immune pathways are upregulated in ACE2(+) cells of all organoids, except the lungs. Besides this, the expression of low‐density lipoprotein receptor is highly enriched in ACE2(+) cells in intestinal, lung, and retinal organoids, with the highest expression in lung organoids. Collectively, this study demonstrates that the organoids can be used as an experimental platform to explore this novel virus disease mechanism and for drug development.
This paper is about using RNA-sequencing to understanding "the virus disease mechanism and for drug development". It would seem relevant in understanding the effect of B.1.1.7 variant.

Thanks to @Ygggdrasil for pointing to this thread.
 
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Related to Genetic mechanisms of critical illness in Covid-19 - Nature Magazine

1. What is the main focus of the article?

The main focus of the article is to explore the genetic mechanisms involved in critical illness caused by Covid-19.

2. Why is understanding genetic mechanisms important in the context of Covid-19?

Understanding the genetic mechanisms of critical illness in Covid-19 can help identify individuals who are at a higher risk of developing severe symptoms. It can also provide insights into potential treatment strategies and help in the development of vaccines.

3. How does the article suggest genetics may play a role in the severity of Covid-19?

The article suggests that certain genetic variations may make individuals more susceptible to severe illness caused by Covid-19. These variations may affect the immune response and increase the risk of developing severe symptoms.

4. What are some potential limitations of studying genetic mechanisms in Covid-19?

One potential limitation is the lack of large-scale studies and data on the genetic variations associated with Covid-19 severity. Additionally, genetic factors are not the only determinants of critical illness in Covid-19, as other factors such as age and underlying health conditions also play a role.

5. What are some potential implications of the findings discussed in the article?

The findings discussed in the article could have implications for personalized medicine, as identifying genetic variations associated with severe Covid-19 could help tailor treatment plans for individuals. It could also aid in the development of targeted therapies and vaccines to prevent severe illness in high-risk individuals.

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