Five genes often found in severe cases of Covid-19

Rh Negative Facts

Rhesusnegative.netDecember 13, 2020December 14, 20204

Revealed: the five genes

TYK2

Creates an enzyme that can lead to inflammation

Is targeted with JAK inhibitors and one already approved for use in humans is baricitinib which treats rheumatoid arthritis

CCR2

Targetable by drugs that are in trials but are not widely used, for psoriasis

Evidence for this gene is not as strong as for other genes in the study, but Dr Baillie says it is still ‘compelling’

OAS1

Is a gene that initiates a signal that activates an enzyme which degrades RNA derived from viruses.

Several other coronavirus have a way of preventing this mechanism. No evidence yet for SARS-CoV-2, but it might be a specific feature that does this.

Targettable by a class of drugs called phosphodiesterase 12 inhibitors.

These are not currently in clinical trials but theoretically would enhance antiviral effect of this system.

IFNAR2

This is a core part of signalling that is responsible to the host antiviral response.

Signalling in this pathway is important in the chance of getting sick.

Relevant in fighting the virus directly, much like OAS1. This is more important early in the disease as later in the disease, virus levels drops and the issue comes from the body’s immune system attacking itself.

DPP9

Known to play several roles in inflammation but the researchers do not yet know exactly where it fits in to the Covid-19 disease progression.

They are therefore unable to make a direct therapeutic prediction.

It is associated with pulmonary fibrosis and might be associated with ‘long covid’.

Genetic mechanisms of critical illness in Covid-19

Five genes often found in severe cases of Covid-19

Rhesusnegative.net

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4 Comments

Richard Youatt December 13, 2020 Reply

Mike:

Many thanks for posting this ! There may be some disagreements between researchers, but I see your summary as 100% spot-on.

I “stick my neck out” and speculate that DPP9 (associated with pulmonary fibrosis) may have some link with the core functions of the Rh proteins. It is too much of a coincidence to be a random chance.
Richard Youatt December 31, 2020 Reply

Today brings detail on OAS1 and COVID19. The preprint article is here https://www.medrxiv.org/content/10.1101/2020.10.13.20212092v4

The non-technical summary is this:

https://torontosun.com/news/world/neanderthal-gene-protects-against-covid-19

A specific form of a protein passed down from Neanderthals protects against severe COVID-19, and medications that boost levels of this protein could potentially help treat the disease, according to a study reported on medRxiv on Thursday ahead of peer review. The protein, called OAS1, is involved in the body’s response to viruses. People with higher levels of the Neanderthal-related form of OAS1 are less susceptible to COVID-19, and if they do become infected, they are at lower risk for hospitalization, intubation and death, the researchers found. “This protective form of OAS1 is present in sub-Saharan Africans but was lost when the ancestors of modern-day Europeans migrated out of Africa. It was then re-introduced into the European population through mating with Neanderthals” who lived more than 40,000 years ago, said coauthor Brent Richards from the Jewish General Hospital and McGill University in Montreal. An earlier study linked a cluster of genes inherited from Neanderthals to higher risks of hospitalization from COVID-19. “These findings further implicate Neanderthal ancestry in COVID-19 severity,” Richards said.
Richard Youatt December 31, 2020 Reply

Further update: (Read from bottom to top for correct chronology.)

From the paper:

“….a majority of present-day people carry this splice 263variant (rs10774671-A), which increases expression of isoforms other than p4626. The ancestral variant 264(rs10774671-G) is the major allele in African populations and became fixed in Neanderthal and 265 Denisovan genomes27,28. However, the ancestral variant, with its increased expression of the p46 isoform, 266 was reintroduced into the European population via gene flow from Neanderthals29, and is also the 267predominant isoform found in circulating blood26. The p46 isoform has been demonstrated to have higher 268 anti-viral activity than other isoforms30.”

On Thu, Dec 31, 2020 at 2:00 PM Justin Loe wrote:
Here’s the paper;
https://www.medrxiv.org/content/10.1101/2020.10.13.20212092v4.full.pdf

On Thu, Dec 31, 2020 at 1:59 PM Richard Youatt wrote:
Interesting at many levels.

I have AA on all three.

Richard

On Thursday, December 31, 2020 at 10:32:31 AM UTC-8 Justin wrote:
protective variants:
rs10774671 GG
rs3741981 GG
rs2660 GG

risk alleles (A for all three SNPs)
Richard Youatt December 31, 2020 Reply

One further comment from me:

That corresponds very roughly to the distributions of the different sub-forms of Rh negative between the European and Sub-Saharan.

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