The new Variant Under Investigation (VUI) was re-designated Variant of Concern (VOC) 202012/01 on 18 December

This is an excellent report by @PHE_UK, but it’s a bit technical so I’ll try to unpick it for you

https://t.co/M9f3zaimF5

1/14

The team at @PHE_uk begin by explaining that on 8 Dec they investigated the surge in cases in the South of England. Only 4% (255/6130) of Kent cases had genetic sequence data, but of these 117 genetically similar cases had been collected between 10-18 Nov

2/14
When looking at national data, these 117 cases were part of a larger cluster of 962 (to 8 Dec) in Kent, NE London, plus a few in rest London, Anglia, Essex

3/14
915 or the 962 cases had additional data: 828 were from November, 79 in Oct, 4 from Sept

90% were from <60 years old (further detail not yet available here)

6 patients had already died

4/14
As of 20 Dec, most cases were in London, the SE and East of England.

Of note, 3 of the main testing labs use a PCR test for 3 different viral genes: N, ORF1ab, S.

The new VOC has a mutation that makes this test negative for S (spike), but positive for the others.

5/14
This 'S-gene target failure' (SGTF) proved useful because 97% of pillar 2 (non-hospital) PCR tests negative for S, but positive for N and ORF1, were this VOC. Using this, it was possible to calculate that VOC is more transmissible, adding about 0.5 to the R value

6/14
We can see here, the proportion of SGTFs in positive tests at one Lighthouse lab. Early on, low level SGTFs were seen due to other strains(blue line), then from Nov the new VOC (red line, also called B.1.1.7) rapidly began to dominate the positive tests

7/14
The new VOC is defined by having 23 mutations.

Because of the way genetics works, 6 of these don’t actually change viral proteins (so-called synonymous mutations).

13 change amino acids of a viral protein (see Figure)

4 remove a small piece of a protein

8/14
Because this VOC has acquired an unusually large number of mutations, seemingly in one step, it is speculated that it might have arisen either in 1 person with a weak immune system (next tweet) or even in another animal (as happened with the Danish cluster involving mink)

9/14
For example, recently a patient on immunosuppressive drugs remained infected (with a different variant) for 154 days before dying. During that infection, the virus acquired many new mutations

https://t.co/f5JWWUOaqy

10/14
N501Y mutation in the S protein of B.1.1.7 & the deletion 69/70 may account for much of its the transmissibility. N501Y is known to increase binding to ACE2, a protein on our cells the virus uses to gain entry. N501Y appears to allow the virus to infect mice too.

11/14
501 is where neutralising antibodies often act, so it's possible that N501Y might affect such antibodies.

Although N501Y has not yet been tested, other mutations at 501 decrease the effectiveness of LYCoV016, a monoclonal antibody developed to treat COVID19

12/14
There is no information about natural antibodies, which, because of their diversity, target many parts of a virus at once. But, vaccination generates lots of different antibodies, so is less likely to be adversely affected.

13/14
There is much still to understand about this variant, but the speed of progress by @PHE_uk and @CovidGenomicsUK is nothing short of breath-taking.

They deserve our thanks!

14/14

More from Health

1/16
Why do B12 and folate deficiencies lead to HUGE red blood cells?

And, if the issue is DNA synthesis, why are red blood cells (which don't have DNA) the key cell line affected?

For answers, we'll have to go back a few billion years.


2/
RNA came first. Then, ~3-4 billion years ago, DNA emerged.

Among their differences:
🔹RNA contains uracil
🔹DNA contains thymine

But why does DNA contains thymine (T) instead of uracil (U)?

https://t.co/XlxT6cLLXg


3/
🔑Cytosine (C) can undergo spontaneous deamination to uracil (U).

In the RNA world, this meant that U could appear intensionally or unintentionally. This is clearly problematic. How can you repair RNA when you can't tell if something is an error?

https://t.co/bIZGviHBUc


4/
DNA's use of T instead of U means that spontaneous C → U deamination can be corrected without worry that an intentional U is being removed.

DNA requires greater stability than RNA so the transition to a thymine-based structure was beneficial.

https://t.co/bIZGviHBUc


5/
Let's return to megaloblastic anemia secondary to B12 or folate deficiency.

When either is severely deficient deoxythymidine monophosphate (dTMP*) production is hindered. With less dTMP, DNA synthesis is abnormal.

[*Note: thymine is the base in dTMP]

https://t.co/AnDUtKkbZh
Let's talk honestly about "informed consent."
Someone with decades of training gives someone with none advice usually packed into 1-3 mins. Huge amount is based on trust. Huge potential for bias built in. But also there is no obligation to provide real alternative options.


I am classified as 'gifted' (obnoxious and ableist term). I mention because of what I am about to say. You all know that I was an ambulatory wheelchair user previously - could stand - but contractures have ended that. When I pleaded for physio, turned down. But did you know...

I recently was chatting with a doctor I know and explaining what happened and the day the physiatrist told me it was too late and nothing could be done. The doctor asked if I'd like one of her friends/colleagues to give second opinion. I said yes please! So...

She said can you send me MRI and other imaging they did to determine it wasn't possible to address your contractures.

Me: What?
Dr.: They did a MRI first before deciding right?
Me: No
Dr: What did they do??!
Me: Examined me for 2 minutes.
Dr: I am very angry rn. Can't talk.

My point is you don't even know if you are making "informed" decisions because the only source of information you have is the person who has already decided what they think you should do. And may I remind you of a word called 'compliance.'

You May Also Like