When will this shit end?

[zahidf]

2 minutes ago, danmarks said:

Reduction in cases slowing to a stop? 'Only' 24percent down on this time last week. Genuinely don't know what some people want to realistically see /expect to happen.

its around 2% down on last week, but the 7 day average is down 24% overall

its a disappointing day infections wise but deaths are going down a lot still at least

[Guest]

 

 

[tigger123]

1 hour ago, zahidf said:

 

If they are going to be using case data for deciding on lockdown easing, then this possible plateauing is coming at the worst time possible for those wanting restrictions to be lifted more quickly, given that the decision on the roadmap is being decided in the next couple days

[zahidf]

"

Germany’s health minister, Jens Spahn, has made a point of saying he would be happy to be injected with the “safe and effective” AstraZeneca vaccine, as authorities in the country voiced their growing concern about the German public’s reluctance to be immunised against Covid-19 with the British-Swedish pharmaceutical company’s vaccine.

According to German government agencies’ own monitoring, only 87,533 out of 736,800 delivered doses of the AstraZeneca vaccine had been administered by Tuesday 16 February.

In Berlin, where the senate has promised the public the freedom to choose between different available vaccines, local media reported that out of 30,000 doses of the vaccine delivered last week, only 990 had been administered so far."

 

I wonder why....

[danmarks]

Yep sorry. Didnt make myself totally clear. I meant the rolling average only as i feel thats a better reflection of trends. 

A bit like the weather/climate change trope.

It's cold this week. There cant be any climate change etc.

Thankyou tho for clearing it up.

[zahidf]

3 minutes ago, tigger123 said:

If they are going to be using case data for deciding on lockdown easing, then this possible plateauing is coming at the worst time possible for those wanting restrictions to be lifted more quickly, given that the decision on the roadmap is being decided in the next couple days

Hopefully just a blip for a few days or an effect of surge testing theyve allowed for. 

I expect them to use vaccine data for the road map on Monday, and hopefully will move away from number of cases and more towards deaths

[Ryan1984]

36 minutes ago, MrBarry465 said:

Just because town centres might not be booming - that move away from the office then generates money elsewhere. It's not a black and white scenario. Why not turn office buildings into residential buildings, in order to keep those town centres thriving? Trying to cling to the old model isn't going to help us. 

Business has been booming in smaller indepent coffee shops and places that were previously in fringe zones. 

I 100% think the workplace should be as mobile and getting population concentration away from big cities, whilst might be bad for some, is generally better for large parts of the population. We need to adapt our economy and evolve it with the world around us, because at this point it's unlikely we will ever go back to what we were 2019 and prior. 

A lot of talk is around how we save central London from a cultural perspective, well to me the answer is simple. Convert all those offices into flats and you know.... actually have people living in central London again.

Doesn’t ‘getting population concentration away from big cities’ perfectly align with the Tories’ pledge to level things up across the nation? Unless they were lying.

[eFestivals]

20 minutes ago, tigger123 said:

If they are going to be using case data for deciding on lockdown easing, then this possible plateauing is coming at the worst time possible for those wanting restrictions to be lifted more quickly, given that the decision on the roadmap is being decided in the next couple days

They'll be looking most closely at data for vaccinated groups, to try and extrapolate how that'll pan out as vaccinations grow.

They're not going to be interested in one days numbers.

[Toilet Duck]

Everyone is worried about variants, but it's a little bit out of proportion (yes, it's good to keep an eye for the moment and also to test what impact they have on vaccine function/transmission/outcome for patients, but so far, I don't see a whole lot that has me unduly worried long term). All viruses mutate, this one is no different and it has all the hallmarks of becoming an endemic, seasonal virus, meaning it will continue to drift (just like the other CoVs). But...we are looking at this from the perspective of the host (worried that it will cause more severe disease or render our defences against it useless)...

From the perspective of the virus, there are other priorities (finding a new host, replicating and repeating the cycle...that's it). There's talk of "fully vax-resistant" variants and other such things, but biologically, they are unlikely. To evade every aspect of our immune response post vaccination/infection, the virus would need to change not just the bits of the spike that neutralising antibodies recognise, but also the bits that binding antibodies recognise, as well as the 90 odd epitopes that T-Cell receptors recognise when they are displayed on the surface of the infected cell (and that's just to evade the immune response elicited by the vaccine, if you gained your immunity through natural infection or if you can still catch it but not develop anything other than asymptomatic/mild/moderate disease after you have been vaccinated, then those low level infections also add in further immunity targeted at parts of the virus that weren't in the vaccine). That's a lot of changes to accrue (while still functioning the same way) and not how evolution/natural selection works. 

Changes that benefit the virus get selected as they confer traits that make the virus outcompete other variants. So, we see selection of changes that make the spike latch onto ACE2 a bit better (as seen in the Kent variant) making the virus more transmissible, we see changes that reduce the affinity of a subset of neutralising antibodies (SA/Brazil/New UK variant) allowing the virus to infect our cells, replicate and spread further before the immune system clears it and after that, there's not much pressure to change a whole lot else (and while we see random changes described in other variants, the specific changes listed above are cropping up repeatedly as hotspots, suggesting that's where the selection pressure is). Lots of other changes arise (there's over 500,000 sequences in GISAID at the moment describing at least 4000 different variants), but they don't lead anywhere as they don't change things that make the virus fitter and thus, they don't become the predominate variant in circulation.

Amid the gloom about variants that will make the virus more virulent, cause more severe disease and evade our vaccines, there's little focus on other changes that appear to be occurring with greater frequency. Way back when we first looked at the Kent variant (B1.1.7) we noted that an ORF8 deletion was also present. ORF8 deletions are becoming more common. ORF8 encodes a protein that blocks the interferon response as well as the mechanism by which our own cells, once they are infected, display parts of the virus to be detected by our cellular immunity. Loss of function of ORF8 allows these key anti-viral mechanisms to occur more efficiently (early studies on ORF8 loss suggested these variants should be less virulent). Its early days, but in the delicate balancing act the virus is undergoing to adapt to its new host (humans), we are starting to see these hotspot alterations repeatedly selected for and the fittest version may well be one that is more transmissible, evades some neutralising antibody activity but its also less virulent as if the host is not incapacitated, they can spread it more freely. A more transmissible virus can lead to higher morbidity and mortality, but if we are protected from that by vaccination, then not only is there little pressure on the virus to adapt more, but there little pressure on us to change that balance either. 

While convalescent sera from previously infected patients has been demonstrated to have some reduced activity against the new variants (either pseudoviruses or actual isolates), it's not non-existent. Pfizer have said that they are happy that they won't have to change their vaccine to deal with the variants as the neutralising antibody response remains robust enough (the Moderna data looks just as good, but they are going to make a new one just in case, as are OX/AZ). And even if it the neutralising activity was completely abrogated, the other parts of our immune system still kick in and protect us from severe disease. We will need to see that definitely proven by clinical outcomes in the vaccinated population, but the fact that severe disease, hospitalisations and death were not higher in trials conducted in places where the new variants were circulating and prevalent is our first such hint that what we see in terms of immune response to the variants will translate into real protection in patients. 

TLDR: Don't get overly stressed about variants. Our vaccines still work and they will still keep you out of hospital and stop you from dying. 

 

[tigger123]

6 minutes ago, Toilet Duck said:

Everyone is worried about variants, but it's a little bit out of proportion (yes, it's good to keep an eye for the moment and also to test what impact they have on vaccine function/transmission/outcome for patients, but so far, I don't see a whole lot that has me unduly worried long term). All viruses mutate, this one is no different and it has all the hallmarks of becoming an endemic, seasonal virus, meaning it will continue to drift (just like the other CoVs). But...we are looking at this from the perspective of the host (worried that it will cause more severe disease or render our defences against it useless)...

From the perspective of the virus, there are other priorities (finding a new host, replicating and repeating the cycle...that's it). There's talk of "fully vax-resistant" variants and other such things, but biologically, they are unlikely. To evade every aspect of our immune response post vaccination/infection, the virus would need to change not just the bits of the spike that neutralising antibodies recognise, but also the bits that binding antibodies recognise, as well as the 90 odd epitopes that T-Cell receptors recognise when they are displayed on the surface of the infected cell (and that's just to evade the immune response elicited by the vaccine, if you gained your immunity through natural infection or if you can still catch it but not develop anything other than asymptomatic/mild/moderate disease after you have been vaccinated, then those low level infections also add in further immunity targeted at parts of the virus that weren't in the vaccine). That's a lot of changes to accrue (while still functioning the same way) and not how evolution/natural selection works. 

Changes that benefit the virus get selected as they confer traits that make the virus outcompete other variants. So, we see selection of changes that make the spike latch onto ACE2 a bit better (as seen in the Kent variant) making the virus more transmissible, we see changes that reduce the affinity of a subset of neutralising antibodies (SA/Brazil/New UK variant) allowing the virus to infect our cells, replicate and spread further before the immune system clears it and after that, there's not much pressure to change a whole lot else (and while we see random changes described in other variants, the specific changes listed above are cropping up repeatedly as hotspots, suggesting that's where the selection pressure is). Lots of other changes arise (there's over 500,000 sequences in GISAID at the moment describing at least 4000 different variants), but they don't lead anywhere as they don't change things that make the virus fitter and thus, they don't become the predominate variant in circulation.

Amid the gloom about variants that will make the virus more virulent, cause more severe disease and evade our vaccines, there's little focus on other changes that appear to be occurring with greater frequency. Way back when we first looked at the Kent variant (B1.1.7) we noted that an ORF8 deletion was also present. ORF8 deletions are becoming more common. ORF8 encodes a protein that blocks the interferon response as well as the mechanism by which our own cells, once they are infected, display parts of the virus to be detected by our cellular immunity. Loss of function of ORF8 allows these key anti-viral mechanisms to occur more efficiently (early studies on ORF8 loss suggested these variants should be less virulent). Its early days, but in the delicate balancing act the virus is undergoing to adapt to its new host (humans), we are starting to see these hotspot alterations repeatedly selected for and the fittest version may well be one that is more transmissible, evades some neutralising antibody activity but its also less virulent as if the host is not incapacitated, they can spread it more freely. A more transmissible virus can lead to higher morbidity and mortality, but if we are protected from that by vaccination, then not only is there little pressure on the virus to adapt more, but there little pressure on us to change that balance either. 

While convalescent sera from previously infected patients has been demonstrated to have some reduced activity against the new variants (either pseudoviruses or actual isolates), it's not non-existent. Pfizer have said that they are happy that they won't have to change their vaccine to deal with the variants as the neutralising antibody response remains robust enough (the Moderna data looks just as good, but they are going to make a new one just in case, as are OX/AZ). And even if it the neutralising activity was completely abrogated, the other parts of our immune system still kick in and protect us from severe disease. We will need to see that definitely proven by clinical outcomes in the vaccinated population, but the fact that severe disease, hospitalisations and death were not higher in trials conducted in places where the new variants were circulating and prevalent is our first such hint that what we see in terms of immune response to the variants will translate into real protection in patients. 

TLDR: Don't get overly stressed about variants. Our vaccines still work and they will still keep you out of hospital and stop you from dying. 

 

Brilliant and fascinating post as always, thanks so much. (Out of upvotes annoyingly)

[zahidf]

7 minutes ago, Toilet Duck said:

Everyone is worried about variants, but it's a little bit out of proportion (yes, it's good to keep an eye for the moment and also to test what impact they have on vaccine function/transmission/outcome for patients, but so far, I don't see a whole lot that has me unduly worried long term). All viruses mutate, this one is no different and it has all the hallmarks of becoming an endemic, seasonal virus, meaning it will continue to drift (just like the other CoVs). But...we are looking at this from the perspective of the host (worried that it will cause more severe disease or render our defences against it useless)...

From the perspective of the virus, there are other priorities (finding a new host, replicating and repeating the cycle...that's it). There's talk of "fully vax-resistant" variants and other such things, but biologically, they are unlikely. To evade every aspect of our immune response post vaccination/infection, the virus would need to change not just the bits of the spike that neutralising antibodies recognise, but also the bits that binding antibodies recognise, as well as the 90 odd epitopes that T-Cell receptors recognise when they are displayed on the surface of the infected cell (and that's just to evade the immune response elicited by the vaccine, if you gained your immunity through natural infection or if you can still catch it but not develop anything other than asymptomatic/mild/moderate disease after you have been vaccinated, then those low level infections also add in further immunity targeted at parts of the virus that weren't in the vaccine). That's a lot of changes to accrue (while still functioning the same way) and not how evolution/natural selection works. 

Changes that benefit the virus get selected as they confer traits that make the virus outcompete other variants. So, we see selection of changes that make the spike latch onto ACE2 a bit better (as seen in the Kent variant) making the virus more transmissible, we see changes that reduce the affinity of a subset of neutralising antibodies (SA/Brazil/New UK variant) allowing the virus to infect our cells, replicate and spread further before the immune system clears it and after that, there's not much pressure to change a whole lot else (and while we see random changes described in other variants, the specific changes listed above are cropping up repeatedly as hotspots, suggesting that's where the selection pressure is). Lots of other changes arise (there's over 500,000 sequences in GISAID at the moment describing at least 4000 different variants), but they don't lead anywhere as they don't change things that make the virus fitter and thus, they don't become the predominate variant in circulation.

Amid the gloom about variants that will make the virus more virulent, cause more severe disease and evade our vaccines, there's little focus on other changes that appear to be occurring with greater frequency. Way back when we first looked at the Kent variant (B1.1.7) we noted that an ORF8 deletion was also present. ORF8 deletions are becoming more common. ORF8 encodes a protein that blocks the interferon response as well as the mechanism by which our own cells, once they are infected, display parts of the virus to be detected by our cellular immunity. Loss of function of ORF8 allows these key anti-viral mechanisms to occur more efficiently (early studies on ORF8 loss suggested these variants should be less virulent). Its early days, but in the delicate balancing act the virus is undergoing to adapt to its new host (humans), we are starting to see these hotspot alterations repeatedly selected for and the fittest version may well be one that is more transmissible, evades some neutralising antibody activity but its also less virulent as if the host is not incapacitated, they can spread it more freely. A more transmissible virus can lead to higher morbidity and mortality, but if we are protected from that by vaccination, then not only is there little pressure on the virus to adapt more, but there little pressure on us to change that balance either. 

While convalescent sera from previously infected patients has been demonstrated to have some reduced activity against the new variants (either pseudoviruses or actual isolates), it's not non-existent. Pfizer have said that they are happy that they won't have to change their vaccine to deal with the variants as the neutralising antibody response remains robust enough (the Moderna data looks just as good, but they are going to make a new one just in case, as are OX/AZ). And even if it the neutralising activity was completely abrogated, the other parts of our immune system still kick in and protect us from severe disease. We will need to see that definitely proven by clinical outcomes in the vaccinated population, but the fact that severe disease, hospitalisations and death were not higher in trials conducted in places where the new variants were circulating and prevalent is our first such hint that what we see in terms of immune response to the variants will translate into real protection in patients. 

TLDR: Don't get overly stressed about variants. Our vaccines still work and they will still keep you out of hospital and stop you from dying. 

 

Thanks! I was thinking the variants stuff was a LITTLE overstated but good to here it from you as well! I saw Edmunds on Peston merrily say 'the Bristol variant is immune to the vaccine' without any context or follow up (or evidence) so I think some scientists need to cool their jets on this as well!

[km9]

10 minutes ago, Toilet Duck said:

Everyone is worried about variants, but it's a little bit out of proportion (yes, it's good to keep an eye for the moment and also to test what impact they have on vaccine function/transmission/outcome for patients, but so far, I don't see a whole lot that has me unduly worried long term). All viruses mutate, this one is no different and it has all the hallmarks of becoming an endemic, seasonal virus, meaning it will continue to drift (just like the other CoVs). But...we are looking at this from the perspective of the host (worried that it will cause more severe disease or render our defences against it useless)...

From the perspective of the virus, there are other priorities (finding a new host, replicating and repeating the cycle...that's it). There's talk of "fully vax-resistant" variants and other such things, but biologically, they are unlikely. To evade every aspect of our immune response post vaccination/infection, the virus would need to change not just the bits of the spike that neutralising antibodies recognise, but also the bits that binding antibodies recognise, as well as the 90 odd epitopes that T-Cell receptors recognise when they are displayed on the surface of the infected cell (and that's just to evade the immune response elicited by the vaccine, if you gained your immunity through natural infection or if you can still catch it but not develop anything other than asymptomatic/mild/moderate disease after you have been vaccinated, then those low level infections also add in further immunity targeted at parts of the virus that weren't in the vaccine). That's a lot of changes to accrue (while still functioning the same way) and not how evolution/natural selection works. 

Changes that benefit the virus get selected as they confer traits that make the virus outcompete other variants. So, we see selection of changes that make the spike latch onto ACE2 a bit better (as seen in the Kent variant) making the virus more transmissible, we see changes that reduce the affinity of a subset of neutralising antibodies (SA/Brazil/New UK variant) allowing the virus to infect our cells, replicate and spread further before the immune system clears it and after that, there's not much pressure to change a whole lot else (and while we see random changes described in other variants, the specific changes listed above are cropping up repeatedly as hotspots, suggesting that's where the selection pressure is). Lots of other changes arise (there's over 500,000 sequences in GISAID at the moment describing at least 4000 different variants), but they don't lead anywhere as they don't change things that make the virus fitter and thus, they don't become the predominate variant in circulation.

Amid the gloom about variants that will make the virus more virulent, cause more severe disease and evade our vaccines, there's little focus on other changes that appear to be occurring with greater frequency. Way back when we first looked at the Kent variant (B1.1.7) we noted that an ORF8 deletion was also present. ORF8 deletions are becoming more common. ORF8 encodes a protein that blocks the interferon response as well as the mechanism by which our own cells, once they are infected, display parts of the virus to be detected by our cellular immunity. Loss of function of ORF8 allows these key anti-viral mechanisms to occur more efficiently (early studies on ORF8 loss suggested these variants should be less virulent). Its early days, but in the delicate balancing act the virus is undergoing to adapt to its new host (humans), we are starting to see these hotspot alterations repeatedly selected for and the fittest version may well be one that is more transmissible, evades some neutralising antibody activity but its also less virulent as if the host is not incapacitated, they can spread it more freely. A more transmissible virus can lead to higher morbidity and mortality, but if we are protected from that by vaccination, then not only is there little pressure on the virus to adapt more, but there little pressure on us to change that balance either. 

While convalescent sera from previously infected patients has been demonstrated to have some reduced activity against the new variants (either pseudoviruses or actual isolates), it's not non-existent. Pfizer have said that they are happy that they won't have to change their vaccine to deal with the variants as the neutralising antibody response remains robust enough (the Moderna data looks just as good, but they are going to make a new one just in case, as are OX/AZ). And even if it the neutralising activity was completely abrogated, the other parts of our immune system still kick in and protect us from severe disease. We will need to see that definitely proven by clinical outcomes in the vaccinated population, but the fact that severe disease, hospitalisations and death were not higher in trials conducted in places where the new variants were circulating and prevalent is our first such hint that what we see in terms of immune response to the variants will translate into real protection in patients. 

TLDR: Don't get overly stressed about variants. Our vaccines still work and they will still keep you out of hospital and stop you from dying. 

 

Yeah I agree 😁

[duke88]

39 minutes ago, zahidf said:

"

Germany’s health minister, Jens Spahn, has made a point of saying he would be happy to be injected with the “safe and effective” AstraZeneca vaccine, as authorities in the country voiced their growing concern about the German public’s reluctance to be immunised against Covid-19 with the British-Swedish pharmaceutical company’s vaccine.

According to German government agencies’ own monitoring, only 87,533 out of 736,800 delivered doses of the AstraZeneca vaccine had been administered by Tuesday 16 February.

In Berlin, where the senate has promised the public the freedom to choose between different available vaccines, local media reported that out of 30,000 doses of the vaccine delivered last week, only 990 had been administered so far."

 

I wonder why....

What did they think was going to happen!

[zahidf]

 

[Suprefan]

 

 

[BobWillis]

Surely it’s going to be pretty difficult to get below 1,000 cases per day when you’re testing c.600,000 people using a test that isn’t 100% accurate?! 
Base rate fallacy isn’t a theory, at some point soon there will be more false positives than real positives, the only question is how many false positives are there from 600,000 tests? 
 

EDIT: and now it sounds like they’re going to drastically increase the number of tests too! 

Edited February 17, 2021 by BobWillis

[tigger123]

15 minutes ago, Toilet Duck said:

Everyone is worried about variants, but it's a little bit out of proportion (yes, it's good to keep an eye for the moment and also to test what impact they have on vaccine function/transmission/outcome for patients, but so far, I don't see a whole lot that has me unduly worried long term). All viruses mutate, this one is no different and it has all the hallmarks of becoming an endemic, seasonal virus, meaning it will continue to drift (just like the other CoVs). But...we are looking at this from the perspective of the host (worried that it will cause more severe disease or render our defences against it useless)...

From the perspective of the virus, there are other priorities (finding a new host, replicating and repeating the cycle...that's it). There's talk of "fully vax-resistant" variants and other such things, but biologically, they are unlikely. To evade every aspect of our immune response post vaccination/infection, the virus would need to change not just the bits of the spike that neutralising antibodies recognise, but also the bits that binding antibodies recognise, as well as the 90 odd epitopes that T-Cell receptors recognise when they are displayed on the surface of the infected cell (and that's just to evade the immune response elicited by the vaccine, if you gained your immunity through natural infection or if you can still catch it but not develop anything other than asymptomatic/mild/moderate disease after you have been vaccinated, then those low level infections also add in further immunity targeted at parts of the virus that weren't in the vaccine). That's a lot of changes to accrue (while still functioning the same way) and not how evolution/natural selection works. 

Changes that benefit the virus get selected as they confer traits that make the virus outcompete other variants. So, we see selection of changes that make the spike latch onto ACE2 a bit better (as seen in the Kent variant) making the virus more transmissible, we see changes that reduce the affinity of a subset of neutralising antibodies (SA/Brazil/New UK variant) allowing the virus to infect our cells, replicate and spread further before the immune system clears it and after that, there's not much pressure to change a whole lot else (and while we see random changes described in other variants, the specific changes listed above are cropping up repeatedly as hotspots, suggesting that's where the selection pressure is). Lots of other changes arise (there's over 500,000 sequences in GISAID at the moment describing at least 4000 different variants), but they don't lead anywhere as they don't change things that make the virus fitter and thus, they don't become the predominate variant in circulation.

Amid the gloom about variants that will make the virus more virulent, cause more severe disease and evade our vaccines, there's little focus on other changes that appear to be occurring with greater frequency. Way back when we first looked at the Kent variant (B1.1.7) we noted that an ORF8 deletion was also present. ORF8 deletions are becoming more common. ORF8 encodes a protein that blocks the interferon response as well as the mechanism by which our own cells, once they are infected, display parts of the virus to be detected by our cellular immunity. Loss of function of ORF8 allows these key anti-viral mechanisms to occur more efficiently (early studies on ORF8 loss suggested these variants should be less virulent). Its early days, but in the delicate balancing act the virus is undergoing to adapt to its new host (humans), we are starting to see these hotspot alterations repeatedly selected for and the fittest version may well be one that is more transmissible, evades some neutralising antibody activity but its also less virulent as if the host is not incapacitated, they can spread it more freely. A more transmissible virus can lead to higher morbidity and mortality, but if we are protected from that by vaccination, then not only is there little pressure on the virus to adapt more, but there little pressure on us to change that balance either. 

While convalescent sera from previously infected patients has been demonstrated to have some reduced activity against the new variants (either pseudoviruses or actual isolates), it's not non-existent. Pfizer have said that they are happy that they won't have to change their vaccine to deal with the variants as the neutralising antibody response remains robust enough (the Moderna data looks just as good, but they are going to make a new one just in case, as are OX/AZ). And even if it the neutralising activity was completely abrogated, the other parts of our immune system still kick in and protect us from severe disease. We will need to see that definitely proven by clinical outcomes in the vaccinated population, but the fact that severe disease, hospitalisations and death were not higher in trials conducted in places where the new variants were circulating and prevalent is our first such hint that what we see in terms of immune response to the variants will translate into real protection in patients. 

TLDR: Don't get overly stressed about variants. Our vaccines still work and they will still keep you out of hospital and stop you from dying. 

 

@Toilet Duckbased on this, do you reckon that case numbers shouldn't be used as a metric for relaxing lockdown once the majority are vaccinated, given that vaccines should prevent us from hospitalisation/death regardless of how the virus mutates?

[MrBarry465]

34 minutes ago, Toilet Duck said:

Everyone is worried about variants, but it's a little bit out of proportion (yes, it's good to keep an eye for the moment and also to test what impact they have on vaccine function/transmission/outcome for patients, but so far, I don't see a whole lot that has me unduly worried long term). All viruses mutate, this one is no different and it has all the hallmarks of becoming an endemic, seasonal virus, meaning it will continue to drift (just like the other CoVs). But...we are looking at this from the perspective of the host (worried that it will cause more severe disease or render our defences against it useless)...

From the perspective of the virus, there are other priorities (finding a new host, replicating and repeating the cycle...that's it). There's talk of "fully vax-resistant" variants and other such things, but biologically, they are unlikely. To evade every aspect of our immune response post vaccination/infection, the virus would need to change not just the bits of the spike that neutralising antibodies recognise, but also the bits that binding antibodies recognise, as well as the 90 odd epitopes that T-Cell receptors recognise when they are displayed on the surface of the infected cell (and that's just to evade the immune response elicited by the vaccine, if you gained your immunity through natural infection or if you can still catch it but not develop anything other than asymptomatic/mild/moderate disease after you have been vaccinated, then those low level infections also add in further immunity targeted at parts of the virus that weren't in the vaccine). That's a lot of changes to accrue (while still functioning the same way) and not how evolution/natural selection works. 

Changes that benefit the virus get selected as they confer traits that make the virus outcompete other variants. So, we see selection of changes that make the spike latch onto ACE2 a bit better (as seen in the Kent variant) making the virus more transmissible, we see changes that reduce the affinity of a subset of neutralising antibodies (SA/Brazil/New UK variant) allowing the virus to infect our cells, replicate and spread further before the immune system clears it and after that, there's not much pressure to change a whole lot else (and while we see random changes described in other variants, the specific changes listed above are cropping up repeatedly as hotspots, suggesting that's where the selection pressure is). Lots of other changes arise (there's over 500,000 sequences in GISAID at the moment describing at least 4000 different variants), but they don't lead anywhere as they don't change things that make the virus fitter and thus, they don't become the predominate variant in circulation.

Amid the gloom about variants that will make the virus more virulent, cause more severe disease and evade our vaccines, there's little focus on other changes that appear to be occurring with greater frequency. Way back when we first looked at the Kent variant (B1.1.7) we noted that an ORF8 deletion was also present. ORF8 deletions are becoming more common. ORF8 encodes a protein that blocks the interferon response as well as the mechanism by which our own cells, once they are infected, display parts of the virus to be detected by our cellular immunity. Loss of function of ORF8 allows these key anti-viral mechanisms to occur more efficiently (early studies on ORF8 loss suggested these variants should be less virulent). Its early days, but in the delicate balancing act the virus is undergoing to adapt to its new host (humans), we are starting to see these hotspot alterations repeatedly selected for and the fittest version may well be one that is more transmissible, evades some neutralising antibody activity but its also less virulent as if the host is not incapacitated, they can spread it more freely. A more transmissible virus can lead to higher morbidity and mortality, but if we are protected from that by vaccination, then not only is there little pressure on the virus to adapt more, but there little pressure on us to change that balance either. 

While convalescent sera from previously infected patients has been demonstrated to have some reduced activity against the new variants (either pseudoviruses or actual isolates), it's not non-existent. Pfizer have said that they are happy that they won't have to change their vaccine to deal with the variants as the neutralising antibody response remains robust enough (the Moderna data looks just as good, but they are going to make a new one just in case, as are OX/AZ). And even if it the neutralising activity was completely abrogated, the other parts of our immune system still kick in and protect us from severe disease. We will need to see that definitely proven by clinical outcomes in the vaccinated population, but the fact that severe disease, hospitalisations and death were not higher in trials conducted in places where the new variants were circulating and prevalent is our first such hint that what we see in terms of immune response to the variants will translate into real protection in patients. 

TLDR: Don't get overly stressed about variants. Our vaccines still work and they will still keep you out of hospital and stop you from dying. 

 

I guess we will find out either way in a few months time 🙂 

[efcfanwirral]

 

[zahidf]

2 minutes ago, efcfanwirral said:

 

Never heard of them.... it MAY be true but I have my doubts. 

[gizmoman]

18 minutes ago, BobWillis said:

Surely it’s going to be pretty difficult to get below 1,000 cases per day when you’re testing c.600,000 people using a test that isn’t 100% accurate?! 
Base rate fallacy isn’t a theory, at some point soon there will be more false positives than real positives, the only question is how many false positives are there from 600,000 tests? 
 

EDIT: and now it sounds like they’re going to drastically increase the number of tests too! 

It's amazing how people on here can understand Toilet Duck's detailed and complex explanations of this virus but can't seem to grasp this basic point about the PCR test, every time it's raised it gets ignored or attempts are made to dismiss it. The true false positive rate I.E. lab error or contamination is probably very small, but the number of positives identified from currently uninfected people must be getting quite high given the number who have now had the virus and who would still have traces of the virus in them, the PCR test as it is being used is too sensitive for identifying infectious people.

[Toilet Duck]

15 minutes ago, tigger123 said:

@Toilet Duckbased on this, do you reckon that case numbers shouldn't be used as a metric for relaxing lockdown once the majority are vaccinated, given that vaccines should prevent us from hospitalisation/death regardless of how the virus mutates?

Ultimately, case numbers will be immaterial. At the moment, they want to keep an eye on them as there is still a large susceptible population, but that’s dwindling. Once over 45s are sorted, not only have you a significantly lower risk in those left, but also a higher proportion of natural immunity as cases have been higher in that cohort anyway, so it’s a completely different proposition to opening up while you still have large numbers of unprotected, higher risk individuals. While I’m not overly worried about variants, hanging on til you have more people protected reduces the risk from them further. If the vaccines don’t suppress transmission (it looks like they will to a degree), the virus will seasonally circulate anyway, so cases become important when people turn up in hospital (we now have treatment regimens that we use for Covid that are different to other respiratory conditions, so knowing why someone has been admitted will help choose the correct course of treatment). It will also remain a notifiable disease for the foreseeable future, so the same kind of surveillance that goes on in the background for a whole host of other communicable disease will continue, but you won’t see it in the news every day. In short, once you have the higher risk categories protected through vaccination, case number are less informative than hospitalisations/deaths as they should no longer be a predictor of future morbidity/mortality...but the super safe option just in case a weird variant emerges is to make sure the susceptible population is a small as possible.

[efcfanwirral]

4 minutes ago, zahidf said:

Never heard of them.... it MAY be true but I have my doubts. 

One of those campaigning organisations- essentially encouraging whistleblowing. The independent sage account and some on it follow them 

Edited February 17, 2021 by efcfanwirral

[zahidf]

2 minutes ago, efcfanwirral said:

One of those campaigning organisations- essentially encouraging whistleblowing. The independent sage account and some on it follow it 

It's too vague as to be meaningless. What are the dates/number of doses/reasons why ifs delayed for one trust only e.t.c. it COULD be true but It feels like a way for them to have a go about the 12 week gap

 

[efcfanwirral]

14 minutes ago, zahidf said:

It's too vague as to be meaningless. What are the dates/number of doses/reasons why ifs delayed for one trust only e.t.c. it COULD be true but It feels like a way for them to have a go about the 12 week gap

 

true - I find it hard to know what a decent source is - it can't be these types of accounts who do have proper doctors etc following them but aren't "official" sources, but then Independent Sage are a bit of an agenda driven mess. But equally Daily Mail and Guardian etc are completely compromised by hard right or hard left idealogy. 

Edited February 17, 2021 by efcfanwirral