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Covid-19 #38: As the Worm Turns


Fragile Bird

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16 minutes ago, Padraig said:

That all makes sense.  But given more and more countries are going down the booster role anyhow, isn't it tempting to look at a booster that is focused  on Delta rather than another dose of the same thing?  Maybe it is too late for this discussion, since boosters have already started in some countries, and it would take some time to approve a modified vaccine.  But the current vaccines still work fine against serious illness, so we did have time.  If countries knew a new vaccine would be available in a couple of months, I think more would have holden off going down the booster route immediately.

I get the concern about further mutations.  But if you hadn't gotten the first vaccine, you'd just get 2 doses of this hypothetical one instead.  There is a chance that this new vaccine would work better on the next big variant than the current one.

Yes, I agree, if you are going to administer a booster, you may as well tailor the booster to the variant that's currently out there.  Initially, that's what I thought they were going to do, but it became apparent they just meant giving another dose of the old vaccine.  It never made much sense to me to administer a third shot of the old vaccine.  To be honest, the messaging from the health agencies regarding the need for boosters is pretty muddled.  The science and justification for administering the booster using the old vaccine is pretty weak in my opinion.

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8 hours ago, BigFatCoward said:

Most of the rest of the world, who have had it much worse than you dont really give a shit about the voluntary unvaccinated anymore. 

Doesn't mean it's right to not give a shit. For now we are doing a good job of saving people from their own stupidity. A society is not judge by how it treats the best of us, it's judged on how it treats the least of us. That applies equally at a material and intellectual level. 

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Somewhat random thoughts on the booster conversation:

1) The variants which have really taken off so far (D614G, alpha, delta) seem to have had a fitness advantage largely brought about by increased transmissibility rather than immune evasion. Ie the virus is evolving to become more human adapted.

2) The major antigen (spike) can only mutate towards increased ACE2 affinity so far - it cannot infinitely evolve towards increased transmissibility and will get to a point of increasingly diminishing returns. When it gets towads that point (if we're not already there, which my gut says we might be*) further mutations will likely be towards immune evasion & reinfection. These may be less (not more) transmissible.

3) Almost all of the variants so far share a half dozen or more of the same substitutions. That includes the potential escape mutants.

4)  This virus is not evolving particularly quickly. A dozen or so amino acid substitutions in billions of generations isn't a high rate of mutation for a virus.

So with all of this in mind it seems insane not to tailor booster shots to Delta like, yesterday.

*I also thought this last year. That turned out well.

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2 hours ago, RhaenysBee said:

Can an adjusted vaccine be developed as fast as new variants pop up? We had two major new variants along with two minor ones just in 2021. As for getting an adjusted vaccine yearly, people are apprehensive about cross-vaccinating for the third shot already. 

Technically a dead delta virus vaccine could be put out to market in a very short space of time. As an adjunct to people already vaccinated with first gen viruses it may well give a significant immunity boost, specifically for Delta.

There is another left field possibility: inoculation. That is simple infection with the virus. But in this case with the OG virus. Vaccine was proved to be very effective at preventing infection and illness with the OG virus. Therefore it should be safe, in theory, to inoculate healthy, non-elderly, double jabbed people, a couple of months after their second vaccination, and this would give a major boost to immunity which may prevent breakthrough infection by Delta in a large proportion of people.  I don't know what the stats say about infection, illness and death in healthy non-elderly vaccinated people with the OG virus. I believe soon after the second jab the overall stat with the mRNA viruses was 96% effective at preventing infection. But that would be across all ages. For the younger and healthier that may be a much higher effectiveness. Also, given it appears most countries are resigned to everyone being exposed to Delta, it could be argued that it is better to be deliberately hit with the OG virus than to wait until you are hit with Delta, if a very high degree of cross immunity is confirmed. The dose can be managed to be just at the infectious dose rate, and ti doesn't necessarily need to be a jab. It could be orally administered like the polio vaccine. Of course the conspiracy community would go absolutely nuts, moreso than it is now. 

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2 minutes ago, Impmk2 said:

4)  This virus is not evolving particularly quickly. A dozen or so amino acid substitutions in billions of generations isn't a high rate of mutation for a virus.

There have been many, many variants, thousands by now, but the vast majority are not of concern because they do not appear to increase infectivity or severity of disease.  There were dozens of known variants all within the first several months of the pandemic, when the numbers of infected was much smaller.  I think this virus mutates at a normal rate that is typical of RNA based viruses, which is relatively high, at least compared with DNA based viruses.

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On 9/14/2021 at 8:33 AM, The Marquis de Leech said:

Jacinda pursuing anything other than Elimination will lose her 2023. The public (apart from David Seymour) are right behind Elimination, even if it means extended lockdowns. After all, we can see the alternative... Sydney.

We have to keep the border closed, because anything else means the destruction of our health system. People understand that.

Well I'm glad there is not an election anytime soon. By 2023 it will probably be settled on whether or not elimination is still a viable option, but without superior vaccinations it is probably not.

People support elimination because of the freedom it offers within our regular lives (outside of international travel). People will not be supporting extended lockdowns, I feel this will be the last one that is complied with. Many companies can still operate at level 4, but there are plenty of others which are causing their owners to lose their entire livelihoods as well as burdening future taxpayers with debt.

This one is particularly bad, much worse for Auckland than last years, and is not working particularly effectively other than to reduce transmission speed. We don't know the exact details over why there are continuously more and more community exposure events that keep leading to more cases. But there are about a dozen previous exposures that are waiting on day 3 tests over the next couple of days, and if that goes badly it will be back to square one. We need some luck now.

I don't think there is any doubt we needed to go ahead with this lockdown, the vaccination rate was far too low, ICU capacity far too low, and I have no doubt that if there was not a lockdown we would have seen many, many deaths and a lot of others seriously ill. But even though the vaccine seems much less effective at reducing transmission than we were hoping for, it does seem very effective at reducing the severity of the disease.

My gut feeling is we will be living with covid inside the community sometime next year. And that will be broadly supported by the public while future lockdowns will not.

Edit - as an aside I had my first vaccination yesterday. Was pleasantly surprised at how efficiently it was being run. I counted 15 staff who were vaccinating roughly 6 people every minute. If that rate was kept up around all the vaccination centers, the country population could be vaccinated in a couple of weeks then the 4-6 week wait and then the second shot. After seeing it in action I'm not entirely sure why I had to wait 3 weeks from the date I booked.  

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4 minutes ago, The Anti-Targ said:

Technically a dead delta virus vaccine could be put out to market in a very short space of time. As an adjunct to people already vaccinated with first gen viruses it may well give a significant immunity boost, specifically for Delta.

There is another left field possibility: inoculation. That is simple infection with the virus. But in this case with the OG virus. Vaccine was proved to be very effective at preventing infection and illness with the OG virus. Therefore it should be safe, in theory, to inoculate healthy, non-elderly, double jabbed people, a couple of months after their second vaccination, and this would give a major boost to immunity which may prevent breakthrough infection by Delta in a large proportion of people.  I don't know what the stats say about infection, illness and death in healthy non-elderly vaccinated people with the OG virus. I believe soon after the second jab the overall stat with the mRNA viruses was 96% effective at preventing infection. But that would be across all ages. For the younger and healthier that may be a much higher effectiveness. Also, given it appears most countries are resigned to everyone being exposed to Delta, it could be argued that it is better to be deliberately hit with the OG virus than to wait until you are hit with Delta, if a very high degree of cross immunity is confirmed. The dose can be managed to be just at the infectious dose rate, and ti doesn't necessarily need to be a jab. It could be orally administered like the polio vaccine. Of course the conspiracy community would go absolutely nuts, moreso than it is now. 

I'm not sure a single inactivated virus vaccine has been approved yet for coronavirus.  Maybe one in China or Russia?  If China has approved one, I would bet that it performs relatively poorly.  The inactivation process, typically heat, chemical, and/or irradiation, generally alters the physical and chemical structure of the virus proteins, which can render them less effective at generating an effective immune response.  It can take a lot of trial and error (years) to come up with an adequate process that results in sufficient inactivation or attenuation of the virus while not damaging the critical proteins too much to allow a good immune response to be developed after inoculation. 

mRNA vaccines and DNA vaccines on the other hand only require you to update the nucleic acid sequence you are delivering to the new variant.  This can be done immediately as soon as the variant of concern has been identified, assuming that an updated spike protein is a sufficient target for new variants.  Theoretically, other proteins can be included in the mRNA or DNA vaccines, but that doesn't appear necessary right now.  Then it's a matter of growing up a batch of the new nucleic acids and packaging it into a lipid vector for the mRNA vaccines, or genetically modifying the adenovirus in the DNA vaccines.  It would not be difficult for the manufacturers to make an updated mRNA or DNA vaccine.

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17 minutes ago, Mudguard said:

There have been many, many variants, thousands by now, but the vast majority are not of concern because they do not appear to increase infectivity or severity of disease.  There were dozens of known variants all within the first several months of the pandemic, when the numbers of infected was much smaller.  I think this virus mutates at a normal rate that is typical of RNA based viruses, which is relatively high, at least compared with DNA based viruses.

The coronavirus RdRP which is shared by sars-cov-2 has a somewhat uniquely high fidelity in the RNA virus world. It has a proof reading mechanism. Far lower mutation rate than most RNA viruses.

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4 minutes ago, Impmk2 said:

The coronavirus RdRP which is shared by sars-cov-2 has a somewhat uniquely high fidelity in the RNA virus world. It has a proof reading mechanism. Far lower mutation rate than most RNA viruses.

I've seen various estimates that suggest that the coronavirus mutation rate is roughly half of the influenza mutation rate, and maybe about a fourth of HIV.  That's really not much of a difference and to me they are all in the same ballpark, especially when you compare it with DNA based virus error rates which are orders of magnitude less.  I would still classify all the RNA viruses as having a relatively high error rate.

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1 hour ago, Ser Scot A Ellison said:

Well, that'll kill the virus alright. Most mouthwashes will do as well.

Still, I suppose it's better than injecting someone with bleach or giving them sunburn on the inside of their bodies. Not much better, but still. 

Edit: snorting too.

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42 minutes ago, Makk said:

Well I'm glad there is not an election anytime soon. By 2023 it will probably be settled on whether or not elimination is still a viable option, but without superior vaccinations it is probably not.

People support elimination because of the freedom it offers within our regular lives (outside of international travel). People will not be supporting extended lockdowns, I feel this will be the last one that is complied with. Many companies can still operate at level 4, but there are plenty of others which are causing their owners to lose their entire livelihoods as well as burdening future taxpayers with debt.

This one is particularly bad, much worse for Auckland than last years, and is not working particularly effectively other than to reduce transmission speed. We don't know the exact details over why there are continuously more and more community exposure events that keep leading to more cases. But there are about a dozen previous exposures that are waiting on day 3 tests over the next couple of days, and if that goes badly it will be back to square one. We need some luck now.

I don't think there is any doubt we needed to go ahead with this lockdown, the vaccination rate was far too low, ICU capacity far too low, and I have no doubt that if there was not a lockdown we would have seen many, many deaths and a lot of others seriously ill. But even though the vaccine seems much less effective at reducing transmission than we were hoping for, it does seem very effective at reducing the severity of the disease.

My gut feeling is we will be living with covid inside the community sometime next year. And that will be broadly supported by the public while future lockdowns will not.

Edit - as an aside I had my first vaccination yesterday. Was pleasantly surprised at how efficiently it was being run. I counted 15 staff who were vaccinating roughly 6 people every minute. If that rate was kept up around all the vaccination centers, the country population could be vaccinated in a couple of weeks then the 4-6 week wait and then the second shot. After seeing it in action I'm not entirely sure why I had to wait 3 weeks from the date I booked.  

That is a total myth. Governments never run out of money or have to burden future generations with debt, unless they cede control of their currency to someone else (like adopting the Euro or those several countries that have adopted the US dollar).

Support for lockdown should continue for as long as the govt can credible state that COVID-19 running relatively freely in the country will kill thousands of people.  Get the predicted number of COVID-19 deaths in the first year below the annual number of 'flu deaths (500) then a large proportion of people will start chomping at the bit. Get the predicted number of deaths below the annual road toll (~250-300) and you are likely to have a majority of people agreeing with opening up. IMO the govt can extend the prospect of lockdowns reasonably well into the future if it sets a death benchmark, rather than a vaccination benchmark, which the vast majority of NZers find to be reasonable. What's your death benchmark? If you think some time next year is when we should allow COVID-19 into the country permanently then you must have a fairly high death benchmark.

The opening up question really is about appetite for death. By implication that means capacity of the health system to treat people as their symptoms demand in a timely fashion, since a stressed health system means more deaths. Given we only have about 180 ICU beds in the whole country, that means we can't really afford to have a rate of ICU occupancy for COVID-19 cases of much more than 60. If the ICU demand for one disease gets much above that then capacity problems will start to hit hard, since the other demands for ICU beds will still be there. At the peak of this outbreak we had ICU occupancy of 6 with active cases being roughly 700. So if we have 7-10K active cases in the country our ICU capacity for COVID-19 will likely be about maxed. So we need to model ICU occupancy as part of our death appetite.

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7 minutes ago, The Anti-Targ said:

That is a total myth. Governments never run out of money or have to burden future generations with debt, unless they cede control of their currency to someone else (like adopting the Euro or those several countries that have adopted the US dollar).

The claim that it is a total myth, is a total myth. One way or another the money is eventually paid back even if it is simply through higher cost of imports. If the country persists in not doing anything about it they end up like Argentina or Zimbabwe. The country cannot repetitively lockdown Auckland and expect the economy to continue to function.

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What's your death benchmark?

There is no simple answer to that. It would depend on the types of people dyeing (vaccinated vs unvaccinated, the age). And what damage is done to those for whom it is not fatal and in the young who cannot be vaccinated. And I haven't given it any thought. What I do believe if you want to run an elimination strategy it is not going to work anything like they are currently doing it. You would need custom built facilities, outside of a main city, and the quarantine stay would have to be greater than 2 weeks (probably 4). Unless of course the next generation of vaccines were effective in preventing transmission which I previously mentioned. 

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2 minutes ago, Makk said:

The claim that it is a total myth, is a total myth. One way or another the money is eventually paid back even if it is simply through higher cost of imports. If the country persists in not doing anything about it they end up like Argentina or Zimbabwe.

"Future generations of taxpayers saddled with debt" is a false narrative with no economic basis that is deployed purely for political purposes. The boogey men of Argentina, Zimbabwe and Weimar Germany are also false narratives deployed for purely political purposes, which fail to understand or acknowledge the underlying causes of why those countries went to shit. Those circumstance are not in danger of being replicated here any time soon.

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7 minutes ago, Makk said:

The claim that it is a total myth, is a total myth. One way or another the money is eventually paid back even if it is simply through higher cost of imports. If the country persists in not doing anything about it they end up like Argentina or Zimbabwe.

Our governmental debt levels are very low by international standards, and governments don't die - they can literally roll-over debt indefinitely (with no-one suffering a drop in life-time living standards, but rather having to defer consumption. It's counter-intuitive, but economics is weird like that). Also, international interest rates are going to be stuck at zero for a long time to come.

As Anti-Targ mentioned, the question here is "how many deaths are we willing to tolerate?" The major factor being that we haven't yet seen the upcoming Northern Hemisphere winter, so can't do anything until well into the New Year.

Anyway, 14 cases today. Lockdown continues to work.

 

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To illustrate: Denmark has roughly the same population as New Zealand, an excellent vaccination rate, and three deaths a day. Would New Zealand tolerate a thousand Covid deaths a year, never mind the extra pressure on ICUs? I am sceptical (I really think the major comparison is the road-toll).

Bonus consideration is that this is September. For all we know, Denmark come December and January will be looking much, much uglier... and Fortress New Zealand much, much more attractive.

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4 minutes ago, The Marquis de Leech said:

Our governmental debt levels are very low by international standards, and governments don't die - they can literally roll-over debt indefinitely (with no-one suffering a drop in life-time living standards, but rather having to defer consumption. It's counter-intuitive, but economics is weird like that). Also, international interest rates are going to be stuck at zero for a long time to come.

We came into the covid lockdown with historical low levels of debt in an extremely robust position. Now it is trending towards the midterm. Yes there is a bit of wriggle room, but it cannot continue indefinitely. Countries that are producing real things (we do OK on food, not much else) are going to come out of this much better off.

13 minutes ago, The Anti-Targ said:

"Future generations of taxpayers saddled with debt" is a false narrative with no economic basis that is deployed purely for political purposes. The boogey men of Argentina, Zimbabwe and Weimar Germany are also false narratives deployed for purely political purposes, which fail to understand or acknowledge the underlying causes of why those countries went to shit. Those circumstance are not in danger of being replicated here any time soon.

The situation is much more analogous than you are letting on. These countries continued to print money for years to maintain a standard of living while their production in real terms was being destroyed (either by themselves or uncontrollable world events which they ignored). If we are locking down Auckland for multiple months a year our own production is going to take a real hit. Even now already at this early stage it is effecting the entire country through shortages of building supplies, exactly when we desperately need to be building more houses. This is real, it is not fictitious scaremongering.

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1 hour ago, Mudguard said:

I've seen various estimates that suggest that the coronavirus mutation rate is roughly half of the influenza mutation rate, and maybe about a fourth of HIV.  That's really not much of a difference and to me they are all in the same ballpark, especially when you compare it with DNA based virus error rates which are orders of magnitude less.  I would still classify all the RNA viruses as having a relatively high error rate.

I'm surprised it isn't much lower than those. I've seen several publications mention the lower mutation rate making it a good vaccine candidate when compared to other RNA viruses. I at least don't think influenza is a great comparison for it in any case - has the propensity for antigenic shift due to the segmented nature of its genome.

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