Coronavirus: The Great Unmasking

[The_J]

I am not sure. I have not worked on the genetics of viruses, but a lot of the investigations on bigger things take the form "what is the effect of this one base change, causing this one amino acid change in this protein". With CRISPR those sorts of questions are answerable at scale. I can imagine running the wild coronavirus receptors through computer modelling to guess at SNP risk variants for binding to human proteins, then CRISPR'ing the good hits into viruses, then testing in cell culture. It is totally the sort of thing you would do if you were worried about a covid pandemic, it would not need to be bioweapons.

Until like... last month or so you couldn't properly predict protein 3D structures, so this is a bit of a stretch.

 

[Narz]

Old (5 months) analyzing school closures.

 

[Samson]

Until like... last month or so you couldn't properly predict protein 3D structures, so this is a bit of a stretch.

You have been able to get a score for how much of a difference an amino acid change will make ot the conformation of a protein for some years. Fitting proteins together is even older.

 

[Sofista]

Here in the UK it is quite the opposite. I went to a couple of places this weekend, full of people without masks not even trying to social distance. Even the staff in pubs are not masked up. It felt weird, and I do not expect it to end well.

Just to offer a different outlook: I went to the supermarket today, then to a pub. Literally everyone at the super was masked, and at the pub we all sat as far away from each other group as we could.

It just might be a local habit, a combination of paranoia and subservience to authority.

 

[innonimatu]

yes and yes... people want normality in their practical daily lives

After all... there are enough other differences that can be picked up for tribal warfares.

To consider:
To get really that > 80%-85% vaccination willingness and vaccination, you do need to prevent that (too many) people entrench themselves in their purity on vaccines.
The pragmatic principle is: never slam the door... always keep the door at a crack, give people escapes without losing their face.

You are still hoping for herd immunity. It can't be achieved, not with these vaccines at least. They're too leaky. Even if you vaccinate 100% of the people you won't achieve herd immunity. Currently that is an impossible goal. Clinging to this hope is a mistake.
You need mucosal immunity, and that's a tough nut to crack. Unfortunately those working on vaccines with that aim were pushed out of the market, and therefore out of both funding and state sponsorship, by the availability of these - to be direct - crappy* vaccines.

It's one of those cases where a vaccine deemed "good enough", coupled with exclusively for-profit development, and with governments wanting their qhick fix now, are screwing us in the long term.

These vaccines have one "public interest" advantage and one only: they do seem to reduce hospital demand during covid peaks. But they won't end them and having seen the irresponsible behaviour of our rules that means they'll just let the "wave" get higher, more people infected, until the NPI are again deployed. So far we've seen that in the US with the official walkback for masking again. And informally, spontaneously, in the UK as people took up masking also. This is not a return to normal.

*Crappy because if they do reduce relative risk, that reduction doesn't seem great and they'll just be used as an excuse to let the absolute risk rise until the hospitals clog again. We'll see come Autumn, classes, the continued attempt to "reopen" as people shift indoors. End result is more people suffering bouts of supposedly "non-serious" covid which will leave them scarred. Something that reduces relative risk may, if used unwisely, actually elevate the absolute risk for everyone. That's what is happening with the vaccination campaign strategy.

 

[innonimatu]

How about you get a vaccine, and stop getting people killed. Either you are a conservative tagging along on their shared delusion, or a full bore Libertarian, a thoroughly meme ideology, that is societal cancer if actually tried. Society requires acting in the collective good, and coercion to that end. If you don't want to participate in society, you can be a shut-in, or go live in Somalia.

How about you stop lying and accusing other people wrongly?

Why would even refusing a vaccine be "getting people killed"? These vaccines are non-sterilizing. Get that trough your thick head. The ones getting people killed were the idiots who told vaccinated people to throw way their masks leading the vaccinated to both catch covid and spread covid. The current covid wave in the US is their fault. The CDC and the current government are a bunch of incompetents.

And if you stopped to think instead of blindly carrying water for them you'd see it. But your partisan agenda is more important huh?

The pandemic will only end because of herd immunity and vaccines. As long as there is still sufficient vulnerable population, the virus will return and will cause another wave.

There are only two endgame scenarios:
1) Enough people are immune (by vaccination and/or fighting off the disease) that so that the virus cannot effectively spread
2) We get regular waves like with the flu. Then you can decide whether you want to break those by having yet another lockdown every few months or go with "who dies, dies" (like with the flu).

The more people get vaccinated and the quicker this happens, the more likely we are going to end up with scenario 1.

It's impossible. Read up on how immunity (and vaccines) work. This is a quick virus, you can only count with antibodies already in the blood to react quickly against it. And those decline fast. Natural immunity will not end this any more than it ended the flu. By extension you cannot hope that vaccination will. But...

I think breakthrough cases have distracted us from the net threat. I've not seen that R is greater than 1 in immunized populations (I.e., between immunized people), though granted I've not really looked.

Finally someone asks a penitent question, instead of simply affirming the blind article of faith that herd immunity will work!

If we keep vaccinating everyone often enough to counter the decline in antibodies, and if those serum antibodies at least reduce the relative risk of getting infected, then we could hope for a R smaller than 1.

But by now I've read enough to be convinced we can't have it this way. Only with immune activity in the places that are actually the entryways for the virus - mucosal immunity...
We know for a fact that people with antibodies are getting infected, it's not just the imunocompromised.
We know that antibody levels decline anyway, which would require a heavy schedule of vaccination. Unattainable, especially worldwide.
We know that this virus keeps evolving and can get around existing antibodies, hence the setback from delta. But there's lambda, gamma I think that is even worse in evading immunity. For me it was game over when I saw the reports out of Manaus, the delta variant's effects only reinforced that conclusion.

I see no reason to hope that R will be <1 in a 100% vaccinated population without NPI. There is no going back to normal this way. It's a dead end. You can still hope, I can't prove this at the moment yet. But I'm pretty sure. And I think it's absolutely insane to waste 6 more months down this road. Plus the costs in terms of credibility for all authorities going along it will be terrible. It will perhaps burn any hope of organizing a different strategy and leave us stuck in a very bleak world.

Just to offer a different outlook: I went to the supermarket today, then to a pub. Literally everyone at the super was masked, and at the pub we all sat as far away from each other group as we could.

It just might be a local habit, a combination of paranoia and subservience to authority.

No subservience, it's just people acting cautious because of all they've lived through already. Good of them not to believe rosy promises and instead taking care. And good for you!

I don't want to have to live that way. None of us do. But while this madness of believing covid to be just about over continues, that's the good thing to do. Don't believe, take care.

 

[Birdjaguar]

Panic-Buying And Transport Lockdowns. In Wuhan, It Feels Like Early Pandemic Again
August 3, 202110:08 AM ET

https://www.npr.org/sections/corona...s-in-wuhan-it-feels-like-early-pandemic-again

...In total, China has confirmed 328 new locally transmitted cases since an outbreak that began last month, the state-controlled People's Daily reported. The new infections have popped up in more than 35 cities in half of the country's provinces and regions, according to The Associated Press....

 

[Kyriakos]

If anything, at least this nice crisis (which already goes on for 1,5 years) has shown that under some circumstances the governments and their media are very willing to drop even the pretense that democracy is paramount.
That, of course, only applies to those countries that are supposed to be democracies in the first place - but most posters here are from those.

I think that the erosion is too deep to fix. Global shaming is really too much, even for our less than stellar, chthonic species.

 

[Arwon]

My territory is at 50% of adults with first doses administered, first part of the country to get there. well over 80% of everyone over 65 has their first dose too, which is well ahead of much of the country.

Age gap there is due to staged eligibility, as is the gap between 1 dose and fully dosed, given the different timings on the vaccines.

 

[FriendlyFire]

Age gap there is due to staged eligibility, as is the gap between 1 dose and fully dosed, given the different timings on the vaccines.

Over 40s was not that long ago, and they are now vaccinating over 18s

Ive tried to get the Pfizer but they reserved it all for essential workers and the elderly, Which makes sense but would have really preferred Pfizer over less effective AstraZenica.
Meanwhile relatives in the US can get Pfizer but refuse the vaccine.

 

[Zardnaar]

Vaccine day tomorrow.

 

[Arwon]

Get AZ as soon as you can, they're both very good, both literally life savers, stop being picky and buying into the nonsense that fuels hesitancy. You should be able to do it at hubs in Sydney now. I got mine at a GP a few weeks ago after Morrison made that announcement for under 40s getting AZ.

 

[Zelig]

Get AZ as soon as you can, they're both very good, both literally life savers, stop being picky and buying into the nonsense that fuels hesitancy. You should be able to do it at hubs in Sydney now. I got mine at a GP a few weeks ago after Morrison made that announcement for under 40s getting AZ.

For an individual’s risk, given Australia’s case numbers, where do the think the age break-even is below which AZ isn’t worth getting?

 

[Arwon]

For an individual’s risk, given Australia’s case numbers, where do the think the age break-even is below which AZ isn’t worth getting?

I don't care

 

[The_J]

You have been able to get a score for how much of a difference an amino acid change will make ot the conformation of a protein for some years. Fitting proteins together is even older.

Yeah, but these things were not very accurate, IIRC.
For the first you'd also have to have the structure already, which for many is just not given. And then we also cannot necessarily predict the effect.
So... yeah, no, this doesn't convince me that much.

You need mucosal immunity, and that's a tough nut to crack. Unfortunately those working on vaccines with that aim were pushed out of the market, and therefore out of both funding and state sponsorship

I might not have the best overview, but I know that there is at least one nasally administered vaccine in development, and I'm pretty sure that is not hte only one.
I also wouldn't know if there is any data which suggests that the current vaccines don't produce IgAs...

These vaccines have one "public interest" advantage and one only: they do seem to reduce hospital demand during covid peaks.

And that's a bad thing?

We'll gonna have to live it like with influenza at the end. If not many people die/get hospitalized, then we're on the right way.

 

[amadeus]

Three weeks since first vaccination, Moderna.

I don’t know how rational this was, but after seeing a group of soccer fans coming from a game* get on the subway, I changed cars, tried to find the one with the fewest passengers, then disembarked one station early (total time on subway approx. 10 minutes, 5-6), gargled, changed masks, and washed my hands before picking up something at the convenience store & coming home and then taking a shower.

Overkill? I’m trying not to take too many supplementary anxiety medications. It doesn’t help that people are morons.

*keeping in mind our state of emergency, the seating is restricted. Should also be noted “delta” is now 60% of cases in this part of Japan, 90% in the Tokyo area.

 

[Hrothbern]

You are still hoping for herd immunity. It can't be achieved, not with these vaccines at least. They're too leaky. Even if you vaccinate 100% of the people you won't achieve herd immunity. Currently that is an impossible goal. Clinging to this hope is a mistake.
You need mucosal immunity, and that's a tough nut to crack. Unfortunately those working on vaccines with that aim were pushed out of the market, and therefore out of both funding and state sponsorship, by the availability of these - to be direct - crappy* vaccines.

It's one of those cases where a vaccine deemed "good enough", coupled with exclusively for-profit development, and with governments wanting their qhick fix now, are screwing us in the long term.

These vaccines have one "public interest" advantage and one only: they do seem to reduce hospital demand during covid peaks. But they won't end them and having seen the irresponsible behaviour of our rules that means they'll just let the "wave" get higher, more people infected, until the NPI are again deployed. So far we've seen that in the US with the official walkback for masking again. And informally, spontaneously, in the UK as people took up masking also. This is not a return to normal.

*Crappy because if they do reduce relative risk, that reduction doesn't seem great and they'll just be used as an excuse to let the absolute risk rise until the hospitals clog again. We'll see come Autumn, classes, the continued attempt to "reopen" as people shift indoors. End result is more people suffering bouts of supposedly "non-serious" covid which will leave them scarred. Something that reduces relative risk may, if used unwisely, actually elevate the absolute risk for everyone. That's what is happening with the vaccination campaign strategy.

Voltaire 18th century: "the best is the enemy of the good"
Robert Alexander Watson-Watt in ww2: "Always strive to give the military the third best because the best is impossible and second best is always too late."
(he was responsible for the UK having radar defense just in time for the Battle of Britain)
The Cult of the Imperfect: https://www.psychologytoday.com/us/blog/am-i-right/201411/the-cult-the-imperfect
Not something fancy. Lean Manufacturing is based on it. Not aiming for the perfect solution but a nurturing improvement process with good enough start conditions and settings.

Nothing wrong with the quick fixes we went through (the hammer & the dance lock-downs) and are now going through: max vaccination rates with the current generation vaccins.
Buying time meanwhile keeping the ship afloat.
Not every captain of the same qualities, not every crew and passengers of the same qualities... but that's life.

You can call it hope... I would call it direction without clear sight what lays beyond the horizon.


On those nasal vaccins.
They are in development and I am not aware of visible signs of obstruction. And yes... this kind of research does take time. Not a pizza in a 380 C furnace.
As it happened there was four days ago an article in Trouw (Dutch newspaper) on one of those nasal spreay vaccins that is being developed in NL by Intravacc.
Novel in this spray is that it uses bacterial membrane vesicles as package for the vaccin.
On bacterial vesicles in general: https://www.nature.com/articles/s41579-018-0112-2

Abstract
Most bacteria release membrane vesicles (MVs) that contain specific cargo molecules and have diverse functions, including the transport of virulence factors, DNA transfer, interception of bacteriophages, antibiotics and eukaryotic host defence factors, cell detoxification and bacterial communication. MVs not only are abundant in nature but also show great promise for applications in biomedicine and nanotechnology. MVs were first discovered to originate from controlled blebbing of the outer membrane of Gram-negative bacteria and are therefore often called outer-membrane vesicles (OMVs). However, recent work has shown that Gram-positive bacteria can produce MVs, that different types of MVs besides OMVs exist and that, in addition to membrane blebbing, MVs can also be formed by endolysin-triggered cell lysis. In this Review, we provide an overview of the structures and compositions of the various vesicle types and discuss novel formation routes, which may lead to distinct vesicle types that serve particular functions.

From a Trouw article of April 2021 in more layman wording:
https://www.trouw.nl/wetenschap/neusspray-uit-bilthoven-mengt-zich-in-vaccinwedloop~b2e2ed7f/

A corona vaccine developed by Intravacc in Bilthoven has passed the first test phase well. The vaccine provides very good protection against the virus in laboratory animals. This means that the company can prepare for the next phase: testing for safety and efficacy in humans. It is expected to start at the end of this year.

Worldwide, twelve vaccines are now fully or partially authorized and more than a hundred are already in that clinical phase. Yet Dinja Oosterhoff, program director at Intravacc, is not afraid that her vaccine will come after a meal like mustard. The world is far from getting rid of the coronavirus and Oosterhoff is convinced that a second generation of vaccines is needed.

Intranasal vaccine
Intravacc's vaccine can then be distinctive, she says. It's an intranasal vaccine – it's given with a nasal spray. “That means the first line of defense is already in the nasal mucus,” she says. “In addition, such a vaccine better prevents the virus from being transmitted. Of all the vaccines that have now been or are being developed, only a few intranasal vaccines are in the clinical phase.”

That is not the only distinguishing feature of the Bilthoven vaccine. Like almost all other corona vaccines, this also focuses on the so-called spike protein with which the virus gains access to the cells. But where other vaccines use a fat globule or a weakened virus to carry the genetic code of this protein, Intravacc has resorted to bacteria. To the vesicles with which bacteria communicate with each other, to be precise. These bacterial vesicles are not only cheap to produce, they are also dead material that cannot multiply in the body of the vaccinated person.

Intravacc already had experience with the vesicles, but then as a vaccine against the bacteria itself. Now they also appear to be suitable as a means of transport in a corona vaccine. At least in lab animals. All but one mouse developed neutralizing antibodies to the virus. Vaccinated hamsters did not become ill after exposure (mice are not susceptible to this virus) and none of them suffered any lung damage.

Clinical phase difficult
That convinces us that the vaccine is effective, says Oosterhoff. “We are now moving full steam ahead towards the clinical trial.” She assumes that the vaccine also produces a cellular immune response in humans; something that has not been looked at in the hamsters because of their specific defenses.

That clinical phase is still going to be difficult. After all, this requires test subjects who have not yet been in contact with the virus or a vaccine. If it is up to Minister Hugo de Jonge, they will no longer be available in the Netherlands by the end of this year. But maybe things aren't going so fast here, Oosterhoff responds.

This is not so important for the first phase of clinical research. This mainly concerns the safety of the vaccine and the participants may already have antibodies against the virus. And for the future, the fact that it is a nasal vaccine also offers opportunities. After all, in the nose, the built-up defenses sink the fastest. Then the intranasal vaccine can show whether it generates a new immune response.

And the update a week ago: all still going well
https://www.trouw.nl/wetenschap/int...-dit-is-geen-mosterd-na-de-maaltijd~b5c0f4ca/

A year ago it seemed the question of whether vaccines would come, and when, now there are some very effective ones available. Intravacc, which is based in Bilthoven, announced last spring that it has developed a vaccine that is safe and effective in laboratory animals. Safety studies will follow in the near future, after which the vaccine can be tested on humans at the beginning of 2022. First on safety, then on efficacy and effectiveness. The vaccine, which has been dubbed Avacc 10, should be available by the end of 2022. How do people from Intravacc estimate their chances?

Jan Groen: “It is a unique vaccine. There are still 272 vaccines under development worldwide. Most are, or need to be, injected. Our vaccine will be administered by nasal spray. That route is followed by only seven other vaccines. And within that group we also use a special technique.

“Scientifically it makes sense to use a nasal spray. After all, the virus also often enters through the nose. Our vaccine therefore immediately attacks the virus. If you introduce a vaccine into the body via a muscle, the local defenses are much lower. And because you apply it in the nose, you also ensure the production of specific antibodies, immunoglobulin A, which form the first defense precisely in the mucous membranes.

“A nasal spray is easier to administer. You must be medically qualified to give a shot. That is why our vaccine would be suitable for use in countries with a less developed medical infrastructure. Also because it is much cheaper than, for example, the RNA vaccines and also does not have to be stored in freezers. And don't forget the Netherlands. One in three adults and half of children have a fear of needle sticks.

As small side step:
Interestingly the fear for needles is here mentioned.
Many more people have issues here than we think.
We are all so d****d social and political correct, that you cannot simply grap all cows at their horns.
When you play cards during lunch break at work and come with some fancy story why you don't want a vaccin... the first remark (at least in Amsterdam workers culture) that you get tossed to your head if you profiled too much as "the tough guy": "ohhh... afraid for needles ?"
I don't want to derogate people afraid for needles, but making a taboo of it, is not gonna help adressing it.
And BTW the fainting of people with needle fear happens mostly after they got jabbed and relax again away from the build up tension and faint from the blood pressure drop. Such people should get their jab lying down on a bed or table.

And back on topic:
Perhaps the transport technique here developed by Intravacc is in the bigger picture more important than their vaccin.
But then another vaccin will make use of the gained knowledge to transport it to the nasal mucus.

 

[AdamCrock]

Nah I don't wanna. I don't trust this, call me what You will I will still not trust in the government , when They've discovered radioactive materials they've made watches, creams, radioactive foot warmers, night lamps and what-not out of the radioactive material - thank You very much.Maybe in a few Years.

 

[amadeus]

Please stay out of this country.

 

[Kyriakos]

Please stay out of this country.