Covid-19 #25: The Prisoner’s Dilemma

[Zorral]

Speaking of vaccination reactions, for those who have them, many report it is the second jab that does it.

https://www.theatlantic.com/health/archive/2021/02/second-vaccine-side-effects/617892/

Quote

 

....Dose No. 2 is more likely to pack a punch—in large part because the effects of the second shot build iteratively on the first. My husband, who’s a neurologist at Yale New Haven Hospital, is one of many who had a worse experience with his second shot than his first.

But much like any other learning process, in this one repetition is key. When hit with the second injection, the immune system recognizes the onslaught, and starts to take it even more seriously. The body’s encore act, uncomfortable though it might be, is evidence that the immune system is solidifying its defenses against the virus.

“By the second vaccine, it’s already amped up and ready to go,” Jasmine Marcelin, an infectious-disease physician at the University of Nebraska Medical Center, told me. Fortunately, side effects resolve quickly, whereas COVID-19 can bring on debilitating, months-long symptoms and has killed more than 2 million people....

 

 

[The Anti-Targ]

34 minutes ago, Impmk2 said:

I'd be surprised if there was no cross protection. The immune system creates antibodies against antigen other than the spike protein receptor binding domain which is being commonly targeted in vaccines, and is also the site that's really concerning with these mutations. Though many antibodies won't be targeting any kind of surface antigen necessary for cell entry (ie not neutralizing) so they may not stop the initial infection, but then may have a limiting effect on disease progression.

That's not even going into the other arms of the adaptive immune response (T-cell mediated immunity) that get even more complicated so I like to pretend don't exist (not an immunologist). 

But I'm also not up to date on the longitudinal studies of the immune response to SARS-CoV-2 infection. If it's dropping off after a year, and cross protection isn't great, reinfection may well be a frequent thing.

 

We already have confirmed cases of re-infection, albeit not common and not leading to significant illness, with the same strain. This suggests an immunologically distinct strain should more readily cause reinfection. The thing about mutations in non-functional antigens is that they are likely to happen more often. Because they generally don't affect the ability for the virus to enter cells and reproduce, these mutations will perpetuate more quickly within the virus population. The only spike protein mutations that will be able to perpetuate are the ones that still allow the virus to attach and enter cells. 

So I would tend to err on the side of caution and assume there is moderate risk, at least, of re-infection when one of these new strains is circulating in the population.

[Padraig]

4 hours ago, Zorral said:

"Israel Is the World’s Most Vaccinated Country. Why Are Cases Rising?"

https://nymag.com/intelligencer/2021/02/why-are-cases-rising-in-israel-the-most-vaccinated-country.html

Hmm.  That does seem to be a wasted opportunity.  Way ahead vaccination wise but a lot of other things not working.  Deaths in Israel are only moderately below their peak at the end of the January.

Reports are saying that vaccinated people seem less likely to transmit coronavirus.  Which is just as well since Israel is unlikely to get to herd immunity since children under 16 are now allowed to be vaccinated yet (and that's ignoring the Palestine question).  See here.

[Impmk2]

12 minutes ago, The Anti-Targ said:

We already have confirmed cases of re-infection, albeit not common and not leading to significant illness, with the same strain. This suggests an immunologically distinct strain should more readily cause reinfection. The thing about mutations in non-functional antigens is that they are likely to happen more often. Because they generally don't affect the ability for the virus to enter cells and reproduce, these mutations will perpetuate more quickly within the virus population. The only spike protein mutations that will be able to perpetuate are the ones that still allow the virus to attach and enter cells. 

So I would tend to err on the side of caution and assume there is moderate risk, at least, of re-infection when one of these new strains is circulating in the population.

I can agree with most of this - though I'd draw a distinction between non-functional and not directly involved in cell binding / invasion. The nucleocapsid protein (for example) apparently gets a significant antibody response, but it almost certainly wouldn't be a neutralizing one. It's main function is in packaging the viral RNA and assembly of the virion (ie functioning as a scaffold for the other proteins to form around). I would be very surprised if there aren't critical portions of that protein which are not at all prone to mutation and could help direct the immune response.

Edit: Just occurred to me that the main primer sets used by the CDC (and we used in a study last year in our lab) are for the nucleocaspid protein, so there are definitely non-variable regions outside of the spike.

[The Anti-Targ]

4 minutes ago, Impmk2 said:

I can agree with most of this - though I'd draw a distinction between non-functional and not directly involved in cell binding / invasion. The nucleocapsid protein (for example) apparently gets a significant antibody response, but it almost certainly wouldn't be a neutralizing one. It's main function is in packaging the viral RNA and assembly of the virion (ie functioning as a scaffold for the other proteins to form around). I would be very surprised if there aren't critical portions of that protein which are not at all prone to mutation and could help direct the immune response.

 

Yes, I should have been more specific about non-functional. Really, every antigen is functional from the perspective of the virus, and any mutation that causes non-viability will terminate that strain.

I guess it's one of the limitations of both the AZ and mRNA vaccines. They only give the immune system one antigen to work on. The most important one to be sure, but the other antigens can and probably do help with the immune response. An inactivated whole virus or a live attenuated virus vaccine would give more antigens for the immune system to play with, and potentially allow for a better immune response to challenge by different strains.

I believe someone is working on an inactivated whole virus vaccine. I don't think there is any work being done on a live attenuated virus.

[Crixus]

Too little, too late: https://www.theguardian.com/technology/2021/feb/08/facebook-bans-vaccine-misinformation

Twitter is also removing vaccine conspiracy threads now.

 

 

 

[Derfel Cadarn]

Just got a call from gp surgery; die to cancellation (probably due to the snow) I can get my jab at 11

[rotting sea cow]

16 hours ago, Fragile Bird said:

Remember the discussion we had recently, maybe in the last thread, I forget, about the length of time it takes to make the mRNA vaccines? At least a month, a length of time some people found hard to believe?

I’ve mentioned I watch CNBC in the mornings, they do a lot of updates on vaccines because people want to be informed investors. They just reported news from Pfizer. Pfizer has announced they are working to speed up vaccine production. Until now the average time to make their vaccine has been 110 days.

Let me repeat that - the average time to make the Pfizer vaccine has been 110 days. With experience under their belts now they plan to get that down to 60 days.

Sanofi signed a contract with Pfizer to help with the end packaging, getting vaccine into vials, where, it was reported, “the bottleneck was occurring”. I don’t think that’s where the bottleneck was at all. The fact is the process is new and nobody had made a human mRNA vaccine before, and never in such quantities.

You might want to read this link.

https://blogs.sciencemag.org/pipeline/archives/2021/02/02/myths-of-vaccine-manufacturing

Derek Lowe has been very illuminating in everything related to vaccines (and medicines too) during these months

According to his educated guess, this is the bottleneck

Quote

Ah, but now we get back to Step Four. As Neubert says, “Welcome to the bottleneck!” Turning a mixture of mRNA and a set of lipids into a well-defined mix of solid nanoparticles with consistent mRNA encapsulation, well, that’s the hard part. Moderna appears to be doing this step in-house, although details are scarce, and Pfizer/BioNTech seems to be doing this in Kalamazoo, MI and probably in Europe as well. Everyone is almost certainly having to use some sort of specially-built microfluidics device to get this to happen – I would be extremely surprised to find that it would be feasible without such technology. Microfluidics (a hot area of research for some years now) involves liquid flow through very small channels, allowing for precise mixing and timing on a very small scale. Liquids behave quite differently on that scale than they do when you pour them out of drums or pump them into reactors (which is what we’re used to in more traditional drug manufacturing). That’s the whole idea. My own guess as to what such a Vaccine Machine involves is a large number of very small reaction chambers, running in parallel, that have equally small and very precisely controlled flows of the mRNA and the various lipid components heading into them. You will have to control the flow rates, the concentrations, the temperature, and who knows what else, and you can be sure that the channel sizes and the size and shape of the mixing chambers are critical as well.

These will be special-purpose bespoke machines, and if you ask other drug companies if they have one sitting around, the answer will be “Of course not”. This is not anything close to a traditional drug manufacturing process. And this is the single biggest reason why you cannot simply call up those “dozens” of other companies and ask them to shift their existing production over to making the mRNA vaccines. There are not dozens of companies who make DNA templates on the needed scale. There are definitely not dozens of companies who can make enough RNA. But most importantly, I believe that you can count on one hand the number of facilities who can make the critical lipid nanoparticles. That doesn’t mean that you can’t build more of the machines, but I would assume that Pfizer, BioNTech, Moderna (and CureVac as well) have largely taken up the production capacity for that sort of expansion as well.

He also just made an article about the fabrication of adenovirus vaccines

https://blogs.sciencemag.org/pipeline/archives/2021/02/08/how-you-make-an-adenovirus-vaccine

It seems simpler but there are some steps that are more art than science.

 

 

[rotting sea cow]

8 hours ago, The Anti-Targ said:

I believe someone is working on an inactivated whole virus vaccine. I don't think there is any work being done on a live attenuated virus.

Sinovac and SinoPharm are inactivated virus vaccines. S. America countries and other regions are receiving millions of doses already. The effectivity is lower than in those fancy mRNA vaccines but it might protect better against new variants. We'll see soon enough I guess.

[rotting sea cow]

@The Anti-Targ & @Impmk2

This is probably the best study on re-infecctions based on NHS data on health workers.

Covid-19: Past infection provides 83% protection for five months but may not stop transmission, study finds

https://www.bmj.com/content/372/bmj.n124

So, it seems that natural infection is as good as any vaccine (but arguably riskier). There are some news that point to higher reinfection possibilities with the S. African variant. E.g.

Can you get reinfected with Covid-19? SA has ‘4 000 potential reinfections’

https://mg.co.za/news/2021-01-19-can-you-get-reinfected-with-covid-19-sa-has-4-000-potential-reinfections/

but I don't know if this has been properly quantified.

and you probably have seen this

Coronavirus digest: German nursing home sees outbreak after vaccines

https://www.dw.com/en/coronavirus-digest-german-nursing-home-sees-outbreak-after-vaccines/a-56491823

apparently the residents are asymptomatic or have mild infections, which is good, but my take-away from all of this, is that herd immunity doesn't exist with covid-19 and we are all going to get infected, vaccines or not. Vaccines are of course our best chance to not get to the hospital, but we are going to be dealing with this for a long time. 

Fortunately we haven't seen any sign that ADE is happening anywhere, which is a relief. On the other hand, I wonder if the virus may still have some nasty surprises under the hood. I had a bad dream about that.

 

 

[The Anti-Targ]

The purpose of vaccination is either eradication of a disease - only been achieved twice globally in history, once in people with smallpox and once in animals with rinderpest, or management of the worst effects of a disease. It seems like SARS-CoV-2 may not be eradicable, partly because immunity may not last long enough in individuals for an eradication strategy to work, partly because we have way more anti-vaxxers than we had (I think) back when smallpox was eradicated, and partly because SARS-CoV-2 may mutate just enough to be able to keep dodging the full force of a vaccine. Many many months ago I observed that there are 2 coronavirus diseases that affect pigs: one a gastric disease which has proven unvaccinatable, one a respiratory disease that is sufficiently vaccinatable to allow for movement of animals from endemic areas to free areas within a fairly short span of time and after a quarantine period. I mused at the time that our coronavirus may be similarly responsive to vaccination as the pig respiratory virus. It looks like immunity is lasting longer than for pigs, but not an impressively long time (years, like the smallpox vaccine) that would easily support eradication.

So, management it is. So long as vaccination helps to make death extremely rare and hospitalization infrequent, then that's good enough and it will allow for populations to move and mix without concern. Hopefully it also prevents long COVID. I think we here in COVID-free(ish) countries are going to have to face up to the fact that we will have to let the virus in by opening our border to quarantine-free travel (pre-arrival vaccination 14 days before departure should slow the entry), the only question is how much vaccination coverage domestically we want to achieve before we do that. My guess for NZ is that with the timeline being vaccination for the gen pop starting after June our border will be closed for most of the rest of the year. The good thing is, we've managed to figure out how to achieve slight economic growth and a reduction in unemployment while keeping our border closed.

25 minutes ago, rotting sea cow said:

Can you get reinfected with Covid-19? SA has ‘4 000 potential reinfections’

https://mg.co.za/news/2021-01-19-can-you-get-reinfected-with-covid-19-sa-has-4-000-potential-reinfections/

but I don't know if this has been properly quantified.

Just like confirmed cases is the tip of the iceberg for total infections, I imagine that 4000 is the tip of the reinfection iceberg.

As to ADE (full disclosure I had to look up what that is), this seems to offer some reassurance, though also a warning about VAH - see below, back in Nov 2020, which seems to have somewhat played out for some vaccines with people with extreme allergy history, https://pubmed.ncbi.nlm.nih.gov/32785649/

Quote

Abstract

Might COVID-19 vaccines sensitize humans to antibody-dependent enhanced (ADE) breakthrough infections? This is unlikely because coronavirus diseases in humans lack the clinical, epidemiological, biological, or pathological attributes of ADE disease exemplified by dengue viruses (DENV). In contrast to DENV, SARS and MERS CoVs predominantly infect respiratory epithelium, not macrophages. Severe disease centers on older persons with preexisting conditions and not infants or individuals with previous coronavirus infections. Live virus challenge of animals given SARS or MERS vaccines resulted in vaccine hypersensitivity reactions (VAH), similar to those in humans given inactivated measles or respiratory syncytial virus vaccines. Safe and effective COVID-19 vaccines must avoid VAH.

 

[IheartIheartTesla]

Microfluidic devices are so precise because they (essentially) make things one drop at a time. This means their throughputs are extremely small, and to go from these devices to essentially 100 million doses boggles the mind. Keep in mind that there are 5-6 orders of magnitude in scale between the large scale drums/baffle tanks he is talking about and a microfluidic device, so it might be that there is an intermediate scale of production that sacrifices some, but not too much in terms of precision while at the same time allowing for a bit larger scale production. Or they have thousands of these devices lying around.

[Fragile Bird]

I’ve been hearing stories that the vaccination rate in Israel has dropped off, and the country is hitting resistance among certain groups, like the ultra orthodox and younger people. This is after about 30% of the country has received two doses.

I had been meaning to mention that I have seen a number of commentators in the US fearing that after the 100 M mark is reached in the US the vaccination rate will drop off. Those fears seem to align with what Israel is experiencing. Part of the reasoning seems to be that Trump so poisoned the atmosphere there’s a very large group in the US that’s very resistant to any taking basic precautions like mask wearing and social distancing and that resistance will extend to the vaccine.

In Canada the flu vaccine is usually taken by 35% to 40% of the population, although it hit 42% in the 2018/19 season. I expect the uptake will be higher for the Covid vaccine, but who knows.

There might be a lot more vaccine doses flowing to other nations sooner than you may think.

Question: will governments mandate vaccine usage? I assume China will, who else?

eta: I thought I’d look up the US flu vaccination rate and in that same 2018/19 season the rate was 49%. The US quotes “age 6 and over” while Canada quotes “age 12 and over”. I was surprised at the idea children over 6 get the flu vaccine in the US, and I wonder how many were in the age 6-11 group in the US. But I assume that at the very least the flu cohort will get the Covid vaccine, although people under 18 (or 16?) won’t be allowed to yet. Still, not great numbers for herd immunity.

[Mr. Chatywin et al.]

Arm is definitely sore this morning, but otherwise there have been no side effects. 

[Paladin of Ice]

17 hours ago, Zorral said:

Speaking of vaccination reactions, for those who have them, many report it is the second jab that does it.

https://www.theatlantic.com/health/archive/2021/02/second-vaccine-side-effects/617892/

 

That was the case with me. I had no reaction to the first shot aside from arm soreness, and while I remember a bunch of the nurses that I work with said they felt tired after awhile (nurses who got the shot at 8 or 9 said they felt ready to drop from fatigue around 2-3), that was it.

 The second shot really kicked our asses. Our location got it last Wednesday, it seems like everyone started reacting that night or the next day, with pretty much everyone feeling the same: fatigue, headache, stomach queasiness or outright nausea, and some (including myself) were also feeling light-headed. I started developing fever and chills Thursday night after having the rest of the symptoms I listed all day Thursday, but the fever and chills vanished almost as soon as I took some Tylenol.

By Friday morning only the stomach issues were left, but it was strong enough that I called out, slept in, and couldn't eat until around 2 or 3 in the afternoon. Since then, however, I've been good.

[Zorral]

3 hours ago, Fragile Bird said:

I’ve been hearing stories that the vaccination rate in Israel has dropped off, and the country is hitting resistance among certain groups, like the ultra orthodox and younger people. This is after about 30% of the country has received two doses.

That's part of it.

[DireWolfSpirit]

3 hours ago, Fragile Bird said:

I’ve been hearing stories that the vaccination rate in Israel has dropped off, and the country is hitting resistance among certain groups, like the ultra orthodox and younger people. This is after about 30% of the country has received two doses.

I had been meaning to mention that I have seen a number of commentators in the US fearing that after the 100 M mark is reached in the US the vaccination rate will drop off. Those fears seem to align with what Israel is experiencing. Part of the reasoning seems to be that Trump so poisoned the atmosphere there’s a very large group in the US that’s very resistant to any taking basic precautions like mask wearing and social distancing and that resistance will extend to the vaccine.

In Canada the flu vaccine is usually taken by 35% to 40% of the population, although it hit 42% in the 2018/19 season. I expect the uptake will be higher for the Covid vaccine, but who knows.

There might be a lot more vaccine doses flowing to other nations sooner than you may think.

Question: will governments mandate vaccine usage? I assume China will, who else?

eta: I thought I’d look up the US flu vaccination rate and in that same 2018/19 season the rate was 49%. The US quotes “age 6 and over” while Canada quotes “age 12 and over”. I was surprised at the idea children over 6 get the flu vaccine in the US, and I wonder how many were in the age 6-11 group in the US. But I assume that at the very least the flu cohort will get the Covid vaccine, although people under 18 (or 16?) won’t be allowed to yet. Still, not great numbers for herd immunity.

I can attest that the bolded is true among the fundy, nutjob, Trumpists in our workforce. One particular military vet that is otherwise eligible to get his shot at the Michigan V.A. hospital has told me he " Refuses to put that poison " in him!

The poison is deep in their Reich mindset. There is no conversation to be had or wasted on them as far as I'm concerned.

 

[mnedel]

I can give you the experience from the hospital I work at. It is in Serbia so we had three vaccines to choose from: Pfizer, Sputnik and Sinofarm. Of about 1000 employees, 400 took a vaccine, majority took Pfizer, some took Sputnik and only a few Sinofarm. I had my second Pfizer dose a week ago. After the first dose, I only had a weakly sore arm, but after the second dose I had severe pain. I also had a low-grade fever and was feeling a bit under the weather. It lasted for a day and a half and after that I was fine. Several other people were feeling weak and tired after the second dose of Pfizer, so much so that they had to leave work early and some took a day off after. One nurse had an allergic reaction to the first dose. She got a rash and tachycardia but it cleared quickly after medication. Finally, one physician had dizziness and nausea that lasted for 2 days after the first shot. Both of them haven't received their second doses yet , hopefully it will be ok. We also have a research division and they are testing the antibodies of all employees who volunteered at 10-day intervals. They want to see the dynamics of antibodies production and how different vaccines are performing. I just received a result, after 7 days from second Pfizer dose, and I have 18000 au/ml antibodies, so its working. Hope this was of interest to read. 

[IheartIheartTesla]

Children in the US can get seasonal flu vaccine 6 months and older. This is part of both the CDC and American Pediatric Association recommendations/guidelines. I just looked this up, and the Canadian pediatric association has similar recommendations. I would be surprised if Canada doesnt have similar numbers for the younger cohort of babies, toddlers and little boys (my son has got the flu vaccine and he is younger than 6)

Younger children are at higher risk than the 6-11 age group, so it makes sense to vaccinate them against the seasonal flu. Luckily they arent as affected by COVID, or we'd have had real issues in getting trials done for any vaccine to be used on such a young cohort.

[Fragile Bird]

25 minutes ago, IheartIheartTesla said:

Children in the US can get seasonal flu vaccine 6 months and older. This is part of both the CDC and American Pediatric Association recommendations/guidelines. I just looked this up, and the Canadian pediatric association has similar recommendations. I would be surprised if Canada doesnt have similar numbers for the younger cohort of babies, toddlers and little boys (my son has got the flu vaccine and he is younger than 6)

Younger children are at higher risk than the 6-11 age group, so it makes sense to vaccinate them against the seasonal flu. Luckily they arent as affected by COVID, or we'd have had real issues in getting trials done for any vaccine to be used on such a young cohort.

Since I don't have children, I had no idea how young they could be when they received the flu vaccine!