Coronavirus

[alloverx]

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14 seniors in a German elder care facility have tested positive for the UK variant. All of them had received the 2nd dose of the Biontech/Pfizer vaccine on January 25.
So far all of them were asymptomatic or displayed only mild symptoms.
The first positive result showed up in tests that were done ~1week after they had received the 2nd dose.

Seems to confirm the assumed possibility that vaccinated people can still get infected and infect others.

The key point (for the vaccine) is that they did not have to go to hospital (I assume) or worse.

 

[NikolaACDC]

Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera

The non-reviewed results might have been mentioned before, but now they have been reviewed. The Biontech/Pfizer vaccine should work against the UK & SA variants.

"Abstract
We engineered three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses containing key spike mutations from the newly emerged United Kingdom (UK) and South African (SA) variants: N501Y from UK and SA; 69/70-deletion + N501Y + D614G from UK; and E484K + N501Y + D614G from SA. Neutralization geometric mean titers (GMTs) of 20 BTN162b2 vaccine-elicited human sera against the three mutant viruses were 0.81- to 1.46-fold of the GMTs against parental virus, indicating small effects of these mutations on neutralization by sera elicited by two BNT162b2 doses."


But

BioNTech/Pfizer vaccine should work against virus variants: Study

"...one limitation of the peer-reviewed study is "that the engineered viruses do not include the full set of spike mutations found in the [U.K.] or [South African] variants," the researchers said."

 

[EVNow]

"...one limitation of the peer-reviewed study is "that the engineered viruses do not include the full set of spike mutations found in the [U.K.] or [South African] variants," the researchers said."

I don't understand why they don't use real viruses - its not like Covid virus is in short supply.

 

[chronoreverse]

OCGN exploded today. Looks like it's also another Covid-19 vaccine. More is good but what makes this one jump so much? Is it purely because they sold stocks at a premium and the grab got so out of hand that it ended more than doubling the premium price?

 

[AlanSubie4Life]

Good news:
https://twitter.com/profshanecrotty/status/1358800645793271808?s=20

(Includes some in-situ data with Ct results in vaccinated individuals.)

Bad news:
https://twitter.com/profshanecrotty/status/1358836370404352003?s=20

Any, these are a couple of nice long threads showing there is a correlation between the antibody titers and the lack of efficacy of the AstraZeneca vaccine.

The good news is: this suggests that the existing vaccines (other than AZ and maybe Novavax) will likely be effective on currently known variants, as has been found so far (still no info on the P.1 variant, though, strangely) - since the correlates of protection do much better for the Pfizer/Moderna vaccines, and somewhat less so for the J&J (which has decent tested efficacy against the South African variant). Novavax does fairly poorly on this variant, as I recall (wouldn't know it from the stock price!).

I don't know what it is about the vaccine design that results in a poor immune response or a less specific immune response (not sure which it is).

There may of course be other correlates of protection not assessed here - and as mentioned in the threads, we really don't know whether AZ will be effective at preventing hospitalization & death with the variants - it's TBD, and obviously very important to know this (a lot harder to determine I think since it's such a relatively rare event). A severe cold is a lot better than hospitalization and death, and if a poorly performing vaccine can accomplish that, it would still clearly be good. We'll see.

I don't understand why they don't use real viruses - its not like Covid virus is in short supply.

I would guess (and it's only a guess) that there would be very strict controls on doing study on actual SARS-CoV-2 virus, rather than virus with constructed spikes or however they do this. I think directly modifying the sequence of SARS-CoV-2 to "see what happens" can relatively easily qualify as gain-of-function research.

For the particular quoted article I guess they're using actual SARS-CoV-2 so maybe not the issue here? Catching up here... don't actually have time to read all these articles so maybe someone else can comment.

Here's the actual vehicle used and a discussion of the considerations...guess it is useful to incorporate markers, etc. Lots of complexity here if you want to dive in! An Infectious cDNA Clone of SARS-CoV-2 - ScienceDirect

Gain-of-Function Research: Background and Alternatives - Potential Risks and Benefits of Gain-of-Function Research - NCBI Bookshelf

 

[chronoreverse]

There are vaccines that use real viruses. But it's generally not as easy to produce, test and manufacture. This is the reason why the mRNA vaccines are considered breakthroughs.

[edit]As for their testing regime, it's probably what they already had on hand (in terms of being well known, controlled and studied). They'll certainly followup on this.

 

[AlanSubie4Life]

There are vaccines that use real viruses. But it's generally not as easy to produce, test and manufacture.

This is the reason why the mRNA vaccines are considered breakthroughs.

He was asking about the viruses used to study the efficacy of the vaccines (tested by using vaccine-elicited sera against these test viruses).

 

[Jeff N]

Novavax does fairly poorly on this variant, as I recall

My general impression was that Novavax seemed to have very strong neutralizing antibody titres against the original virus (stronger than Pfizer/Moderna) and similar reports of efficacy near 95%. As far as I know, Novavax is using the same basic spike protein with pre-fusion stabilization mods so it’s not surprising that it seems to get similar results (AstraZenica does not have the stabilizing mods). Novavax is just making the spike proteins pre-vaccination while the mRNA vaccines are creating the spike proteins post-vaccination.

Despite excellent results on the original virus, Novavax reported efficacy of only about 60% on test volunteers in South Africa who were HIV- (or about 50% on all test volunteers combined).

I wonder what the basis is for assuming that Pfizer and Moderna will have substantially higher efficacy on the South African variant than Novavax.

Maybe Novavax triggers a less robust T-cell immune response (we don’t know yet since this is hard to measure)?

Or, maybe the assumption that Pfizer and Moderna will get 70-80% efficacy against the South African variant is just wishful thinking since we don’t have actual in-field test data for them yet?

 

[Feathermerchan]

Has anyone thought that we don't need to get to ~80% vaccinated to reach effective herd immunity? It seems to me that mask wearing and social distancing are kind of like a poor vaccine in that it slows/stops the spread of the virus.
Flame me if I'm wrong.

 

[Jeff N]

Has anyone thought that we don't need to get to ~80% vaccinated to reach effective herd immunity? It seems to me that mask wearing and social distancing are kind of like a poor vaccine in that it slows/stops the spread of the virus.
Flame me if I'm wrong.

Sure, but I think people were hoping that mass vaccination would succeed enough to get rid of the need for distancing and most of the mask wearing.

 

[chronoreverse]

Has anyone thought that we don't need to get to ~80% vaccinated to reach effective herd immunity? It seems to me that mask wearing and social distancing are kind of like a poor vaccine in that it slows/stops the spread of the virus.
Flame me if I'm wrong.

There's no reason to flame that since it's pretty much fact. Not every person can be vaccinated which is why it's important to get as many people vaccinated as possible as well as continue to use measures like social distancing and masks.

Over time, this can likely burn out the virus from the population. Then the measures can be dialed down like in New Zealand.

 

[TEG]

These breakthroughs on the mRNA vaccines are amazing, but are tempered by how much easier it is getting for various lab to engineer new virus mutations/modifications.

Some unthinkable scenario where some rogue lab tries to blackmail the world by saying they will release a virus where only they have the vaccine/anecdote. Like a nightmare from a science fiction movie.
Hopefully the ethical labs all develop the capability to quickly understand what nature might cook up, but also anything an evil lab might try to unleash so our "antivirus" software is better than any engineered virus someone might release someday.
This is not only to counter some evil action, but also to counter any lab leak mistakes that could happen when they are doing GoF tests to test how a new vaccine might work against some previously hypothetical threat.

We ought to be prepared forever more to have logistics in place for global mRNA vaccine updates to be pushed out rapidly when needed.

 

[chronoreverse]

Putting nefarious virus-makers aside, this crisis was a good jumpstart for the mRNA vaccine makers to build out mass production.

Imagine if the cost comes down to be comparable to flu vaccine production. Not only would it be a great boon to flu vaccine effectiveness (in good years where they predict correctly), this production capacity also means that new viruses like a hypothetical SARS3 could be knocked down far more quickly.

 

[Jeff N]

This gives more detail:

This helps satisfy my curiosity...

Endocytosis - Wikipedia

Yep, that’s the video I linked to a week ago.

Coronavirus

It turns out that the video may be a bit misleading.

The video is illustrating the TMPRSS2 infection pathway used against lung cells in which the virus’s RNA release is triggered by the TMPRSS2 cut and the virion (the complete virus) only needs to partially merge past the cell’s outer membrane.

There is an independent pathway for cells without TMPRSS2 (like kidney cells) in which the endocytosis triggered by the spike connecting to the ACE2 receptor needs to result in a completed endocytosis. In that pathway, the virion is fully engulfed through the outer membrane into the cytoplasm inside the cell and then the virion rides an internal highway built out of protein (microtubule) and is dragged further into the cell by a little protein motor (seriously). As the virion is dragged further into the cell, a proton pump mechanism causes the PH to be lowered (become more acidic) and this change triggers an enzyme called “cysteine protease cathepsin L” to take over the function of TMPRSS2 and make a cut to the spike protein which triggers the release of the virion’s RNA.

There is more than one “highway” and “protein motor” mechanism inside cells so I might have those details slightly wrong but it’s the right general idea. Probably, the engulfed virion is dragged into the cell using a dynein motor similar to this computer graphic simulation of a kinesin motor:

These two pathways are partially described in this article from last summer.

https://www.sciencenews.org/article/covid-19-coronavirus-hydroxychloroquine-no-evidence-treatment

The underlying research paper being reported in the article has now been officially published:

Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2

 

[AlanSubie4Life]

general impression was that Novavax seemed to have very strong neutralizing antibody titres against the original virus (stronger than Pfizer/Moderna) and similar reports of efficacy near 95%.

I can't keep track...I don't remember this specific comparison vs. the original virus.

Moderna/Novavax titers look similar here: SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral Spike vaccines

Or, maybe the assumption that Pfizer and Moderna will get 70-80% efficacy against the South African variant is just wishful thinking since we don’t have actual in-field test data for them yet?

Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization

Having a hard time keeping track, but yes, I think that assumption is just based on the neutralizing titers being very high still for Pfizer/Moderna (only down by a factor of 6-8 or whatever).

It seems to me that mask wearing and social distancing are kind of like a poor vaccine in that it slows/stops the spread of the virus.

Yes, that's why we need to keep that up. They're all interventions - but some are non-pharmaceutical. We can crush this virus to near zero, when we combine them all. If everyone does it. But unfortunately a lot of people think it's a hoax, don't mind dying, and inexplicably don't want to wear an N95 mask.

 

[EVNow]

The good news is: this suggests that the existing vaccines (other than AZ and maybe Novavax) will likely be effective on currently known variants, as has been found so far (still no info on the P.1 variant, though, strangely)

Depends on what you mean by effective.

Coronavirus

The above post shows a lot of seniors getting infected and possibly transmitting the UK variant even after 2 doses of Pfizer. So, basically the idea of herd immunity is out with the new variants and given vaccine hesitancy etc we'll have to just learn to live with Covid in the long term. A depressing thought.

 

[AlanSubie4Life]

Depends on what you mean by effective.

A vaccine that prevents hospitalization is huge. That's what I mean by effective. Any vaccine that does that is likely to reduce transmissibility as well, and will help us reduce spread and make it easier for NPIs to work. Not to mention it will bring hospital overload to an end. We'll see. Obviously the ideal is one that provides complete immunity and eliminates transmission as well.

The above post shows a lot of seniors getting infected and possibly transmitting the UK variant even after 2 doses of Pfizer. So, basically the idea of herd immunity is out with the new variants and given vaccine hesitancy etc we'll have to just learn to live with Covid in the long term. A depressing thought.

It would be great to have more info on this case. The date of the article and the details on that were so sparse (I did look) it was impossible to interpret. How many seniors total in this facility? What % were infected? When did they start showing symptoms? When was the first known infection? When did they test positive? Presumably not all at once... When did they get their second dose relative to the actual infection? It takes 3-4 days and possibly a bit longer to develop a full antibody response to the second dose.

So I think that particular incident is so lacking in details it is hard to draw conclusions. Additionally, it's in an immunoscenescent community; we expect that elderly will not represent the norm (that's why we all get vaccinated!!!), and we don't even know the attack rate in this community! What if it were 14 seniors out of 150 vaccinated seniors, with a handful of symptomatic cases, with most being asymptomatic? Would that change your conclusion?

So it's very hard to draw a conclusion from that. So little information that it is not useful. We know for sure that after just one dose of Pfizer you have antibody levels far below those that are shown to be neutralizing for the South African variant, so you would expect lower efficacy if an infection took hold around the time of the second injection.

Additional links providing all these key details would be helpful.

In any case, for the B.1.1.7 variant specifically, the results for Pfizer and Moderna in vitro and in vivo in trials have been extremely promising. And there is even data out there now (I believe) showing reduced transmissibility.

 

[rxlawdude]

Depends on what you mean by effective.

Coronavirus

The above post shows a lot of seniors getting infected and possibly transmitting the UK variant ...

"Possibly transmitting" is not helpful. So far, early data suggests transmission is substantially reduced post vaccination (and a couple of weeks after the last injection).

 

[EVNow]

Has anyone thought that we don't need to get to ~80% vaccinated to reach effective herd immunity? It seems to me that mask wearing and social distancing are kind of like a poor vaccine in that it slows/stops the spread of the virus.
Flame me if I'm wrong.

You would be somewhat right if a party that represents about half the voting population in the US hadn't made masks a culture war issue. I guess if the ex-president says don't wash your hands after using the restroom - all these people will follow that too.

Let's ignore that for a moment. With the new variants even that 80% won't work because of reduced efficacy and increased transmission.

The idea of herd immunity is to get rid off the virus in order to not have to socially distance / wear a mask (or for people like me end complete isolation). Periodically recurring bouts of infections in large sections of the population, with increased probability of ever more potent mutations - which can cause serious damage to your (or your family & friends) organs is not a happy situation to be in.

 

[Jeff N]

The above post shows a lot of seniors getting infected and possibly transmitting the UK variant even after 2 doses of Pfizer. So, basically the idea of herd immunity is out with the new variants and given vaccine hesitancy etc we'll have to just learn to live with Covid in the long term. A depressing thought.

That’s a bit pessimistic. I think it shows we will need a booster shot this fall that is based on the spike protein from the Brazilian/South African variants.

Maybe the virus will continue to mutate with similarly effective antibody escape changes after that but we don’t actually know yet. At worst, we might seem to need an annually booster shot at the same time as people get their flu shots.