Coronavirus

[Jeff N]

Good overview of how the Pfizer and Moderna vaccines are ordered and then make their way from the factory to local clinics.

This is how America gets its vaccines

 

[AlanSubie4Life]

We’ll have to get an additional 3rd shot in the fall.

Probably true.

I've not posted here in a long while - was hoping this vaccine is the light at the end of the tunnel. Not so sure anymore. New variants, vaccine hesitancy probably means we won’t get to herd immunity anytime soon.

I'm not worried about this much at all. The vaccine hesitancy may be a thing, but the vaccines are so effective it may not matter much as long as we take SOME precautions to reduce R.

As far as the immunity in the face of variants is concerned, I am not too worried, and optimistic. There doesn't seem to be any evidence of significant escape which results in severe disease, at this point.

It’s just that it has evolved some changes to its spike protein that cause antibodies formed against the original virus to no longer function well on some mutated variants found commonly now in South Africa and parts of Brazil (and probably will be common in the next few months in the USA and elsewhere).

Yep, and they appear to largely be convergent. Which means that the reformulated mRNA boosters will likely be the end of the road for the virus, since further mutations are probably not going to be significantly advantaged. But it seems like existing vaccines will probably work well enough. I don't know whether 'original antigenic sin' will apply to the new boosters or not, but hopefully not (I don't really understand exactly when that is an issue). As you say, those other elements of the immune system also appear be working well in this case, too.

My guess is the P.1 variant from Manaus is overly feared due to a study that was just wrong. I'm guessing that study wasn't correct and Manaus was never close to herd immunity, though I remember the study being sort of convincing. But we'll see; once we see a paper or two published on serum neutralizing activity against this variant, we'll have a much better idea - and maybe I'll be eating my words and excessive optimism!

All the available or soon to be available vaccines in the US seem to work really well, including J&J, and unless something very surprising happens with these variants, this pandemic will be over. People might still be contracting the variants, but there's not a lot of evidence that people who are vaccinated have severe or critical disease; the vaccine appears to be very protective against severe disease.

I expect large scale outbreaks in the US will come to an end (with some continued mitigation measures kept in place) in late April or May, when a significant (100 million) people have been vaccinated (obviously vaccination will continue through the summer, though). Focus mid year will then move to how to make the rest of the world safe and make travel to other countries possible.

At least I hope so!

 

[TEG]

Nope, many viruses including Coronaviruses really do follow the key and the keyhole analogy — the keyhole being an ACE2 enzyme on the surface of many types of cells in your body. That receptor is indeed normally intended for human biological purposes.
Angiotensin-converting enzyme 2 - Wikipedia
The image in your post is showing endocytosis which is one of several ways that various things can be brought inside of a cell through its membrane. This mechanism is used for normal cell functioning but the virus hijacks normal endocytosis in order to get inside. In order to begin endocytosis, one of the spike proteins (the keys in this analogy) that stud the outside of the virus physically attaches itself to an ACE2 (the keyhole) on the surface of the cell by randomly bumping into it and thus triggers the endocytosis to begin.

Thanks for the videos.
So the mental struggle for me over this was the idea that ACE2 is a keyhole and COVID has the key, but our antibodies would attack only COVID, not other things with an ACE2 key.

bkp_duke said "the spike protein is a foreign protein. That is what the vaccine is priming your immune system to see and react to."
So if the COVID spike protein is a "foreign protein" what do we call the regular biological processes that use the same "keyhole" in ACE2 for normal interactions?
Is it like those things have a different "shaped" key that can still open the ACE2 lock, but enough different looking that our antibodies, and the response from mRNA vaccines don't see those as a threat?

 

[AlanSubie4Life]

Is it like those things have a different "shaped" key that can still open the ACE2 lock, but enough different looking that our antibodies, and the response from mRNA vaccines don't see those as a threat?

Yeah they are only 7 amino acids long.

 

[Jeff N]

My guess is the P.1 variant from Manaus is overly feared due to a study that was just wrong. I'm guessing that study wasn't correct and Manaus was never close to herd immunity, though I remember the study being sort of convincing.

On the other hand, the new Novavax vaccine seemed to indicate that 1/3 of their vaccine phase 3 trial participants in South Africa had been previously infected last spring with the original virus but I think I read that the limited test data indicate that those people got (re)infected with the new South Africa variant just as often as the participants who were not previously infected with the original virus. In other words, having been previously infected with the original virus gave them an immune response that didn’t prevent them from being infected again with the new variant. In fact, for those 1/3 who were infected last spring the Novavax vaccine was effectively a booster on top of their original immune response and yet the overall efficacy of the vaccine was still reported as 50-60% against the new variant.

Since the South African and Brazilian (B.1.351 and P.1) viruses have converged on many of the same major spike mutations that would be consistent with a significant fraction of people in Manaus being reinfected now with the new variant.

Still, the data is rather limited so we don’t really know with any precision.

I expect large scale outbreaks in the US will come to an end (with some continued mitigation measures kept in place) in late April or May, when a significant (100 million) people have been vaccinated (obviously vaccination will continue through the summer, though).

I’m not that optimistic given that the variant viruses are expected to become common in that timeframe. The high efficacy of the current vaccines against the original virus but possible so-so efficacy against the new variants would make it even more likely that the variants would quickly become dominant then.

Even though the vaccines seem to be very protective against severe disease regardless of variant, if lots of people are still becoming ill symptomatically due to a variant virus with moderate disease then the more frail victims (because of advanced age or co-morbidities) may end up in the hospital anyway — just not in the ICU. The variant viruses are also allegedly 30-50% more transmissible which means their R values are higher and thus the threshold percentage for herd immunity is higher. There is also some uncertainty about how often vaccinated people can get the virus asymptomatically and how effectively they can retransmit it which would also factor into the herd immunity calculation.

I was optimistic things would largely go back to normal by next fall but the variants have raised a lot of questions. Normal times might get pushed back until a year from now. I hope things turn out better!

So if the COVID spike protein is a "foreign protein" what do we call the regular biological processes that use the same "keyhole" in ACE2 for normal interactions?
Is it like those things have a different "shaped" key that can still open the ACE2 lock, but enough different looking that our antibodies, and the response from mRNA vaccines don't see those as a threat?

Bingo. Note that the original virus and the new variant viruses both attach well to the ACE2 receptor even though their spike protein shapes changed enough so that some of the original virus antibodies no longer work well. Our immune system is good at recognizing expected normal proteins and leaving them alone.

 

[EVNow]

I am also in the Seattle area, and have experienced the frustration in working through the WA State website. However I had also signed up for the Virginia Mason "notify me when an opening is available" waitlist. For those outside this area Virginia Mason is a large Hospital and medical services provider here locally. It was kind of frustrating not being able to check status, the only information was on their website saying that they are overwhelmed with demand. Yesterday I got a notification that I was eligible to sign up for an appointment. I interacted with some very slick software that someone at VM or Amazon has put together on very short notice and have an appointment tomorrow at the Amazon/VM super vaccination site where I have to show a QR code to even get in. It is very frustrating to keep checking for appointment availability, the waitlist idea works well even though you are in the dark about where you are in the line.

That’s good. I signed up at VM sometime back. Haven’t heard from them - but then I’m in the last category within 1B (multigenerational) - so i’m fine with seniors getting their shots first.

I think the worst are QFC and Safeway. You have to search at each store to see if they have a vacancy. It’s always the billion dollar companies that have the worst software.

I don’t see how older people can navigate through all this complexity without help.

 

[jerry33]

I don’t see how older people can navigate through all this complexity without help.

Older than what?

 

[EVNow]

Older than what?

People in their 80s or late 70s.

Some of them might be savvy - most people I know in that age group would struggle.

 

[TEG]

Is there any sense if people asymptomatic to original COVID would also likely be asymptomatic to the new mutations?

 

[TEG]

People in their 80s or late 70s.
Some of them might be savvy - most people I know in that age group would struggle.

Be careful there. I once suggested that the Tesla UI was better for younger people, and got chewed out by some 80+ers who said that it is a stereotype to suggest they would have trouble learning new UIs. Those "sharp as as a tack" late seniors don't like being pigeonholed.

 

[TespaceX]

Focus mid year will then move to how to make the rest of the world safe and make travel to other countries possible.

At least I hope so!

More like how to persuade the rest of the world to accept that travelers from the US are safe enough to loosen restrictions.

We have extended family throughout Eastern Asia. Besides the strict testing and quarantine requirements, the general consensus is they’re not too happy seeing American tourists.

 

[AlanSubie4Life]

On the other hand, the new Novavax vaccine seemed to indicate that 1/3 of their vaccine phase 3 trial participants in South Africa had been previously infected last spring with the original virus but I think I read that the limited test data indicate that those people got (re)infected with the new South Africa variant just as often as the participants who were not previously infected with the original virus. In other words, having been previously infected with the original virus gave them an immune response that didn’t prevent them from being infected again with the new varian

Yep, it’ll be interesting to get the full analysis here with info on exactly what happened and how severe the initial illness was and how severe the follow up was.

I am still optimistic that the boosted mRNA vaccine will be effective against these variants - unlike the protein-based vaccine.

I would like to know from an immunologist whether there is reason to think that the immune response to the Novavax protein-based vaccine is likely to be different than that of the mRNA types - if so would provide some basis for why Novavax did not do as well against variants.

I’m not that optimistic given that the variant viruses are expected to become common in that timeframe. The high efficacy of the current vaccines against the original virus but possible so-so efficacy against the new variants would make it even more likely that the variants would quickly become dominant then.

Yeah, certainly a possibility but based on the analysis (in-vitro) of antibody response of Pfizer so far, without even taking into account the other immune responses, I am very optimistic about the extremely strong ability (only six times less effective) of it to counter the known variants so far (the P.1 being an unknown right now, which I am sure we will know more about shortly).

But there are certainly many missing pieces of the puzzle right now. I think it will become more clear what the prospects are in the next several weeks.

More like how to persuade the rest of the world to accept that travelers from the US are safe enough to loosen restrictions.

I’m assuming a much better vaccine rollout in the US and reaching herd immunity in the US faster than many other countries. Not every country. But most.

 

[Jeff N]

Yeah, certainly a possibility but based on the analysis (in-vitro) of antibody response was of Pfizer so far, without even taking into account the other immune responses, I am very optimistic about the extremely strong ability (only six times less effective) of it to counter the known variants so far (the P.1 being an unknown right now, which I am sure we will know more about shortly).

The Pfizer study seems to be a bit of an outlier. Their results were rosier than the recent Moderna study. Unlike, Moderna, the Pfizer study ignored the K417N mutation and also left out other mutations from their pseudo-virus assays. The results seem to be worse on the variants if you use all of the mutations rather than just a subset (some kind of synergistic effect).

The Pfizer study overall seemed flimsier.

This new study from folks mostly at Columbia University is much more comprehensive and includes testing on plasma taken from Pfizer and Moderna vaccine trial subjects along with pseudo-virus assays done individually on nearly all of the individual mutations.

Generally, the vaccine/immunology experts seemed to make more optimistic predictions about how well the Novavax and J&J vaccines would do against the SA and Brazil variants and were disappointed by the new results reported.

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

I dunno. Time will tell.

 

[AlanSubie4Life]

I dunno. Time will tell.

Yep. At least this paper says only 6-8x worse.

They definitely need to roll those other vaccine boosters ASAP, regardless of whether the vaccines remain protective. I wonder if they will do a blend, or what? I guess it depends on if the new vaccine is “backwards-compatible” - have not heard anyone discuss that yet. I assume it would be 6-8x less effective, but maybe not. We can’t just ignore the old variants, of course.

 

[byeLT4]

Take an ENT appointment for another example. A patient goes in concerned about a sore throat. The doctor looks inside, but says he’ll want to take a look further using a scope. Little does the average patient know that simple scope procedure will be billed for hundreds of dollars ($500+ in many instances). Would any regular Joe know to ask whether that will cost extra? There’s definitely no time in that brief appointment to figure out how much it will cost exactly.

Literally just went through this. Ear issue, had to go to primary physician to get referral. Copay 10 bucks. ENT visit copay 10 bucks BUT...... Ear needed a vacuum cleaning LOL. Go to pay and was told- "the cleaning is not covered under your copay visit" *clicking on computer* "oh wow, glad I checked, it'll be 95 dollars with your insurance, I was about to charge you a lot more but your insurance covers xx percent and blah blah toward your deductible". And of course I need to go back in two weeks...

Keeping this on topic, we dodged a bullet at the house. Wife's coworker who she works in close proximity with tested positive last Friday but the wife has had both tests come back negative.

 

[cwerdna]

Dodger Stadium's COVID-19 vaccination site shut down after protesters gather at entrance

A post on social media described the demonstration as the "Scamdemic Protest/March." It advised participants to "please refrain from wearing Trump/MAGA attire as we want our statement to resonate with the sheeple. No flags but informational signs only.

"This is a sharing information protest and march against everything COVID, Vaccine, PCR Tests, Lockdowns, Masks, Fauci, Gates, Newsom, China, digital tracking, etc."
...
Protesters carried signs that read "Save Your Soul TURN BACK NOW," "CNN IS LYING TO YOU," "RECALL GAVIN NEWSOM" and "TAKE OFF YOUR MASK." Some handed out pamphlets to motorists who had their windows down. Some cars blared their horns as they drove by.

Protesters spoke through bullhorns: "Turn back while you can," one man said. "You're a lab rat."
...
The incident marks the latest protest by small groups opposed to basic coronavirus safety measures such as face coverings.

Following demonstrations by anti-mask groups at shopping malls, grocery stores and homeless encampments, the Los Angeles City Council earlier this month bolstered restrictions and subjected some violators to financial penalties. Following a unanimous vote, the council ordered city attorneys to draft a law that would impose fines and penalties on those who refuse to wear a mask at indoor businesses when requested to do so by management, as well as on individuals who refuse to wear one when “invading someone’s personal space.”

Earlier in the pandemic, maskless demonstrators gathered at retail outlets, including Erewhon Market in the Fairfax district, a Target on Beverly Boulevard and the Westfield Century City mall, sparking a backlash from shoppers and employees who felt harassed.

In one video, a demonstrator said he had tested negative for the virus and called a customer at the grocery store a “mask Nazi.”

Sigh... we need plenty of idiot spray for these people. SMH

 

[Jeff N]

Just out....

“We’re very worried,” said Francis Collins, director of the National Institutes of Health. “All it’s going to take is a couple more mutations on top of that, and you’re really going to have to start worrying.”

There is also the issue of reinfection. Collins said Friday that he is troubled by information from the biotech company Novavax, maker of a vaccine that proved effective in clinical trials, that the new variant circulating in South Africa showed signs of eluding natural immunity among volunteers who had previously survived an infection with the more common coronavirus strain. The Novavax vaccine was strikingly less effective against that variant, called B.1.351, than against other strains.

“That is something I had not seen before,” Collins said of the reinfection claim. “It is very tentative, and the numbers are not huge, but I would be alarmed if natural infection . . . is not sufficient to provide immunity.”

https://www.washingtonpost.com/heal...41722e-627c-11eb-9430-e7c77b5b0297_story.html

 

[cwerdna]

Meanwhile, at least two months ago, this guy over at chevybolt.org who isn't a doctor and says he was previously infected by COVID-19 asserted that he's invulnerable. Then he went onto cite 11 years (I've never heard his comparison before) to which someone else replies, that's wrong.
Corona virus and oil crash
Corona virus and oil crash

I wonder how many other people out there who've recovered from COVID-19 infection have similar thinking: they're invulnerable or will be so for 11+ years? Sigh...

 

[AlanSubie4Life]

Meanwhile, at least two months ago, this guy over at chevybolt.org who isn't a doctor and says he was previously infected by COVID-19 asserted that he's invulnerable. Then he went onto cite 11 years (I've never heard his comparison before) to which someone else replies, that's wrong.
Corona virus and oil crash
Corona virus and oil crash

I wonder how many other people out there who've recovered from COVID-19 infection have similar thinking: they're invulnerable or will be so for 11+ years? Sigh...

The main argument against that guy, should you choose to make it, is that there were only thousands of SARS cases. So it did not undergo significant evolution. So reinfection by SARS wouldn’t generally happen, just like it does not generally happen with SARS-CoV-2.

Now, on a different topic from the claim he was making...there is allegedly some cross-protection against COVID-19 if you got SARS, but I am not sure that that has been rigorously studied - it would be difficult to do so. And that isn’t the argument he was making anyway.

That being said, I think, like him, that in a year we’ll likely be in a pretty good spot - assuming we actually try to take some strong measures to suppress the virus whenever we have an opportunity (spring time, when vaccinations have occurred, but perhaps spread of variants has not become too bad (I am not sure the timelines will allow this since the variants are likely going to cause problems in just a few weeks, if they do cause issues)). We certainly can’t just assume it is going to go away. It’s going to take work and the sooner we attempt to eradicate it (cases to zero, like I said in April) the better.

 

[Jeff N]

This is from the discussion conclusions in a recent paper from a well-regarded researcher in South Africa. The paper itself is fairly technical (link below):

“While higher titres of neutralizing antibodies are common in hospitalized individuals, however most SARS- CoV-2 infected people [with no or mild/moderate symptoms] develop moderate neutralization titres. >>>>Therefore, the data herein suggest that most individuals infected with previous SARS-CoV-2 lineages will have minimal or no detectable neutralization activity against 501Y.V2 [AKA B.1.351 AKA South African variant]. <<<<”

SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma