PlagueWatch 2020-23 - Coronavirus

[budwom]

The Vermont on-line system started up today for the 75+ crowd, and somewhat amazingly, it worked right off the bat for friends of mine...jabs start on Jan 27, they got slots on Feb 3 (it's anticipated it will take 5-6 weeks to vaccinate that group).

[jtelander]

"Pharmaceutical company Merck announced Monday it is discontinuing development of its Covid-19 vaccine candidates after early studies showed immune responses were inferior to natural infection and other Covid-19 vaccines."
https://www.businesswire.com/news/ho...tic-Candidates

[MChambers]

Moderna says its vaccine is effective against the "British" and "South African" variants, but "the reassuring news that vaccine-elicited antibodies remained effective against concerning new variants was tempered by an ominous finding. Those antibodies were less efficient at neutralizing the South African variant in a laboratory dish — a sixfold reduction in response foreshadowed by a small, but mounting body of evidence that has trickled out showing that the variant may have the potential to elude parts of the immune response."

https://www.washingtonpost.com/healt...virus-variant/

[Mike Corey]

As Dr. Eric Feigl-Ding noted on Twitter (he's a great follow, btw):

6x less efficient doesn’t mean no protection against #B11351, it’s still good but not as good as before. As a precaution, Moderna announced it will launch two new studies—including adding a third shot of its current vaccine to boost its two-dose regimen.

[rsvman]

As Dr. Eric Feigl-Ding noted on Twitter (he's a great follow, btw):

If (or when) the virus mutates away from the protection offered by the current vaccine, there will be no point in giving a third shot that will only succeed in boosting the titer of an antibody that won’t neutralize the new variant.

Fortunately, given the mRNA design, it should be fairly simple to make a new vaccine that covers the new mutation, and give that instead. It wouldn’t surprise me if it turns out that the virus fairly quickly mutates away from our herd immunity once it is established, which will require the companies to re-engineer the vaccine, perhaps over and over again.

[Jeffrey]

Fortunately, given the mRNA design, it should be fairly simple to make a new vaccine that covers the new mutation, and give that instead. It wouldn’t surprise me if it turns out that the virus fairly quickly mutates away from our herd immunity once it is established, which will require the companies to re-engineer the vaccine, perhaps over and over again.

Do you predict annual vaccinations for many years? If so, do you predict on-going vaccine effectiveness around 95%?

Under that scenario, heaven help the fools who never get vaccinated.

[rsvman]

Do you predict annual vaccinations for many years? If so, do you predict on-going vaccine effectiveness around 95%?

Under that scenario, heaven help the fools who never get vaccinated.

It depends on how quickly escape mutants arise, and also on how long vaccine-generated immunity lasts. We don't really know the answers to either of these questions right now, so it is tough to say.

It wouldn't surprise me if we end up having to get vaccinated every year. Maybe we will get an mRNA flu vaccine, too, and maybe eventually these can be combined. I think it unlikely that a two-shot series would be needed at any point after this initial campaign.

[PackMan97]

If (or when) the virus mutates away from the protection offered by the current vaccine, there will be no point in giving a third shot that will only succeed in boosting the titer of an antibody that won’t neutralize the new variant.

Fortunately, given the mRNA design, it should be fairly simple to make a new vaccine that covers the new mutation, and give that instead. It wouldn’t surprise me if it turns out that the virus fairly quickly mutates away from our herd immunity once it is established, which will require the companies to re-engineer the vaccine, perhaps over and over again.

...and this is why we (as a world) were foolish in not locking this down and stamping it out. Now it's pretty much guaranteed to be with us for a long time as it mutates around the world and we chase it with vaccines. It's going to end up costing us a lot more in the long run than it would have in the short term.

Just out of curiousity, what makes viruses like this mutate a lot vs something like measles, various pox, polio, etc?

[Jeffrey]

It depends on how quickly escape mutants arise, and also on how long vaccine-generated immunity lasts. We don't really know the answers to either of these questions right now, so it is tough to say.

It wouldn't surprise me if we end up having to get vaccinated every year. Maybe we will get an mRNA flu vaccine, too, and maybe eventually these can be combined. I think it unlikely that a two-shot series would be needed at any point after this initial campaign.

Thanks... great news on only a single shot, being most likely, in the future! Combined with the knowledge we will gain from initial manufacturing and distribution, we should be able to vaccinate, half the initial amount, much more efficiently and timely, in the future.

If we get an mRNA flu vaccine, would it most likely have an effectiveness of at least 75%? That would be awesome!

[CDu]

...and this is why we (as a world) were foolish in not locking this down and stamping it out. Now it's pretty much guaranteed to be with us for a long time as it mutates around the world and we chase it with vaccines. It's going to end up costing us a lot more in the long run than it would have in the short term.

Just out of curiousity, what makes viruses like this mutate a lot vs something like measles, various pox, polio, etc?

Colds do (which is why people keep getting them). Flu mutates rapidly as well (which is why the flu vaccine isn't terribly effective).

[budwom]

If (or when) the virus mutates away from the protection offered by the current vaccine, there will be no point in giving a third shot that will only succeed in boosting the titer of an antibody that won’t neutralize the new variant.

Fortunately, given the mRNA design, it should be fairly simple to make a new vaccine that covers the new mutation, and give that instead. It wouldn’t surprise me if it turns out that the virus fairly quickly mutates away from our herd immunity once it is established, which will require the companies to re-engineer the vaccine, perhaps over and over again.

per the NY Times, Moderna has already announced they are working on a "new form of the vaccine that can be used as a booster shot."https://www.nytimes.com/live/2021/01/25/world/covid-19-coronavirus

[tbyers11]

As Dr. Eric Feigl-Ding noted on Twitter (he's a great follow, btw):

This is the key take home IMO. The Moderna work shows that their vaccine still works against the South Africa variant. 6-fold lower neutralizing Ab titers does not mean 6x less efficacy. Which many articles are directly or indirectly stating. Another epidemiologist Twitter take (https://twitter.com/zeynep/status/1353737006921228288)

Plea to media: this isn't a good headline. It makes people think the vaccine is six times less effective against the new variants (FALSE!) when the news today is *excellent*: The vaccine continues to work well against the new variants. That's the headline.

We don't know how much of a nAb response to COVID is "good enough". It is quite possible that six-fold less is good enough. For a relevant example from Flu. There has been enough work over the years to know that a Flu HAI Ab titer of 40 generally correlates with reasonable protection. If you vaccinate with a new flu strain you can easily get an acute post-vax titer of ~2000. 6-fold less than 2000 would still be well above the threshold for "good enough"

EDIT: link to Moderna press release in which they state "Despite this reduction, neutralizing titer levels with B.1.351 remain above levels that are expected to be protective". I'll try and find the pre-print on bioRxiv later and see what the numbers look like. I assume they based their statement on nAb levels in convalescent sera which is the best marker we have to date

[rsvman]

Colds do (which is why people keep getting them). Flu mutates rapidly as well (which is why the flu vaccine isn't terribly effective).

This is not true with regards to “colds.” In the first place, common cold has well over 150 different causes, so you would get colds over and over again even without any mutation. Some of the viruses that cause common cold mutate and some don’t.

Generally, the answer to the question of why some viruses mutate a lot and other don’t is two-fold:

1) DNA polymerases have an editing function, so when random mistakes are made during replication, they are corrected. Accordingly, DNA viruses mutate very little, if at all.

2) Although all RNA viruses make mistakes in replication, most mutated viruses have a survival disadvantage, so they are outcompeted naturally. When infection with an RNA virus produces protective immune responses, and a large population develops immunity, it sets up a situation in which a rare mutated virus may actually have a competitive advantage, rather than a disadvantage.


In short, there are two things required for mutated strains to become clinically relevant; first, the virus must mutate with regularity, and second, there has to be evolutionary pressure exerted on the wild-type virus.

[SoCalDukeFan]

In my opinion you have to be relentless and alert.

I received news from a friend that I could get a shot in a nearby city who had shots for 3 days. I get day 3. Evidently people from my area got the shot on day 1, but for day 2 or 3 you had to live in that city or be a health care worker. Then I received news that CA opened up to 65+ and local grocery store was taking appointments. Got one. Then LA County said health care only and lost the appointment. Last week I saw in the news that LA Supervisors were meeting with the Health Dept to pressure to open up to seniors. Went to the sign up site, signed up even though I was not a health care worker. About an hour later sign ups for seniors allowed and I was in. Got my shot last Tnursday.

Friend got his shot on Sunday. His wife went wife him and even though she did not have appointment they signed her up and gave her a shot.

My under 50 year old daughter just got an appointment for Feb 1. LA county is giving shots to volunteers so she will direct tariff or take temperatures or something for a day. It took her two days to trying to get the appointment. All volunteer spots seemed to be filled for the next two week.s

SoCal

[jtelander]

It depends on how quickly escape mutants arise, and also on how long vaccine-generated immunity lasts. We don't really know the answers to either of these questions right now, so it is tough to say.

How will the duration of vaccine-generated immunity be determined? Will it be primarily based on the outcomes of participants in the trials?

With regard to issues with virus variants, I hope that the Pfizer and Moderna will publish quantitative data on the effectiveness of their products on known variants and wonder how those studies will be conducted.

[jtelander]

I got
my appointment cancellation phone call from Cone Health today because the State didn’t ship them this coming week’s allowance of vaccine. Grrrrrr.

NC hospitals are canceling appointments as state routes vaccine doses to mass events. Someone is Charlotte may have received your dose.

https://www.newsobserver.com/news/co...248720070.html


On a related note, we received our 1st doses of the Pfizer vaccine yesterday at the mass vaccination site at the Fairgrounds in Forsyth County (an hour away from home). It was very well run. They were running ahead of schedule and we finished and on our way home in 30 minutes. Our injections were administered by members of the Army National Guard.
My county (Alamance) is limiting vaccinations to persons aged 75 and older.

[tbyers11]

How will the duration of vaccine-generated immunity be determined? Will it be primarily based on the outcomes of participants in the trials?

Yes, that will be the first data. The neutralizing Ab (nAb) data from the 6 month timepoint from the Phase 1 subjects should be coming soon. 3 month data on a much larger group from Phase 3 not to far behind. The nAb data is a likely correlate for protection but too how long it truly lasts you will have to follow the Ph3 subjects and actual vaccinees and see if or when they might have a COVID infection

With regard to issues with virus variants, I hope that the Pfizer and Moderna will publish quantitative data on the effectiveness of their products on known variants and wonder how those studies will be conducted.

Ask and ye shall receive (https://www.biorxiv.org/content/10.1...948v1.full.pdf). Moderna published a pre-print today in which they tested sera from non-human primates (NHP) and humans who got the vaccine in a pseudovirus neutralization assay against pseudotyped lentiviruses engineered with the key variants or combinations of variants. In NHP and humans they see that the UK variant (B.1.1.7) nAb responses were indistinguishable from vaccine strain. In NHP and humans they see that reduced nAb levels to the SA (B.1.351) variant were ~6-fold lower. (Figure 4 human data from the preprint below) However, the actual nAb titer to B.1.351 was a titer of ~1/300. It is only 8 humans but that is typically a fairly strong value and all subjects completely neutralized. Also, these results are in line with recent (Wang 2021 reference in the preprint) work that showed 2.7-fold nAb reduction with a subset of the SA mutations in ~20 people.

COVID variant.jpg

Additionally the NHP titers remained above those previously found to be protective in NHP challenge studies (when they gave NHP with nAb titer at or above this level they were protected from infection).

Overall, data looks very promising that the Moderna, and likely Pfizer, vaccine will work well against the UK and SA variants. They still need to test in a live-virus neutralization assay (the gold standard) but it takes time to grow real virus (vs lentiviral vectors) and to date PsV and live virus have shown very similar results for SARS-CoV-2.

[Tooold]

This is not true with regards to “colds.” In the first place, common cold has well over 150 different causes, so you would get colds over and over again even without any mutation. Some of the viruses that cause common cold mutate and some don’t.

Generally, the answer to the question of why some viruses mutate a lot and other don’t is two-fold:

1) DNA polymerases have an editing function, so when random mistakes are made during replication, they are corrected. Accordingly, DNA viruses mutate very little, if at all.

2) Although all RNA viruses make mistakes in replication, most mutated viruses have a survival disadvantage, so they are outcompeted naturally. When infection with an RNA virus produces protective immune responses, and a large population develops immunity, it sets up a situation in which a rare mutated virus may actually have a competitive advantage, rather than a disadvantage.


In short, there are two things required for mutated strains to become clinically relevant; first, the virus must mutate with regularity, and second, there has to be evolutionary pressure exerted on the wild-type virus.

Very helpful explanation!

[jimsumner]

Some numbers on why the Triangle isn't getting vaccinated.

https://www.wral.com/triangle-hospit...ible/19490271/

[Lord Ash]

My school district in northern NJ has kept a six foot radius for all people and masks required.

Now, because of parent pressure, they are starting to look at just a three foot radius, so they can get more children in the building.

A lot of teachers, including me, are very, very nervous about this.