COVID-19 ongoing thread part 2

[AniThyng]

Wait why won't the immune system produce antibodies for the N protein to fight off the infection, since the S protein is already mutated beyond recognition? At that point why wouldn't the response be the same as unvaccinated?

[Tribble]

The covid virus has 2 key parts; the spike (S) protein which allows the virus to enter & infect cells, and the nucleocapsid (N) protein which is in charge of all the viral reproduction once a cell has been infected. The former can and does mutate rapidly and has a ton of mutations available to it, the latter is pretty stable and doesn't have many mutations available, if it mutates too much the virus can't reproduce anymore and dies.

When an unvaccinated person is infected with covid, the immune system will produce antibodies for both the S and N proteins. Since the N protein remains fairly similar in all variants of the virus, the immunity you get after recovering from an infection provides broad immunity against all variants regardless of how much the S protein mutates. If you got the original or Delta strains, your immune system will still recognize and fight off Omicron and all the other variants going around right now.

With the vaccines, all of them except Sinovac target the S protein alone, and this worked well when they were initially released. The problem is most people who were vaccinated fail to develop antibodies for the N protein after being infected with covid, which initially wasn't a problem since the S protein antibodies alone were enough to stop the infection or at least prevent serious symptoms. This is no longer true. Current variants of the virus have evolved enough that the S protein portion of the virus is no longer recognized by the S protein antibodies in the vaccinated person, so if you don't have the N protein antibodies you're effectively unprotected. Most people were vaccinated don't have and don't develop antibodies for the N protein, which means they can be repeatedly infected with the current variants of covid.

IF this paper is confirmed, we done fucked ourselves good.

If the variants continue to evolve to bypass the current S proteins covered by the vaccine, wouldn’t that mean that the immune system would be introduced to more of the N proteins as more cells are being infected?

What prevents the immune system from learning the N protein if the virus isn’t being stopped by S protein antibodies?

Is it taking longer to for the immune system to fully recognize the N proteins since current S protein antibodies are still partially effective?

If so, that the vaccines are still good enough to stop a serious enough infection where N protein antibodies are generated in large amounts is not necessarily a bad thing, right? I’d rather have a few asymptomatic infections / colds vs being totally unvaccinated and rolling the dice. Plus IIRC current vaccines are still based solely on the original version of Covid, and they are currently testing ones specifically for Omicron.

We get yearly flu shots without fuss, not that surprised that we’ll need them for Covid tbh.

[aerius]

Wait why won't the immune system produce antibodies for the N protein to fight off the infection, since the S protein is already mutated beyond recognition? At that point why wouldn't the response be the same as unvaccinated?

It's likely some form of original antigenic sin, where the immune system gets stuck in a loop and fails to adapt. We don't know why this happens, but it was known to happen in the failed animal trials they did for previous coronaviruses such as SARS.

There was another study where they looked the immune system cells & antibodies of vaccinated subjects in more detail and found that it just kept producing antibodies for the original strain when it was exposed to the current variants.
https://www.biorxiv.org/content/10.1101 ... 1.full.pdf

VDJ sequence analysis revealed significantly higher heavy chain V-domain11
somatic hypermutation (SHM) rates of BA.1/WT bivalent B cell receptors (BCRs) than that of12
BA.1-specific BCRs (Fig. 2i ), which implies bivalent memory B cells were further affinity-13
matured compared to BA.1-specific memory B cells. Together, these suggest that post-vaccination
infection with Omicron BA.1 mainly recalls WT-induced memory B cells, supporting the “original
antigenic sin” theory.

[aerius]

*snip*

I think you need to read the paper again.

These data show that, among the participants with PCR-confirmed Covid-19 disease, anti-N Ab seropositivity at a median of 53 days post diagnosis occurred in 40% of the mRNA-1273 vaccine recipients vs. 93% of the placebo recipients. While an increase in seroreversion cannot be ruled out, given the short time frame the more likely explanation is a vaccine-induced reduction in seroconversion. Anti-N seropositivity correlated with illness visit SARS-CoV-2 viral copy number, with each log increase in viral copy number nearly doubling the odds of anti-N seropositivity at the PDV. As the viral copy number on the day of the illness visit in mRNA-1273 vaccinated Covid-19 cases has been shown to be 100-fold lower than that in placebo recipient Covid-19 cases,9 the lower anti-N seropositivity in the mRNA-1273 recipients could be partly explained by their reduced exposure to N-antigen. However, strong vaccine effects remain; at 2.0 log10 copies/ml the predicted probability of seroconversion was 0.15 for vaccinated Covid-19-cases compared to 0.71 for placebo recipient Covid-19 cases. This may be due to a difference in the live virus replication between vaccine and placebo recipients, which cannot be differentiated by the RT-PCR test. Another potential explanation is that the vaccine has much larger effects on reducing replication outside the nose, as was shown in a study evaluating the mRNA-1273 vaccine against SARS-CoV-2 challenge in a non-human primate model.

Which makes sense, the paper states those who took the placebo had a higher viral copies so the body produced more antibodies to fight it off.

Also, the study included 1789 participants (1298 placebo and 491 vaccinated) and of those infected, 648 were placebo and 52 were vaccinated.

Nope. See figure 2. Vaccinated subjects have a significantly lower chance of developing N antibodies at any given level of viral load.

[Soontir C'boath]

From reading other papers, it looks like the Sinovac vaccine also has the same effect in lesser anti-N response.

However, I don't think it should be discounted as mentioned before that just about half the people who took the placebo contracted Covid while only 10% of those who were vaccinated got it. And this study was done prior to Delta and Omicron variants and given hospitalizations since then has continued to show it was mainly those who were unvaccinated who were being hospitalized. I'd say it's still a rather damn good idea to have taken the vaccine.

[phongn]

N-antibodies are not neutralizing antibodies and the extent that they protect you against COVID-19 remains uncertain. They might even interfere with the production of actually neutralizing antibodies (which will dock with the spike). I am not yet convinced of aerius' thesis, and OAS is really more a concern about your B-cells' response to the spike, not to something very different (N). We also know that a third dose of the wild-type booster has broadened the antibody response sufficiently that your body is generally able to tackle Beta and Delta (though much less confidently Omicron)

It's possible that T-cell responses against the N protein will aid in the eventual immune response; but we know that response takes like 5+ days, so you're likely going to get sick.

(As an alternate explanation to OAS, maybe a vaccinated immune system's response to the spike is sufficient that it generally does not need to produce non-neutralizing antibodies against the N protein. If you're swimming in S nAb, you're fine!)

[aerius]

Israeli data disagrees.
https://www.israelnationalnews.com/news/309762
This was from last year when Delta was the dominant strain, natural immunity was far better at preventing infection than vaccination.

With regards to Omicron and boosters, well, let's see what's going on where I live.
https://covid-19.ontario.ca/data
Boosters sure as hell ain't working, and there's only a marginal difference between 2 dose and unvaccinated people.


My opinion is that OAS isn't proven yet, but it's definitely on the table. There's something concerning going on which results in vaccinated people being repeated infected in a fairly short period of time, it could be OAS or it might be something else that's gone wonky with the immune systems of those who got the shots.

As for the "swimming in S antibodies", could be something to that. Antibody levels for the S protein were something like 6-10 times higher with vaccination vs. infection & recovery, but they also dropped off at 40% per month vs. 4-5% for natural immunity. When Pfizer was doing the early trials they tested 10,30, and 100ug doses and settled on 30ug since antibody levels weren't any higher at 100ug but side effects got worse.

[Soontir C'boath]

It's not a secret that Omicron hit a shit ton of vaccinated people. I very likely got it. However, thankfully it is a mild form of Covid.

Although I shouldn't be surprised given Ontario is where Doug Ford is seated. I like how the page doesn't put the hospitalizations in per 100,000 like the other data. However, if you want to see its effectiveness. Take a look at the chart below for deaths and you will see that those who were unvaccinated were hit hardest in all adult age groups back in the Jan/Feb of 2022 spike.

And you're going to forgive me if I'm not going to take it as gospel from what looks like a right wing Jewish rag.

[LadyTevar]

I just got my 3rd booster last week, and felt like shit for four days.

There's news that infections on the rise in WV, and a recent large SCA event in PA had 4 people show symptoms the day or two after, so those who were there are testing like crazy -- including my brother who was there the whole weekend.

We've lost this fight I think.

[PainRack]

I just got my 3rd booster last week, and felt like shit for four days.

There's news that infections on the rise in WV, and a recent large SCA event in PA had 4 people show symptoms the day or two after, so those who were there are testing like crazy -- including my brother who was there the whole weekend.

We've lost this fight I think.

In terms of ???

If it's with regards to US trying to reduce casualties, that's true .

The trough of this wave was 300 deaths daily. China death tolls total from the Delta/Omicron wave is less than 200.


The problem here is the US has a VERY decent chance of ending this. Get everyone vaccinated, get a booster of 80-90%, although arguably hybrid infection present in the US means you might not need a booster and we can see extremely low death tolls


Singapore 96% vaccinated and over 80% boosted now has a tough 12 ICU cases, 50 of which require oxygen and 300 patients in hospital/observation (we have the hospital capacity/Covid treatment facillities to monitor all potential high risk Covid patients. )

https://www.channelnewsasia.com/interac ... al-2188506

[phongn]

Israeli data disagrees.
https://www.israelnationalnews.com/news/309762
This was from last year when Delta was the dominant strain, natural immunity was far better at preventing infection than vaccination.

Come on man, actual data releases please. And if that's Delta against two doses, not three, that doesn't change my thesis.

Also, a real infection does all sorts of other things that a vaccine response doesn't; it doesn't mean that the N antibodies are doing something. In-vivo replication effects might well be broadening the response (and giving more targets for T-cells to identify).

We're also seeing that prior infection from Delta isn't cutting it against Omicron (particularly newer Omicron variants) either, but that vaccination + delta recovery is.

(Addition: CDC MMWR published some data early this year against Delta and Omicron BA.1)

With regards to Omicron and boosters, well, let's see what's going on where I live.

Which ... I said about Omicron.

My opinion is that OAS isn't proven yet, but it's definitely on the table. There's something concerning going on which results in vaccinated people being repeated infected in a fairly short period of time, it could be OAS or it might be something else that's gone wonky with the immune systems of those who got the shots.

It could be the human immune system just not being very good against coronaviruses, too! That's been long observed; people just don't seem to have lasting immunity. And also, people who got infected but were not vaccinated are getting reinfected, too. Given that the body usually takes ~5 days to really marshal defenses against a disease, one that rapidly reaches the contagious phase well under that mark is going to present a challenge for any sort of sterilizing immunity.

As for the "swimming in S antibodies", could be something to that. Antibody levels for the S protein were something like 6-10 times higher with vaccination vs. infection & recovery, but they also dropped off at 40% per month vs. 4-5% for natural immunity. When Pfizer was doing the early trials they tested 10,30, and 100ug doses and settled on 30ug since antibody levels weren't any higher at 100ug but side effects got worse.

US data now shows that Moderna's 100ug dose is somewhat superior than Pfizer's 30ug dose and more durable.

Also natural immunity nAb levels tend to be low, anyways, versus the enormously higher level of an mRNA vaccine, and the mRNA nAb levels plateau higher than a natural infection (or than from the adenovector, protein subunit or inactivated vaccines).

[phongn]

In the interests of full rigor, there is a recent paper in Science that describes OAS in prior-vaccinated and prior-infected people.

[Broomstick]

When an unvaccinated person is infected with covid, the immune system will produce antibodies for both the S and N proteins. Since the N protein remains fairly similar in all variants of the virus, the immunity you get after recovering from an infection provides broad immunity against all variants regardless of how much the S protein mutates. If you got the original or Delta strains, your immune system will still recognize and fight off Omicron and all the other variants going around right now.

With the vaccines, all of them except Sinovac target the S protein alone, and this worked well when they were initially released. The problem is most people who were vaccinated fail to develop antibodies for the N protein after being infected with covid, which initially wasn't a problem since the S protein antibodies alone were enough to stop the infection or at least prevent serious symptoms. This is no longer true. Current variants of the virus have evolved enough that the S protein portion of the virus is no longer recognized by the S protein antibodies in the vaccinated person, so if you don't have the N protein antibodies you're effectively unprotected. Most people were vaccinated don't have and don't develop antibodies for the N protein, which means they can be repeatedly infected with the current variants of covid.

IF this paper is confirmed, we done fucked ourselves good.

First, as someone who was infected by Covid: The Original Virus you can have a subsequent, second infection. Granted, round two - after vaccination and boosting as well - was MUCH milder than the first. So mild, in fact, I didn't realize I was sick and it was only because multiple contacts all called me on one morning urging me to get tested did I realize I had a second covid infection, but I did get it twice, confirmed by PCR testing.

Natural immunity is not an absolute shield. An anti-vaxxer I know who boasts he's never has a vaccine in his life is currently on his second covid infection. Fortunately, neither of them have been serious.

Second, it still seems that vaccination and boosting still reduces the severity of the illness if you do catch it. Since the primary purpose of the vaccine was to reduce your chances of severe illness or death that seems to have been a win, even if doesn't prevent all infection. So... the question is, have these mutations essentially negated ALL protection from the vaccines, or just reduced their effectiveness?

It looks like the vaccines might need to be tweaked either now or in the future, which was something that was always a possibility.

I'm not sure "we done fucked ourselves good" in this instance. It does bear watching, though.