Thread by @NickAnderegg

Big picture, these findings are bad for EVERYBODY, but ESPECIALLY for those still clinging to the fantasy of "natural immunity."

The takeaway? It's unclear if ANYONE has strong immunity to COVID infection!

Here's a deep analysis thread, written for a general audience!

1/many

The paper is fairly complex, but the takeaways are pretty straightforward, so I'll start with the highlights!

Method is robust, data collection was EXTENSIVE: It's a longitudinal study (follows the same individuals over time) with regular nasal swabs and blood draws!

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Because they have blood draws from just before each wave, it's the perfect data to examine the immunity conferred by prior infections.

Because South Africa had a low vaccination rate at the beginning of Omicron, this is also great data for examining natural immunity!

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This study is also an important contribution to the overall body of knowledge, because much of what we know of SARS-CoV-2 antibody dynamics comes from vaccine studies. In comparison, much less is known about the dynamics of serum antibodies in natural infections.

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Now, there's one thing to keep in mind before we continue: This study looks at serum antibodies in unvaccinated people. We already know that the mRNA vaccines induce less-robust mucosal (airway lining) immunity, but a stronger serum (blood) antibody response,...

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...which means that for all the results we see here, vaccinated people will likely have much higher serum antibodies, but less-robust mucosal immunity.

As we go, consider what this flipped pattern implies for the ability of the vaccines to PREVENT transmission/infection!

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As for the potential for immunity acquired via infection, the rapid evolution of SARS-CoV-2 has consistently meant that more recent variants are more transmissible, even with equivalent levels of antibodies in the blood.

Of course, the antibodies also decline over time!

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See, this is actually a follow-up to their previous study that DID find "immunity conferred by prior infection reduced the risk of reinfection," BEFORE the Omicron wave began.

Will this pattern of infections conferring immunity continue for Omicron?

[Spoiler: Hell no.]

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During the Delta wave, 34% of the cohort was infected:

- 42% of those WITHOUT prior infection were infected
- 17% of those WITH prior infection were infected

This indicates that, up until that point, prior infection did confer SOME (but not full) immunity to infection.

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But even at that point, issues with the cross-neutralization were starting to show. Those infected with Beta variants had lower detectable levels of neutralizing antibodies against the Alpha variant, because the antigens mismatched!

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Things changed A LOT when Omicron entered the picture.

During the Omicron wave, 67% of the cohort was infected:

- 77% of those WITHOUT prior infection were infected
- 61% of those WITH prior infection were infected

So like... what immunity?

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Boiling it down:

- Between the Alpha and Delta waves, there was a **1.47-fold reduction** in neutralizing antibody levels due to waning.
- Between the Alpha and Omicron waves, there was a **4.01-fold reduction** "attributed to the immune-evasive properties of Omicron."

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That was the actual data analysis portion of the study. They used the same data to build a model that can be used to understand how prior infection protects against reinfection! (simplified explanation in alt text)

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Prior infection reduced risk of reinfection by 61% in the Delta wave, but only by 37% in the Omicron wave.

Prior antibodies were responsible for 37% of the protective effect in the Delta wave, while they were responsible for 11% in the Omicron wave.

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More importantly, there is a MASSIVE difference in the risk of passing on Delta or Omicron reinfections to other members of your household:

Delta: 78% less likely to pass on a reinfection than a primary infection
Omicron: No differences between primary and reinfection!

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Simply:
- "[When] prior immunity is not sufficient to block reinfection with the Delta variant, infection-induced immunity [reduces] transmission."
- "Omicron not only evades prior immunity's protection against acquisition of infection but also [allows] onward transmission."

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The important parts:
1. Direct protection of prior infection is reduced by half every 4 months.
2. Direct protection (not nAb) is responsible for 89% of Omicron protection.
3. In total, risk of onward transmission of Omicron is "reduced" by -17% if it's a reinfection.

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So while prior infections did, at one point, have a protective effect against further SARS-Cov-2 infection, that hasn't been true since the beginning of the Omicron wave. The mutations just escape the immune system too well.

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There is a tiny bit a good news, however! This finding shows that, although acquired immunity seems to primarily operate at mucosal sites, the neutralizing antibodies are adequate for monitoring how well vaccines match the variants in circulation.

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When it comes down to it, Omicron is a tricky little shit. Prior infection with Omicron seems to *barely* prevent reinfection with other variants of Omicron, which means you can theoretically get it over and over and over and over and over.

And if you recall,...

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The vaccines induce a much stronger serum neutralizing antibody response than they do a mucosal immune response. So not only has nobody ever actually said that the vaccines can *prevent infection*, but it's looking like in the Omicron era, they can't!

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You should still get updated vaccinations! Serum antibodies do have SOME effect, and the vaccines definitely do seem to have an impact in preventing severe COVID. Additionally, Novavax may induce a more broadly neutralizing antibody response than the mRNA vaccines!

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But it also means that we can't rely on our immune systems to stop the spread of COVID. The Omicron variants are just too immune-evasive for that anymore. Until we have next gen vaccines, we need other tools to prevent the transmission of Omicron!

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You know what the virus CAN'T evade? Electrostatically charged fibers.

An N95 respirator is engineered to filter airborne particulate. SARS-CoV-2 is airborne particulate.

Wear a respirator to protect yourself and others. It's really THAT simple.

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It's a solid paper, and IMO it shows how we can't vaccinate (or "hybrid immunity") our way out of a problem that has SPECIFICLLY adapted to evade our immune systems! WHY ISN'T THAT OBVIOUS!?

Source:

My annotated copy:

25/25nature.com/articles/s4159…
dropbox.com/scl/fi/g1ffj3f…

The answer is *conceptually* very simple, but difficult to do in the real world! We need next-gen vaccines which:

1. Elicit robust mucosal immunity
2. Targets antigens OTHER than the S protein

The spike is easy to target, but CHANGES more easily!

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Additionally, things like soluble ACE2 receptors may complement vaccines:

For example, if a nasal spray containing soluble ACE2 receptors could bind to the virus before it ever touches a cell, it could have significant prophylactic effect!

27/25 sciencedirect.com/science/articl…

Vaccines elicit an immune response that is meant to target a very specific antigen protein, but lots of little changes can make the antigen presentation change—even if the receptor is uses stays the same!

Soluble ACE receptors would be, essentially, decoys!

28/25

Definitely not a dumb question! I only ever imply it, but YES, we are still in the Omicron era!

All of the BA*, BQ*, XBB*, EG*, HK*, and JN* variants are Omicron.

Oddly enough, the BA.2 family actually seems to be making a comeback this year!

29/25

Well, this is fucking hilarious!

Someone quoted this to say I don't know what I'm talking about because... I apparently think intramuscular vaccination prevents transmission?... in a thread where I point out that it absolutely doesn't

Try reading for once in your life!

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