Thread by @FSBuchholzer

I read through a new preprint today which is potentially important: medrxiv.org/content/10.110…

Based on randomized data, the study examines to which extent the vaccinated (Moderna) and unvaccinated develops anti-nucleocapsid antibodies after a subsequent SARS-CoV-2 infection.

🧵

While our Covid vaccines exclusively target the spike protein, we are some that have argued that infection would induce broader and longer-lasting (natural) immunity than vaccination, because immunity is induced against greater parts of the virus, not just the spike proteins.

We were fed the inane & illogical idea that 💉 would produce superior immunity than having cleared the🦠

This is despite that for essentially all infections known to man, natural immunity is superior.

The postulate was gradually moderated to equipotency;

https://twitter.com/mikebarnkob/status/1450152114769043459?s=20&t=UmlQqJiHrbvliPBsXe76vA

We now know that almost all will be (and have now been) infected atleast once, so in the context of mass 💉on top of that (mainly before), there are several important research questions that needs to be answered:
How much worse is vaccine-induced immunity, compared to infection?

Is the immunity towards SARS-CoV-2 dominated by your last exposure (nothing,🦠 or 💉)?
Is the sequence of exposure(s) important?
🦠...
🦠-> 💉...
💉-> 🦠...
Present vaccines are based on the index (Wuhan) variant & especially omicron is packed with mutations in the spike protein

This is where nucleocapsid (anti-N) antibodies might come in handy, because if you have immunity to a larger share of the virus genome, then it will be harder for the virus to develop immune escape properties like those of omicron, which essentially completely evades 💉 immunity.

The preprint investigates this, but to my astonishment, the data is from prior to the delta and omicron variants, despite acknowledging that the hypothesis was formed during data collection in 2020..

They have been sitting on this important dataset for more than a year.

The data is from an RCT testing Moderna vs placebo, so high quality evidence.

The authors analyzed serum for anti-N antibody from participants that had a SARS-CoV-2 infection during the blinded phase of the trial, *or* at baseline.

The results are potentially important.

For baseline negative participants (no prior infection at enrollment), receiving 2 doses of Moderna and then being infected was associated with significantly blunted anti-N responses in terms of % developing antibody:
💉💉 ->🦠 -> 40% w. anti-N
Placebo ->🦠 -> 93% w. anti-N

Vaccination thus had a negative effect on the formation of anti-N antibody.

When I read this at first, I thought that this was just due to suppression of virus replication (vaccine doing its job). The authors tested whether this could explain their results, but it couldn't.

For the same 🦠copies per ml in nasopharyngeal swap samples collected at illness visits, the unvaccinated were subsequently much better at producing anti-N. Only at quite high viral loads did the two groups approximate in the ability to produce anti-N antibody.

This pattern was markedly different if infected at baseline (seropositive/PCR+ when randomized).
There was then no difference in anti-N production, indicating that infection-vaccination sequence is important.

🦠 ---> placebo ---> 95% w. anti-N
🦠---> 💉 💉 ---> 96% w. anti-N

What are the implications of this?

N protein can generate a robust T-cell response, is well conserved and does not recombine frequently. Anti-n immunity is likely important.

It is unknown whether patterns are the samewith omicron as well, or with other COVID vaccines.

The reduced capacity to produce anti-N was seen after dose 2 only, not after dose 1. So what happens after dose 3, 4?

Is the blunting sustained, increased? Is this important?

Perhaps a good idea to investigate these questions rather than vaccinating everyone blind-folded.

There are those of us that consistently argued that we should stratify the 💉 strategy targeting risk groups that are likely to die or get hospitalized from COVID, rather than rolling out mass 💉 to all age groups because eradication was futile anyways.

https://twitter.com/FSBuchholzer/status/1491471401836023811?s=20&t=t5F9o7Xf1dMyQgSgjCqXuQ

We warned of the possibility of antigenic sin.
We should vaccinate to prevent disease, not mild infection. If COVID 💉 blunts your immune response to subsequent COVID 🦠and you are old and moribund, where vaccination likely saves your life (or prolongs it), it is not a big deal.

But for children and healthy young adults, the balance of potential costs and benefits is very different.
A good proportion will experience even just short-term 💉side-effects equivalent or worse than whichever possible disease symptoms, if they even discover their infection.

Next winter, we shall survey the different combinations in detail⤵️
#1 🦠 ---> placebo ---> 95% w. anti-N
#2 🦠---> 💉 💉 ---> 96%
#3 💉 💉 ---> 🦠---> 40%
#4 Placebo --->🦠 ---> 93%

#3 is by far the most common trajectory people has taken through the pandemic.

🧵fim