Longitudinal analysis shows durable immune memory after SARS-CoV-2 infection

Quote from [1]:

- "The cumulative incidence of SARS-CoV-2 infection remained almost zero among previously infected unvaccinated subjects, previously infected subjects who were vaccinated, and previously uninfected subjects who were vaccinated, compared with a steady increase in cumulative incidence among previously uninfected subjects who remained unvaccinated."

Right now there is no scientific consensus that full vaccination of previously infected individuals provides any additional protection that is meaningfully beneficial. In fact there is a lot of evidence pointing the other way - supporting the idea that vaccination strategies should be highly targeted at only the most vulnerable populations.

[1] Necessity of COVID-19 vaccination in previously infected individuals https://www.medrxiv.org/content/10.1101/2021.06.01.21258176v...

If I had to cite a single preprint to support the assertion, it would probably be this one:

https://www.biorxiv.org/content/10.1101/2021.04.15.440089v4

Obviously this study also has limitations: it speaks only to Ab levels, while obviously the overall immune response is a lot more complicated.

I agree with the "waving of preprints" claim. Unfortunately, hyperskepticism, rejecting drawing conclusions because of the inevitable limitations of any study, is also a politicized position, and unfortunately I see a fair amount of that as well.

What!? This is an extraordinary claim that you state with zero evidence. It relies entirely on the naturalistic fallacy.

Not only is it possible for vaccines to confer better immunity but there are clear ways to test this empirically, which studies certainly have, like this one:

https://www.cdc.gov/media/releases/2021/s0806-vaccination-pr...

It looks at reinfection rates of unvaxxed people who had COVID vs vaccinated people.

Citation needed.

And in particular it has been shown that natural immunity produces a much broader set of antibodies that may allow the immune system to cope with variants better.

I’m not advocating natural immunity btw. I completely agree people should get the vaccine.

They are not "as immune as they can hope for" and would benefit from vaccination, after having had COVID, in that respect.

Links posted already, but mainly https://www.healthline.com/health-news/why-you-need-to-get-v...

Anyway, available sources so far seem to suggest greater immunity from the vaccine.

https://directorsblog.nih.gov/2021/06/22/how-immunity-genera...

Merriam-Webster definition of straw man: a weak or imaginary opposition (such as an argument or adversary) set up only to be easily confuted

Stating the actual side-effects of one course over the other is neither weak nor imaginary.

https://www.cdc.gov/mmwr/volumes/70/wr/mm7032e1.htm?s_cid=mm...

I doubt it?

I supposed even if the logistics is questionable, we should try to distribute it to people who are actually going to use it.

The risks of amputation are relatively well-known and understood.

The risks, especially long-term, of mass, imperfect vaccination, using an entirely brand new development technology; not well known. Not understood. Are there long-term, rare side-effects of the vaccine we don't know about? Will the imperfect nature of the vaccine and its rollout cause wider evolution of vaccine-resistant coronaviruses? We don't know.

Its a ridiculous comparison because one of these things is dangerous; the other has unquantified risk.

That's why "First, Do No Harm" is such an important foundation of medical ethics. We are dealing with systems more complex than you can even imagine; between the human body, multi-human interactions, and planet-scale resource allocation during a pandemic. There is a LOT we don't know.

This doesn't mean you shouldn't get vaccinated. I have. Many people should. The benefits are well-known and understood; they're pretty strong. But it does mean, maybe there's a middleground we need to find which doesn't involve demonizing and ostracizing the people who choose not to. We should be better at understanding each-other, and understanding how dangerous unknown risks can be, especially when we're put into a position of making decisions out of fear.

The other wrinkle (and possibly the most important one) is that we don’t want to create a system where antivaxxers have an incentive to deliberately infect themselves and/or others.

https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/anti...

>The first vaccines distributed in the United States induce antibodies to S protein. Thus, presence of antibodies to N protein indicates previous natural infection regardless of vaccination status, while presence of antibodies to S protein indicates either previous natural infection or vaccination.

This is a blatant oversimplification & misrepresentation of the article you referenced, and the paper which it cites [1]. The paper makes no claims that vaccine induced immune responses are more or less superior than the immune response induced by natural infection.

Quote from [1]:

- "Specifically, antibodies elicited by the mRNA vaccine were more focused to the RBD compared to antibodies elicited by an infection, which more often targeted other portions of the spike protein."

Counterintuitively, this property of the current mRNA vaccines - the induction of an immune response highly targeted toward the spike protein RBD - when combined with compulsory mass vaccination, could result in widespread proliferation of vaccine resistant variants [2][3][4][5]. This is a serious concern that is on the radar of many top experts in the field.

The second and third order consequences of mass vaccination using an imperfect vaccine are anything but simple, and very much pose a public health risk.

When you consider the evidence supporting the fact that natural immunity is at least equally effective as vaccination (a few more supporting references here [6][7]), it becomes very difficult to defend the idea you're advocating:

> it's simple enough: pretty much everybody (over 12 until trials complete) should get vaccinated

[1] Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection https://stm.sciencemag.org/content/13/600/eabi9915

[2] Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein https://pubmed.ncbi.nlm.nih.gov/33909660/

[3] SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern https://science.sciencemag.org/content/early/2021/06/30/scie...

[4] mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants https://www.nature.com/articles/s41586-021-03324-6

[5] Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens https://journals.plos.org/plosbiology/article?id=10.1371%2Fj...

[6] Necessity of COVID-19 vaccination in previously infected individuals https://www.medrxiv.org/content/10.1101/2021.06.01.21258176v...

[7] Antibody Responses 8 Months after Asymptomatic or Mild SARS-CoV-2 Infection https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920668/

The health policy in some countries e.g. in France (and maybe large parts of Europe?) actually allow you to have an "health passport" just because you recovered from Covid recently enough.

It would actually be illegal in France to privately require proof of vaccination if not exceptionally allowed by a narrow law (as a general principle, medical information are very protected here).

Some Covid vaccines have been forbidden for people under a specific age limit, although they were allowed for a while, but the risk has eventually been reassessed after a few suspects side effects (very very rare, but considered a risk important enough to change the policy, esp since the risk of covid itself decrease greatly the younger you are, and there are arguably safer alternatives in other models of vaccines).

Of course it is still probably "on average" better to get vaccinated on top of recovering from Covid, and of course the comparison with amputation was probably over-the-top (at the very least it should have been stated as a risk of "amputation" with a very very low proba); but overly constraining people is debatable -- especially when tons of factor are hard to be synthetized to "everybody should just get vaccinated right now, unconditionally, -- and accept to be privately controlled by anybody -- or they are horrible antivax people and people will die because of them"; not everybody has the same amount of social contacts with the same categories of people and/or live in the same kind of city and accommodations, public health is not something that appears in empty social contexts just because of raw numbers and models, etc.

Yes it probably would be better if "everybody" was vaccinated. Willingly. And if we had decades of feedback to convince people. And if they were vaccinated against other diseases too. Now welcome to the real world and think of how to navigate efficiently with imperfect knowledge, including how to avoid entirely dismissing concerns.

Primum non nocere certainly does not to be dropped and hopefully will not: the situation is shitty but will become clearer with time, and if we detect either more risks or more safety for various vaccines hopefully the policies will evolve accordingly, and individual opinions too. Note that they already are not completely binary and that it is still kind of hard to decide from which age we should allow / incite / require vaccination -- and the "optimal" solution probably depends on the coverage of the rest of the population too.

And that's because of that very principle. There is no exact obvious point where all-in starts to be required. It maybe would be useful to make regular-flu shots more or less mandatory (and now even the interest of flu-shots is debated by serious scientists because it may be counter productive for the state of the immune system latter in life; or that may depend on people -- maybe new strains of covid would yield to similar debates in a few years?). They are typically not.

That being said my current understanding make me wish more people go get vaccinated, but just do not pretend it is all black & white and that people should not have subtle/reserved opinions.

Rejecting a medical intervention is a right people have. It doesn’t matter it’s because of 5G, fertility, medical conditions or them merely not being in the mood to take the vaccine.

To measure immunity you need to see who gets re-infected and how seriously. Of what I've seen, those studies either show no difference or an advantage for natural immunity.

I don't think the information that natural immunity might be better, is all that helpful. But the growing evidence that it is (at least) as good, is very relevant, since it means vaccines can be prioritized to those who have not yet had Covid-19.

And people who have had it, should certainly not be discriminated against in any way.

Which is why a common anti-vax argument is sow doubt about the harmful effects.

I noticed a few options:

a) conspiratorial: "the government is lying about side harm"

b) anecdotal: "I personally know at least 3 people who couldn't walk after the vaccine. Do you call me a liar?"

c) hyper-skepticism: "how can we know if it long term side effect? Yes it's proven safe for X months, but what about in Y month? what about Y years?"

I found it hard to defuse such positions with "just more data". They seem to be memes (crafted or just evolved?) that resist quite strongly to data.

Which I suspect may be the underlying reason studies are showing the vaccines are more effective than getting covid.

The issue at hand is that those who have been vaccinated and/or recovered from COVID seem to be able to contract the disease again, even to the point where they can be infectious to others, even if they don’t get terribly ill or even show symptoms.

I'm not a doctor or biologist, but I've been learning over the past year. For instance, people generally think of things like "infected", "sick", and "contagious" as being the same thing (or nearly the same thing). If you're talking about one person in everyday context, that's fine. If you're talking in a clinical or epidemiological context, you have to be more careful.

> Is this offering anything more substantive than you own bias and suspicions?

My take-away from the article is that they found all the bits of the immune system primed for long term protection after covid infections. Which is not entirely unexpected, this is what happens with sars, also.

> Is there any response that could get you to consider that the comment "anything which doesn't make people more fearful must be suppressed" is as harmful or even more harmful than the media itself?

I got pretty fed up the news other day when the front page of the BBC led with the an article about leaked CNN memo and three unnamed employees who were fired for not getting vaccinated, and another about Jennifer Aniston apparently cutting off contact with unvaccinated friends. I felt manipulated. I consider stuff like this to be propaganda, not news. It reminded me that I need better sources for covid information, like statnews.com, to get away from such things.

I'd rather see more facts and less adjectives in the news. I'd rather that politicians justify their actions based on numbers, not vague statements. It doesn't seem like the general public is trusted with the facts, but are rather fed a lot of alarmist information.

I imagine the parent poster's assumption is that it would be front page if this study said that natural immunity expires quickly, but we won't see this good news about long lasting immunity on the front page.

> More than 7,700 new cases of the virus have been detected during the most recent wave starting in May, but just 72 of the confirmed cases were reported in people who were known to have been infected previously – that is, less than 1% of the new cases.

> Roughly 40% of new cases – or more than 3,000 patients – involved people who had been infected despite being vaccinated.

Optimistically both vaccine and natural immunity are good, but the numbers above seem to indicate that natural immunity is significantly better.

I think, given the difference in response, the term natural immunity makes sense. You have to choose something and I don’t think ‘natural immunity’ says anything about vaccine immunity being unnatural.

The antibody memory made from a Natural Infection seems like it would be much richer and have much more variety than the mRNA vaccine.

I would imagine the attenuated virus vaccine would be closer to Natural immunity.

Interestingly this means if you have natural immunity and are a regular blood donor you shouldn’t get the vaccine since it deprives the healthcare system of a lifesaving treatment.

[1] https://www.redcrossblood.org/donate-blood/dlp/coronavirus--...

It's not clear to me that you've presented any counter evidence. I will try to outline my thoughts on your comment to help the discussion.

[1] is another primary source beyond the OP that demonstrates the durability of the immune response from natural infection. We are in agreement that in principle the immune response from vaccination should also be durable due to relying on the same underlying mechanisms of the immune system - in fact I am unaware of any literature which demonstrates otherwise. So your point about [1] doesn't seem particularly relevant to me.

> Reference [2] is...it says just as much about the efficacy of vaccination as the efficacy of natural immunity

Yes you're right, and that is a relevant quote you pulled from the abstract. Again, I think we're actually in agreement here - the findings support my original claims.

> Read reference [3] to understand why natural immunity doesn't cut it. Note that widespread natural immunity causes the same positive selection pressure as widespread vaccine deployment

You seem to be missing the central thesis of [3], here are the relevant excerpts:

- "The spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the molecular target for many vaccines and antibody-based prophylactics aimed at bringing COVID-19 under control."

- "Such a narrow molecular focus raises the specter of viral immune evasion as a potential failure mode for these biomedical interventions. With the emergence of new strains of SARS-CoV-2 with altered transmissibility and immune evasion potential, a critical question is this: how easily can the virus escape neutralizing antibodies (nAbs) targeting the spike RBD?"

- "Our modeling suggests that SARS-CoV-2 mutants with one or two mildly deleterious mutations are expected to exist in high numbers due to neutral genetic variation, and consequently resistance to vaccines or other prophylactics that rely on one or two antibodies for protection can develop quickly -and repeatedly- under positive selection."

- "The speed at which nAb resistance develops in the population increases substantially as the number of infected individuals increases, suggesting that complementary strategies to prevent SARS-CoV-2 transmission that exert specific pressure on other proteins (e.g., antiviral prophylactics) or that do not exert a specific selective pressure on the virus (e.g., high-efficiency air filtration, masking, ultraviolet air purification) are key to reducing the risk of immune escape"

- "Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities"

We are in agreement [4] and [5] are not an indictment against vaccines - but again you seem to be missing the most important and highly relevant findings which support my claims.

For example from [4]:

- "The acquisition of the L452R substitution by multiple lineages across multiple continents, including the B.1.617.1 and B.1.617.2 lineages emerging in India (54), is suggestive of positive selection, which might result from the selective pressure of RBD-specific neutralizing Abs"

- "Our data support that the SARS-CoV-2 NTD evolved a compensatory mechanism to form an alternative disulfide bond and that mutations of the S signal peptide occur in vivo in a clinical setting to promote immune evasion."

- "Understanding the newly found mechanism of immune evasion in emerging SARS-CoV-2 variants, such as the signal peptide modification described herein, is as important as sequence surveillance itself to successfully counter the ongoing pandemic."

For example from [5]:

- "different individuals immunized with the Moderna (mRNA-1273) or Pfizer–BioNTech (BNT162b2) vaccines produce closely related, and nearly identical, antibodies."

- "To avert selection and escape, antibody therapies should be composed of combinations of antibodies that target non-overlapping or highly conserved epitopes"

- "We speculate that these mutations emerged in response to immune selection in individuals with nonsterilizing immunity."

> Reference [6]...did you read it? It's about vaccines which protect the host(keep them alive), but still keep them infectious (capable of transmission). None of the COVID-19 vaccines do that...

You are incorrect - the current spike protein focused mRNA based vaccines do not guarantee sterilizing immunity - that means you can be vaccinated yet still get infected and transmit the virus to others. Please cite your sources if you're going to make such claims.

Basically, subsequent shots are security updates.

The paper you link actually says that the memory B-cell populations appear to be maintained after the waning of the antibodies. B-cells are the cells that remembers and creates antibodies in response to an antigen (like the spike protein on the surface of the virus).

[1] https://en.wikipedia.org/wiki/Dunning%E2%80%93Kruger_effect

A high-school biology class will give you good general priors and instincts about how things generally work and is as good as you're gonna get trying to understand what's going on currently without a relevant degree or a few years of hindsight for the politicization to die down. Infections generally leave antibodies behind therefore I'm going to assume people who have been infected have some immunity to this variant. Masks reduce the spread of spit therefore I'm going to assume they are generally useful to combat the spread.

I'm sure this will strike some as being anti-science but having seen how the sausage gets made wrt science and medicine I don't trust myself or the journalists to interpret or qualify the new results we get every week.