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

https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00203-2

by briefcomment • 5 years ago

195 190 5 years ago

wpasc• 5 years ago

Can any of the findings from the properties of how natural immunity works be guided in to future COVID 19 vaccines?

Given how the pharma companies are examining anti-body half life, exploring booster shots, and considering vaccinations against variants (like lambda), can any of the learnings go into a more durable, more broad vaccine?

hprotagonist4• 5 years ago

https://www.nature.com/articles/s41586-021-03738-2

did it already.

briefcomment6• 5 years ago

I think GP is referring to the fact that boosters are being pushed, which implies vaccine immunity is not persistent. It has certainly been pushed since when that study was published.

ajross• 5 years ago

Vaccine immunity IS "natural" immunity. It works the same way, by exposing the body's immune system to virus components such that they product a response. The only difference is that with a vaccine those components don't add up to a viable organism.

But yes: expect newer vaccines tailored to currently-circulating strains to appear; the existing mRNA vaccines produce copies of the spike protein sequenced more than a year ago. That's what we've done for influenza for decades, though not with the same kind of precision.

chuinard• 5 years ago

Damn you got downvoted real quick.

kfprt• 5 years ago

It's not quite the same, delivery (mechanism/location/encapsulation) is different.

JimBlackwood• 5 years ago

Sure, but there is a real difference in response between vaccine/virus.

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.

nickthemagicman6• 5 years ago

How is an mRNA strand that encode for a single very specific protein on a virus the same as the entire virus?

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.

User232• 5 years ago

The Red Cross disagrees[1]: “One of the Red Cross requirements for plasma from routine blood and platelet donations that test positive for high-levels of antibodies to be used as convalescent plasma is that it must be from a donor that has not received a COVID-19 vaccine. This is to ensure that antibodies collected from donors have sufficient antibodies directly related to their immune response to a COVID-19 infection and not just the vaccine, as antibodies from an infection and antibodies from a vaccine are not the same.”

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--...

csours2• 5 years ago

Just a note to non-immunologists - Immunity means different things to health and science professionals vs the general public.

Edit: I'm not going into detail in this comment because I am not an immunologist and I cannot express clearly and correctly what the difference is, but just be aware that "Immunity" may not mean 100% protection in the way that the general public thinks that word means.

umanwizard• 5 years ago

Don’t leave us hanging - what does it mean?

not2b• 5 years ago

If I understand correctly, it means that the immune system launches an immediate response to the new infection, it doesn't mean that the immune system successfully defeats the new infection, just makes it more likely. And then there's the problem of variants.

URSpider94• 5 years ago

I’m still learning, but the concept of “sterilizing immunity” has started to come up recently. What I infer from cursory reading is that “immunity” means the body will mount an immune response immediately upon exposure to the virus, but it doesn’t mean that an infection won’t take hold. “Sterilizing immunity” means immunity strong enough to prevent the virus from growing at all.

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.

csours2• 5 years ago

Sorry this is incomplete, but "Natural Immunity" means a person's immune system will mount an effective response to an infectious agent. However, that person may still be infected, and may be contagious to some degree while the body is fighting off the contagion.

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.

nickthemagicman6• 5 years ago

As a person with a biology degree who took several immunology courses.

I'd be curious to see what your various definitions are.

hprotagonist4• 5 years ago

https://www.nature.com/articles/s41586-021-03738-2

vaccines also produce durable and persistent immune responses. Primary antibody titers wane, but the system itself remembers and can regenerate them when challenged.

see https://news.ycombinator.com/item?id=28107714 for contra "but muh boosters", which i suspect is what's helping me collect downvotes.

nickthemagicman6• 5 years ago

Natural immunity may work better considering the vaccine requires booster shots every 12 months according to the Pfizer CEO.

https://www.cnbc.com/2021/04/15/pfizer-ceo-says-third-covid-...

Valgrim2• 5 years ago

The requirement for booster shots may be for increasing immunity to variants, not the original virus. If you survived the original virus and got an immunity out of it you are just as vulnerable to variants as anyone who got the vaccine.

Basically, subsequent shots are security updates.

orbifold• 5 years ago

Not really the anti-body count decays more quickly compared to that of a natural infection and does so dramatically especially for older people: https://www.thelancet.com/journals/lancet/article/PIIS0140-6.... This is the underlying reason that there is talk of boosters.

rcpt• 5 years ago

Older people has to have some sample bias since those without strong immune systems died.

Valgrim2• 5 years ago

It is normal for antibodies to decline after an immune response, it doesn't mean the immunity is gone, the immune system remembers how to produce them when needed.

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).

015a2• 5 years ago

Its important to keep studies like this in mind when talking with people who refuse to take the vaccine because they "already had COVID". In a very real sense, if natural antibodies are durable, persistent, and effective; the vaccine is an unnecessary medical procedure. Doctors would not cut off your legs for no reason; that would be unethical. The vaccine is a medical procedure like any other; if the benefit is questionable, it would be unethical for doctors to administer it.

Yet, we have an increasing number of venues, workplaces, and events which are requiring proof of vaccination to participate. This is forcing both people who already have antibodies, and even people who can't make antibodies (e.g. immunocompromised, solid organ transplant, etc), to undergo a medical procedure for little to no benefit.

Primum non nocere

mxxc2• 5 years ago

it is a scandal, especially considering the amount of non-immunised people at risk in the rest of the world. i fall in that category (recovered) and i would even pay to give my vaccines away.

kiba• 5 years ago

It is not being used by people who should get said vaccine here in the states, and it is questionable if we even have the logistics to enable it.

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

IAmGraydon• 5 years ago

Comparing it to an amputation is beyond ridiculous. If you have to make leaps of logic like this, you know your argument is extremely weak.

briefcomment6• 5 years ago

Ok, doctors would not administer steroids for long term use for minor pain, that would be unethical and highly dangerous (except they do, from first hand experience)

015a2• 5 years ago

You're right; its a ridiculous comparison.

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.

mercora• 5 years ago

how easy is it to test for these antibodies for a layman? could people actually easily get tested prior to considering a vaccination?

5424582• 5 years ago

The test is easy, but has a relatively high false positive rate. It also may use up lab resources that could be put to other uses.

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.

briefcomment6• 5 years ago

It's available and getting cheaper pretty quickly. Hopefully others can chime in, seems like a promising path to take.

lazyjones3• 5 years ago

There are commercially available antibody tests that can distinguish between antibodies from natural infection and from the common vaccines.

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.

landemva2• 5 years ago

In my experience, the finger prick blood test cost $25 and 15 minutes. This test is for blood antibodies. This is not the test for active infection, such as nasal PCR.

deanclatworthy2• 5 years ago

As far I’m aware this is an American thing. I’m from Finland (no vaccine pass yet) but travelling in Germany/Austria right now. They have the concept of 3G (don’t ask me to translate) but basically you can’t eat, drink or stay anywhere without either a vaccine, recovery or negative test.

There is a pop up antigen test facility about 100m from the restaurant where anyone can go get a quick negative result and go do their thing for a set period of time. I’m conflicted on this given the inaccuracy of the antigen tests.

I’m currently sat in a restaurant typing this message, and have been served food and drink and yet to be asked to verify my EU certificate of vaccination. So your mileage may vary.

ithkuil8• 5 years ago

Most of the pushback I hear here (Italy) about the ability to just get tested as an alternative to vaccine certification is the cost. It's perceived as a tax on the freedom to not vaccinate.

maxerickson3• 5 years ago

To a first approximation, the American thing is to not have any requirements for entry. There's a few employers and cities departing from that policy.

treeman79• 5 years ago

I had covid in November. Have had it again the past week and a half. It was a rough time the first time, but not as bad as when I had pneumonia.

Now, A constant mild sore throat and a lot of bad headaches. Otherwise not much.

raphlinus9• 5 years ago

I know this thread is catnip for the antivax contingent that reliably appears, but this argument has several problems.

First, our vaccines provide a stronger immune response than infection, as has been well documented by now[1]. Vaccination on top of prior infection boosts the response[2].

Second, the harm from the vaccine is minimal, and comparing it with an amputation is ridiculous (in spite of the large number of superstitious people who believe otherwise).

There are subtle arguments to be made for adjusting vaccination (one shot is almost certainly enough) when prior infection is documented, but from a public health perspective it's simple enough: pretty much everybody (over 12 until trials complete) should get vaccinated, and if they did, illness and death would decrease dramatically.

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

[2] https://jamanetwork.com/journals/jama/fullarticle/2782139

peteradio7• 5 years ago

[1] is not generally supportive of your very broad statement. You must qualify you statement with some indication of this stated limitation: "carrying “single letter” changes in a key portion of their spike protein"

criticaltinker9• 5 years ago

vaccines provide a stronger immune response than infection

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/

temac• 5 years ago

Maybe the comparison with amputation is a little over-the-top but let me illustrate with a few other real-world examples why this kind of concern is not completely illegitimate.

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.

blub• 5 years ago

I haven’t seen almost any comments on HN which can be qualified as anti-vaccine, so I find your assertion unjustified. But the real issue I have with such comments is that now apparently someone that does not want a specific medical treatment is being smeared as “antivax”.

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.

spfzero2• 5 years ago

I don't think you can state that the vaccines provide a stronger immune response. There is a lot of evidence to the contrary, including this OP. They may provide a stronger single-antibody response as measured at some point in time, but there's no evidence that that results in "better" immunity.

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.

asddubs• 5 years ago

interesting, over here in germany if you (provably) had covid you don't have to get vaccinated to enter places requiring that or a test

l33tman• 5 years ago

I think the EU timeout for the proved infection is 6 months unfortunately. So someone in the EU decided that a COVID infection's protection only lasts 6 months.

rvp-x• 5 years ago

I am under the impression that a lot of places consider recovered cases as equivalent to fully vaccinated.

pfisherman3• 5 years ago

I think other comments may have pointed this out already, but there are several problems with this line of reasoning.

When deciding on whether or not to administer a procedure or treatment, one must consider the balance of potential harms and benefits, while accounting for uncertainty.

In this particular case, the potential for harm from the vaccine is quite low (this is borne out by the data), and the benefits are mostly unknown. The potential harms of NOT taking the vaccine are mostly unknown (data is still coming in), and the potential benefit of that course of action is quite low. So it seems like the positive expected value / utility decision here is for them to get the vaccine.

In your comment you use the analogy of a procedure with a much different risk / benefit profile. So that does not really hold up. A much better analogy would be something like routine screening for prostate cancer once you pass a certain age.

ithkuil8• 5 years ago

In this particular case, the potential for harm from the vaccine is quite low (this is borne out by the data),

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.

Retric2• 5 years ago

This line of thinking assumes you can reliably separate people that have had covid from those that haven’t. In the real world requiring vaccines for everyone means vaccination of people that thought they had covid but didn’t.

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

lamontcg• 5 years ago

A vaccination isn't cutting your legs off.

First of all, if you've recovered from COVID then you've fought off the whole virus before, not just the spike RNA. You shouldn't have issues with the vaccine.

Secondly, you could have had mild COVID and if you were "young" (under 30) then your innate immune system may have been sufficient to clear the virus and you may not have formed a lasting humoral immune memory.

Third, you may have had a false positive with a high Ct.

And Fourth, many people never got tested, and people really cannot self-diagnose (particularly the people in the USA who think they caught it in late 2019).

If you've caught COVID just take the vaccine, you've already had the spike RNA in your body once. You're like an open water swimmer worried they might drown in the pool.

Of course I really suspect that this argument is being made in bad faith so people have a backdoor to avoid vaccination and to undermine vaccination mandates. And the harm caused by the virus spreading vastly exceeds the putative harm done by an "unnecessary procedure" -- just look at Florida right now.

Woodrow503• 5 years ago

Question: I’ve got the vaccine. I get a breakthrough case.

Is this a “best case” scenario for durable immunity?

jron• 5 years ago

This seems like the most important unasked question. Common sense would suggest the best case would be vaccination followed by repeated exposure to the virus yet hardly anyone is talking about it.

jjtheblunt3• 5 years ago

i wonder if that's what normally happens in nature across many viruses. like a primed immune system exposed to a new variant runs a minor "software update" now and then.

unanswered• 5 years ago

Real facts that people won't like to hear: anyone who thought differently probably needs to retake a high school biology class.

ebiester• 5 years ago

The problem is that you think a high school biology class is sufficient to understand the broader implications.

What is the limitation of this study? For example, in the context of the paper, "immunity" means that your immune system mounts an immediate response. Do the antibodies created attack variants equally effectively relative to vaccines? Are they better? Worse?

This paper is one data point. Your high school biology class won't teach you how to understand the limitations of the paper. That's why we have people who study this for decades.

Don't mistake your "high school biology class" with expertise.

BrianOnHN3• 5 years ago

This is a great example of the Dunning–Kruger effect[1].

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

ad404b8a372f2b9• 5 years ago

I suspect nobody commenting here is equipped to analyze critically the science being done either on the virus or the vaccine, yet everybody speaks with authority on what's relevant and what's bullhockey.

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.

dzink• 5 years ago

Immunity persists for a while but doesn’t seem to stop the new variants. Another study shows that re-infection with Covid is a lot more likely in unvaccinated people than in vaccinated.

lazyjones3• 5 years ago

Data from Israel shows that vaccinated people have a 6.72 times higher chance to get infected than previously infected people: https://www.israelnationalnews.com/News/News.aspx/309762

mikem1703• 5 years ago

That's interesting!

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.

jetpks• 5 years ago

Do you have a moderately credible source on this? The linked is pushing a radical right-wing hard-line anti-vaccine agenda too hard to be considered remotely credible or trustworthy. It also does not link to primary sources.

thih9• 5 years ago

Do you or anyone else have a link to the other study?

tchalla4• 5 years ago

Now, a new NIH-supported study shows that the answer to this question will vary based on how an individual’s antibodies against SARS-CoV-2 were generated: over the course of a naturally acquired infection or from a COVID-19 vaccine. The new evidence shows that protective antibodies generated in response to an mRNA vaccine will target a broader range of SARS-CoV-2 variants carrying “single letter” changes in a key portion of their spike protein compared to antibodies acquired from an infection.

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

SideburnsOfDoom3• 5 years ago

Not to disagree with the effectiveness of immunity gained by getting Covid-19, but also:

"The evidence shows that protective antibodies generated in response to an mRNA vaccine will target a broader range of SARS-CoV-2 variants ... compared to antibodies acquired from an infection."

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

"Vaccination offers longer, stronger immunity"

https://www.jhsph.edu/covid-19/articles/why-covid-19-vaccine...

"Why a vaccine can provide better immunity than an actual infection"

https://theconversation.com/why-a-vaccine-can-provide-better...

"Why You Need to Get Vaccinated Even If You’ve Already Had COVID-19"

https://www.healthline.com/health-news/why-you-need-to-get-v...

And also, vaccination is a much, much safer way to get antibodies, than via getting sick with Covid-19.

eightysixfour2• 5 years ago

To add to the list:

"Kentucky residents who were not vaccinated had 2.34 times the odds of reinfection compared with those who were fully vaccinated (odds ratio [OR] = 2.34; 95% confidence interval [CI] = 1.58–3.47). These findings suggest that among persons with previous SARS-CoV-2 infection, full vaccination provides additional protection against reinfection."

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

rubatuga3• 5 years ago

Observational evidence of course, meaning plenty of confounders.

criticaltinker9• 5 years ago

Here is a paper (not yet peer-reviewed) which presents statistically strong evidence (N = 52,238) that vaccinating previously infected individuals provides practically no benefit [1].

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...

briefcomment6• 5 years ago

Probably not as clear cut as that. The OP study suggests that vaccines can be improved from learnings from natural immunity.

"Overcoming the challenges to end the pandemic is accentuated by the recognition that SARS-CoV-2 can undergo rapid antigenic variation that may lower vaccine effectiveness in preventing new cases and progression to severe disease. Our findings show that most COVID-19 patients induce a wide-ranging immune defense against SARS-CoV-2 infection, encompassing antibodies and memory B cells recognizing both the RBD and other regions of the spike, broadly-specific and polyfunctional CD4+ T cells, and polyfunctional CD8+ T cells. The immune response to natural infection is likely to provide some degree of protective immunity even against SARS-CoV-2 variants because the CD4+ and CD8+ T cell epitopes will likely be conserved. Thus, vaccine induction of CD8+ T cells to more conserved antigens such as the nucleocapsid, rather than just to SARS-CoV-2 spike antigens, may add benefit to more rapid containment of infection as SARS-CoV-2 variants overtake the prevailing strains."

timr2• 5 years ago

I am a believer in vaccines, but you're mischaracterizing the first link by selective omission. You've cut out the critical words of the sentence (emphasized):

The new evidence shows that protective antibodies generated in response to an mRNA vaccine will target a broader range of SARS-CoV-2 variants carrying “single letter” changes in a key portion of their spike protein compared to antibodies acquired from an infection.

The paper shows that vaccines produce a more diverse antibody response to the RBD, which is one portion of the spike protein. They admit that natural infection produces antibodies targeted to other portions of the spike protein (also, presumably, to other parts of the virus, though that isn't discussed in this press release):

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.

Is this evidence that vaccines are "better" than natural infection? No. It can't be. The paper shows that there's a difference between the antibody responses, but beyond that, it's impossible to know what the practical impacts of that difference might be from this paper.

This is a perfect example of the political weaponization of pre-prints that has happened throughout the pandemic. People read these things, don't fully understand what they're reading or what questions they answer, and immediately jump to social media to start waving them around like team flags (and worse, people who should know better -- like Francis Collins -- seem to encourage the behavior. This PR seems to be trying very hard to mislead, without actually stepping over the line.)

This is an interesting paper, but it is in no way a definitive statement about the relative benefits of vaccination vs. natural immunity.

SideburnsOfDoom3• 5 years ago

Thank you for adding nuance. This topic is indeed in sore need of more nuance.

raphlinus9• 5 years ago

Thanks for trying to bring more precision to the discussion. I also cited that blog post elsethread, and, having reviewed it, agree it's not the single best piece of evidence. It establishes a narrow result which suggests a generally better immune response from vaccines, but does not prove it.

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.

mike006323• 5 years ago

"It can't be."

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.

phkahler• 5 years ago

We can cherry pick papers all day long to support or refute the idea that having had Covid19 is equivalent/better/worse than getting the vaccine. Anyone being honest can see that the jury is still out on the issue. But I can state 2 things with certainty. 1) having had it does offer some degree of immunization. 2) there is a lot of evidence that those spike proteins do damage. Given that, I dont know why some people lump previously infected folks in with anti-vaxxers. It's not even close to the same thinking.

mmcnl2• 5 years ago

there is a lot of evidence that those spike proteins do damage

Citation needed.

nickthemagicman6• 5 years ago

I love how the top comment is links to 4 opinion piece articles two of which are from healthline.com and theconversation.com.

"Citations"

My high school English teacher would be disappointed in this site.

I'm sure there's a bunch of actual scientific articles below that are flagged because they are going against the narrative.

Don't ever change HN.

arein32• 5 years ago

you can look at jewish data

for a highly vaccinated population 50% newly infected are unvaccinated, 50% are vaccinated and only 1% are getting the virus the second time

amanaplanacanal• 5 years ago

I assume you mean Israeli data?

mbgerring2• 5 years ago

“Acquiring” natural immunity also has the following side effects at a much higher rate than the vaccine:

- Death

- Hospitalization

- Chronic illness, which can include long-term neurological impairment

I feel like it’s important to keep that in mind if you’re either advocating “natural immunity” as a public health strategy, or considering it a personal strategy.

slumpt_5• 5 years ago

Vaccination also has more durable immunity than natural immunity in this case. Without those risks you outline.

nickthemagicman6• 5 years ago

* Citation needed.

wizzwizz4• 5 years ago

I expected this for the mRNA vaccine, but source?

anonuser1234566• 5 years ago

I’m not sure this is clear. Yes, this is what has been stated in the media, but I have yet to see data to back the claim.

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.

briefcomment6• 5 years ago

That's a strawman. Can you instead address this particular bucket: people who have had Covid, and are now wondering if they are as immune as they can hope for, considering all other available interventions.

SideburnsOfDoom3• 5 years ago

people who have had Covid, and are now wondering if they are as immune as they can hope for, considering all other available interventions.

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...

plorg• 5 years ago

I absolutely don't think it's a strawman. Nearly to a person, the people in my life who have not gotten vaccinated and have not yet gotten Covid-19, if asked, have been making this argument: it's not that bad, it's not worth getting the vaccine.

ramraj07• 5 years ago

Actually being infected with Covid (symptomatic) probably does confer the best immunity possible, for sure. You should still get vaccinated after that though, because research suggests that vaccination can significantly help alleviate long COViD symptoms which a large fraction of patients have. Haven’t seen actual numbers on the immunity boost conferred by post-Covid vaccination though (no reason to think it’ll not add at least a slight bit).

jchw• 5 years ago

Not being or knowing people applicable to the comment does not make it a straw man.

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

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

daveguy2• 5 years ago

Identifying the relative effects of two courses of action is nowhere near a straw man.

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.

eightysixfour2• 5 years ago

This study shows that those who have had COVID but are unvaccinated have 2.3x the risk of reinfection compared to those who had COVID and are vaccinated. 246 patients, 492 controls.

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

ClumsyPilot• 5 years ago

Well unfortunately COVID forgot to ask my opinion before gifting me with one for free

mbgerring2• 5 years ago

I’m sorry you got sick, and I’m glad to see this study suggesting you have durable immunity! I worry that since it’s dated July 14 it may not have enough data on the Delta variant to be useful in considering your risk going forward. I hope you remain in good health.

chiefalchemist• 5 years ago

Links please. If those at risk aren't given the jab then counts of death and hospitalizations are going to be skewed against the natural immunity.

landemva2• 5 years ago

Much of the death toll centers on those who are already sick, obese, and otherwise compromised. Age groups of children and young adults show remarkable resilience to infection. There is not one outcome.

AnthonBerg• 5 years ago

So you would have us call to those who are already tired and add death to their burden?

I doubt it?

nicoburns• 5 years ago

There is nevertheless a significantly lower incidence of negative effects from the vaccine than from a covid infection in all age groups.

nullc• 5 years ago

“Acquiring” natural immunity also has the following side effects at a much higher rate than the vaccine: - Death

The pfizer vaccine clinical trial had equal rates of death among vaccine and placebo recipients, FWIW.

I don't believe any RCT has validated the claim that vaccination reduces the recipients chance of death.

(Nor has any validated that parachutes save lives, I suppose!)

rossdavidh• 5 years ago

...more or less like most infections, as has been known for centuries. And yet, due to the current "anything which doesn't make people more fearful must be suppressed" attitude, this kind of thing is news. Or would be, if the U.S. newsmedia were willing to report it, which I suspect they will not.

BrianOnHN3• 5 years ago

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

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?

Asking because I'd like to better understand how to address people with your beliefs in the future.

mikem1703• 5 years ago

Not the poster you are replying to, but I'll bite, out of curiosity about your thinking...

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.

dang• 5 years ago

All: I know it's an activating topic, but this thread has tons of comments breaking the site guidelines. That's not ok.

If you're going to comment, make sure you know the rules and stick to them: https://news.ycombinator.com/newsguidelines.html. That means making substantive points thoughtfully.

If you want to put down or yell at people on the other side of this $hot-topic, or any topic, please do that somewhere else. We're trying for a little better than internet default here.

DantesKite• 5 years ago

I could see a case to vaccinate people even if they have natural, durable, and long-lasting immunity to Covid-19 after infection if it makes their immunity even stronger.

criticaltinker9• 5 years ago

This paper further supports the fact that naturally acquired immunity to SARS-CoV-2 is 1) robust and 2) durable.

1) Robust means the immune response recognizes many different parts of the virus.

2) Durable means the immune response remains detectable - and likely effective at protecting the individual - for a long period of time.

A robust immune response is important because it provides a certain degree of protection against variants of the virus.

This robustness is why some people hypothesize that natural immunity provides better protection than vaccination - however this hypothesis has not been conclusively proven in the literature yet. If you're aware of primary sources that say otherwise please share them.

For now, all available evidence strongly suggests that individuals with naturally acquired immunity are at least equally well protected as individuals who have been vaccinated. Here are a couple more supporting references [1][2].

As a final point - in the literature there is some evidence & concern that the current mRNA vaccines induce an immune response which is highly targeted toward the spike protein [3]. When combined with mass vaccination campaigns, this creates tremendous selective pressure that can further enhance the fitness of the virus, and lead to increasingly infectious or virulent variants [3][4][5][6].

It's clear that vaccination poses little additional risk - but also little benefit - to previously infected individuals, and consequently our vaccination campaigns should be highly targeted toward vulnerable demographics to reap the most benefits and minimize the risks to public health.

[1] SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans https://www.nature.com/articles/s41586-021-03647-4.pdf

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

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

[4] 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...

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

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

bmer2• 5 years ago

Reference [1] is applicable to how our body handles an immune response to the viral infection in general: i.e. whether naturally acquired, or through controlled vaccination. Natural infections were, naturally focused upon, in order to understand the baseline dynamics of viral infection.

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

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.

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, and:

Finally, our work suggests that immune evasion requiring one to two mutations occurs within months, raising the prospect that this phenomenon will further shorten the duration of natural immunity...

The paper goes on to provide (under Discussion) a series of strategies for developing a vaccination system that takes into account modelled viral evolution. Can't come up with strategies like that for natural immunity, apart from: "periodically re-infect individual"...which is exactly what vaccines do, in a controlled manner.

Reference [4] and [5] are research tabulating mutations the virus is undergoing to counter both natural acquired and vaccine-mediated immune responses. It is not an indictment against vaccines, but just like paper [3], provide strategies on how to update vaccines. That updates will be required is not a surprise to anyone. Viral evolution has long been known of, and no one expected the emergency COVID-19 vaccines to be effective until the end of time.

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...

criticaltinker9• 5 years ago

Are you trying to refute the claim that natural infection confers immunity that is at least equally as protective as vaccination?

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.

andy_ppp• 5 years ago

I wonder if having had different less deadly coronaviruses also gives some immunity?

randymercury• 5 years ago

That was a theory around why certain countries have fared relatively well, places like Cambodia and Vietnam.

Their populations could have been exposed to similar viruses and would have had some built in immunity.

rpmisms• 5 years ago

I saw someone citing this a few days ago: having had the common cold recently can lessen your covid symptoms. He didn't source it, but on its face, it seems to make sense.

mensetmanusman• 5 years ago

If having COVID imparts as much future protection as the J&J vaccine, there is an ethical argument that one could make:

help vaccinate the poor who want it instead of adding to the asymptotic protection of the rich. Else, people might argue we should all have n- booster shots to get even better protection, when we still don’t have enough for the entire world. Vaccines are currently zero sum.

YPCrumble• 5 years ago

If twenty percent of the population has had covid, and fifty percent has been vaccinated, say we assume half of the twenty percent isn’t an overlap. Wouldn’t that put us much closer to the herd immunity number of seventy percent than we’ve been thinking? And that if infections continue at a high pace, shouldn’t we reach that level very soon?

raphlinus9• 5 years ago

The idea of being at or near herd immunity has been pushed so many times since the start of this pandemic, and each time those hopes have been dashed.

The threshold needed for herd immunity has been revised upward since the 70% figure was widely discussed. First, the R0 for the delta variant is almost certainly higher than for earlier variants. I am personally skeptical of claims in the 8 range, but they are widespread, especially by public health professionals, in contrast to, say, virologists, who tend to point to antigenic drift as a mechanism that could explain the rise in delta prevalence.

Also, vaccine effectiveness is a factor in the herd immunity threshold, and that is also reduced a bit off earlier high estimates, partly because of variants and partly because of antibody waning.

So my best guess is that herd immunity is now permanently out of reach. I'd love to be proved wrong on that, though.

nradov• 5 years ago

The CDC estimates that 36% of Americans have been infected.

https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/burd...

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

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