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Comment by seren | Hacker News Reader

From my understanding if you had an mRNA vaccine, your body was only exposed to an artificial spike protein, so effectively you have spike specific antibodies.

On the other hand, if you had a real infection by the virus, you likely have antibodies for the spike protein and other part of the virus like the shell. So from my layman understanding, the immunity should be more resistant to a mutation of the spike protein.

That being said I also know someone who got Covid 2 times, once in march 2020 and once in april 2021. (Confirmed by PCR the 2 times). The second time was much milder, but still she had to stop working for a week (versus one month the first time). It is still possible it was a defective test the second time, and something else than Covid.

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Some time ago i listened to a respected Argentina scientist (that lives and works in France) saying something: “we can’t confirm nor deny anything about COVID, given the poor quality of scientific procedure we follow in testing”

He was complaining of lack of scientific rigorousity with testing (at least in France) and he compared it to the “behind the scenes” of a restaurant’s kitchen.

For example, he was saying that the “informal” rate of contamination of tests were off the charts, but surprisingly, nobody was doing a thorough, official contamination analysis.

What I’m saying with all this is that: your friend thinks she had COVID twice. Or even, her doctor thinks so. But it’s hard to trust anything with our given situation.

PS: I’m not saying she didn’t have it twice. It might be possible. It just sucks how bad we’ve been at science these past 2 years and how easily we’ve been overwhelmed by “operative” tasks.

Edit: his name is Pablo Goldschmidt[0] and he works in France (not in the UK as I originally stated). Here's the interview (in spanish, also WARNING, the site sucks and is full of ads): https://marcelolongobardi.cienradios.com/pablo-goldschmidt-l...

[0] https://www.researchgate.net/profile/Pablo-Goldschmidt

This is also why you never want your DNA to end up where it can be used for false accusations against you. Lab work isn't trustworthy against mistakes.

Paranoid a bit much?

Just because you're paranoid doesn't mean they aren't after you!

Elon Musk got himself tested 4 times the same day in 2020. 2 positive 2 negative.

That's not surprising or particularly notable for a rapid antigen test, which is why they're not used as a full replacement for a PCR test in most countries.

The BD rapid test he used seems to be one which a paper [1] indicates has a lower positive percent agreement than a PCR test.

Rapid tests in general, compared directly to PCR, seem to do even worse with one paper [2] finding a symptomatic sensitivity of 72% and an asymptomatic sensitivity of 58%.

[1]: https://pubmed.ncbi.nlm.nih.gov/33023911/

[2]: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD...

And a reminder that he did in fact have covid. A funny tweet that explains the trade offs of that kind of test: https://www.newsweek.com/space-karen-response-elon-musk-vira...

I was

Day 0: Antigen positive Day 1: PCR positive Day 8: Antigen positive Day 9: Antigen negative Day 10: Antigen positive Day 10: PCR negative Day 11: Antigen negative Then 10+ negatives after

> That being said I also know someone who got Covid 2 times, once in march 2020 and once in april 2021. (Confirmed by PCR the 2 times). The second time was much milder, but still she had to stop working for a week (versus one month the first time). It is still possible it was a defective test the second time, and something else than Covid.

For what it's worth my girlfriend is currently recovering from her second bout of covid. She had it first about a year ago and then second about a month and a half ago. Confirmed by PCR test and antibody tests afterwards as well as totally consistent symptoms. The first time knocked her out totally about a week and left her tired for a few weeks while the second time knocked her out totally for maybe 2 1/2 weeks and she's still quite weak now 6 weeks later, so the second case has been much worse.

Obviously just anecdotal, but getting it twice does happen and the second time apparently can be worse.

My hypothesis is that people who got Covid once and recovered feel safe, thus start doing more risky things and have more exposure to potential Covid carriers.

So the second time the viral load may be much higher, which leads to worse symptoms.

Do you think this is true in your anecdotal experience?

In general that's certainly possible, but I don't think it is in this case. My girlfriend and I were pretty relaxed late last summer (a couple months after she got sick) to early winter when we had low case count, but after that we became very careful again when the cases got high. Since then we've both been very careful.

Her job has just been a bit of a cesspool of cases. It just keeps going around and around and eventually it got her too.

Another possibility is different variant which is deadlier. However everything is just speculation at this point.

Seems like it is the other way, at least according to his paper[1]:

> Previously infected individuals developed higher Ab titers to the vaccine than those who have not been previously exposed. These results indicate that mRNA vaccination rapidly induces a much stronger and broader Ab response than SARS-CoV-2 infection.

[1] https://www.biorxiv.org/content/10.1101/2021.04.15.440089v4

The fact that previously infected people have higher titers to the vaccine implies nothing about the effectiveness of the vaccine -- it implies that the human immune system works, and recognizes the spike protein when it is re-introduced. Extrapolating from this to conclude that the protection is therefore better is an unsupported leap. The authors are trying to piggyback on previous work that claims that antibody levels correlate with immunity, but there's a huge difference between someone who has never had Covid, and someone who has.

The abstract does say that vaccinated people have higher titers than naturally immune people, and this can be considered evidence:

> mRNA vaccination induced much higher Ab levels especially against the RBD domain and significant cross-reactivity against SARS RBD and S1 was also observed.

That paper demonstrates that the vaccine provides a stronger response to the part of the virus that the vaccine tries to get you to respond to than actually getting sick does.

It does NOT demonstrate that the vaccine provides any response to other parts of the virus. And it almost certainly does not, while getting sick does.

It also DOESN'T address the question of which provides a better response to novel variants of COVID-19.

> So from my layman understanding, the immunity should be more resistant to a mutation of the spike protein.

This is probably not true. But I don't know of any medical evidence one way or the other.

First, your innate immune system could clear the virus, at which point you have no immunity at all.

Second, your immune system could lock to some random piece of the virus that easily mutates.

Third, your immune system could lock on to some random piece that is common. Oops. Autoimmune problem incoming.

Fourth, your immune system could lock to some piece of the spike protein that mutates quickly (apparently the immune system "likes" 3 particular regions around the spike protein --one of which mutates quite freely).

With the vaccine, your immune system is primed to the spike protein and the particular region that is expressed in the vaccine. It's very targeted.

I had Covid, but I went and got the vaccine anyway for exactly these reasons.

I thought it was sort of the other way around; that your immune system is keying into some fairly random and subjective set of dna features on the specific viral strain you've been infected with.

But that with the mRNA vaccines, your body is being explicitly taught about the spike protein, nothing more, nothing less. So provided any future infection employs a spike protein, you have immunity. The question is, what are the odds that sars-cov2 would evolve an entirely different mechanism from the spike protein? My impression was that's pretty unlikely, and why there's so much confidence the mRNA vaccines are robust against variants.

I know absolutely nothing about this subject and frankly am unqualified to even participate in this discussion. I'm just hoping someone who is can clarify/correct my understanding if it's totally misinformed.

Its unlikely to evolve an infection mechanism besides the spike protein. There will be plenty of mutant evolutionary deadends that live and die in a few days.

Based on work from similar coronaviruses, the spike protein was quickly identified at the beginning of the pandemic as an important component for viral binding to the ACE-2 receptor. It is one protein component of the viral shell, but has proven to be an excellent target, given its induced immune response to the mRNA vaccines.

Covid will not be able to mutate away from using the spike protein, but it will continue to evolve mutations within the protein as it responds to selective pressure. Fortunately, when the body creates an adaptive immune response through antibody or the T-cell receptor, this response is polyclonal. Think of it as not a single antibody to spike but rather a population of antibodies, all targeting a variety of residues on the protein. This is why most immunologists are not terribly worried about the variants that have emerged wrecking all of our immunization efforts—those variants are usually based on just a couple of mutant residues and so will not (generally speaking) be able to evade the population of antibody and t-cell responses that have been generated. You may have heard about monoclonal antibody therapies to covid ... those, unfortunately, are very susceptible to mutation because if a critical targeted residue mutates, you could lose all efficacy of the drug.

The only answer to rapidly mutating pathogens is an entire inducible population of neutralizing proteins in each of us and it’s no coincidence that we have this defense. If we didn’t, our species could not be here right now.

> You may have heard about monoclonal antibody therapies to covid ... those, unfortunately, are very susceptible to mutation because if a critical targeted residue mutates, you could lose all efficacy of the drug.

Depends if the therapy works on the virus itself, or your body's response to the infection.

I think most of the monoclonal antibodies are working on your body's (over)response, so mutations shouldn't change much. Same with corticosteroids.

But Nucloside/tide analogues on the other hand or anything else working against viral processes/replication, oh yeah.

I should have been more clear about the monoclonals I was referring to, which are those targeting the virus itself (1).

You may be thinking of the targeted immune modulators against inflammatory cytokines like TNF-alpha (2) and IL-6 (3). Some of those are antibodies, others are pieces of antibody fused to other proteins. Regardless, those types of treatments would not be affected directly by viral mutation, whereas the first type I described above have already been shown to be less effective with existing mutations (4).

1. https://en.m.wikipedia.org/wiki/Casirivimab/imdevimab 2. https://en.m.wikipedia.org/wiki/Casirivimab/imdevimab 3. https://www.covid19treatmentguidelines.nih.gov/immunomodulat... 4. https://science.sciencemag.org/content/371/6531/850

Doesn't the virus bud off of the host cell's lipid membrane and not have a protein / capsid membrane for the immune system to be able to fingerprint? The spikes are the only thing visible to the immune system is my understanding, at least of viable virus.

Other innate immune processes destroy any extracellular RNA if the virus is ruptured etc.

What if you have the vaccine, and then get exposed to the actual virus? Would it be the best of all worlds as the existing antibodies would prevent a full on infection but your body would also learn more generalized attacks against the virus? Or would it not be enough exposure to warrant the latter?

That’s what I think and is why I actually wanted to get the virus 2+ weeks after vaccination.

You want to get the virus so that in the future you don't...get the virus?

1. You could control the timing and your circumstances so you can quarantine etc, as opposed to having it unplanned, maybe while traveling

2. Supposedly symptoms and forward-transmission will be milder/less right after a vaccination as opposed to months later.

Yeah:

1. Be super healthy 2. Have full vaccine effectiveness 3. Relatively quarantined

Now you’re gonna have the strongest defense. In the future you won’t unexpectedly get it and have any chance of infecting people around you. You chose when to get it. Smart all around, but very counterculture.

It makes sense if people who have recovered from Covid and are presumed immune are exempt from lockdown measures.

By coincidence, my uncle got the covid nearly at the same time he got his Pfizer shot. Later, the symptoms became too serious. It seems that the vaccine didn't have enough time to protect him. He went to the hospital where he discovered he got the covid. He was under oxygen for weeks. Luckily, he recovered, but lost so much weight and now feels very weak. This is just one example, I don't know whether it would be different or similar in general. Nevertheless, it is still a reason to think that maybe it is not a good idea.

>So from my layman understanding, the immunity should be more resistant to a mutation of the spike protein.

There have been several studies that suggest vaccination provides stronger immunity to mutations. Here's one titled Vaccine-induced immunity provides more robust heterotypic immunity than natural infection to emerging SARS-CoV-2 variants of concern:

https://www.researchsquare.com/article/rs-226857/v1

Did any of these studies compare people who were vaccinated with people who had COVID19 at the same time relative to sampling? In this paper the two groups are separated in time, making it very hard to interpret the results. The effect could simply be due to difference in antibody titer at different times from infection.

Your evidence is contradicting your opinion!

Yes, that's what "that being said" means. It introduces something that contradicts that which was previously stated.

I'll admit to not understanding why, but "consensus" seems to be that the vaccine confers greater resistance to variants than does natural immunity- perhaps the natural immunity is over-fit to the one virus, whereas the spike is a necessary component to the whole family?

That said, I've also seen oft repeated that what you get is immunity*, aka resistance to the worst symptoms. Mild infections are still to be expected as possible, and Covid 19 will join the ranks of common-cold causing organisms.

My impression was rather it's consensus that the vaccine provides more predictable immunity, which is the most important thing if you want to set policy. So recommendation in most countries I checked is to get the vaccine, even if you had Covid, cause it's the same dose for each patient and we have much better data on efficacy, whereas immunity from infection is much less predictable and traceable.

If she was out for a month and then again for a week, it sounds like a compromised immune system more than anything else, assuming she isn't elderly.

> Confirmed by PCR

What was the cycle threshold? The problem with this whole manufactured pandemic is that all the numbers and tests are bullshit because people are doing bad science. The massive relief bills introduced financial incentives to do bad science. It’s institutional failure at a massive scale.

Positive tests, hospitalisations and deaths are highly correlated. How could that be if the test are bullshit?

What do you mean by “highly” correlated? Source?

Do a google for “COVID PCR ct cycle threshold” and you’ll come across loads and loads of good articles about how the meaning of a positive PCR test is relative to the cycle threshold.

Basically any country in this list: https://www.worldometers.info/coronavirus/

Or one from only Belgium with hospital admissions and posivety rate to correct for the amount of tests taken: https://epistat.wiv-isp.be/covid/covid-19.html

Hospital admissions and deaths follow positive tests like clockwork.

Sure it's possible to fuck up pcr tests if you're doing them badly, but there are no indications that that is happening at a significant scale.

How do you account for huge jumps in excess mortality across multiple countries? What about the antibody tests? Lateral flow tests? Genetic sequencing? 10% - 20% of positive tests in the UK are sequenced - wouldn’t you raise concerns if all the samples you were sequencing were false positives?

Is it all a conspiracy? Without a single whistleblower? To what end?

Yes, it's all a conspiracy. The whistleblowers will come. Hopefully before the aliens reveal themselves due to the UFO disclosures. /s

What a strawman. Nobody is saying that COVID doesn't exist. Nobody is saying that people haven't died from COVID. Nobody is saying that excess mortality cannot be attributed to COVID. Are you making a good faith effort to understand what I'm saying? Have you done the google search I referenced above?

The presence of the virus (colonization) is much different than being infected by the virus. There's such a thing as viral load.

The phrase “manufactured pandemic” fits with all the conspiracy talk I have seen. Help me understand how I can interpret this differently.

I should also add this, from here [1]:

> Clinical specimens for sequencing should have an RT-PCR Ct value ≤28.

The sequencing you're referring to does not happen on the samples that I'm suggesting are false positives -- at least, it doesn't happen in the US. The CDC does not want those samples.

[1]: https://www.cdc.gov/vaccines/covid-19/downloads/Information-...

>It is still possible it was a defective test the second time, and something else than Covid.

Now that the whole world has gone banana over a virus outbreak, it's really important to look at and understand how these tests work. Just because she tested positive does not mean she was really sick with covid, nor does it mean that the test was defective if we assume she didn't have it. It's not an on/off thing, it depends on how exactly they test and how the results are interpreted.

You can see from the figures released by various governments on testing rates vs cases that the false positive rate on tests is very low (< 1%, probably less than 0.2%). There have also been a few documented cases of catching it twice, so this is very rare but possible. So either cause is possible in this case, and the tests are really quite reliable as tests go.

>You can see from the figures released by various governments on testing rates vs cases that the false positive rate on tests is very low

This sounds like circular logic, or I'm misunderstanding what you mean. How were these "cases" confirmed? By testing? It would help if you cited the figures where the reliability of the tests can easily be seen.

Btw, my point was exactly that the issue isn't with the test itself but the interpretation thereof. Most people do not understand how they work and so they don't understand that even healthy people can test positive depending on the criteria we use to define "positive". But positive doesn't mean sick and it doesn't necessarily mean infectious either. By itself it doesn't mean anything.

To take one example the uk gov reports testing around 1 million a day for an extended period with only 2-3k positive and there is no strong correlation between testing rates and cases. That indicates a very low false positive rate - a significant false positive rate would give a higher baseline and a stronger correlation.

Of course there is strong correlation between testing rates and cases. If you don't test clinically you can't know you have them. Tanzania for the longest time didn't do any testing at all and as a result officially had 0 cases.

You've not supplied any data supporting your false positive hypothesis.

https://coronavirus.data.gov.uk/

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