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Comment by jaynetics | Hacker News Reader

Even more consequential than the fact from the headline is the preliminary result that a spacing of 12 weeks does not seem to reduce efficiency.

I wish my country and others would take note and give priority to handing out as many first doses as possible, but my hope for such quick adoption of scientific findings has been rather diminished by the whole event.

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Its typical of vaccines for longer spacing to improve the efficacy. This is why for most vaccines you get your booster spread out by a lot more (like 1 year). So generally speaking, the expectation was that it would improve efficacy and it did.

Another study supporting "First doses first".

The first dose prevents hospitalization. Right now, for every second dose we give, that's a decision to deny someone a life-saving dose in favor of someone already protected. What a strange prioritization to make.

The bright side is that, if the rate of vaccination continues to increase, those denied the first dose now should still get the first dose soon after. Let's hope we don't hit some manufacturing bottleneck.

The problem is the lack of certainty. Most suspect that you won't lose protection by waiting longer than the suggested timeline, but what you really don't want to do is sleep-walk into throwing away the currently administered doses.

Frustratingly, I'm guessing the timelines for a study on the durability of single dose moderna/pfizer would take about as long as it will take to ramp up production.

That's not how the immune system works though; you aren't "throwing away" the currently administered doses if you wait until after immunity declines to give the booster dose.

Unless this virus is magically different from every other virus we create a vaccine for, waiting longer for the booster will create a better / longer-lasting immunity afterwards.

No, some vaccines wear off relatively quickly: https://www.sciencemag.org/news/2019/04/how-long-do-vaccines...

So it's very important to follow the protocol here as much as possible until we know otherwise.

Immunity wearing off doesn't mean a booster won't work. The memory cells will still hang around at some level, so when you apply the booster, you'll get longer lasting immunity at that point. In fact if anything, providing the booster within 3-4 weeks is likely to hamper the durability of the booster-induced immunity.

I’m confused by what you are trying to prove. The issue isn’t whether people believe what you are arguing. As far as I can tell, most experts seem to believe something along these lines is most likely.

The question is whether or not they have verified it in this context.

The point is that the booster is moot if you're walking around unprotected until you get it because the first dose has worn off. No one here is arguing that a second shot wouldn't bring your immunity back up. The problem isn't the efficacy of the second shot. It's the delay during which you are much less.protected.

As for 3-4 weeks being too short, I'm not aware of any specific research there. But I'll assume you're right, and also tell you it's irrelevant: If a booster in 3-4 weeks improves efficacy, but doing it later would work even better, that does not mean we should wait longer: We still need the boost now. All your point means is that we should also do a second booster at some optimal time further down the road.

But it's not a choice between vaccinating one person with one dose and vaccinating one person with two doses. It's a choice between vaccinating one person with two doses and vaccinating two people with one dose apiece.

If you try to give the person a second dose, that means you're causing another person to be walking around completely unprotected.

I completely agree that, once we know if or when immunity starts to drop, we should absolutely maximize # of people getting shots instead of maximizing the immunity level of people getting the shots which is a relatively incremental increase anyway. I'm not sure we have that data though, and until we do have that data then we need to proceed with a known protocol that maximizes immunity.

Because if the vaccine wears off quickly. Then, the issue of the second person it moot. Vaccinating them becomes a net 0: Person A that got the first vaccine is losing their immunity while second person is gaining immunity.

However, assuming the pharmaceutical companies can & are massively ramping up production, and given that the logistics network for distributing & administering the shot is improving, We will hopefully get to the point when all of the above is completely irrelevant because there will be ample supply and ample bandwidth to administer the dosesto everyone.

I think in the short term we also get a little bit of a boost from the folks who have already been infected. AFAIK, their resistance may not last long-- as little as 6 months perhaps. But in terms of getting spread rates under control, and assuming twice as many people have been infected as the official record shows (which might be conservative, it's just educated guess) Then that means in addition to those getting vaccinated, We have about 55million formerly infected people that should have some level of resistance.

Anyway, thanks for an interesting conversation.

A strong argument against this is the potential to apply selective pressure for virus variants that escape antibody binding. After the first vaccine dose, antibody titer in the blood is lower than it would be after 2 doses. Some of the new variants are better at escaping antibody binding, but with high enough antibody titer in the blood, they can still be cleared. Using only 1 dose risks not having enough antibody to eliminate an antibody-escape mutant.

It will be a strong argument when there's more evidence. Do we have any example of significantly stronger viral adaptation in the presence of a vaccine that successfully stimulates the immune system? Even a full course of the less-effective vaccines would still be risking this. The AstraZeneca and Sinovac vaccines only have an efficacy of around 70% after all.

You're correct that there's never been an experiment on the scale of the current pandemic, but there is a long history of demonstrating that viruses rapidly evolve to escape antibodies, and that this effect is enhanced under direct selective pressure.

Late 2020 there was a paper published where they demonstrate this effect for SARS-Cov-2 in human cells, then they look for those variants in humans and find that they were already infecting humans, demonstrating this selection activity happens in the wild [1]. I totally hear you about the 1 does vaccine argument. I think the kicker is two-fold. First, we do not know whether vaccinated individuals can still be infected with and spread COVID. Second is the rollout is currently very slow. You could imagine a scenario where enough folks are vaccinated to add pressure, but not reduce widespread transmission. If the data comes out that you can't transmit covid after the first dose (and I believe that Moderna has this data, but not ready to publish), I think the answer is clear to delay the second dose. But I think it is the absence of the transmission data, not whether evolution will happen to the virus, is part of the reasoning for the current strategy of completing the vaccination course in the ~3 week timeline.

[1] https://elifesciences.org/articles/61312

> The first dose prevents hospitalization. Right now, for every second dose we give, that's a decision to deny someone a life-saving dose in favor of someone already protected. What a strange prioritization to make.

Does 1 dose prevent the spread of COVID19?

If it requires 2-doses to get a true "efficacy" (lower spread), then it might be more worthwhile to push 2-doses, rather than 1-dose (where everyone gets "less sick", but the virus continues to spread exponentially).

Real problem: 1-dose wasn't really tested on a large "phase 3" style 10,000+ person test. Its impossible to answer this question (yet). It will take further testing to know.

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I think there's something to be respected about sticking with what was tested, even if the scientific theory argues for a different approach.

Just because the theory says so, doesn't mean that the theory is true (at least, not until the theory is well tested).

Doing something different and hoping for the best just because its kinda correct theoretically is... overly optimistic. I wouldn't necessarily be against it, but it makes sense to stick with what was formally tested.

As for whether 1 dose prevents spreading: for many countries, in particular UK, the current bottleneck is hospital occupancy, and that is overwhelmingly people over 70 - something like 60% IIRC.

If 1 dose, followed by a 2nd some time, can cut that number down a lot (some people won't get Covid, and few will get a bad one), hospitals can be freed and start returning to their usual work - cancer treatments etc. That's a big win. I think it's still the case that more people die of cancer than of Covid.

But that said, I also worry whether the vaccines will work with the longer spacing - I hope results like this show us they would.

> As for whether 1 dose prevents spreading: for many countries, in particular UK, the current bottleneck is hospital occupancy, and that is overwhelmingly people over 70 - something like 60% IIRC.

Preventing the spread of COVID19 has an exponential effect on all stats.

If 1-dose only reduces the symptoms (but continues the exponential spread), then 20% vaccination rate means that you have 20% fewer hospitalizations after a month.

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In contrast, if 2-dose prevents the spread, then 10% vaccination means 10% fewer spread *PER GENERATION* of COVID19.

That's 90% of the hospitalizations in one generation (~1-week period). After 2-weeks, you have ~81% hospitalizations. After 3-weeks, down to 73%. After 4 weeks, only 65%.

Controlling the spread is the #1 health priority that has exponential effects. I'd take 1/2 the vaccination rate if we have a better chance at tackling the exponential-spread issue.

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