[hannob]

I found the intro very confusing, tbh.

Particularly the "no increased risk of all-cause mortality". I mean, if we assume the vaccines worked, we'd certainly expect a decreased risk of all-case mortality (because "all-case mortality" certainly includes "covid mortality"). Reading "no increase" seems to imply "it doesn't change anything". Yeah, technically, the sentence does not say that ("no increase" can mean "no decrease" or "no change").

You have to read further below to get what should be the real message on all-cause-mortality: "Vaccinated individuals had [...] a 25% lower risk of all-cause mortality". I think that should've been in the first 1-2 sentences.

[eddieroger]

Frame it as the safety of the vaccine, not the efficacy of it. If it was about efficacy, it would lead with the 25% lower risk because of COVID safety. But, these days, there are people who think vaccines are dangerous just because, so saying that taking the vaccine or not has equal mortality puts that to rest (or at least does for those who find science real).

[zosima]

The reduction in all-cause mortality was independent of covid deaths.

Which seems to suggest that there was big differences between the groups other than the vaccination.

This of course does not change that the vaccine seems mostly safe, but it definitely calls in to question whether the protection against covid death was vaccine-mediated or due to some other difference between the groups.

Therefore this paper is moderately strong evidence for the vaccine being safe, but quite weak evidence for the vaccine being efficacious.

[pygy_]

The vaccinnated group was 1 year older on average, and had mode cardiovascular risk factors.

Covid has long term health consequences, and these are proportional to the severity of the acute infection.

People who died of a stroke of a heart infarction 6 months down the line were not counted as "covid death", even though covid is known to increase their incidence in the next year.

[pygy_]

Another factor that may play a role: the people who chose not to take the vaccine may be prone to taking bad decisions more broadly, leading to a higher mortality rate.

[oldgradstudent]

If true, that means the groups are different in many other aspects other than the vaccine.

The study does not control for the differences. No causality can be inferred.

[disgruntledphd2]

I mean, it's plausibly something around trust in medical authorities which correlates with both vaccine and other treatment refusal.

[lesuorac]

Covid hospitalizations where half in the vaccinated group (as % of pop) than unvaccinated. That's extremely desirable when you're in a situation where you have do dedicate whole wings (and then some) of hospitals to a singular disease.

Sure, it's not a silver bullet but it's at least stainless steel.

[zosima]

I am speaking about what the paper shows.

There are other sources of evidence for efficacy. This paper is not a very strong source of evidence for efficacy due to some obvious uncontrolled difference between groups.

[gopher_space]

I wouldn't bother critiquing methodology without current, masters-level experience in the domain. I make incorrect assumptions when I'm even narrowly outside my own lane, and end up asking questions that clearly demonstrate e.g. my inability to parse fig. 4a.

[zosima]

I wouldn't bother commenting if I were hallucinating figures. There is no figure 4a.

If you look at figure 4 in the supplemental material you also see, per your expertise, that covid vaccine protects against traumatic injury. However even adjusting for the protective effect against traumatic injury there is still quite a large protective effect against all-cause mortality. So the beneficial effect of the vaccine is not solely caused by its protective effect against traumatic injury.

Or it could be, bold proposition I know, that there is a difference between the groups that both protects against traumatic injury and protects against all-cause mortality, independently of the vaccine.

[_DeadFred_]

OP's point was more 'How would you measure unvaccinated people that lived because vaccinated people weren't filling the ER, so there were beds/staff to spare'?

That unvaxed outcome would need to go in the 'vaxed lives saved' column somehow, or else it looks like 'outcomes were the same either way' because the lives saved from vaccination spill over into the non-vaxed group because the vaccine prevented the healthcare system from melting down.

[stocksinsmocks]

I don’t think it’s possible to know anything conclusive about the safety for a few decades and a generation or two of affected kids can be observed. Given that finding harm would embarrass important aristocrats, I don’t think that evidence would ever be found in the foreseeable future. That mRNA and lipid nano particles were never found to be safe until the exact moment of crisis is awfully convenient for its investors.

I say decades because of the study below. Certainly, the authors could have published it for engagement bait or malice or some reason.

https://www.gavinpublishers.com/article/view/detection-of-pf...

[vineyardmike]

Where do you get decades? That study says 200 days.

[xracy]

I interpret this as the comment saying "we won't know how this affected things until decades from now." Which can likely be attributed to existing vaccine skepticism and is unlikely to result in them changing their opinion in the next ever.

What I think a lot of people who are anti-vax miss is the risk of the vaccine compared to the risk of COVID. They feel like they're being asked something risky in a vacuum, when in fact, they're being asked for something with (as best as we can tell) limited risk against a backdrop of a dangerous virus that killed millions and caused a global pandemic.

Even if they could demonstrably prove the vaccine created a higher risk of outcomes for people who took it, the risk compared to getting COVID is de minimus, and the likelihood of getting COVID is high. I would be surprised if there was a significant population of people who had avoided it at this point.

[ifyoubuildit]

> What I think a lot of people who are anti-vax miss is the risk of the vaccine compared to the risk of COVID

Why do people still frame this as either/or? How many people out there didn't get covid after they got some number of shots?

The only real scenario is covid with n shots, where n >= 0. In other words, when you got covid, how many shots had you gotten.

(Not anti vax myself, though generally avoid whatever drugs I reasonably can)

[stocksinsmocks]

You really aren’t going to know how this MRNA in egg and sperm cells are going to affect offspring until you have offspring to observe. Effects like wolbachia could take multiple generations to observe.

[velcrovan]

mRNA can't cause wolbachia. Wolbachia is a bacterium that actually lives inside cells and gets transmitted through eggs to offspring. it's a persistent organism that reproduces. There's not a way for mRNA to grow bacteria.

mRNA is just a molecule that breaks down, and the mRNA in these vaccines is extremely fragile and temporary. Once injected it enters whatever cells are nearby (muscle cells)and ribosomes read it to produce the inert spike protein. The mRNA itself is gone within hours. Your cells have enzymes specifically designed to break down RNA because cells naturally produce and dispose of mRNA constantly as part of normal function.

The mRNA in vaccines never enters the cell nucleus where DNA is stored, so it can't integrate into your genome or affect reproductive cells in that way. And it doesn't replicate itself either.

And millions of babies have been born to vaccinated parents by now. If the effects you are talking about were even possible they would definitely have shown up by now.

[rainsford]

Obviously there are confounding variables besides vaccination status, but I find it pretty compelling that the decrease in COVID mortality among the vaccinated group was significantly larger than the decrease in all-cause mortality of that group. This suggests whatever the difference was between the two groups, besides vaccination, either had a much larger impact on COVID than other causes of death or that the vaccine had some positive impact.

One example of the former explanation I could imagine is that people who got vaccinated against COVID were probably also more likely to take other preventative measures, like wearing a mask or avoiding larger crowds of people. Those precautions would be more likely to be effective against a contagious disease like COVID but less likely to protect them against some other causes of death like heart disease.

I'm not sure how likely I find that as an explanation compared to the alternative that the vaccines provide at least some level of protection. My observation was that widespread measures specifically meant to defend against COVID, like masking and social distancing, largely went away well before the end of the time period covered by this study, at least in the US.

Amusingly, I suspect the anti-vax contingent would likely be bothered by data suggesting anything the COVID vaccinated group was doing differently protected against COVID, since their position seems to largely be that not only is the COVID vaccine useless, but so are any other measures meant to reduce the spread.

[disgruntledphd2]

I think that's mostly fair, but given that we can't randomly assign vaccine administration this sort of study is the best we're gonna get.

Like, the major takeaway is that the vaccine is safe, I think that we've already established that it works to reduce Covid hospitalisations.

[jmull]

> but quite weak evidence for the vaccine being efficacious

That’s directly contradicted by the results of the study. E.g.,

“Vaccinated individuals had a 74% lower risk of death from severe COVID-19 (weighted hazard ratio [wHR], 0.26 [95% CI, 0.22-0.30]) and a 25% lower risk of all-cause mortality (wHR, 0.75 [95% CI, 0.75-0.76])…”

It’s pretty clear a lot of unvaccinated people who died of covid would be alive today had they gotten vaccinated.

(I would point out the current yearly vaccine they are putting out is potentially a different story since covid is changing and so is the vaccine. I’d talk to my dr about whether to get that or not.)

[pama]

The simple explanation is that the causal agent for the excees of the non-covid deaths is the same SARS-CoV2 virus, but death comes later and not at the acute phase of the disease.

[Chris612]

If the vaccine was randomly administered among the study population, I'd buy this as the simple explanation.

Not sure it follows so cleanly with the actual study setup

[pygy_]

There is plenty of evidence beside this study.

[underlipton]

There was a study that showed that cancer patients who receive a MRNA COVID vaccine live longer. This could also be for extrinsic reasons, but IIRC the study considered the reason to be a pronounced immune response that also attacked cancer cells.

So there's a chance that the vaccine provokes a general immune response that's protective against a number of mortality-causing issues.

[DebtDeflation]

A 25% reduction is huge, even if you account for the fact that people who get vaccines tend to be more health conscious to begin with, when you consider that outside of the very sick and very old Covid has a mortality rate under 1%.

[soperj]

1 out of 100 when billions are getting it is gonna be a large number. Mortality rate has gone down substantially since the vaccines.

[ceejayoz]

I like to ask people who talk about a 1% mortality rate if they'd go to a football game in a stadium with 100k seats if 1k of those seats randomly had a small bomb attached.

[altcognito]

> Covid has a mortality rate under 1%.

I hate it when blanket statements like this creep in.

Which Covid? The initial version was definitely more deadly than later versions.

What about future covids? Are you willing to guarantee every version of covid from here on out will be less deadly? It is the general case to be true, but it is not some sort of law.

[a_cardboard_box]

Yes, but they incorrectly called it all-cause mortality under Findings. "Mortality" on it's own would be fine. "Mortality from other causes" would be better.

[disgruntledphd2]

It's a term of art. The audience for this paper would understand, rather like many denizens of HN know what TDD is.

[a_cardboard_box]

The paper doesn't even use it consistently. At first it uses "all-cause mortality" to mean "all causes except COVID", and then in the results section it uses the same phrase to mean "all causes including COVID". The whole purpose of terms of art is to increase the specificity of language, but they're not doing that here. Their usage of the term is confusing.

Edit: I'm wrong. I could have sworn it said that the groups had similar all-cause mortality, but it doesn't.

[Timon3]

Where do you see them using "all-cause mortality" to mean "all causes except COVID" in the beginning? I skimmed over all uses of the term before the "Results" chapter, none of them seem to exclude COVID deaths?

[groestl]

A common pattern you'd find in reliable research papers is that authors tend to understate their findings, which in practice strengthens the impact of their conclusions.

[simonster]

The problem is that 25% lower risk of all-cause mortality is too big to be explained solely by the vaccine. The reduction is similar when excluding deaths due to COVID-19, and is probably driven by people who got the vaccine being different in some ways that the observational study isn’t controlling for.

[hannob]

Yeah, but there's a plausible explanation for this: Likely, people who get vaccinated also are more likely to do other things to improve their health.

[bluGill]

If you don't get the covid vaccine you probably do other risky things. Not get other vaccines, don't see the doctor about various issues...

[TheBigSalad]

Could it mean that lots of Covid deaths are being attributed to other things?

[bloqs]

Not getting the vaccine is statisically correlated with distrust in traditional medicine, and suceptibility to giving undue attention and credit to unfounded and unsound practices.

[btilly]

This is a general problem in many technical fields.

People in a technical field, learn to "chunk" complex phrases. Their natural communication style becomes complex. Which makes them hard to understand to those outside of the field. If they want to be understood, the solution isn't to try to educate the world. It is to educate themselves. To learn how to write simply and directly.

Depending on the readability test used, the section up to "Introduction" - which is supposed to be readable - is somewhere between advanced high school and university. See https://www.online-utility.org/english/readability_test_and_... or other free tools to test it. That's bad. The percentage of Americans who can read this text is below the percentage who could read, say, a plain language version written in Spanish. We should expect people to misunderstand. We should not expect this paper to convince.

[acjohnson55]

Papers like this are designed to fit into the conventions that allow knowledge to compound. Not that the conventions are perfect at doing this.

I would suggest that rather than changing this convention in a big way, there needs to be good pathways for communicating the most important takeaways to the general public. Unfortunately, there's kind of a chasm between academia and popular science.

[btilly]

With all due respect, I disagree.

You are providing the standard excuse. It is our job to advance knowledge. It is someone else's job to communicate it to a broader audience. It's just too bad that nobody is stepping up and doing that other job.

I don't buy it. In my experience, most scientific papers can easily be rewritten into simpler language. The act of trying to do so often catches mistakes - thereby immediately improving how well we are advancing knowledge. The resulting paper is easier to read. This makes it more likely to become better known. Both within its subfield, and in a broader audience.

The habit of doing this makes us better communicators. Which also helps academics in various other parts of their job. Including teaching the next generation.

Furthermore, easier to read papers are easier for science popularizers to understand. Which makes it more likely that the work will be popularized.

Yes, it is tempting for academics to deflect responsibility for their role in being understandable. But it is a mistake for them to do so. Their ability to communicate in an understandable way is their responsibility. The few that take up that responsibility benefit themselves.

[acjohnson55]

I'm not saying it's someone else's job to communicate to a lay audience. Simply that a research paper doesn't have to be a self-contained device for doing that and accurately describing the research to people who already have a lot of background knowledge on the topic and methods.

I guess I will say that I have thought for a long time that serializing research into linear documents seems archaic at this point.

[creer]

It would be nice if academics would move to BOTH publishing the technical write up, AND a more understandable write up of their interpretation of the result (in more detail than the one liner which is in all abstracts.)

The technical writeup is necessary. It's what spells out what they specifically claim to have done, and the specific results. "Specific" being highly technical and fundamental in the scientific community understanding the paper correctly. In particular, the in-depth statistics of many such papers is simply too complex for most of the population to understand, and that's fine. The technical write-up uses terms of art which do not mean what civilians read in them. (And while it's hard to do studies larger than this one, this is all the more essential in smaller studies.)

The interpretation would be useful because it's just plain dangerous to let your PR department write that. Even if they consult you. And it is interesting to focus on what the scientists themselves think they achieved. Both what they deliberately went for, and any ancillary result they think they notice. In this case in particular, they are very focused on this safety aspect, and they seem to not want to give too much attention to the efficacy aspect (which they probably did not plan for and is then suspect.)

[ceejayoz]

Eh, it's an important point. "It made COVID things much better, and it didn't make other unrelated things worse."

[hervature]

Looking at Table 2 and as the name suggests, COVID is included in "all-cause" mortality. Your statement does not follow because it could have made COVID outcomes better yet "all-other" causes worse for a neutral "no increase in all-cause". If you look at Table 2, you can see that the vaccinated group is less mortality in all diseases. That being said, as much as I think this is over-stated, this is very much a correlation thing because we all know that unvaccinated individuals live their lives differently compared to vaccinated individuals. Even accounting for similar statistics, the one group is prone to higher death rates not because they are unvaccinated but because of the reason they are unvaccinated.

[ceejayoz]

Read again.

> After standardizing the characteristics of vaccinated individuals to those of unvaccinated individuals, we observed a 25% lower standardized incidence of all-cause death in vaccinated individuals compared with unvaccinated ones…

> Vaccinated individuals had a lower risk of death compared with unvaccinated individuals regardless of the cause of death.

> All-cause mortality was lower within 6 months following COVID-19 vaccination, regardless of the dose administered, compared with the control periods...

[hervature]

You should read my statement again.

If COVID vaccines reduces COVID deaths by 100% and increase everything else by 0.01%, you will still have a reduction in "all-cause" mortality yet your chances of dying by anything else has increased. I already said Table 2 does not show this is happening and in fact vaccinated individuals have better outcomes across the board. However, people are drawing this conclusion (even though they are correct) incorrectly without looking at the data.

[ceejayoz]

> If COVID vaccines reduces COVID deaths by 100% and increase everything else by 0.01%…

But you already agreed this is not the case, in your comment:

> If you look at Table 2, you can see that the vaccinated group is less mortality in all diseases.

[binary132]

GP is saying that indicates there is some other factor involved in reducing all-cause mortality, since it is probably reasonable to believe the mRNA vaccines were not improving mortality rates of other diseases, and that therefore the sampling of these populations is not random.

See this comment: https://news.ycombinator.com/item?id=46164643

[purpleflame1257]

It's interesting that they leave things at 18-59. Do they later stratify into 18-28, 29-38, 39-48, 48-58?

[ceejayoz]

Looks like they do, yes.

> A stronger association was observed among individuals aged 18 to 29 years, although the underlying reasons remain unclear and warrant further investigation.

[amluto]

> "no increased risk of all-cause mortality"

My take is not quite as charitable as most of the comments, although my objection only barely applies to this particular paper. Biomedical research has long tradition of a very specific type of analysis: hypothesis testing. Roughly speaking, you make a hypothesis and test your data for compatibility with the hypothesis. In this paper, the authors are comparing two hypotheses: (a) there is an increased risk of all-cause mortality or (b) the increase in risk is zero or negative [0]. And the statement you’re quoting from the conclusion section sure sounds like it’s saying that the authors found that the data was consistent with (b) but not with (a).

Researchers love this. There are lots of papers with fancy-named tests with which one can do this analysis. Regulators often demand it.

And it produces papers that are correct in a fairly literal sense but miss the point entirely. For example, “we found no evidence that vaccines increase the risk of autism”. I, too, can look under my bed or study four people and find no evidence of anything at all about vaccines and autism, and I would be more or less justified in making that claim.

And because of this, you need to read papers very carefully to see what you can actually conclude. “No evidence” means a lot more in a large (“high powered”) study than in a small, weak study.

The right way to do this is something like “we looked at such-and-such data and found, with 95% confidence, that the increase in risk of X is <= 0.2%” or even that “the change in risk is <= -25%” (check out that minus sign!). If I look under my bed, I will find evidence that the increased absolute of autism caused by vaccines is <= 100%, and I didn’t need to study anything to confirm that :)

Fortunately, this particular paper has the silly throwaway starting you’re complaining about in a few places but is otherwise mostly on the right track. Quoting from the Results section:

> Vaccinated individuals had a 74% lower risk of death from severe COVID-19 (weighted hazard ratio [wHR], 0.26 [95% CI, 0.22-0.30]) and a 25% lower risk of all-cause mortality (wHR, 0.75 [95% CI, 0.75-0.76]), with a similar association observed when excluding severe COVID-19 death. Sensitivity analysis revealed that vaccinated individuals consistently had a lower risk of death, regardless of the cause.

IMO that should have been the headline. The latter sentence there is giving some indication that the result is robust and that the researchers didn’t flub it or get unlucky in quality of their data.

P.S. The fact that the vaccines seemed to reduce the risk is death from causes other than severe covid is interesting. I wonder how much is reducing death from complications of COVID other than “severe covid”, how much is behavioral changes (vaccinated whole socializing more and leaving their houses more), and how much is bizarre off-target effects of the mRNA vaccines. Here’s an example of a surprising off-target benefit that no one understands well:

https://www.science.org/content/blog-post/mrna-vaccines-and-...

[0] I think. I didn’t reread it enough times to rule out the other common test: is the data consistent with the hypothesis that the risk didn’t change at all, which is also sadly common. But I’m moderately sure I’m right in the context of this paper.

[exceptthisthing]

Because this whole paper is bullshit and is a bias confirmation report

It assesses persons "who were alive on November 1, 2021"

That tantamount to saying "for people alive January 1st 1950, the Second World War was not a significant cause of mortality"

Can you see how ridiculous that sounds?

[biophysboy]

No, because the same conditional is applied to both participant groups. Its good to specify a time frame.

[hervature]

While you are being downvoted, this is actually an astute observation. However, your point is working against you in this case. If the vaccine was actually deadly, the unvaccinated individuals who survived the pandemic would be having better health outcomes. This is not what they found. If they included the pandemic in this study, the deaths by COVID would be much worse in the unvaccinated group.

[dwroberts]

> That tantamount to saying "for people alive January 1st 1950, the Second World War was not a significant cause of mortality"

That’s a nonsense comparison because the thing they are studying is the vaccine, not COVID itself. The vaccine was available at minimum, what, end of 2020? Exposure being defined as first dose May-October 2021 does not seem unreasonable at all (and probably not arbitrarily chosen right - it’s probably something to do with the availability of data)

[gus_massa]

It's a good observation, but I expect that even considering only people alive in 1950, survivors of the Hiroshima bombing or concentration camps (or a few other events), still have long term problems that increase mortality.