Vox did a piece on this[1]. Basically, if you're young, the risk of death is about equal to a kidney donation, which is a procedure we allow.

Participating in a trial like this could save many more lives than donating a kidney. And, if you live in e.g. NYC, there's a decent chance you're going to get COVID anyway, trial or no.

Separately from that... y'know, there are currently lots of health care workers taking care of COVID patients—frequently without proper PPE—and getting sick from it. If we as a society have agreed this is worth the risk, why not a challenge trial to develop a vaccine?

I'm honestly a little surprised there's even a debate about this. The choice seems pretty clear to me.

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[1] https://www.vox.com/future-perfect/2020/4/9/21209593/coronav...

> Vox did a piece on this. Basically, if you're young, the risk of death is about equal to a kidney donation, which is a procedure we allow.

I haven't seen the Vox article, but if that's what they said, it's total bullshit and irresponsible journalism, and I'd request that you do your part by not repeating that.

The first kidney donation was in 1954. We have 66 years worth of data--plenty of time for many kidney donors to live out their lives and have the problems caused by kidney donation, so we have a pretty good idea of what the long-term effects of kidney donation are.

We don't know what the long-term effects of coronavirus are because nobody has had it and then lived long term. The first case we know of was in November 2019--five months ago. Vox can't say that "if you're young, the risk of death is about equal to a kidney donation", because we do not know what the risks are. If scientists infected a bunch of 20 year olds with Covid in 2020 and by 2050, 40% of them die of lung cancer before the age of 50, is that something you'd be cool with? Because that might be reality--it's impossible to know.

To be clear, I'm not saying Covid-19 causes lung cancer. I'm saying we cannot possibly know ANYTHING about the long term effect of Covid-19. We shouldn't assume that it causes lung cancer, but we also shouldn't assume it's no more dangerous than a kidney donation. We shouldn't assume, period. So statements like, "if you're young, the risk of death is about equal to a kidney donation" are lies. And I would implore you to not spread that misinformation because it potentially has deadly consequences.

I take your point, but calling the comparison "lies" based on the possibility of long-term implications we know nothing about seems like a big stretch to me. We don't know the long-term effects of 5G either.

> If scientists infected a bunch of 20 year olds with Covid in 2020 and by 2050, 40% of them die of lung cancer before the age of 50, is that something you'd be cool with?

If it saves the lives of a bunch of nurses in the process? I don't know—I think I'm cool with a possibility of it, yes. Especially when those same people could also catch the virus naturally.

Also, I edited my original post to add a link to the Vox article. It's quite a bit longer / more expansive, and worth a read.

> I take your point, but calling the comparison "lies" based on the possibility of long-term implications we know nothing about seems like a big stretch to me.

I had gone through my post and removed all the places where I called it "lies" because I intended to say that this arose from ignorance rather than malice, albeit irresponsible ignorance from journalists whose responsibility it is to share information. I must have missed that one, my apologies for the accusation.

> We don't know the long-term effects of 5G either.

Geez, did you get this from Vox too? The bands used for 5G didn't just spring into existence: they've been around and used[1], albeit deployed on much smaller scales than 5G will be. We have long-term data on the effects of adjacent bands, and a few different ways of modeling how electromagnetic radiation affects the body. The data we have is certainly from much smaller deployments than 5G will be, so it's true we don't know all the long-term effects of 5G, but we at least have enough data to put some bounds on how horribly 5G could go wrong. For starters, we know that it doesn't have a 40% chance of killing everyone exposed to it in the next 30 years with lung cancer, because an effect that large would show up even in the more limited data we already have. And if it does turn out to cause some problem with even a minute fraction of that severity, we can turn off the 5G and stop the cause of the problem.

We don't even have a clear lock on the short term mortality rate of coronavirus and we can't stop the spread with the flip of a switch. Where, exactly, is your confidence coming from here?

> If it saves the lives of a bunch of nurses in the process? I don't know—I think I'm cool with a possibility of it, yes.

> Especially when those same people could also catch the virus naturally.

The worst-hit place in the US is NYC, with 141,754 confirmed cases currently. Even if we assume unconfirmed cases 5 times that, we're still talking single-digit percentages of the population infected. And cases are going down. So yes, people could catch the virus naturally, or, as is much more likely, they could not catch the virus, if we continue taking the recommended measures that are working.

Certainly populations like health workers working directly with the infected are at much higher risk than the general population, but there's still a very significant chance they don't get infected. And even if the chance of them not getting infected were negligible, the solution would be to give them proper PPE, training, and other protections, not to say, "Hey you're probably going to get it any way, so let's just deliberately infect you to test vaccines that may not work."

[1] https://ethw.org/Millimeter_Waves

5G was, in hindsight, not the best example to throw in there. It came to mind because because I was having an orthogonal discussion on Hacker News a few months ago about 5G safety and radiation modelling. One commenter there said something like (heavily paraphrasing):

> You cannot tell me what effect 5G will have on the body in 50 years, because no one has tested it. Who knows what might happen?

And y'know what? Technically speaking, he or she is absolutely right: despite our best modelling, we can't really know what deploying 5G at this scale will do in 50 years, and we won't know until 50 years from now! All we can say is, this are what we've extrapolated from the models we have.

Is there specific evidence to suggest that COVID-19 will cause extremely high rates of lung cancer in 30 years? If not, we're just in the messy realm of "anything could happen," which is both true and not particularly useful.

I think you have to compare the (very real!) risks of a challenge trial with the risks of not doing a challenge trial. Maybe it does only speed up development by two months, and the number of health care workers and other members of the public who will die in that time is low enough to not be worth risking the lives of study participants. But that is a question we need to actually look at and consider!

> Is there specific evidence to suggest that COVID-19 will cause extremely high rates of lung cancer in 30 years?

Perhaps not "extremely high", but there are lots of other cases where viruses attacking human tissue much less severely are known to cause cancer. HSV causing cervical cancer is probably the most obvious example, but there are many others.

This is well outside my area of expertise, but what I've read leads me to believe that the way viruses reproduce is particularly prone to resulting in mutations in the human cells it attacks.

It would surprise me a bit if Covid19 didn't increase the chance of cancer at some level, although it might be a very small effect.

> I think you have to compare the (very real!) risks of a challenge trial with the risks of not doing a challenge trial. Maybe it does only speed up development by two months, and the number of health care workers and other members of the public who will die in that time is low enough to not be worth risking the lives of study participants. But that is a question we need to actually look at and consider!

That's true. No questions should ever be off the table.

But it didn't sound much like asking a question when you said upthread, "I'm honestly a little surprised there's even a debate about this. The choice seems pretty clear to me." That's why I responded the way I did.

I'm surprised there's even a debate about whether it's ethical in theory. As in, I see doctors overly attached to the "do no harm" mantra to the point where the alternative isn't being looked at.

I didn't mean to imply a cost-benefit analysis shouldn't be done.

> Even if we assume unconfirmed cases 5 times that, we're still talking single-digit percentages of the population infected.

Wasn't you point just that we shouldn't assume? I know that there are models looking at a possibility for only 1% of cases being confirmed. That's been in Sweden and not NYC, but just throwing a 5 out there doesn't make a lot of sense.

Okay, what number do you think is the worst possible case? Is there a reason to believe that there's a nearly 100% chance that people will get infected?

It's true that 5 was just a number out of a hat, but I think you'd have a hard time picking a big enough number that it invalidates my point. Even if you pick 100 as you're claiming, you're still looking at a double-digit percentage chance of not getting infected, which you're taking away from people by deliberately infecting them.

Incidentally, saying "If we assume" is different from saying "We can assume". I'm not assuming that number, I'm merely highlighting it as one of the many possibilities.

> Okay, what number do you think is the worst possible case? Is there a reason to believe that there's a nearly 100% chance that people will get infected?

Based on the number of people testing positive for the antibodies ([0] something like ~21% of random tests in New York), and given that the average estimated R0 is really high, I think ~100% of people being infected by this time next year is a pretty reasonable assumption. This also indicates that the death rate we previously estimated is much lower in reality. Infecting a few more young, healthy people and supervising their health seems a pretty good deal for the world at large.

[0] https://www.livescience.com/covid-antibody-test-results-new-...

Well, I'd love to see that actual study and peer reviews of it. A previous study saying something similar turned out to be done by a hedge fund manager who used it to argue for reopening businesses, and while peer review is still pending, preliminary reviews by other scientist have called it bullshit (only in nicer terms). So you'll excuse my skepticisim here.

Well that settles it, we better wait 30 years before we start testing a vaccine because otherwise it may be dangerous. And then wait 30 years again before releasing it.

Or, you know, test the vaccine the same way we test the flu vaccine every year, which takes a few months, and doesn't require abandoning basic medical ethics.

There are actually steps we can take to speed this up without abandoning medical ethics. It certainly makes sense to have the first human trials be on medical workers, because it has the highest chance of producing benefit for them, and the results will be clearer in populations with a higher infection rate.

But we're not talking about those because you guys would rather talk about injecting people with coronavirus based on a poor understanding of both risk and medical ethics.

It would be curious to see the Vox piece and I do hope someone drops a link in here. It would be most interesting to know if they were comparing it to the initial procedure (surgery + complications) or lifetime experience (Additional risk of death due to the remaining kidney failing).

That said, I feel like your points are a bit overstated. We now have 66 years worth of Kidney transplant data to show it's safe for both parties, but a lot of people needed to participate in what was a new, risk, experimental surgery to get us to this point.

At some point people have to be willing to take a little bit of risk to get data that could save untold lives and relieve unquantifiable suffering.

Additionally, if COVID-19 does indeed have some horrible long term effect, the cost us having less data or less valuable data now will have a much larger consequence than could ever be suffered by these volunteers.

> We now have 66 years worth of Kidney transplant data to show it's safe for both parties, but a lot of people needed to participate in what was a new, risk, experimental surgery to get us to this point.

Uh, technically that's true, but the risks are not the same. The first successful kidney removal (nephrectomy) was in 1869. It wasn't for a donation, it was for a woman suffering an uncloseable fistula which, without the operation, would have killed her. So what exactly was she risking? By the time someone was allowed to volunteer to donate a kidney in 1954, nephrectomy had the better part of a century's worth of data and refinement of technique.

Compare this to the risk you're proposing: With current measures which seem to be working, there's a good chance that most people don't get infected. So you're proposing that healthy individuals who would likely not contract the virus, be intentionally infected with a disease which he only have an approximate mortality rate for, and that we have no idea of the long-term effects of.

Surely you can see how the first risk fits withing "First, do no harm", while the risk you're proposing simply doesn't.

Good points. Only obvious solution is to give to the health care workers and you have your control group.

I'm sure that the Vox article said "from what we know so far", but even if it didn't say that, isn't it obvious? We can only talk from current knowledge.

> but even if it didn't say that, isn't it obvious?

If it's obvious then it should be equally obvious that a comparison with something that has long term knowledge is nonsensical.

1. Part of current knowledge are the facts that a) we don't know the long-term effects, and b) those long-term effects might be horrific.

2. It's apparently not obvious, because people on this thread seem to not have thought of it, and when I pointed it out, they've argued vehemently against it.

I'd happily volunteer to participate.

By the same argument, we also don't know the long term effects of drugs and vaccines that haven't been in use for a very long time

>If scientists infected a bunch of 20 year olds with Covid in 2020 and by 2050, 40% of them die of lung cancer before the age of 50, is that something you'd be cool with?

If the vaccine works then we'll all be dying of lung cancer in 30 years.

You, and the vox article, seem to assume that the risks are all associated with COVID19 in the trial as similar to those normally associated with COVID19 in the human population..

One of the issues with vaccine development is that vaccines can result in worse infections [1].

If the issue was just “this might not work, but it won’t cause any harm”. You would obviously give this to healthcare workers immediately. But that does not appear to be the case.

[1] https://www.pnas.org/content/117/15/8218

Well, I assume the challenge trial would be done to test efficacy after you've tested safety. Is this aspect substantially different than with any other vaccine trial?

The difference is right now healthcare facilities and providers are overloaded, so if there are adverse effects of a trial that require treatment, people could end up dead. Normally you would have hospitals ready to handle such cases, but there's zero guarantee of that today.

I'm sure we can all agree that trials with the potential to require medical intervention shouldn't take place in areas with overloaded hospitals. But most areas of most countries don't have overloaded hospitals right now.

All phases will be testing for safety to varying degrees.

So... a challenge trial at phase III will still have risks. Right now, I don’t think we have any vaccines ready to enter phase III?

COVID19 does seem to be actively spreading in the population currently. So I don’t think there would be an issue finding participants for a phase III trial.

At the point that we’re ready for phase III trials. If there is no population where COVID19 is actively spreading, perhaps challenge trials could be considered?

How do you test vaccine safety in a month? Shouldn't we be concerned with long term effects too?

Yea. I'm not an antivax person. I got my meningitis shot in Uni, tool all the ones I needed when going overseas like Typhoid ... but I know about Vioxx and I am weary of stuff rushed to market. I'm not in a high risk group, so I would want to wait a year or two personally.

I realize for many that won't be an option. But with the way things are going in America right now, I'm afraid it might not be an option for anyone; it may be a requirement just to get a job or go to school. That frightens me.

Long term, vioxx has actually been somewhat vindicated as all other nsaids have been shown to cause equal rates of heart attacks. That is, your ibuprofen is just as dangerous, but no one is demanding it be recalled.

Yes. Last time we rushed a vaccine during a pandemic we got pandemrix.

That was approved in Europe but not the US.

1 in 55000 people who took pandemrix got narcolepsy.

The risk is small, but the outcome is a severe debilitating illness that requires constant care for the rest of their life.

We may decide that risk is acceptable, but we need to know about it.

Thanks for the reference. Reading the wikipedia article on the topic, I get the impression that side effects that develop slowly (e.g. more than 3 months post vaccination as in this case) will either not be detected at all or it will be almost impossible to attribute them to the particular vaccine (esp. if you get a different one each year). What is really bothering me is the overall "debuggability" of the vaccines/medication. I mean, people developing them simply have no clue about the different mechanisms by which they can cause harm to the body. Let alone any adverse effect when combined with e.g. over the counter drugs or supplements.

I'm not disagreeing with your logic. The risk would be reasonably low if the subjects are young and healthy.

However, you can still get similar information by just dropping the control arm in this trial. Give a bunch of people the vaccine and exposed them to the virus. Sure it's not as good as having an untreated control arm, but you're also reducing the risk of someone in the control group dying.

The data is of very little use without a control. You could compare it to overall Coronavirus death rates, but those numbers are biased in all sorts of ways (for instance, fully asymptomatic cases).

I would disagree with "very little use". Uncontrolled trials are done all the time. You basically collect "nature history" data and compare it to that.

In addition, the mechanism of vaccines is very well know. You can vaccinate and measure antibody formation.

You could still develop a vaccine without a control and have confidence that it works.

Pretty sure uncontrolled trials are common at the latest stages of drug development. It's called a single-arm trial.

Source: I once participated in a phase III open-label single-arm trial.

They exist, but are usually not sufficient to support a drug or vaccine approval.

The standard is two well controlled studies, but additional open label trials may be used to address specific health authority concerns.

If you are interested, you can look up the other trials the drug may have gone through.

But if you donate a kidney, then you’ll now have a pre-existing condition. Which means you’ll be denied access to health insurance.

In which country?

Take a guess.

Not sure. Definitely not the USA, as pre-existing conditions no longer disqualify you for insurance.

As with bizarrely restrictive FDA regulations on, e.g., face masks, the famous conservatism of IRB committees is another thing that the COVID19 story should motivate us to re-examine.

But a large majority will be exposed to the virus eventually anyway, if things keep going as they are. So what's the added risk if you're exposed earlier rather than later?

That you are exposed while there is no known working treatment yet. Many attempts are in the works out even trials, but nothing proven. In the near foreseeable future, there might be one.

One reason to have the lockdowns.

No, the reason for the lockdowns was to increase the chance that people will find care in the hospitals.

I shudder at the thought of a government locking people up because a treatment might, at some point in the future, be found.

It is of course besides the point but I find it extremely optimistic to expect that a treatment can be found that will significantly reduce deaths when deaths mostly occur in patients of very advanced age or with significant underlying conditions.

Is there anything promising at the treatment front right now? My impression is that there was an initial group of candidates for repurposing that have on closer investigation all turned out to be not quite as helpful as hoped.

Are you sure? Challenge studies have been conducted in recent years for Norovirus[1] and Whooping Cough/Pertussis[2]. Admittedly, less is known about Coronavirus, but both those two can be dangerous.

1. https://www.ncbi.nlm.nih.gov/pubmed/25210140

2. https://clinicaltrials.gov/ct2/show/NCT03751514

Do you know the death rate of an american submariner in the Pacific?

I don't think they are going to infect people intentionally. They are giving the vaccine and control to healthcare workers who are naturally very likely to be exposed throughout he course of their work. They will then compare the infection rates between the two groups.

I don't think they are exposing them in any way different to how they would be exposed without taking the vaccine.

It's just vaccinate then let them do normal UK life.

It would have to be done outside the US.