Good, but the real question is whether the immune system will "remember" the vaccine for long enough. From [1]:
> Although the magnitude of neutralizing antibody (nAb) responses correlated with disease severity, there was a rapid decline in nAb titres in most patients within 3 months after onset of symptoms. [...] However, the consequences on secondary immune responses and their ability to prevent reinfection remain to be determined.
The immune system works that way that even single digit amount of antibodies can start a chain reaction very quickly.
I don't think it's possible to say a yes or no answer if somebody has immunity using a lab test today.
Though, the vaccine is only needed to last long enough to eradicate the virus. If mass application of vaccine can plunge the r-factor well below 1, it should be more than ok if its protection only lasts 3-4 months.
Hypothetically speaking if you were a front-line worker exposed to the public and the vaccine only worked reliably for 90 days wouldn't you get it quarterly? It seems like the prudent approach to get r0 well below until we can drain the reservoir of disease because as others have noted, getting enough vaccines deployed simultaneously globally could be a challenge.
If it's really down to a single company not being able to manufacture enough then it's time to open up the vaccine to licensing and let other companies pile in.
> If it's really down to a single company not being able to manufacture enough then it's time to open up the vaccine to licensing and let other companies pile in.
The world is facing a few problems like this, where the structures of the economy are getting in the way of doing real work. Climate change is another one. If cost wasn't an issue, and everyone was paid by some infinite coffer, we'd have switched to green energy years ago and it wouldn't have been controversial at all. Only now that it's cost effective are we switching en masse to green energy, and we're having to drag economies kicking and screaming away from coal even still.
The community seems to be second to capitalism at every turn, and whilst I know it's not a new thought, it's becoming more and more prevalent that we've made societies devoid of the capacity for community effort.
Edit: Thought I'd clarify, my point is that our governments are meant to supply the community capacity through paying for work with our taxes, but often structures that benefit private businesses win out.
More specifically, you're hopeful that the company manufacturing the vaccine would actually open up to licensing, but they don't have to, and the US has consistently shown it's disdain for compulsory licensing. It would be an exception for them to force the company to license a vaccine, and it's not like pharmaceutical companies have an ethical track record in the US. If it came down to money vs community health, I would absolutely expect money to win out in the US. It already does. Worse yet, the US has bullied other countries into tightening their own compulsory licensing laws, in order to protect US pharmaceutical companies.
A friend in an ED just told me that 90% of her colleagues tested positive for antibodies but many of those worked the entire time and didn’t have symptoms.
There have been a few recent studies of cruise ships and meat packing plants with universal masking. In those cases an extremely high proportion of cases were asymptomatic.
To be clear, higher than in other cruise ships and other meat packing plants.
That’s the possibility, that lower viral load led to milder outcomes.
There was also a swiss military study where one group only got infected after distancing implemented. Positive cases, but no symptoms. Earlier group’s cases had symptoms.
How long does it take to vaccinate the entire world?
If the each contaminated person transmits it to two other people, you'll need to keep half of the people immune to each at any single time. If you are doing this by vaccines, you'll need to give it to half of the people on that immunity window.
At a billion doses per year it’s still 8 years to manufacture the vaccine for everyone. That’s assuming no supply chain issues. Moderna needs 2 doses which means only 500M protected per year which pages it to 16 years. I think the Oxford vaccine needs only 1 doses but because it uses a weakened virus there’s a chance a person develops covid-19.
Then you need to administer something like 300 doses per second globally, if you have 1B doses.
This is also assuming the virus doesn’t mutate during that time (it mutates very slowly but it could still happen).
The vaccine really needs to give multi-year protection otherwise it won’t be viable in the long run.
To be honest, there is probably a power law graph in play here when it comes to how many people are infective and infect others. If we can vaccinate / prevent spread in the demographics that are prone to mixing a lot / threaten spread, we can quickly curb it and then focus on people who are less likely to contract it / spread it around.
It feels like some of the demographics most likely to spread have overlap with groups unlikely to accept vaccinations.
Source: Live in Lansing MI where the nutty politicization of this issue is out of hand and there are redneck “anti-mask” protests seemingly once a month.
This is certainly the case. I don't have a link, but one study suggested 80% of cases were from "super-spreading" events, with one person infecting many others.
It doesn't actually use covid-19 virus so i doubt there's a chance of developing the disease from the vaccine. maybe it will have other side effects but covid-19 won't be one of them.
What would it take to ramp that up? The flu shot only lasts a year (for entirely different reasons, but still!), and in that case, we actually need to adapt the drug itself each season.
Moderna's vaccine does not require two doses, they administered two doses as part of their phase 2 trials to test for adverse reactions. They are only doing a single 100 µg dose for their phase 3 trials, and it's likely that will be the dose in the final vaccine:
Moderna has plans to be able to manufacturer 1 billion doses a year. AstraZeneca has announced plans to manufacturer 2 billion doses a year, with plans to produce 300 million doses by the end of 2020. The Chinese firms Sinopharm and Sinovac are ramping up their production right now, and will produce 200-300 million doses by the end of 2020. With all the other firms developing a vaccine it seems highly likely we could produce enough vaccine to vaccinate the entire population of the Earth in a single year. Now distributing and administering that much vaccine is another story, but manufacturing will not likely be the bottle neck.
I agree with your overall point that to put the fire out, you've got to extinguish all the embers.
But, as an alternative to synchronization, you could also require vaccinations for everyone who travels.
If a country gets it under control within its borders, it could require visitors to show proof they either (1) have tested positive for the disease and then recovered or (2) have been vaccinated recently enough (but not too recently) and also tested negative for the disease.
That way, you'd know they do not have it and have some degree of protection against picking it up while traveling to your country.
The unfortunate side effect if this became standard is that there may be far less motivation for wealthier nations to help poorer nations vaccinate everybody.
I don't entirely disagree that it might remove some motivation. But right now the whole world is in crisis, and I don't think gaining leverage by tying everyone's fates together is the best solution.
Anyway, the travel restrictions I mentioned would hardly be bulletproof. Vaccinations don't confer 100% immunity, and tests aren't 100% accurate. So countries could still reduce their risk by supporting worldwide vaccination.
Also, this might be a moot question if we can't produce enough vaccines to do it all at once.
If the immunity lasts for 4 months, we are talking about yearly vaccinating 200% of the population.
It's not impossible for countries with a small population, but AFAIK the flu is the largest scale vaccination in the world, and we are talking about something 4 times larger (than those countries that vaccinate the most - how are China and India numbers?).
But then, this seems to be the worst case with a reasonable likelihood. Things will probably be better.
I think we will be more limited by supply rather than willingness. Locking down for months has much more economic impact than one shot for each citizen even for poor country.
I don't think so; you couple a short term vaccine with testing and tracing so that you use it to break transmissions locally. If this was (god forbid) something with the transmissability of Measels then that would be useless.
In epidemiology, we determine "heard immunity" by calculating the proportion of the population that is in the Recovered (R) compartment (either through natural or artificial means). If your proportion that is in R is greater than 1-(1/R0) the incidence of the disease will start to decline.
Thankfully the R0 of SARS-COV-2 seem to be around 1.4–2.5 (meaning you need ~30% to ~60% recovered), so a vaccine would be actually very effective. I highly suspect "Travel to Europe" (i.e. international travel) may still be delayed for a long bit until we've gotten around to ~50-60% immunized, but it's tough to say.
Interesting, I wonder if when we're developing the vaccine, ability to easily mass produce the vaccine is a factor... I imagine the biggest issue once we have a vaccine is going to be how to get it out to everyone quickly enough... like I can see critical care workers and then maybe elderly and it being this really long time before it can be available to everyone... or do you start mass production of the vaccine and avoid distribution until you have enough to get everyone vaccinated so that you have the protection period of 3-4 months? Interesting to think it's not just the science of the vaccine but also the application of the vaccine that can be a factor... In the meantime it's promising that we're also learning how to treat the infection better and better...
Recently talking with my dad about all the situation and the vaccines, he brought up a case he studied when doing an MBA in the 90's: a vaccine where they used rats as bio-reactors. In tests and trials the vaccine was great, but it was so hard to produce and care for thousands of rats during the incubation period that in the end it wasn't economically viable.
He vaguely remembers the case as something from the 50's or the 60's and todya we have better technology all around. But yes, I understand that most labs working on vaccines do take into account the potential difficulties in production.
The economics will be different (more interesting/tempting) indeed. The point of the anecdote was that vaccine fabrication has been understood for a long time in the context of the scale it's required (again, the case was from the 50s-60s). I don't think any of the "promising vaccines" that are being tested now would fall in the trap of such a production scaling problem. Labs know this will be demanded in the billions.
That will be a really interesting question for the modellers, because vaccinating those who pose the highest danger of spreading the disease might have a much greater impact. If side effects turn out big you might even end up wanting to vaccinate everybody but the elderly.
Yeah, this is one big thing that's pulling the delivery times closer vs historical timelines.
Governments essentially said "If you can demonstrate reasonable efficacy and safety, go ahead and start mass production. If your Phase III trials fail, we'll make you whole and dump the doses in a landfill."
Otherwise, you had to wait the entire Phase III duration before even starting production, whereas now you'll essentially have viable vaccine on Day 0 when the Phase III trail concludes.
Not to belabor the point, but "r-factor" isn't the correct term here. If we're using a SIR model that assumes patients go from Susceptible (S) to Infected (I) and Recovered (R), we can still assume some proportion of patients can move back to the (S) compartment (i.e. losing immunity, what that is in reality for COVID obviously has a debate that I will not address here).
The "r-factor" (also called R_0, or attack rate), described the rate at which people once exposed to the virus move from S->I. The proportion of patients in (R) should not fundamentally change the r-factor.
That said, I do think your fundamental assessment in that moving more people from (S) directly to (R) would decrease the rate at which the disease spreads.
I think you're right. That said, I do wish that people would be a bit more precise (and focus less on generic and confusing jargon) in their language however when discussing epidemiology.
If you're lowing the number of additional people an infected person infects with a disease, that's measured by a lower basic reproduction number (Rx), which was what the poster above was talking about.
It being artificially reduction is kind of given as it a vaccine, but as the basic reproduction number is being used to measure the number of reproductions from each [known] infected person within population groups it seems like THE measure of a vaccine's impact.
You seem to be talking about something else entirely.
Given the USA's total failure at the presumably easier task of wide-scale testing, the notion that we could manufacture and distribute a novel vaccine in this time frame seems completely impossible. Maybe other countries could have success.
How much of that failure was manufacturing capacity, vs. bureaucracy? IIRC there was a California lab doing some testing that was shut down by the CDC... so manufacturing wasn't the bottleneck (maybe it's now? I don't know)
The federal government has already sent billions to vaccine manufacturers to get the ball rolling. It's named "Operation Warp Speed" and the goal is to have 300 million doses of a vaccine by January.
nAbs don't last forever, for any infectious virus. That's what T-Cells and B-Cells are for. This vaccine showed a T-Cell response, which means it SHOULD last long enough. T-Cells from SARS survivors have lasted 11+ years. But we won't know until 2-3 years from now. We can't wait that long. I say ship it to production now, and do a v2.0 release later.
This is a very dangerous approach and would just add fuel to the antivax fire. Even if drugs/vaccines are effective that does not mean that they do not come with severe side effects. Imagine injecting the whole population with Thalidomide...
>This is a very dangerous approach and would just add fuel to the antivax fire.
I still haven't wrapped my head around antivax...
I mean, isn't that the product of poor education and lack of mandatory vaccination programs?
Where I'm from, you can't even sign-up children in school if they don't have the proper mandatory vaccinations - and school is mandatory, which makes it impossible to evade.
If they don't get the parents because they didn't take their child for vaccines (which is almost impossible because you're assigned a family doctor and he would flag it), they will get them when they'll sign them up for school. If they don't sign them up, social services all over them by then.
I know there are antivax people here, but they basically just avoid taking flu shot, all the rest they had to have them at some point. Hell if they cut themselves and need stitches, they will get a tetanus shot.
> I still haven't wrapped my head around antivax...
It's a tough one in some ways, but more gets down to how you define what an antivaxer is.
I have a friend who will never have another flu shot and be weary of this vaccine - WHY, well he had his first ever flu jab a few years back, which had bad side effects for him and he lost hearing due to it in one ear. Hence, he's very weary of such vaccines now and yet, some people would label him an antivaxer! I don't think he is as he is basing his opinion on self education and more so, experience as well as he don't push his choice decisions onto others.
See medicines and vaccines have side effects, most people won't get any, some will get a few and a very few will have adverse effects.
My worry is those who have had bad experiences and maybe more prone to side effects in some medicines due to genetics etc, get labeled as antivaxers and their very real personal experience is overlooked and they are viewed as crackpots when talking to medical advisers in the future, let alone society.
But then for me an antivaxer is somebody who actively promotes the non-use for everybody period and run with that. Now I don't know anybody like that, but can see how some may of come about via a few edge cases and propergating that onto the whole. That is a case of needing education.
If some people want to make an informed choice about individual vaccines based upon their medical concerns that are real and not anxieties - well, that's how it should work. Though if they actively promote their choice onto others, well, that's not right and what I would class as an antivaxer.
Me, I sent email to to the research folks offering to be a human lab rat if it helped speed up vaccine development, not that i'd call myself a provaxer - just case of the maths made sense and as spoke said - the lives of the many outway the lives of the few. Besides I'm still here :-). But I can respect an informed choice made by some, as long as they don't feel the right to impose that free choice of theirs onto others.
There are a very low number of antivaxers. Oddly enough, a lot of Measles outbreaks happen in strict religious communities with private schools that wouldn't be subject to vaccination laws in public schools anyway.
The media has totally blown antivaxers out of proportion. On top of that, there are many people who are very much for MMR, Polio and most of our standard vaccinations, but are weary of newer vaccines like HPV (and get thrown in with all antivaxers).
Some vaccines aren't very effective. I was turning in my vaccination records for school once and I was missing my 3rd Hep B shot. You have to have 3 of those in a few months, and if you miss one, you have to start over. A biologist I knew said it only had a 60% take rate, and was one of the most common vaccines that had to be taken again for hospital staff (who are given antibody tests to see which vaccines they need).
And on top of all of that, look at what happens when a vaccine is rushed. In the 1970s, 60 Minutes did a documentary on the rush to make a Swing Flu vaccine. Millions were vaccinated with no ill effects, but there were healthy adults that did have long term, permanent neurological damage:
I had to stop getting flu shots because they'd make the entire side of my body on the injection arm, hurt for days. I'd get extreme fatigue and soreness. It wasn't as bad as the flu of course, but it was painful enough I decided to stop getting them. I had an asshole friend tell me it was psychosomatic (all in my head). I get all my other shots (including Typhoid and Meningitis when travelling abroad) and had no adverse reaction.
So I make an active choice that I'm not going to do flu vaccines.
This entire situation is dangerous because we're talking about personal autonomy vs some ideological concept of communal good; and we're not discussing it with the delicate discussion and nuance it deserves. You can throw around terms like "antivax" and "antiscience" and it's a religious statement at that point, because you're not addressing the very real ethical concerns people have.
Hep B is effective and the effectiveness window is being extended as time goes on. When I took Hep A/B vaccine I was told that it would last for 10 years. Right now the estimate is at 30 years.
There are a variety of anti-vax philosophies. At one extreme is the people who thinks that all vaccines are harmful. I don't actually know anyone in that camp. I do know people who believe that we have many well-proven vaccines, but we give them too early, and prefer to wait for their infants to become toddlers. I know other people who are fine with the schedule, but oppose mandatory vaccinations because of the details in the legislation that has been proposed - much of the legislation includes a blanket statement of "and any other future vaccines" which opens to door to a corrupt government mandating new drugs for reasons other than health. That last camp isn't against vaccines at all, they just want some controls around the process of how a new vaccine is added to the list.
In Poland, where I am from, there is both obligatory vaccination programme and schooling; yet the antivaxers are plentiful. The obligation to vaccinate rests on the parents (+requires their approval from what I understand) and their current GP so if they are creative they can avoid vaccination of their kids.
This also affects recommended vaccinations, like HPV. In Denmark, media coverage of alleged side effects led to a substantial drop (or delay) in vaccination against HPV (Hansen et. al, 2018).
I think they mean don't block the release for not knowing whether it confers long-term immunity. I don't think they mean to remove all conditions (like safety) for blocking the release.
They were talking about long term protection. Realistically it only needs to last a year or so. After all the flu vaccine is only valid for a year because it evolves so quickly.
As for safety, that's the entire point of these three phases of trials. seeing if its effective is a nice bonus, but in reality to see if there are any problems like there were with the dengue fever jab.
> I say ship it to production now, and do a v2.0 release later.
I commented on that part. And yes, it seems to be safe in healthy subjects (Phase I). The OP wants to move from Phase I to production immediately. I take an exception to that approach and I agree with you that there is a point in doing the three phases. The later of which actually focus on effectiveness as well.
Shipping something that's not effective is counterproductive. Being vaccinated would affect people's behaviour, if you told them that they should not change their behaviour back to pre c19, you would be just faced with questions on what's the point of vaccination.
Obviously nobody will force you to get the vaccine. A lot of people will be ready to take the minimal amount of risk. I assume you are not forced to work from home while taking care of kids at the same time :)
It is not about me; and I actually think that if there is a safe and effective vaccine that vaccination should be obligatory.
This was just a Phase I (healthy subjects) and most of drugs/vaccines are successful at this stage.
Drugs are not software, you cannot ship a broken product and then fix it. Even if it is safe, but not effective, it would do more harm than no vaccination, as vaccinated people would change their behaviour.
But what exactly is long enough? Compared to repeated lockdowns, even monthly vaccine reinjections would be a relief because ramping production is easier than locking down. We don't really need perfect immunity, we just need to force average spread per infected to a value significantly lower than one and even a vaccine that turns out ineffective for a fraction of the population could be a major contributor to that. The most important concern is side effects, particularly antibody-dependent enhancement. Once production is the bottleneck things can only get better.
Considering we already do this once per year for the flu, its not even that unreasonable of a measure if its necessary to do monthly, bimonthly, quarterly, etc.
It would probably start to depend on the person. If you live in New Zealand where covid has been eradicated, then why risk it. If you are a front-line medical worker in Georgia, you probably want the vaccine.
Somewhere in the middle things would get iffy and ethically interesting. The front-line medical worker is probably well-compensated. The essential workers at the grocery stores and warehouses are not.
Hopefully the vaccines are safe and effective and all of this remains a hypothetical.
It is inaccurate to describe New Zealand as "shut off from the rest of the world".
Trade and communications are running normally. Outgoing international travel is allowed, but of course hardly anyone wants to until the overseas COVID situation settles down. Inbound international travel is bottlenecked on the quarantine system while NZers overseas keep returning here, but that won't last forever because there is a finite number of them, so at some point non-citizens/residents will be able to travel here with a 14-day quarantine requirement and an associated cost (about $4K each). That will work for students, immigrants and long-term visitors. Short-term international tourists are really the only group that will be effectively blocked long term if we don't get a vaccine.
last thing you want is long term effects being harder than the disease itself. Even moderate effects will undermine trust in vaccines and the world absolutely can not afford that. I hope we’ll thread carefully here.
The median age of death from COVID is about 80, and those people have serious existing health conditions. Statistically people in this group will have a life expectancy of about another 5 years. This is not a group that you have to worry about side-effects.
The death toll from COVID lockdown is so much higher - from excess suicides, poverty, crime and violence - that anything we can do to alleviate the panic and get back to normal life is worth it.
So what oh what could the government do to alleviate the issues from lockdown? Weird they could give the PEOPLE of the country the bailout money. They could extend the the unemployment credit. Unfortunately they are not thinking in that manner and it will lead to a huge depression which could cause those issues you are mentioning. Although I would like it see some actual stats that say "suicides, poverty, crime, and violence" are actually more deadly than the disease. If people in the United States had been a little less selfish (or didn't think of this as a politics game) maybe we wouldn't still be deep in the midst of the first wave of this with many states losing any progress they made. Our leadership in Washington (all of it not just POTUS) has failed us just to keep the stock market high and all their cronies rich while the rest of us suffer.
Would like to see a discussion about whether it is a false dichotomy.
I mean, in an ideal population set where people acted rationally, it might be. In the real world, where fear motivates counterproductive behavior, it’s hard to imagine a different scenario where you don’t slow the economy (associated harms) while trying to mitigate the virus.
> Would like to see a discussion about whether it is a false dichotomy.
Another topic on HN that showed up today was "any claim without a URI should be treated as suspicious," which I would broaden to, as the kids say: "bring receipts." If you're going to implicitly (or explicitly) claim that the harms of a lockdown in response to a pandemic are greater than the harms caused by the pandemic itself, you should at least put a little effort into explaining why, and include at least some links to studies or informed discussion that support your claim. Just backing it up with "the truth of my claim should be clearly obvious to even the most casual of observers" is rarely good enough.
I don't think anyone has seriously claimed you can mitigate the virus's spread without slowing the economy, or that slowing the economy doesn't come with associated harms. The question was and remains what the balance is. Is there any evidence to back up the claim in the thread above that "the death toll from COVID lockdown is so much higher?" Higher than what? The projected death toll from no lockdown at all? When someone makes a claim about the economic damage from the lockdown, are they taking into account studies that try to project the economic damage that no lockdown would have caused?
You realize you’re talking about likely more than a million life years lost already? Potentially much more damage when you consider dalys
due to long term sequilae as well.
How much more can we expect if things simply “get back to normal”. Hard to say but obviously a gigantic loss. I’m also highly skeptical of claims that #1 suicide, crime, violence have increased significantly. Source? Poverty/economic disruption is obviously a massive damage that cannot be understated either.
But I’m highly highly skeptical that countries who try to ignore the problem like Brazil, USA will end up economically more successful than countries with strong countermeasures like South Korea, Taiwan, New Zealand, and many others. Beat the virus to fix the economy.
At some point there is an inflection point where it makes sense to “give up” and accept that countermeasures are more costly than the benefit they provide. Clearly every day we delay and have high rates of infection, and the longer the vaccine takes, we move closer to the “give up” side of the calculation. I’m not at all convinced we’ve reached that point yet and we certainly hadn’t reached it at the point the federal administration gave up.
Making antibodies is a hugely expensive process in the body. You'd only want to do it for mortal dangers like Smallpox. So I'm pretty sure our body decides if it's worth it. The reason colds are endemic is that they aren't worth having a special forces team training to take them out of circulation at all times. You can just have the army look at it when there's an issue.
Do you have a source for this? I don't know much about immunology, but I know a little bit, and I don't think it's that thoughtful of a process. We have antibodies for all sorts of diseases, certainly not just for things like smallpox. This article suggests colds are endemic because they mutate too quickly for antibodies to be effective: https://www.technologynetworks.com/immunology/news/why-dont-... but we still make antibodies for them.
We make antibodies, that's not the analogy I'm using, and I am studied in immunology. Some diseases are so harmful, our body keeps antibodies floating around perpetually in case we encounter it (e.g. smallpox). Coronaviruses are mild enough that we can "remember" it with t-cells and spin up antibodies as needed. Part of what bones do is this antibody production process, and it requires more energy than vital organs.
> Although the magnitude of neutralizing antibody (nAb) responses correlated with disease severity, there was a rapid decline in nAb titres in most patients within 3 months after onset of symptoms. [...] However, the consequences on secondary immune responses and their ability to prevent reinfection remain to be determined.
[1]: https://www.nature.com/articles/s41577-020-0405-3