It took two days to develop Moderna’s vaccine
theness.com
theness.com
My brother is a doctor and he got his Pfizer shot yesterday. Less than one year has passed since the first case in the USA. I consider this one of the great accomplishments of science. It will go unnoticed by many idiots on social media but it is an amazing achievement by all the scientists and doctors involved.
Any more deadly (like Ebola) it becomes incredibly scary and people likely do whatever it takes when they see people around them dropping like flies (especially in horrific ways).
Any less deadly (basically the yearly flu) and it becomes easy to ignore and just becomes part of the background process.
COVID is somewhere in between. Deadly enough that hundreds of thousands of people are dying unnecessarily. But can still feel a million miles away for so many people.
This was not a good "training pandemic".
Was it not though? I assume you'd want a pandemic deadly enough for that convinces a majority of the populace that it's a serious event (to encourage downstream change to better prepare for a worse pandemic), while at the same time not causing people to drop like flies. As you stated, anything less severe would be taken less seriously. To have something to be taken more serious, it has to be more deadly.
Despite the denialism we currently have, it seems to have made the world recognize the importance of preparation.
But most countries deemed those actions too extreme and economically damaging so instead let it come spread and do way more damage.
So many failures got us to this point.
In my country we have destroyed economiy due to 10 years of incompetent greedy politics which had killed it already. People are out of work because of that.
Now the pandemic has made sure no one will recover at an acceptable rate, because new politicians also struggle to find the balance.
At this side of the planet we are screwed at such a hard rate, its amazing I can still feed myself, pay utilities and internet and be medically insured
Vietnam isn't a paragon of wealth and competent administration today, there is no good reason our public health departments should not have been able to perform equally or better than their equivalents in Vietnam.
We have mandatory two week quarantine for all arivals, stores lose their business licenses if they let anyone in without a mask. Schools, cinemas, gyms, clubs are all closed.
We’re hoping things will open up again in two weeks.
Ebola requires direct contact with bodily fluids, it's not nearly as easily transmittable as Covid. Note that seasonal flu levels are at historic lows [1, 2], despite Covid raging to the point where many US states' ICUs are filled to capacity.
[1]: https://www.scientificamerican.com/article/flu-season-never-... [2]: https://www.nature.com/articles/d41586-020-03519-3
More evidence of the pervasive political attitude that’s “science-based” but more like modern day fundamentalist fire-and-brimstone “anyone smiling wrought all the suffering in the world” Christianity.
I don't need to hold my hand in a fire to know not to touch fire again.
Giving someone pain/suffering to teach them a lesson is just abuse.
[1] https://www.cdc.gov/flu/pandemic-resources/2009-h1n1-pandemi...
I believe there's been a misunderstanding where people think COVID is more dangerous to elderly people because they just tend to be generically vulnerable to a lot of disease.
That's not the case, however. If you compare death rates within different age groups, the risk for elderly is dramatically higher, even in comparison to other diseases that tend to be worse in old age (yes, exactly, such as the flu).
We're still waiting to see the fall-out of long COVID.
I'm an athlete, and my cardiopulmonary bits are essential to my sense of well-being.
/Acey
If you told anyone, on their death bed, "if you had run 25 km a week since [n-15 years] you would have been able to move better / dance with pretty girls / play [tennis | golf | etc] until two years ago," I think most people would say WHY DIDN'T YOU TELL ME.
/Acey
The profile to date is not close enough to home for most (white) middle class Americans. But that lack of fear to some extent, at this point, is statistically justified. That is, once you get outside the sweet spot the chance of death declines.
The virus is real. The deaths are real. However, despite the media hyperbol (and complete lack of basic lack of understanding of data and data analysis) how those deaths are distributed is uneven. Very much so.
History rhymes and we are doing our best. Please don't blame others ala "Those who ignore the past are doomed to repeat the mistakes"... We will have much more possibilities and views in the future though and are currently blind(er) compared to that.
This would cause the "Bob had it and he's fine!" mentality to spread as it currently is.
An example of this may be HIV.
And it would be worth knowing the numbers before jumping on the fear wagon. Is it 1 in 10 young people or 1 in 10,000?
Not trying to minimise the seriousness of COVID, but simply suggesting there is no evidence of serious long term impact to the majority of cases.
I think lack of evidence is more a symptom of limited information.
There is also the minority opinion that some forms of dementia are due latent viral infections.
[1] You don't guillain barre syndrome takes years to recover and is absolutely traumatic.
Something that spreads like measles and kills 5%, maims some, etc.
1) massive mutation rate, altering exterior structure making a single vaccine impossible (e.g. influenza)
2) touch-based transmission, with 72 hour surface viability
3) incredibly "ugly" death process (e.g. ebola) with huge risks for health care providers
4) high death rate but very slow deaths
Let's say pregnancy, a new Star Wars movie, or birth; transferred from parent to child, "activates" inside the newborn and then kills the parents too.
Moderna zeroed in on the spike protein thanks th large amount of previous research on SARS-CoV-1. Vaccines effective in animal models of SARS were developed based on this approach starting around 2004:
https://www.pnas.org/content/101/17/6641
The article continues:
> The win-win here, however, is that the more we develop a universal vaccine platform, the more we can have the best of both worlds – fast plus safe and effective. But this also means we need public buy in, which requires reassuring the public about the process and the strategy. It also means reassuring the public that the process has not been politicized, and that objective experts are driving (something the TA did poorly).
The MRNA approach requires an understanding of viral vulnerabilities and a lot of animal studies prior to the synthesis of a vaccine candidate. Again, that seemingly fruitless work with SARS more than a decade ago was the key to the success of Moderna and Pfizer today.
It's a lesson that should not be forgotten but probably will.
The other thing to keep in mind is that the Pfizer and Moderna approvals represent the first ever large-scale use of MRNA vaccines in humans. That substantially lowers the barrier to entry of new vaccines based on the same platform.
To my knowledge, that kind of understand does not exist because coronaviruses have been largely ignored historically, with the exception of SARS and MERS.
And we've been trying for decades to get a broad-spectrum or even single-dose-forever vaccine for the flu, so far without much to show for it.
Then later if you get the virus, the immune system already recognizes that protein and takes care of the virus.
Question: why do we need to have our cells make the protein? Couldn't we synthesize and distribute the protein itself and inject that?
Question 2: what happens to the cells that take in the mRNA and make the protein? Do they just make a certain amount of it, then go back to normal?
Or do they keep making it for the lifetime of the cell, and stop doing whatever that cell is normally supposed to do?
Or do they get killed doing this, much like if they were infected by the virus (except, of course, that unlike the with the virus, what they are making is not viral, so the maximum number of cells that would be killed making the protein is equal to the number of mRNA strands in the injection)?
2. Yes the cells go back to to normal after the mRNA degrades. The mRNA does not last long, it is like data in ram vs data on a hard drive.
See this video:
Proteins are chemical compositions - useful machines. Each one (especially outside the context of a cell) requires custom environments to be kept stable. And the processes to manufacture them require other organisms - from which you must now purify that (unstable) protein. And it’s not self-replicating so if you need weekly doses of Ng of material for X doses, you need to produce that much material. RNA solves all of these issues. RNA is a template of common composition that can encode any protein (same chemistry, but in different orders can encode for any arbitrary protein). It can be synthesized in a chemically defined system. And it can persist long enough to produce many generations of proteins. And it can even sometimes be designed to be self replicating. From a theoretical perspective it’s so much better than delivering a custom-purified shot to your blooodstream - different for each virus.
The second question is the hard part - delivery. With the advent of ‘gene therapies’ we needed easy to deliver DNA and RNA to living human cells. We’ve come a long way here and have a number of technologies (oftentimes co-opted from viruses) that range from permanent integration into the cell’s genome (lentivirus) to transient (AAV [see Oxford’s vaccine]) to chemical transfection (Pfizer and Moderna). The RNA in these vaccines is chemically more stable than normal RNA, so it will have half-lives of weeks rather than hours inside cells - but it will degrade after a time and the cells will no longer produce the protein. Proteins in a cell have half-lives of hours to days and even stabilized RNA will be less than a month. After that the material produced by this 'vaccine' will be degraded and gone. However, at that point, the immune system will have permenantly 'encoded' antibodies for the shape of the produced spike protein.
Skip to around 12:30 in here: https://www.youtube.com/watch?v=35Idb_lCU4o
He goes through the entire biochem process. Even the cells infected with the mRNA will need to be removed by the immune system using cytotoxic T-cells, so they need to get the chain process going.
The reason we have "memory" for viruses is because a ton of random stuff in our immune systems evolved to multiply exponentially when they come in contact with viruses or proteins that indicate certain infections. It's a lot of stuff and you can't just inject that memory in; you have to stimulate the immune system to create them at a very large scale.
It's not just antibodies. There are memory T-cells, parts of the complement system that get activated; a whole host of things.
My issue is that our immune systems are incredibly complex, and there are a lot of components to this "memory" that are not entirely understood. Every other vaccine is an inactivaed virus (via heat treatment) or attenuated (virus run through other hosts to make it less dangerous to humans). The first vaccine was just a close relative: cow/horse pox instead of smallpox. The former are not dangerous in humans, but seem to produce the same immune memory.
The mRNA vaccines are at attempt to say, "Let's strip out all that other stuff and find just the thing we need." But our immune systems are incredibly complicated. It will be interesting to see if these things actually work at scale.
The trials were to make sure the vaccine is safe in a short about of time. It's not really going to test effectiveness until deployed at scale.
I don't think that this is accurate.
2. Yes, the mRNA is ultimately degraded. But part of the process of developing the vaccine is fine tuning the precise rna sequence in order to achieve the desired half life.
“In October 2013, DARPA awarded Moderna up to approximately $25 million to research and develop potential mRNA medicines as a part of DARPA’s Autonomous Diagnostics to Enable Prevention and Therapeutics, or ADEPT, program”
In a Sci Fi movie maybe the virus has a long delay, you're infectious for a month with no symptoms, then drop dead in seconds. But in the real world that's less likely the more extreme it gets.
One thing that did make this virus more dangerous was that many humans became infectious significantly before they realised they had symptoms. With some viruses you get symptoms, then (sometimes as a result of the symptoms) you become infectious, making it easier for public health messages to be effective. "Stay at home if you have symptoms" is extremely effective if people aren't vectors until 12-24 hours after the symptoms are obvious, but almost useless if they're infectious a week earlier.
I'd argue that countries which think the lesson is "We developed a vaccine quickly, good job" are mistaken. The lesson was just, "Elimination strategy works" and the many countries that didn't even attempt that got lucky they weren't decimated for their incompetence.
Ironically, a disease with a much higher case fatality rate probably would’ve killed fewer Americans, since we’d be more aligned on stopping it, and it would have a greater tendency to burn itself out.
Not unless it was much higher, like 10% whole population fatality might do it but merely twice as much death wouldn't move the needle.
It's because of one of the most literal examples of survivorship bias. No living people have ever died as a result of taking some particular obviously unsafe shortcut, so they can rationalise it as OK, even though intellectually they know it's a very bad idea. Each time this unsafe shortcut kills somebody, all the living people still have no experience of dying from that shortcut because the one person who experienced the other outcome is now dead.
Close calls can help a little bit, gradually, but the effect is slow and unevenly distributed.
> it would have a greater tendency to burn itself out.
One reason I particularly point at elimination strategy (beyond the, in my opinion obviously related fact that it worked) is that zero cases has a categorically different impact than merely low numbers of cases that result from hoping a lower R-number will cause it to "burn itself out". You get to zero only one case at a time, tracking and tracing everything, getting right into the details, whereas these vague statistical approaches do not do that.
Lots of countries or regions have tried to "flatten the curve" but that's not actually a way out, it's just to buy time. Now, in this case if you bought enough time (maybe 18-24 months) you get a vaccine. But not all diseases are like that, and we could not be confident this was one.
Getting to zero is instead a (painful) permanent fix that allows you to really open up (within the country or region at zero). New Zealand's international tourist economy got a kick in the head, but its people are alive, much of everyday life is already how a lot of us in the North are hoping 2021 will be - its message this summer is "Make summer unstoppable" with small adjustments like wearing a mask on the plane, or tracking where you visited with QR code scanners - but otherwise a pretty normal vacation season, concerts, sports events and so on.
Nobody asks the people who died in the war if it was worth it.
Wilfred Owen did not live to see the end of that war.
It was at first astonishing to me that the same words are etched into the Arlington cemetery amphitheatre, but of course that's almost why Owen refers to them. At the time the building was constructed it would have been the thing to do - to portray death in war as a noble sacrifice.
Owen's point is that there's nothing noble about choking to death in a fog of gas, of so many dying so far from home, war is not noble or patriotic, it's horrible.
People take something far more seriously if someone they know, especially a family member, friend, immediate colleague, etc, dies of it, compared to if the only deaths they know are stranger deaths reported in the media. So I don’t think it is true that people will ignore something unless they personally die from it, if your spouse or child or parent or best friend or boss dies from it you will take it very seriously.
I don't personally know anyone who has died from COVID. As far as I know, I don't know anyone who knows anyone who has died of it either. Probably the majority of people are in the same boat as I am. Not saying I don't take it seriously, but I'm sure I'd take it even more seriously if someone I knew died from it.
(A work colleague got sick with it, had to go to spend some time in hospital due to breathing difficulties, but has since recovered – that obviously raises the psychological impact of it for me a bit, but they live in another country, if they lived in the same country, even same metro area, as me, the psychological impact for me would be greater.)
The worst case I can think of is an ubiquitous animal vector (rats? mice?) that only gets a mild form of the disease but can spread it, while people fall dead all around.
Obviously, it was made worse by people blaming cats and killing their best defense.
I think the scariest combo would be long incubation time + transmissibility while asymptomatic + high lethality when symptoms appear. This type of virus would spread far and wide before it’s detected, and would also be very deadly.
Here’s one link: https://medical.mit.edu/covid-19-updates/2020/07/how-long-sy...
Contact tracing protocol is built around this, so I’m sure other references exist as well.
For example, by “something like hiv” do you mean something that acts very slowly, but eventually kills you? That indicates a low viral reproduction rate - which means you’re spreading far fewer virus particles than something like covid, thus a low transmission rate, even if airborn.
Do you mean “attacks the immune system”? How does it get airborn, if it’s in the relatively few immune cells in the lungs? I suspect if you inhaled an aerosol of hiv particles you might catch it, but it doesn’t have a way of getting in the air.
Again, not an expert/wild speculation, but I think the risk of something fast acting, highly transmissible, and highly lethal, is more of a concern than a slow-acting lethal virus.
If the strategy is 'everybody stay at home' then it work in the same way shot gun works in eliminating cancer. It works but the cure is worse than the disease.
https://i.stuff.co.nz/business/123696832/gdp-jump-of-14-per-...
Also from the article:
However, Stats NZ national accounts manager Paul Pascoe said the effects of Covid-19 on different industries had varied “and for some industries these may persist for some time”.
The rebound was not enough to make up for the lost activity during the lockdown period, with GDP in the 12 months ended on September 30 down 2.2 per cent on the prior year.
Not a country: florida, it is one of the state in the usa that has the least covid related restriction. They are doing very well. Went there myself to visit recently.
Its not hard to see why lockdown is not worth it. According to cdc, covid has very very low ifr :
0-19 years: 0.00003
20-49 years: 0.0002
50-69 years: 0.005
70+ years: 0.054
“ Assume that the differential Swedish approach dampens the GDP fall this year by 1 percentage point. This represents a gain of approximately $5.6 billion. Also suppose that the approach has caused 5,000 extra deaths — a reasonable guess from comparisons with other Nordic countries. How could one estimate that loss of life in economic terms? The value of a statistical life, used by the Swedish Transport Administration in its cost-benefit analyses of investment in traffic security, is approximately $4.6 million. Using this number, the economic cost of lost lives would be as high as $22.9 billion — clearly outweighing the benefits from the smaller GDP fall. One might argue that the value of lost lives should be set much lower, as the vast majority of deaths have been among elderly people, with fewer years left to enjoy life: 89 percent of the dead in Sweden have been above 70 years of age, and 67 percent above 80. One reaches the break-even point in my calculation if one lowers the value of an average life lost to $1.12 million. For the Swedish approach to be “profitable,” the average life lost must be valued lower than that.”
https://www.washingtonpost.com/outlook/2020/10/20/sweden-eco...
Yes, and more than one. Community transmission was eliminated several times.
The point is to compare the strategy to others.
Subsequent small outbreaks have not triggered a lockdown because their government remained confident it understood the scope of the infection although one leak got close, they asked people not to travel into central Auckland for a day or two at one point and sealed off a residential building while they tested everybody who lives there.
They anticipate continuing to have occasional small outbreaks detected, e.g. a border worker gets infected, infects a family member before a test spots it - and their plans assume they will either quickly achieve confidence they've contained the outbreak or they'll lock a region or if necessary the entire country back down to eliminate.
For example at a press conference the press basically wanted to know if the government was imagining people should prepare to pay for an extra week's accommodation on vacation in case they can't return home (obviously unaffordable to many families) but the government seemed to be more thinking about if you've left a week's cat food and instructions for a neighbour, do you have a way to tell them they need to feed your cat for an extra week? So, personal anxieties rather than population scale ones, the government can pick up a hotel bill but it can't bring your pets back to life.
The lockdowns were worth it IMO. Especially now we see it ravaging the rest of the world becoming more and more severe. That just feels totally foreign to me since we only experienced a very mild outbreak initially, followed by a tiny one a bit later on.
NZ is a good place to be.
Some people have lost businesses, jobs or careers and they're going to be less happy about that.
From my day to day perspective my life is very normal. I remember the level of background anxiety grew rapidly the more it spread into the community in the initial outbreak. The second and third waves around the world look increasingly terrifying.
I'm calm. Im at peace. That suits me perfectly.
The results in NZ are only subjective if you pull some elaborate contortions, NZ has done well.
My understanding is that a big part of why this one was so fast was that Moderna had experience digging into SARS previously, and that led them to immediately focus on the spike protein this time around. Without that prior experience I expect it would have taken longer? (But likely still pretty fast.)
As http://cis471.blogspot.com/2012/08/seeding-internet-cost-gov... lays out, the government spent $25 million on ARPAnet, the first packet switched network and the granddaddy of our current Internet. So it was actually the same figure as this grant. (There were followup investments from the government, but the whole thing was around $125 million.)
Yet I can use writing to send a letter to someone so that they try to hurt you with a breaking wheel, if you get what I mean ;-)
The internet is great, how we use it may not be.
I don't have twitter, rarely delve into comment on most news sites and Youtube. Browse and sometime comment on Reddit and here. I prefer here, less shouty.
When you are able to talk to thousands or millions of people without having to have connections, its a wonderful thing. The friction arises from a number of things; contrarians who love to argue, trolls, governments/companies who are trying to influence opinion but also people who have a genuine different opinion and are unwilling to listen to the other side.
I did enjoy the internet more when it was younger but at the same time, there was a less diverse population on it then.
The point being, if a novel deadly virus was discovered tomorrow, how fast could Moderna develop a potential vaccine?
If a new pandemic emerges from a less well understood family of viruses for which we don't have any good preclinical vaccines, it could still take decades.
Sticking the genome into synthetic mRNA isn't the rate limiting step, it's knowing to target the spike protein, inserting the stabilizing proline mutations, &c and also having experience getting safe and protective responses from a similar vaccine for a related virus.
> The question ultimately comes down to risk vs benefit. We need to get over our evolved but suboptimal instinct to avoid directly causing harm preferentially over passively allowing harm to occur. In the end, the amount of harm is all that matters. In a situation like this, delivering a vaccine as quickly as possible while maintaining sufficient safety and efficacy, there is a sweet spot somewhere that minimizes disease, death, and disruption. We want that sweet spot, even it if means delivering a vaccine that has not been tested as much as we would like. It would mean accepting more risk form the vaccine in order to reduce risk from the pandemic.
I'm generally against pharmaceutical companies charging ridiculous prices for their drugs, but we've benefited from the fact that they use this money to pursue risky research opportunities. If the chance at a big payoff wasn't there, big pharma might not have had this in the hopper. Government funding alone probably can't incentivize pharma to continue pursuing long-shot bets at their current level. Now I have to think about which option I would prefer- cheaper prescriptions or a better chance at being prepared for catastrophic events.
But that's a complete, uneducated (but I think, logical) guess.
https://arstechnica.com/science/2020/11/astrazenecas-best-co...
Or it doesn't come out because they are good at keeping it secret.
Considering high-level officials in the government apparently never received the vaccine, I would be surprised if the people involved in the research took the vaccine.
Then again, maybe secret was kept extremely well. My intuition is, if POTUS knew about it, he would have been telegraphing such on twitter back in the summer months.
Being able to go to concerts and sports events and theatres safely is pointless if there aren't any concerts or sports events or theatres open.
If you've got elderly loved ones you want to keep safe, you'd need to vaccinate them, not yourself.
And if all you want to do is go to the shops without a mask, while everyone assumes you're a dumbass? You don't need a vaccine to do that.
If the vaccine substantially reduces viral load, and degree and period of contagiousness for those who receive it, as well as reducing the risk of illness (which AFAIK it does, while falling short of sterilizing immunity), and you are the elderly loved ones main interface to the outside world, getting vaccinated on top of other precautions provides a real benefit.
OTOH, if you have to choose one to be vaccinated, it's them, not you. If you do this for lots of elderly family members, getting yourself vaccinated may be better than getting any one of them vaccinated, though. And, of course, of you are doing an off the books pre-approval use of the vaccine, accepting the risk of unexpected side effects for yourself may be more reasonable than imposing them on, or even suggesting them to, someone else who may be in a more fragile state.
https://www.cidrap.umn.edu/news-perspective/2020/12/fda-anal....
> He said the findings reflect an impact on blocking transmission and are very encouraging, hinting at mucosal immunity. "The data aren't conclusive but support this key benefit," he said.
Of course, if in the end vaccines don't prevent transmission, then they don't prevent transmission. But we don't know that they don't do that.
I know a friend that got the Moderna vaccine that way. Technically, it was double blind, but it is fairly obvious whether you got the real vaccine or not.
That was hearsay, though, and I don't have access to the internal protocol.
1) CDC reports 5101 deaths for the 35-44 years ago group. I assume YTD with "Date" being "recent".
https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm
2) My reading of the 2018 (best I found sorry) mortality table for 35-44 age group would put death by covid as the 5th leading cause of death. Just between suicide (7521) and homicide (3304).
https://www.cdc.gov/injury/images/lc-charts/leading_causes_o...
Note that "flu and pneumonia" for that age group was just 956 - putting it at #9 for leading cause of death in the 35-44 age group.
So I think covid is a bit more than "just the flu".
Don't be afraid of covid killing you. Be afraid of it turning you into a mentally disabled cripple who can't catch his breath until you die of heart failure twenty years before your time.
Edit: Oh and just for kicks, there's recent evidence it causes erectile dysfunction too.
In June estimates were that 1 in 5 people who needed intensive care for covid were left with permanent damage.
> People infected with the coronavirus may be left with permanent lung damage. Doctors are reporting growing numbers of people who still have breathlessness and coughing months after falling ill with covid-19, and whose chest scans show evidence of irreversible lung scarring.
> The numbers of people affected aren’t yet known, but estimates are as high as one in five of those who needed intensive care treatment for covid-19. Permanent damage is sometimes seen after other kinds of chest infections that can cause similar lung inflammation to the coronavirus, such as flu and pneumonia.
> In a study in Italy, which was one of the first European countries to be hit by the coronavirus, doctors are scanning the lungs of people three months after they fell ill. Although the full results aren’t yet in, Paolo Spagnolo at the University Hospital of Padua estimates that 15 to 20 per cent of those treated in intensive care at his hospital for covid-19 have scarring. “We have to be prepared in the future to manage these patients.”
https://www.newscientist.com/article/2247086-the-coronavirus...
What is not shown at all is that it turns you into a “mentally challenged cripple.”
> Because none of this is remotely evidence-based.
I won't be surprised if Covid ends up being slightly more or slightly less correlated with post-infection issues, but we have seen no credible evidence of this at all, much less evidence that we should worry Covid turns you into a "mentally-challenged cripple."
So GP's statement is partially true.
Money is a bad metric but it does boil things down to one measure. I’m sure these aren’t measured the same way but the effects haven’t been similar. Flu $90b per year versus the covid cost of $16t.
I mean that miiiight have something to do with the fact that we basically ignore the flu despite tens of thousands of deaths every year. Whereas with Covid we collectively decided to shut down the entire world.
Some of those countries are "not sitting pretty right now" because they ended their lockdowns.
The answer is not "lockdowns don't really do any good." The answer is "don't prematurely end your lockdowns." Now that can be burdensome. You can do a middle ground (limited re-opening). That works too, but you have to be very careful and keep a close eye on case numbers and shut down totally as soon as cases ramp up. California tried to do that in the latest surge, but was a little late in implementing the newly stringent measures and even further So. Cal. "resisted" the newly stringent measures and are now suffering mightily.
True
>All of it is a “limited re-opening.”
Yes, but the issue is how limited was the limited re-opening. I live in the U.S., but ALL of my colleagues are in Europe. It's anecdotal, but my understanding is that the re-openings throughout EU were quite closer to the "unlimited" side than the "total lockdown" side of the spectrum.
>Perhaps respiratory viruses spread much more effectively in the winter versus the summer
The presence of an additional explanatory factor does not prove the absence of an alternative explanatory factor. They could both be true, and almost certainly are true. That is: lockdowns work; without lockdowns, you have Bergamo in Jan-Mar 2020 (mass death); COVID spreads better in winter.
I'm 35, and am not super-worried about dying of covid; it's certainly possible, but not hugely likely. However, I'm extremely worried about being a vector.
Question: what would be the likely reasons for that? In particular, is it almost certainly going to be due to whatever carries the mRNA, or could the mRNA itself be the problem?
If it is the carrier in which potential safety issues lie, does that mean that once we have one successful safe mRNA vaccine for virus A, then when some new virus B comes along an mRNA vaccine for B that uses the same carrier is going to be as safe as the vaccine for virus A?
If so, does that mean for future new viruses, the mRNA approach will let us go right into effectiveness testing, skipping phase 1 safety testing?
I'm sure that it would ruin the data for later vaccines, but if high-risk people just take each new vaccine as it starts trials, their data doesn't have to count towards the actual trial.
A vaccine can make a disease worse by priming the immune system to overreact and attack the entire body when a single cell is infected.
The more we know about a vaccine the more confident we are. The flu vaccine is changed every year without long safety studies: we have learned enough about how people response to the flu vaccines in use to not need them anymore. When the same process is used to make a non-flu vaccine though we still have to start over because there isn't any way to be sure.
You are quickly getting beyond my area of knowledge though. I didn't answer all of your questions because I don't know.
https://en.wikipedia.org/wiki/Dengvaxia_controversy
Dengue fever is a strange and terrible disease where -- unlike most infectious diseases! -- contracting it once can make future infections worse through autoimmune mechanisms (if I remember correctly, you typically become immune to the particular strain that caused the first infection, but may become more susceptible to severe reactions from a later infection involving a different strain). Apparently the Dengvaxia vaccine, while effective at reducing the chance of dengue infections, also has an effect similar to surviving an infection: it increases the chance that an infection will result in severe disease. That makes it a more complicated question whether it's a good health intervention in particular circumstances, and in the Philippines there was a big scandal where a childhood immunization program using it may have reduced the total number of people who contracted dengue, but also increased the severity of the worst cases.
To my knowledge the pathogens that cause COVID-19 and dengue fever are extremely different, but it seems logically possible that there could be a COVID vaccine that greatly reduced people's chance of getting sick at all, while also increasing the chances of severe symptoms for those people who did get sick.
It only invalidated certain types of HIV tests. The impact would be that some subset of existing HIV tests would have to be abandoned. That would impose a cost on the health system.
The real issue is that there were other vaccines being developed that were equally effective but which did not have this drawback. If this was the only vaccine available, the health system would have worn the burden of changing HIV test regimes; given several other effective vaccines are becoming available, it wasn't clear that the cost of imposing massive changes on HIV testing regimes was justified.
The first part is hard to guess without knowing what's in those delivery methods.
mRNA, or RNA in general, can form secondary structures which in theory could affect the the cell machinery. Depending on the details this could produce side effects to the cells that take up the mRNA. This would probably be localized and a strong secondary structure may inhibit translation also, rendering the vaccine ineffective. This can be checked in silico and in vitro during design to some certainty.
The protein product I would guess is the most likely to cause problems. Essentially you can encode any protein in mRNA, so you could make the cells that take it in produce snake poison, for example, if you wanted to. Depending on how the virus protein is modified, and how it reacts with the cells/body when present apart from the rest of the virus it assembles with could bring all kinds of side effects. The severity probably depends on what exactly it interacts with, and if it's only local or it gets into the bloodstream etc.
I think this information should be made open so that other countries/companies can produce vaccines with the higher temperature requirement, not to mention that the public should know these differences and why they exist. There's gotta be more factories that have the necessary equipment, but the plans just aren't available.
https://www.npr.org/sections/health-shots/2020/11/17/9355633...
There are costs to calculated Utilitarianism. The damage to public confidence in vaccines springs to mind. If a vaccine is provably killing 1% of those receiving it, yet saving the lives of 2% (and more once herd immunity is reached) it may raise some alarmist criticism (to say the least) over the safety and advisability of getting vaccinated. Making it harder to convince the public to get vaccinated at all.
Other costs are, mis-estimating the ultimate death toll may lead to killing more up front than was strictly necessary. Or the vaccine may have side effects down the road, shortening lives or diminishing quality of life (sterilization? memory loss? immune system compromises?).
Unless all the costs are factored in, Utilitarianism become a guess, and can be used to serve profit or social agendas. The law of unintended consequences will loom large.
We have a vaccine protocol for a reason.
If that can already be calculated, calculated utilitarianism could take it into account.
2) the word "approved" is misleading. Of you change this to say "banned" or "not banned", this reads very differently. The requirement to ban everyone from taking a vaccine in order to mitigate some extreme long tail event and maintain public confidence is hard to justify on utilitarian grounds, but pretty much any other ethical framework.
Developing the mRNA technology was of course decades of research, but now it is ready to be used. It also helped, that the SARS-virus was very well researched, so like with software, it the vaccine wasn't created "from scratch". It used the knowledge already present about these viruses. This means, while you might not get a vaccine against a random virus in two days (no HIV vaccine available yet), adjusting the vaccine for slight variations of the SARS-cov-2 virus, should be a very quick process.
We know, this time with hindsight, that it would have saved hundreds of thousands of lives and billions of dollars if we'd used their product on day 3.
Can we develop a protocol that can tell us that so we can use this tech on day 10 next time? Then we can save those lives.
you still need to make sure the vaccine actually works in trials and has no severe side effects. It takes one, and only one minor vaccine scandal to completely blow the trust of the public in public health.
There is no linear risk/reward when it comes to vaccines. You need to be incredibly confident that they are safe or else you're going to screw yourself possibly for decades.
It's not. They can't. Not even remotely close.
They're so far off the claim it's embarrassing they even said it. They couldn't write 1% of Twitter in a weekend.
Twitter circa 2006, they could clone the basics of it. And only because someone else already showed them what to do so they don't have to burn much time thinking very much or go through many learning iterations.
That may (or may not) have been the effect (at least within a narrow family of similar viruses), and is definitely something they market about their “mRNA platform”, but their immediately-previous mRNA vaccine work which was ongoing when they shifted to SARS-CoV-2, was specifically directed at MERS-CoV, another very similar betacoronavirus of significant public health impact (though a lot less widespread than SARS-CoV-2 has become.)
As far as I know Moderna and Biontech tried different variants of their vaccine. And to determine how well those work you have to do some animal experiments, and that is always much slower than designing and synthesizing mRNA sequences.
The mRNA vaccines were the fastest ones, and they worked better than expected. So I think there is a lot of promise in the technology, but further speedups are hard because they're in the clinical study part.
Earlier phases could have been accelerated as well. For mRNA vaccines, deleterious effects are unlikely, inefficacy is the likeliest problem. It might be possible to be challenge testing (highly informed) volunteers within a week of a novel virus being isolated.
On a similar note, national stockpiles of RT-PCR machines and reagents would allow widespread testing within the same week.
If I’m right, these indicate moral failures deeply embedded within our political and medical systems. Better luck next time.
You’d run the risk of have a non-representative sample and wrongly estimating the effectiveness of the vaccine as well as possibly missing side effects.
How would you attract volunteers for these less-safe clinical trials? Pay them money?
And you'll get volunteers. It's a rational decision for effective altruism. Say you face a 1% chance of death but a 50% chance of substantially contributing to saving a million lives. If that's technically possible, highly informed people should have the opportunity to make that choice.
I believe some of the earliest challenge testers were the developers of the drug themselves.
1. Vaccinate humans and animals and see if they create antibodies and test if they can neutralize the virus.
2. Infect animals on placebo and vaccine on purpose.
3. If it improves outcome, infect humans on the vaccine.
The old system could be run in parallel
"The OPV is less expensive and easier to administer, and can spread immunity beyond the person vaccinated, creating contact immunity. It has been the predominant vaccine used. However, under conditions of long-term vaccine virus circulation in under-vaccinated populations, mutations can reactivate the virus..."
The other point is, you have made a completely new human-transmissable virus. How do you reliably prevent it from mutating into something more dangerous?
Risky, though, because if it turns out to be less benign than we thought - or mutates in such a way as to become lethal - we've just started a second pandemic.
> Since the platform itself is pre-tested, we won’t need to do months of testing before distribution. Still, we may need to do some testing on the specific vaccine. Perhaps much of this testing can be done with computer modeling, and some with animal testing.
and
> The question ultimately comes down to risk vs benefit. We need to get over our evolved but suboptimal instinct to avoid directly causing harm preferentially over passively allowing harm to occur. In the end, the amount of harm is all that matters. In a situation like this, delivering a vaccine as quickly as possible while maintaining sufficient safety and efficacy, there is a sweet spot somewhere that minimizes disease, death, and disruption. We want that sweet spot, even it if means delivering a vaccine that has not been tested as much as we would like. It would mean accepting more risk form the vaccine in order to reduce risk from the pandemic.
Think of the crazy amount (highlight on the crazy) of opposition you have to vaccines now. Imagine if you get one vaccine with just a slightly higher amount of negative reactions, and even a few deaths that were clearly vaccine-caused, due to rushing the approval process. You will have set back public health decades.
Look at covid: its fatality rate is actually quite low, well well below 1%. If we give the vaccine to everyone, you need to have extremely low adverse reactions for it to be a net positive because we're giving it to so many people.
I feel that these types of articles that argue "We need to get over our fundamental human irrationality" are pointless, because we are, after all, human.
60 Minutes did a segment in 1979 on the failed Swing Flu vaccine that didn't build protection for most, and that left many with long term paralysis. Some of them went back to normal after a few months, both there were enough that lost motor control that they had a class action lawsuit.
The fact that all the pharma companies in this release are immune from civil liability, and the FDA is also immune from civil liability, does not bode well for confidence.
so when, for example, someone gets raped after a night out while intoxicated or dies due to alcohol overdose after joining a frat...is the socially acceptable response now "poor decision, didn't assess risk correctly."?
Everyone in society would have been better off if I had been permitted that. America could have paid me and 49 others a million dollars each and come out wayyy ahead (since direct exposure tests will yield results way faster). Then a 3 month safety protocol and we're off to the races.
But I can make that choice because I am comfortably above subsistence. If I do it, you know it's because it's a combination of bravado, bragging rights, and this money I could survive without.
But if you actually allow the market to price this, the real price for the tester is approximately $10 in sub-Saharan Africa, and we know he's on below subsistence and is really trading his body for another few days of life. We find that doing this is abhorrent.
An interesting effect that inequality prevents us from Pareto optimal actions and improving the human race as a whole.
1. Run challenge trials, but don't pay participants in money. Talk up the danger and risk, and publicize the heroism of the people who volunteer. Make a spectacle of it. If you ask for fifty heroes, is there any doubt that you'd get them?
2. Pay participants, but impose a minimum price they need to be paid in order to assuage people's squeamishness. That hypothetical guy in sub-Saharan Africa might be exploited at $10, but if he's getting paid $1,000,000 then he has practically won the lottery.
Either of these would be a big improvement over the status quo, where challenge trials aren't run at all and countless people die because of it.
Any of these are good solutions.
The normal yearly influenza vaccines are also fast for example because they are well known platforms and also the antigens repeat historically and are thus (relatively) well tested.
I guess my point is that the problem of the vector to get the antigen in contact with the immune system is orthogonal to the problem of selecting the antigen for overall cross reactivity and efficiency and the latter is still a difficult and timeconsuming problem.
A COMPUTER took two days to develop the vaccine. Think about that.
But this is a very exciting and important development. Akin to a moon landing.
How many diseases will be treatable or curable in the near future with this technology? Do any cancers have characteristics that can be used to direct our immune systems to go after them with this technology? I suspect a few might.
[1] https://www.biorxiv.org/lookup/doi/10.1101/2020.06.11.145920
Another analogy would be something like "It took X days to design Blue Origin's New Glenn".
The industry will make a lot of money out of that sure, but I have my doubts where this is going.
The virus started spreading in 2019 ...
There are also trials for therapeutics such as inhaled steroids; something doctors in certain regions have been prescribing off-label for months and claim to have very high success rates. Yet organizations like the NIH are saying they shouldn't be used until the trials/studies are done... and they've been saying that since August.
Honestly, I'd rather more effort be put into seeing if existing therapeutics can be used to reduce the effects of moderate/severe COIVD.
Let's face it. The drug companies got millions just to attempt to develop these vaccines, many of those attempts which will be failures. They don't care. They already have tax payer money from countries all around the world. This is a push to the first mRNA vaccine out, so the Gavi Health Alliance can start pushing more of them.
There is a huge money incentive we're ignoring. It's not on this particular vaccine; it's on all the future vaccines--some which have already been developed and never made it through all their trails/approved--and the billions they stand to make from them.
In another infection, your cells still get infected, but the infection is just stopped very quickly. HIV has inscription and reverse transcription enzymes in it, so it can actually glue its sequence into your DNA. It changes your DNA enough to replicate it, but not enough that your cells change their structure so your immune system can't recognize them as infected (and those changes can cause your immune system to fail over time: AIDS).
Even if your body is primed to deal with HIV infections, if the infection happens, it's already too late.
I'm not sure who antiviral drugs like PREP work, but you'd need something like that permanently in your system.
India's death rate has been much lower than the US. Part of this is because they're already doing widespread cholecalciferol roll-out.
If cholecalciferol is not on 2021's CDCs/FDA/AMA number one recommendation list for pre-Covid control, I will have considered the AMA a complete and utter failure in the united states.
Edit: Also https://www.youtube.com/watch?v=ha2mLz-Xdpg
https://www.sciencemag.org/news/2020/09/why-covid-19-more-de...
Average age in the US is 38.
This probably accounts for the difference in death rate.
> We didn’t understand early on what a major risk factor obesity was. … It’s not until more recently that we’ve realized the devastating impact of obesity, particularly in younger people,” says Anne Dixon, a physician-scientist who studies obesity and lung disease at the University of Vermont. That “may be one reason for the devastating impact of COVID-19 in the United States, where 40% of adults are obese.”
First of all it seems unlikely people in India don't get enough vitamin D, it is a lot further to the south and inside the area that should have enough sun year round.
I don't think you can compare death rates in India and USA, the healthcare and accountability is just way different. Even though it is not great for the poorest ~50% in USA, it is really not good for the poorest ~90% in India. Those numbers are made up, but meant to illustrate that real healthcare in India is mostly for the wealthy.