Coronavirus: Oxford vaccine triggers immune response | Hacker News Reader

Coronavirus: Oxford vaccine triggers immune response

bbc.co.uk

415 pointsceocoder355 comments

It seems like they tested for antibodies, but this article makes no mention of challenges to the real virus.

It's important to remember that vaccines for previous coronaviruses (SARS/MERS) had reports of generating anitbodies, but also causing immunopathic responses or immune enhancement syndrome:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335060/

https://www.pnas.org/content/117/15/8218

>Is it safe?

It's really really to early to say yes or no, and the fact that the article tries to make a claim either way, is worrying. Vaccines for new families of viruses traditionally take years or decades to develop. We still don't have vaccines for retroviruses like HIV/Herpes (and it may not be possible due to the nature of those viruses).

I've had all my vaccinations; I'm not an anti-vaxer. But I do have concerns on trying to push out any novel vaccine in less than two years without adequate testing.

Although this virus has killed many, the risk factor for it is nowhere near high enough to warrant an emergency vaccine. There are trials underway for inhaled steroids that look very promising, and there's a good chance this virus will burn out in our population long before a truly safe vaccine comes to market.

Having a viable treatment option seems much more valuable and safer than vaccinations in this particular case.

> We still don't have vaccines for retroviruses like HIV/Herpes

HIV is so fundamentally different that it doesn't make sense to include it as a comparison here.

> there's a good chance this virus will burn out in our population long before a truly safe vaccine comes to market.

The virus isn't just going to "burn out" anytime soon. 143k deaths in the US already, and we likely haven't even hit 10% of the population being infected yet.

Treatments will help pull the death rate downwards, but without a vaccine we're likely looking at multiple hundreds of thousands more deaths.

> HIV is so fundamentally different

Coronaviruses are very different. We've rarely had any this deadly before. All vaccines are different; they're not one blanket thing. Smallpox vaccines are attenuated virus (a virus that has mutated to be benign in humans; in the case of Smallpox, the first vaccine by Jenner was injecting people with Horsepox).

Most Influenza vaccines are heat treated/inactivated virus.

In all cases, vaccines try to produce antibodies and force our immune systems to develop a memory for a virus we haven't actually been exposed to. As shown in the links above, this might not work at all for coronavirus.

To some extent, the actual interactions of vaccines, are somewhat opaque. This In A Nutshell video shows a very small part of the adaptive immune system, greatly simplified:

https://www.youtube.com/watch?v=BSypUV6QUNw

> The virus isn't just going to "burn out" anytime soon

Exponential growth doesn't go on forever. It has to hit an inflection point:

https://www.youtube.com/watch?v=Kas0tIxDvrg

The more deadly a virus is, the faster it does burn out. It runs out of hosts to infect or everyone develops an immunity. SARS/MERS may have had lower outbreaks because of how much more dangerous they were.

If you graph fatalities on a logarithmic scale, you'll see we're already well past the inflection point in the US:

https://aatishb.com/covidtrends/?data=deaths

The cases are going up, but the fatalities are not, indicating there may be a lot of over-counting. Keep in mind people who test positive but die of a car wreck are counted as COVID19. All these people getting surgery after 3 months are required to get tested just for their surgery, and a positive antibody test counts as an active case, even if they're not sick or have the virus at all.

It's so bad in the UK they've stopped reporting fatality numbers due to issues with the data.

> Coronaviruses are very different. We've rarely had any this deadly before.

SARS and MERS.

> Keep in mind people who test positive but die of a car wreck are counted as COVID19.

I'd like to see evidence that this has happened, that's it's not some freak outlier, and that it has any meaningful impact on the reported death toll. Looking at excess mortality, it looks like deaths have been under-reported, if anything. It's getting tiresome to see people trotting out the anecdote about someone getting in a car wreck and being counted as a CoVID-19 death.

> Keep in mind people who test positive but die of a car wreck are counted as COVID19.

In Colorado there was lawsuit over this, because there was a case of a college age man dying of alcohol poisoning but he tested positive for Covid-19 so was counted as a Covid-19 death per CDC regulations. So the Colorado Health Department now tracks two numbers: people that died with Covid-19 and people that died because of Covid-19. As of right now the first is 1,752 deaths and the second is 1,615 deaths. Statistically it's not a huge difference, you can see the numbers here:

https://covid19.colorado.gov/data/case-data

> Statistically it's not a huge difference

8.5% isn’t significant?

These numbers aren't directly comparable. They're reported on different timescales, because determining cause of death takes longer than determining that someone who died had CoVID-19.

In the UK, there are the daily public health england tallies, which are unrelaible and include anyone who has died and tested for covid.

Then there are the stats from the ONS where they have actually verified that covid is the cause. The numbers are not very different.

I know that all vaccines are different, the thing I take issue with is using HIV as evidence that a vaccine for this virus might take decades to develop, despite all the current evidence to the contrary.

> The more deadly a virus is, the faster it does burn out. It runs out of hosts to infect or everyone develops an immunity. SARS/MERS may have had lower outbreaks because of how much more dangerous they were.

At what point is the virus going to "run out of hosts to infect" or reach a point where "everyone develops an immunity"? Everything I've read from epidemiologists seems to indicate we're a long ways away from that. We're not going to get a free pass from herd immunity anytime soon (https://covid19-projections.com/us estimates that the US is at 8.4% total infection so far), and we can't count on it just burning itself out. It's a bad combination, where it's not deadly enough to quickly burn itself out like SARS/MERS, but has a death rate higher than something like the flu, and is very transmissible.

> The cases are going up, but the fatalities are not, indicating there may be a lot of over-counting

I'm very skeptical of the over-counting claim, without evidence. And I don't think it's quite true to claim that fatalities are not going up. The 7-day rolling average of deaths in the US has been climbing since around July 5th.

> It's so bad in the UK they've stopped reporting fatality numbers due to issues with the data.

If the UK where really serious about the actual covid death toll they should address the huge discrepancy between the reported covid deaths and the excess mortality during the pandemic. Not a good look for the UK.

Nearly all countries have a discrepancy there, if you can find the figures. You can find some for the US here, though not a single, unified figure - https://www.cdc.gov/nchs/nvss/vsrr/covid19/excess_deaths.htm

Interestingly enough the weekly UK excess death figures went negative at the end of June, meaning less people died that week than in previous years. Presumably this is due to the huge number of deaths in care homes in previous weeks.

The UK got a 65k people over mortality over the last months, for 45k official COVID-19 victims. So if anything the UK is undercounting COVID-19 victims.

See https://www.ft.com/content/a26fbf7e-48f8-11ea-aeb3-955839e06... for excess mortality in a few countries. Many victims are not counted.

Nearly all countries are like this AFAICT the US coronavirus deaths figure is around 140k, but the full excess death figure is somewhere around 170k (it's difficult to find good figures, some are here - https://www.cdc.gov/nchs/nvss/vsrr/covid19/excess_deaths.htm )

There are already plenty of stories of empty ERs - people with chest and abdominal pain aren’t coming in.

You cant lump all excess mortality into the Covid bucket.

In many countries, e.g. France, excess mortality and COVID-19 victims match very closely. Sure there may have been more untreated cardiovascular events, but there were also a lot less accidents and it seems it evened out...

>It's so bad in the UK they've stopped reporting fatality numbers due to issues with the data.

They were reported again today. They weren't stopped because they were bad but because there were descrepencies between the counting for each nation of the UK.

There is more to the immune system than antibody production. A lot of the focus is on antibody production, because it is easy to measure. T Cell responses, for instance, can be very durable for coronaviruses--for instance, people who recovered from SARS in 2003 still have a T Cell response when exposed to a protein from that virus (https://blogs.sciencemag.org/pipeline/archives/2020/07/15/ne...).

The Oxford/AZ (https://blogs.sciencemag.org/pipeline/archives/2020/07/20/ne...) and the Pfizer team (https://blogs.sciencemag.org/pipeline/archives/2020/07/20/mo...) have both reported T Cell responses induced by their vaccines.

Robus T Cell responses should be protective, but we are still mapping that out for SARS-CoV-2 (https://blogs.sciencemag.org/pipeline/archives/2020/07/15/ne...).

> Keep in mind people who test positive but die of a car wreck are counted as COVID19.

This simply isn't true.

> Vaccines for new families of viruses traditionally take years or decades to develop.

Traditionally many things used to take an awful lot longer than it does now (e.g. gene sequencing). Technology advances.

Also, this vaccine was based on an earlier one developed for MERS so they weren't starting from scratch.

> We still don't have vaccines for retroviruses like HIV/Herpes

That's completely irrelevant because they're very different viruses. Vaccination for a coronavirus should be a lot easier.

> But I do have concerns on trying to push out any novel vaccine in less than two years without adequate testing

It is undergoing extensive testing. Tens of thousands of people are currently being given the vaccine. The timeline is not really relevant; what counts is the testing that is carried out.

I'm sure the Oxford University team has given proper consideration to safety.

> That's completely irrelevant because they're very different viruses. Vaccination for a coronavirus should be a lot easier [than for retroviruses like HIV/Herpes].

Why is that? Uneducated guess: because of the rapid mutations of those viruses and the way they go dormant and hide?

There's no known natural immunity for HIV. Vaccines work by triggering an immune response, but if there isn't an immune response that works, a vaccine won't be effective.

It's a bit more complicated than that. HIV does generate antibodies. Your body does fight HIV and remove it from your system. (The rapid test for HIV tests for those antibodies. If you test positive, you still need a viral load test).

The trouble with HIV is during the infection process, it has an reverse transcriptase enzyme and an integrase enzyme, the two of which allow it to build DNA sequences and alter the host DNA. It permanently alters the host, allowing the virus to continue reproducing.

There are some people for which this modification does nothing (long term non-progressives), but the for the majority of human beings, their immune system collapses within a few months or years (without treatment).

Thanks for the clarification. After I sent that message I was thinking that my understanding was probably way too simple.

> Traditionally many things used to take an awful lot longer than it does now (e.g. gene sequencing). Technology advances.

This may be true with chips and gene sequencing, but is not true for vaccines. The waiting period for vaccines is mainly for safety and efficacy, not waiting on technology like the other two.

We may become more certain some vaccines are safer given intrinsic properties, but that probably won't result in any statistically noticeable difference because it's very hard to tell how a vaccine will behave without actually trying it as far as I understand it.

I agree. There are so many variables whose interaction is influenced by each individual's unique immune expression, that we need to measure more of those variables for everyone to start identifying common patterns. I would hope that each vaccine volunteer has a minimum amount of testing (>= https://science.sciencemag.org/content/early/2020/07/15/scie...) before and after each vaccine dose. It would also be very beneficial to measure their HLA genetic SNPs (see GSK's MERS vaccine induced narcolepsy in 2009). Transparency and increased measurement of immune data will help improve and/or customize vaccines so that they are effective and safe.

I find it disturbing that a post like this gets downvoted. You've said nothing off-the-wall here. A downvote is not a rebuttal or an unceremonious verdict on the validity of your thoughts. Seriously not a fan of downvotes for this reason...just a blight on public discourse.

To get back on topic, I'd really like someone to explain in some way that makes sense to me (because I've heard none--maybe I'm just incorrigible, thought) how a mandatory vaccine is justifiable for a disease with an extremely high survival rate that elderly people who've already exceeded the average life expectancy are disproportionately at risk for.

You're only looking at the death rate. Take a look at the hospitalization rate (~20% for all age groups) and the amount of resources it takes to just keep one person alive. ICUs and hospital staffs are stretched to the brink. People indeed are surviving, but at great expense, and the hospitals have said they can't keep this up much longer. In Houston, TX there was a doctor who had worked 117 days straight and had to be relieved by Army Medical personnel (https://abc13.com/health/85-soldiers-arriving-to-help-treat-...). There's just not enough ICU beds and medical staff to go around. Once we run out of hospital resources, the death rate will jump 5-10x. If that happens, you're talking 20+ million deaths in the U.S., on pace with the 1918 pandemic if not worse. If you think the economy is bad now, wait til 20+ million people suddenly aren't shopping anymore.

Lastly, consider all of the people who have "recovered" but haven't really recovered, this includes the young 20-30 yr old crowds. There's hundreds of support groups now focused on post-corona-syndrome where people are 100+ days into the recovery but still have symptoms, including brain damage, neurological issues, strokes, kidney failures, shortness of breath, etc. It seems as if the older people are dying, and the younger patients are surviving, but with long-term damage.

Another way of putting is that lockdowns won’t end with a vaccine, they’ll end if there was enough hospital capacity for congressmen and rich people.

Why not build more hospitals?

Because it takes years, and even longer to ramp up the capacity fo medical and nursing schools to staff all of them. Because having ICU beds doesn’t prevent deaths, only reduce them, so a large percentage of the population will still die. Because a vaccine is cheaper and better.

It takes a long time to build doctors and nurses.

Can you provide links regarding post covid symptoms

I would love to see the hundreds of support groups. This is an urban myth about the long term damage.

I can agree that there is very very limited research on the long term impacts (since this is so new) - but thousands of people are struggling to recover from this - often people who were not dangerously ill with covid to start with. The 'long haulers' covid group my wife is on has had people uncovering heart scarring, nerve damage and other issues when they have been lucky enough to find a supportive doctor. Most are currently not seeing specialists as they cannot get referrals or the waiting lists are long.

I have no idea if there are 'hundreds' of support groups - my wife is on a couple that largest of which has approaching 10000 members. Every time I post about her progress to Facebook I find more friends or friends of friends who know of people that haven't yet made a connection to a group of or who are only newly considering themselves 'long term ill'. Given what we know now, and the large wave of cases, there are many more people who will be suffering long term symptoms in the months to come.

I really hope there is no long term damage - but I think you have to admit it is too early to say that with any confidence. The impacts or Ebola and SARs are well understood, so I'm not sure why people find it so hard to believe in the issues covid causes.

Article: ‘I feel helpless’: three people on their grueling Covid-19 recoveries

https://www.theguardian.com/us-news/2020/jul/20/coronavirus-...

‘I feel helpless’: three people on their grueling Covid-19 recoveries

https://www.theguardian.com/us-news/2020/jul/20/coronavirus-...

Hopefully this will trigger people to take CFS seriously, resulting from COVID or otherwise.

I really hope so. My wife is currently about 120 days into her post covid issues. Covid itself wasn't too bad for her but the symptoms she's had since it went have been far far worse, and for a long time the doctors just tried to fob her off. She's a normally active and healthy person who right now can't play with or even read a book to our kids. She cannot do anything at all which is incredibly depressing for her. That said lately she's felt some very gradual improvement, but from the group she's on she knows not to push it - it might be 4 or more months until things are more normal - who knows.

I'm sorry to hear about your wife, that sounds awful. I also had post COVID issues, I couldn't get out of bed for a month and was very low energy for three. The doctors did nothing for me but luckily I have now recovered on my own. I tried eating lots of vegetables and lean meat (as per official nutritional recommendations) and it made me worse. I remember building up the strength every day just to chop the vegetables, eat and go back to bed. When I told my Doctor they dismissed it. I recovered on a diet of fatty red meat (1-2lb per day), milk, cream, eggs and fruit. The diet could be a timing coincidence but on the other hand maybe my Grandmother was on to something feeding me beef stew when I was ill as a kid.

There will be a law suit over how CFS patients are currently treated: https://www.virology.ws/2020/07/15/trial-by-error-nice-on-ex...

You might want to follow it. I will be.

Thanks, very interesting.

She's been avoiding fats has she's had both reflux and is trying to eat an anti inflammatory diet. Will see if she fancies a change of tactics.

I also get acid reflux with excessive fat. The key is to eat it with enough protein and carbohydrate in the same sitting and not to lie down after eating. Fat also makes protein easier to digest and of course protein is key to building yourself back up after fatigue and inability to exercise. I would avoid some fats such as sunflower oil or vegetable oils (except olive oil) which are inflammatory. Coconut oil is good because it contains lauric acid which is anti inflammatory. I also avoided starchy carbs which tended to knock me out and eat them only in small amounts paired with easy to digest sugar such as fruit juice. Simple sugars from fruit are not inflammatory despite bad press. It's essential to keep blood sugar up because if you are already fatigued its easy to get hypoglycemia. Consuming fruit juice before meals considerably reduced my post meal fatigue. I went from unable to stand up after eating to feeling better after eating.

Current dietary recommendations are the same for everyone and implicitly assume you are slightly overweight and sedentary, consuming a caloric excess. In America many people die of obesity related diseases and dietary recommendations based on the epidemiological data reflect this. When you are weak and frail in bed it amazes me that Doctors still recommend the same diet based on this data. It took me so long to realise why salads and lean protein were making things worse. I needed more calories! More protein, fat, sugar, all the 'bad' stuff to build myself back up. Of course I'm assuming your wife has lost weight while ill as I did and this doesn't apply otherwise.

Call this anecdata, but here's part of a weekly update from a friend, ~45yo male, and his post-covid struggle:

“I am trying to keep my weekly covid journal going. We are still in about month 4 post infection.

Some good news is my breathing is slightly better. When everything is bad all small improvements are noticed. Could be from OTC blood thinners or that my lungs are getting better. Still have a super hard time breathing, but it is just a bit less difficult. I am also in a near constant state of fatigue, but am unable to easily sleep because of the other symptoms. My MRI revealed no vessel or tissue damage to my brain from the stroke, so maybe not a stroke or just not sever enough to cause damage. It did reveal a small cyst on the brain, but that seems to be common in covid recovery patients and no one knows why yet. The stroke like symptoms maybe related more to the hypoxia and not a stroke. I see a nuerologist this week and they will decide the next steps. The symptoms are still there though - dizzy, off balance, difficulty with sentence formation, difficulty getting facts from brain to mouth or hands to type, memory issues. Super frustrating.

My cardiologist has sent me for a new test that takes highly detailed xrays of the heart. After deciding what/how much damage is in my heart valve they will decide the next course of treatment. Other than the damage, he says my heart is healthy.

Passed my breathing test, so capacity is OK and volume/flow is good. The worry and science now is saying the breathing troubles I am experiencing may be related to tons of micro-clots in the lungs. They have been discovering these during autopsy of covid deceased (hopefully deceased) patients. My next steps of healthcare relate to all these specialist working together. I can not start blood thinners for my stroke prevention until I am sure I will not need heart surgery. I can not go down the path of heart surgery until there were sure I can both breath effectively and not have a stroke. I am fortunate for good doctors that are at the front edge of treatment for covid patients. Some of the care is "we just have to wait", that is OK but frustrating because in the mean time I am at the mercy of me neighbors to do the right things and not re-infect me and I have to stay socially isolated. The latest science is showing that antibodies are not retained in over 85-90% of cases of infection, meaning there is no natural immunity. This includes me, I showed no antibody after 10 weeks. This is worrisome since I am sure I would NOT be able to survive another round, since I barely survived the first one. "

Thank you for sharing this. The non-fatal COVID experiences have been grossly underreported, IMO, given how prevalent and severe they are.

The thought of dealing with permanent lung and brain damage for the rest of my life is pretty terrifying, and seems disturbingly common even in age groups with a low fatality rate.

Take a look at the hospitalization rate (~20% for all age groups)

0.66% of NYC residents have been hospitalized (https://www1.nyc.gov/site/doh/covid/covid-19-data.page). Antibody tests show that at least 20% of NYC was infected, and that's likely an underestimate (antibodies take weeks to show up and may soon drop to undetectable levels). So the hospitalization rate is at most around 3%.

Once we run out of hospital resources, the death rate will jump 5-10x. If that happens, you're talking 20+ million deaths in the U.S

That's just not going to happen. There was essentially uncontrolled spread in NYC, and the hospitals were strained but not overwhelmed. The hospitalization and death rates in currently hard-hit states are much lower than peak NYC, and may already be at a plateau.

It seems as if the older people are dying, and the younger patients are surviving, but with long-term damage.

This is a real concern, but I'd like data rather than anecdotes.

https://gis.cdc.gov/grasp/COVIDNet/COVID19_5.html

This shows clear counter evidence to the claim of hospitalization rate being ~20% for all age groups. This CDC data shows a steep increase in the hospitalization rate as age increases.

Not sure where you are getting your information.

Don't worry about early downvotes too much. It doesn't show grey based on percentage of downvotes, it shows grey when it goes below 1 point. So if one guy votes it down soon after it's commented, it goes grey. Others usually come along to correct it.

What does "extremely high survival rate" mean? Around 0.5% of people who get this virus die. For a highly transmissible virus, that's incredibly scary. It means that left unchecked, around a million people will die in the US alone. That's a massive public health issue. Requiring people to accept a safe vaccine is completely reasonable and proportionate.

> elderly people who've already exceeded the average life expectancy

Letting hundreds of thousands of people (in the US alone) with easily a decade left to live die of a preventable disease is not ethical. What you're writing sounds extremely callous.

Not all people are going to get infected. One result of the Heinsberg study in Germany was that living together with an infected person only resulted in ~43% chance of infection. With more people living together the chance even went down to 18%.

Also the numbers of Covid-19 are mainly following a Gompertz model - like a seasonal virus that starts big and then fizzles. The high R-Values people talked about in the beginning aren't a real thing.

Michael Levitt in the beginning already calculated the outbreak in China perfectly. He made good Videos to explain the basic math. https://www.youtube.com/watch?v=hCgPf1SuPNY https://www.youtube.com/watch?v=Uw2ZTaiN97k https://www.youtube.com/watch?v=8aHrx68IT7o

Maybe take a look at some f'/f in a logchart... It's easy to do - just look at death per day/total.

Some countries are easy to model (e.g. Germany) - US is difficult with policies and outbreaks coming from different sides, ... - but some states are not that difficult to understand)

> One result of the Heinsberg study in Germany was that living together with an infected person only resulted in ~43% chance of infection.

If you're living in an area where the virus is circulating, you are likely to eventually be exposed many times. Getting lucky once is not enough.

> like a seasonal virus that starts big and then fizzles. The high R-Values people talked about in the beginning aren't a real thing.

They're absolutely real. Seasonal viruses come back every year, so if this is like the flu, then we have to worry about another major wave in the fall.

Epidemics can slow down for two reasons:

* Increasing immunity. Herd immunity is a long way off in most places in the world. Even places that had some of the worst outbreaks, like NY city, have only had ~20% infection rates.

* People change their behavior, causing R to decrease. Social distancing, mask-wearing, enforced lockdowns, quarantining of infected people, quarantining of exposed people - these can all lead to slower spread of the virus.

> Michael Levitt in the beginning already calculated the outbreak in China perfectly.

The epidemic was suppressed in China through a massive government and societal response. It would have been far worse if there had been no reaction. Because of the reaction, most of the country was spared the experience that Wuhan had. If all containment measures were to end today, the epidemic would flare up again and millions of people would die over the next several months.

The only way to permanently dampen the outbreak is to achieve a high level of immunity. That can either be through a vaccine, in which case almost nobody will die, or it can be through herd immunity, in which case many millions of people will die worldwide.

> If you're living in an area where the virus is circulating, you are likely to eventually be exposed many times. Getting lucky once is not enough.

It's not about how often you're exposed to the virus but about how long and how intensely. Living with someone is pretty much the worst case.

Where did you get your 0.5% from?

According to Johns Hopkins in the UK more than 15% of those who get it die, for the US it is 3.7%. The link says those numbers were updated this morning so they are current.

https://coronavirus.jhu.edu/data/mortality

That percentage being higher only helps that guy's argument though

I don't mind if it does or it doesn't. I haven't seen a source for the 0.5%, everything I had seen had higher numbers, so I thought I would ask. But remember kids, not knowing, being curious, and asking questions is frowned upon on HN.

15% of those who test positive die. Most infected people are unlikely to be tested in the UK unless they are admitted to hospital.

There is “case fatality rate” and there is “infected fatality rate”. The CDC has estimated the IFR, but the value varies based on assumptions. https://www.google.com/amp/s/amp.usatoday.com/amp/5269331002

How can you still push lies like that? The mortality rate is nowhere near 15%. Rather within 1%. Case fatality ratio is a ratio to confirmed cases, which in a country where people have been told to stay at home if they are sick and not get tested for most of the peak of the pandemic is a massive underestimation of “people who get it”. Spreading false information like that is irresponsible.

Saying they're lying is kinda optimistic. Plenty of people don't know the difference.

Come on, we are not in March.

That makes it even sadder. I'm sure everyone had the choice to learn the actual level of danger (to the extent it's known) but believing in a higher mortality rate makes it easier to panic. And if you don't panic, you're seen as irresponsible and/or hating humanity.

I didn't see a reference for your number so I went looking for data, that is what I found. Hence I asked where your data came from.

>How can you still push lies like that?

Still? that is the first time I have posted that, so I not sure what you mean by still.

No I mean we are 6 months into this pandemic. I can understand people making this mistake in Feb or March. But by now there is no excuse. There is a lot of FUD being pushed by people on HN. In your case it may be an honest mistake but I am getting tired of people quoting numbers that are alarmist and just false.

> how a mandatory vaccine is justifiable

Where did the "mandatory" come from?

If a vaccine is promising but unproven, the sensible thing is to make it available to those who want to take the risk.

I agree that for a mandatory vaccine, you want a high level of certainty.

And the odds of a vaccine being literally "mandatory" in democratic countries are essentially nil. No one is breaking down doors and holding families down to get their vaccines.

(What is possible is that schools and even workplaces require proof of vaccination once one is widely available if there is still a widespread virus risk. That could arguably be fairly coercive but it's important to distinguish from being "mandatory.")

Why is it important to distinguish things required by most schools and workplaces from literally mandatory ones?

While a widespread vaccine requirement to be physically present in places that will be important to many is a fairly big stick, it's still a far cry from vaccinating people by force. Certainly I might well favor the former but would be horrified by the latter.

That is a very subtle and impractical distinction, similar to making an argument that you are merely being pedantic instead of deceptive :/.

It isn't since working is practically mandatory in our society and going to school is even legally mandatory in many jurisdictions.

I also think many people in high risk categories (age, preexisting health issues, essential or health care workers, teachers, other professions involving crowds and risk) will be very eager to vaccinate. It doesn't have to be mandatory for high demand and high use.

> Although this virus has killed many, the risk factor for it is nowhere near high enough to warrant an emergency vaccine.

> there's a good chance this virus will burn out in our population long before a truly safe vaccine comes to market.

That's the reason for the down-votes, and for once I think it's actually appropriate. The rest of the post was fine, but those are some wildly controversial - if not completely incorrect and reckless - assumptions to make. For one, it's too early to make definitive statements like these. As far as I know, public health experts have made it well known the risk factor is enormously high and so it's worth being proactive than reactive. Clearly there's an enormous amount of effort in getting an emergency vaccine out and I would think for good reason. Nobody on HN is qualified to make statements on this, especially if they're not actively studying this disease or they're not a public health expert.

>We still don't have vaccines for retroviruses like HIV/Herpes

Good thing this isn't a retrovirus.

>But I do have concerns on trying to push out any novel vaccine in less than two years without adequate testing.

They started on this vaccine about 9 years ago, originally for the first SARS/MERS. They just gave it to 1,077 people and all 100% produced the desired effect, and the worst symptom reported was fatigue/headache that resolved on its own within 24 hours, or sooner if taken Tylenol/paracetamol. We're losing ~150,000 people worldwide EVERY MONTH to this virus, how many more months/deaths should we wait until we're sufficiently satisfied that it's safe?

I feel like your reply is a bit dismissive of a very real problem.

I don't understand anything about biology/vaccines or anything else relevant - but there have been several stories in history of medicine that was thought to have no side effect, that ended up being taken off the shelves because it was more dangerous than first thought.

If we're going to inject a few hundred million (if not a few billion) people with something, we need to be really really sure it won't harm then, and considering the fact that COVID has a mortality rate of 1%-ish, the vaccine has a huge burden of proof.

And more importantly to anything that I say as a non-expert - most experts on these issues seem to think you need at least ~10 months of human trials, if not more.

> I don't understand anything about biology/vaccines or anything else relevant - but there have been several stories in history of medicine that was thought to have no side effect, that ended up being taken off the shelves because it was more dangerous than first thought.

That’s the entire point of a Phase one trial. Vaccine studies may be a little different in their numbering, but the intent of a phase one trial is to figure out if the treatment is safe. The effectiveness is a separate question.

https://www.cdc.gov/vaccines/parents/infographics/journey-of...

Yes. It worked out so well the last pandemic (2009 swine flu). The vaccine had no side effects in the trials (healthy people 20-55), but caused narcolepsy for children, leaving them disabled for life. This affected over 500 children in Sweden and Finland, and an unknown number across the world.

https://en.m.wikipedia.org/wiki/Pandemrix

No one knows if this vaccine has similar side effects, what if it causes elevated risk of lung cancer?

Drugs are comparatively safer, given the time frame of the pandemic.

What about long-term side effects?

> They just gave it to 1,077 people

That's a good start. But for example, how many of them were pregnant, and at what stages? I would guess none. That would be the most famous way to get this wrong.

I hope they are thinking hard about the optimal roll-out strategy, though. It should surely be faster than in normal times. It might well be that you should run very very large not-quite-trials as the first stage of general distribution, and watch their evidence in real-time.

Right, we should just test on nobody instead.

Of course we're gonna test this on the healthiest, least-likely-to-accidentally-die humans, what's the point?

They explicitly did a pregnancy test on everyone who can be pregnant to preclude the possibility, just in case.

But then we have no idea how those vaccines will work in the real world where, when we need N% immunity achievement for herd immunity, a >N% of the population is not considered healthy (and also haven't been proven safe for). There have definitely been cases in which pregnancy is excluded from studies to prove safety with horrible consequences to pregnant people and their children.

It seems entirely logical to me to first test on healthy young people. It's a big step forward from mice! You might learn a lot.

But there are quite a few more steps from there to treating the population.

Are you aware that rushed vaccines for pandemics have caused serious side effects that were not discovered until too late? This is not a theoretical concern. A study of 1000 people for 2 months is not nearly enough to detect the kinds of issues that have occurred in the past, let alone novel issues.

We need to ensure that the vaccine is extraordinarily safe. "But it saves more people than it kills" is not an argument people accept, unfortunately. If this vaccine kills anyone, the antivax fallout could be worse in the long run than just letting the virus run its course.

Good thing there are more studies after this...

Come on now, we gotta start somewhere

>>We're losing ~150,000 people worldwide EVERY MONTH to this virus, how many more months/deaths should we wait until we're sufficiently satisfied that it's safe?

Before vaccinating 7 billion people with a vaccine done in a year we should think at least twice, Darwin Award in global scale and all. Let them vaccinate 80+ year olds or people with one foot already in the grave, but be very careful before doing it in a massive scale.

I agree with your response, it's a logical concern.

However we're going to try dozens of vaccines on probably 500k-1m people in total globally before deploying them in an increasingly broad way. The next stage of the Pfizer-BioNTech trial is going to be 30,000 in July/August.

It's easy to make decision for other peoples lives without consequences for yourself.

I'd just add that nearly 20% of participants experienced a fever of over 100F after the vaccine, and about half felt feverish. Though, like you say, these numbers were reduced for participants that took Tylenol.

So less than 1 per 1,000 would die or suffer other damages from the vaccine. Apply this to 300M and you get 300K people.

> We're losing ~150,000 people worldwide EVERY MONTH to this virus,

For context: That is 0.0002% of the world's population.

0.0002% of a very large number like 7 Billion is still a large number and worth worrying about. Also the number is per month.

per capita numbers are useful context but sometimes the total number is also important context that is worth worrying about. In this case a tiny percentage of a very large number results in a large enough number to cause concern.

The absolute number of cases is large, but so is the collateral damage. Both scale with the population so the trade-off doesn't depend on any absolute numbers and citing them is simply misleading.

0.0002% per month is still just 0.0024% per year. Don't forget that more than 1% of the population die each year to begin with.

Where do you draw the line between 'vaccine' and some other, similar but distinct technology?

For me, the things being developed are not 'vaccines' but are a different thing entirely with a similar intended purpose.

Some balance needs to be struck. In addition to the virus being harmful to health, the mitigation measures in place to reduce spread are highly disruptive to society.

I don't think we can wait until the risk is zero, after all the risk of allowing the virus to continue is far from zero. You talk about unknowns, we don't know the long-term impact of the disease either. Damage to the heart and lungs, oxygen deprivation of the brain, the impact extends beyond a boolean live or die.

> Although this virus has killed many, the risk factor for it is nowhere near high enough to warrant an emergency vaccine.

There might be a benefit in pushing it out to over 75s who are at severe risk from the virus (IFR 19%), or even over 65s (3%). Agree that it's not worth the risk of a barely understood vaccine on kids.

> Although this virus has killed many, the risk factor for it is nowhere near high enough to warrant an emergency vaccine. There are trials underway for inhaled steroids that look very promising, and there's a good chance this virus will burn out in our population long before a truly safe vaccine comes to market.

I think your perception of the numbers are a little off here. In the UK, we were loosing 1100 people a day entirely through covid (https://coronavirus.data.gov.uk/) That was most from a few hot spots like london. (less than 10% of the population.) We were very close to overwhelming hospitals. when a hospital system is overwhelmed you get a very large spike in deaths, because stuff that's treatable isn't treated

without lockdown, those deaths would have grown exponentially. Something like 200-400k preventable deaths.

so, if we want to get out of lockdown, we need to have something to reduce the spread of the virus. One way is heard immunity (thats what the US is doing, and its not going very well) another is vaccine.

Now, given the UK example, if the vaccine causes 10 deaths, and 1000 severe reactions(ie hospitalised) thats still better than the 200k deaths and close to a million cases with complications

Deaths arn't the whole picture, its the people that recover with life altering injuries as well.

The WHO says there is only one worse thing than a bad pandemic, and that's a bad vaccine. Because not everybody is exposed to the pandemic, but in principle everyone is exposed to the vaccine.

That doesn't counter your point, but we'll need up to phase 3, to have enough coverage to make sure your statistics hold. But indeed, the risk seems to be balanced against 5 years waiting for any long term symptoms to show.

When did the WHO say that? I’m not disagreeing, just have not seen them talk about it like this.

It seems like there's a real chance everyone will be exposed to this pandemic sooner or later. My take is calculate the risks and act accordingly. Arguing moral priors first and statistics second is best reserved for when people aren't already dying in droves.

In the link:

>COVID-19 associated UK deaths

>Deaths of people who have had a positive test result

These are people who died who tested positive for the the virus not people who died as a result of having the virus. Not very useful numbers since the virus spreads in hospitals.

It's actually even more useless than that. The wording has to be taken entirely literally: in the last few days it was discovered that PHE was reporting a COVID death as anyone who ever tested positive and who has subsequently died. Not of COVID. Not even with COVID. Someone who has ever had it, and then died any time later for any reason at all.

Under this definition COVID-19 is a terminal disease from which nobody ever recovers. If it hadn't been noticed, the English death toll would eventually have matched the case count.

Matt Hancock was apparently furious when he found out, now a review of PHE has been triggered as they've been serving the UK with bogus stats for months. Notethe coviddata site says PHE wasn't even deduplicating tests until 2nd July. So "case count" before then was also misleading. 30,000 positive cases vanished overnight and that assumes they did the deduplication correctly, but the government is so bad at data handling that at this point it's unclear if any stats can be trusted.

This stuff is really important and it's clear a lot of people on HN are in denial about it, because each time it gets brought up a torrent of downvotes follows. The COVID stats are wrong. They're not even just useless, they're actively misleading. They lead to beliefs like this one:

In the UK, we were loosing 1100 people a day entirely through covid

which is not true and has never been true. It's a belief based on assuming the stats are measuring what actually matters/what people want to know. In reality the stats are measuring what's easy to measure. It leads to huge over-reaction to what is in reality an extremely mild virus.

There are two sets of stats here, one from Public health england (PHE) and one from the Office for National Statistics(ONS).

I am referencing the ONS when I say 1100 people a day, why? because the ONS stats can be compared to many years previous. PHE ones are collected by some consultancy company and are trash.

The average daily death rate is found here: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsde...

> In reality the stats are measuring what's easy to measure. It leads to huge over-reaction to what is in reality an extremely mild virus.

The stats are measuring how many deaths are occurring above the normal average death rate for that period. _something_ caused an extra 1100 deaths a day.

Sure you can say covid is a _very_ mild virus. It might be for some, but out of my friends that have had it (as in tested positive) 1 desaturated to 88% every night. 1 had a fever for 14 days(as in bedbound) 3 had a week long fever, 5 were asymptomatic 3 had epic shits for a weeks. All of these people are < 40. of the people that were > 40 and tested positive, all 3 died. However that's because at the time they were only testing inpatients.

So, with the greatest of respect, you can take your "mild virus" and "its really not 1100 extra deaths a day" and shove it up your arse.

The source you cited is https://coronavirus.data.gov.uk/ which isn't reporting excess mortality, that site reports data from PHE and other regional bodies. As you know, those values are wrong, which is why they're now labelled as "COVID associated deaths", a label which speaks to the meaninglessness of the values.

Excess deaths is an entirely different statistic. We can assume total mortality is correct, but that says nothing about what causes it. For example, many excess deaths are clearly not caused by COVID because COVID isn't mentioned on the death certificate, but rather some other problem, even with the ultra-lax reporting and suddenly changed death certificate standards that the UK has introduced.

In reality lock down has caused some deaths. The virus has caused some - or slightly accelerated some, it's not really clear how much life-years reduction has really taken place given the absolutely on-average mortality profile.

I'm very sorry to hear about your friends, but bear in mind "epic shits" aren't even a recognised symptom of COVID. It's a respiratory disease. There's a lot of conflation going on where people are reporting things that aren't COVID as if it was some new but hitherto unknown side effect of the virus. In reality, other kinds of illness didn't stop because a new virus turned up and people can still get sick with the flu or many other diseases - as they do every year - even though COVID is more well known by this point.

> "epic shits" aren't even a recognised symptom of COVID.

http://med.stanford.edu/news/all-news/2020/04/stomach-compla...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172493/

And thats just two, there are many more. Bear in mind they were _all_ covid positive. It wasn't someone saying "I had the snuffles". Lab confirmed covid cases. They are also medical, either nurses or doctors.

> In reality lock down has caused some deaths. The virus has caused some - or slightly accelerated some, it's not really clear how much life-years reduction has really taken place given the absolutely on-average mortality profile.

excess mortality in april was ~880(with smoothing) people a day. but sure, its all just a conspiracy.

Given that the normal causes of excess death have been significantly truncated: driving, drinking and sports, its fairly reasonable to assume that standard causes of death have dropped. We can expect significant spike in deaths from chronic conditions such as cancer, diabetes and copd, but that takes time.

> ultra-lax reporting and suddenly changed death certificate standards that the UK has introduced.

https://assets.publishing.service.gov.uk/government/uploads/...

actually its been tightened up, and been told to be more specific. Normally an old person dying in a home is put down to "old age", or, if they fall down the stairs: "terminal event" (falls are a massive killer) before you start talking about attending doctors, none of that happens in practice. Its whoever needs the ash cash that certifies the death.(it depends on the consultant. I know of one who managed to buy a porche with the ash cash. Although I think the payments have stopped now) Or if its outside hospital, who ever answers the phone.

Look, I'm never going to change your mind, but just look at those stats. Something caused a huge spike. That spike started dropping before lockdown ended. That looks like a standard epidemic curve to me. I don't see how it can be reasonably read differently

Given that the normal causes of excess death have been significantly truncated: driving, drinking and sports, its fairly reasonable to assume that standard causes of death have dropped

Gosh, where did you get this idea from? Is this a new talking point from somewhere?

Taking the UK again as an example, road deaths are rare and stable at about 1700 per year or about 32 per week:

https://www.gov.uk/government/statistics/reported-road-casua...

Overall weekly deaths are 10,000 or so (outside of spike times). Even if the roads became totally empty tomorrow you wouldn't be able to see the difference, it'd be lost in the noise. And obviously lockdown doesn't lead to empty roads: people must still drive to deliver goods, engage in urgent business and so on, so reduction in weekly deaths due to less driving would in reality be less than 32.

As for drink - do you really think people drink less when locked up on their own for months on end? They don't, they drink far more:

https://www.cambridge-news.co.uk/news/uk-world-news/bored-br...

Finally, deaths due to sport?! In an average year in the UK between 15-25 people "die accidentally in athletic/sporting areas" according to the ONS. Deaths due to sport aren't relevant on the scales we're talking about.

Look, I'm never going to change your mind, but just look at those stats. Something caused a huge spike

I am looking at the stats. That's why I consider COVID to be mass hysteria.

Yes, there's a spike in some countries. It's not in any way describable as huge. UK spike matches the famous plague years of 1998/1999/2000. I don't remember any particular special disease in those years:

https://swprs.files.wordpress.com/2020/06/uk-flu-comparison....

In other countries like Switzerland literally nothing happened different to previous years:

https://swprs.files.wordpress.com/2020/07/schweiz-todesfaell...

Staggeringly, in Germany this supposedly deadly disease killed nobody at all when measured using excess deaths:

https://swprs.files.wordpress.com/2020/06/sterbefallzahlen-d...

Yet according to the official stats 10,000 people died of COVID. Clearly this claim can't be true. Where are all these excess deaths?

What's happening here is a highly infectious but virtually harmless virus has been labelling an ever increasing segment of the population as COVID positive. A tiny number of these people really do get hurt by the virus, but that's not important in the grand scheme of things: apparently even the common cold can kill 8% of the elderly. With basically any virus, and especially flu, you can get alarming stories of battles with death by people who were apparently healthy - just search for them and you'll find them. It doesn't by itself mean the virus is dangerous, which is always a relative term.

What happens if you randomly label a huge and ever-increasing section of the population, then measure their health? You get "COVID associated deaths" (which means nothing, it's just a statistical artifact) and you get an ever-widening array of "associated symptoms", because you're measuring normal health activity but re-assigning the cause. So I admit defeat on the "epic shits" point - I should know by now not to say COVID is a respiratory disease and thus can't cause $RANDOM_SYMPTOM, because public health has lost its mind and is publishing papers on random correlations all over the place. The fact that correlation doesn't imply causation has been totally lost.

How can you convert a not very dangerous virus into an excess death spike? Well, it'd cause a small spike by itself anyway, but if you want to make it bigger doing things that increase the spread of every virus sounds good to me: things like flushing all the sick people out of hospitals into care homes, creating panic in said care homes that leads to abandonment (https://www.bbc.com/news/world-europe-52014023), locking people indoors where they're coughing all over each other, putting people into depressions etc.

> If it hadn't been noticed, the English death toll would eventually have matched the case count.

In about 60 years or so.

>> In the UK, we were loosing 1100 people a day entirely through covid

> which is not true and has never been true.

Excess death stats (all cause deaths over and above the average for the time of year) are available[1] and peak at 12000 in a week or about 1700 a day. I'd say you deserve your downvotes in this case.

[1] https://www.reddit.com/r/dataisbeautiful/comments/htgq14/oc_...

The inability to use data is maddening.

Excess deaths is not the same thing as "deaths caused by COVID". This conflation relies on the assumption that you can virtually empty hospitals out and have no effect on mortality at all, which is absurd. What are all those surgeons doing, exactly?

If COVID is so deadly, why do some countries show no difference in excess deaths vs previous years?

> Excess deaths is not the same thing as "deaths caused by COVID". This conflation relies on the assumption that you can virtually empty hospitals out and have no effect on mortality at all, which is absurd.

I know that excess deaths aren't the same as deaths caused by COVID. The idea that you can lockdown in week 13 and have 12,000 excess deaths per week 3 weeks later because hospitals were "virtually empty" also seems absurd. Emergency healthcare remained available and the messaging was that people should still go to hospital if they were ill. I do expect deaths because routine healthcare was limited during lockdown, including people who died during the period of lockdown because they couldn't get hospital treatment (https://www.theguardian.com/society/2020/may/08/more-people-...), but without further evidence, I'd be sceptical that this was the dominant effect.

I'm not sure what you're claiming here: are you saying that deaths because people couldn't access healthcare are almost entirely the cause of the UK's excess death peak? What is your evidence for that claim?

> If COVID is so deadly, why do some countries show no difference in excess deaths vs previous years?

https://www.economist.com/graphic-detail/2020/07/15/tracking... has Germany's recorded COVID-19 deaths and excess deaths as 8,538 and 7,549 respectively, and Switzerland's at 1,668 and 1,567. Your question seems to boil down to "why did some countries do so much better at containing the epidemic than others?" I don't know, although Germany and Switzerland seem better organised than the UK so that might have something to do with it.

The idea that you can lockdown in week 13 and have 12,000 excess deaths per week 3 weeks later because hospitals were "virtually empty" also seems absurd ... Emergency healthcare remained available and the messaging was that people should still go to hospital if they were ill.

The problem is lots of things that sound absurd related to COVID end up being true. Our intuitions are not a good guide to an event that's never happened before. So we rely on data, but it's hard to interpret and can be wildly misleading.

For instance, here you express an intuition that people would have continued going to the hospital because "the messaging was people should still go". In the UK? Definitely that wasn't the case. People were told they had to "save the NHS" and that there was a massive programme of field hospital construction because the government was certain they were going to run out of beds. They were told there was a deadly virus and they shouldn't leave their homes. The government ran advertising campaigns that looked like a promo for a zombie movie.

This slaughtered hospital admissions:

https://assets.publishing.service.gov.uk/government/uploads/...

Total attendance dropped from about 18,000 a day to more like 9,000 per day. It halved overnight. Your intuition about what people did was quite wrong. Even today admissions have not fully recovered.

We don't know how many of those people really needed to be there or else they'd die. But it seems the halving was independent of people's medical needs: cardiac admissions also halved. They went from around 500 per day to more like 250 per day. So that's 1750 missing cardiac ER admissions per week. Some of those people certainly will have died.

And hospitals not only emptied themselves, flushing sick people (with many viruses) into care homes where they then spread them around. But they also refused to take sick people from care homes, so deaths in care homes tripled but deaths linked to the virus only account for half of the increase (and "linked to" is very vague, there are many incorrect classifications there):

https://www.telegraph.co.uk/news/2020/04/27/care-homes-see-r...

We agree that there's absolutely a critical question about why some countries saw an increase in excess deaths and others saw nothing happen. Clearly if this is genuinely the same virus, and it's the same tests that are detecting it so it must be, then the differences are likely be explained by differing actions taken by governments.

When put in context, Germany didn't actually see any excess deaths, look at the graphs:

https://www.destatis.de/EN/Themes/Cross-Section/Corona/Socie...

If you showed the top three lines to someone who didn't read the news and asked them to pick the year with the scary epidemic, they'd say 2018. There's just no evidence of anything happening in these graphs - the slightly elevated above average number during the "epidemic" is identical in size to the slightly under-average death rates before it started. Sadly you do see people cite figures like "deaths were elevated by X% compared to the same week last year", which is misleading. We'd expect these numbers to wander up and down around the average over time. Yet they supposedly have 200,000 confirmed cases. The most reasonable explanation is that COVID is essentially re-labelling people, and when they die they're labelled as COVID deaths instead of other causes.

In Switzerland excess mortality looked pretty much the same as in 2017 (e.g. peaked at the same levels):

https://www.bfs.admin.ch/bfs/en/home/statistics/health/state...

Again, there's just no evidence of anything unusual happening here. If you showed the graphs to someone who didn't know about COVID they'd never imagine anything was happening. The "spike" is relative only to a smoothed rolling average, but such "spikes" are common and happen in many years, so it's not unusual when compared in a more granular way. If COVID had never been discovered we'd have seen these excess death rates and simply assigned them to the flu, as happens every year.

In the UK the excess death rate was higher, but still no cause for alarm. It matches the famously deadly winters of 1998/1999/2000. Hmm, I don't remember any such deadly winters. People were saying the world would end because of the millennium bug, not any other kind of bug :) Clearly there's a loss of proportion here. When I pointed this fact out to a friend, he was confused for a moment and then tried to argue that maybe we are just much more caring than people were in 1999, so death rates and reactions are incomparable! How silly!

The question is not whether people died because of COVID induced panic. There is abundant evidence they did, especially in care homes:

https://www.bbc.com/news/world-europe-52014023

https://swprs.org/covid-19-a-report-from-italy/

https://samnytt.se/aldreboendets-personal-kan-inte-svenska-a...

The question is merely what proportion of it was due to that.

Comparing winter excess death peaks, where government interventions (like lockdowns) didn't occur, with COVID19 peaks doesn't tell you what would have happened without the interventions. You (I think) say the interventions caused the peaks (or maybe that they're no worse than winter flu peaks so govts shouldn't have intervened, you're not clear on your exact view). The experts say the interventions stopped the COVID peaks from being higher. They also reduced flu deaths as a by-product (https://twitter.com/AdamJKucharski/status/128766013743239577...).

> Again, there's just no evidence of anything unusual happening here.

In Switzerland, something unusual certainly happened compared to 2017, namely a peak outside winter flu season (https://www.bfs.admin.ch/bfs/en/home/statistics/health/state...). What caused that, in your view?

In Sweden, where the government stopped short of a full lockdown but messed up care homes by refusing to hospitalise people with COVID19 symptoms (https://www.bbc.co.uk/news/world-europe-52704836), excess deaths also peaked (https://en.wikipedia.org/wiki/COVID-19_pandemic_in_Sweden#Ex...). Were the Swedes also panicked into not going to hospital? What did the care home deaths die of?

To return to the question which started the thread, the PHE stats in the UK overestimate by including people who died for other reasons after a positive test, but this effect cannot have caused anything like the error in the statistics that you claim: a back of the envelope calculation based on typical lifespans (http://julesandjames.blogspot.com/2020/07/mountains-and-mole...) gives 20 wrongly-counted deaths per day. If you're claiming that the panic lessened that life expactancy by keeping people out of hospitals, I'd note that even if every single missing cardiac case dropped dead, that's 250 people per day, no where near the 1700 we were seeing at the peak. If PHE continues to count old positive tests now, it will matter, because there are many fewer deaths in total.

> Now, given the UK example, if the vaccine causes 10 deaths, and 1000 severe reactions(ie hospitalised) thats still better than the 200k deaths and close to a million cases with complications

The anti vaccination optics, of a vaccine killing people, would be so bad the resulting vaccination resistance could lead to millions of deaths.

Yes, statistics maybe say that it would be a good deal now. But if you assume it fuels the antivac fire and decreases measles vaccination by 10% for the next 10 years, then we are looking at a death toll 10-100 times larger than COVID in the future, from that disease alone.

SARS-COV-2 has approximately 5 times the fatality rate as the measles.

Measles also only infects a person once. Preliminary data is pointing toward covid immunity lasting for only a few months.

Do you have a source for that? All I've seen is evidence that antibodies disappear after a while in many subjects but that is not at all the same thing.

That's a good point. I've done some more reading, prompted by your comment, and it looks like

Other coronaviruses typically do have reinfection about a year after first infection: https://www.medrxiv.org/content/10.1101/2020.05.11.20086439v... - with antibody reduction occurring after about six months.

I know there have been a few people who appeared to clear the virus but subsequently tested positive again - I don't know enough about the details here. Vox article with more links: https://www.vox.com/2020/7/12/21321653/getting-covid-19-twic...

I hope that reinfection with this virus is less likely, but I don't think we yet have any data to suggest that it is much different than existing coronaviruses.

> Preliminary data is pointing toward covid immunity lasting for only a few months.

As far as I know, that's not true at all.

A King's College study has shown that the level of B cells in former patients blood declinened quickly after a few months. Still there has yet to be a study on T cells level and T cells seem to play a more important role than B cells in covid immunity.

FWIW Greater London is approx 13% of the UK population, and the London metropolitan area is approx 21%. Intentional under and over counting of the size of London is pretty common depending on the interlocutor's agenda

> One way is heard immunity

Without a vaccine - wouldn't herd immunity just be letting the virus spread and then let Darwin take over, more or less?

This is precisely what it is.

It was the approach taken initially by the UK, and it is the one currently being taken by sweden.

The article actually _does_ mention challenges to the real virus, at the end of the "What are the next steps in the trial?" section:

> There are also calls to perform "challenge trials"[1] in which vaccinated people are deliberately infected with coronavirus. However, there are ethical concerns due to a lack of treatments.

[1] https://www.bbc.com/news/health-53426367

You are misunderstanding the point of this study. This is a Phase 1 study designed to show that the vaccine itself doesn't directly make people sick and to measure their antibody responses via blood tests.

The on-going Phase 2/3 trials in the UK, South Africa and Brazil are designed to establish the efficacy of the vaccine under viral challenge. The idea is that you vaccinate a bunch of people (and an equally-sized control group) and wait around until a subset of them test positive for the virus. Then you unblind the groups and make sure that the people who got sick were in the control group. You also check for ADE (antibody dependent enhancement) to make sure the vaccine doesn't amplify the strength of the virus.

All your questions are valid, but this study doesn't claim to answer them. Those results are still forthcoming. Additionally, the risk of ADE is well understood and carefully considered in the design of these trials.

(Disclaimer - I'm a participant in the UK Phase 2/3 trial)

Thank you for participating and for sharing these details!

It's still good to see such questions being raised in the community, especially when someone knowledgeable on the matter (such as yourself) has an educated response.

It is slightly different than a regular Phase 1 study because there's a control arm. I suspect they want to use the data as a complement to the Phase 2/3 results in the unfortunate case the volounteers end up positive for the virus.

The OP was critiquing the media reporting on the study not the study itself so I think your suggestion that the OP misunderstood the point of the study is off base.

The OP did not claim that the study sought to answer the questions posed. The article does answer the question 'Is it safe?' with the word 'Yes' so I believe you are actually in agreement with the OP and the OP did understand that it is really early to say that, hence the critique.

> Although this virus has killed many, the risk factor for it is nowhere near high enough to warrant an emergency vaccine.

Sure reads to me like the OP is attacking the idea of developing a vaccine, not the media coverage.

To me, it seems like OP is attacking the idea of releasing the vaccine to the general public without due diligence. That’s different than developing it.

> (Disclaimer - I'm a participant in the UK Phase 2/3 trial)

I have always thought those medical trials are conducted under an NDA against the patient, meaning you do not only not know what group you are in, you are not even allowed to tell you are being observed in such a study (to prevent accidental unblinding).

How would you expect to obtain informed consent without the patient knowing they're in the study?

Being in a trial does not guarantee you get the investigative candidate because many trials have control arms without an intervention (hence a double-blind randomised controlled trial). Neither you or the doctor know which arm you are in during a double-blinded trial because placebo effects are very well known and have to be accounted for during the drug development process. This very much depends on the study design and phase of the study. Informed consent will take a patient through these factors, but it does not mean they are guaranteed to get the intervention. There are studies which have been stopped before the trial hit its end-points as it was deemed unethical not to give patients in the control arm the intervention because it proved so effective.

Nothing indicates that the commenter knows if he's in the placebo group or the real thing group. He just said he is participating in the study, that could mean he's in either group.

The thing is someone else participating in that same study may read that and experience an unintended placebo/nocebo/antidote effect. You are not supposed to dicslose you are in such a clinical trial. The ancestrals misunderstood that as not telling the test subject that he is being tested. You could also neutralise that consent effect by making the group of consent broader than the group of study, by adding two more controls such that one group (reverse intervention group) takes a drug that acually worsens the disease (I see the possible objections, but this alone will make the study complete faster), and one takes just nothing (neutral group-those would be sent back by telling them they are diagnosed negative, but actual diagnosis will be recorded in their files), in addition to a placebo group.

> You are not supposed to dicslose you are in such a clinical trial.

They never asked that or made us sign anything to that effect.

In this Phase 3 trial, they are measuring prevention of disease across ~10,000 people. They just want to see who tests positive for COVID and how sick they get. In this Phase, they aren't asking most groups about side effects or any subjective questions about symptom severity or anything like that where reading that someone was in a study would influence our opinion.

There is no NDA in this trial. For the control, they used an unrelated approved vaccine with very similar expected side effects to prevent accidental unblinding.

The one thing we agreed to do was not to get an antibody test as that would unblind ourselves.

It's my understanding that phase 1 trials of this sort are designed simply to show that the potential vaccine generates a response in the recipient and doesn't causes any significant adverse effect. Phase 2 & 3 are where the the potential efficacy of the virus and the issues you raise are explored.

> Although this virus has killed many, the risk factor for it is nowhere near high enough to warrant an emergency vaccine.

I strongly disagree with this sentiment. In the ideal world we would have both a treatment and a vaccine, but a vaccine is much preferable: even if it grants immunity for only a year it still allows for better logistics than a treatment. A treatment is also an unknown cost while the cost of producing a vaccine is fairly well know. Also there are loads of people who are at high risk and cannot survive COVID if they got it. Herd immunity and actual immunity from a vaccine is their only option for staying alive. Lastly, your comment makes it sound like steps are being skipped here. They are not. This vaccine along with others is undergoing the same three phase study approach as any other candidate for any other virus. The difference is that sometimes phase 1 and 2 are combined which puts the people in those trials at risk, but based on your comment I don’t see that as being one of your concerns (based on the part about how well yeah a lot of people died but it doesn’t warrant an emergency vaccine). It does not cause risk to anyone else and for successful phase 1 & 2 trials you can assume the vaccine is safe for the populations tested in phase 3. Once all three are cleared, the vaccine is just as safe as any other.

I know to a lot of people it may feel like corners are being cut but I have seen zero evidence for that. We are saving time by doing things like combining phase 1 & 2, expediting review and paperwork by prioritizing these candidates over other drugs, and in this particular case by manufacturing the vaccine while it’s still in trials, gambling that it will actually work. So far the Oxford vaccine looks to be the most promising of all so I would say it’s a good gamble, but then again only a small portion of that $1.2b is mine (coming from US tax dollars and AstraZenica coffers).

A true emergency vaccine is the only one that’s currently approved for use: it’s been approved as an experimental vaccine by the Chinese military for use by the military for one year. That particular vaccine doesn’t have phase 2 or 3 results actually published and the preliminary data from phase 2 doesn’t look as good as the Oxford one. That is the kind of thing I would personally hold off on, but not something that’s gone through all three phases and been independently reviewed.

The article doesn't go into it, but the actual paper[1] states that this vaccine has "has previously been reported to be immunogenic and protective against pneumonia in a rhesus macaque challenge model", and cites to [2].

[1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

[2] https://www.biorxiv.org/content/10.1101/2020.05.13.093195v1

>>Is it safe?

>It's really really to early to say yes or no, and the fact that the article tries to make a claim either way, is worrying.

This is exactly what the phase 1 trial (the result which were just released) tries to establish -

>Phase I trials were formerly referred to as “first-in-man studies” but the field generally moved to the gender-neutral language phrase "first-in-humans" in the 1990s;[5] these trials are the first stage of testing in human subjects.[6] They are designed to test the safety, side effects, best dose, and formulation method for the drug.[7] Phase I trials are not randomized, and thus are vulnerable to selection bias.[8]

https://en.m.wikipedia.org/wiki/Phases_of_clinical_research

Can some one please explain to me. Why are we focused on vaccine. Seems like vaccine is about 40% - 60% effective. With highly infectious disease is vaccine even effective? Would be good to hear from some one with a bit more medical knowledge

> But I do have concerns on trying to push out any novel vaccine in less than two years without adequate testing.

This sounds like how you get zombies. I’ve seen this movie before.

> We still don't have vaccines for retroviruses like HIV/Herpes

Herpes is not retrovirus. It just have a latent phase where inactive viral DNA is in the cytoplasm of infected neurons.

The actual paper:

https://marlin-prod.literatumonline.com/pb-assets/Lancet/pdf...

> ChAdOx1 nCoV-19

If I didn't have the context of 2020 and this article, I would swear that was an auto-generated random password.

may be in 10 years this will become our new correct horse battery staple

ChAdOx1 would certainly make a good IRC handle.

And then there are the "ChAdOx versus Virgin Coronavirus" memes.

Chimpanzee adenovirus-vectored Oxford vaccine #1, targeting novel coronavirus 2019 (aka SARS-CoV-2).

Seems pretty well-named.

It's accurately named. All I can say is "well-named" is in the eye of the beholder, and I'm fairly certain you're not in marketing.

It won't get a trade name until it goes to market.

We just don't normally hear about pre-market drugs in mainstream media.

It is good preliminary news. The real question if this vaccine prevents you spreading the disease or effectively turns you into an asymptomatic spreader. There also outstanding questions if this works well for elderly people, as vaccination are generally less effective if you are older. Basically news worth a small cheer, not an exuberant celebration quite yet.

and also, how much time one people will be imune, and if new doses will be needed to reinforce the response of the imune system. People are saying September as a date for the vaccine to be avaliable, but it seens to be still many questions to answer before that.

If everyone gets the vaccine then does the distinction matter? Genuine question not rhetorical.

Logistically you can't give everyone the vaccine at the same time. If immunity is only temporary (few months) front line hospital staff are likely going to get vaccinated before the rest of society.

Even if it's made mandatory, which may not happen, manufacturing and distributing enough vaccines for everyone to get one will take years. Ideally we want to get everything back to normal once we have enough vaccines stocked up to strategically deploy in hot spots, but if the vaccine doesn't severely reduce the disease's spread that strategy won't be effective.

a) It would take months not years. b) you don't need to have _everybody_ vaccinated.

If vaccinated persons still transmit the virus, I would think herd immunity is irrelevant. Am I incorrect there?

I suppose technically, if you were actually just as contageous as a sick person for as long. Hard to believe that would be the case though.

How can you transmit a virus which is not able to use your body to replicate itself?

It would matter for those who can’t be vaccinated (the immuno compromised, very young children) or for those whom the vaccine might not be effective (very elderly with weak immune responses)

It would also matter for eradicating the virus. If it keeps circulating, and vaccines only provide protection for less than a lifetime, then we will have to keep vaccinating just about everyone in the world indefinitely. Any place that falls into civil strife could also expect a virus outbreak eventually.

It would still be great to have vaccine that merely made the virus without effect! But eradication would be better.

There are a lot of diseases that everybody gets vaccinated for routinely and regularly. I thought the assumption was this was going to be one of those, it is just a (currently unknown) matter of how frequently you'd need to get it.

Are any epidemiologists talking about possibly eliminating it completely? Seems like the toothpaste is out of the tube for that.

Yes. Devi Sridhar has mentioned it as a goal, fairly sure I have seen others.

We have only eliminated one virus globally (smallpox) but plenty of others have been eliminated nationally. Then to travel to those countries from a country where the disease is endemic you generally need proof of vaccination.

There are also many countries that have basically eliminated the virus at present. They’re not going to want to import the virus just because other countries failed.

Once you have two things the probable future becomes clear: a vaccine, and very fast tests. Combined, they will make it fairly easy for a well governed country to eliminate the virus.

Then, any entering traveler from an endemic country would require proof of vaccination and a quick test at customs to confirm. That would keep the virus out of eliminated countries.

After that it would be a global effort to eradicate the virus country by country, just like we’ve been doing with other diseases such as polio.

A key feature of sars-cov-2 is that it is not like the flu. Coronavirus spreads in clusters and this is containable.

> then we will have to keep vaccinating just about everyone in the world indefinitely.

Which is to say, it'll be like the seasonal flu and not a pandemic. Yeah, we can tolerate that.

Well, it really depends on the timeframe. If we need a new one every two years, no problem. If every six months, that’s worse.

Current flu vaccine coverage is 24-50% depending on jurisdiction, once per year. So, aiming at, say, 80% coverage twice per year would be 3-6x the current level of flu vaccination effort.

Not awful, but tiresome.

You don't need 80% coverage though. Influenza would be a pandemic too (and has been!) but is well controlled by the existing regimes. There's nothing all that notable about covid really, beyond its novelty. Once the bulk of the population has some immunity, even if incomplete and even if it needs a regular refresh, we hit herd immunity: R0 drops below 1 and the disease stops spreading. There's no reason to expect this to work any differently.

The answer to your question is in the article. This is not an attenuated virus, nor is it variolation, it's a modified other virus (common cold) with some proteins added and does not cause an infection, it just stimulates antibodies.

It has been heavily modified, first so it cannot cause infections in people and also to make it "look" more like coronavirus. Scientists did this by transferring the genetic instructions for the coronavirus's "spike protein" - the crucial tool it uses to invade our cells - to the vaccine they were developing.

> It has been heavily modified, first so it cannot cause infections

Amusingly, lives would probably be saved if they had kept the base virus used for vaccination infectious. It's just the common cold, and the side effects are currently only a headache and fever, so getting the vaccination virus secondhand would be better than getting coronavirus, and you'd be protected after.

Common colds can occasionally be serious for people who are severely immunocompromised in other ways.

The problem is not the vaccine, it is when you actual contract COVID-19 later on. If the vaccine sufficiently suppresses the symptoms, but doesn't actual prevent infection, there is a change you can spread the virus asymptomatically.

I see how that's important. On the other hand, it's not as big of a deal to spread the virus if everyone has protection from the symptomatic risks. We should still shelter in place, but even turning active cases into carries would reduce loss of life (presuming we continue regular testing so people can KNOW if they are a carrier)

> On the other hand, it's not as big of a deal to spread the virus if everyone has protection from the symptomatic risks

Assuming everybody got the vaccine in the same instant, which they would not.

> We should still shelter in place, but even turning active cases into carries would reduce loss of life (presuming we continue regular testing so people can KNOW if they are a carrier)

We've all seen how people are behaving right now: "Oh I'm young, forget about grandma". How do you think they'd behave knowing that they've been vaccinated? It's important to consider the sociological conditions in which an intervention is deployed. Unfortunately, our present society has a very large number of self-centred individuals.

This is a great way to turn the anti-vaxxers, hahah.

The more people take the vaccine, the less society bothers to social distance and other low-tech things, the more dangerous not taking the vaccine becomes.

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.

[1]: https://www.nature.com/articles/s41577-020-0405-3

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.

Here’s a source if anyone’s interested.

https://www.nature.com/articles/s41586-020-2550-z

Very interesting, thank you!

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...

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 :)

I'm pretty sure it will be mandatory in a lot of countries, but it will probably be done in waves.

It won't be mandatory but you probably won't be able to work and your kids won't be able to go to school.

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.

>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.

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 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:

https://www.youtube.com/watch?v=hMUeZ4vz6cU

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.

HPV shots are safe and effective.

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.

but thats not quite what OP was hinting at.

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.

We can ship placebo right now.

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.

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.

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.

And you must also syncronize it internationally.

In Canada 42% of the people got the flu shot in 2018-2019, up form 36% two year prior [1].

[1] https://www.canada.ca/en/public-health/services/publications...

That looks high. I wonder how it compares with other countries.

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.

In England n England, flu vaccine uptake in people aged 65 years and over has fluctuated over time between 71% and 75%.

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.

The big difficulty with flu isn't _usually_ a production shortfall, though; it's that people don't want to get the vaccine.

COVID is much scarier than flu, which should encourage people.

Whenever I hear concerns about vaccine production capacities I have to think of https://en.wikipedia.org/wiki/United_States_aircraft_product...

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.

Is a billion doses a year an arbitrary number?

I'm not sure about Oxford but for Moderna a billion doses a year is accurate[1].

[1]: https://cen.acs.org/business/outsourcing/Moderna-picks-Lonza...

It doesn't mean they can't produce significantly more doses than that.

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.

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:

https://www.fiercebiotech.com/biotech/moderna-finalizes-desi...

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.

They absolutely need 2 doses. That is how they have been conducting all their tests. Read the last line of the article you linked.

Also based on the results from the study, two doses are necessary because one dose didn’t elicit a strong enough result but two did.

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.

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.

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.

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.

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.

https://academic.oup.com/cid/article/52/7/911/299077 https://en.wikipedia.org/wiki/Compartmental_models_in_epidem...

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 has been on a red ward (ie the very front lines) and still hasn't gotten it after 4 months.

Either they were symptomless or with good discipline and PPE you can limit its spread quite successfully.

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.

Less exposure to virus = not enough to get symptoms, but enough to develop antibodies?

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.

> mass application of vaccine

Is anyone optimistic about that?

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.

I would guess that the economics of production of a COVID-19 vaccine will be significantly more attractive than other vaccines.

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.

> and then maybe elderly

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.

AIUI, mass production of the Oxford vaccine has _already_ started.

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.

One interesting byproduct of this is that we may end up with multiple vaccines becoming available at the same time.

I wonder will people comparison shop.

Expect it'll be quite some time before there's enough open-market inventory available that we have the option to shop (2H 2021).

Governments have too much incentive to purchase and distribute all they can get their hands on.

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.

https://www.mcclatchydc.com/news/coronavirus/article24377546...

https://www.reuters.com/article/us-health-coronavirus-fauci-...

Don't they know we need the vaccine by Tuesday, November 3rd??

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.

https://en.wikipedia.org/wiki/Compartmental_models_in_epidem...

I'm pretty sure they're talking about Basic reproduction number[0] from context.

[0] https://en.wikipedia.org/wiki/Basic_reproduction_number

My point still stands; vaccines do not change R0. They artificially move people from S -> R.

Sounds like they are talking about Re -- effective reproduction rate -- right?

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.

https://en.wikipedia.org/wiki/Basic_reproduction_number#Effe...

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.

Interesting question, I guess, but the world CANNOT WAIT for studies of long term effects.

If this turns out to work in the short run, we should deploy it. Not wait 2 years while the pandemic rages to produce the perfect science paper.

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.

> The death toll from COVID lockdown is so much higher - from excess suicides, poverty, crime and violence

That's the same false dichotomy we've been hearing since the pandemic began.

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?

We know that covid is killing people at least ten years early. https://www.gla.ac.uk/news/headline_720672_en.html

We know that many people do not have comorbidities.

The mean age of patients admitted to ICU is 60.6 years (white people), 55.4 years (non-white).

88% / 93% of people were able to live without assistance in daily activities before admission.

https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports

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.

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.

https://mobile.twitter.com/erictopol/status/1276153119492186...

Perhaps delaying till the "give up" part is the point. Pushing the cost of the pandemic from the top to the bottom.

Except those people don't pay with money, they pay with blood.

Do you have any sources for your factual claims?

You wouldn't want a purported vaccine to kill more people than the virus itself, no? To avoid this, statistics and multistage tests are used.

Agreed.

You may have misunderstood my point.

Agreed.

I may not have articulated my point well.

> but the world CANNOT WAIT for studies of long term effects.

We said that before, and we got Pandemrix.

Vaccination is safe. It's important we get as many people vaccinated as possible, and one of the ways we do that is by maintaining the safety.

https://en.wikipedia.org/wiki/Pandemrix

https://www.narcolepsy.org.uk/resources/pandemrix-narcolepsy

https://www.cdc.gov/vaccinesafety/concerns/history/narcoleps...

> resulting in 3.6 additional cases of narcolepsy per 100,000 vaccinated subjects.

That is obviously much better than the current Covid situation.

What if instead of narcolepsy it's cancer? Wouldn't that be worse then covid?

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.

> If you live in New Zealand where covid has been eradicated, then why risk it.

Because it’s only “eradicated” in New Zealand so long as they wish to remain shut off from the rest of the world.

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.

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.

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.

I'm curious why the share price slide after the mainstream news.

Sure, there have been rumours about the Lancet paper for a few days, maybe these were priced in already - and AstraZeneca has promised to manufacture it at cost or near cost. Still weird the market reacted this way

https://markets.businessinsider.com/news/stocks/astrazeneca-...

Outside of publicity, I don't see this as having an enormous impact on profits. Companies will be compelled to produce the vaccine in any event, and will be compensated, but I can't imagine governments would be purchasing the vaccine for any large markup.

The problem is that this is a money-losing proposition. If ten companies attempt to produce a vaccine, spending X, and two of them succeed (before the rest), with the government paying each double their development costs (2X), that means that the expected outcome of developing a vaccine is -0.6X.

As a result, we should expect that most companies will only make a token effort.

I think it depends on the company, AstraZeneca CEO already said a while ago they will be manufacturing this at cost or near cost, this is a time for big pharma to give back. Some drug companies like Gilead though have very high markup, paid by the taxpayer.

And some bioteh companies with mRNA vaccines in phase 1/2 trials like Moderna and Biontech, or protein treatment like Synairgen have seen share prices skyrocket.

I guess the assumption is they will be collecting fees from the IP and/or future contracts for other drugs if this works out.

“Buy the rumor, sell the news”

https://www.ig.com/en/trading-strategies/-buy-the-rumour--se...

Oxford vaccine is among the front runners. This is really good news. They plan to finish their final trials before October this year.

If all goes well, we should be looking at major relief by this year's end.

That's unrealistically optimistic. The best case scenarios I've heard have it being deployed to healthcare workers late this year, and then hopefully be made available across the globe to approach the herd immunity threshold by the end of 2021, at least in some countries/communities. End of 2021 is an optimistic timeline to be talking about "major relief", and that's assuming no one messes with vaccine availability... Until then, we all need to take this extremely seriously and do everything we can to prevent spread.

They plan to make a million doses available by September, possibly more:

https://www.reuters.com/article/us-health-coronavirus-oxford...

Is a million doses "major relief"?

Certainly not, but considering there should be 100M available by the end of the year, it seems like they are scaling up the production line considerably

That just about covers NHS employees.

A million doses is barely a whisper of a drop in the ocean.

Beyond what others have said about a million doses being a drop in the bucket, the more significant bottleneck will likely be the lack of syringes and glassware to administer the vaccine, rather than a lack of dosages.

Fauci has stated early 2021 as the goal for mass vaccination in the US if everything goes right. Provided that it works and provided that hundreds of millions of doses will be ready by EOY, and provided that the US govt. has already ordered enough of them - we can hope all the stars align. For the whole world, yes, it will take much longer than that.

"The UK could be vaccinated for Covid-19 by Christmas, says Oxford vaccine developer" https://www.lbc.co.uk/radio/presenters/matt-frei/coronavirus...

>If all goes well, we should be looking at major relief by this year's end

While the news is encouraging, I think we need to pump the brakes a bit. It is very common for vaccine candidates to show promising cellular results (formation of neutralizing antibodies) and then utterly fall apart during actual efficacy testing (not actually prevent infection in people, or even actually make the infection worse when it happens). This is why most vaccines take 10-15 years to develop.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

The paper (I'm sure it's been posted somewhere in thread). Surprisingly readable (if you have a basic understanding of immunology and Google), go check it out.

The TL;DR is they administered the vaccine to many people and compared the immune response, as measured by various immunology assays, and it elicited a noticeable response for every assay very close to the same responses from actual COVID patients. There were plenty of mild to moderate side effects, but they were reduced quite a bit using paracetamol (Tylenol, basically)

” Levels of T cells peaked 14 days after vaccination and antibody levels peaked after 28 days. The study has not run for long enough to understand what long-term immunity may look like.”

”Is it safe?

Yes, but there are side-effects. There were no dangerous side-effects from taking the vaccine, however, 70% of people on the trial developed either fever or headache. The researchers say this could be managed with paracetamol.”

This sounds like really good news, anyone with medical background disseminate this further?

Edit: here is the lancet article posted on /r/COVID19 sub and extract

https://www.thelancet.com/lancet/article/s0140-6736(20)31604...

Background:

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2.

Methods

We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18–55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5×10¹⁰ viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606.

Findings

Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493–1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96–317; n=127), and were boosted following a second dose (639 EU, 360–792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R²=0·67 by Marburg VN; p<0·001).

Interpretation

ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support largescale evaluation of this candidate vaccine in an ongoing phase 3 programme.

I am wondering how the vaccine genetically impacts on these people who are already recovered from Covid-19.

I would imagine that people who've already recovered from covid-19 wouldn't need/get a vaccine, but I am not a doctor.

Not everyone that (allegedly) gets the vaccine develops antibodies because there are other components of the immune system that destroy the infection prior to the need of developing antibodies.

Even in those that do develop antibodies, they are finding those antibodies are undetectable after some short time period.

I understand that. I am not a doctor either. Let me rephrase my question more concretely and hopefully someone can answer it.

I am curious to know whether the immunity to covid-19 will become stronger or weaker if those people who've already recovered from covid-19 get a vaccine.

> people who've already recovered from covid-19 wouldn't need/get a vaccine,

It is not known how long immunity from having covid-19 lasts, and there have already been a few cases of apparent re-infection.

So yes, they would likely benefit from a vaccine.

https://www.vox.com/2020/7/12/21321653/getting-covid-19-twic...

https://www.timesofisrael.com/israeli-doctor-diagnosed-with-...

Terrible. I thought the immunity would last forever.

We should not expect indefinite immunity. With other human coronaviruses that cause colds, immunity typically doesn't last forever, so you can catch the same coronavirus when it comes around again a few years later.

This is not yet known about covid-19. But the claim that you can get it again "three months later" is eye-catching in how short a period that is, and hopefully is quite rare.

The team behind the ChAdOx-1 vaccine have said that similar vaccines they worked on in the past (SARS1, MERS) triggered the immune system in a different way than getting the virus itself and it's expected that the vaccine-derived immune response would last longer than natural immunity. They have re-tested people they immunized for SARS1 and they still showed immune responses over a decade later.

So the idea is that the vaccine would still be potentially useful to those who have already had the disease.

I see. Thanks for sharing the information.

question about this and vaccines in general... would this be beneficial to someone who already contracted the disease? at the early stages at least? would it help that person recover faster or lessen the effects of the disease?

My web search suggested that normally existing vaccines aren't helpful this way, but that there is ongoing research on "therapeutic vaccines" that would be.

https://www.webmd.com/vaccines/features/treating-disease-wit...

The article says none are currently available as treatments for any infectious disease.

We might be talking about different things, but many vaccines are potentially useful post-infection particularly for slower diseases, as it doesn't necessarily help the actual infection, but can help prevent it from spreading to new cells.

It's highly dependent on the disease, how it spreads, etc. But it is a thing.

one thing about the Oxford vaccine is that when vaccinated you are still able to pass on the virus , despite having the anti-bodies to fight it. It's excellent news nonetheless

edited with some references

https://www.telegraph.co.uk/global-health/science-and-diseas...

https://www.independent.co.uk/news/health/coronavirus-vaccin...

Why is that the case with the Oxford vaccine? Can you elaborate?

I'm curious what they meant as well. Perhaps what they meant was the potential period where the virus is replicating in the body before the immune system detects it and kills it. I suppose even someone with the vaccine would have a very short-lived period of viral replication? Or perhaps they simply meant that humans could be fomites (eg, it gets on someone's hand, then they shake your hand, etc?)

Honestly I'm just guessing here. I suspect this is not a real concern.

This is a little bit of a misnomer. Anybody can pass on the virus. If you have it in your nose and you sneeze, you'll spread it everywhere. If you have it on your hands and you touch high-traffic surface areas, you'll spread it. The point is that if a high number of people are vaccinated, then it won't matter if the virus fragments are spread, as long as it's not causing disease then it doesn't matter.

That was true for the monkeys that were challenged with huge viral loads. We don’t know if it will still be true for humans who encounter normal loads.

You are reporting very misleading information as if it were a fact. No one knows that to be true in humans, not even the creators of the vaccine.

In a very limited test of a small number of monkeys who were directly injected with high levels of the virus, those monkeys still had the virus in their noses and might have been able to pass it on (in theory).

That has very little value in telling us what the vaccine will do in humans in the real world. No one will know until the Phase 3 trials are complete. It's still possible that the vaccine will be totally effective, partially effective or completely ineffective in protecting humans. That's why we need the Phase 3 trial results to know if this vaccine "works".

Prof Sarah Gilbert, from the University of Oxford, UK, says: "There is still much work to be done before we can confirm if our vaccine will help manage the Covid-19 pandemic, but these early results hold promise."

This article text should be much earlier.

> However, all these approaches are at the absolute boundary of science and have not been proven to work before. More traditional methods of vaccine development are also being investigated. The company Valneva is taking the whole coronavirus, inactivating it and then inject it.

One name for approaches "at the absolute boundary of science" is research. Only one company is named as developing an actual vaccine. We need new category names for the many competing treatments which are still in research phases, including those which utilize genetic engineering.

It's a little worrying that the UK already ordered 100 million doses of the vaccine, even though it hasn't passed trials yet.

I understand that tons of resources are being poured into making a vaccine, which will make developing this vaccine a lot faster.

However, this still makes me worry that the media ( and the UK government in part ) is showing false potential false hopes to people that read this article. Yes, we might get a vaccine next year, but we might never get a vaccine either.

At this point I'm becoming more worried about distribution rather than finding a working vaccine.

One in six people (in the UK) said they'd refuse a vaccine if it became available, and another one in six weren't sure. (YouGov poll)

It might make distribution to reach herd immunity difficult.

I might be wrong on this, but wouldn't that still be fine in order to achieve herd immunity?

I distinctly remember reading something that said 60% was the minimum threshold required to ensure that the virus spread as a greatly reduced rate.

It's all estimates, of course, but there's some good reading about what factors effect the herd immunity threshold here: https://en.wikipedia.org/wiki/Herd_immunity#Mechanics They estimate 50-83% vaccination threshold to achieve herd immunity for COVID-19. I believe the citation is this study, but I admit my ability to read scientific papers is lacking: https://pubmed.ncbi.nlm.nih.gov/32433946/

Right now they are saying that 95% had a substantial immune response. But we do not know whether it is substantial enough and lasting enough. Imagine that it is both for less than 70% of vaccinated. 5/6*0.7<0.6 (and yes, 0.7 is to prove a point).

We need more information than that poll. Someone unwilling to take a brand new vaccine is not inherently the same as some loony anti-vaccer. It’s not obvious to me that it would be sensible to be first inline for one of these vaccines that have been developed so quickly.

Indeed. With a US presidential election in November, any vaccine delivered in October and touted by the current administration will be met with extreme skepticism, even by those who routinely take vaccines.

Remember hydrochloroquine?

>any vaccine delivered and touted by the current administration will be met with extreme skepticism

That would be the most unfortunate irrational, anti-science behaviour that people could have, especially given the criticism of the same administration as anti-scientific.

It's 100% reasonable to doubt and verify anything coming out of the Trump administration, at this point. "extreme skepticism" is the correct response to have. No idea why you call that "anti-science" and "irrational".

(Honestly: Crossing fingers the vaccine won't come out of the US so this situation is avoided)

This administration literally touted drinking bleach to fix the Coronavirus. I'm not going to self-righteously criticize people that are a now more than a bit sceptical of medical claims coming from the Trump Administration.

I dislike your use of the word "literally" immediately preceding something that did not, in fact, literally happen.

yeah that's really sad. Having a pandemic during an election year was a bad idea :)

There's a big difference between the hydroxychloroquine fiasco and a developed vaccine. Hydroxychloroquine was something that showed early promise and seized upon by one political side but when it didn't live up to the hype it was seized upon by the other political side.

A vaccine is developed over time and the results released for all to see at each stage in the development. It's much harder to over-hype a vaccine and I think politicians learned their lesson.

IMO, in the US at least, if you refuse the vaccine then insurance should require cost of Covid19 treatment to be 100% patient paid.

That’s like asking MSM patients who don’t wear condoms to bear the entire cost of HIV medication.

There's election year vaccine precedent: Gerald Ford in 1976 with an "upcoming" swine flu. It's one of the reasons that Jimmy Carter defeated Ford.

Sadly, the vaccine was rushed and botched. Some people ended up with Guillain-Barre.

In the case of hydrochloroquine, Trump was saying "this is bigly magical" and every expert around was urging caution. With a (proper, tested) vaccine expert opinion would be a lot more friendly. People do consider the source; most people would not take medical advice from a hotel magnate (even people generally friendly to Trump were mostly cautious of the chloroquine and disinfectant imbibing stuff), against advice of actual doctors.

That said, mass availability of anything by November is probably optimistic.

herd immunity isn't an all or nothing.

HTT targets for influenza is 40% while SARS requires 80%.

This is a very good and important point. In a good year, if we can convince 40% of the eligible population to get a flu shot, imagine the challenge to get the >= 60% coverage needed to confer herd immunity. Just having a good, safe vaccine available isn’t enough. We have to convince an unusually large number (compared to influenza) of people to get vaccinated, and I worry about how hard that will be.

It's my opinion that the coronavirus vaccine may be different.

Workplaces are going to require people to have the vaccine come back to work if only for liability reasons. I haven't run into workplaces requiring a flu shot and I've worked food service my whole life.

Vaccines required by workplaces or schools have higher compliance with the recommendations than The flu vaccine. COVID-19 vaccine could well be legally required at all schools, and potentially even legally required at workplaces as a condition of opening (certainly healthcare and allied fields would likely require it the way they do TB vaccines; the larger the mandatory population, the less compliance you need in the voluntary population to reach any given overall target.)

This might be a case where we do in fact have to override the idiots and force it upon people. Endangering yourself with your own gullibility and stupidity is fine, but endangering myself or my loved ones? Nope.

I agree but consider Measles, much more infectious and hits children the hardest. As far as I know, there is no federal law requiring forcing a Measles vaccine on parents.

On the other hand, Covid19 is affecting the economy and we're not having any of that in the US after the shutdown devastation so maybe a law requiring a vaccine is in the cards.

edit: thinking about it for a second, i don't see a law requiring it working. The lunatics would go crazy, there would be states refusing to enforce the law. Maybe some sort of incentive would work better, like a federal tax credit for proof of vaccination or something.

There is absolutely no way the government is going to force this vaccine on people. Not in the land of the free. Not in the land of "face masks violate my rights" They could write all the laws they want - it'll be unenforceable without popular buy-in.

DOesn't this mean that the only people at risk are the people who don't get vaccinated?

The rest of us will be fine, right?

Not really. A vaccine is never 100% effective.

I thought the Smallpox vaccine was, or basically was? That's how we were able to eradicate Smallpox by giving everyone the vaccine.

You only need to the vaccine to lower the spread to an unsustainable level, and the disease will fizzle out.

The challenge for smallpox was more to do it in every remote corner of the planet.

A countermeasure could be that stores & restaurants etc will only allow vaccinated people to enter.

How would you implement that without causing an increase in subjective/race/religious discrimination? US Americans even oppose to national identity cards.

I'm guessing the forcing function will be public schools. Students who have been vaccinated will be allowed back. Others will not (or will be required to wear masks). Schools might even require that entire families be vaccinated before the kids are allowed back.

Call me cynical.

1. This vaccine race seems like "first one gets eternal glory" scenario, which might pressurise scientists to take shortcuts, which may be bad.

2. Even with successful vaccine trials, wouldn't take atleast an year to setup supply chain capable of distribution?

3. Virus mutates very fast, is it possible that all these early vaccine trials resulting in super virus which can't be killed by any kind of immune system.

1. Pretty easy to assay the vaccine itself and the blood of vaccine recipients and figure out (1) is it what they're saying it is? and (2) does it do what they're saying it does?

2. No. Google around for this; there's plenty of info on how this can be done more quickly. Also, "even if we find a vaccine it will take a year or more to produce it at scale" is no reason not to develop one or to celebrate progress in such development.

3. Possible? Uh, sure, yeah, most things are possible. Probable? I'm not aware of any evidence suggesting that "early vaccine trials result in super virus" is a remotely probable scenario. If you are aware of any such evidence, please post it here because I'd like to read it and update my view accordingly.

> 2. Even with successful vaccine trials, wouldn't take at least a year to setup supply chain capable of distribution?

My understanding is that at least some of the vaccines are being produced at scale while the trials are still ongoing, in the hopes that they will be successful and a huge supply will be needed.

From what I am hearing the antibodies that you get from having the actual virus do not provide protection from re-infection for very long. I cant find the source but I think it was a Medcram lecture. Would antibodies be from a vaccine be more effective at preventing infection then getting the actual infection? I thought usually it was the other way around.

We will never eradicate this disease due to the large number of anti-vaccine folks.

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With something like this, you really do. The first vaccines are unlikely to be 100% effective, and may not last very long, so to get close to eradication we'd have to see very good take-up rates.

We still do because if there are too many anti-vaccine people that would prevent us from reaching herd immunity.

I do worry about anti-vaccine people. I don't think that because someone falls for propaganda they should die from a preventable disease. Their kids shouldn't either.

The good news is that if you always drive sober, you don't have to worry about drunk drivers.

The reality is, no vaccine is 100% effective (immune response isn't a binary thing), and the are lots of people that can't be vaccinated for medical reasons. Every person who is not vaccinated by choice is wilfully exposing others to risk.

My understanding is that with the flu shot scientists and epidemiologists essentially make an educated guess as to which strains are going to be prevalent in a particular year.

Why is COVID-19 different where the expectation is that one vaccine will prove a panacea. The virus has already shown that it can mutate similar to the flu vaccine.

Influenza is a family of related viruses. COVID-19 is actually the disease caused by the virus. SARS-CoV-2 is the actual virus, and it is only a single virus in the family of coronaviruses. Other coronaviruses include SARS-CoV, MERS-CoV, and a host of others which just cause a subset of the common cold.

This should be compared more to something like the H1N1 outbreak, which was a single influenza virus that was particularly deadly for some subset of people. That was just one type of influenza.

Stupid question - why will a coronavirus vaccine take so long even when they say people are working at an incredible pace if we can produce a new flu vaccine each year? Are scientists guessing strains multiple years in advance so there is time to produce a vaccine or something?

Its not stupid. Its a new vaccine, to treat a new virus thats is in a class of virus thats never had a vaccine.

if that makes any sense?

the yearly flu vaccines are tweaks to an already understood vaccine, (minor releases) Sometimes there are major releases but thats for a jab that targets a different class of flu (h5n1 vs h1n2)

this is an entirely new vaccine, for a virus that has never had a vaccine, so its more like a v1.0 release on a new platform.

The flu vaccine is simply deactivated flu virus that is grown in eggs. The big issue here is that coronavirus is “smart” enough to not reproduce in eggs.

Also notice this trade-off [edit: I'm saying this with a neutral tone, and not implying anything, so that a more informed person can elaborate on it]:

[quote]

Is it safe?

Yes, but there are side-effects.

There were no dangerous side-effects from taking the vaccine, however, 70% of people on the trial developed either fever or headache.

The researchers say this could be managed with paracetamol.

[/quote]

Unrelated PS: What's the deal with these one-sentence "paragraphs", BBC? I think I know the answer: it is the "modern medicine" for lack of attention spans. (What about the side effects to this...)

Unrelated PS-2: I didn't notice that someone else here has already quoted the above part. Sorry for the duplication.

Don't the regular flu vaccines have the same side effects?

I'm not denying it; just merely noting it, hoping more clueful people than me can comment on it :-)

Yes. Although I know intellectually that I should get an annual flu shot, my animal brain kicks in every time to remind me that I feel crappy for a day or three after each one.

The BBC style guide suggests breaking up paragraphs and using bullet points like this as they are easier to read on a digital screen than dense paragraphs of text:

https://www.bbc.co.uk/academy/en/articles/art201310101127407...

Ah, thanks for the pointer; I can understand that reasoning. But I hope that doesn't really get stretched too far.

I mean, as they say, it can be managed with paracetamol (acetaminophen; extremely cheap, and safe when used as directed). If the only side effect is a treatable fever for a few days, then that doesn't seem like a real problem.

Obviously, the concern would be that these might not be the _only_ side effects, and this is why vaccines are subject to extensive testing. But if this is all that emerges, that's really good news.

This sort of thing is a common side effect of the seasonal flu vaccine, too.

At 1077, this is indeed a promising result. I genuinely hope this isn't yet another marketing stunt(of which we've seen a lot lately). Mind you,

> The vaccine - called ChAdOx1 nCoV-19 - is being developed at unprecedented speed.

Seriously? Did they ask a 9 year old to pick a nickname?

Lol, it stands for Chimpanzee Adenovirus Oxford. Not too unconventional a name.

Chimpanzee Adenovirus Oxford type 1

the 'nickname' follows a standard nomenclature for this kind of thing.

Chadox does sound like a new brand of underarm deodorant though

My first thought when I saw the name : https://en.wikipedia.org/wiki/Les_Shadoks

>> "When one tries continuously, one ends up succeeding. Thus, the more one fails, the greater the chance that it will work."

Philosophy of French '60s cartoon birds eerily similar to modern software development methodologies

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