A summary of recent vaccine and related developments. Feel free to ask any questions you have, and please correct me if I've made mistakes.
1) So far we have 7 vaccines being administered globally. Two based on mRNA (Moderna, Pfizer/BioNTech) that are the first vaccines of this type to ever be approved, and several based on established methods such as using inactivated or attenuated viruses. The mRNA vaccine technology is a fantastic development and bodes well for stopping many other diseases. There is considerable scope for improvement, though, because right now they are more finicky - the Pfizer/BioNTech vaccine needs to be stored at an incredibly cold -70 C and this will cause supply chain problems in developing countries (Moderna's seems to need about -20 C which is not easy but much more achievable). The Oxford/AstraZeneca vaccine uses a different, older method that ships a piece of the coronavirus DNA into you inside a chimpanzee virus that will not harm you. It should be much easier to store and transport. One Chinese and one Russian vaccine use the same method, and another two Chinese vaccines use killed/inactivated viruses. All require 2 doses to achieve full immunity, but in a few weeks we may see a single-dose vaccine from Johnson & Johnson approved.
2) If we focus only on the vaccines developed and tested in Europe & North America, the bottom line is: with very few exceptions (see next point), get any vaccine that is available to you. It does not matter if you get one that is 70% effective (Oxford/AstraZeneca) instead of one that is 95% effective(Pfizer/BioNTech and Moderna). The point is not just to protect yourself: it's to reach herd immunity. If everyone gets even the less effective vaccine, we will have reached herd immunity. Effectiveness at this point is much less important than ability to produce, distribute and administer the vaccine.
3) SAFETY: (i) There are very rare (EDIT: very roughly on the order of 1 per 100k to 1 million doses) severe allergic reactions reported to the Pfizer/BioNTech vaccine, possibly linked to the lipid nanoparticles used in it. These are also used in the similar Moderna vaccine, so we may see a few such issues with that too. If you have severe allergies to one of the ~10 ingredients used in the vaccine (they are quite simple), you may want to wait for another vaccine such as the Oxford/AstraZeneca. If you just have a lot of allergies in general, it doesn't look like there's any reason to worry. Please get the vaccine! If the high proportion of people who have some allergies decline to get vaccinated, we won't hit herd immunity until many more people die. (ii) Pregnant women (and possibly other at-risk groups) were excluded from most trials. We still don't know if the vaccines are totally safe for them and have not collected sufficient non-trial data to understand this well. It's very probably safe but we don't know for sure. Still recommended for these people to get vaccinated but I haven't read enough - do your own research.
EDIT: Please reach the comment about safety below from a medical doctor who knows his stuff.
EDIT 2: I should also note that minor side effects (headaches, swelling, pain, mild fevers) are quite common.
4) We know little about the 3 Chinese and 1 Russian vaccines. They were approved much faster without the large scale trials that have taken several months in the West, but not ever deployed at large scale (anyone know why?). They remain untrusted because of a (justified) lack of faith in the Chinese and Russian governments. But they remain underrated and if the data do back up their efficacy - and the Sinopharm vaccine seems to have been very effective in UAE trials - they may have saved many lives because of the speed of their deployment. They are also going to be much easier to store and distribute than the mRNA vaccines (but not the Oxford/AstraZeneca vaccine), so may be important in large parts of the developing world.
5) Protection is not immediate. For the Moderna and BioNTech/Pfizer vaccines, it seems to develop 7-14 days after getting the first dose. For the Oxford vaccine, it's quite clear there is protection after 21 days and possibly before, but they do not seem to have shared results from before this date (let me know if you have seen this). So once you get your shot, keep distancing for a couple of weeks.
6) All the present vaccines require two doses. But there's good evidence that even one dose of the Moderna and BioNTech/Pfizer vaccines (and I think the Oxford one too) provides strong protection. Investigating that ought to be top priority - we could potentially double our vaccine supply overnight if one dose protects! That buys us several weeks and tens to hundreds of thousands of lives (!) while production of these and other vaccines ramps up. Even if one dose does not provide lasting immunity, we don't need that immediately if we can immunise a large proportion of the population quickly. When they are available, we may be able to take additional doses of the same vaccine, or even a different vaccine. This has some risks but there appears to be evidence that a mix of vaccines could even be more effective (under investigation). The question is: is it worth risking tens to hundreds of thousands of lives because we are not sure that one vaccine provides lasting immunity? To put it in more personal terms: if you had two doses available, would you and your partner each take one, or would one of you take both?
7) The vaccines have been tested primarily for their ability to protect people from falling ill. And they do an excellent job. But there's a possibility that it does not prevent people from acquiring and transmitting the virus. That would be worrisome, because it could make tracking spread even harder given our lousy testing regimens in most places. But this seems to be quite unlikely, for multiple reasons. Among others, asymptomatic people pass on the virus to a much lower degree than symptomatic ones, so just reducing the proportion of symptomatic cases should reduce spread. You may hear about this worry, and it's mostly scientists being very cautious about not overstating what the vaccines do.
8) There's not yet enough data about efficacy in old people for at least the Oxford/AstraZeneca vaccine (EDIT: and apparently the Pfizer/BioNTech vaccine), which is strange and annoying. Some vaccine approvals were held up for weeks because regulators judged that companies had not recruited enough minority populations to validate efficacy in a broad enough segment of the population. Surely recruiting old people - the group overwhelmingly most likely to die if infected - ought to have been a priority?
9) The vaccines will quite likely provide more effective and longer-lasting protection than natural immunity (the advantages of intelligent design). Get it even if you have had Covid.
10) The vaccines very likely protect against the new UK & South Africa strains you've been hearing about. We won't know for sure for a while, though.
11) Every day of delay thus far and in the future has cost in the range of tens of thousands of lives. The first and worst reason for this is horrifyingly inefficient bureaucratic procedures, which I've railed about before. The US and Europe made us wait for 2-3 weeks before reviewing the vaccine data for approval while more than ten thousand people were dying every day, and about 2 hours of review were needed (most stuff was previously reviewed and approved). This is not being careful and competent. The fact that some grumbling from a German minister was enough to get the EU to bring forward its vaccine review date by 3 weeks tells you how useless the waiting periods are. The common rejoinder to the calls for speed is that we need to be slow to maintain public trust. I don't agree. Sure, people are sceptical of vaccines. Do these people deserve the heckler's veto? How many tens of thousands of lives are we willing to sacrifice to mollify a few antivaxxers?
12) But the problem is not just bureaucracy. It is also the ethical objections that epidemiologists and doctors have. A terror of 'human experimentation' prevented challenge trials (intentionally exposing volunteers to the virus) in spring and summer and is now being used to stifle efforts to evaluate single-dosing of vaccines to double vaccine supply. Similarly, queasiness about experimenting on at-risk populations such as pregnant women means that the vaccine was not tested on them. We are now basically leaving the decision about whether to get vaccinated to these people without data or guidance. Is this the ethical solution, or a cop-out? We have successfully avoided sins of commission by avoiding tough decisions at the probable cost of tens to hundreds of thousands of lives so far. These sins of omission of people in charge (and the public health community) are either because they have not thought through costs and benefits appropriately, or because they are using reasoning that they are not explaining.
13) Care is obviously warranted, as public scepticism of vaccines is a worry that we want to avoid. But requiring that we have very strong evidence from multiple rounds of testing may have cost hundreds of thousands of lives now. Was this worth it to reduce the possibility of errors? To maintain trust in the system so people will listen to them about future vaccines and medication? Perhaps it is! But I'd like to see that defence made explicitly, instead of deflection through claims that vaccines may cause bad side effects. A million people have died since July, when Russia and China had deployed vaccines. If by this time we had been able to deploy widely even a fairly ineffective vaccine with a few bad side effects, how many more people would be alive today? And we are still losing 10 thousand people a day! How ineffective do the vaccines have to be, or how bad do the side effects have to be to justify this extra time?
14) I think these and other errors are in part because we are outsourcing our decisions about ethics to people who do not merit deference in these matters. Scientific expertise and ethical expertise are not the same thing. Challenging the ethics of a choice is far more defensible and legitimate than challenging a scientific conclusion - and even scientific conclusions are frequently wrong! Recently, a major healthcare organisation in the US recommended that elderly populations should be a lower priority than frontline workers because the latter are more racially diverse. Arguing against conclusions like this is not an argument about science but about values. Scientists and the healthcare community have expertise that can help inform decisions, but we have no special insight into ethics and values. 'Follow the science' is terrible guidance when the answer is not one that science alone can answer, and is usually a cover for political preferences. This year, it appears that the values of the healthcare community have led them to argue for some choices – and these have been taken at face value without requiring a justification or a discussion of the trade-offs we face.
15) While I'm on the mistakes of the public health community: even the excellent scientists within the community that I get most of my Covid information from show signs of risk aversion and groupthink. Many insisted in Feb - April that vaccines would take a minimum of about 2 years to develop, and some advocated for policy based on that timeline. They have not been challenged on this because the downsides of being wrong are asymmetric - but as a community, they were very wrong and in a predictable way (too cautious). I shared in spring that a vaccine within a year seemed plausible based on what I was reading from economists, who understand markets, political systems and incentives better. And here we are with a selection of vaccines in about 9 months. Most of those 9 months have actually been spent on trials - the actual design and creation of the vaccine by Moderna seems to have been accomplished by February. There has also been plenty of wagon-circling and questioning of credentials in response to legitimate challenges to the value judgements and assumptions of the healthcare community (notably when the majority of them chose to endorse the Black Lives Matter protests).
16) The supposedly incompetent American and UK governments seem to have done far more good by incentivising and investing in production and testing of medication and vaccines (through Operation Warp Speed & RECOVERY) than any of the European governments or the EU, and that doesn't even mention the fact that the UK caught the new virus strain through its far better genome sequencing efforts (REACT-1). Europe now faces the prospect of watching while the US vaccinates 100 million people by early spring while it waits for vaccinations to become available to it. I don't read local news in Europe but can't understand the lack of outrage over its appalling incompetence this entire year.
17) Finally: poor countries are being prevented by rich ones from using emergency exceptions to global trade rules to supply themselves with vaccines. The companies that made the vaccines should be compensated and I believe in financial incentives for medical development. But if a pandemic is not a time to waive some of these rules to save hundreds of thousands of lives, then when is? American and European governments should be shamed by their own citizens for this abuse of the system.
----------------
In response to a comment suggesting that caution was warranted because of serious problems with SARS/MERS vaccine tests in animals:
I'm quite willing to believe there were reasonable fears of failure and bad side effects. But the major side effects should have been the easiest to pick up - I imagine the issues you mention would have been evident in phase 1 trials. The later phases (to my knowledge) help to quantify efficacy, rarer side effects, and use a more representative sample of the population. This slow, staggered approach may be good in ordinary circumstances, though I'm somewhat sceptical given how irrational the system has revealed itself to be. But my argument is that speed ought to be a much higher priority given that we are in a pandemic in which millions will die.
It seems to me that players in the system have consistently been far too eager to stick with standard protocols. Many times during this pandemic, there have been suggestions about ways to accelerate the process, and these have been quickly swatted down with arguments that amount to "Trust us and stay the course".
A more rational approach would have considered the costs and benefits of staying the course and of trying different approaches. Human challenge trials were one early possibility, and there are now discussions about having hybrid phase 2 & 3 trials for future vaccines. How many lives would we have saved if these and other similar ideas had been considered seriously this time around? If speed had been a priority for the organisations reviewing and approving vaccines, and not just the companies manufacturing them?
Not trying to impute any particular views to you, of course. I'm just aggravated at how badly our societies have failed this, and the suboptimal way that science and scientists have featured in the discussions and planning.
----------------
A helpful comment by a medical doctor (NOTE THAT I DID NOT WRITE THIS):
"....To expand on point 3.ii: As you mentioned, pregnant/lactating and pharmacologically immunosuppressed patients were excluded from the Pfizer and Moderna trials. The American College of Obstetrics and Gynecology (ACOG) has recommended that patients do NOT need to be tested for pregnancy prior to receiving the mRNA vaccine and that the vaccine should be offered to pregnant/lactating women. Again, there is no specific data for this population so this will likely be a personal decision. I have a few female physician colleagues who are nursing infants and elected to be vaccinated.
For immunosuppressed patients we again have no data but have a few considerations; the mRNA vaccine MAY not be as effective given a lessened ability to mount a robust immune response. The mRNA vaccine should not, however, be considered more dangerous in this population. As with the MMR and older shingles vaccine, live-attenuated vaccines should be avoided in immunosuppressed individuals."
1) So far we have 7 vaccines being administered globally. Two based on mRNA (Moderna, Pfizer/BioNTech) that are the first vaccines of this type to ever be approved, and several based on established methods such as using inactivated or attenuated viruses. The mRNA vaccine technology is a fantastic development and bodes well for stopping many other diseases. There is considerable scope for improvement, though, because right now they are more finicky - the Pfizer/BioNTech vaccine needs to be stored at an incredibly cold -70 C and this will cause supply chain problems in developing countries (Moderna's seems to need about -20 C which is not easy but much more achievable). The Oxford/AstraZeneca vaccine uses a different, older method that ships a piece of the coronavirus DNA into you inside a chimpanzee virus that will not harm you. It should be much easier to store and transport. One Chinese and one Russian vaccine use the same method, and another two Chinese vaccines use killed/inactivated viruses. All require 2 doses to achieve full immunity, but in a few weeks we may see a single-dose vaccine from Johnson & Johnson approved.
2) If we focus only on the vaccines developed and tested in Europe & North America, the bottom line is: with very few exceptions (see next point), get any vaccine that is available to you. It does not matter if you get one that is 70% effective (Oxford/AstraZeneca) instead of one that is 95% effective(Pfizer/BioNTech and Moderna). The point is not just to protect yourself: it's to reach herd immunity. If everyone gets even the less effective vaccine, we will have reached herd immunity. Effectiveness at this point is much less important than ability to produce, distribute and administer the vaccine.
3) SAFETY: (i) There are very rare (EDIT: very roughly on the order of 1 per 100k to 1 million doses) severe allergic reactions reported to the Pfizer/BioNTech vaccine, possibly linked to the lipid nanoparticles used in it. These are also used in the similar Moderna vaccine, so we may see a few such issues with that too. If you have severe allergies to one of the ~10 ingredients used in the vaccine (they are quite simple), you may want to wait for another vaccine such as the Oxford/AstraZeneca. If you just have a lot of allergies in general, it doesn't look like there's any reason to worry. Please get the vaccine! If the high proportion of people who have some allergies decline to get vaccinated, we won't hit herd immunity until many more people die. (ii) Pregnant women (and possibly other at-risk groups) were excluded from most trials. We still don't know if the vaccines are totally safe for them and have not collected sufficient non-trial data to understand this well. It's very probably safe but we don't know for sure. Still recommended for these people to get vaccinated but I haven't read enough - do your own research.
EDIT: Please reach the comment about safety below from a medical doctor who knows his stuff.
EDIT 2: I should also note that minor side effects (headaches, swelling, pain, mild fevers) are quite common.
4) We know little about the 3 Chinese and 1 Russian vaccines. They were approved much faster without the large scale trials that have taken several months in the West, but not ever deployed at large scale (anyone know why?). They remain untrusted because of a (justified) lack of faith in the Chinese and Russian governments. But they remain underrated and if the data do back up their efficacy - and the Sinopharm vaccine seems to have been very effective in UAE trials - they may have saved many lives because of the speed of their deployment. They are also going to be much easier to store and distribute than the mRNA vaccines (but not the Oxford/AstraZeneca vaccine), so may be important in large parts of the developing world.
5) Protection is not immediate. For the Moderna and BioNTech/Pfizer vaccines, it seems to develop 7-14 days after getting the first dose. For the Oxford vaccine, it's quite clear there is protection after 21 days and possibly before, but they do not seem to have shared results from before this date (let me know if you have seen this). So once you get your shot, keep distancing for a couple of weeks.
6) All the present vaccines require two doses. But there's good evidence that even one dose of the Moderna and BioNTech/Pfizer vaccines (and I think the Oxford one too) provides strong protection. Investigating that ought to be top priority - we could potentially double our vaccine supply overnight if one dose protects! That buys us several weeks and tens to hundreds of thousands of lives (!) while production of these and other vaccines ramps up. Even if one dose does not provide lasting immunity, we don't need that immediately if we can immunise a large proportion of the population quickly. When they are available, we may be able to take additional doses of the same vaccine, or even a different vaccine. This has some risks but there appears to be evidence that a mix of vaccines could even be more effective (under investigation). The question is: is it worth risking tens to hundreds of thousands of lives because we are not sure that one vaccine provides lasting immunity? To put it in more personal terms: if you had two doses available, would you and your partner each take one, or would one of you take both?
7) The vaccines have been tested primarily for their ability to protect people from falling ill. And they do an excellent job. But there's a possibility that it does not prevent people from acquiring and transmitting the virus. That would be worrisome, because it could make tracking spread even harder given our lousy testing regimens in most places. But this seems to be quite unlikely, for multiple reasons. Among others, asymptomatic people pass on the virus to a much lower degree than symptomatic ones, so just reducing the proportion of symptomatic cases should reduce spread. You may hear about this worry, and it's mostly scientists being very cautious about not overstating what the vaccines do.
8) There's not yet enough data about efficacy in old people for at least the Oxford/AstraZeneca vaccine (EDIT: and apparently the Pfizer/BioNTech vaccine), which is strange and annoying. Some vaccine approvals were held up for weeks because regulators judged that companies had not recruited enough minority populations to validate efficacy in a broad enough segment of the population. Surely recruiting old people - the group overwhelmingly most likely to die if infected - ought to have been a priority?
9) The vaccines will quite likely provide more effective and longer-lasting protection than natural immunity (the advantages of intelligent design). Get it even if you have had Covid.
10) The vaccines very likely protect against the new UK & South Africa strains you've been hearing about. We won't know for sure for a while, though.
11) Every day of delay thus far and in the future has cost in the range of tens of thousands of lives. The first and worst reason for this is horrifyingly inefficient bureaucratic procedures, which I've railed about before. The US and Europe made us wait for 2-3 weeks before reviewing the vaccine data for approval while more than ten thousand people were dying every day, and about 2 hours of review were needed (most stuff was previously reviewed and approved). This is not being careful and competent. The fact that some grumbling from a German minister was enough to get the EU to bring forward its vaccine review date by 3 weeks tells you how useless the waiting periods are. The common rejoinder to the calls for speed is that we need to be slow to maintain public trust. I don't agree. Sure, people are sceptical of vaccines. Do these people deserve the heckler's veto? How many tens of thousands of lives are we willing to sacrifice to mollify a few antivaxxers?
12) But the problem is not just bureaucracy. It is also the ethical objections that epidemiologists and doctors have. A terror of 'human experimentation' prevented challenge trials (intentionally exposing volunteers to the virus) in spring and summer and is now being used to stifle efforts to evaluate single-dosing of vaccines to double vaccine supply. Similarly, queasiness about experimenting on at-risk populations such as pregnant women means that the vaccine was not tested on them. We are now basically leaving the decision about whether to get vaccinated to these people without data or guidance. Is this the ethical solution, or a cop-out? We have successfully avoided sins of commission by avoiding tough decisions at the probable cost of tens to hundreds of thousands of lives so far. These sins of omission of people in charge (and the public health community) are either because they have not thought through costs and benefits appropriately, or because they are using reasoning that they are not explaining.
13) Care is obviously warranted, as public scepticism of vaccines is a worry that we want to avoid. But requiring that we have very strong evidence from multiple rounds of testing may have cost hundreds of thousands of lives now. Was this worth it to reduce the possibility of errors? To maintain trust in the system so people will listen to them about future vaccines and medication? Perhaps it is! But I'd like to see that defence made explicitly, instead of deflection through claims that vaccines may cause bad side effects. A million people have died since July, when Russia and China had deployed vaccines. If by this time we had been able to deploy widely even a fairly ineffective vaccine with a few bad side effects, how many more people would be alive today? And we are still losing 10 thousand people a day! How ineffective do the vaccines have to be, or how bad do the side effects have to be to justify this extra time?
14) I think these and other errors are in part because we are outsourcing our decisions about ethics to people who do not merit deference in these matters. Scientific expertise and ethical expertise are not the same thing. Challenging the ethics of a choice is far more defensible and legitimate than challenging a scientific conclusion - and even scientific conclusions are frequently wrong! Recently, a major healthcare organisation in the US recommended that elderly populations should be a lower priority than frontline workers because the latter are more racially diverse. Arguing against conclusions like this is not an argument about science but about values. Scientists and the healthcare community have expertise that can help inform decisions, but we have no special insight into ethics and values. 'Follow the science' is terrible guidance when the answer is not one that science alone can answer, and is usually a cover for political preferences. This year, it appears that the values of the healthcare community have led them to argue for some choices – and these have been taken at face value without requiring a justification or a discussion of the trade-offs we face.
15) While I'm on the mistakes of the public health community: even the excellent scientists within the community that I get most of my Covid information from show signs of risk aversion and groupthink. Many insisted in Feb - April that vaccines would take a minimum of about 2 years to develop, and some advocated for policy based on that timeline. They have not been challenged on this because the downsides of being wrong are asymmetric - but as a community, they were very wrong and in a predictable way (too cautious). I shared in spring that a vaccine within a year seemed plausible based on what I was reading from economists, who understand markets, political systems and incentives better. And here we are with a selection of vaccines in about 9 months. Most of those 9 months have actually been spent on trials - the actual design and creation of the vaccine by Moderna seems to have been accomplished by February. There has also been plenty of wagon-circling and questioning of credentials in response to legitimate challenges to the value judgements and assumptions of the healthcare community (notably when the majority of them chose to endorse the Black Lives Matter protests).
16) The supposedly incompetent American and UK governments seem to have done far more good by incentivising and investing in production and testing of medication and vaccines (through Operation Warp Speed & RECOVERY) than any of the European governments or the EU, and that doesn't even mention the fact that the UK caught the new virus strain through its far better genome sequencing efforts (REACT-1). Europe now faces the prospect of watching while the US vaccinates 100 million people by early spring while it waits for vaccinations to become available to it. I don't read local news in Europe but can't understand the lack of outrage over its appalling incompetence this entire year.
17) Finally: poor countries are being prevented by rich ones from using emergency exceptions to global trade rules to supply themselves with vaccines. The companies that made the vaccines should be compensated and I believe in financial incentives for medical development. But if a pandemic is not a time to waive some of these rules to save hundreds of thousands of lives, then when is? American and European governments should be shamed by their own citizens for this abuse of the system.
----------------
In response to a comment suggesting that caution was warranted because of serious problems with SARS/MERS vaccine tests in animals:
I'm quite willing to believe there were reasonable fears of failure and bad side effects. But the major side effects should have been the easiest to pick up - I imagine the issues you mention would have been evident in phase 1 trials. The later phases (to my knowledge) help to quantify efficacy, rarer side effects, and use a more representative sample of the population. This slow, staggered approach may be good in ordinary circumstances, though I'm somewhat sceptical given how irrational the system has revealed itself to be. But my argument is that speed ought to be a much higher priority given that we are in a pandemic in which millions will die.
It seems to me that players in the system have consistently been far too eager to stick with standard protocols. Many times during this pandemic, there have been suggestions about ways to accelerate the process, and these have been quickly swatted down with arguments that amount to "Trust us and stay the course".
A more rational approach would have considered the costs and benefits of staying the course and of trying different approaches. Human challenge trials were one early possibility, and there are now discussions about having hybrid phase 2 & 3 trials for future vaccines. How many lives would we have saved if these and other similar ideas had been considered seriously this time around? If speed had been a priority for the organisations reviewing and approving vaccines, and not just the companies manufacturing them?
Not trying to impute any particular views to you, of course. I'm just aggravated at how badly our societies have failed this, and the suboptimal way that science and scientists have featured in the discussions and planning.
----------------
A helpful comment by a medical doctor (NOTE THAT I DID NOT WRITE THIS):
"....To expand on point 3.ii: As you mentioned, pregnant/lactating and pharmacologically immunosuppressed patients were excluded from the Pfizer and Moderna trials. The American College of Obstetrics and Gynecology (ACOG) has recommended that patients do NOT need to be tested for pregnancy prior to receiving the mRNA vaccine and that the vaccine should be offered to pregnant/lactating women. Again, there is no specific data for this population so this will likely be a personal decision. I have a few female physician colleagues who are nursing infants and elected to be vaccinated.
For immunosuppressed patients we again have no data but have a few considerations; the mRNA vaccine MAY not be as effective given a lessened ability to mount a robust immune response. The mRNA vaccine should not, however, be considered more dangerous in this population. As with the MMR and older shingles vaccine, live-attenuated vaccines should be avoided in immunosuppressed individuals."