Here's the second of two back-to-back Covid posts focussed on vaccines and evolution. The first part can be read at https://www.mridulkthomas.com/covid/30012021-part-1.

Some parts of this post are moderately speculative and based on a general understanding of evolution and not a deep understanding of viruses. Take with a pinch of salt, and I welcome criticism of these thoughts. 

Terminology: 
I will refer to three mutations: N501Y, E484K and K417N. 
And to three variants of the virus: the UK variant (B.1.1.7), the South Africa variant (B.1351) and the Brazil variant (P.1). I'll skip the dots and say B117, for example.

1) Mutations happen spontaneously when nucleic acids like DNA and RNA are copied, because the process is imperfect and some of those copies have errors (to oversimplify a bit). Most mutations tend to be very bad for the organism (I mean the virus) because they stop some part of it from working and many parts are necessary. These mutations are immediately 'lost' because the organism (the virus) cannot reproduce itself, so we never get to see these mutations that are damaging to the virus even though they are the majority. A small number of mutations will tend to be only slightly bad; they will arise and then slowly die out over a few generations because they are less good than their relatives without the mutation. Some mutations have no real effect and just get passed on without changing anything. A very tiny proportion can make the organism better (for the virus that is, it would be worse for us). 

2) This is a bit more complicated with a new virus like this one. An organism that has been around for a long time has evolved and adapted to its environment. Evolution never stops, but the easy adaptations - the simple changes that cause big improvements - have already happened, and so it's extremely rare for a mutation to help much. But a new virus has not had the time to do that. It's suddenly experiencing a totally new and different environment after many generations of adapting to life in bats. So there are many more possible ways for it to get better at growing and spreading in humans (that is, make it worse for us), and the number of possible mutations that can help it get better is likely to be much larger. We are very lucky that this virus mutates quite slowly. We've had hundreds of millions of infections so far and perhaps trillions of virus particles generated, but only a tiny handful of mutations have arisen that have clearly helped the virus i.e. made it worse for us. 

3) We cannot rely on evolution to make this virus safer for us. A common but incorrect idea is that the virus will necessarily evolve to become less deadly over time. There is some evolutionary logic to this notion. A dead host cannot transmit the virus, the thinking goes, so variants that are less likely to kill their hosts should be more successful at being transmitted. These variants should therefore take over from more lethal ones. It's a nice story but there's little evidence that this happens in other viral diseases. And even the logic fails completely with Covid. The reason is that people infected with Covid pass on the virus mostly within the first week of their infection. If they die, it happens about 2-3 weeks after that. So whether the infected person lives or dies does not affect transmission of the virus. Evolution will not necessarily push the virus to become less lethal because it does not even 'see' whether the infection was lethal or not. It might become less lethal. But the opposite is perhaps equally possible: the virus could evolve to become more lethal. There's a small amount of evidence from the UK that this has happened. People infected with the UK variant there are thought to have a death rate that was 30% higher than previous strains (more evidence needed to be confident in this). I should note that a possible 30% increase in the probability of dying from Covid is very bad news, but it's not as terrifying as it sounds at an individual level. It's about how much worse your risk of dying from Covid would be if you were ~2 to 3 years older. 

4) Of the many mutations we have seen in the viruses we have sequenced from around the world, the most noteworthy right now are mutations N501Y, E484K and K417N. You'll probably hear more about them in the next few weeks. The names denote the position and nature of the change in a protein. For example, N501Y means that a mutation changed the amino acid at the 501st position on a protein from asparagine (symbol N) to tyrosine (symbol Y). All three of these mutations alter a specific part of the 'spike' protein that the virus uses to attach itself to our cells. Some of our vaccines are designed specifically to elicit antibodies from us that will attack this protein in the virus. This is because it's a distinctive target (different from other viruses and antigens), the virus needs it to have a particular shape to attach to our cells, and because of this it probably evolves more slowly than other parts of the virus. But this protein has evolved in several virus variants, and the changes have had a variety of effects. 

5) To simplify some terminology: a variant / lineage / strain is a group of viruses that have descended from a common ancestor and share similar sets of mutations. If new mutations arise in a variant that make it seem different enough, then we deem the viruses with those new mutations a new variant. We give the variant a new name, just like we name strains of wheat or rice. But the way we name virus variants is dizzyingly complicated and unintuitive. There are multiple scientific names, and some of them are named after important mutations (which can occur in multiple variants, remember). So the 'UK variant' is also called B117 by some scientists and 501Y.V1 by others. Geographical names are considered bad because they can lead to negative publicity for the associated place. But the alphanumeric gibberish of B117, B1351 and B11248 (renamed P1) is incomprehensible at a time when we desperately need clarity. In the future I think we should name these like hurricanes or after random objects (apple/banana/cantaloupe). For now I would stick with the geographical names for simplicity. 

6) From some fantastic lab studies, we have a pretty good understanding how some mutations have caused a few variants to spread more quickly. The mutation N501Y evolved independently in all three variants we are most alarmed about - the UK variant B117, the South Africa variant B1351, and the Brazil variant P1. Remember that mutations arise at random, so the fact that this one arose independently in 3 variants that all spread more rapidly is strong evidence that it matters a lot. We know even more: N501Y probably increases transmission rates because it makes the virus better at attaching to our cells. Another mutation E484K is present in the South Africa and Brazil variants and is the most concerning of the mutations we understand. Among other properties, E484K appears to give the virus more protection against antibodies (our own or manufactured monoclonal antibodies). This makes our vaccines less effective against variants with this mutation and probably also makes reinfection with these variants more likely. This may be true of another mutation K417N as well, which is also present in both the South Africa and Brazil variants. It's possible that E484K spread quickly because it allowed variants with this mutation to reinfect people who had already had Covid from earlier variants (quite uncertain, under investigation). There are many more mutations that we don't understand quite as well as these three. They likely modify how the main mutations mentioned earlier work. For example, N501Y has arisen in some other variants that don't seem to spread faster - so it's possible that it needs to be combined with some other mutations to help the virus, or that the combination helps them a lot more than N501Y by itself. The opposite is also possible; some mutations may make N501Y less helpful to the virus. We still don't understand these combinations well, and they will matter in the near future. 

7) I want to highlight the distinction between mutations and variants, and explain why we are worried about both. The same mutations can occur in multiple variants, either because it arose independently or because they inherited it from a common ancestor. The mutations I talked about above evolved independently in the UK, South Africa, and Brazil variants. Each of these variants also have other mutations that make them distinctive. The South Africa variant B1351 has the mutations N501Y, E484K, K417N and several more that we do not understand well. We keep track of which geographic regions some specific mutations are found because we know that they make the virus more dangerous to us. It is useful to know, for example, that E484K is found in most of the viruses in a country - people there may have less protection against the viruses they face. But because we don't understand many of the mutations well, we also need to track variants that are more dangerous; they may possess a particularly potent combination of mutations. For example, we know that the South Africa variant B1351 spreads faster and that we have less protection against it from vaccines, even if we don't fully understand all the mutations that cause that to happen (E484K is part of the story but probably not all of it). The next few months are going to involve plenty of discussion both of new mutations and new variants. There will be new variants that arise that have some of these same mutations as well as new ones. We will have to worry about these new variants, but we don't know how much to worry because we don't know about how the other mutations they will carry affect the virus. And there will also be new mutations that arise in some of these existing variants, which may lead to them being designated new variants - just like a single species of mammal can over time split into multiple species that we will give separate names. 

8) Now that large numbers of people have been infected in many places, and we are ramping up vaccinations, many more people will have some immunity against the virus. This is a tremendous change in the evolutionary landscape. I expect to see the rise of a broader range of mutations & variants as a consequence. Why? Mutations that earlier may not have increased the spread of the virus much could now make them more successful (i.e. worse for us). Many mutations probably exist which earlier may not have conferred much benefit to the virus and may even have made the virus worse (which would be good for us, and would lead the mutation to die out). But if these mutations allow the virus to get around our antibodies (whether from a vaccine or previous infection) even partially, they now confer a huge advantage for the virus. Imagine a change to shape of the protein that the virus uses to attach to our cells. You could imagine a change that makes it slightly worse at attaching to our cells. Normally this would make it less infectious than background Covid strains and so viruses with this different protein would die out. But if the new protein shape is different enough that it is not 'recognised' by our antibodies, this mutation will now confer a huge advantage to the virus and will spread. It's possible that E484K spread because of this. It is not likely to be the only such mutation - we should expect to see many more in the coming months. 

9) I want to reiterate that vaccination is going to massively improve our situation, and fast. Despite the spread of these variants, we should be able to get deaths down to negligible numbers in developed countries in months by doing this, and life will start to return to normal there. But developing countries will wait much longer for vaccination because of terrible planning: we have failed to build the manufacturing or distribution capacity needed to vaccinate a large chunk of the world's population quickly, and we should have. This is not even a moral argument. It is in the interest of rich countries to speed up vaccination in poor ones because large, partially-vaccinated populations will be a reservoir for evolution of variants that can return to rich countries and possibly evade their immunity then (again, this is fixable with updated vaccines, which can be designed quickly). 

10) What can you do? Get vaccinated as soon as you can. Wear good masks (N95/KN95/FFP2) from now till at least a couple of weeks after your vaccination. Once you're vaccinated, you still might want to be a bit careful for a while. I will probably wear some mask in crowded or indoor spaces till cases are very low. But I think people who argue you should continue isolating as before even after vaccination are out of their minds. Go hug your friends and family once you've got some immunity. I sure as hell will. 

I've been busy working on tracking Covid variants with Brooks Miner (www.covidvarianttracking.com & @CovidVariants on Twitter) so haven't written a Covid update in a while. Here's the first of two back-to-back posts focussed on vaccines and evolution. I would strongly advise you to get any vaccine you have access to, with strong caveats for the Bharat Biotech Covaxin vaccine in India (zero data, shady govt. practices), and weaker ones for the Chinese & Russian vaccines I discussed a few weeks ago (some data available, seems okay if it is reliable): 

1) What you probably already know: the UK variant and the South Africa variant spread substantially faster than background strains - somewhere between 30% & 70%. A Brazil variant with some of the same mutations probably spreads at a similar speed. The UK variant has increased rapidly in Denmark, Ireland, Portugal, and now Switzerland - the picture has been pretty bad in these countries in recent weeks. Check our maps at the link above and you see cases of it have been detected in most parts of the world. Though many are from travellers, it's too late for many/most countries to avoid outbreaks. But where it is still at low frequency, there is probably a 2-4 month window before this variant (or one of the others) forms the majority of cases. The South African variant is also being detected much more widely now, with many more cases from African countries (which generally have poorer genetic surveillance systems in place) and clear signs of community transmission in the US. The Brazilian variant P1 seems to be wreaking havoc there but has not really spread outside it yet - as far as we know. 

2) What you can do: distance yourself even more strictly for now, and get better masks. Buy yourself N95/KN95/FFP2 masks without valves and wear them. If you don't have access to these, wear multiple layers of masks. Before we got our FFP2s, we were wearing cloth masks on top of surgical masks for some additional protection.

3) These variants and similar ones will likely cause an increase in case loads in many countries that are lagging on vaccinations (most of them). This is NOT inevitable! The UK & Ireland were the countries worst hit by these faster-spreading strains - and they have seen cases decline rapidly since they put in place additional protection measures. It's still possible to control this, and we must do everything we can to. The vaccinations give us an additional edge in this race, but the same old measures - masks, distancing, quarantines - are sufficient if done well. 

4) We have data on 2 new effective vaccines (Novavax, Johnson & Johnson) but there are good reasons for concern in the medium to long term. These new vaccines have been tested recently and we can evaluate their performance against the new variants. Both are very effective against most Covid strains but Novavax is slightly less so against the UK variant B117 (~85% efficacy vs. 95% for older variants). Both also considerably less effective against the South African variant B1351: approximately 60% instead of 90% for Novavax, 60% vs.70% for Johnson & Johnson (the values may be more similar for serious infections). We've had good reason for some weeks to think that antibody responses against the South African & Brazil variants are less effective, and this shows that those reductions matter in the real world. It also probably means that all the other vaccines will also offer less protection against at least these two variants, as well as others that are not yet on our radar. Yet again, there's been misleading public health messaging around this, I'm afraid. 

5) 60% effectiveness is very good and you should definitely get vaccinated! And the protection against serious infections seems even better (if you fall ill, it appears to be milder). If the virus could not evolve any more, a 60% reduction in infection rates everywhere would end the pandemic. But they will continue to evolve (see next post about this). If 60% reflects vaccine effectiveness now, additional evolution should reduce that number as more mutations arise in these variants. At least some of those mutations will make the virus even better at getting around our antibodies. Vaccine makers are creating new forms of the vaccine that will specifically target the mutations in the new variants. The mRNA vaccines from moderna and Pfizer/BioNTech are particularly good for this - they can be retooled in weeks. But it's a moving target and our vaccine manufacturing and distribution capacity (not to mention our political and administrative capabilities) lag well behind the viral spread. 

6) [Warning: speculation] If antibodies from the vaccines are less effective against these variants, it also seems likely that antibodies from an earlier Covid infection will be less effective. Immunity is about more than antibodies and reinfections are rare now. But I would expect that getting infected a second time will be more likely with the new variants. 

7) I want to underscore that we can get ahead of this and avert much loss of life from these variants in developed countries at least. Remember that an infected 80-year-old is 100 times more likely to die than a 40-year-old, and about 1000 times more likely to die than a 20-year-old. If countries prioritise the most vulnerable populations (basically the elderly) for vaccination, then they should avoid most deaths even if the variants continue to spread. This would be a massive success and is actually quite likely. Israel has given nearly 60% of its population at least one dose! The UAE is at about 30%. The UK about 12%. The US is at 8% despite its very public failures on many counts. The EU is lagging badly at 2.5% and has been hit by a string of bad news, with many expected vaccine deliveries being delayed. All these numbers are way lower than they would have been if governments had reacted competently, but they still represent real and important progress. I expect to see rapid declines in deaths in the next few weeks starting with Israel and the UAE, but also the US and the UK, partly driven by vaccination and partly because the deaths caused by the Christmas travel will fade out soon. We might see flare-ups again because of these variants, but I would expect deaths in most of these places to remain low even if infections rise again because the elderly will be vaccinated.

8) The medium-term outlook (~few months) is more scary in the developing world, which is at the back of the queue for vaccines. Most African countries have not started vaccination because they could not pay as much as developed countries. They are not expected to make major progress on vaccination till 2022, and some might take till 2023 to complete. There has probably been large-scale underreporting of cases and deaths from many of these countries, and the rise of fast-spreading variants could quickly drive new outbreaks even in countries that have controlled their spread (and many developing countries have done so, which should shame the developed ones).

9) The long-term outlook is complicated because a pandemic that is still out-of-control in some parts of the world threatens even those parts that have been vaccinated. Every outbreak offers more opportunities for evolution, which you cannot stop. The best way to avoid this mess was to not give the virus trillions of opportunities to mutate and therefore 'find' some of the rare mutations that help it. In other words, stopping the pandemic early on. That ship has sailed. The next best is to reduce community transmission now so that in addition to vaccination, we deny the virus opportunities to accumulate new mutations that will help it spread in the face of antibody defences. It will be impossible to sustain this effort for another 2 years while we get every developing country vaccinated. In that time, additional mutations will quite likely arise that will lead to variants with a stronger ability to evade our antibodies re-entering developed countries (see next post). 

10) It therefore continues to be overwhelmingly valuable even for developed countries to invest in production facilities for vaccines. And in optimising the entire supply chain. The reason why some places got 6 doses instead of 5 from their Pfizer vials is that they were using special syringes that wasted less liquid - how many lives can we save by producing more 'low dead space syringes'? We are not in the endgame yet and the benefits of these investments outweigh the costs by several orders of magnitude. One estimate is that moderna & Pfizer will earn about $10 billion from the vaccine; the economic losses due to Covid are so far in the region of $5 trillion. Just give them all more money to make more and faster. I'm astounded that the EU delayed vaccines by - among other things - negotiating strongly for lower prices and for manufacturers to be held liable for problems.

The new Covid variants are alarming. Brooks Miner and I build a dashboard to track the spread of the major ones:  http://covidvarianttracking.com. We plan to update this daily.

I don't think there's a similar tool out there, so please do share this with anyone interested.

Features to be added soon: the proportion of new cases in a country caused by each variant, percentage of the population vaccinated, and how long it should take for the fast-spreading variants to dominate in new cases.
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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.

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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.

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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."