Mridul K. Thomas
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ecology - phytoplankton - functional traits

01.01.2021

2/1/2021

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An urgent update about the UK covid strain, about which I'm alarmed. So excuse the wordiness of this post. Keep in mind that none of what I write below is certain. I'd say there's about a 70% chance that the new strain spreads much faster (>50%) than existing strains of covid. Here's how we know that and why it is terrible news. As always, I'm not an expert in this, please correct me if you spot errors.

1) We already knew that the strain was rising to dominance in the South and East of the UK, starting in September. It's now been found all over the UK, across Europe, in the US, South America, Middle East, Australia, Asia...basically everywhere they've had time to look.  Brooks Miner has helpfully made this map showing where cases are being found: https://public.tableau.com/profile/brooks.miner#!/vizhome/MapVariants/Dashboard. So far very few cases detected outside the UK but we have almost certainly missed many, many more. In the US and several European countries, there's already good evidence of local transmission, at least on a small scale. If we're very lucky, it hasn't had time to spread much - but this is looking increasingly unlikely.

2) See my last post for what we knew a few days ago. The main new information we have is twofold. (i) Virus levels in people with the UK strain seem to be 10-100 times higher than people with other strains on average (although with huge variation between individuals). This *might* be because of biases in the data - this sudden rise in testing may mean that cases are now caught earlier, before the immune system has reduced virus levels. But the most plausible explanation is that this is a real biological difference. It would also explain why the strain is transmitted so much more - people infected with it are producing more viruses and (presumably) expelling more as well. (ii) There's also some moderately persuasive data showing that people infected with this strain recently have infected more people themselves (more precisely, the secondary attack rate was about 50% higher). Along with the rise to dominance of the strain in the UK and what little we know about the mutations, these pieces of information point towards this being a real and dangerous phenomenon. There isn't consensus about this and there are still some puzzling pieces - we don't have clear evidence of rapid rise in other European countries though the opportunity has been there. But if true the implications are disastrous and I'm very glad countries did not wait to react. They will have to do much more, and fast.

3) What does a 50% rise in transmission mean? It's very, very bad - much worse than a 50% increase in how lethal the virus is! That's because we are talking about increasing the speed of an exponential process - like compound interest for your bank account, or GDP growth rate. I'm just going to steal this excellent example from Adam Kucharski on Twitter to explain what it does. Remember that R = reproduction number, or number of people 1 infected individual will go on to infect on average (so the goal is to get R below 1, which means a decreasing epidemic):

"As an example, suppose current R=1.1, infection fatality risk is 0.8%, generation time is 6 days, and 10k people infected (plausible for many European cities recently). So we'd expect 10000 x 1.1^5 x 0.8% = 129 eventual new fatalities after a month of spread... Now suppose transmissibility increases by 50%. By above, we'd expect 10000 x (1.1 x 1.5)^5 x 0.8% = 978 eventual new fatalities after a month of spread."

So increasing the fatality rate by 50% would kill about 60 more people in a month, but increasing the transmission rate by 50% would kill 850 more. And the 1 month time horizon is arbitrary. If you look a bit longer it gets even worse, at least till the virus has infected so many people that it has limited its pool of people to infect (which is what approaching herd immunity means).

Full thread at https://twitter.com/AdamJKucha.../status/1343567425107881986

4) It took from September to December for the strain to rise to a majority or near-majority across several regions in the UK, despite lockdowns. Lockdowns reduced R below 1 for other strains - but not this new one. Measures that used to be enough to reduce R below 1 and control the pandemic are no longer sufficient (this is a complicated topic but FWIW, I don't think stay-at-home orders were or are necessary). We need to take measures that earlier would have reduced R below 0.67 for the earlier strains, because a 50% increase in 0.67 = 1 (R would have to go ever lower if the strain spreads more than 50% faster, which remains possible). This is incredibly difficult. There are only a small handful of countries in the world that have ever reduced R below 0.67 in the past year. In recent months, it looks like only Azerbaijan and possibly Cambodia, Belgium and Papua New Guinea have done it, and that's assuming we can trust the numbers. (R estimates from https://epiforecasts.io/covid/, which covers most but not all countries). Some of the harshest lockdowns in the world have not driven R this low - and we need to do this now, in the face of an exhausted populace with an angry and conspiratorial minority. I don't think we will do it.

5) If we cannot control spread (which is possible but seems unlikely to me), rich countries may just about get ahead of this by going all out on vaccinations as fast as possible (assuming the vaccines protect against it, which is still very likely). It will probably take 1-2 months before this strain rises to dominance in countries other than the UK and some countries are well-placed to take advantage of this. Canada and the UK have already taken the wise decision to not hold on to people's second doses but to vaccinate as many people as possible with the first dose right away. The UK is going further by stretching out the period between the first and second dose to vaccinate more people. This is going to be extremely controversial because this is not how the vaccines were tested and they are going on the expectation that immunity will reduce quite slowly. It's a risky but warranted measure in my opinion. It slightly increases risk to individuals being vaccinated - which is why many doctors will hate it - but will save many more people in the population (see my last post for a related discussion of ethics). The US is not taking these steps but is distributing huge numbers of vaccines. It is failing miserably in administering them so far (potentially wasting many doses), but I expect this will turn around and they will have ~60-100 million people vaccinated by March. This will make it much harder for the strain to spread, and since they will vaccinate old people first, the number of possible deaths should be much lower by April despite the new strain. The EU will take much longer to get vaccines, and there is also surprisingly high vaccine scepticism (40-60% in France unwilling to take it!). Given that there is already community spread on the continent and it was already doing a bad job controlling the previous strains, I expect the new strain to spread rapidly. I'd put a high probability on the situation across Europe getting much worse by early March because of the new strain (several assumptions here, and I really hope this is wrong). Again, targetted vaccinations could ameliorate this substantially, but Europe has a lot of old people and not many vaccines. Germany expects to begin mass vaccination only by March or April, by which time 1/3 to 1/2 of the US will probably be vaccinated. For a comparison with a more competent response, Israel has already vaccinated nearly 50% of people over 60, and about 10% of its whole population.

6) My biggest concern is developing countries that have just about been able to control spread. For example, India has had covid numbers reduce steadily since September (this merits its own post) with R at about 0.8 to 0.9 for several months. Increase that by 50% and we're quickly back in an exploding epidemic in a country that has already been hammered by covid; its economic consequences alone have undone several years of poverty reduction, which almost certainly has led and will lead to a large loss of life. And because rich countries have monopolised (to exaggerate only a little) doses from all the approved and soon-to-be-approved vaccines, a majority of the population may not be vaccinated even by end-2021, when Europe and North America are well on the road to recovery. The Chinese and Russian vaccines may help poor countries a great deal if they are effective (as seems increasingly likely) and production can be rapidly ramped up, because it seems likely that they will be shunned by developed countries. But overall, it's hard to escape the feeling that in 2021 and likely beyond, developing countries will continue to bear the brunt of bad policy in developed countries.

7) And at the risk of flogging a dead horse, I hope the last 2 points bring home just how much good we might have done by evaluating, producing and distributing vaccines faster. The vague desire to preserve confidence in the system and to not cause risk to individuals has led to the loss of countless lives already, with many, many more to come. If nothing else, 2020 should have made you more sceptical of governments and bureaucracies, even those run by well-intentioned experts.

8) We don't know yet if the UK strain is more lethal. You will see reports saying it's not different, but these are based on very limited case numbers that are being overinterpreted. We just don't know, and there's a decent chance that it actually is more lethal because of the increased virus numbers. It may be a while before we have enough data to evaluate that with any confidence.

​9) What can you do? (i) Talk to people you know about vaccinations! If you have questions about them, chime in here or contact me and I'll try to help you find an answer. I would strongly recommend you get any vaccine you have access to right now, but there's a lot of very reasonable uncertainty and concern about them. If you have training in science or medicine, please talk to friends and family about this - you might be surprised at just how common worries about vaccination are. (ii) Pressure your governments to get vaccines out ASAP if you have any influence. (iii) Avoid people especially for the next week, since many will have returned from meeting family over the holidays - that might lead to a spike in cases by late January. (iv) Expect case loads to rise in Feb even if the conditions are presently improving where you are, and plan accordingly. Don't make plans for late Feb or March. (v) Otherwise, do the same things we've been talking about for months, but remember that there's now less margin for error. Don't meet people indoors, in semi-enclosed spaces or in crowded outdoor spaces. If you must be indoors, wear a mask and push hard for better ventilation. Don't mistake the surface-cleaning and hand-sanitising for actual safety, those do not achieve much and only give the appearance of safety.
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23.12.2020

2/1/2021

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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."

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21.12.2020 #2

2/1/2021

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The basic story so far about the new UK virus variant (/strain?) is that there was a surge of cases recently in the South and East of England. A surprisingly large proportion of them were of a new variant (of which there are thousands - but most behave/function exactly the same way). It's possible that this is a fluke and the strain just got lucky. But it (1) seems to have overtaken all the other local strains, and (2) also possesses multiple mutations that earlier studies of other strains had suggested may contribute to increased spread.

The South African strain shares at least one of these mutations and also appears to be increasing in prevalence there, which is sort of an independent test of the hypothesis, albeit (I think) with weaker data.

So too early to be sure, but good reason to be alarmed and to take action. However, these strains are likely elsewhere already. One hopes that they are at a low enough level that they will not spread, but so far attempts to contain spread have been disastrous in Europe and the US. The quick action to suspend travel now is good, but it doesn't mean much if uncontrolled spread within borders is tolerated. The more people get infected, the more mutations will randomly occur in the virus - and some of them may increase spread, or make it more lethal, or make it harder to defend against with natural immunity or with our present vaccines (only increased spread has been suggested for this new variant, not the other possibilities). Allowing the virus to run free through your population is idiotic for many reasons, it turns out.


EDIT: Going based on prior knowledge, the vaccines *probably* protect against these strains too. But we have no data about this and it's far too early to be confident. Wearing masks and avoiding other people definitely protects you.

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21.12.2020 #1

2/1/2021

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FYI, we don't know with high confidence whether the new UK [or South African] virus strain is more contagious. But it seems very plausible. It's also quite plausible that this strain is already in other countries too - the UK does better monitoring than most places.
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The vaccines are here. Be safe till you get yours. Meet friends outdoors if possible.
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02.12.2020

2/1/2021

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If you're in the US, it's probably worth isolating yourself even more post-Thanksgiving break - whether you travelled or not. It's quite likely that cases will spike in the next 7-10 days because of everyone else's travels. Even if there are few cases in your town now, meeting people means that you will be exposing yourself to the risk levels of other parts of the country that may be in much worse shape.

And if you're in Switzerland, maybe avoid members of parliament? They just celebrated a 70-year old politician's birthday in the parliament building with crowds singing and playing wind instruments maskless. And then tweeted proudly about it.
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01.12.2020

2/1/2021

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In response to a question about whether covid was circulating in the US in December 2019:

I think it's quite unlikely to be true. This is the best thread about it that I read: https://twitter.com/trvrb/status/1333647437869633537

Summary:

1) It's probably cross-reactivity from seasonal coronaviruses (as the authors discuss themselves). If I understand correctly, there was only 1 sample in the entire study that tested positive to the most COVID-specific assay (S1-specific Ig). 39 samples tested positive for less specific tests.


2) The raw numbers are not very persuasive (3/519 tested positive in their 'true negative' set of older samples, vs 39/1912 in the set they were evaluating). It's a convenience sample and the authors themselves argue that inferential statistics are inappropriate. But if you ignore the convenience sample and do a Fisher's Exact Test, you get p = 0.02 (not my analysis, see linked Twitter thread). Not very convincing.


3) 39/1912 is about 2%. If you ignore the convenience sample and assume that it is true and representative, where were all the dead people? The hospitals would have been flooded. Also, at least one big testing campaign done in Jan turned up nothing.


Basically, it's an awfully weak result to hang such a major conclusion on. And it's in conflict with a fair amount of other evidence. So I'm quite sceptical and inclined to ignore it, at least until more evidence is provided. It's not impossible but this evidence is too weak to shift my priors meaningfully.

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24.11.2020

2/1/2021

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While sharing the story of a friend who was infected with covid twice: 

There could well be long-term effects of the illness, even for the young.

In most parts of the world, the situation now is worse than it's ever been since this started. We have 3 vaccine candidates that should be here in months. Hold on! Don't give up on being careful now - we could be past this in a few months. If you must meet family or friends for holidays (better if you don't), use masks and ventilation (a few open windows makes a big difference) where possible. If you are unsure about what measures are effective or anything else, please ask and I'll hunt down whatever information you need.
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28.07.2020

2/1/2021

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Coronavirus news #8. As always, please point out my errors. Not an expert in this specific domain, but I have relevant training and am trying to keep up to date. Which is becoming harder and harder, so read this - and everything else on the topic - with a sceptical eye. I encourage those of you with relevant expertise to also spread your understanding as best you can.

1) Despite improvements in treatment, the number of reported daily deaths continues to climb globally, albeit slowly; it's now about 5500 per day, which is an underestimate. Brazil, India, Mexico and the US account for a big chunk of those, with Colombia apparently set to join that group. In all of them the number of daily reported cases is stable or increasing. And the fraction of tests that are positive in those countries is increasing over time, which means that we are missing more and more cases. The fraction positive is perhaps stable in the US, but there are additional wrinkles there. The US is seeing increasing time lags between the test being administered and the result being declared, especially in the states with the biggest outbreaks, so the true fraction positive is quite possibly still increasing. South Africa is also probably in very bad shape; there are reports that the true number of deaths is more than twice as high as the reported numbers, and the fraction of positive tests is skyrocketing. And South Africa is the worst on the continent, but there have been large increases in cases in many African countries recently, after a long period when they had done very well.
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2) We've now got better evidence that some people have pre-existing immunity, or at least produce antibodies that probably confer some immunity. This had been suspected for South-East Asia; now, a study of blood samples in the UK collected before the pandemic found antibodies that neutralise the virus. In the 6-16 year age range, 60% produced these antibodies; it was very low in older people. These neutralising antibodies were probably formed in response to other coronaviruses that cause the common cold, and their similarity to SARS-COV-2 likely provides some protection (though we do not know this for sure). This is one small study in the UK, but it seems to have been reliably done. If confirmed, it could be very important, especially if some poorer countries have had higher exposure to these coronaviruses & greater prevalence of immunity. More details at: https://twitter.com/KevinWNg/status/1286600426264158213

3) We also have some good vaccine progress! 3 vaccines looked promising in phase 2 trials, which check for safety. They showed the signs that we associate with them being effective (stimulated antibody production), though these trials could not test if they actually protect against COVID. They have now started phase 3 trials to test this specifically. A fourth vaccine has been approved by China on an emergency basis without phase 3 trials, and many more are still in phase 2. At least one of the phase 3 vaccine teams has built up massive manufacturing capacity, so if it works, we could start to see vaccines being widely distributed in months. Distribution is a challenge that needs to be discussed globally, because it is likely to come down to a power struggle, especially given the US govt's recent behaviour on this front.

UPDATE: 2 more vaccines entered phase 3 trials on July 27.

4) We also have more and more evidence of bad non-lethal effects of COVID. A few studies now have found fairly long-lasting effects well after the virus has been cleared from the system. The latest in a study that seems to have been done well, is that nearly 80% had worrisome heart symptoms at least 2 weeks after being deemed fully recovered. Most of these patients were never even hospitalised; they had mild cases. An earlier study in Italy more biased towards severe cases found that ~90% had serious symptoms after recovery from COVID, including fatigue, chest pains, joint pains, and more. More than half had 3 or more of these symptoms. Some less-rigorous work suggests long-term lung damage may be common too. So even as our ability to save lives improves, it's really important to remember - and remind people - that this is a horrible disease even if you survive.

5) Binary thinking has been a massive obstacle to good decision-making. Politicians, administrators, health organisations and members of the public have all defaulted over and over again to a yes/no framing: masks/distancing/lockdowns/medicines either work or do not work. This thinking is simply wrong, with rare exceptions such as the idiotic notion that 5G causes COVID. Almost every measure is somewhere between 0% and 100% effective, and we need to consider the costs and benefits when deciding whether to use them. This seems like such a trivial point that I've not bothered to make it before, but it keeps coming up in people's objections, so I guess we need to argue this explicitly. Standard masks appear to protect wearers by filtering out 60-70% of viruses (they do an even better job of filtering out the viruses you exhale/sneeze/emit, of course). That's well short of perfect but a huge improvement on 0%; they are also cheap and so we should obviously use them. Especially because (i) getting a smaller 'dose' of viruses likely means you get a milder infection, and (ii) combining multiple somewhat-helpful measures can get the effective reproduction number below 1, which would kill the pandemic.

6) The last point is relevant to vaccines because in a few months, we are going to be in a very complicated situation. The first vaccines we get are very likely to give us imperfect protection; they may reduce the probability of infection by something like 50-60%. They may come with some side-effects - hopefully mild ones, but we don't know. Even in the small phase 2 trials, a fairly high proportion of people had mild side-effects. With more people, we might find rarer but more dangerous ones. Some people will quite possibly die of those side effects, because even a very rare, relatively weak side-effect across billions of people is likely to cause a few deaths. And because we will try to distribute these as fast as possible, there will be accidents caused by failures of process and quality control. Taking these vaccines will still save a huge number of lives, assuming we do not discover bad side-effects too late in this process. This is going to be a hard message to communicate, especially because multiple vaccines will arrive in succession, with different characteristics and side-effects. Different vaccines will also end up being distributed in different places. Which specific vaccine you get may depend on complicated geopolitics, supply chains, pre-existing government investment, corruption/kickbacks, and more. It is going to be very easy to spin a conspiracy around this. There is going to be a flood of anti-vaccine rhetoric, aided by people's fears of multinational corporations and foreign countries, opportunistic politicians, lousy science journalism that focuses on individuals cases of side-effects (both real and imagined) while ignoring the big picture, and terrible science communication by governments and health organisations that deny the side-effects to tell an oversimplified story. So please start to talk to people you know about what to expect! We need to discuss this now and not wait till the story is told by the usual clowns.

7) Of the trillions that are being shovelled into the world's economies to try to keep us afloat, only a tiny fraction is being deployed towards actually stopping or curing COVID. Less than 10% of US spending relating to the virus is directed towards stopping it. Even from a purely financial perspective this is insane - if we could stop this pandemic just a few weeks earlier, we would save trillions! A government that cared only about money and nothing about people's well-being still ought to be spending orders of magnitude more (or at least many times more) to provide tests, protective equipment, medication and vaccines. There's also a very strong argument to be made for offering free masks, free testing, incentives to get tested regularly and quarantined, and more. Somehow, 7 months into this process, in a large part of the world including the US, India & most badly-affected places, we are still short of protective equipment and tests, and contact tracing is rudimentary at best (even Switzerland seems to do a mediocre job of it, though I don't know enough to be confident). Even the massive increase in testing capacity in the US is something of a sham. In many places, test results are being reported 1-2 weeks later. Nobody is quarantining in that period, which means that the testing is effectively useless at preventing spread.

8) This fear of damaging the economy continues to drive countries & regions towards reopening too early or taking action too late. This is a massive failure on multiple counts because: (i) the economy will not recover while the threat of more outbreaks looms over us, despite the cavalier idiots who go to nightclubs in the middle of a pandemic, and more importantly (ii) it takes much longer for new cases to halve than for them to double. We now finally have fairly good data on this. Delaying measures by 1 week prolongs the need for lockdown or other strong measures by about 3 weeks. And in Switzerland, which has seen about 2000 deaths, starting the lockdown 1 week earlier could have saved about 1600 lives; starting it 1 week later could have cost another 6000 lives (based on a study that seems reasonable to me: https://www.medrxiv.org/con.../10.1101/2020.07.21.20158014v1). 7 months in, and the basic lesson to act quickly is being ignored. Our health and governance institutions have failed us in many countries.

​9) For months, we have had multiple methods to do rapid testing at home. There are even paper-based tests which would cost 1 or 2 dollars, and give results in an hour or so. They are a bit less sensitive, but could be deployed at massive scale to monitor whole populations. Why are we not using this? In part because this requires approval and deployment by healthcare agencies. And these have been and continue to be atrocious. The WHO & CDC have spread wrong and disastrously damaging messages. The WHO screwed up the distinction between 'presymptomatic' and 'asymptomatic' with dire consequences for people's perception of risk. It is just now acknowledging the possibility that the virus might be airborne, something we have known for months. The CDC is now advocating that universities reopening in Fall do NOT do mass testing of students because the possibility has not been properly studied. This message is not just completely wrong, it is devoid of any logic - the burden of proof is on the party saying mass testing does not work because of all the evidence we have in favour of it. The CDC also keeps changing its recommendations for what universities, churches and other institutions should do based on US govt. political priorities. The FDA has possibly been the worst of them all, holding up important, scientifically-valid steps consistently, such as the cheap tests I mentioned. It only just approved pooled testing, a simple and important method I wrote about in March and that we have used since the second world war. We may need these organisations to exist in some form, and their work has been hampered by political meddling, such as the US govt's decision to exclude the CDC from the data aggregation process. But everyone should seriously downgrade their belief in them for now. And I say this as someone temperamentally and politically inclined to favour these institutions.

10) At least part of the big drop in the probability of dying once you are infected is because we have made many small improvements in medical care. One that I missed is that doctors now turn very sick people onto their bellies for extended periods of time, which apparently improves how much oxygen they get. This seems to help a lot though I'm not sure of any study about this that specifically shows that it reduces COVID mortality. It's remarkable to me that this simple step may save a lot of lives.

11) Some of the most common antibody tests are apparently testing for the wrong antibodies; the ones being tested for do not provide protection. They are probably correlated with the right ones, but it's not great news: https://www.nytimes.com/.../coronvirus-antibody-tests.html .

​12) That ghastly IHME model that I griped about in March and April continues to influence policymakers in many countries. Despite months of criticism and many much better models, this continues to grab headlines despite being a trainwreck. The IHME predictions for the near future do worse than the *baseline prediction*! That is, using just the average deaths from the previous week gives you a more accurate prediction than this stupid model. Please just ignore it and downgrade your belief in any claim based on their predictions.

13) There's yet another push for hydroxychloroquine by the usual gang of idiots in the US. Far too much money and scientific effort has gone into that already; the most wildly optimistic scenario appears to be that it does very little. This electioneering propaganda does not just affect the US, which would be bad enough. The garbage they pump out is picked up and spread in the developing world too (including by people I know), where people are less clued in to the ins and outs of the insane US political landscape and how it distorts pretty much everything. The consequences are global.

14) I continue to be very uncertain about the progression of the pandemic in India. The number of new cases per day has followed a slow but steady exponential for several months, with very little deviation from that trend for several months. Tough (but terribly planned) lockdowns, reopenings, changes in policy, wide variation in medical systems and political leadership across states, and yet the overall pattern has been incredibly stable. The fraction of positive tests has been going up, so the true picture might be a slightly faster exponential than the simple one. But overall, it seems strange and I can't explain it. Some amount of immunity within the population and the lockdowns would help explain why the increase has been slower than elsewhere, and much slower than I anticipated. But I cannot understand why there's been so little change in the trend through time. I really hope we can trust the data. I don't expect it to be great, but I presently have no specific reason to suspect fraud. We desperately need some random sampling of the population to understand what's going on, but that is a massive challenge in a population as complex as India's.

UPDATE: Well, I guess there is evidence of bad/fraudulent data reporting from India. This is still at a local scale but could be important if it's widespread, which is probable: https://www.bmj.com/content/370/bmj.m2859 & https://scroll.in/.../to-battle-covid-19-india-needs-to....

UPDATE 2: And now national-scale information: https://www.medrxiv.org/con.../10.1101/2020.07.19.20157248v1
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19.07.2020

2/1/2021

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In response to a question about evidence that surfaces are not spreading the virus: 

Good question, I wondered whether I should write more about it then. I think one's prior beliefs/priorities matter a lot here, so let me be explicit about mine first. I think there's a limit to how many precautions people will follow, especially over the length of time we need to stop this pandemic. The more things we ask people to do, or the more complex they are, the less likely they are to be followed. And if people stop following some guidelines and nothing bad happens, they will be more likely to stop following other, more important ones too. So it's important to focus efforts on getting people to follow a few important and simple guidelines for the sake of general compliance. At the individual level, it can be perfectly rational to go beyond these guidelines. With that as preamble:

Essentially nobody challenges the idea that transmission by fomites (particles on surfaces) is possible. The question is whether it happens in the real world, and at a frequency that's high enough for us to mandate/suggest specific actions. The WHO considers fomites to be a plausible mode of transmission, but their report also states: "Despite consistent evidence as to SARS-CoV-2 contamination of surfaces and the survival of the virus on certain surfaces, there are no specific reports which have directly demonstrated fomite transmission". Their communication of scientific evidence has been poor, so I looked into what epidemiologists & virologists were saying, especially on Twitter. After months of contact tracing around the world (albeit much less than ideal), I've encountered discussion of only 3 cases where transmission by fomites (particles on surfaces) may be more plausible than other explanations, and that's being generous (see first Twitter thread below). Even these cases are very far from certain. And infection rates within households seem to be lower than one would expect if surfaces were important for transmission.

Since it's hard to show a negative, there's no paper I can point you to which spells this out clearly, or states precisely what the relative risks of surfaces vs. droplets/aerosols are - the numbers are still unknown! But the specialists have generally downgraded their perceptions of the risk of surface transmission, though they hedge their public statements appropriately. See the articles & tweets linked below.

Three caveats: (a) it's a hard topic to study, so it's possible that fomite transmission has happened where contact tracing has been unsuccessful, (b) fomite transmission may have been incorrectly attributed to aerosols in spaces like offices, and (c) since hand-washing and sanitising was one of the major initial recommendations, we may have stopped transmission via fomites in the real world. If we ease up on that, it may start to happen.

Despite those caveats, I think that the balance of evidence so far suggests that surfaces are not important. I understand the desire to take precautions, but personally don't sterilise things I bring home, and did not do this even when the risks were higher here. I have recommended to concerned family that they could consider just leaving things on a balcony for a while if they wanted to be very safe. Virus numbers on plastic decrease by a couple of orders of magnitude in two days in cool, dry conditions; it's much faster when warmer and more humid, and on most other surfaces.

[I've linked to a few papers below, but they seem less helpful than they appeared. I found the threads on Twitter more helpful because they were to the point and open to immediate challenge from other experts.]

Papers:

https://www.nejm.org/doi/full/10.1056/nejmc2004973 (can survive on surfaces)
https://msphere.asm.org/content/msph/5/4/e00441-20.full.pdf (...but decays faster at higher temp & humidity)
https://academic.oup.com/.../doi/10.1093/cid/ciaa905/5868534 (hospital surfaces have viral RNA but no viable viruses found)
https://www.thelancet.com/action/showPdf?pii=S1473-3099(20)30561-2 (much-publicized commentary, not the most useful, I think)
https://wwwnc.cdc.gov/eid/article/26/9/20-1798_article (suspected fomite transmission, weak evidence and could well be aerosols)
https://wwwnc.cdc.gov/eid/article/26/6/20-0412_article (suspected fomite transmission, weak evidence and could well be aerosols)
https://www.cdc.gov/mmwr/volumes/69/wr/mm6914e1.htm... (suspected fomite transmission, weak evidence)

Articles:

https://www.who.int/.../modes-of-transmission-of-virus... (WHO report mentioned above)
https://www.krisp.org.za/.../StAugustinesHospitalOutbreak... (hospital outbreak in which physical contact or fomites are suggested but without much evidence, see page 20) ". Summary at https://www.sciencemag.org/.../study-tells-remarkable...
https://www.cbc.ca/.../coronavirus-surfaces-groceries... (general article, several experts offer their opinions)

Tweets:
​
https://twitter.com/DiseaseEcology/status/1279097818351726592 (good thread summarising the best known case while highlighting its rarity)
https://twitter.com/Bob_Wachter/status/1263673015591530496
https://twitter.com/CathNoakes/status/1282230720778457088
https://twitter.com/firefoxx66/status/1260905943933620226 (see rest of the thread too)
https://twitter.com/TheBinderLab/status/1254166676515454978
https://twitter.com/LucyStats/status/1282112670230106112 (contrary opinion)

UPDATE a week later: A recent Atlantic article on the topic summarises this pretty well: https://www.theatlantic.com/ideas/archive/2020/07/scourge-hygiene-theater/614599/ 

​It does lean a bit on that commentary piece that I thought was not very helpful (among other things, it misrepresents the goals of the papers on rate of viral decay on surfaces). But that's a minor weakness.
0 Comments

13.07.2020

2/1/2021

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Picture
I mentioned in my last post that an increase in US virus deaths was expected this week after 2 months of steady decline.

Well, it's here (see bottom right graph).

Earlier, cases were increasing but deaths decreasing. This mismatch had multiple possible explanations, and this week's reversal supports the main one I wrote about - that we had been catching cases earlier than before. There were more hopeful explanations, such as that we had shielded vulnerable populations successfully.

The worse news is that this will probably grow for weeks. First, because we've got about 4 weeks of case increases baked in. Second, because many of the recent cases were from young people. Given the competence with which this has been handled, they have probably passed them on to older people, who will fall sick later and start to die later, but at much higher rates.

What a shitshow.



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In response to a question about whether the daily death curve would eventually match the daily cases curve, implying about 4k deaths per day (after accounting for undertesting in April):

Mercifully the better projections don't foresee anything quite that extreme; it looks more like 4-6k per week rather than per day. I don't fully understand why that is, but I think it's largely because the age distribution of recent cases has skewed younger and younger. That has reversed recently (see this plot for Florida, for e.g. https://twitter.com/.../status/1283134585665200131/photo/1) and that will probably show up as an increase in another 3-4 weeks. Big uncertainties, as you know, especially because this involves forecasting policy and behaviour to some extent.

Those forecasts I mentioned: https://covid19-projections.com/us & https://viz.covid19forecasthub.org/. (The first shows deaths per day, the latter per week).


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    Why I did this

    I am not an expert on Covid, viruses, or vaccines, but I am a scientist with relevant training. I believe we have a responsibility to clearly communicate science to the public, especially in emergencies. So I started to write summaries of Covid developments on facebook in March 2020 to help friends and family understand the situation as it unfolded. This is an archive of those posts (created much later).

    I also tracked the spread of alarming Covid variants for a few months at http://covidvarianttracking.com/ and mapped the consequences of faster variant spreading at https://tabsoft.co/2YwHCmZ.
    ​

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