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.
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
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.
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
