CharonY

There is a WaPo article outlining how WHO in conjunction with the US officials have developed WHO policy and has provided the US with early information regarding the outbreak, https://www.washingtonpost.com/world/national-security/americans-at-world-health-organization-transmitted-real-time-information-about-coronavirus-to-trump-administration/2020/04/19/951c77fa-818c-11ea-9040-68981f488eed_story.html

That is an important factor but can somewhat be somewhat addressed by using ELISA instead of rapid tests. The former provides quantitative information which provides a bit more information (but not certainty) regarding possible immunity.

It does look like that they may not have found the right reviewers. Often reviews are long and iterative in nature and I don't think they are good for these fast turnaround papers where we have to assume a lower certainty.

I think in this context it would be good time to have a read what wet markets are: https://www.cnn.com/2020/04/14/asia/china-wet-market-coronavirus-intl-hnk/index.html Also a more common source for zoonotic diseases. Pigs are a good reservoir where assortment of human, swine an avian viruses have been observed and which have been implicated with the 1918 flu pandemic (though not quite clear) and obviously the 2009 swine flu pandemic.

That reads to me like a revision of the facts. By January 30th China reported more Covid-19 cases than there were SARS worldwide and over 200 deaths. They were in total lockdown and reports were coming in that their healthcare system was at the breaking point. Daily deaths were steadily increasing with a slowdown only toward the end of February. Who would see that numbers as state there is no chance of it breaking out? In order to ascertain that, folks needed to ramp up testing in their respective countries and do entry checks and follow-ups. Epi-studies suggest that the lockdown has delayed spread, but it was unknown what was happening at the same time in Europe or US as folks (as some acknowledge) delayed contact tracing. Cases especially in New York were more frequently caused by travelers from Europe than China, for example. It was pretty much in plain sight, the only thing that was not known is how much spread was going on outside of China. This is not something that China could have measured in any form. There were early positive cases detected outside China but testing was not ramped up. The high death rates we see were mostly driven by community infections. Also I will note that I did not claim that there were no deaths in December (at that time point folks did not have a means to proper diagnose it anyway) but I have not seen reports either that they were plenty. The linked article only shows an overall revision of the total count but after a brief skim I did not see timelines attached. Perhaps you can point those out (not that it matters). But again, let's say folks were uncertain about the December numbers. What, again, about the numbers in February? What, numbers would you say would have to be reported to trigger responses? Double the numbers of SARS? That would be Feb 2. Triple? Feb 5. I do understand the need to balance risk for health and economy to some degree. But at the same time, I (and plenty of my colleagues) expected contingency plans that would be triggered once it became clear that things would not hold. This would include a task force that would centrally collect and advise on data, stashing and distributing test kits, check availability of critical health systems (such as ventilators and PPE). At the same time less invasive measures would be implemented (again with central reporting). As well as perhaps limiting big events. Now after the fact we heard that contact tracing was only partially done in e.g. Germany, where they gave up after a few searches, where folks still had large carnival and sports events (and again only partial tracing after they realized infected folks were there). What I find worrying that leaving Trump aside, there were folks like folks in the German RKI who have downplayed risks, not because, but despite the data coming out of China.Other German virologists have been far more worried and starting demanding to have actual plans in place. Which did not come until March. So to be fair, it is not only the US that is failing (though it is doing it spectacularly) but as you said, others have been dragging their feet. One difference that I have observed however, is that in Germany instead of blaming, say, China, they are looking at why their predictions were so off and pinpointed lack of contact tracing as one of the biggest issues (together with initial low testing rates). While I may be dismayed regarding their slow response, at least there is hope for improvement.

So what clear information do you think was missing? After the initial reports Vietnam, Taiwan, South Korea Singapore used that information and started countermeasures. Again, the US and Europe did not start moving until March, so why do you think that knowing something in November would have made a difference if they did not react to the full-blown epidemic in January/February? IF they had reacted immediately after China released data, than they could have claimed that knowing things earlier would have made a difference. But the over one month gap invalidates that. Right now some folks pretend that the information coming of of China since January did not exist which is silly. Even if there was uncertainty in the correct response (which will always exist, in outbreaks you are always over or underprepared) yet things only started moving once it was undeniably there (i.e. in Italy). And again, meanwhile other countries were moving but folks did not learn fast enough from them. I see plenty of criticism mostly by the US but also France and other countries so I do not think that they are quite happy with them. At the same time I want to know what, precisely that impacts or medical preparedness, science and strategy. Because what I am seeing (and what you are also stating) is that because of China fudging something, the rest of the world just could not react. I have several times outlined not only that they could, and should, but also that some actually did. So again, what precisely do you think was hidden that stopped a proper response. It is not the November/December data as folks who reacted using the January data successfully avoided a full lockdown, whereas others who still did not respond (or at least provided emergency plans) had worse outcomes. It was a decision at that point not to anything with all the measures that were going on and getting caught by surprise in March is just myopic, to put it nicely. The reason is that if there was crucial data missing to mount a proper response, we need to know what it is and how to collect it. If on the other hand it is only used as an excuse for lack of planning, then it would imply that we will be caught off-guard next time around again.

Indeed, for medical devices this is usual the step when the overall parameters are set and the equivalent of a prototype emerges. Using that initial validation and testing will be conducted to see whether the desired parameters outlined in the previous stages have been met and so on. Once that is all positive the next step is to go through actual trials and only after that we can implement them diagnostically. That being said, research can be done even with poorly or untested systems. It is just important to document those limitations. There are already fully developed antibody tests around (with various sensitivity and specificity) and some may already be allowed in some countries to test for certain purposes.

There are not a lot of such fundamental literature as biology is a quickly evolving field. It is also a far less structured than mathematics, with research on various levels (say molecular vs physiological) having different levels of insights and so on. As such what can be recommended to be a good read may change. I think for beginners, medical microbiology books are usually the easiest to understand. They are a bit more superficial but one can understand them easier. I have heard good things about Basic Medical Microbiology from Patrick Murray. Understanding related mechanisms requires a solid foundation in molecular biology as well as cellular physiology, which is an additional field of study.

No doubt. Folks in the midst of it will only have limited capacity to correctly categorize each death, though I believe that Italy has one of the higher post-mortem tests. In Wuhan for quite some time they counted suspected cases as confirmed ones after using MRI, as they were running low on test capacities and/or wanted to have faster reporting. Everyone involved knows that data is imperfect and will remain for quite some time in most countries.

A few things, the coverage varies a lot between different countries also the case when folks are being tested. Considering that a lot of outbreaks are actually localized rather than nation-wide (depending on size of the country). One thing to look at that sometimes is helpful is how many tests come back negative. Italy also does some post-mortem testing, which other countries don't for example. So roughly 15% of all tests currently administered still come back positive. Contrast that with South Korea where less than 2% of all cases come back positive. The "real" fatality rate is probably lower than the 2-3% reported for the simple reason that many asymptomatic folks will remain unknown. What we start doing now is testing for antibodies that will detect "invisible" infections. Some preliminary local data has been provided for Germany for example (in Gangelt, one of the hotspots of infections) and the death rate there when accounting for undetected cases was closer to 0.4%. In other words the observed crude death rate is also a factor of tests being administered as well as the other factors Stranger mentioned. And of course there is also a matter of definition, as some calculate it based on symptomatic cases exclusively, i.e. case fatality. This basically would only count the likelihood of dying after developing symptoms (a couple of countries including China have waffled a bit in terms of what to report as a case). Again, it would be silly to assume that the world would have reacted differently if China had reported a few percentage points higher or lower. With regard to testing, the reporting was a bit all over the place. Typically two or more tests are administered and initially Italy for example listed counted each test but I think they switched to individuals at some point. That caused a bit confusion to calculate test coverage and makes some data not comparable. Other Countries (such as Germany or US) either did not publish a totals list or referred to individual states (which may or may not have reported). With regard to reporting, I know I got test numbers from Wuhan (via the provincial reporting)a while back but I do not know enough Chinese to effectively dig out data. There was a report in the province in Guangdong which showed about 320,000 tests at the end of February (or 2820 tests per million people). It does look that only from 66 countries we can get convenient national data (although again, they may be different in terms of what is being reported). The correction of death rates on the other hand does look more like an attempt at transparency rather than obfuscation. Most countries will under report deaths unless they do post-mortem testing in all suspicious cases. And countries with limited capabilities will obviously under report more. To be clear, China is definitely not a source that can be trusted with the same level as many other countries. While there is no evidence of systematic data manipulation they could, in theory reduce overall positive as well as death numbers, thus keeping the ratios constant (again, no evidence that they did). But, and this is the important bit, even if they did, and even if they are in a worse shape than they seem to be, it is no freaking excuse for the other countries to not at least create emergency plans and scenarios the moment China started reporting on the outbreak. Cases outside of China (including US) were already been reported leading up to February but without evidence of community spread. So why wasn't there more contact tracing or any kind of travel screening (as shown in other countries shutting down borders is not even necessary). I am repeating myself here, but it is not about whether China is a reliable partner or not. It is about why folks did not act even with the available information (regardless whether they were 100% accurate or not, as you will never get perfect data in a novel outbreak). Infectious disease experts have been making some noise early on and the CDC has made all the right statements come February. And then there is the gaping lack of action until Italy was hit and Europe was starting to get nervous. I suspect much of it is because often Europe looks toward the US in these situation as especially Germany is often unwilling to take lead. Germany produces a lot of the components for the tests and has decent capacity of PPE production and I think I got a notification sometime around March where only then they were asked to increase their production. I.e. folks did not think that they needed the surplus (which is why the first weeks in Germany there was an abysmal rate of tests until they managed to ramp it up). There was a whole lot that could be done and it is perhaps no surprise that countries with with SARS experience responded better. What the rest of the world needs to understand is that infectious diseases will be with us and regardless where you live, there is always a chance for deadly outbreaks. The tendency to think that if something happens elsewhere will never impact us or that where we live is clean and disease-free is an illusion. I am expecting that this situation is a teachable moment for countries that ignored the pandemics and epidemics that have been less consequential for them, but am dismayed that some countries (including China and the US) are instead playing the blame game, as if diseases would care about any of that. There is some evidence that higher viral loads correlate with worse outcomes. Studies are limited, but I can dig them out if you want.

Macron is getting some flak from it, but at least he is referring to a scientist whose data may not be great but has otherwise a good reputation. If Fauci was pushing it and Trump being in support, it would probably also look different. Folks outside of Brazil have pretty much given up on Bolsonaro. He has not the same impact on the Western world so they do not bother roasting him, I suppose.

I think evidence is clear that children are carriers ( but often under tested) what is unclear is whether they are spreaders. Data is lacking here.

Oh sure, the studies do not really support the claims. What I meant is that it is not strong enough to outright dismiss it, either. I.e. I think it is to early to scrap it, but I suspect better data will come form some of trials with other therapeutics which are randomized and have actual controls.

Oh yeah, I think that is the follow-up to a follow-up (the second by Molina study showed no beneficial effects). But critically, the study was more set up like a case or observational study rather than a efficacy test. At this point the data looks inconclusive to me.

Well, also it is a good excuse to get out of the lab for a bit.

I am not talking about whether China might or might not have been forthright or who is more or less honest. That is not terribly productive in itself, and I am mostly concerned about facts we know or which are missing. What I am saying is that if there was a cover-up, it does not appear to had any functional consequences. Therefore there was no reason to not to heed the warnings. Or conversely, stating that folks were taken by surprise due to China hiding the infection is ridiculous, given the massive lockdown on the 23rd of January and the inaction of e.g. the US between then and March. If they hid something, and the something does not change our knowledge on the infection, why would it matter? It would then all be a discussion about who is bad and who is not, and not about whether the information is reliable and useful. And that is a very dangerous stance, because you are essentially saying we should throw out all the data from China as they are all wrong. Luckily (or sadly) by now we also have data in other countries that a very similar picture, pretty much invalidating that assumption. And here is the other thing, we are science oriented forum, so data is king. If we look at that dispassionately we (so far) do not find strong evidence of any meaningful manipulation (aside the points I mentioned before, which are not really hidden). So I am asking, what is the benefit of just assuming things with evidence, other than becoming more vulnerable to manipulation and spin? There is already the narrative that the one pushing the responsibility to WHO and China rather than acknowledging failures in own responses. Because from the latter we can learn and improve, but the former will keep us in blissful ignorance (until the next outbreak hits). Let me be clear, there are two major narratives, mostly pushed by the US at this point. One is that the inability of China (or willingness) to report on the original clusters of pneumonia up to the end of December has cost the world time to react. The issue with that is even after that only few countries started to implement measures whereas the US and others have done little until March. And there are emerging reports that intelligence services have notified folks of these clusters of infections almost as soon as the Chinese CDC, and drew their own conclusions (but apparently not resulting in any reactions from the administration) And even in March before the lockdown, folks were not asked at airports regarding their travels. So that does not line up. Associated with that is that folks could have closed borders earlier. The issue with that one, is I believe that either in the US or Canada more infections were coming from Europe than from China.Which is why the big world-wide waves started actually way later than anticipated (as China was shutting down). The second is that China is hiding some big secret, which, for some reasons, does not change epidemiological data in any relevant way. So not only it is not clear what is missing, it also fails to show any impact (at least on the scientific side of things). But again, it does not impact folks to learn about the virus, nor to implement meaningful measures, as you insinuated earlier (how can it if it does not change the meaning or interpretation of the published data?). If one does not take responsibility to ones own failures (in China's case free distribution and discussion of information, in the US' case acting on actually available information and in many other countries learning from timely and effective responses in other countries), these issues will crop up again. And there is not guarantee that the next one will not have an origin in, say, North America.

It is a big unknown. Antibody testing is going to be the next stage for better understanding of epidemiological coverage.

That is nonsense. Plenty of folks took it seriously, their pandemic responses teams activated early January. China shut down whole provinces and tanking their economy and risking unrest. That alone was a strong signal (and WHO raised their warning levels at the same time). I mean seriously, what would have been a warning sign if not that? Obviously China (as well as other countries hit by SARS) took it seriously at the latest toward the end of January (again, there was an unprecedented shutdown). Other countries, including US and Europe did not react until late February to March. Folks such as the RKI in Germany have acknowledged that they should have done more contact tracing, for example. In addition it is a weird cover up that managed to create perfectly predictive data. So far transmission rates, lethality, effects of age and comorbidity all seem to line up with data all over the world so either they new the correct numbers and fudged it to much or they covered up something that had no impact on our undersanding. In that case if something was covered up, what would it even theoretically be? Everything that happened in China is now happening elsewhere with the same intensity (or worse, depending on the response). So what is being covered up that so well matches all observations so far? I do not expect the Chinese government to be forthright, but it is silly to assume that this causing in poor responses elsewhere as, again everything that came out of China so far was shown to be fairly predictive. In addition to all that, there was also data coming out from countries that started early testing, so by February we also had range of strategies on display, including total lockdown (China), enhanced contact tracing eventually followed by testing (e.g. Taiwan, Singapore, Vietnam, South Korea). Well, or nothing.

It is weird, isn't it? Is it only me or are bio papers getting sloppier in the last one or two decades?

There is a difference between let's conduct a trial to see if it works vs. "just ask your doctor to take it. I think it works." One is following procedure and creating scientific evidence. The other one is pushing gut feeling.

The suppression of free speech by the Chinese government is definitely wrong. However, I am skeptical regarding large-scale misinformation for several reasons. The biggest one is that one strictly follows the data, everything we learned from China so far largely lines up with models with data from other countries. For example, if they were covering up deaths, by now we would see an unexplained shift in fatality rates outside China, but that does not seem to be the case. They did change the reporting several times, including not counting asymptomatic cases as infected, but it kind of makes sense from a clinical viewpoint, as they isolated all cases but treated symptomatic and asymptomatic cases differently (and moved the former to the latter category once symptoms manifested, it is an inelegant way to avoid double counting). But all it did was to increase the published death rate. So if there is huge cover-up of sorts, it is unclear what they hid, as at least on the scientific side of things regarding the virus nothing has fundamentally changed in our understanding.

The issue there is that the WHO cannot force countries to run their health system in a specific way. Even a single country might report things differently in each province/state/ prefecture. Taiwan had a task force from the SARS days that spring into action. South Korea quickly assembled one. Likewise Singapore. One could have emulated them (or not weakened ones own pandemic response team, for example).

Ultimately we don't know yet. It is atypical to many other respiratory diseases, but a working hypothesis is that it is because children do not mount cytokine storms. Another one is that symptoms are amplified by accumulated lung injuries/damages and that younger folks just have healthier lungs.

Exactly. Children are likely asymptomatic carriers and generally live with folks that are older...

Well from what I have seen the US has been heavily pushing the anti-Chinese narrative and China has responded in kind. Both are crap, but I am not sure whether the saying actually fits well here.