Corona

Showing posts with label Corona. Show all posts

Friday, April 16, 2021

Antigen rapid tests much less effective for screening than previously thought according to top German virologist Drosten

Hidden in a long German language podcast on the pandemic Prof. Dr. Christian Drosten talked about an observation that has serious policy implications.

At the moment this is not yet based on any peer reviewed studies, but mostly on his observations and those of his colleagues running large diagnosis labs. So it is important to note that he is a top diagnostic virologist from German who specialized on emerging and Corona viruses and made the first SARS-CoV-2 PRC test.

In the Anglo-American news Drosten is often introduced as the German Fauci. This fits as being one of the most trusted national sources of information. But Drosten has much more expertise, both Corona virusses and diagnostic testing are his beat.

Tim Lohn wrote an article about this in Bloomberg: "Rapid Covid Tests Are Missing Early Infections, Virologist Says." And found two experts making similar claims.

Let me give a longer and more technical explanation than Tim Lohn of what Prof. Dr. Christian Drosten claims. Especially because there is no peer reviewed study yet, I feel the explanation is important.

If you have COVID symptoms (day 0), sleep on it and test the next day the antigen tests are very reliable. But on day zero itself and especially on the one or two days before where you were already infectious they are not as reliable. So they are good for (self-)diagnosis, but less good for screening, for catching those first days of infectiousness. The PCR tests are sensitive enough for those pre-symptomatic cases, if only people would test with PCR that early and would immediately get the result.

Figure from Jitka Polechová et al.

In those pre-symptomatic days there is already a high viral load, but this is mostly active virus. The antigen test detects the presence of the capsid of the virus, the protective shell of the virus. The PCR test detects virus RNA. When infecting a cell, the capsid proteines are produced first, before the RNA is produced. So in that respect one might expect the rapid tests to be able to find virus a few hours earlier.

But here we are talking about a few days. The antigen test can best detected capsids in a probe sample when epithelial cells die and mix with the mucus, which takes a few days. So the difference between the days before and after symptoms is the amount of dead virus material, which the rapid tests can detect to get reliable results. That is the reason why in the time after symptom onset the antigen tests predict infectiousness well. But in those early days possibly not.

This was not detected before because the probes used to study how well the tests work were mostly from symptomatic people; it is hard to get get positive probes from people who are infectious before they are symptomatic. Because you do not often have pre-symptomatic cases with both a PCR and an anti-gen tests, also the observations of Drosten are based on just a few cases. He strongly encouraged systematic studies to be made and published, but this will take a few months.

In the Bloomberg article Tim Lohn quotes Rebecca Smith who found something similar:

In a paper published in March -- not yet peer reviewed -- researchers led by Rebecca L. Smith at the University of Illinois at Urbana-Champaign found that, among other things, PCR tests were indeed better at detecting infections early on than a Quidel rapid antigen test. But the difference narrowed after a few days, along with when the different tests were repeatedly used on people.

The article also quotes Jitka Polechová of the University of Vienna, who wrote a review comparing PCR tests to antigen tests:

“Given that PCR tests results are usually not returned within a day, both testing methods are similarly effective in preventing spread if used correctly and frequently.”

This is a valid argument for comparing the tests when are used for diagnostics or as additional precautions for dangerous activities that have to take place.

However, at least in Germany, rapid tests are also used as part of opening up the economy. Here people can, for example, go into the theatre or a restaurant after having been tested. This is something one would not use a PCR for, because it would not be fast enough. These people at theatres and restaurants may think they are nearly 100% safe, but actually 3 of the on average 8 infectious days would not be detected. If, in addition, people behave more dangerously, thinking they are safe, opening a restaurant this way may not be much less dangerous than opening a restaurant without any testing.

So we have to rethink this way of opening up activities inside and rather try to meet people outside.

Friday, November 20, 2020

Yes, it makes sense not to have diner parties while the schools are still open. Think of it as a Corona contact budget.

Can the kids go to school in restaurants

Jessica Winter, editor New Yorker

Analogies can be enlightening. Bad faith actors will always find something to nit pick, but for those interested in understanding analogies can help to open a toolbox of existing ideas and argumentative structures.

I wondered whether it may be useful to talk about Corona contacts as a budget.

It would avoid arguments like "if churches can be open, why can't we have concerts under similar conditions". "If you cannot meet indoors with more than 15 people, then why are schools open? Math!"

One would never argue "if we just bought his flat, why can't we buy a summer house?" Maybe you have the budget to buy a summer house, but buying a flat does not mean you can also afford the summer house.

Similarly in the political realm: "if we can have social security, why can't we have a basic income (social security for all)?" For me a basic income is freedom, fulfilment of human potential and prosperity, but you will have to find the money. "If we can spend 10% of our GDP on healthcare as an average OECD country, why can't we spend 20%?" You can, and America does, but it will still be hard to find the funding for the additional 10% if countries with universal health care wanted to destroy their system and adopt the American partial system.

When it comes to budgets it is immediately clear that you have to set priorities and invest wisely.

The reproduction number of the SARS-CoV-2 virus is between two and three. Let's assume for this article that it is two to get easier numbers. This means that one infected person on average infects two other people. If we reduce number of infectious contacts by more than half the virus would decline.

The "on average" does a lot of work. How many people one person infects varies widely. As a rule of the thumb for SARS2: Four of five infected people only infect one other person or none, while one in five infects many people. It is only two on average.

And you have to average over a population that is in contact with each other. When in France no one has any contacts, while in Germany life continues as normal, the virus will spread like wildfire in Germany. But if inside the city of Bonn half of the people disappear, the remaining people have less contacts than before. The remaining half should not especially seek each out for the analogy to hold.

How does this analogy help? If we look at the budget of a country like Germany, it makes clear that we should look for reductions where we spend a lot. Work, school, free time. I am as annoyed by the anti-Corona protests as many complaining about them, but compared to 80 million inhabitants that see each other at work and school (indoors) every day, these protests, even if they were really big, are a completely insignificant number of contacts. And the right to protest is a foundation of our societies and should thus have a high priority. I think it is fine to mandate masks at protests and if you do so you should uphold the rule of law.

Less than 20% of Germany is younger than 20. So we could afford to spend our contacts there and ask the other 80% to do more. People often argue that children not going to school is disruptive for the economy. I would also argue a pandemic last one year is a large part of their lives, while additionally young people mostly do this to protect others. There is naturally no need to squander our budget, we could require older kids to wear masks to reduce the effective number of contacts, install air filters or far UC-V lights in class rooms or reduce the number of days children go to school.

Some feel we should close the schools to protect teachers, but the main reason to care about avoiding contacts is, even now, not about the people being infected today, but about the spreading the virus and all the people who will die because of that.

If we life above our contact budget most of the dying happens after several links in the chain of infection and no longer close to the school: The teacher or student infects 2 others, they infect 4 other, 8, 16, 32, 64, 128, ... Those 128 will reside all over the city/county, if not state and have many different professions. If we would life within our Corona budget and the level of infection would be and stay low, the entire community, including teachers, would be safe.

The exponential growth of a virus also nicely fits to the exponential growth of money in your [[savings account]]. I added a link for young people. A savings account used to be a place where you would keep you money and the bank would give you a percentage of the amount as a thank you, which they called "interest". People who are into money and budgets likely still remember this and how it was normal to "invest" money to have more money later.

When the press talks about exponential growth, I tend to worry they simply mean fast growth. Economic growth is much slower than the pandemic, but when it comes to money people get glowing eyes and talk enthusiastically about compound interest and putting something aside for later.

Similarly when a society invests in less contacts, we can have more freedom later. Even more so because once the number of infections is low enough track and trace becomes much more efficiently and you get double returns on investment. Like an investment banker who has to pay less taxes because ... reasons.

At least the financial press should know the famous example of exponential growth: the craftsman who "only" asks the king for rice as payment for his chessboard: one grain on the first square, two on the second, four on the third square and so on.

What is true for infections is also true for hospital beds and ICU beds. Once half of your patients are COVID-19 patient, it is only a matter of one more doubling time and the capacity is filled. Exponential growth is not just fast, it overwhelms linear systems like hospitals where you cannot keep on doubling the number of beds.

If we let it get this far we are forcing doctors to choose who lives. Who is in the ICU too long and would likely stay there a long time while this capacity could be used for multiple new patients. Who is removed for the ICU to die. A healthy society does not put doctors in such a position.

With good care around 1 percent of people die in the West (in young societies in Africa less). Supporters of the virus tend to use this number or even much lower fantasy numbers. However, if we let it get out of control like this, ignore the exponential growth and the delay between infections and deaths, the hospital care would collapse and a few percent would die.

Many more people need to got the hospital. In Germany this is 17%. A recent French study reported that after 110 day most patients are still tired and have trouble breathing, many did not yet work again.

At the latest when the hospitals collapse people will reduce contacts, even if not mandated. It is much smarter make an investment earlier, to reduce our number of infectious contacts earlier.

A well-know American president said it is smart to go bankrupt. It is smarter to make money.

Investing early pays of even more because then more subtle measures are still possible, while in an emergency a much more invasive lockdown will be necessary and, for those that only care about money, more damage to the economy will be done.

(As many of my readers are interested in climate change, let me add that I find it weird that when it comes to protecting the climate people often talk about it as a cost and not as an investment that will pay good dividends in the future, just like any other investment. If you mind that our kids will thus have it better than we have it, you can finance the investments with loans, like any business would.)

Sunday, August 30, 2020

A primer on herd immunity for Social Darwinists

Herd immunity has been proposed as a way to deal with the new Corona virus. In the best case, it is a call to slow down the spread of the SARS-CoV-2 virus enough so that the hospitals can just handle the flood of patients, in the worst case it is a fancy term for just doing nothing and let everyone get sick.

Trump often talked about letting the pandemic wash over America. Insider reports confirm he was indeed talking about herd immunity. When I first heard claims that Boris Johnson was pursuing herd immunity, I assumed his political opponents were smearing him and trying to get him to act, but it seems as if this was really his plan. Of all world leaders Jair Bolsonaro may be most in denial about the pandemic, which he calls a little flu. He also advocated herd immunity. All these leaders have downplayed the threat, which by itself helps spread the decease, and advocated policies that promote infection, leading to more infected, sick and dead people.

America and Brazil lead the COVID-19 death rankings unchallenged with respectively 187 and 120 thousand total deaths and around one thousand people dying every day the last month. The UK is the country with the most COVID-19 deaths in Europe, while it was lucky to get it late.

This "strategy" has a certain popularity among Trump-like politicians. I do not think they know what they are doing. Scientific advice tends to come from a humanist perspective where every life is valued. Such advice is naturally rejected by Social Darwinians, who in the best case do not care about most people. While these politicians naturally see themselves as more valuable than us, they tend not to excel in academics. So let me explain why herd immunity is also a bad policy from their perspective, even if up to now people from groups they hate had a higher risk of dying.

Herd immunity

If we do not take any preventative measures one SARS-CoV-2 infected person infects two or three further people. This may not sound like much, but this is an example of exponential growth. It is the same situation of the craftsman who "only" asks the king for rice as payment for his chessboard: one grain on the first square, two on the second, four on the third square and so on.

If we assume that one person only infects two other people, that is that the base reproduction number is two, then the sequence is: 1, 2, 4, 8, 16, 32, 64, 128, 256, 512, ...

1024,

2048,

4096,

8192,

16,384,

32,768,

65,536,

131,072,

262,144,

524,288,

1,048,576,

2,097,152,

4,194,304,

8,388,608,

16,777,216,

33,554,432,

67,108,864,

134,217,728,

268,435,456,

536,870,912, ...

Those are just 30 steps to get to half a billion and the steps take about 5 days in case of SARS-CoV-2. So that is half a year. With good care 1 to 2 percent of people die, that would be at this point 5 to 10 million people. Do be highly optimistic and it is still 2 million people.

This will naturally not happen in reality. People will take action to reduce the reproduction number, whether the government mandates it or not. And at a certain moment an infected person will not infect as many people because many are already immune. If the base reproduction number is two and half the population is immune, the infected person will only infect one other person, that is the effective reproduction number is one.

The actual base reproduction number is most likely larger than two and reality is more complicated, so experts estimates that the actual herd immunity level is not 50%, but between 60 and 70%. More complication is that it is possible that people are sufficiently immune to avoid getting ill again, but the immunity may not prevent people from getting infected and transmitting the virus. There is a strong case of a 33 year old man from Hong Kong, who got infected twice, but did not get ill. If this were typical, herd immunity would not exist.

You may have heard experts say that once this immunity level has been reached, that the pandemic is over. But this does not mean that the virus is gone. Europe needed several months of an effective reproduction number well below one to get to low infection numbers (and the virus is still not gone). This was after a drastic decrease in the effective reproduction number (R) due to public health measures, in case of herd immunity it would initially be around one, and only very slowly go below one.

Say that when we reach R = 1 when one million people are infected, the after one step later (5 days) another one million people are infected. One million of 30% of the world population is not much. So also R will still be almost one. In other words, it would take several years for the virus to go away even in the best case. In the worst case, the virus mutates, people lose some immunity and new babies are immunologically naive. So most likely SARS-CoV-2 would stay with us forever.

Reaching herd immunity will not help Trump. He will still be bunkered down in the White House surrounded by staff that is tested every day so as not to infect him, while the calls on others do go out, without a good testing system, and die for him. Trump's billionaire buddies will still need to lock themselves up in their mansions or high-sea yachts, counting how much richer they got from Trump's COVID-19 bailout. The millionaire hosts at Fox News will stay at home telling others to go out to work even if their work place is not safe and to accelerate the pandemic by sending kids to schools even it the schools are not safe. They will still need to wait until there is a vaccine. The herd immunity strategy only ensures that up to that time the largest number of people have died.

When the virus is everywhere, good luck trying to keep it out of elderly homes. In 2016 Trump won in the age groups above 50. The UK Conservatives had a 47 point lead among those aged 65+. In Brazil Bolsonaro had a 16 percent point lead for people older than 60. They will be the ones dying and seeing their friends die. This is not helpful for the popular support of far right politicians.

The elite may think that it will be the poorest 70% that get infected. Far right Republicans may hope that it will affect Democrats and people of color more. It is true that at the moment poor people are more affected as they cannot afford staying at home even if their place of work is not safe. It is true that initially mostly blue states and cities were affected in America.

Let's take the theoretical case where the poorest 70% are infected or immune and the richest 30% still immunologically naive. As soon as one of these 30% are infected, it will spread like wild fire as rich people tend to hang out with rich people, so the virus would easily find two or three rich people to infect next.

That is one reason why it is too simple to equate a base reproduction number with a herd immunity of 50%. This would be the case if the population were perfectly mixed. But any network were the immunity level is not yet 50% is up for grabs. In the end everyone will get it, rich or poor, red or blue.

The only Social Darwinists for whom this pays are billionaires who have their own private hospital, with their own nurses, doctors at their mansion. They would have a chance of 1 to 2 percent to die. While if they manage to convince the people to go for herd immunity and not even to stay below the carrying capacity of the hospitals around 5% of the population would die. That is a 2 to 3% survival difference. Not sure that is worth getting all your politicians kicked out of office.

It naturally also helps the high frequency traders. Like the Mercer family who funded Trump in 2016 when no one thought he was a good investment. They have made so much money from the chaos Trump produces. Up or down the high frequency trader wins. Down goes faster. They live their lives on chaos, suffering and destruction. I presume they have a private hospital, they have the money.

But for the average Joe Social Darwinist there are nearly no gains and it is bad politics. It hurts your country compared to more social democratic countries and at home it helps lefties get into power and implement disgusting policies that help everyone.

Monday, April 20, 2020

Corona Virus Update: the German situation improved, but if we relax measures so much that the virus comes back it will not be just local outbreaks (part 32)

The state of the epidemic has improved in Germany and we now have about half number of people getting ill compared to the peak we had a month ago. This has resulted in calls to relax the social distancing measures. The German states have decided that mostly nothing will happen the next two weeks, but small shops will open again (and some other shops) and in some states some school classes may open again (although I am curious whether that will actually happen, German Twitter is not amused).

An estimate of the number of new cases by the date these people got ill. Similar graphs tend to show the new cases for the date they were known with the health departments, by looking at the date people became ill, which is often much earlier, you can see a faster response to changes in social distancing. In dark blue you see the cases where the date someone got ill is known. In grey were it was estimated because only the case is know, but not when someone became ill. In light blue is an estimate for how many cases will still come in.

So in the last episode of the Corona Virus Update science journalist Korinna Henning tried to get the opinion of Christian Drosten on these political measures. He does not like giving political advice, but he did venture that some politicians seem to wrongly think measures can be relaxed without the virus coming back. The two weeks that the lockdown continues should be used to prepared other measures that can replace the lockdown-type measures, such a track and trace CoronaApp and the public wearing everyday masks.

Another reason it may be possible to relax measures somewhat would be that the virus may spread less efficiently in summer. It is not expected to go away, but the number of people who are infected by one infected person may go down a bit.

When the virus comes back, either because we relaxed social distancing too much too early or because of the winter, it will look differently from this first wave. This first wave was characterized by local outbreaks. A second wave would be everywhere as the virus (and it various mutations) are spreading evenly geographically.

Korinna Henning asks Drosten to explain why it is easier for him to call COVID-19 a pandemic than for the World Health Organization. This question was inspired by Trump complaining that the WHO called the pandemic too late. Drosten notes that it has political consequences when the WHO calls the situation a pandemic, but that does not influence the situation in your country and what Trump could have done.

Really interesting was the part at the end on some possible (not guaranteed) positive surprises.

Prof. Dr. Christian Drosten, expert for emerging viruses and developer of the WHO SARS-CoV-2 virus test, which was used in 150 countries.

The situation and measures in Germany

Korinna Hennig:

What's your assessment, how long would [the reproductive rate] have to stay below one for it to have a really long-term effect and we're not going to say that at some point we have to close all the schools again.

Christian Drosten:

I believe there is talk of months [in a report by the Helmholtz Association]. I can well believe that this is the case. However, this is not the path that has been chosen in essence [by the German government], but rather - I believe - the idea has arisen that the intention is to keep it within the current range, perhaps by taking additional measures to reduce the pressure a little more.

That is an important point of view, and one that needs to be understood. It is not primarily a question of saying that we have now achieved a great deal, that the measures have already had a considerable impact. And now we are simply letting them go a tad, because we no longer want to. Then at some point we will have to take a look and then we will have to consider how to proceed, that is one view.

The other is that everything will work out fine. Sometimes you can hear that between the lines. I have the feeling, particularly among the general public, that many people, even in politics, are speculating that it will not come back at all, that it will not pick up any momentum. Unfortunately, that is not what the epidemiological modelers are saying, but it is generally assumed that, if nothing is offered as a counter-offer to this relaxation of measures, it will really get out of hand.

And the idea is, of course - and this is a very real idea in Germany - that people say that they are now relaxing these measures to a small extent, but to a really small extent. It is rather the case that corrections are being made in places where we think we can perhaps get away with it without the efficient reduction of transmission suffering in the first place. And now, in the time that has been gained by the decision, it is preparing to allow other measures to come into force. And this of course includes the great promise of automated case tracking.

The cell phone tracking ... doesn't have to do the job completely, but you can combine it. You could say that there is a human manual case tracking system, but it gets help from such electronic measures, while you introduce these electronic measures. After all, this is not something that is introduced overnight; there must be some transition. I believe that the few weeks of time that have now been gained once again can be used to introduce such measures, and that is where a great deal of faith comes from at the moment.

Of course, there are other things to hope for as additional effects, such as, for example, a recommendation on the wearing of masks by the public. That could have an additional effect. Of course there will also be a small additional effect on seasonality. We have already discussed this, and there are studies which say that, unfortunately, there is probably not a large effect on seasonality, but there is a small effect on seasonality.

That is where things are coming together, so that we hope that the speed of propagation will perhaps slow down again overall and that we will at least be able to enter an region over the summer and into the autumn, where we will unfortunately see the effect of winter coming again, a possible winter wave, but where we will then have the first pharmaceutical interventions. Perhaps a first drug, with which certain risk patients could be treated in an early stage. Maybe first use studies, so efficacy studies of first vaccines. This is the overall concept, which one hopes will work.

Currently one infected person infects 0.7 or 0.8 other persons (RO, the reproduction number). That is behind the decline in the number of new cases. Theoretically you could thus allow for 25% more contacts while still being in a stable situation. I would be surprised if the small relaxations decided for the next two weeks would do that. I do worry that these relaxations make people take to problem less seriously and that can quickly lead to 25% more contacts.

I would personally prefer this decline to continue until we get to a level where containment by manual tracking infected people and their contacts becomes an effective way to fight the epidemic; Mailab explains it well in German.

If we get the tracking of infected people with a CoronaApp working, it would matter much less at which level of contagion we start, but I do not expect that the CoronaApp will be able to do all the work, it will likely need to be complemented by manual tracking. With the current plans, according to rumours in the media, placing less emphasis on privacy of the users, I worry that too few will participate to make any kind of dent. An app were we can only hope and need to trust that the government keeps its side of the bargain and does not abuse the data would also be less useful in large parts of the world where you can definitely not trust the government.

That some states are already starting with opening up some classes is in principle a good thing. But it goes too fast, the schools are not prepared yet and I see quite some backlash coming. If done well, by opening a few school classes we could have learned how to do this before we do more and we could study how much this contributes to a higher reproduction number R0. If we are lucky maybe hardly; see the last section on possible positive surprises.

Summertime

The flu normally goes away in summer, this is not expected for SARS-2, but the reproduction number could be 0.5 lower, that is that one infected person would infect half a person less. Without measures it is expected to be between 2 and 3 and we have to keep this reproduction number below 1 to avoid that the situation gets out of hand again. The summer may thus help a bit, which could mean less stringent restrictions.

It is not well understood what exactly makes the summer harder for the flu and even less for SARS-2. One aspect is likely that people are outside more and ventilate buildings more, which dilutes and dries the virus. Also when it comes to schools, it may be an option to do the classes outside, where the distancing rules could be less strict than indoors.

Museum could create large sculpture gardens outside for the summer. As the conference centres are empty and unused they could be used as social distancing museums. The empty hotels could be used to quarantine people who might otherwise infect other people in their households. We have to support the hotels anyway to survive until the pandemic is over.

I have often dreamed of conferences while walking outside in nature. You could transmit the voice of the speaker with a headset. The power points slides with Comic Sans would be missing. This may be the year to start this as alternative to video conferences. (Although there would still be transport.)

World Health Organization and Trump

Korinna Hennig:

Could you briefly explain again what the difference is when you say here in the podcast for example: Yes, we have a pandemic in an early phase. And the WHO is still hesitating for a very long time. What is the crucial difference when the WHO makes such an assessment?

Christian Drosten:

So I am only an individual and can give my opinion, which you can follow or not. You can take me for someone who knows what he's doing. Or you can say: He's just a fool and he says things here.

Of course, this has different consequence with the WHO. In the case of a UN organisation, this has certain consequences, not only when it comes to saying that this is a pandemic, but also, and especially, when it comes to saying that this is PHEIC, i.e. Public Health Emergency of International Concern. That is a term used in the context of international health regulations. This then also has consequences for intergovernmental organisations. This scope has certainly also led to delays in all these decisions by the WHO.

Of course there are advisory bodies. After all, the WHO is not a person, but an opinion-forming and opinion-collecting organisation. Experts are called together, committees that have to vote at some point and where there is sometimes disagreement. And then they say that we will meet again next week and until then we will observe the situation again. This then leads to decisions that are perceived as a delay by some countries. This is an ex post evaluation of the WHO's behaviour.

At the moment this is again all about politics. And it is about a decision by Donald Trump, who has now said that he is suspending the WHO payments, the contributions, because the WHO did not say certain things early on.

It was, of course, known relatively early on from individual case reports that cases had already been introduced in the USA. And now to say that it is a pandemic that is taking place in all other countries ... So the statement that this is a pandemic is to acknowledge the situation, that this is far is widespread. This has nothing to do with the assessment for your own country. Since you know, it is in your own country, you have to ask yourself: Will do I act or not?

Korinna Hennig:

And there are of course financial liabilities between countries that are linked to the WHO.

Local outbreaks in wave 1, everywhere in wave 2

If there is a second wave, it will not look like this first wave.
Christian Drosten:

What happened in the case of the Spanish flu was this: We also had a first wave there in some major US cities - that is very, very well documented - that caught our attention. However, it did not occur in all places, but was distributed extremely unevenly locally. It was conspicuous here and there, and elsewhere people did not even notice that this disease existed at all.

Even there, even at that time, people were already working with curfews and similar things. This was also happening in spring, by the way. Then it went into the summer and apparently there was a strong seasonal effect. And you didn't even notice the disease anymore. And under the cover of this seasonal effect - we can perhaps now envisage this as, under the cover of the social distancing measures that are currently in force - this illness has, however, unnoticed, spread much more evenly geographically.

And then, when the Spanish flu hit a winter wave, the situation was suddenly quite different. Then chains of infection started at the same time in all places because the virus had spread unnoticed everywhere and no one had paid any attention to it. This is of course an effect that will also occur in Germany, because we do not have a complete ban on leaving and travelling here, and of course we do not have zero transmission either, but we have an R, i.e. a reproduction number that is around or sometimes perhaps even slightly below one. But that does not mean that no more is being transmitted.
So you can look at our homepage, for example, at the Institute of Virology at the Charité - we have now published a whole set of [virus] sequences from Germany. You can see that the viruses in Germany are already very much intermixed, that the local clustering is slowly disintegrating and that all viruses can be found in all places. So let me put it very simply.It is slowly but surely becoming very intermixed. ...

We'll be in a different situation when winter sets in. ... Suddenly you'd be surprised that the virus starts everywhere at once. Of course it is a completely different impact that such a wave of infection would have.

What I find interesting to see it that there is nearly no difference in virus activity between cities and rural regions in Germany anymore. If anything, just looking at the map below, I have the impression that rural regions have more virus activity. On the other hand, in the beginning, I feel there was more activity in the cities.

Yesterday's map of the RKI, the German CDC, of the number of new cases over the last week per 100,000 inhabitants. The larger cities are denoted by a small red dot, the location of the smaller cities can sometimes be seen as a smaller region in a different colour. The darkest region is an outbreak, which was likely due to a strong beer feast.

Positive surprises

Christian Drosten:

It is also quite possible that there will be positive surprises. For example, we still know nothing about children. It is even the case that in studies that are very systematically designed, this effect is often still left out. We know from other coronavirus diseases, especially MERS, that not only are children hardly affected, but they are hardly ever infected. Now the question is, of course, whether this is also the case with this disease, that not only they do not get any symptoms and are therefore not so conspicuous in the statistics, but that they are somehow resistant in a certain way and that they do not even have to be counted in the population to be infected. So what is 70% of the population? Is it possible to consider the 20 percent of children as finished, because they do not get infected at all? In reality, only 50 percent of the population need to be infected? This is a big gap, which can also be interpreted as a great hope.

And there is something else - we are anticipating that, epidemiological modellers are doing that, and they are taking that into account: That there may be an unnoticed background immunity from the common cold corona viruses, because they are already related in some way to the SARS-2 virus. It could happen, however, that certain people, because they have had a cold from such a corona virus in the last year or two, are protected in a previously unnoticed way.

All I want to say is that we are currently observing more and more - and a major study has just come out of China in the preprint realm - that in well-observed household situations, the secondary attack rate, that is to say the rate of infected persons who become infected when there is an index case in the household, an infected person, is quite low. It is in the range of 12, 13, 14 percent. Depending on the correction, you can also say that it is perhaps 15, 16, 17 percent. But it does not lie at 50 or 60 percent or higher, where you would then say that these are probably just random effects. The one who didn't get infected wasn't at home during the infectious period or something.

How is it possible that so many people who were supposed to be in the household are not infected? Is there some sort of background immunity involved?

And there are these residual uncertainties. But at this stage, even if you include all these residual uncertainties in these models, you still get the picture that the medical system and the intensive care unit capacity would be overloaded. That is why it is certainly right at the moment to have taken these measures. We must now carry out intensive research work as quickly as possible, as we clarify issues such as: What is really wrong with the children? Do they not get seriously ill, but are they in fact infected and are giving off the virus and carrying it into the family? Or are they resistant in some way? The other question that we absolutely must also answer is: why do relatively few, perhaps even cautiously put, unexpectedly few get infected in the household? This is a realisation that is now maturing so slowly.

As I said, a new preprint has just appeared from China, and a few other studies suggest that this is the case. The Munich case tracking study, for example, has already hinted at this a bit. You have to take a closer look at that. Is there perhaps a hitherto unnoticed backgroundimmunity, even if only partial immunity?

That wouldn't mean that we were wrong at this point in time, and what we have done now was wrong. At the moment, even if you factor in these effects, you get the impression that it's right to stop this, that we're not getting into such a rampage that we can no longer control. But for the estimation of how long the whole thing will last, new information could arise from this. It could then be - and I would like to say this now, perhaps as a message of hope - that in a few weeks or months, new information will come out of science that says that the infection activity will probably stop earlier than we thought because of this special effect.

But I don't want to say that I can announce something now. These are not hints from me, or data that have been available for a long time, but that I wouldn't want to say in public or anything. Rather, they are simply fundamental considerations that we simply know too little about this disease at the moment. And that the knowledge, which is actually growing from week to week, will also influence the current projections.

Other podcasts

Part 31: Corona Virus Update: Don't take stories about reinfected cured patients too seriously.

Part 28: Corona Virus Update: exit strategy, masks, aerosols, loss of smell and taste.

Part 27: Corona Virus Update: tracking infections by App and do go outside

Part 23: Corona Virus Update: need for speed in funding and publication, virus arrival, from pandemic to endemic

Part 22: Corona Virus Update: scientific studies on cures for COVID-19.

Part 21: Corona Virus Update: tests, tests, tests and how they work.

Part 20: Corona Virus Update: Case-tracking teams, slowdown in Germany, infectiousness.

Part 19: Corona Virus Update with Christian Drosten: going outside, face masks, children and media troubles.

Part 18: Leading German virologist Prof. Dr. Christian Drosten goes viral, topics: Air pollution, data quality, sequencing, immunity, seasonality & curfews.

Thursday, April 16, 2020

Corona Virus Update: Don't take stories about reinfected cured patients too seriously (part 31)

Prof. Dr. Christian Drosten

The last Corona Virus Update Podacast with specialist for emerging viruses Prof. Dr. Christian Drosten had two main topics. The internationally most important one is about press reports that cured patients would be reinfected or even that people may not become immune after recovering from the disease. ThEN WHat AbOuT hErD iMmUNiTy?

I have seen people who are normally careful and well informed talk about these "reinfections". However, it is very likely just a problem with measurement accuracy when in the final stages of the disease the amount of virus becomes very low and hard to detect, especially in samples taken from the throat.

The other half of the podcast was about a study on the spread of SARS-CoV-2 in the German municipality Heinsberg. A region not too far from Bonn were there was a big early outbreak after a Carnival party. At a press conference some preliminary results were presented without any detail on the methods, on how these results were computed. The numbers suggested less people may die and more may be infected without knowing it.

There was first a wave of publicity praising the results and discussing the political implications. Then after consulting scientists there was a wave of publicity claiming the study was rubbish, while all the scientists had said was that they did not have information on the methods and thus could not comment. Sometimes they explained the kind of information they would need to have and that was spun into the study doing this this wrong, which was not claimed. On social media people started attacking the Heinsberg scientists or those asking for more information, which can only be based on whether they liked the numbers (politically) because they knew about the methods even less. For a day Germany looked like the US culture war. Social media has a mob problem that needs addressing.

It was not a glorious hour for science reporting by (probably mostly) political journalists. Anyway because this is much ado about nothing until we have a manuscript describing the methods and purely German I have skipped this part. I was nodding a lot, yes those are the kinds of problems you have interpreting measurements, yes you really need to know the measurement process well to assess the results. There are so many similarities between sciences.

It may still be fun for the real virology science nerd to learn the kind of details that matter to interpret a study. They can read the German transcript.

The basic problem determining whether someone is ill

Korinna Hennig:

Over the weekend there have been several reports from China and South Korea about patients who were considered to have recovered or were discharged from hospital and have now tested positive again. So this is not about antibodies, but about the actual virus detection in the throat swab, for example, or from the lungs. Is it conceivable that the virus is reactivated? You also examined the course of the PCR tests on the Munich patients.

Christian Drosten:

This phenomenon can be described as follows: A patient is discharged from the hospital, verified as corona negative and as cured. And a moment later - it could be days, three or four days, or even up to seven or eight days - the patient is tested again. And suddenly he is positive for the virus in the PCR. It is said that the patient may have become newly infected, or in reality he was not immune at all, although he survived the disease. Or the virus has come back again, and you know certain infectious diseases, herpes viruses are the prime example, which can always come back.

One asks the question: is this perhaps the case with this new virus? Unfortunately, there are still very few precise descriptions in the scientific literature of how the virus is excreted in patients in different types of samples, for example in swabs taken from the throat or in lung secretion, also known as sputum, or in stool samples - these are all the types of samples we know that the virus is detectable. Only a few studies have so far described how this behaves over time in relation to excretion.

We have made and published one of them. We have made an overview picture of this excretion over time in nine patients from Munich. ... This shows the detection limit of the polymerase chain reaction. And you can see clearly, especially towards the end of the disease process, when the patients recover, that there is still virus present. It is sometimes detectable, sometimes for a few days in a row, then again for a few days in a row it is not detectable. This always jumps above and below the detection limit.

These are simply statistical phenomena that occur. A PCR can only test a certain sample, a certain sample volume for virus. There are statistical distribution phenomena which mean that the virus has in principle been there the whole time, but the test cannot always detect it. You have to picture it like this, I often explain it to students like this: you have a swimming pool full of water and goldfish are swimming in it. And there is no doubt that they are there. But now you take a sample from this paddling pool with a bucket, blindfolded. And then you may have a goldfish in your bucket and sometimes not. Still, one would not deny that there are goldfish in the swimming pool. ...

Reporting of the results

And now the question is simply how to deal with it. I can tell you that here in Germany something like this would not happen, because we have a culture here, where results like this are questioned relatively quickly and rules are always seen with the possibility of an exception. In other words, a German health authority would practically say: well, okay, that's obvious, that's what happened now.

But in the Asian culture of public health there is a much greater strictness in dealing with such rules. That is not so bad. I don't want to criticize it now. It is simply a cultural difference that when such a rule is established, it is adhered to.And when it is then said that we now agree that a patient who has been PCR negative twice in a row, we define him as cured and discharge him. ...

It is a thoroughness to say: No, this rule will not be questioned now, this is no exception, but we just enter it into the table. The patient was tested negative twice and now he is positive again. And now we test a few hundred of such discharge courses and enter all this in the table and discuss it only after we have the table completely. Then we write this together and write a scientific publication about it. This is exactly what happened, several times.

These scientific publications are now in a public resource and readable, but now this discussion process is starting. So, now it's starting with people reading such publications, who perhaps do not know the details and say: What is this? It looks like a reinfection. What is going on with this virus? And it's being spread again through even more discussion channels. This creates excitement and uncertainty.

As a scientist, I would prefer the "Asian" process, that is the cleaner data, where you know exactly what happened. You have to understand the measurement process, but the scientific literature is for scientists.

I like the movement to open science, which makes it easier for people to participate in science and also for scientists to do science, but the scientific literature is not written for normal people and it will lead to problems when people with half-knowledge start reading the scientific literature. In this case it was probably innocent, in many cases bad actors abuse this to mislead the people.

Study one

How the samples were take for one of the studies was not fully clear, as can happen with preprints.

So it may well be that at one point when the patient was discharged, they simply took swabs from the throat, and at another time they may have looked in the lung secretion that someone coughed up. Such things can happen, these are two different types of samples.

And we know well, that the lung secretion stays positive much longer after discharge. And we also believe that it is not infectious for others. Using cell culture virus isolation studies, which we also did in our publication we tried this. We already believe it's no longer infectious. We've never been able to isolate an infectious virus. ...

Study two

In the other study it is actually more interesting, it is a bit more explicit. They examined 172 patients beyond the point of discharge. In 25 of them, the test was positive again, on average after 5.23 days after discharge. There it is also clearly stated, the discharge criterion was two negative throat swabs in a row.

So: The patient had to have a negative throat-swab twice, then he was discharged as cured. But we know exactly that the throat-swab is the sample that becomes negative earliest in patients. So in the second week of illness, many patients no longer have a positive throat-swab on most of the days that one tests, while stool and sputum are still reliably almost always positive.

And then it is said that of these 25 patients, 24 patients had severe histories. For me, this indicates that if someone has a severe history, he will of course be discharged later. Then he will be treated in hospital for a longer time. And especially with these patients we know that the virus in their throat is almost always completely gone. So the virus in the throat has had time to be eliminated. So in severe cases, the throat swab is no longer positive after this long time.

Let me set a break here to let this sink in. If it were really a problem of people being re-infected because they did not acquire immunity, it would be the patients who got most ill, who did not acquire immunity. If it really were a matter of immunity, the opposite would be more logical.

Then it is said that 25 patients have been diagnosed as positive. But in 14 of them, the laboratory test was positive again after they had been discharged from the stool, i.e. not from the throat-swab, and this tells me that we have exactly this mix-up here. For we know that the stool samples in particular remain positive for the virus for a long time, and I have to say that here too, by the way, we have not found any infectious virus in them. This is probably again only dead, excreted virus.

And with others it was throat swabs, which then tested positive again. But then we have to say again, a throat swab can also contain naturally coughed up lung mucus. You cough up the stuff and it sticks to the back of your throat.

You can see from the way in which it was done methodically and from the samples in which it was found, and also from the type of patients, that people say that these are patients who have been seriously ill for a long time, that there is a risk of falling into this trap, into this confusion. I would even suspect that the authors themselves simply know that this "mistake" could be present here. ...

Other podcasts

Part 28: Corona Virus Update: exit strategy, masks, aerosols, loss of smell and taste.

Part 27: Corona Virus Update: tracking infections by App and do go outside

Part 23: Corona Virus Update: need for speed in funding and publication, virus arrival, from pandemic to endemic

Part 22: Corona Virus Update: scientific studies on cures for COVID-19.

Part 21: Corona Virus Update: tests, tests, tests and how they work.

Part 20: Corona Virus Update: Case-tracking teams, slowdown in Germany, infectiousness.

Part 19: Corona Virus Update with Christian Drosten: going outside, face masks, children and media troubles.

Part 18: Leading German virologist Prof. Dr. Christian Drosten goes viral, topics: Air pollution, data quality, sequencing, immunity, seasonality & curfews.

Tuesday, April 14, 2020

Opening up Germany in a Randomized Controlled Trial

It is now clear that for now Germany has managed to avoid spiralling into a situation where the new Coronavirus overburdens the healthcare system. In fact, I think we can say that the number of cases is declining.

So in Germany the discussion has started about slowly opening up society again. On Wednesday the 15th of April the government wants to decide what to do next week. While the number of confirmed infections is going down, I feel it would be good to basically keep the current measures in place for two more weeks. This would lower the numbers to where the tracking and tracing of infected people becomes an effective way to keep infections down, which means less restrictions long-term.

But we could use this two weeks for an experiment, which will help us make better decisions. The best experiments are [[randomized controlled trials]], where you have two conditions and randomly one of them. This is typically how new medicines are tested. Here one would randomly assign a pill or a placebo to patients.

In case of COVID-19 measures the two conditions could be a relaxation of measures or not. Because this is about the spread of a virus in a community, you cannot randomly select people, you will have to randomly select regions. As Germany is a federal state, a logical selection would be randomly assigning states, but you could also do it for municipalities. That would be better scientifically, but harder to implement.

Without mitigation measures one infected person infects 2 or 3 others. We have to bring this number below 1 to stop the epidemic. About half of the infections are transmitted by people with symptoms and half by people before they have symptoms. Some are transmitted by people who will never get symptoms and some via the environment, without direct contact. So quarantining people (with symptoms) is important, but not enough, we also need to reduce the number of physical contacts between people without symptoms, that means basically all of us. But it does not have to go to zero, which is why essential people are still working and supermarkets are open.

So we have to decide which physical contacts to allow until we have a cure or a vaccine and which ones we do not. This is a compromise between how important the contact is and how dangerous it is. Keeping supermarkets open is clearly important, people have to eat. Most dangerous are close contacts, with many people, over a longer time, inside buildings. Parties with thousands of people are clearly dangerous and, while nice, less important.

Those two decisions are easy, supermarkets open, parties closed.

The most difficult decision I see is about whether to open or close school.

On the one hand, this would be important. We cannot have our kids locked in at home, children need to move. We cannot have them miss school for one and a half year, the more so as this sacrifice does not help them as school children do not get ill. Children not going to school also prevents many parents doing essential work from going to work or working from home efficiently.

On the other hand, going to school would be dangerous. With many children, this means an enormous number of contacts. And it will be hard to change the behaviour of kids at school to reduce the contacts. (Within one class I am not even sure whether we should try.)

What makes the decision even harder is the uncertainty in how infectious children are. We know they can be infected, but as they do not have many symptoms, they may be less efficient in spreading it than adults.

So studying the influence of opening schools would be a good use of a randomized controlled trial. You could do this carefully by only having one or two years go back to school. Rather than switching from compulsory schooling, to closings schools, back to compulsory schooling, we could also make it voluntary. Parents who are in a health risk group could then opt keeping their children at home. While parents who most urgently need to work could opt to send their children to school.

Whatever we decide, I think it would be a good use of our time to use it for an experiment that helps us make better decisions about a disease we do not know much about yet.

Monday, April 13, 2020

A privacy respecting track and trace app to fight Corona is possible and effective

An app to track and trace infections seems to be a promising way out of the lockdowns. Tracking the contacts of infected people is a main strategy to fight this epidemic as long as we do not have a cure or vaccine. It is the main strategy used in South Korea and they are able to keep the number of new infections below 100 per day with it.

When the virus spreads more widely, like in many countries who did not take the virus serious enough soon enough, it becomes difficult for the health departments to track and trace so many people. In addition, a part of the contacts will not be known to the infected person and will thus not be tracked; for example, someone sitting next to you on public transport or in a restaurant.

How the app works

For the last case South Korea uses GPS information from mobile phones. I am not comfortable with the state having all that location data, but fortunately there is a better alternative. This is a great cartoon explaining how contact tracing can be done fully respecting privacy. The short version of this is below.

The Chaos Computer Club (CCC), German's most reliable technology activists, explain the conditions to make this work and have promised to warn about bad apps. I am happy use such an app and will listen to the CCC for advice. The CCC is comparable to America's [[Electronic Frontier Foundation]].

Let's hope data brokers Google and Apple getting involved does not mess this up. At least one group of scientists who started this approach are hopeful Google and Apple will help. We need many people participating, so we need something everyone can embrace.

How effective it is

A recently published study published in Science claims that such fast contact tracing could be as effective as a lockdown if 60% participate & 60% heeds its warnings.

To compute this they first estimate how the virus spreads; this paragraph can be skipped if you are not interested in the scientific basis. They estimated how long the incubation time is (5.5 days). On average it takes 5.0 days between one infected person and the next to show symptoms. So the moment someone gets ill, the people they have infected have started infecting other people. They estimate that on average 1 person infects 2 others. (This is a low value, other studies tend to find between 2 and 3.) The direct transmission from a symptomatic individual to someone else ("symptomatic transmission") explains 0.8 infections of those 2 infections. So even if if we theoretically would remove this fully the number of infections would still grow exponentially. Infected people infect 0.9 people before they show symptoms ("Pre-symptomatic transmission"). People without symptoms infect 0.1 people ("asymptomatic transmission"), while "environmental transmission", infections where people did not meet, account for 0.2 infections.

So it is important to be fast. This is the advantage of the app over a health departments trying to reach people by phone and email. Still it is worthwhile to both do manual and app tracing. A person from the health department calling you telling you your friend or colleague is ill and explaining how quarantine works is likely more effective than a notification by your phone. For this manual work to be effective we need to get the number of new infections down.

The speed of the testing is an important part of this strategy. It will thus work better in countries like Germany with a strong testing program than in America where much less testing is done, which in the short term makes the numbers look better, but does not make the situation better. The paper also studies how effective it would be if people with symptoms can warn people before being tested. This is naturally faster, but false warnings triggered by hostile actors can abuse the system. To avoid this one can tie the app to test results, where the health care providers can give the app user a code in case of a positive test.

When the app warns someone that they have been in contact with an infected person, this person will have to go into quarantine. This will work better in a country with paid sick leave and when the government gives the warning of the app the same status as "sick certificates" from the doctor.

The proximity detection by Bluetooth is far from perfect, so there will be false positives, but I would argue that that is still better assuming everyone had contact with an infected person and putting all of society on lockdown.

Enough people will have to participate. Fortunately it does not have to be all, apparently 60% is already enough. The privacy invading app of Singapore only has a take up of 10 to 15%. I would personally not use such an app, I'd rather take a small risk dying than giving a government really dangerous powers, while I would be happy to use the above described one. So I would expect the adoption of a decent app to be higher.

One would install the app to help others, so this may work less well on countries where the ruling class has pitted groups against each other to solidify their power. Ross Anderson from the UK is pessimistic about the adoption of such an app. I am quite optimistic. But we will have to do the experiment. Do note that when reading the second opinion of Anderson that I feel he does not accurately describe how the app would work; part of my text above is based on such misunderstandings others may have.

Prof. Dr. Christian Drosten, one of the main virologists in Germany who specializes in emerging viruses, thinks the app could work to reduce infections. In a recent podcast of the public radio channel NDR Info he talked about the app:

This is a study from the group of Christophe Fraser, certainly one of the best epidemiological modelers. It's a very interesting study, I think. It's published in Science. ...

The main outcome of the study is that you are too late with a simple [manual] identification of cases and contact tracing, because the whole thing depends on identifying symptomatic patients. So it really comes down to the last day. ...

And you can say in a nutshell, if the epidemics ran at the same speed as in the beginning in Wuhan ... then you could already lower R0 below one. This is amazing.

There are a few caveats on that. It is then said that in reality the speed of propagation in Europe is already faster than it was at the beginning in Wuhan. There are certainly several reasons for this. Population density, behaviour of the populations, but also how far the infection has already progressed. This of course makes it even more difficult again, so that a higher degree of cooperation among the population is actually needed. ...

You could combine such an App, for example by other general factors that reduce the transmission of the infection, such as wearing masks. ...

[The study models a situation where] there is no general lockdown. Companies can work, schools can teach, everything can work, but not for everyone at all times. There will come a time when you have this message on your mobile phone: "Please go into home quarantine." If you could then show this and your employer would say: Well, that's how it is, home quarantine this week. Then I find, that is at least a very interesting model one should not refuse thinking about.

Drosten can naturally only judge the effectiveness. The Chaos Computer Club (CCC), German's most reliable technology activists support the technical concept. It naturally depends on implementation details and while they will not recommend an app, they have promised to warn about bad apps. I will listen to the advice of the CCC.

Electronic Frontier Foundation makes clear that a trace and track app can only be part of a package of measures and rightly emphasise the importance of consent.

Informed, voluntary, and opt-in consent is the fundamental requirement for any application that tracks a user’s interactions with others in the physical world. Moreover, people who choose to use the app and then learn they are ill must also have the choice of whether to share a log of their contacts. Governments must not require the use of any proximity application. Nor should there be informal pressure to use the app in exchange for access to government services. Similarly, private parties must not require the app’s use in order to access physical spaces or obtain other benefits.

Individuals should also have the opportunity to turn off the proximity tracing app. Users who consent to some proximity tracking might not consent to other proximity tracking, for example, when they engage in particularly sensitive activities like visiting a medical provider, or engaging in political organizing.

A German conservative politician wanted to force people to use the app. He did not have a good day on social media. Well deserved. That is the most effective way to destroy trust and in times of Corona we need high compliance and thus solutions that have broad support.

The German National Academy of Sciences, Leopoldina, recommends three measures to replace the lockdowns. 1) Such an app. 2) Massive testing. 3) Everyone wearing simple masks in public. (In German.)

In the Netherlands, Arjen Lubach asks many questions on how such an app would be used. (video in Dutch.) Would your boss be allowed to force you to use such an app? Would this be a condition to use public transport? Would a restaurant be allowed to require customers to use an app? Would you be forced to share your random numbers when you find out that you are infected? Could you turn off the app? Could you ignore the warning of the app?

I had not considered many of these questions because I considered it natural to each time opt for the most free option and expect that that leads to much more people participating and thus to the largest effect. Any force to use the app would only make sense on a societal level. A boss or a restaurant has no advantages from such a measure, just like the users themselves only help society, not themselves.

My impression is that a main reason Germany got through this pandemic with only a blue eye is that the population was well informed, understood the danger, knew what to do and was very cooperative. It is relatively easy in science, but I have seen a huge part of people working from home well before there were any rules to do so. Meetings were cancelled well before the limits for the maximum number of participants went down to that level.

The alternative to so much compliance would be quite draconian rules and a lot surveillance and enforcement, leading to much more violations of freedom and economic damage. Thus I would expect that the best way to make the app a success is to respect the privacy of the citizens and respect their autonomy to make the right decisions. In countries were this is not possible, I am sceptical of the app helping much, except if they go full China and most countries do not have the enormous repressive system that would necessitate.

Where I do agree with Arjen Lubach is that we have to have this discussion now. It is not a matter of using the app or not, but how do we want to use it. We should have that discussion before we introduce it. Just like we should discuss all other measures and whether and when they can be relaxed. Even if we do not know exactly when yet, we can already discuss what has priority, opening school, shops, restaurants or car factories?

Disclaimer. In am just a simple climate scientist, not a virologist, nor an epidemiologist or encryption specialist. I had wanted to stay out of this topic and not pretend to be an instant Corona specialist, but the dumb people do not show such restraint and only few actual experts speak up. Those that do, report that they find it unpleasant. As a climate scientist I am unfortunately used to the well-funded hate mobs trying to bully others into silence and will not let myself be intimidated. Plus a large part of this post is about societal issues, where everyone should participate, not just experts.

Friday, April 10, 2020

Corona Virus Update: exit strategy, masks, aerosols, loss of smell and taste (part 28)

Prof. Dr. Christian Drosten

Today's podcast had a wide range of topics, from the proposal for an exit from the lockdown by the German National Science Academy, to face masks (which is one of their proposals), to transfer of the SARS-CoV-2 virus by droplets and by tiny airborne particles (aerosols), how long a patient is contagious and a new study on the loss of smell and taste as a symptom of COVID-19.

The Corona Virus Update Podcast is an initiative of the German public radio channel NDR Info. Today science journalist Anja Martini does the interview with Prof. Dr. Christian Drosten. He is an expert for emerging viruses at the [[research hospital Charité]]. Fittingly the hospital was founded outside the city walls of Berlin three centuries ago to help fight an outbreak of the bubonic plague, which had already depopulated large parts of East Prussia.

An exit strategy

In the previous podcast Drosten talked about a study, which suggested that a mobile phone app, which can help trace back contacts of infected people, would be quite effective in reducing the spread of the virus. About as powerful as a lockdown.

Three day later the German National Academy of Science, Leopoldina, recommended three measures, which could become an alternative for a lockdown. 1) This app, 2) more testing, 3) wearing simple masks in public.

[EDIT: It goes viral in America that Apple and Google will somehow help with such apps. That most of the work is already done by governments is not something that gets much millimetres, while it is not that clear to me what Apple and Google will contribute. They say first an API. Maybe that helps to make different apps interoperable? In a second phase they want to integrate it in the OS. If that means that the data (also) goes to Apple and Google, that would be an efficient way to kill the project.]

Leopoldina presents a model, which suggests this would be enough to keep new infections per day close to zero in May, although they also show data from South Korea, which has a similar strategy, were there is still a decent amount of new infections going on. So the model does not capture reality fully.

Anja Martini:

The Leopoldina, the National Academy of Science, issued a second statement from its working group on the virus at the end of last week. You are also part of this working group. ... It recommends - over and above the measures that we have already taken so far, in other words keeping our distance - hygiene and quarantine in the event of suspicion, isolation: Consistent wearing of masks, including in local public transport and at school, more tests, including random tests, and the use of cell phone data, which we have already discussed here. If this is done, the number of people infected by an infected person could, according to the calculations, be reduced to less than one by the middle or end of May. Even if, after Eastern, more public life were to be gradually allowed again. That is cause for optimism for the time being, isn't it? Please explain this prognosis to us!

Christian Drosten:

Of course, one looks for ways to get out of the current measures. And an organisation like the Leopoldina, which is made up of scientists, also looks at the latest scientific data. Just last week we discussed a study published in "Science" about the effects that can be expected from such mobile apps, i.e. mobile phone apps that allow much more detailed and faster case tracking.

We can simply track a certain number of infected people at the local health departments. At some point, the capacity runs out. You can't make an infinite number of phone calls and contact an infinite number of contacts and tell them to stay home and so on. It just runs out at some point. A mobile app is not exhausted that quickly and it also gets behind it much faster. That's the one provision there.

If the modelling study on the impact of this app is right, this should do most of the work.

So one can wonder why masks are additionally proposed by Leopoldina. My impression from previous podcasts is that Drosten is quite sceptical of masks. While there is evidence that they reduce the amount of viral material an infected person produces, there is not much evidence on how much they would contain the spread of the virus.

Maybe that lack of strong evidence is why Drosten wonders whether people would be persuaded to wear the masks. I do not see much of a problem, but maybe I am too optimistic. Wearing a mask is a much smaller limitation than staying at home. And I recently came by this beautiful photo of California during the Spanish flu, where people are wearing masks at an outdoor barber shop. Another culture not used to masks that were willing to wear them when needed.

You can achieve considerable increases if you add some general effects [additional measures] to this very special tracking via mobile apps. A general effect can be the wearing of masks if everyone does it. In our society, we certainly do not have the best starting conditions to let everyone wear masks. There will quickly be people who say they don't want to, they don't see the point or they can't do it.

We have currently, of course, an additional argument in public, namely: you cannot buy any masks at all, because there are none. That is why it is of course not very promising at first to consider what would happen if a general obligation to wear masks were to be imposed ad hoc?

This is a relatively complicated phenomenon, ... to impose such a thing in a society where the whole thing is not culturally anchored and not trained. That is the one difficulty. It is of course taken into consideration in a forum like the Leopoldina, where social scientists, psychologists and so on are also represented. This is precisely why the totality of the expertise is represented, not only life scientists are in it, but also sociologist.

Types of masks

Christian Drosten:

We have hardly any scientific evidence that says that self-protection through simple masks works. Of course, there are much more complicated, elaborate masks for special wearers, i.e. for certain occupational groups, who also provide self-protection.

But these masks have actually never been available in large numbers. They are not so easy to produce so fast, as far as I know. By the way, they are also not easy to wear for everyone. You have to imagine that here in medicine there are preliminary occupational medical examinations for employees who have to wear these very safe self-protection masks in their professional life. Not everyone is able to do this, for example, if there is any doubt, the medical profession must carry out lung function tests. And something like that cannot be recommended for the normal population.

I am not sure I understand his claim on the simple masks:

With these [simple] masks it is the case, there is no scientific evidence of a benefit for self-protection. There is, however, starting evidence, which has not been very virus-specific so far, for the protection of others. But this of course presupposes that really everyone, everyone, everyone in society, in public life, must wear these masks.

I would expect that when half of all people do it you get half of the effect. But maybe Drosten means that for this to help for your own protection everyone would have to do it. Also if only half would do it, to help the others, one could expect that the participation drops. That is a kind of [[public goods game]] It could also be that he does not expect much of an effect and that half would thus really not be worth it.

Droplets and aerosols

A large part of the podcast was about the difference between droplets with virus and aerosols. Droplets would be defined as being large enough to drop to the ground by gravity within a minute, while aerosols can stay in the air for hours. It was a long and nuanced discussion about evidence on how these particles are produced and removed, how infectious they are and how important they are.

People are worried about the aerosols, about "airborne virus" because it means that you could be infected without having noticed someone coughing. But in the end the droplets are most important: "we are pretty sure that the vast majority of the viruses that are released in these diseases of the upper respiratory tract ... are these larger droplets - and they fall to the ground". So to focus on what is important, I only translated a small part:

Christian Drosten:

These large droplets over five microns (and they can can be much bigger, they can also be 100 micrometers, i.e. a tenth of a millimeter, so that you can really see them with the naked eye) - these are the droplets that we are talking about in a droplet infection. In other words, what you give off - which is part of a moist speech [when people spatter when they talk], for example, but also comes out when you cough or sneeze - and which falls to the ground within a radius of one and a half to two meters.

In this research into the common cold, we are pretty sure that the vast majority of the viruses that are released in these diseases of the upper respiratory tract (i.e. the diseases that mainly occur in the throat and nose) are these larger droplets - and they fall to the ground. Much of our precautions and infection prevention considerations are based on this insight.

Then there is something else, namely aerosols, whose particle size is less than five micrometers. For the experts, it must be said that this is of course not a sharply defined size, and an aerosol that really floats in the air and stays in the air longer, the actual droplets are even much smaller, they are less than one micrometer in size. ...

If I release such a droplet and it floats in the air in front of me, then it starts to dry and then it becomes smaller. The smaller it gets, the more likely it is that it will remain in the air for a long time. But at the same time there is another effect, namely when this droplet gets smaller and smaller, it will eventually be too small for the virus, and the virus will dry out and will no longer be infectious.

So on the one hand aerosols are potentially more problematic by staying in the air longer, on the other hand they are likely less contagious, while many studies only analyse whether virus is present, not whether the material is infectious. Reading such studies one should pay attention to this difference.

How long is someone contagious

An interesting preprint studied how much virus could be found in hospital rooms of COVID-19 patients.

Christian Drosten:

Wipe samples were taken - in 30 different hospital rooms, from 30 different patients, all of whom had the disease, in a hospital in Singapore, from all kinds of surfaces, and tested them for virus again.

By the way, I have to add here, in all these studies, especially the last study that we discussed first, and this one too, it is always only a viral detection of RNA and not of infectivity in the cell culture.

Anja Martini:

In other words, a virus that can be detected, but which possibly no longer infects anyone.

Christian Drosten:

Right, exactly. A desiccated virus, it still has the same amount of RNA and you can still detect it. None of this means anything directly about infectivity right now, it just means that virus has got there.

And here it is the case that a lot of deposited RNA has already been found in these samples. In the floor samples, for example, more than half of the wipe samples were virus-positive, i.e. viral RNA could be detected - which suggests that the virus is deposited to a considerable extent, which is a sign of the fact that the virus is in fact deposits considerably, which favours the concept of a coarser drops.

But then, something else and very important, I think: With these 30 patients were these virus swab samples always positive only in the first week of symptoms. In the the second week, when the patients were still definitely sick the wipe samples were no longer positive. So no more virus settles on the surfaces, was accordingly also no significant virus concentration more in the room air.

Note, this is just one study. Decisions should be based on all available evidence and an uncertainty estimate.

Infection via surfaces

If I understand it right, when someone coughs in their hands and then shakes hands, that is seen as droplet transmission and not as transmission via a surface. This route is important and a reason for the advice not to cough in your hands and to wash them regularly.

Anja Martini:

The insight we have from this is that we are infected via the air we breathe, via coughing, via aerosols, and not, as is a question much asked by listeners here, what is actually the case with infection via surfaces?

Christian Drosten:

Infection via surfaces themselves has been modelled, for example, in the study by Christophe Fraser that we discussed last week. He comes to the conclusion that perhaps ten percent of all transmissions could function via surfaces at all.

Many people I talk to don't really believe in the relevance of surface transmission. ...

We do not currently assume that this virus is significantly transmitted via surfaces. The current measures to prevent transmission are aimed at preventing both droplet and airborne transmission, especially - to say it again - droplet transmission. And the studies that have now been discussed here, that have now been published, do not suggest - even if small-droplet aerosols have been detected - that this mechanism would be the main focus.

Anja Martini:

This means, once again asking from the consumer's point of view, ... can we actually neglect surface disinfectants in our private lives?

Christian Drosten:

I am almost sure that it is not worthwhile to pay a lot of attention in the household to treat all kinds of surfaces with disinfectant. In a hospital, of course, this may be different. ...

My impression is that this was scientific "may", which mostly means "will". We sometimes talk in a somewhat weird way.

Images from television, for example, in China, where tanker lorries are driving through the streets with disinfectants, I think that has more of a psychological effect on the population than a real effect in curbing the transmission of infection.

I love those videos of teams with disinfectant sprayers walking through the streets as if they could be eye to eye with a terrorist any second.

Loss of smell and taste

Anja Martini:

What does a possible disease or even an infection with the virus actually do to the sense of taste and smell? This was already something of an observation in the press. There was also a Belgian study. Now there is one from Iran based on an online questionnaire.

Christian Drosten:

Yes, I think it's a very interesting study. There are already clear indications. In the Munich patient observation we have already seen a loss of the sense of taste and smell in almost half of the cases. So this has already been published.

There is now even a functional study that has just been published - and it says that it is a very specific type of cells in the olfactory system, in the nose, in the olfactory bulb, that is actually infected and affected by this virus.

But that is not what we want to discuss here. Interestingly, it is a study from Iran. I think it is simply great to see that this kind of useful research also comes from a country that is highly affected and where we all know that the data situation is unclear. The science there has to work in a difficult system, has also difficulties, for example, to get certain reagents. But but here comes a very interesting study, from the preprint realm, to the public.

Iranian scientists conducted a survey - also supported by apps and the Internet - and reached 15,000 people with this survey. Of these, 10,000 actually had a loss or impairment of the sense of smell. In fact, 76 percent of these 10,000 patients - an impressively large number - had a sudden loss.

You can tell the difference between saying that suddenly I couldn't smell anything anymore. Or whether you say, well, I just had a cold. And 75 percent, a similarly high rate, actually had influenza-like symptoms. So now that not only a runny nose is part of it, but also a noticeable fever and so on. This was clarified by questionnaires.

83 percent also had a loss of taste, which was also described, also in the Munich patients, so that a loss of taste is also involved. They could no longer taste or smell anything. ...

And if I suddenly couldn't smell anything anymore in my everyday life, I would stay at home and try to clarify what is going on with me at the moment, in the current situation.

Other podcasts

Part 27: Corona Virus Update: tracking infections by App and do go outside

Part 23: Corona Virus Update: need for speed in funding and publication, virus arrival, from pandemic to endemic

Part 22: Corona Virus Update: scientific studies on cures for COVID-19.

Part 21: Corona Virus Update: tests, tests, tests and how they work.

Part 20: Corona Virus Update: Case-tracking teams, slowdown in Germany, infectiousness.

Part 19: Corona Virus Update with Christian Drosten: going outside, face masks, children and media troubles.

Part 18: Leading German virologist Prof. Dr. Christian Drosten goes viral, topics: Air pollution, data quality, sequencing, immunity, seasonality & curfews.

Pages

Friday, April 16, 2021

Related reading

Friday, November 20, 2020

Related reading

Sunday, August 30, 2020

Herd immunity

Related reading

Monday, April 20, 2020

The situation and measures in Germany

Summertime

World Health Organization and Trump

Local outbreaks in wave 1, everywhere in wave 2

Positive surprises

Other podcasts

Related reading

Thursday, April 16, 2020

The basic problem determining whether someone is ill

Reporting of the results

Study one

Study two

Other podcasts

Related reading

Tuesday, April 14, 2020

Related reading

Monday, April 13, 2020

How the app works

How effective it is

Related reading

Friday, April 10, 2020

An exit strategy

Types of masks

Droplets and aerosols

How long is someone contagious

Infection via surfaces

Loss of smell and taste

Other podcasts

Related reading

Most read posts

Search this blog

Blog archive

Follow blog feed