Episode 54- A Recommendation for the Autumn

If you are able and willing to help me with these translations, please PM me on Reddit ASAP. My schedule is getting busier, so any help is appreciated.

DISCLAIMER: I am not a doctor or a healthcare practitioner, nor do I have a master's or a PhD. I am not a native German speaker either- I only know German as a foreign language, one I learned using whatever resources I could get a hand on. If my translation conflicts with that of anyone belonging to any of the groups mentioned above, please refer to theirs instead of mine. Needless to say, if an official translation, done by a scientific translator comes out, then refer to that instead of this one. I am simply a medical student who admires the work of Dr. Drosten and colleagues, and I would like to provide unofficial translations of the podcasts so that they may be helpful to those who do not speak German.For corrections, please reach out to me on Reddit and send advice in. I apologize in advance for any errors I have made. There are some footnotes at the bottom of this translation.

Original release date: September 1, 2020
Original audio: https://mediandr-a.akamaihd.net/progressive/2020/0901/AU-20200901-1544-3500.mp3
Original transcript: https://www.ndr.de/nachrichten/info/coronaskript222.pdf

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ANNOUNCER: NDR Info. The Coronavirus update.

HENNIG: Compared to other countries, Germany is still doing very well. There are calculations based on research at the University of Oxford that say that if the USA had handled itself the same way Germany has, then 70% of the deaths during the first months of Covid-19 could have been prevented- around 80,000 people. But the number of new infections in Germany is measurably higher. We are back in our podcast, and would like to see how far research has come. I would like first to clear something up, because there have time and again been some people voicing their frustrations on social media—yes, we have taken a break from the podcast, but neither Dr. Drosten nor I took a two month vacation.
Dr. Drosten, as a researcher, you have done a lot of work, including research into SARS-CoV-2. What were you mostly concerned with over the summer?

DROSTEN: Yes, for me, this was a very busy summer. I had, in principle, two weeks of vacation. A week at the beginning and a week at the end, and between them, a trip to the grandparents. But we haven’t gone on a three week vacation. It wasn’t, as I initially thought, only basic science research, though we did do that as well. We have started on two studies, which I find very interesting and really also very important. We have published them in journals and have already made a first revision to one. They revolve around the question: is the virus changing? Does the virulence, the ability of the virus to cause disease, change over time? You can test certain aspects of this. But I will not say anything about this, otherwise I may be over-interpreted. In another study, the MERS virus is being studied—not the SARS-2 virus at all, but another highly pathogenic coronavirus that is transmitted to humans via camels and can be found in Arabic regions in North and East Africa. Then, many very practical questions came, which I worked on in the background. For instance, how could rapid tests be processed more quickly? We have already talked about rapid tests in the podcast in May, maybe even in April.

HENNIG: Antigen tests…

DROSTEN: Exactly, antigen tests.  We have heard about these here, in the public as well, where people say that they come quickly. In reality, it’s not as easy as is sometimes said on TV. There is a long regulatory process. Everything must conform to the law. I have tried to help out a little with this. And then the big question about mass testing via PCR—a lot of consultation is needed for this. It is not always the case that the highest political bodies are consulted, but also regulatory bodies, for instance federal authorities, state authorities, who have many, many questions. Laboratory work should also be done in the background. It was therefore a summer with a  lot of practical work, in order to anticipate things that will be very important during the autumn.

HENNIG: We would like to talk about the question of testing in the course of this episode. There are many things that have been somewhat confirmed over the summer by clinical observation studies, but also due to results and evidence from laboratories. For you, was there anything surprising in your field of expertise?

DROSTEN: That’s actually the impression that I have had over the past days, that there haven’t been any surprises over the summer. Many of the studies that we have spoken about, which appeared in big journals over the summer, have been officially published. New studies have appeared, which have supported what we have anticipated in preprints and in small studies. There aren’t really any truly new insights that would have had a direct change in the control or the handling of the pandemic  over the last two months of the summer, nothing that anyone would call “game-changing.”

HENNIG: There are, however—how do I say this—different things that have been somewhat supported. I will try to summarize two of them. Researcher are fairly sure that the virus is primarily transported in the air, via aerosols. And regarding the effectiveness of masks, there is still uncertainty, but we do know that they are more effective than they were thought to be at the start of the pandemic—we have mentioned this in the podcast as well—and may even work to a limited degree as self-protection.

DROSTEN: Correct, you can say this. The topic of masks is complex. We have talked about it many times in previous episodes. There is the question of wearing them when it’s uncomfortable to wear them—should we wear them then? I don’t want to argue scientifically about this now. I will only give an example which I have not yet heard in public discourse, and yet is still rather pertinent. “Wet speech”, namely infection via droplets from one’s saliva—droplets that fall to the ground within 1.5 meters of their origin, are hindered by a mask. That is clear. The question, however, is how things are with aerosols? With aerosols, one can say that the droplets in these exhaled aerosols are so small that a poorly worn mask cannot hinder them. They are therefore exhaled through the mask, and are also inhaled through the mask. This should be explained.
There are clearly imperfections with masks. This is a matter of fact. Thus, the protective potential of masks for oneself and for others is, taking these considerations in mind, somewhat smaller (than thought). Now we have a consideration that should really also be known—these aerosols do not disperse uniformly when they arise. When an aerosol has been in a room for one or two hours, it will be present everywhere in the room. Let us imagine cigarette spoke. I sit down in a room and light up a cigarette. In the beginning, the cigarette smoke is only present around me. It is present around my head, where I sit, but it is not present everywhere in the room.

HENNIG: But you would have blown it in the face of someone sitting opposite you.

DROSTEN: Yes, I shouldn’t do that. But this is where I want to go with my argument. A study has shown that the entire room would be contaminated with cigarette smoke If I smoke the whole time, this is clear. One can’t do anything else with a mask. You would breathe in cigarette smoke in any case. If I imagine, however, that I come to a situation, let’s say a supermarket or something, where I wouldn’t stay in the room so long. If I were to meet an infected person and am concerned about aerosols, then around this person would be an area with a high concentration of aerosols. The question would be: would I inhale the aerosol or not? If both I and they have a mask on, then the aerosol would go through the mask. But I wouldn’t directly contact me. I wouldn’t be able to blow the cigarette smoke in their face. And this is a consideration that one should keep in mind, that regarding this cigarette smoke, there is a high local concentration, which I would not like to inhale. Similarly, there would be a high virus concentration (around the infected person) which is infectious.
I would like to give another example. I believe many of us remember the time before the pandemic, where it was normal to meet up. For instance, during meetings, at the table, in an event, people would talk with each other. People didn’t have masks on and could smell other people’s breath. The smell of one’s breath—this is caused by aerosols. There are also gases there, not just moisture, not just droplets of saliva, but for our simplified discussion it would be enough to say that that’s all they are. Could you imagine the same situation, being in a buffet with someone and speaking to each other while you are the same distance apart, but both of you have masks on. Can you imagine if you would still notice the smell of the person you’re talking to’s breath?

HENNIG: Or if they had eaten garlic.

DROSTEN: Exactly, you would not notice this. “Not notice” can be translated as, “I would not be infected so quickly.” And that is something that those who have doubts about the effectiveness of masks should take note of.

HENNIG: In any case, they cause a reduction, even if they don’t work 100%. I would like to take a look at another aspect which our listeners have asked about a lot—the question of whether survivors are immune to SARS-CoV-2 . Antibodies can actually disappear, studies have shown. But that isn’t all bad news, as we have already learned from this podcast: there is also cellular-level immunity. How robust can this be? What do we know for now about this, Dr. Drosten?

-----IMMUNE AFTER SURVIVING AN INFECTION?------

DROSTEN: Yes, it is so, other studies have been published. We have somewhat anticipated this, that studies would come. There are many aspects that one can summarize. For instance, it is true that there is cellular immunity. And this appears to be very robust. A study has shown for instance that in people that have survived SARS-1, (cellular immunity) is more evident in most SARS-1 patients from back then, even now, 17 or 18 years later. This memory T cell reaction shows that cellular immunity exists. These aren’t effector T cells, not CD8 cells (the cytotoxic T cells that go after the virus themselves) and not B cells, which produce antibodies, but these are the “switches” of immune memory, so to say, which are still able to function after such a long time. And this is obviously a completely different time period as that when antibodies are detectable.
One must also say that even with antibodies, the detectability is lower in a few laboratory tests. The antibodies will, if accurately measured, not completely disappear. What disappears is the neutralizing activity of antibodies. If measured properly, this can be seen often. That is simply because the IgA and IgM antibodies disappear, but not IgG antibodies. And these are completely normal occurrences in every infection. That is very much to be expected, and so should be accurately measured with more diagnostic tests. If you follow such patients, then you will notice that there will be fewer [antibodies], but there will not be a complete lack of them. If we know for a fact that there are a few patients here and there that the antibody levels decrease completely to zero, the question would be—what does this mean? Then we come to the fact that there is a sort of memory in the immune system. And for patients, this is practically the same, whether there are detectable antibody levels in the blood or not, but as soon as the patient comes into contact with the virus, immunological memory kicks in and there will be antibodies again. In principle, more quickly than the virus can spread in the body. And the virus will then be stopped. The immune system functions like this.
Laboratory testing is an indication, but it does not show everything about immunity. This is why I am sure that for the time period we are looking at regarding the pandemic, (survivors) will be immune. This isn’t a question of whether one would be immune for all of eternity after a single infection, but rather a question of whether an infected person would be immune for the rest of the pandemic, let’s say until the end of 2021, this is the time period we’re concerned with. I will not say that the pandemic will last until the end of 2021 in any case. I hope that we will be able to control certain things about the pandemic through vaccines, such as the high death rate in older age groups, and that in doing so, the danger of the pandemic will have passed. But we are thinking of a timeframe lasting until the end of 2021, I am very sure and very optimistic that all patients that have lived through an infection are immune up till now. Immune does not mean that laboratory tests will always show positives. That can also mean that such a patient, if they were to be in contact with the virus after a year, would have a superficial infection. That means that patients may have a mild throat ache or even no symptoms at all, but the virus would be detectable via PCR, a small, brief replication, but one that would not lead to serious lung inflammation. And above all, [I hope] this virus, detectable in laboratory tests, will not grow to such a concentration that it will lead to another chain of infections, in other words further transmission.

HENNIG: There is the report of the case of a man in Hong Kong who was infected early on in the year, with classic symptoms and who PCR tests detected the virus in. After travelling on vacation he was completely asymptomatic, but was retested and found to be positive. Is that a case of what you described in your theory?

DROSTEN: Exactly, this can be such a case. But I also don’t believe that this is the most common outcome, but rather that these are rarities. At the moment it is hard to say how many per cent of all patients are affected by this. I would not be surprised if in the end this would be over one, or maybe over five per cent. But that would probably not make an impact on the spread or danger of the virus. What we have here is a media phenomenon. We have a group at a university which says: Wow, we have found a rare case, which we will publish and make a huge fuss with the press about, a press release. The media would grab hold of this and reduce it to say: “A man was infected twice. Does this fail to square up with immunity? Does this mean that a vaccine would not work?” No, of course not. That is merely a struggle for attention. One can see that as these press releases went through the media, other scientists latched onto this and said, “We announce that we have also observed such a case.”

HENNIG: For instance, in the Netherlands.

DROSTEN: Exactly. We have not yet summarized this as a journal article. But we will say now, in advance, that we have also found this. All of that is just an attention-gaining enterprise. That does not depict the medical reality and normal cases.

HENNIG: Considering all of this, what role is played by the different viral strains discussed previously?

DROSTEN: This particular group of SARS viruses in all their diversity, all of the viruses within that group, which started in Wuhan and spread all over the world and differentiated, are unbelievably similar to each other. This doesn’t mean that we can say that there are different viral strains, which we have for instance with the different common cold viruses. For instance influenza, you can’t compare them at all. This virus is still very knew and very undifferentiated. Using particularities in their viral sequences, we can differentiate a number of clades (the more specific taxonomic groups underneath a larger one [i.e. SARS-CoV-2]). There is, however, very little indication as to whether they are dangerous or transmittable. A variant which we have spoken about in the first half of the year is the D614G mutant. There is a substitution in its surface glycoprotein. There are indications—only with surrogate systems, however, not with real viruses but rather only with model viruses where for instance something would take up an HIV virus which would contain this mutant glycoprotein from the SARS-2 virus—there are indications that the buildup of glycoproteins is more efficient if this mutation is present. In pseudo-virus systems, one would see more surface proteins per particle.
We don’t know at all whether this is the case in a real SARS virus. One can say that this leads to a scenario where the infectivity of cells is somewhat higher in cell cultures. One could also say however, that up until now there is no real evidence for this, whether in model systems or in epidemiological data, that more sickness is to be observed with this mutant. There is some decent evidence, which should still be taken with a grain of salt, that say that the transmission rate is greater with this viral variant. Only, however, by a small amount, it’s not massive, but very small. And there is no evidence that the disease-causing potential would have changed as a result.

HENNIG: We’re still keeping this in mind in our podcast. I would like to move, however, to the current situation and take a look at the numbers. A classic question that we journalists like to ask again and again is the question: where are we? Is this the beginning of the second wave? What is the connection between tests and infection numbers? Again and again do we receive requests for more information. Do we have a higher incidence rate, higher numbers of new infections, maybe only because more people are being tested?

-----MORE TESTS: HIGHER NUMBERS OF INFECTIONS?-----

DROSTEN: These are relatively complex arguments. The question of testing, however, depends somewhat on where you’re testing. Let us imagine the situation in March, during the first wave. We tested patients that have typical symptoms—we would naturally find the virus more often. Let’s say that we test 100 people, maybe seven or eight of them would be positive. If we test in a situation where we would have in principle a smaller incidence in the population, and where we have stopped asking about symptoms but rather allow anyone to be tested if they want to, then we would have far fewer positive results. Two situations have thus been mixed up in my entire argument. I don’t know if you might have noticed this—I have talked about a scenario concerning time period and another concerning indicator groups.

HENNIG: In other words, based on place.


-----ARE WE IN THE SECOND WAVE ALREADY?-----

DROSTEN: Exactly, or we could say a social or a medical scenario. Or I could say, we’re in the first wave, or maybe we aren’t. The question is, what is the real incidence rate? And the second consideration is: do we test every symptomatic patient or do we test whoever? These scenarios end up completely falling apart. Thus it is very difficult at the moment to summarize all of this. It is true, for instance, that if we take a look at the amount of testing, it is very, very high. It is pushing the medical laboratories to their limits, and we are actually finding very, very few positives. If you take an accurate look at this, it would not be so, that if we compared the situation now to that in May, June, when we had a low incidence rate, when we stopped everything and then gradually loosened up, and saw that the number of cases didn’t go up so dramatically afterwards, we tested at a relatively high rate. We cannot say that we find more infections at the end of July or August solely because of the larger amounts of tests conducted. We would also have to see a decrease in the frequency with which sicknesses are detected. That has not happened. So the current numbers are real if you relate them to the previous numbers.  I believe that you can reliably say that in May and June we had a smaller incidence rate as in July and August. Nevertheless, it is probably true that back then, and even now, the number of infections in the population has been somewhat underestimated. One reason for this is that we simply can’t test everybody. The other reason is, and this is an especially pertinent consideration now, that the sort of patients we have now are different from those we had then. The age-specific incidence rates have changed a lot. After the spread, after the first wave, we had relatively high incidence rates in the middle-aged and elderly, but in total we had lower incidence rates. And now, young people are suddenly starting to celebrate and get infected and even to travel. All these things are happening at the same time. We also have many cases of people who have harmless, mild infections, because younger people have milder infections. At the same time, if for instance I was in an illegal “techno-party”, then I would have the tendency to hide my symptoms and not allow myself to be diagnosed. Because then I, a 20 year old, would have to say that I was at an illegal party. Five days later, I would have throat aches, which I wouldn’t go to the doctor for. If I was responsible, I would stay at home for three or four days, shut myself away and say that everything will be fine. This scenario has probably come to pass relatively often, without us noticing. We have had such cases before, let’s say in May, but certainly less often. Such things have not been taken into account. I am aware that I am speaking of a hypothetical situation, but I am doing so to show that if you think about such a situation, and find out that there’s a hidden dimension lying underneath it, then there may be a second or third or fourth layer underneath as well. At some point, it should be recognized you can’t grasp every single one of these effects that play a part in this complex conglomerate we call “population”. I will give another example, this topic of people returning from vacation. This is not easy to describe. We have many different sorts of these people. Some come from areas with low incidence rates, some come from areas with higher rates. They have behaved very differently on vacation. Not all of them go on holiday—some are simply visiting their families. And there are also people from different cultural contexts who may not have been in contact with only their families, but with other social circles. And this in countries with completely different incidence rates, who may deal with the pandemic differently. Countries that may even treat it as harmless. All of this plays a role. We cannot think about this in purely technical terms such as sensitivity or laboratory capacity. The human element changes everything, and is very hard to grasp.

HENNIG: We also cannot simply compare statistics to each other, even if they both point in a similar direction. You have said that with those around 30 years old, the Robert Koch Institute has recorded positive tests among them, despite the “hidden infections” you have described?

DROSTEN: The Robert Koch Institute is very precise in its preparation of data. There is no other national health authority that I know of that is so precise and adept. These numbers are the best that we have. We can therefore turn to them. Of course, in the reporting systems, there are sometimes corrections that need to be made. These occur because reporting involves doctors, both laboratory-based and clinicians, government doctors, which ask more questions and think about things and make epidemiological estimates here and there, in which for instance it is asked: “Just a moment, you are not the only case in your family. Can we test your entire household?” This would then correct things, such as the tendency of people to hide their illnesses.
That is why we depend on these numbers. They are not wrong and the progression of these numbers, in other words that there are more cases now than before, is not wrong. A the moment, we can see that we now have fluctuations, a little more now, a little less in areas of low incidence, these increases and decreases—there are surely a number of artifacts here.
For instance, the decision to suddenly test more people returning from vacation, has surely had a great effect. We have such cases where, sometimes to a large degree—this is the case in some federal states—40% of new diagnoses are of people who have just returned from vacation. That influences the statistics as well as how we should understand these statistics. There is a difference, someone with a positive PCR test may have come from another country, where the outbreak is really occurring, and had already recovered from the infection. Despite the positive PCR, they would no longer be infectious.

HENNIG: The virus wouldn’t be carried back here [in Germany].

DROSTEN: Exactly, it is really positive, there is no doubt about the medical diagnosis. However, one should see this source of infection very differently than, for instance, someone who shows early symptoms and reports to a health office and says “I feel ill, I wish to be tested. By the way, five days ago I was at a big grill party and it was cold in the evening there. All of us therefore went inside and danced for three hours. I have not met the 50 people there since. But a few of them told me that they were experiencing the same thing over the telephone.  That is to be judged differently. We have two cases, both of which have positive PCRs, but the epidemiological implications and the danger are very different depending on whether the cluster source is in another country, in a country you’ve gone on vacation is, or if it is at a grill party in the city, here and now.

HENNIG: We have spoken about these clusters in Episode 44, about the question of the unequal distribution of cases. This example of a grill party, then, is an example of what people are talking about when they say, “We are trying to control the number of new cases so that we can trace back individual cases in order to discover clusters of infections. In other words, to see who went where with whom. How long can we keep this up? Can we continue to control the number of new infections, as is being attempted at the moment? Or will they continue to spread?

DROSTEN: It is very difficult to say when this will happen. There are questions that get asked all the time. One of them is, “How are things now?” Are we in the second wave? Is it happening now? It isn’t helpful to say, “There is no such thing as a second wave.” Or to say, “The second wave will certainly come.” And yet someone else would say, “This is really just a long first wave.” These are just words, but there is something else lying behind them. I would like to introduce a phenomenon that I have explained before in the podcast. I have often said that we don’t see whole contact networks. I have said this when we considered the topics of prevalence and the rise of herd immunity. I have said that not only does the percentage of the immune population have to be around 70%, but the R0 must also be below one. There are also other effects, namely the availability of contact networks. What we have here is another theoretical topic—that of percolation.

HENNIG: A mathematical model which originated from physics.

DROSTEN: Yes, it came from physics. And it made its way to the fields of infection ecology as well as infection epidemiology. Epidemiology is, medically, a special case of ecology, one could say. The basis of epidemiology is ecology and, one could also say, mathematics. I would say ecology. In any case, in ecology, it is an accepted principle, but isn’t very well known, especially within the German-speaking world. I must take a moment here, before I give a scientific example and introduce a publication that I fished out yesterday evening, before we can give a visual introduction to what we must clear up about the progress of the second wave. I will begin with three relatively simple examples.

HENNIG: Maybe we should define the word “percolation”. This is to do with fluids seeping through something, right?

DROSTEN: Yes, “seep” is a good word. Let us imagine a coffee filter, not a modern espresso machine, but a good old coffee filter, one that you put over a container. Nowadays you just add some water. But those who know how it used to be done know that they were pre-brewed. You first poured a little water onto the coffee, mixing it. What you would then see is that nothing would come out of the bottom at all. You keep pouring onto the top, nothing comes out.

HENNIG: The filter would be full of water first.

DROSTEN: Exactly. The coffee powder would be wet, but not enough to seep through. Now we can imagine that normally, you’d pour everything all at once and then the coffee would flow through. When done slowly, however, drop by drop, then you would notice a long time pass without anything happening. The coffee would become wetter and wetter but we would not be able to see that. We would only see ourselves adding water to the top without anything coming out at the bottom. And so this happens, minute after minute. But at some point we would get to a point where for every drop I add to the top, a drop would exit from the bottom. If I were to stop adding water, nothing would come out. That is the first example of percolation. What happens in reality is that there is a network of very small pockets in the coffee powder through which the water seeps. At some point this network of holes will link up to form a passage. Water passes through this passage because there is a connection, albeit one that is crooked, not straight, a winding route through the coffee powder from above to below. An example that I unfortunately don’t find so good. I will thus give two more examples.
An example is the game Connect Four. Let us imagine that we have yellow and red chips which we randomly arrange within the plastic grid, ensuring that we have a 50/50 mix of yellow and red chips. If we do so, we might not be able to trace a path of red chips from the top to the bottom. We have to go from red chip to red chip within this grid. The path doesn’t have to be straight, but there should be a path. Statistically, we would always be able to find a path if around 50% of the chips are red. What about a scenario where the clusters of red chips and yellow chips will be distributed in such a way that there will always be a path between the red chips? You can imagine that if we have an 80/20 distribution, in other words 80% red chips, 20% yellow, there will always be a path. I would like to make things a little more concrete with another example. Let us imagine that, instead of the grids we have with Connect Four, we have a wooden frame, let’s say a wooden box. On the underside and on the top we have two electrodes. Imagine filling this wooden box with spheres, which will arrange themselves in a certain pattern. Half of these spheres are made of wood, the other half of metal. And the question that we are asking is: what ratio of wooden spheres and metal spheres do we need so that, assuming the box is full, that there are no gaps in this lattice of spheres, from the bottom left hand corner of the box, what ratio of metal to wooden spheres do we need to ensure that there will be an electric current between the electrodes because of the presence of a string of metal balls in contact with each other?

HENNIG: A path through the box, so to say.

-----INFECTIONS DUE TO CLUSTERS-----

DROSTEN: A path through the box, an electrical path. One can analyze this mathematically and find out that there are measurable physical, mathematical rules that state what ratios are needed for current to pass through. We can actually change these ratios and find out that the current doesn’t flow here, it doesn’t flow there—and then suddenly it does. If we repeat these experiments we can find that these aren’t completely out-there phenomena, but are rather statistical occurrences, even if sometimes you can find whole sequences of metal balls even if there are only a few metal balls in total. You would perhaps find a current in such an experiment by chance.
Let us imagine the simplest case, a straight diagonal line of metal balls. All of the rest are wooden balls. There would certainly be very few metal balls and yet we would see an electrical current. If around 50% are metal balls, we would almost always see an electric current. With over 50% metal balls, then it wouldn’t matter how we distribute the balls, we would practically always see an electrical current.
And thus we come to an example from infection ecology and a 2008 paper published in Nature. This I s a study where an animal population was studied, and—

HENNIG: In jerboas, I believe.

DROSTEN: The great gerbil, to be more precise. For the zoologists here, Rhombomys opimus, a subfamily of gerbils, which are rodents. The genus is Rhombomys, the scientific name (with species) is Rhombomys opimus. These were studied in Kazakhstan. An infectious disease model was tested, using Yersinia pestis, the pathogen which caused the bubonic plague. These are transmitted not only by normal rats, but also by these rodents. What was observed here was a percolation phenomenon reflected in reality. And the authors begin to argue in this study. In all of these models of epidemiology, we have the R0 value. All of us know that if the R0 is greater, the infection is spreading. But all of these population models assume panmixia, in other words, random mixing. Theoretically, each organism is equally likely to have contact with any other organism for a certain period of time. This is an assumption that simply isn’t the case. That is a generalization and simplification in R0 calculations. Modern models still assume this in their calculations. But when one speaks of such things in the general public, they will be over-simplified and become unclear, and so, within the general public, there will be little consideration given to such effects. I hope everyone can still follow me?

HENNIG: Yes, we can.

DROSTEN: Okay. Here we have an animal that lives in familial groups. These groups live in underground cave systems. These are networks that have an extent of 10 to 30 meters, that’s how far these animals’ underground cave networks are. But they don’t dig more than this, they’re too lazy for that and they simply don’t need any more space to live. This is how their families live. And these animals do so in a relatively free, barren steppe landscape. There are always gaps, just like in a Connect Four grid, visible from satellite images. In this Nature paper, which will be cited in the References, there is a satellite image. It is astonishing to see that the picture looks almost like a Connect Four game, these holes arranged just like in a grid. Every hole is, from an outside perspective, a bit like a 30 meter network of caves in which a family of great gerbils lives. They either carry the plague or they don’t.
It is transmitted over fleas, which are a vector. But what one can observe here is very simple. One can pick out circles of three or four kilometers around certain points, which would be like replicates, and if one were to look at these areas, they may see a family group that has Yersinia pestis, the cause of the plague. But if you were to zoom out more and more, would you still be able to detect Y. pestis? In other words, be looking at larger circles, not observing just one replicate at a time, but many replicates in parallel. That would be like observing a large area of land, I don’t know how many counties large, practically, it would be the same. And now there is an interesting and relatively easy hypothesis—if the disease continues to replicate as the R0 predicts it would, then the higher the population density in the area, the more infections there will be. The more rats, or the more people there are in a space, the better a virus would be at spreading within. Or a bacterium, Yersinia pestis is a bacterium.

HENNIG: The more people that can form contact networks and build bridges within?

DROSTEN: Yes, there would be more susceptible people. That is all based on susceptibility, this R0 model. The more susceptible people we have within an area, the better the pathogen will spread. There must be a linear or at least regular relationship there. If you take a look at this, this is only so on small scales, not in large ones. If we look at the key point, as we have seen, an infected family group, if we look at another situation, at what happens if the population density is higher, or where more of these underground caves are populated (this is really what all of this is based on), then the more animals there are, the more infections. And you’d have to look everywhere, because the infection spreads in the same way everywhere.

HENNIG: Over the whole area.

DROSTEN: Over the entire area, exactly. What you’d actually see, however, is that this only applies to smaller scales. However, if we test more families, let’s say a kilometer from the original observation, test large family groups, then is it the same—the more animals here, the more infections we see? If you expand your area some more and ask this question, then we would still find an infection three or four kilometers away from the central family group, and we would make an interesting observation. Especially if you compare situations like this where you have even higher population densities…you could talk of increasing the population density as if this was an experiment. But this is not an experiment, but in the last analysis observational ecology, but so cleanly designed that it’s effectively the same as an artificial experiment. We increase the population density and suddenly we see a threshold effect, where we keep adding and adding and adding [infected rats]—and we would find no infection transmissions. And then suddenly there would be one.

HENNIG: Why?

DROSTEN: Let’s describe this again: we pick a point and we observe other animals around it. We see a regular relationship, where the greater the population density, the more infections there around around the point. If we increase the population density of the entire area of study, then we would find more infections around said point. But if we look at larger areas around such a point, in other words, if we increase our area of interest and test animals further away within this area, then we can keep increasing the population density, and there wouldn’t be any infections at the very edges. At some point, we would increase the density and suddenly, even the edges would be infected, and would stay infected. We increase it even more and there are even more infections—this is a sudden effect, a threshold effect.
Back to the initial example, at first the coffee gets wet, and then it starts to drip through. But this threshold effect exceeded in the coffee filter is also exceeded in nature, in infection ecology, in the great gerbils.

HENNIG: Does this mean that there are transmissions between individuals?

DROSTEN: Yes. What lies underneath is this: these infections are transmitted in clusters. These family groups are local clusters and they only have limited contact with each other. Every so often a flea, or even another gerbil goes over to another group neighboring theirs. But essentially, these animals are clusters, local clusters, which are closed off. And in order for an infection to spring from cluster to cluster to cluster, it takes a bit of effort. But the more animals per cluster, the faster this will occur. If there are more jumps, from cluster to cluster to cluster, then 30 jumps are needed, there must be so and so many infections—there must be so many animals or so many fleas or whatever you like, I am talking rather diffusely about the term “infection mass”, such a mass of infections must be present before we have a breakthrough. Similarly, in the example of the coffee filter, a relatively large amount of water must be present before it can seep through. And when we come to SARS-2, we can very well imagine what we actually have in the population. We know that these infections spread a lot in clusters, this is what is meant by the term “over-dispersion.” We have chains of transmission made up of individuals. But these chains connect the clusters. That is something like a great gerbil moves from one hole to another, from one familial group to another.

HENNIG: But these chains of transmission sometimes break apart, but with clusters, this happens less often because so much is happening at the same time.

DROSTEN: Exactly, such is the case with great gerbils too. There’s always a mouse or a rat running from one infected family to another. But disease transmission doesn’t always occur. Maybe they aren’t carrying any fleas on their fur. And this can be seen as well in viral illnesses, even in those demonstrating over-dispersion. In the population, there are local clusters. One should say temporal local clusters, because, for instance, a birthday party would be a cluster for a period of time where the virus spreads a lot. Maybe the people would meet up more often. Maybe this would be made up of one’s dorm-mates plus their friends. That would be like a social group, a cluster, an occurrence of infections. But these people would naturally, sporadically make contact with other clusters, perhaps another student dorm, that they are normally separated from. Or perhaps in a short gathering, at sports or during free time, or the birthday party of someone’s parents, 600 kilometers away, who they have visited last Sunday and perhaps carried the infection to.

HENNIG: That would be the flea moving from one cave to another.

DROSTEN: A flea that moves during the infectious period of its illness, two or three days before the start of symptoms or four or five days afterwards. Within this short period of time, the infection is transmitted, these incidences may occur. However, in the general population, we have clusters, groups, that are loosely and poorly connected. You can imagine an infection raging in one area, and that we would detect it. But this would subside by itself, because the connectedness of such a cluster isn’t great enough to spread something that suddenly appears. We have a term from ecology and population science for this, namely, metapopulation.
If we call such a cluster a subpopulation, a population viewed through the perspective of the infection, a population of susceptible individuals, then through the connectedness of clusters over all groups, or we could say over the entire country, the whole breadth and geography of the country, a transmission network, a metapopulation, would arise, because these weak connections between clusters would suddenly be strengthened because there are so many infections, and suddenly the current would pass through, to use the example of the wooden and metal balls.

HENNIG: Is that the threshold which you would say we should talk about regarding the second wave?

DROSTEN: Yes. I will not talk about a threshold here, since I cannot speak as accurately about it as other scientists. There are those who can model this, but I am not among them. I am a virologist. I am not a theoretical epidemiologist. Theoretical epidemiologists can model this, but do not have the parameters, the basic knowledge for this. We don’t know how big a cluster is in Germany on average, that is related to the population. It may be different in Germany and in India, it certainly is.

HENNIG: And in Italy.

-----HOW THE THRESHOLD EFFECT WORKS-----

DROSTEN: Mobility in the population, the average travel distance, the size of a household, the magnitude of social situations—all of these are confounding factors or influencers that come into play. I cannot say exactly where the threshold is, but I as a scientist can only say that I am explaining the principle of threshold. There certainly are these threshold effects. We shouldn’t ignore them. The existence of such effects is probably the reason that we can keep on living, that the wave of infections rises and falls, or, to quote Hendrik Streeck, there is a long-lasting wave, where the numbers are sometimes high, sometimes low. It can go out of control at any time, and we don’t know when. We only know that it can.
And I hope, along with everyone in the public, that this doesn’t happen in Germany. But I will say that there is a possibility that we may delude ourselves if we say, “Everything is going well at the moment, we should continue as before.” Without noticing, we may have a situation where people hide their infections and we aren’t looking at the real numbers as often and therefore such clusters arise, clusters that we might not notice at all, and then we would have a sudden percolation effect, in other words, a threshold effect, where suddenly, the conditions change. And we would see all of a sudden an increase in reported cases every day. We wouldn’t know what has happened, but there would be an increase. Something must then happen. I have the feeling that this is what we are seeing in Frankfurt.
In France, this happened. Over there, just as in Germany, many measures were implemented and the mood was positive. And suddenly, there were more cases. An interesting consideration is: why are things so different? A reason that probably suffices is that in France, there were simply more cases during the first wave. The French lockdown was more aggressive than ours, but maybe there were more remaining cases than we had. We cannot evaluate this, nobody can quantify this. But that would be an explanation for what we are now seeing. I don’t think anybody in France did anything wrong. I believe that there were percolation effects and that maybe they were reached in France and not here—so far.

HENNIG: It is somewhat more important to look at recommendations for the autumn. How can we attempt to prevent reaching a threshold, reaching this threshold effect? You have said that testing is not a cure-all, we can’t test the virus away—there was that whole kerfuffle in Bavaria(1)—we must concentrate on clusters. How accurate is this?

DROSTEN: Yes, this is to do with the factor of time, as I have written about.

HENNIG: A guest piece for the weekly edition of Die Zeit, “Strategies for the Autumn”.

DROSTEN: Exactly, that was what it was called. The headline was, “A plan for the autumn.”(2) By the way, my headline was “A recommendation for the autumn”, but that wasn’t used.

HENNIG: We’ll read it as “Recommendation.”

----HOW A CONTACT DIARY CAN HELP----

DROSTEN: I wrote that because I felt that after a month had passed and we didn’t make any any more episodes of this podcast, that something should be mentioned in public, something that would trigger discussion, and that had something new to say. I did not want to give any strong recommendations that were to be implemented immediately. Neither did I want to say that everyone was doing something wrong. Rather, I wanted to summarize a few aspects of our new scientific knowledge, if you would like to think so, from the first half of the year, including our podcast, which would be nice if people were to put a large part, or even all of it into action. As a thought experiment at first, but then also as a personal recommendation of how to behave from a university professor who perhaps thinks theoretically as well as practically.
From these scientific considerations come ideas on how to behave, which must be consciously tested in reality as well. I am very pleased that in the background—this is not visible at the moment—those talking a lot on TV aren’t talking about this because they aren’t involved at all in the background activities which have arisen. But I can say that in many senate chancelleries and ministries, in health offices and authorities, people are thinking about this, about whether they may be able to apply parts of these ideas. And these ideas are based on what I am saying: what we are doing at the moment is in no way wrong. I am not saying that we should pass judgment on the current recommendations. Or that we should concentrate on the problems, or that we are going in the wrong direction. I have read and heard such formulations in public. This isn’t what this is about.
This is about people recognizing what is happening at the moment. In the current situation, it is the right thing to do, to control this background activity, this mass of infections, to trace and cut off these infections, these thin lines between clusters. This is important. Then there is the concern of what would happen if we exceed a percolation limit and if things go somewhat out of control and the health authorities , especially those in the area of the excess, where the incidence rate is rising rapidly, say, one after another, “We can’t do anything more, we can’t trace cases anymore?”
That is something that was very visible during the first wave. That happened with health offices. The question is: what then? Under the current conditions, we let things go on as usual, but in an emergency situation, it is only right to declare a lockdown. Someone must come in and say, “Right, contact prohibitions here, travel bans there”, for instance. We are thinking about the clusters and the thin connecting lines, that are often drawn by cars or trains or whatever within the country. These must be stopped, perhaps regionally, maybe for an entire federal state, or maybe for a whole region.

HENNIG: Because too much time is lost when it comes to tracing, during which further infections can occur?

DROSTEN: Exactly, you simply wouldn’t be able to follow them anymore. And at the same time, from day to day, there would be more cases. And we know exactly that with a month-long delay, we would have more hospital transfers [transfers to other hospitals when a hospital is at full capacity]. At the moment, there are only a few, because we have young patients who aren’t severely ill. But this is a matter of a few weeks, after which the elderly will be infected again. And then the intensive care units would be busy again. These should be prevented before it happens, not when it does. With ICUs, if you play catch up with the situation, you will be beaten every time. That is the wrong way to go. That is what has happened in England, in New York, in Italy. If you wait until the ICUs are full, it will be too late.

HENNIG: We have not reached that point yet.

DROSTEN: Yes, you can’t avoid this. At the moment, we are far removed from this. The consideration is, however, how without a lockdown, without even a regional lockdown, we can take some positive ideas as strategies and say that there is a way out. There is another possibility by which we can go about this, without a lockdown. There is a certain logic to it. What I am talking about is that we know that this illness spreads, to a large extent, in clusters.
There is a model by which to handle this, namely, the Japanese retrospective cluster strategy. A single person, Hitoshi Oshitani, a very perceptive epidemiologist, had a lot of influence and, in a country that in its first wave had a lot of cases coming in from China, was able to control the pandemic before its healthcare system was overwhelmed. This was during the first wave, very early in the year, not in May and June, where the infections were also very high in Japan, when these measures were taken down and everything was generally more relaxed. In Japan, people didn’t concentrate solely on cluster strategies, but also on wide-reaching contact measures, even without a lockdown.
This retrospective cluster strategy entails, for instance, let’s say I have a confirmed diagnosis, I say that this patient sticks out, they have had symptoms for two, three, four days, and then I have the lab results back—what do I do with them? There is the classic problem, to prevent the patient from infecting other people without you noticing. Looking forward, I could have them sit down in front of me say I would say to them, “You are probably infectious. Please keep your distance from others.” From then on, there would theoretically be no further infections. But we can also say, “Think for a moment. You have probably been infectious for four days now. Who have you been in contact with during this time? Please write down the names for me.” I would then contact them as a government doctor, as I would fear that they were also infected. Maybe the first of them are already symptomatic or infectious without knowing it. Symptomatic without knowing it—this perhaps mean a little itching in the throat which they don’t take seriously. And we would say to them, “Okay, go into quarantine for a certain period of time, at the moment, the rule is 14 days. If symptoms appear, get yourself tested immediately, and don’t be in contact with others because we need to prevent this infection from being transmitted further. That is the classic procedure.
In Japan, other things were also strongly implemented, things that were also implemented in Germany according to current guidelines. It is only a question of how much these are implemented and whether all of this can be done in the health offices. First I want to explain what happened in Japan. I would also like to reiterate that in German health offices, this was done when possible, but not given the highest priority. In Japan, further questions were asked: “Where could you have been infected a week ago? Where did you go with this? Can you remember whether you were in a cluster situation?” Then the patient asks, “What is a cluster situation?” And then there would be a list of typical social situations, culturally specific ones. For example, in Japan, the karaoke bars. There are few of them here. Here, we would probably ask, “Did you celebrate Carnival?” Or, “Were you at a large event, perhaps a family event? Did you visit relatives? Did you—as a matter of course, around a week ago, when you could have been infected, around the plausible time period this could have happened—were you perhaps at a course in a school or somewhere like that?

HENNIG: A fitness studio would be an example of such a situation.

DROSTEN: Exactly, where many people are present within a small area. These questions must follow a concrete list, so that it wouldn’t be easy to fantasize or think of abstract possibilities. The doctor can say to the patient, “Okay, we’re thinking of a situation involving more than 20 people, most likely within a closed room, most likely within a period of time 15 minutes or longer. And perhaps you know if any of the people there have any symptoms now.”  Most patients would give up and say, “I don’t know at all. Do you know who you were in contact with a week ago? Okay, yes, maybe, I am in a bowling club. That’s what comes to mind.” Then more information comes. If you present the patients with a list from which they can pick concrete situations, they would then say, “Yes, here on the list, it says “bowling club.” I’m not in a bowling club, but I am part of a bowling association. That’s a similar thing, right?” And this is the idea, to convey a certain amount of information by giving examples of situations and letting patients ask questions. At the same time with the patient, there’s the idea of cooperation of the general population, this is one of the most important points. The offices and the government and whoever is officially responsible, can no longer do this alone. If we want to get through the autumn, even if we exceed the percolation threshold and run into problems again, we will only be able to do so with as much cooperation from the population as possible. Not everyone will help. We will never have a situation where everyone helps out. Some people don’t understand this well enough. Some people are fundamentally opposed to this. Let us forget about them. We don’t have to have everybody cooperating, but a large portion, even if half the population helps out, a lot will have been one. People who say, ‘Yes, I am doing this and am starting a contact diary today,” according to what I wrote in the article in Die Zeit, and not according to what some people have made of it in the public sphere. They would then say, “Drosten has gone off the rails. These diaries will never catch on, nobody will do that.” You cannot really misunderstand what has been said in the article unless you do so intentionally. These are meant as records of clusters.

HENNIG: Thus, with these diaries, we can do what the Corona-Warn-App wants to do?

DROSTEN: Yes, a miniature contact diary, in which I say, “Okay, I must write down who I had contact with.” You can’t do this, everyone knows that. We have the app for that. If you have that, all good. And if not everybody has it, you have to shrug and say, “Well, this is how it is in a democracy, not everybody will do that.” But what everyone can do is to keep a cluster contact diary, which every evening I write in and think to myself, “Was I in a cluster situation?” I do this myself. I write in it every evening and every three or four days, I find that I am in a cluster situation. I don’t count my family. I don’t count my closest work spheres, my closest work groups, which I see every day, because we have special measures here in the institute. We always wear masks and so on. That is almost like a medical work space, because of personal protective equipment and other rules. I am only concerned with day-to-day situations. I am, for instance, a professor at a university. Sometimes I proctor examinations, these have recently begun to take place in person, I would be in a room with 15 or 20 people. People keep their distance, there are so-called Corona Rules, everyone must sit far apart from each other and so on. Regardless, I write this down. That can be a cluster. If I have symptoms within a week and the doctor asks me, “Have you had cluster contacts?”, I could say, “Yes, on my list it says that a week ago, I was at this examination.” Many people who have professionally or socially different contacts will have other such situations. Someone may say for instance, “On my list it says that last Thursday I was at a game with my hockey team. We were not only out on the field, but it started to rain. We went back inside and sat for an hour in the changing rooms and chatted.

HENNIG: Family calendars would be good in combination with this.

DROSTEN: I believe everyone understands what I am talking about. This includes family celebrations and so on as well. The aim is simple, to ask: when did I have a cluster contact? It would be somewhat easier to have a published list of typical cluster situations. This has another effect. One could say, “Just a moment, what I’m doing now is also on the cluster list. Maybe for the next few weeks, since I am a thoughtful member of society and want to do my part, I will not take part in this hockey game, even though it’s technically allowed.

HENNIG: Exactly, even though it’s technically allowed. We say that we are dancing with a tiger here. We are trying to carry on living with the virus and at the same time limit the incidence of infections, which means that even if certain situations are allowed, they will be documented well enough.

----TRYING TO LIVE WITH THE VIRUS----

DROSTEN: Yes, exactly. You prepare this information for the health authorities in order to make it easier to follow source clusters. That is the main question. There are two different clusters which cannot be kept apart without cooperation from the population. The first is the registered cluster, where I ask a newly-infected and diagnosed person, “Wher ehave you had contact with many people during the past few days?” And then I would call those people. Could they have been infected by the patient sitting in front of me? That is a registered cluster. From a strict, academic perspective, these must be differentiated from source clusters. These are those by which this patient might have been infected. That’s the big problem, that within this cluster a group of infections could have occurred over a long period of time, and the patient sitting in front of us would be only an indicator of an unknown source cluster of around 10, 20, 30 or even 50 people, of which over half may be infected without any of them knowing.
That is what I have written about, that we can find new methods of diagnosis, different types and different ways. One of them would be very easy to explain here. Take a source cluster full of unrecognized infections. Before we start to test all of them, to call them, to take them to the doctor or a testing site or wherever and wait for the laboratory to send the results back, the laboratory may be overloaded, and the whole process would take four or five days. During this time, so many new infections could occur while we wait for the tests. When such a source cluster is identified, every single person must isolate themselves at home without further ado. The health authorities already do this if they can. For instance, if another case is identified or if symptoms arise, then health office doctors are able to say, “Okay, everyone who attended this course, who attended that family party must stay at home or in quarantine.” Really, all of this is a quarantine and we would be mixing up the terms. I have done so as well, because there is confusion between isolation and quarantine, in both cases there are diagnosed cases and possible cases—I speak of a “cooldown time” for this cluster. The cluster should be left to “cool down”, during which everyone within it stays at home.

HENNIG: But not 14 days long, as is currently done?

DROSTEN: We are getting to this. The problem that health office doctors have to deal with is the problem of reality, and I know this because I have spoken with many, many, many representatives from health offices from all over Germany over the phone, which phone us because we are a conciliary laboratory(3), and who speak with me directly and are bothered by the regulations and speak to me frankly. They say in such situations, “I know that I must really isolate people. But if I were to do that, then the district authorities call my boss and then they get angry at me. Or maybe some employer calls a politician and the politician gets cross with me. Thus there are always compromises that need to be made. This is why even if the health office doctor may have strong suspicions of the presence of a source cluster, they must allow testing to be carried out first in order to obtain more evidence. Not only two cases [have to be shown], but perhaps three or four. At some point, it’s no longer up to them to provide evidence and then isolation begins. But by then transmission may have occurred.
These source clusters have special properties. They proceed very synchronously and can easily get out of hand. Many people would be infected within a certain period of time, and will become infectious. And I have to catch them now and not in a week’s time, at which point they will no longer be infectious. The infection would have, however, been transmitted to other clusters. And then we would be in completely unknown territory. We would not be able to follow them, we wouldn’t have the power to do so. We wouldn’t have the manpower or the ability to call them. This is why I will make a recommendation based off of new data we have from infection kinetics. Simply put: we know that by the time whoever is diagnosed with PCR receives their results, they are no longer infectious at all. Why is this? Because diagnoses are mainly symptom-based, which by the way I find appropriate for the current situation in Germany. Maybe it’d be different in America, but in Germany, it is so. Realistically, if I were to be tested, the laboratory would need three or four days. Even if labs have a turnover time of 24 hours, it is different in reality. Over here we have probes being transported, over there a fax has gone missing because this number doesn’t lead anywhere and the wrong fax number was given for the transmission of these results. Someone, perhaps a doctor, would go and say, “That can’t be real, we don’t have any sickness here at all. Go home and then you’ll be better.” Such things happen, and you don’t have to blame anyone for this. These things are human and make it so that in reality, three or four days pass most of the time before someone obtains their results, and that coincides with the start of symptoms. But the infective period begins two days before the beginning of symptoms and ends, realistically speaking, four or five days after the beginning of symptoms. This means that the day that results arrive is the last, or second to last day that that person remains infectious. The viral load would by then be very small. Knowing this, it is almost nonsensical to say to that person, “Stay at home for 14 days.” They would then no longer be infectious. It is more important to look backwards. And here we consider an interesting compromise. We know that it is painful for employers, for district authorities, for I don’t know who, for local politicians to keep these source clusters under quarantine. They try to place that responsibility on health office doctors. It would therefore be good for the doctor to be able to reply with something new, a way out, namely, when the doctor can say, “Dear Mr. District Officer, we only need five days now. We don’t need 14 days, we need only five. We are implementing a short quarantine. The weekend is included within these five days. In other words, only three work days will be lost.”

HENNIG: This would mean that the burden on everyone, even the economic burden, would be lessened. But would going from 14 to five days still allow us to prevent new infections as much as possible? Or do we just have to live with the risk?

DROSTEN: In making this suggestion of five days, I am going towards the limits of epidemiology. This is a tenuous theory, to say that after five days the infectivity is gone. But this is a consideration of what can be done in order to avoid a de-facto lockdown. It doesn’t help anyone to put all suspected school classes, all suspected workplaces under weeks-long quarantine. It must be shorts. I have something else to suggest to epidemiologists in order to calm this situation down, namely, free testing. My suggestion is that five days shouldn’t be wasted on testing, but rather, that testing occurs when the five days have passed. In the end, the question is whether this necessarily means that everyone within the source cluster is infected. Or, we want to know whether everyone or only a few people are infected, but we want to know something more regarding diagnostics. We want to know if they are still infectious after these five days. In other words, this difference between testing for infectivity versus testing for the presence of infection—to me, this is important.

HENNIG: But how are we to measure this? It is not yet clear, if I have been correctly informed, how much virus I need to infect another person. How high must the viral load be?

DROSTEN: Yes, courage and pragmatism are needed, as well as good instincts and a good knowledge of clinical virology, to give a number. That is really what should be done. We must also have a number for how small the viral load must be in order not to be infectious anymore. A measurement, perhaps how many virus particles per swab test or per milliliter of fluid. For the insiders listening to us, there was a New York Times article a few days ago that didn’t talk about a viral load of a million copies, but rather a Ct value of 30 was suggested. This is only good at first glance. If you look more closely, you will see that the Ct values vary between different chemical mixes and between PCR machines. A Ct value of 30 in a certain laboratory is not the same as a Ct value of 30 in another.

HENNIG: You must explain the concept of Ct value for those who don’t read the New York Times.

DROSTEN: Okay, for the non-insiders, this refers to a “threshold cycle”, the cycle of amplification at which a signal starts to become visible. It is a measure of how many copies there are at the beginning of the reaction.

HENNIG: The amplification of genetic material?

DROSTEN: Yes, exactly. We have spoken earlier in the year about PCR. We use it to quantify the viral load. It is a reference point for viral load, but it is a little imprecise and for medical laboratories working under quality control, it isn’t enough. I don’t see a problem with labs in the USA saying, ‘Let us define a Ct value.” I don’t find this wrong, I would do the same thing as well. But I understand the point of the quality-oriented medical laboratories that want to do things more specifically. They want to calculate according to standards. We are in the process of doing something like this. We are creating a reference preparation which laboratories can easily obtain and use in their machines. Then you would know with what Ct value this value that I have mentioned, one million copies per smear test can be applied to. In one laboratory this value might be 28, in another 30, and in another 27. We are currently in an interview, so I will not give out recommendations or talk about guidelines. I am only giving a number so that people can imagine these scenarios. Maybe, when we are in internal discussions with experts from different institutions, including the Robert Koch Institute, we will not have a value of one million but something else, because the experts must come to an agreement. I am merely saying this so people can imagine. I’m thinking of one million copies.

-----NEW HELP: ANTIGEN TESTS-----

DROSTEN: (cont.) People from the laboratory can then say that this calibration allows you to say that at a certain viral load, a patient isn’t infectious, or that at this viral load, the patient is probably infectious. You could write about this in addition to other findings. I would not be in favor of having to say, “a patient has a Ct of 28” because nobody would understand that. And this cannot be standardized between laboratories. Rather, I would be in favor of saying, in the Interpretation section of the findings, which is part of the medical report: “The amount of detected viruses does not suggest a high infection risk based on surrogate criteria.” You must use regulations that have legal weight in case there are ambiguities, that signal up to where the responsibility of lab physicians extend, and from where the responsibilities of health office doctors begin. Such results would require communication between laboratory doctors and health office doctors. Thus it is important to consider these regulatory principles before saying on TV: “Now you have to change the whole system.” Many experts have to talk about this among themselves first. But I believe that things are generally moving in the right direction. Within the system, we don’t have anyone stopping anything, but we do have a certain precision, which requires a certain amount of time. Maybe we still have this time. Now for something else. With these one million copies I would like to make a suggestion—at the moment, we have currently been trying to validate antigen tests in the laboratory for weeks. Slowly we have come to find that there is a sensitivity limit that these antigen tests can relatively reliably reach. Think for a moment what this means. Imagine, within the medical system, we would be trained to work with this information about infectivity. We would try. We want to make it a normal thing, to be able to test for a cooldown time and then say, “The infectivity is this high, now you can come out of isolation.” If we bring this into daily practice, then maybe in a few months, this would be a great help. These are the antigen tests.

HENNIG: That they would go faster.

DROSTEN: They could be carried out on site. They’re like pregnancy tests. They have as of now not yet been licensed and made publicly available. There are a few publicly available products, but these are not available in high enough quantities. They would partly be sold out. But maybe in a few months they will be approved. And there would be opportunities for production, for instance in Germany. Experts are already coming together and figuring out how we could produce enough in Germany to avoid the supply of these products from breaking apart. At that point, one could think of having every health office doctor in Germany, and every assistant to the health office doctors, in a position to visit the patients at home with the test strip and say, “We are at day five. Let us do the test, it won’t take so long. Whoever is negative can go back to work tomorrow.” Then, all these problems with diagnostics, with the long duration of time required, and the possibility of overloading laboratories, and all of this, as well as the high costs—all of this would be solved in one stroke. My suggestion of million copies is based on my experiences, as I am myself working in a laboratory in order to validate these tests, and I have long had the feeling that these tests from different producers can end up in this situation with their sensitivity limits. If we do this, we would be in the position to take the next step and say, “Now we are switching to antigen tests, and we can say that their sensitivities are equivalent.” In other words, we could say, “If the test is positive, the patient is infectious. If it is negative, we will declare them non-infectious.” Not infectious, mind you, but not uninfected. Because of lower sensitivity, you have to test for the presence of infection with PCR. Antigen tests are not enough, they are not sensitive enough. Nevertheless, people would still slip through the cracks without you noticing because they may have small viral loads when they are taking the tests. But what matters most to the health office doctor would be to take the person out of isolation and be able to say to them, “Great, even though you may have had symptoms and may have been positive, the test is telling me that right now you aren’t infectious anymore and can go back to work.”

HENNIG: This means that contacts in such a cluster must, in the end, be PCR tested. If you say that contacts should go into isolation for five days and then get tested for free, can it be that there would be too much uncertainty, because you would be using antigen tests that aren’t sensitive enough?

DROSTEN: Yes, of course. It is also the case that in the early phases, these antigen tests wouldn’t detect an infection for a day or so, while PCR would. Nevertheless, this should be said, this suggestion that I am making here is an emergency measure which can’t be perfect. Here, we’re thinking of getting through a particularly difficult time, where not everything is possible, and not everyone can get PCR tested. Then there are further problems over the horizon regarding diagnostics in the autumn, about which we must speak. Now, we have to figure these things out. Then, if I write something like this, I must also anticipate certain eventualities and points of criticism and write accordingly. These are thoughts about the future that, of course, everyone hopes will not be implemented into our general strategy because we wouldn’t have a second wave. It would be good if that were so. [We hope that] we won’t have to implement them in an emergency, where we say, “We are standing with our backs to the wall. We recognize as well that we can’t do PCR tests on every single contact person, this simply isn’t possible. We must blindly isolate. At the end of the period of isolation or period of quarantine, we must test. We simply can’t test most of the others because it’s not possible. And maybe this would help us to keep the incidence rate under control and to proceed without a lockdown.” That is what this is all about. I imagine a situation, of which I have written about, a thought experiment, where we stand with our backs to the wall and are only able to implement a regional or even national lockdown. And this would be, I believe, rather difficult to say. We must not argue about this here. This is where it all comes from.
And I would like to say that what happened with rapid testing has happened here, people have jumped the gun, and interviews are to be seen on TV with people who aren’t completely up to date regarding these topics and may have just picked up on them in passing, from discussions among their colleagues or whatever, but don’t even do diagnostics themselves, and then say, “Antigen tests now: what is actually happening now in Germany? They exist already, we must license them at once. And PCR, this is all rubbish. They are all probably not infectious at all.” Sadly, it isn’t this easy. In reality, it takes a long, long time to implement these, because there are laws. And then there is the issue of justice. These days, we hear accusations from all sides that PCR is all just hocus pocus and that the virus doesn’t exist at all. That it’s just RNA fragments. In reality, Drosten has just thought all of this up to earn money. And there is no pandemic, in any case, not in Germany. People hear these things and can only say in reply: these diagnostics labs in Germany all work in accordance with in vitro diagnostic guidelines with certified tests. They work under comprehensive quality control systems that speculation about whatever conspiracy theories there are completely ignore. All of this is tested within the system. There is no such uncertainty like this. There is no instance of this error, that some cold virus causes a false positive in this test. Or that such a thing would be blindly reported. And that these cases would be reported in the statistics. There are no such things. These are fantasies because we work according to the law in medical laboratories with tests that abide by the laws. There are laws for antigen tests too. And we must adhere to theme. We cannot dismantle them. We can only strive to move forwards with our combined strength to keep in line with the law. The first thing that must be done is to get a CE certificate, a European certificate by testing the process of production and the analytical quality of the test, so that they can be used as an in vitro diagnostic. We must reach this point. We can consider whether we can take some shortcuts by saying, “We will only allow this test to be administered by a medical office doctor under mild quality clauses, only by a medical office doctor.” This is being juridically and regulatively tested in the background, but not in the “Heute Journal” and not by Maybrit Illner. But in the background, by people who are truly involved with the methods and the material.

-----A TIMEFRAME FOR VACCINE DEVELOPMENT-----

HENNIG: What do you believe would be a good timeframe for all the corresponding things to have been validated and for it to be determined, which limits are to be applied?

DROSTEN: A safe estimate would be December, if everything goes well. To achieve this, our forces must be combined. I can tell you that this very much depends on politics. And this includes everything up to the laboratories which develop these. At the moment, there really are good people involved with this. But this does not belong in the public sphere, because these are processes where legal matters have to be coordinated. We can see now with all this misinformation in the public, how damaging and divisive it can be for these things to be carelessly discussed in public. We can see how established laboratory processes and established medical practice is being dismissed out of destructiveness and self-aggrandizement.

HENNIG: This means that legal safety precautions are greatly beneficial. We make sure to adhere to them during vaccine development as well.

DROSTEN: Yes, exactly the same thing with vaccines.

HENNIG: Important for the medical office doctors and for everyone concerned.

DROSTEN: I would like to say that if a professor with a lot of professional experience and thought towards the future writes something in “Die Zeit”, then this would always be considered an academic suggestion. And if the doctors from the Robert Koch Institute say, “Dear Dr. Drosten” or “Dear Christian” (I am also this informal with my colleagues), “you have missed something”, then I would say, “Oh yes, yes. I have missed that, I would never say to you to go ahead and do whatever anyway. But I am right.” And then I give an interview on TV and insist that I am right—that is simply misconduct. One should not do this, especially not as a scientist. There is always reality, and I would never expect that a suggestion that I write somewhere in “Die Zeit” be 100% implemented. Maybe nothing would be implemented at all because all I have done is speculate. But I should say that I have taken a look at things and think that a few things should be done. Especially since internationally, the exact same ideas that we have anticipated and spoken about months ago are emerging.

HENNIG: Let us take note: there are things we need to discuss. There exist strategic suggestions for an emergency program in the autumn and ideas about how we can live with the risk of the virus and try to limit the incidence of infections and to prevent its spread. Dr. Drosten, to conclude, even though personal recommendations are difficult and everyone must know for themselves which risks they can and want to definitely make do without, you have said at the beginning of the podcast that you have visited your grandparents with the family. What would you say to those who ask how they can go about this as well? Should we continue, just as early on in the year, to keep a distance, both outside and in closed rooms, from people at risk, people with pre-existing conditions and the elderly?

-----KEEP FAR AWAY FROM GRANDPARENTS?-----

DROSTEN: At the moment, we have a low incidence rate, but this is difficult to assess. We must admit to ourselves that we do not know exactly where the virus is. It may be that the factors reported by, or reported to, the Robert Koch Institute have been underestimated by a factor of two. It may be by a factor of 20. I never said this early on in the year, a factor of 20. At the moment this may be so because of the many social effects—think back to “Party People”, who at 20 years old wouldn’t really mind their symptoms, and at the same time know that they really shouldn’t be at these raves. And the many travelers, who might not be be very culturally open at all and may actually stay away from doctors. There are all these phenomena at the moment—because we don’t know at all where the virus is. We know however which situations we can avoid in order to prevent viral transmission on our end. And here we have, to a degree, the difference between, “I think only of myself,” and, “How do I stay safe while visiting Grandma and Grandpa?” And then I would think about other people and how I would behave probably. These things  would then follow.
If I for instance wanted to visit Grandma with the kids, then it would be good to consider, “This week,” (I am speaking of the period of time coming up), “This week, we have autumn vacation, this is the first week of the autumn vacation. The kids don’t have to go to school and the baby doesn’t have to go to the daycare. Maybe we could spend a week in a “preparatory quarantine”, and make sure the kids spend almost all their time at home and meet up with only a few people and just spent a little time with the family.” This may not last an entire week. That may only be a week, or maybe a short working week plus the weekend—these considerations. Or maybe you could do that in the middle of two weekends, a more familiar preparatory quarantine, a preparatory isolation. And then you would go on to visit relatives knowing that most likely, nobody within the family was infected within the week, or if at all, they were infected before the isolation week—which is relatively unlikely if within the entire family, nobody showed a single symptom. That would be very unlikely.

HENNIG: Even if the incubation time may be longer?

DROSTEN: The incubation time can be longer, and then it would be a game of chance. This is perfectly clear. But we want here to speak about how we can limit the risk with good judgement and by being sensible. We would do so if we would say, for instance, “As a family, let us spend a week in quarantine. If nobody shows even the slightest symptoms in a week, then it’s as good as certain that nobody here is infected. And then we can go off. Within this closed off family group we will visit Grandma and Gandpa for a few days and will stay in this closed off group. This is how you might proceed if you had no access to diagnostics. And then you also have to say that right now, we have a low incidence rate. Most likely, there isn’t a high risk [of infection]. There are still regional differences. Someone who for instance lives in Mecklenburg-Vorpommern would not have the same risk of infection as someone who lives in Bavaria, or in Baden-Württemberg or North-Rhine-Westphalia, right now this is the case. We should recognize this. What I want to say is that people should be informed about the current situation of the epidemic where they are. People have to talk with their grandparents, if they are living with them, and tell them that things are still dangerous. It would be absurd to do a preparatory quarantine before visiting them if they carry on a pretty social life before visiting them because nobody else is interested in the elderly, least of all in social contexts. That is sadly something that I have been seeing more and more, especially in the elderly, who are retired and have a lot of time. They watch Youtube videos which they can access on their iPads, in which these truly destructive and divisive theories, which end up costing lives. I think a bit of control or some questions would be good for the elderly, such as: “What do you see at the moment, do you feel that you are in danger? How are you behaving?” That is perhaps more important than the constant fear that I am holding everyone back.

HENNIG: Dr. Drosten, many thanks for everything up to and including today. We will remain in contact. It will be 14 days before we speak again. Next week this podcast will still be going on, but the next time we will speak with each other will be on the 15th of September, two weeks from now on Tuesday. Many thanks, Dr. Drosten, till next time.

DROSTEN: Till next time.

HENNIG: Of course, you (our listeners) will not be without an update until then. Next week I will speak to our new addition to the podcast, Professor Sandra Ciesek, leader of the University Clinic in Frankfurt-am-Main who as many of you have heard, will be alternating with Dr. Drosten. Of course, we will remain scientific—Professor Sandra Ciesek is researching the coronavirus with her team, but she has had many years of experience as an internal medicine specialist, and therefore has a very special perspective on the needs of patients. If you have any questions, then please send them to our email address, [email protected]. I would also like to say something worthwhile before I leave. We have spent almost half a year on the Coronavirus Update, but never thought that this podcast would be so successful, with more than 60 million downloads. But what is really pleasing about the Coronavirus Update is that many have discovered the medium of podcasts, which is why I would like to say that in the AED Audiotheque there are yet more podcasts, for instance our other scientific podcast Synapsen (Synapses), in which we speak about many different topics. Currently the topic is racism, and how much it plays a role in research. Or the new NDR literary podcast Eat, Read, Sleep, in which you can get tips about books as well as literary history, and you can find out what is really up with the “Eat” [in the title], what the point of it is. These can be found in the AED Audiotheque, where, naturally, our Coronavirus Update is as well. More information can be found at ndr.de/coronaupdate, with Dr. Drosten and Sandra Ciesek alternating every week. I am Korinna Hennig, thank you so much for listening to this first XXL, extra long episode after the summer break. Till next Tuesday.


-----NOTES-----
1.) More than 40,000 tests carried out on Bavarians returning from vacation took more than the usual 7 days to arrive.
2.) “Ein Plan für den Herbst“ , available at https://www.zeit.de/2020/33/corona-zweite-welle-eindaemmung-massnahmen-christian-drosten
3.) A type of laboratory within the German health system that deals with a wider range of potential pathogens than usual.