Sunday, 29 March 2020

Corona Virus Update: Case-tracking teams, slowdown in Germany, infectiousness (part 20)

The Corona Virus Update, part 20, of Tuesday the 26th of March was about whether the South Korean strategy of case-tracking teams is something for Germany as well, what the data on the number of confirmed infections tells us about the spread of the virus in Germany and about a new study on the infectiousness of the virus and what that tells us about how to contain it.

This podcast is produced by the German public radio broadcaster NDR. Science journalist Anja Martini interviews Professor Christian Drosten, just like every day. He is the head of the Virology Department at the Berlin Charité, which is one of the main research hospitals in Germany. As a scientist he can speak more freely than, for example, the director of the RKI, the German CDC. He specializes in emerging viruses and developed the WHO test for the new Corona virus.

Case-tracking teams in South Korea

Can we learn anything from how South Korea handled the situation? Too long, didn't read: South Korea is very strong in case tracking. They test a lot and have many people working to track contacts of known infected people. This produced good results for fighting one big outbreak, but there are still new infections and we will have to see how well this strategy works in future.

Christian Drosten:
There are case-tracking teams that can follow every infected person and look: Who has there been contact with? Where are the contacts now? The contacts are isolated and monitored and so on. I think that is simply not feasible here, if only for personnel reasons. That's why the question of whether you can learn anything from it is a bit futile.

But it's also true that one shouldn't be fooled. For a very long time, there was the impression in Korea that the outbreak is now actually under control. But what's often forgotten to say is that a big part of the initial outbreak in Korea was a single event. ... And of course you could follow that very well. Of course, you have a list of participants and can say: Okay, they were all there, and we're really going after them now.

But this effect is now over in Korea. This transmission event is now so far in the past that it has been captured. And that has done a lot to bring down the curve in Korea right now. But what I am now hearing from Korea is that individual transmission chains are now starting up all over the country, because of course there have been other cases registered in parallel via multiple channels (let's consider the proximity to China). And that just now in Korea the new infections are clearly increasing, because it's not this very focused measure any more, but suddenly you have to be everywhere. And I could do that I imagine that this will also no longer manageable in Korea, to be everywhere at the same time. But in general, they do case tracking very carefully. And I have a feeling can do this better simply by staffing levels than we in Germany.

Spread in Italy and Germany

Anja Martini:
Italy is now going into the third week of quarantine. The first experts are now breathing a sigh of relief because the number of deaths has not increased any further. How much can we already tell from these figures and this development? How much can one learn from this, and what can we trust?
Christian Drosten:
So the number of cases [infections], which in Italy are apparently not so easy to count because probably not so much diagnosis is made, are the absolute numbers of infections. But of course what has to be counted are the deceased. And it takes on average about three weeks between the onset of symptoms and their passing away. Or between the infection, you have to say correctly, and death. And that's why that's the effect that happens in the statistics. A curfew and other quarantine and isolation measures were put in place three weeks ago. And now you can see the effect, even on the deceased. And that is unfortunately almost a natural constant that can be observed. It just takes three weeks.

And you see it more quickly with [infection] cases in countries that can detect the cases very reliably. ... But in this short period of maybe ten days at the most, we want to see that the increase in new infections is already decreasing, at least in a system, a country where we are already close to reality with diagnostics - which we hope we are in Germany. ... I would be very pleased if this were to be confirmed in the next few days. But one must also say that we will have to wait a little longer. It has to last a few days, this effect, before you can see: So you can see something.
The next paragraph required quite some explanations to interpret the science-speak of Drosten. I hope I did it right. He seems to be saying that already in this early phase the number of cases is decreasing compared to model computations based on the past. That means that the spread of the virus has become less efficient, likely due to all the policy measures taken. Even more summarized: the policies seem to work.
"[The number of infections are] perhaps already now in this early phase, the expected values [from models] are changing compared to the observed values. So there seems to be a difference, which is good. [Because this suggests the model parameters about how the virus spreads are improving] And if it stays like that for the next few days, then you will look at it for a while. And then, for example, in this difference you have a new basis for readjusting models. [Estimating how the policies have affected the spread of the virus] And then mathematicians and modelers in Germany will actually be called upon to take and evaluate this data and then to prepare it for policymakers, for example."
This will also affect the number of deaths, but the coming weeks it will still rise.
We will of course see changes in the deceased with a two or three week delay. Incidentally, we also have to remind ourselves, and I would perhaps like to say this again now, that despite the measures that we already have at the moment, the number of deaths will of course continue to rise, because this effect will continue. And this, too, will be reflected in model calculations. That will of course also be important, because it will give an insight into the seriousness of the cases. And this severity of cases must be taken into account in terms of hospital capacity.

So this kind of epidemiological modelling that is needed here at the moment is not just a pure description of the situation of the cases, but must also take into account when we reach the capacity limit of the medical system. So completely different figures have to be included, such as the number of beds or the number of ventilation places.

And in the very near future, the question will be posed to the scientific community: Where do we stand now? How can we now readjust? Must we leave the current measures as they are? Or can we relax the brakes a little in some places, because it is not just a pure, naked scientific consideration, but also because scientists are well aware that the current measures are of course causing great social and economic damage. And these things have to be weighed against each other.
Around Eastern we should have a better assessment of the situation.

Infectiousness study

Anja Martini asks Drosten about a new study from Hong Kong. He first explains how scientific publishing has changed due to the time pressures of the epidemic. If you are not interested in that you can skip the next long quote.

(The quote provides anecdotal evidence that without peer review scientists would focus much more on studies from well-known groups and that peer review thus helps outsiders gain the credibility they need to have people invest time in their work. I have a blog post on that.)

Christian Drosten:
This is a study that has been published on a preprint server. At the moment we have this very fast situation in scientific publication activity. Normally the review process of a scientific contribution takes weeks or even months. So sometimes it goes from a scientist to a journal. They don't send it to the journal for review. Then you send it to another journal and they send it out. The reviewers need two months, then the comments come back. And then the magazine says: "Fix it, please. And then another month goes by.

And you can't afford that right now with epidemiological research. And that's why at the moment, scientific articles are actually placed in online resources, the so-called preprint servers, as they are written. There are two very big ones, called bio-archives and med-archives.

I always go through them like this. I have to sort a lot of things, because they are not peer-reviewed scientific articles. That means there's also a lot of dead wood. There are a lot of things that you won't see officially appear in this form later on, because they won't survive the review process. That means, what I always do in my free minutes is that I look at the things that appear in a new way. And things that I think are of such a high quality, that will survive any review process, that's really well done, I discuss these things here sometimes. So then I say: this is interesting data. And so it is with this study here.

It comes from Hong Kong from a very well-known epidemiological modeling group, Gabriel Leung.
It is important when a patient is infectious.
[The study was about] when does this disease actually become infectious? Already before the symptoms or with the symptoms or after the symptoms? And this is very important, because with the old SARS corona virus we can briefly sum up: It was so easy to contain because it only becomes truly infectious long after the symptoms start, in the average patient.
Drosten himself also had a small study on this topic. Currently still a preprint (not peer reviewed).
This study has also already shown that the virus replicates in the throat in the early phase of infection and that the virus is clearly detectable in swabs even in the very earliest swabs to such an extent that it is already on the descending branch even on day one and two in swabs. So the further one waits - and if one takes smears from a patient every day - the fewer and fewer, right from the beginning.
The new study found the same result, but with many more patients.
These authors found exactly the same thing in a group of 94 cases in Guangdong, i.e. in southern China near Hong Kong. ... And they saw that from day one the virus was on the decline. That means the peak of the virus must be before the first day.
The new study also quantified how long it takes to be infected.
Then they did something very interesting, something purely epidemiological: they also looked at transmission cases in the same context, namely 77 couples, 77 patients, where it is known that one person infected the other, and they looked closely: How long did it actually take?
I did not understand the explanation of how this works, but the key word is "[[Serial Interval]]". The result was:
The median is 5.2 days, the mean is 5.8, so this is a somewhat skewed distribution, but still with very close averages, so 5.2 to 5.8, you can say is the series inteval.
So the time to infect someone is about the same as the incubation time.
They also calculated the incubation time from their own earlier, very well done study: 5.2 days mean incubation time. This is of course interesting, because we have here a phenomenon where practically the serial interval is almost as long as the incubation time. This tells us that the average patient waits for the symptoms after infection for as long as it takes to transmit the infection between two patients. And if you look at it that way, it means that not only do we have a mean onset of transmission on the day the symptoms start, but probably before that as well. So the average patient is basically transferred [infected] on the day the symptoms start, but this is just the average patient. Some patients are not transferred until after the start of their symptoms and unfortunately some are transferred before the start of their symptoms. ...

it can be said that infectivity starts two and a half days before the onset of symptoms, on average. And the so-called area under the curve, i.e. the area covered by this probability curve, before the onset of symptoms, is 44 percent. In other words, it can be assumed that 44 percent of all infectious events occurred before the infective person was even ill. ...

This also means, of course, that if you lock yourself up at home as soon as the symptoms begin, you have already infected people if you allow a normal social life to continue. So this means that with normal rules of infection protection in case of a noticed illness you cannot contain this disease. There has to be social distancing in a targeted way, where the aim is to change behaviour - and not to identify symptoms and isolate the sufferers. That simply will not work with this disease.

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 26: Corona Virus Update on Vaccines: clinical trials, various types, for whom and when.

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 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.

Related reading

Corona Virus Update with Christian Drosten podcasts and transcripts (one day later).

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