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Igor Rudan: How Epidemiologists Used Numbers to Protect Croats from COVID-19

By 22 March 2020

As Igor Rudan/Vecernji list writes on the 20th of March, 2020, Croatia was the country with the lowest percentage of newly COVID-19 infected persons in Europe during the two weeks from March the 2nd to the 17th, 2020, which means that our "first line of defense" did an excellent job and lasted the longest. Then we went into quarantine at the right time, at a much earlier stage of the spread of the epidemic than everyone else did.

Now that we have all become "Quarantine Croatia", yesterday, I joined forces with our famous mathematician Toni Milun to explain together just how we came to be in this situation at all.

In mid-January 2020, a number of friends from Croatia suggested that I start a new popular science series on Facebook in order to follow the COVID-19 epidemic in Wuhan. I called my Chinese colleagues at the time, asking them to briefly describe what was happening to them. They conveyed a few simple but very helpful messages to me. What surprised me the most was the thought of putting 56 million people in quarantine for an extended period. That, then, on January the 17th - so, just two months ago - sounded like a completely radical idea. But when I found out more, and then one week later - on January the 23rd and 24th - I saw that they'd indeed closed off Wuhan and fifteen other cities, I realised that it was an almost surreal event, one that was certainly worth watching. Thus, on January the 29th, the ''Quarantine Wuhan'' series of texts began.

My Chinese colleagues told me that more and more people with some sort of unusual pneumonia began to show up at Wuhan's huge hospitals on a daily basis. That would usually drag on on for about ten days without responding to any sort of antibiotic therapy.

Some people soon required additional oxygen or mechanical support to help them to breathe. If the doctors themselves became infected, the fear would grab them. How could it not? It was an unknown cause of pneumonia, and about one in ten patients would die even with hospital treatment. But what would surprise them was that the infected doctors had generally mild symptoms. They didn't understand how it was possible that these infected patients were in such a poor condition but the infected doctors seemed much better if the cause of their respiratory infection was the same.

The answer to that enigma, however, was hiding outside the hospitals, in the very streets of Wuhan with its eleven million residents. To epidemiologists, such a rift of symptoms was a clear signal that an epidemic had to have been spreading rapidly among the population of that city for some time. It can cause different symptoms in different people. In the vast majority of those infected, the symptoms will be mild or moderate, so they will never report to the hospital. Symptoms would be worse in about fifteen percent of people, and they'd require extra oxygen. Only the remaining five percent of those infected would end up in critical condition, in need of respiration and intensive care. They also noted that when doctors transmit the virus to other patients in the hospital, it also kills about one in ten people infected. Mostly those who already have other serious illnesses. Men, smokers and older people were the most high risk groups.

The doctors in the hospitals saw only that extreme part of the spectrum of the sick - serious and critical cases. Other infected residents, those with mild and moderate symptoms, walked around Wuhan normally. There, they spread the epidemic at a rapid speed. Epidemiologists in Wuhan realised that the new illness would therefore not kill every tenth person it infects, but maybe every 100th person, maybe even every thousandth.

The number of deaths in the hospitals could be used as a numerator, but all infected residents of Wuhan outside the hospital should have been placed in the denominator, ie, the numerous people with milder symptoms spreading it around. At the beginning of the epidemic in this city of eleven million people, no one knew if there were just a thousand, ten thousand, a hundred thousand or maybe a million [infected people]. So quarantine had to be declared. Most importantly, then, it was urgent to stop the exponential spread and then slowly explore what was going on.

It then became clear to them that COVID-19 was not an illness that primarily kills owing to the sheer severity of its symptoms. This was an illness that kills with an incredibly high rate of spread among the community. This spread leads to a tremendously rapid increase in the total number of infected people, and thus five percent of critically ill people, day by day. The critically ill people then cannot receive adequate care. That is why, for every deceased person who couldn't be saved, there are several others who probably could be, but they all came in for treatment at the same time.

This overloaded the hospital's intensive care facilities. My colleagues in China have told me that, after all the bad news from Wuhan, it will probably surprise us how relatively mild it is for most infected people, whether tourists or seafarers bring it to our area of the world. They told me that the illness itself should not feared, but its rapid spread should be. Therefore, three things are crucial to its control:

(1) The spread from China to other countries should simply be stopped by the "first line of defense" - the constant isolation of the infected people and their contacts. This approach had previously proved successful and stopped two previous coronaviruses, SARS and MERS, although both of them had managed to spread to more than twenty countries from China and Saudi Arabia. It was therefore likely that this would work for COVID-19.

(2) We must be extremely careful if a virus manages to break through the "first line of defense" by mere chance. That is when all those infected people with milder symptoms will start spreading it to the population very quickly, aided by the "super spreaders" that infect many individuals. Then the rate of increase in the number of cases can make anyone unpleasantly surprised and entirely unprepared.

The reason is that the infections we're confirming today reflect the spread of the infection days earlier, and not the current situation. Between the infection and the diagnosis of the symptoms, there is a period of "incubation", which lasts about a week. Therefore, if we diagnose 100 infected people on Saturday, we gain information about the spread of the infection since last Saturday. But during those seven days, the virus has spread rapidly, so today it has, in fact, infected more than 1,000 new people. But they will only become visible to us next Saturday. This is the problem of "silent", invisible, exponential growth, which isn't intuitive to the human brain.

In short, the actual current state of spread of the COVID-19 infection is always significantly worse for us, as the current number of confirmed cases indicates - about ten times worse. Therefore, if the virus breaks through the first line of defense, the key decision will be to declare quarantine as soon as possible so that the virus doesn't manage to escape and grow exponentially. And the effects of quarantine will not be visible for the next day, but only in a week's time. Until then, terrible losses will be suffered if a state of quarantine is declared too late, as is happening these days in Italy.

(3) Of course, we must take great care to prevent the virus from entering our hospitals or nursing homes, as it can create a huge amount of death there among patients who are already impaired. These three points are the standard epidemiological measures of protection, so it was quite clear what to do when COVID-19 knocked at our door. I began to closely monitor the results of the quarantine effect in Wuhan, but also a comparative increase in the number of cases in Europe, and Toni Milun showed how that works in a video.

The most important day of this COVID-19 pandemic, at least so far, was probably February the 8th, 2020. Thanks to several consecutive days of declining infections in Wuhan, it became clear that the epidemic in China was beginning to wane and would virtually be extinguished over the coming weeks. It was great news for all of us. That meant that the COVID-19 epidemic could be suppressed even if the virus broke through the first line of defense.

From that February the 8th until February the 21st, things were constantly getting better globally. The number of newly infected individuals in China had been steadily declining. China's surrounding countries, already taught by experience with SARS - Singapore, Hong Kong and Japan - "caught" the virus from China in their first line(s) of defense. They controlled it with a stricter regime along borders, with frequent testing and the isolation of the infected and their contacts. They didn't even need a quarantine, the first line of defense measures produced results.

Furthermore, with the exception of three cases in Australia and one case in Argentina, there were no recorded deaths from COVID-19 in the entire Southern Hemisphere. It gave us all a huge amount of hope that COVID-19 would actually prove to be a seasonal virus and disappear from the Northern Hemisphere with the arrival of late spring and summer. And in Europe and the US, very rare cases were easily ''captured'' by the front lines of defense.

Since February the 21st, however, South Korea and Iran unexpectedly came into focus. The first country had a really awkward incident, which I'll describe in one of the following sequels as an example of another successful way to fight this virus. They were able to extend their first line of defense without quarantine. On the other hand, very little was clear about Iran. I was worried that this country could eventually become the biggest problem with COVID-19 because it was the first less developed country in which the virus began to spread freely. On the positive side, however, Iranian epidemiologists are very adept at combating infectious diseases.

I also noticed that Italy jumped from 3 to 20 cases on February the 21st. I thought, maybe it's some group travelling together. But on a day-to-day basis, on February the 24th, Italy already had a total of 229 infected people, while other European Union (EU) countries had only a few cases and controlled that with their first line(s) of defense.

When I landed in Zagreb four days later, on February the 25th, Croatia discovered its first infected citizen after they were tested. Italy, just across the ''way'' from us, already had 322 infected people by then. The virus had already penetrated their first line of defense by then, so I expected that they would declare a quarantine for at least Lombardy the next morning.

If they'd already registered 322 infected people, it meant that the population was already significantly more infected than that. However, the situation in all other EU countries was still calm. The first lines of defense in the EU were expected to successfully control the entry of the virus. One country can always be isolated from another if that is needed, and Italy is pretty well isolated anyway. I was hoping, in fact, that my colleagues in Italy would have additional reports from China, so they probably calculated their hospital capacity and knew what they were doing. I assumed that they wanted to preserve Italian tourism and the economy for as long as possible and prepare people for quarantine, which they'd obviously have to declare as the first in Europe.

In Zagreb, therefore, I was really amazed by the panic that gripped people when they heard that our first case had been recorded here. I knew that our first line of defense could easily deal with sporadic infections, and globally the situation was getting better day by day. For epidemiologists, the most important of all indicators was the transition of the exponential growth of all newly infected people, from the onset of the epidemic in Wuhan, in a linear way, which was greatly slowed down. It was exponential until about February the 17th, and linear from February the 17th to March the 1st. After this "linear" period, the epidemic is expected to enter into a final stage, ie - a curve alignment and then a decrease in the number of new cases. Tony explains that nicely in a video, too.

All of the available data at the time fueled the real hope that the virus was indeed seasonal, and that the first lines of defense of all developed countries would successfully stop it. We knew then that just about all Chinese provinces had already stopped it, from which it had expanded from the Hubei province, to some thirty of them. Japan, Singapore, and Hong Kong had also succeeded. So why wouldn't it be stopped by the EU and the US?

Owing to all that, panic in Zagreb didn't really seem appropriate to me. As my return coincided with the first recorded case, the cameras of many televisions ''stumbled'' upon me unexpectedly during a guest appearance at Edward Bernays, where I gave a lecture upon invitation. At that time, I tried to appease all of the journalists, as well as the general public, knowing that all epidemiological measures were functioning globally, that the virus was already under control in China and held back by the front lines of defense elsewhere.

When asked what kind of ailment was approaching us, I compared it to "more severe flu, but for which we don't have a vaccine." As an epidemiologist, I knew that severe flu alone was equal to about 650,000 deaths a year, and without a vaccine, well over a million.

It didn't seem to me that COVID-19 could ever reach those figures, given that it had been effectively halted in China at less than 5,000 deaths, and elsewhere the situation was quite calm. But what I wasn't aware of was how little of a danger people in Croatia associate the flu with today. Unfortunately, this misunderstanding still follows me around in many conversations with people today. Then, on March the 1st, I explained on Sunday at 2 that you really shouldn't panic in Croatia, because unless the virus mutates, it can hardly endanger more than 0.5 percent to 1 percent of all infected people.

That it will not endanger the younger age groups, but mostly those over fifty years of age. And it can't even infect us all, because infecting the entire population must also be self-limiting at some point when collective immunity is acquired. With all these predictions, nothing has changed to this day. After that show, however, completely incredible things began to happen, like from something out of a nightmare designed for an epidemiologist.

First, on March the 3rd, WHO Director Tedros Adhanom announced that the COVID-19 death rate so far had been 3.4 percent. This was not inaccurate in any way, as he listed it as the death rate among all positively tested people but not all of those who were infected. Therefore, it wasn't useful information to the public. Specifically, the figure is a combination of the death rate of hospital infections among the elderly and sick from Wuhan and Italy, which was as high as 5 to 10 percent, and the death rate when the virus has spread in the community, which is typically about 0.5 to 1 percent. Therefore, it isn't actually representative of either situation.

But how do you explain to anyone now that the director of the World Health Organisation in Geneva doesn't understand how confusing it is for the concerned public to quote such a figure, perhaps five times the one that is really more applicable? To make matters worse, he was first opposed by US President Donald Trump. He called that number "wrong," and he was largely correct in doing so. Suddenly, it put me in a situation where I had to explain to many that I wasn't underestimating the danger of COVID-19 when I said that the death rate, applicable to the whole population, could be 0.5-1 percent. And next to me, opposite to the director of the World Health Organisation in Geneva, was Donald Trump alone. No wonder the people who trusted me the most were already quite mad at that point. Fortunately, many other experts came forward over the next few days, confirming the estimates of 0.5-1 percent.

Thus, the days of March the 5th to the 7th were spent trying to explain the applicable rate of death, in three consecutive posts. All of this at least served as a great article in Index.hr with answers to 20 questions about COVID-19, which, I hope, helped many to understand more about the threat we're facing and reduce the noise. However, in these discussions, of course, I kept looking into the numbers of newly infected people around the world through the corner of my eye.

Suddenly, not only was the situation in Italy no longer clear to me, but the situation in the whole of Europe became a blur. What is everyone waiting for, why don't they declare quarantine? On Saturday evening, March the 7th, Austria already had 79 cases, Sweden 161 cases, Belgium 169 cases, Switzerland 268 cases, Spain 500 cases, Germany 799 cases, France 949 cases... and Italy had 5883 confirmed infected people?!

I looked at all these figures and I was deeply concerned - but I just couldn't believe the Italian situation. It has been revealed that they already had at least 60,000 people spreading the infection around, and that number was to grow exponentially for at least another ten days, even if they were to have declared quarantine the very next day. In any case, it was then quite clear that everyone in Europe would have to be quarantined, regardless of the fact that we in Croatia were still holding up with our first line of defense.

The next day, on March the 8th, Lombardy was quarantined, but the news leaked to the media too soon. Numerous students fled to the south of the country, spreading the contagion. The whole of Italy was then quarantined. On the same day, March the 8th, I explain in my post "The Justification of the Huge Quarantines" and the problem of exponential growth in numbers infected as a key problem of the COVID-19 pandemic.

It was already quite clear by then that we'd be quarantined in Croatia in a few days. I started counting when it would be best to declare a quarantine in Croatia. I estimated that the first major jump from 10 to 20 infected people would be a good time. The number of infected people who were suffering more could then, with a little luck, see it stop at figures where our health system would have a good chance of helping everyone, with a truly minimal number of serious cases of infection.

That jump, from 14 to 19 infected people, happened on March the 11th. At 3:00 on March the 12th, I immediately posted a status entitled "Contrast is the mother of clarity", explaining that we now have the option to either quarantine very strictly for the next 30 hours and then cure the severely ill as they emerge or let the virus spread to save the economy and preserve normal life, but also prepare for a fair number of deaths. I knew that our epidemiologists were looking at these figures and thinking about them, so I wanted to give them the support from science that they weren't wrong. It is, however, a completely unbelievable decision to invite the whole nation to temporarily self-isolate.

In our case, that decision was further complicated. Namely, we're holding the rotating Presidency of the European Union and we have only 19 infected people, and we could close our borders. Other countries, however, have hundreds and thousands of infected people, numbers that are growing exponentially, but they aren't even thinking about such a move yet. I was pleased to see that as early as Friday, March the 13th, a decision was made to close the schools, sending a message to the population that Croatia was withdrawing into self-isolation.

We locked our country up exactly when we needed to, so we shouldn't have too many infected now, and again, Toni Milun assesses the details in his video. Toni and I joined forces today to show that Croatia was the country with the lowest percentage increase in newly infected people in Europe during the two weeks of March the 2nd to the 17th, which means that our "first line of defense" did a great job and endured for the longest period of time.

Then we went into quarantine at the right time, at a much earlier stage of the spread of the epidemic than everyone else. This has already prevented a very large number of infections so that we don't have to treat them. It has helped us in all steps with the legacy of the great Andrija Stampar, but also with our relatively recent war experience that EU countries don't have. But if anyone thinks this is the end now, I'm afraid he's living in fantasy land. This is just the end of the beginning.

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Translation by Lauren Simmonds, Editor of Total Croatia News. 

For the latest on the coronavirus in Croatia, follow the dedicated TCN section

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