If we don’t stay home during a quarantine, our healthcare professionals in Croatia will not have to worry about several hundred people who are suffering from COVID-19 more severely, which our health system can handle, but several thousand of them, which it can’t. That difference is now our responsibility.
Pandemics, like the world wars, are dynamic events with an uncertain outcome. In these times, things can quickly change from stage to stage. When encountering a new, unknown and invisible opponent such as this coronavirus, surprises are always possible. That’s why we should remain vigilant, but shouldn’t panic. It takes a cool head to make all of the important moves and respond to challenges at the right time, relying on scientific evidence and valid information.
The virus can always surprise us with its mutation. Random mutations of its genetic code can change the severity of the symptoms it will cause. They can also change the rate of its spread among the population. On the other hand, there are several lines of defense at our disposal that, depending on the behavior of the virus, can be activated at the right time. Compared to the situation only three weeks ago, today, I have to make it clear that the epidemiology profession has significantly changed its perception of the danger of this new coronavirus.
By constantly collecting information from many countries, we now have a better understanding of the ways in which it poses a threat to us. I will try to explain here why the attitude of the epidemiologists has changed and why we now really MUST stay disciplined in our homes for at least a month.
I’ve written before that this is already the seventh coronavirus to try to adapt to the human species. The first four cause common colds and have been harmless to humans. The fifth, the SARS epidemic, however, was terribly dangerous. It killed as many as 10 percents of the people it infected. It expanded in 2002 from the Chinese province of Guangdong to more than 25 other countries but was stopped everywhere using the first line of defense.
The sixth one, the MERS epidemic, was even more dangerous. It killed as many as one-third of those infected. It spread from Saudi Arabia to more than 25 other countries. But then, again, it was stopped by the first line of defense. That line of defense includes the isolation of patients and all of their contacts.
When the epidemic of the seventh coronavirus, with COVID-19 as its causative agent, erupted in Wuhan in January 2020, it isn’t surprising that the epidemiologists’ interest was primarily focused on the death rate among those infected. The reason is that the death rates for SARS and MERS were so terribly high — 10 percent and 35 percent, respectively.
It was soon realized that the death rate among the most severe cases and hospital patients in Wuhan was about 5–10 percent when it came to this new coronavirus. However, it was only valid for the most severe cases that came to the hospital there, but not for anyone infected in the community. Infected doctors, like most patients in the population, had a significantly milder clinical presentation. Therefore, it was necessary to determine as soon as possible the rate of death among those infected.
We got our first idea of the actual death rate of infected people when the work of Z. Wu and J.M. McGoogan were published in JAMA back at the end of February. It was based on a major report by the Chinese Centre for Disease Control, based on 44,672 COVID-19 positive patients in all Chinese provinces. The authors showed that the death rate in the Hubei province was 2.9%, but they knew it was unrealistically high. This is because, at the earliest stage of the epidemic, the overwhelmingly severe cases that came to hospitals were tested, and there was no time at the height of the epidemic to test many in the community. A much more realistic estimate, therefore, was among those who tested positive outside the province of Hubei, on the front lines of defense of all other Chinese provinces. This death rate was 0.4%.
This means that for every 200 people with COVID-19 if given adequate medical care, only one person would die, or even less than that. Confirmation of that came from South Korea, where an unusual incident occurred. A community epidemic happened there, behind the front lines of defense. The authorities there went forward with massive population testing. Thus, the path of the virus among the population was constantly monitored and all the infected were isolated.
For such a very deep first line of defense, South Korea also had enough money, experience, and all the other necessary facilities. Some 10,000 people were tested daily. Based on the first 140,000 tests, the rate of deaths in the community was estimated to be about 0.6%, again — one in two hundred, and quite similar to the estimate for all Chinese provinces outside of Hubei. These two figures are also very close to the estimate I made on the 1st of March when being a guest at the TV-talk show “Sunday at 2.00 pm”. There, I predicted that COVID-19 case-fatality rate, when spreading among the community, should be somewhere between 0.5–1% or even less — depending on how large is the denominator with all those infected.
In addition to the case-fatality rate among everyone who was infected, it was also important for epidemiologists to know what the chances of a cure for all those who end up in hospitals are. It’s important to evaluate these prospects when the patients aren’t treated in the face of a booming epidemic when medical teams are also infected and local hospitals are overloaded. Under those conditions, their chances of survival would be smaller. Therefore, we needed to understand their chances of survival when the conditions are more favorable and the health system is prepared.
We learned these outcomes from the work of W. Guan et al., Published in the NEJM journal. On February the 28th, they released a series of 1099 patients with laboratory-confirmed COVID-19 infections from 552 hospitals in 30 provinces in China. This was a representative pattern of hospital treatment outcomes for China, in an environment where adequate care could be provided to all those infected. The estimated mortality rate of those with COVID-19 who end up in hospital was 1.4%, which was indeed much less than the first experiences in Wuhan.
Based on these two key pieces of information about COVID-19 — that is, that it can kill only one in 100–200 infected persons in the community and one in about 50 to 100 hospitalized persons — the epidemiologists in the western world could breathe a bit more easily again. It no longer seemed that they we were dealing with such a dangerous infection. This was reflected in the reaction of the world stock exchanges: Dow Jones was at 24,720 points on the 28th of February and then it rose to 27,087 points on the 3rd of March. This means that it gained 10% in just five days after COVID-19 mortality rates in China and South Korea became clearer.
The reason is that stock market investors have been in constant contact with leading epidemiologists in those days. They were interested in the developments literally hour by hour. The view of the epidemiology profession during those five days was that we were likely to suppress the COVID-19 pandemic soon. These were exactly the days when I found myself in Zagreb and gave my first estimates to the Croatian media after the first COVID-19 patient was confirmed in Croatia on the 25th of February.
The epidemiological profession’s view at the time was that the primary epidemic, in the City of Wuhan and in the province of Hubei, had been in continuous decline from the 8th of February throughout the end of February; then, that the first lines of defense were able to stop the virus in some thirty Chinese provinces, each one of them with tens of millions of inhabitants; furthermore, that the virus was successfully halted on the first lines of defense in Japan, Taiwan, and Singapore — i.e., the countries that have the highest human traffic with China. In addition, even in South Korea, where an unforeseen epidemic occurred in the community, it was managed by intensive testing, with as many as 10,000 tests carried out per day.
For the epidemiologists, those developments were almost a “deja vu”, i.e. entirely similar to the scenario that was already seen with SARS and MERS. That same scenario was now being repeated for the third dangerous coronavirus during the last days of February and the first days of March 2020. As was the case with the two previous epidemics, here we also had a primary focal point in the City of Wuhan in the Hubei province. It was suppressed by a large and strict quarantine, as the ultimate line of defense. All secondary foci were controlled by primary lines of defense. None of the epidemiologists thought at the time that European and North American countries wouldn’t be able to stop it in the same way.
At that point in time, the epidemic seemed very close to being extinguished. Even the World Health Organisation delayed declaring COVID-19 a pandemic. It did it only about ten days later, that is, on March the 11th, because things had changed to such a dramatic extent. What, then, changed so much between the period of the 28th of February and the 3rd of March, when the epidemic seemed practically overpowered, and the 11th of March, when the World Health Organisation declared a pandemic and the need for the absolute highest degree of caution?
According to the current understanding of the situation that most epidemiologists can offer, the virus somehow got a foothold behind the first lines of defense in northern Italy. Some media blamed this on Chinese migrant workers in the textile industry, other on tourists from Wuhan, third on business people returning from China, but it is too early to be sure. In ant case, an epidemic that no one knew about began to quietly spread in the smaller cities of Lombardy and behind the Italian line of defense.
There are many people living in northern Italy who went skiing in late February and early March. Across European ski resorts, they spread the infection enormously to the Swiss, French, Austrians, Germans, Belgians, Dutch, British and Spaniards, as well as citizens of many other countries in northern and western Europe. This is probably also because the spread of coronaviruses is generally favored by lower temperatures. The current picture of the spread of the epidemic and of the hardest-hit countries is in line with these developments. Moreover, an infamous Champions League football game between Atalanta from Bergamo, Italy, and Valencia from Spain, helped the virus to be passed from Italian footballers and supporters to Spanish ones which later led to an epidemic in Spain.
As I described above, from the 3rd of March to the present in many EU countries, most notably in Italy, which was one week ahead of the others, the number of infected people started to increase at an incredible rate. If the virus breaks through the first line of defense, we know that its growth will be exponential, but the human brain can hardly understand what that really means. In linear growth, anything added in the fifth week of expansion will represent one-fifth of all cases so far. In the tenth week, a tenth. We know that and it is logical. But when it comes to exponential growth, everything added up in each coming week will account for the vast majority of all cases, and anything that has happened before will seem irrelevant compared to just one week previously.
I wrote about the dangers of exponential growth and the need to introduce major quarantines in Europe on the 8th of March and offered the option of strict quarantine for Croatia on the 12th of March. But I have the impression that even in mid-March, the leaders of some EU countries still didn’t understand what the real danger of COVID-19 was. Thus, this coronavirus doesn’t kill primarily because COVID-19 is medically particularly severe in most patients, but mostly because it spreads so incredibly quickly among humans.
Because of this, this coronavirus generating a huge number of patients in a very short time, about 5% of which will experience an extremely serious condition. If we were able to provide each one of them with optimal care in a timely manner, almost all the seriously ill would be saved. But if everyone gets sick at the same time, we can’t provide them all with appropriate care. That is why the majority of severe coronavirus cases will die. This is how this coronavirus has been killing so many people in Italy. They could have tens of thousands of patients suffering severely, who may not gain access to intensive care and respirators.
The reason for the deaths in Italy was not, therefore, the severity of coronavirus per se, but rather that the danger of a rapid and exponential spread was not realized quickly enough, meaning that the quarantine was declared too late.
The incredible spread rate of this coronavirus is shown in this example. Below this paragraph, it is shown what happens when the number of new cases is increasing by about 26% per day compared to the previous day. This was quite a realistic scenario for many European countries. The table first shows the days since the epidemic began. In the second column, the number of those infected with the virus is shown. It’s important to understand that those infected with the virus have not yet been diagnosed with COVID-19 because they do not yet show any symptoms. Nonetheless, they can spread the infection over the next week while looking quite healthy. Only when they show symptoms of the virus a week later will they find themselves in the third column, as those who are “sick.” This means that when testing the number of patients on any given day, we should expect that the actual number of infected people in the population is already about ten times higher.
DAY 0 = 1 INFECTED = 0 SICK
DAY 7 = 10 INFECTED = 1 SICK
DAY 14 = 100 INFECTED = 10 SICK
DAY 21 = 1,000 INFECTED = 100 SICK
DAY 28 =. 10,000 INFECTED = 1,000 SICK
DAY 35 = 100,000 INFECTED = 10,000 SICK
DAY 42 = 1,000,000 INFECTED = 100,000 SICK
DAY 49 = 10,000,000 INFECTED = 1,000,000 SICK
Croatia has now passed day 21 and is moving towards day 28, but has declared a quarantine on time. Most EU countries have passed the 35th day and only then did they declare quarantine, so they can expect as many as 10 to 100 times more infected people than Croatia. Italy declared quarantine when it was nearing its 42nd day and probably already had hundreds of thousands, if not millions of people infected.
There are several other interesting things about this exponential spread of this infection. Namely, small countries are in more danger of it than big ones are. The virus will spread exponentially among people using their mutual contacts, at the speed shown in the table above. It doesn’t matter how many inhabitants there are in the country in which it is expanding. This is why smaller countries will be relatively more severely affected than large ones.
For example, Italy, with its 60 million inhabitants, can withstand the spread of the virus for 42 days, causing as many as 1 million people to become infected. Of these, about 5%, i.e. 50,000 of them, will become seriously ill. This is too large of a figure for their few thousand intensive care beds, and many cannot be provided with the assistance they need. Therefore, the Italian death toll from COVID-19 could be in the tens of thousands. However, not all the severely ill will die, because many will only require oxygen for their treatment and will not need a respirator.
This means that in Italy, as many as one million infected people could lead to some 25,000 people being of a very high risk of dying. But even in such a scenario, it should be understood that only 1.6 percent of all Italians would get infected with COVID-19 at all because Italy is quite a large country.
In addition, 99.97 percent of Italians will survive the epidemic, which is important to understand for some future discussions on this topic. But, if COVID-19 had expanded exponentially in a much smaller country, it could have done significantly more damage relative to the entire population, in relative terms. Things that happened in Italy should be put in an additional perspective. The scientific paper by A. and G. Remuzzi published in the March 2020 issue of Lancet showed that the average age of the first 827 deaths in Italy was 81 years and that more than two-thirds had diabetes, cardiovascular disease, cancer or were ex-smokers.
So these were the same people who probably would’ve died of the flu if they had not been vaccinated against it. Furthermore, in the scientific work of Rosan et al. published in International Journal of Infectious Diseases in 2019, at least 20,259 deaths in the 2014–15 season, and a total of 24,981 deaths in the 2016–17 season, were directly or indirectly attributable to influenza in Italy, even with vaccination. This means that the total number of deaths in Italy from COVID-19 could eventually be at least roughly comparable to those figures if the number of infected and dead continue to decline in the next few days.
However, taught by the experiences from back at the beginning of March, I’d also like to add that this is the view of the epidemiological profession on the state of affairs at the moment, to this day. Any new contingency — such as the realization that the virus has indeed mutated and become more dangerous for younger people, or a repeated escape of the virus into an exponential spread, could change that view once again. Epidemics are dynamic and unpredictable events.
What we need to know now is that in the period from the 3rd to the 17th of March 2020, Croatia was still managing to maintain its first line of defense to a significant extent. It was at a time when the largest number of European countries already had exponential growth and uncontrolled spread in the community. This lead to a very large number of infected people with serious clinical issues, that could no longer be helped. But in those fourteen days Croatia had about 15–16% daily increase in the total number of infected people, while among the thirty other countries in Europe, Denmark was the worst with a 44–52% increase.
Then, after the 17th of March, Croatia introduced quarantine measures. If we’re to believe the numbers, we in Croatia should, therefore, deal with at least 10 times less severely ill people than other Europeans, and as many as 100 times less than the Italians. But that will only be valid if we all stay in our homes and do not leave for a month. If we ruin all the good that Croatian health experts have done so far, which would also include careless exposure and socializing, the virus will continue to spread rapidly in Croatia.
In such a case, our health care professionals wouldn’t just need to worry about a few dozen or several hundred people with a severe clinical picture, which our health system can certainly handle; instead, they would need to manage a few thousand of them instead. They simply cannot cope with such large numbers. However, that difference depends entirely on us now. We need to remain patient in our homes for a month.
But then, just when everything was being done the right way in Croatia, we were hit by this unfortunate earthquake in our capital city, Zagreb. I watched people go out into the streets after the earthquake struck, talking to each other in shock. Then, scared as they were — many people from Zagreb drove to the south of the country, to the coastline, likely taking the virus with them. They took it to the areas where we have significantly less capacity for intensive care. So, it was a totally incredible turn of events.
Because of this, we can no longer predict the numbers. The number of infected people could be much higher than planned for by Croatian epidemiologists. Instead of a total of about 3,000 infected, it could now grow to a much larger number.
All this is beginning to remind me of the finals of the World Cup in football two years ago. First, Croatia opened that game against France better than anyone could have hoped we would. That part would be analogous to holding our “first line of defense” between the 1st and 17th of March. During that period, we had the lowest percentage increase in the number of cases among the 30 countries across Europe. Then, we scored an unfortunate own — because, the coronavirus managed to find its way into our hospitals in Zagreb city from various European ski resorts, but also through the emergency services. It managed to penetrate the places where we least wanted it.
But then, we “equalized”, as we did against France — we managed to trigger the lockdown and declared quarantine just at the right time. This would have prevented a large number of infections. But then came the earthquake in Zagreb, people went out onto the streets, the virus spread through conversation and then some people, scared as they were, even carried it down south to the coastline where we don’t have much capacity for intensive care. That resembled the events in the football game again — an unfortunate handball in the penalty area, a referee checking it on VAR and awarding the penalty to France. That’s why we all need to be our goalkeeper Subasic now, but this time we simply have to defend that penalty. And in order to block it, we just need to stay home for one month.
FACEBOOK: Professor Igor Rudan
Image credit: Hrvatski nogometni savez (HNS)