With this in mind, let us now look at the Italian and other EU countries’ reaction to their own epidemic, in view of what Croatia did. In the early stages of infection spreading in a country, one or two infected persons are usually detected daily.

Personally, I advised the Croatian authorities and public through social networks to start seriously thinking about social exclusion measures when they noticed a first notable shift from the first 10 confirmed infections towards the first 20 infected people. On the 12^th of March, I posted a Facebook status entitled “Contrast is the mother of clarity”, which was viewed and shared by many thousands of my fellow Croatians who have been following my popular science series on the pandemics — “The Quarantine of Wuhan”. This status has also been shared by many online and printed newspapers and media in Croatia, including radio stations [18]. In that status, I suggested that Croatia should consider a large quarantine because we had already jumped from 14 to 19 infected people the day before. However, I also warned them to weigh this decision carefully against economic implications and their expected long-term effects on health. The very next day, on the 13^th of March, a decision was made in Croatia to close the schools [18,19].

That meant that, up to that point, Croatia completed two of the most important tasks in this pandemic. The first task was to hold its first line of defence. This was being achieved through the identification of infected cases imported from other countries and their isolation, and that of all their contacts. Croatia completed this first task better than the other EU countries, based on an average percentage increase of cases between the 3^rd of March and the 17^th of March. Then, from March 13^th, Croatia also began to introduce social exclusion measures at the right time, thus successfully carrying out the second key task in controlling its own epidemic. Many credits for this should be attributed to its epidemiologists who work at the Croatian Institute for Public Health.

But, what went wrong with these two measures in Italy and other EU countries? On the 21^st of February, the number of confirmed infected cases in Italy jumped from 3 to 20. As Italy is a more populous country than Croatia, it might have still been too hasty to send all of Lombardy into quarantine based on this. But on the 22^nd of February, the jump was from 20 to 62 cases, and this should lead to some serious thought about social isolation measures. A couple of days later, on the 24^th of February, they reached a situation very similar to that in Wuhan before a strict quarantine: the number of confirmed infections jumped from 155 to 229. This was particularly worrying in Italy because they did not seem to proactively test at that time, either.

The “jump” from 155 to 229, in combination with the Wuhan experience, should have suggested that they would have at least 50 000 infected people under the predicted curve of the epidemic wave and they were just seeing its early beginning of it. Such a large number would imply that about 2500 affected would require intensive care units. At the time, Lombardy had only about 500 such units in government/state facilities and another 160 in private health care facilities [20]. As early as the 24^th of February it was clear that there would be many deaths in Lombardy weeks later. With epidemics, everything goes awry because the infected get sick a week later, and some of the patients then die ten to twenty days later. This “time delay” is a critically important factor that needs to be taken into account.

However, even then, the Italians did not declare a quarantine. They did not do so on the 29^th of February, either, when the total number of infected people rose from 888 to 1128. Those figures implied that in mere days they would be having about 15 000 newly infected people each day. They did not declare quarantine on the 4^th of March, either, when the number of infected people exceeded 3000, and when the world stock exchanges started to fall again. It had then become clear to most epidemiologists who have been advising global investors that an unexpected tragedy was about to unravel in Italy and this was now inevitable. At that point, Italy already had at least 30 000 infected people spreading the infection. The quarantine was declared for Lombardy on the 8^th of March [7]. The day before, the number of cases had already risen, and exponentially so, to as many as 5883.

To appreciate the problem with epidemic spread in the population behind the first line of defence, this is similar to borrowing €1000 from someone on the 29^th of February with an interest rate of 26% each day, meaning an interest rate of 26% on top of that the next day, and so on. Furthermore, there did not seem to be enough clear and decisive communication with the public. The news of the quarantine for Lombardy was, in fact, leaked to the media before it was officially announced. This led to a quick ‘’escape” of many students to the south of the country, to their homes, carrying the contagion with them. As a result, on the 10^th of March all of Italy had to be quarantined [7].

In an already difficult situation, where every new day of delay meant another thousand or more people dying, as we can all notice these days, there were numerous media reports warning that the population may not have taken those measures as seriously as the Chinese when they introduced orders to their population in Wuhan [21,22]. Any indiscipline under such grave circumstances could have allowed the virus to take yet another step quite easily. With each new step, another 26% of interest was added to everything before that, and then 26% on everything on everything before that again. That is the power of exponential growth, characteristic of the free spread of the virus in the population.

Many Italians and then Spaniards, as well as residents of several other wealthy countries in Europe, had their lives cut short by their lack of recognition of the dangers of exponential function during the spread of the epidemic. Delaying quarantine for a week made the epidemic ten times worse than it should have been. Delaying it for two weeks made it a hundred times worse. And after two weeks of it being finally proclaimed, all those who may have not taken the orders seriously enough would have made the epidemic several hundred times worse. This means that, in Italy, and possibly in Spain, too, we are now observing the COVID-19 epidemic that is more than a hundred times worse than it should have been in a country that was much better prepared for the response, such as Singapore, Taiwan, Hong Kong or the United Arab Emirates.

To appreciate what is happening in Italy, it is enough to think of this sentence alone: at least 100 times fewer people would die each day if quarantine had been declared 2 weeks earlier and had the population stuck to the recommendations. During those fourteen days between 23^rd of February and 7^th of March, they allowed the virus to spread freely and infect a huge number of people – maybe even up to a million, or perhaps more, it is very difficult to know at this point. This would mean tens of thousands of people in need of intensive care, with about ten times fewer units available nationwide. About half of those who fall seriously ill will not survive without the necessary support. At this point, whenever we hear that 1000 people died in Italy in one day, we should know that the casualties would only add up to 10 had the quarantine been declared just a couple of weeks earlier. I appreciate that it seems implausible that the delay of a political decision like the introduction of quarantine by just two weeks may mean the difference between 100 deaths and 10 000 deaths in the 21^st century. However, I am afraid that this is, unfortunately, the reality of the exponential growth of the number of infected during an epidemic.

What does this mean for the public in countries like Croatia, who were confused and in awe of the events in Italy? They should know that they did not observe what the COVID-19 epidemic should actually look like in a country where the epidemiological service and its communication with those in power works well, as it does in Singapore, Taiwan or South Korea. In Italy, we have unfortunately noticed the consequence of a free spread of the epidemic for too long. Such a development was not predictable. The biggest surprise of this pandemic to date to the community of epidemiologists is, undoubtedly, the lack of response by the authorities of many EU countries to the apparent spread of the pandemic at an exponential rate for weeks, leading to a very large numbers of infected people in a very short time. It is even more surprising that, although the Italian example exposed this problem quite clearly, a similar scenario is now happening in several other European countries.

How and why could this happen in Italy and then in other countries in the European Union (EU)? I will try to offer at least some hypotheses. First, EU countries have been living in prosperity for decades, focused mainly on their economies. Aside from the economic questions, they have not had any challenges that they’ve had to answer to swiftly and decisively, that would measure up to this one. Back in the 1960s, vaccines were introduced against most major infectious diseases, especially childhood ones. Malaria is no longer present in Europe and tuberculosis has been treated similarly for decades. The challenge of HIV/AIDS in the 1980s is now being successfully controlled with antiretroviral drugs. Liver inflammation is treated mainly by clinicians. The impact of influenza is controlled through vaccination, while rare zoonoses are resolved with immunoprophylaxis. Even sexually transmitted infectious diseases (STDs) are no longer as significant since the vaccine for Human Papillomavirus (HPV) was licensed.

The last real epidemic that concerned Europe was the Hong Kong flu, which occurred back in 1968 and 1969. The broad field of biomedicine offers such a wide range of exciting career paths to all those students who study it these days, but the epidemiology of infectious diseases is not really one of them – or, at least it hasn’t been in Europe for a very long time. It has probably begun to seem like an archaic medical profession to the majority of students and young medical doctors. It seemed to belong to the past for the European continent, which made it one of the least attractive things to specialize in.

Even the rare epidemiologists who specialized in infectious diseases have begun retraining for chronic non-communicable diseases, due to the aging of Europe’s population, which is particularly the case in Italy and Spain. It seems that at least some EU countries may have fallen victims to their own, decades-long success in the fight against infectious diseases. They faced this unexpected pandemic with few experts that could have had any experience in these events. Asian countries, as well as Canada, have had enough recent experience with SARS and MERS, but some European countries seem to have forgotten how to fight infectious diseases. If it were not for the legacy of the great Croatian epidemiologist, social medicine expert and global public health pioneer Dr Andrija Štampar, and the relatively recent war in Croatia, it is difficult to say whether or not Croatia would be as ready as it has proven itself to be.

Another factor that would understandably undermine the Italian response was that no one before Italy, in fact, could have observed how fast COVID-19 was spreading among the population. The greatest danger of COVID-19 is its accelerated, exponential spread when it breaks through the first line of defence. But, before Italy, only the Chinese in Wuhan and the Iranians had experienced the free spread of the infection among their population. After five days of monitoring the number of infected, the Chinese had to quarantine the entire Wuhan, and then further 15 cities a day later, in order to contain the virus. They did not know how many infected people were there outside of Wuhan’s hospitals. For Iran, however, only a few knew exactly what was happening, as that country is significantly isolated internationally due to political reasons. The Koreans, however, had a limited local epidemic but not an uncontrolled free spread — they caught the virus using their first line of defence.

That is how the Italians ended up becoming the first country in the highly developed world to monitor their epidemic spreading uncontrollably among the population. The only estimate of the rate of spread of the virus to date has been in the scientific work of Li et al. from the 29^th of January [23]. However, it was difficult to subsequently determine R0 parameter on the first 425 patients in Wuhan. The estimate of the R0 for COVID-19 in their article was 2.2, but with a very wide confidence interval – from 1.4 to 3.9. It is a bit of tough luck for the Italians, again, that they calculated the lower bound of the confidence interval to be 1.4 exactly. This figure is well known to all epidemiologists, it’s the rate of the spread of seasonal flu in the community. It should come as no surprise that many epidemiologists would guess that, with more data, R0 for COVID-19 would start converging more towards 1.4. Unfortunately, the more recent data suggests that R0 is more likely to lean towards 3.9, implying an incredibly fast spread. Thus, the greatest danger of COVID-19 remained unrecognized in Italy until the 8^th of March quarantine measures. At least 100 times fewer people would be dying in Italy these days had they declared a quarantine for Lombardy two weeks earlier than they did.

Just a few days ago, an extremely useful piece of scholarly work, authored by Onder et al., became available [24]. Their contribution finally provided answers to the three great unknowns about COVID-19. Many hypotheses have been presented in the media to explain the developments in Italy since the very outbreak of the epidemic, but thanks to just one simple table, we can now dispel most of them.

The first is the question that has plagued us for a long time – how dangerous is COVID-19 for younger age groups? It is clear that the media will tend to single out individual cases of death in younger people, as they are of most public interest. However, it is interesting that until recently, we didn’t really have decent data on this in the public domain. The first reason was that the Chinese Centre for Disease Control reported all deaths in the Chinese epidemic using age groups structure that contained a very large age group of “30-79 years”. It only separated children up to 10 years, then adolescents up to 20 years, then 20-29 year-olds, followed by this broad age group (30-79 years) and those who were 80 years or older. That is why the work of Onder and colleagues is commendable, as they subdivided this large group from China into 10-year age groups. This finally allowed a comparison between the first 1023 deaths in Wuhan (up to the 11^th of February) with the first 1625 deaths in Italy (up to the 17^th of March). The comparison is shown in Table 2.It gives us some very important insights.

First, in Italy, more than half of the deaths initially were among people who were older than 80 years of age, and a total of 88% of the deaths occurred among the persons over 70 years of age. So, contrary to the impression that individual media reports can easily make, COVID-19 is a very dangerous disease mainly for old people. Moreover, a recent study by A. and G. Remuzzi [25] showed that, among 827 deaths in Italy, the vast majority of those people were already severely ill with underlying diseases, such as cardiovascular disease, diabetes, and malignancies. This is what epidemiologists expected because a more severe flu would have had a similar effect if there was no vaccine available. However, I doubt that the general public has the proper insight into this issue from the prevalent media reports.

Second, it was suggested in the media across Europe that the virus in Italy may have mutated and become much more dangerous. However, Table 2 shows that death rates by the age of 70 are practically the same in China and Italy. Then, although the case fatality rate appears to be about 50% greater in Italy than in China for the age group 70-79, this does not suggest that the virus may have mutated. It is known that in Wuhan, many of the affected with a severe clinical presentation of COVID-19 could rely on the two newly built hospitals and respiratory aids that the military had brought in from other parts of China [26]. They also had medical teams coming in from other provinces [26]. In Italy, however, there were not enough respirators for this age group, and there weren’t enough doctors either, as many of them themselves became infected [16,20]. For those two reasons I would, in fact, expect even a larger difference between Italy and China than the one we are seeing, so I would not attribute this observed difference to the impact of the virus itself. And finally, the reported difference in case-fatality rates for the oldest age group should also not be attributed to the virus. It is more likely a consequence of the fact that Italians of Lombardy live, on average, longer than the Chinese of Wuhan [27]. Therefore, there are significantly more people in the oldest age group in Italy, ranging to much higher ages, so the two oldest groups are not really comparable. The average age of the Italians in the age group “80 years or older” is significantly greater than the average age of the oldest Chinese age group. Therefore, the table shows practically equal death rates across all age groups, on sufficiently large samples, meaning that the virus did not mutate in Italy from the virus we see from Wuhan, at least not until the 17^th of March, 2020.

Third, and perhaps most importantly — this chart has now made it quite clear that COVID-19 does not, in fact, kill people under the age of 50 unless they have some sort of underlying disease, or some unknown “Achilles heel” in their immune system that makes them particularly susceptible to the virus. There are such cases with every infectious disease. They are also present during the flu epidemics, but they are extremely rare. This suddenly gives us another possible strategy for quarantine exit, where children and those under 50 years of age could first emerge if they do not have any underlying illnesses. Here, after this table, it already seems like we are beginning to have an increasing number of options to get out of quarantines and learn to live with this virus until the vaccine becomes available. However, at least a few more studies need to be carried out to confirm that this age group can be substantially protected, to provide reassurance that the virus is not becoming more dangerous for those younger than 50 years, too.

There is another strangeness to the situation in Italy that will not be intuitive to the general public. The actual number of deaths attributable to COVID-19 in Italy will not be possible to estimate for several months after the epidemic finally ends. Namely, at present, due to the sole focus on the epidemic, most of the cases of death of very old people who have been diagnosed using a throat swab have been attributed to COVID-19. However, once the epidemic is over, it will be necessary to compare the deaths in individual areas of Italy with the average for the same months in the previous few years. It could be shown that a part of the already ill would have died in the same month, or a year, even without being infected with the new coronavirus. It is possible that among some of them COVID-19 accelerated this inevitability by a few weeks or months. Some of the deaths observed during the epidemic in Italy may need to be reclassified later and attributed to underlying diseases in accordance with expected levels, and those above expected levels will then be attributed to COVID-19.

This article provides an explanation from the epidemiologist’s point of view for most of the events reported so far in Italy, and then followed in Spain and other European countries. A combination of an early relaxation over this epidemic, systematic lack of expertise in the field of epidemic infectious diseases in Europe, likely inexperience in containing epidemic spread in this generation of health workers, relaxed immigration regulations for workers in certain industries, Champions League football event and a series of further misfortunes and omissions have all been implied so far in the media as contributors to the late withdrawal of Lombardy into quarantine. This allowed, through exponential growth, for a large number of people to be infected in a very short time – far too large for health systems of Italy and other EU countries to cope with. Severe forms of illness led to many deaths due to respiratory failure. In 88% of cases, people over 70 years of age died, who had underlying illnesses in the large majority of cases. This viewpoint is based on the first 1625 deaths in Italy, and by the time of this writing, there are now more than 10 000 dead. Given the size of the population, this would correspond to 670 deceased in Croatia. If Croatia manages not to follow the numbers of deceased seen in Italy, this will mostly be attributable to social exclusion measures being introduced early enough for its health system to come with severe cases.

These days, the people of Italy, Spain and other European countries are suffering large losses. A significant underlying cause may be the problem that the human brain simply cannot intuitively grasp the power of exponential growth, nor that two weeks of delay could make the difference between 100 and 10 000 deaths. Any physics enthusiasts will know the quote attributed to the great Albert Einstein, who is often cited saying that compound interest, which leads to exponential growth, is “…the most powerful force in the Universe”, or “…the eighth wonder of the world. He who understands it, earns it; he who doesn’t, pays it.” [28].