As Index writes on the 9th of March, 2020, prominent Croatian scientist and epidemiologist Igor Rudan, wrote a comprehensive text for Index in which he answered twenty key questions about coronavirus (COVID-19). Croatian scientist Igor Rudan is a member of the Royal Society of Edinburgh and the founder of the 21st Century School.
Here are twenty questions and answers on coronavirus from a highly respected and cited Croatian scientist. We have translated and transmitted Igor Rudan’s text for Index in full:
”In this text, I’ve summarised the issues that I see most often lead to misunderstandings or cause some confusion about the new COVID-19 pandemic. I’ve offered all of these answers from the perspective of a scientist who has been involved in this field internationally for two decades. My answers seek to offer a view that is scientifically based on the data which is currently available about this pandemic, as well as the experience of previous epidemics and pandemics caused by respiratory viruses.
However, I’d like to emphasise the fact that there is still a number of ambiguities regarding the new COVID-19 pandemic and that scientists are closely monitoring its development and gathering new evidence, which is why this pandemic needs to be taken seriously and adhered to by all public health experts. In the event of this situation worsening, one should also be prepared for preventive public health measures such as avoiding public gatherings and quarantines at home.
1. Is this one of “those” infectious diseases that will decimate us and which will take its place in history?
The history of the genus ”Homo” and the dozen human species we know of today through excavation was determined by the fight against infectious diseases. It’s likely that the species that are no longer around today are largely extinct due to the spread of infectious diseases. We should be happy that we no longer live in the times of great epidemics and pandemics that once decimated our species. A huge number of people died during their childhood or youth.
The most severe medieval infections killed up to every third person, and before the discovery of the microscope, people couldn’t even know why it was happening to them. No one thought that tiny, invisible, living microbes could cause these diseases. People assumed that some heavenly punishment for their sins had come upon them. We should, therefore, be happy because we’re living in the age of this advancement of science and medicine.
Since 1940, many bacterial diseases have begun to be controlled by antibiotics, and since 1960, many virus and bacterial diseases have had vaccines developed for them. Unfortunately, we don’t have a vaccine for all infectious diseases. As we see in the example of this pandemic, new viruses continue to transfer over from other species to us because history hasn’t ended with the advent of our generation but instead it just continues.
2. Could science have expected the COVID-19 pandemic?
It could have, because this is already the seventh coronavirus to try to make itself at home within the human population, trying to adapt to us and use us as its reservoir. Specifically, we exist together on a small blue-brown planet in a vast dark universe. We share it with tens of millions of other species. They all strive to survive until further notice. More than 99 percent of all species that have ever existed on Earth have failed to survive to this day. That is why viruses must constantly transfer themselves to new species and thus expand their reservoirs. They must choose the winning species because they can’t reproduce on their own. Their survival depends on the survival of the species that is their reservoir.
People are currently an interesting potential viral reservoir. We’re expanding and multiplying rapidly – from about a billion and a half individuals, we’ve grown to about seven and a half billion in the last 130 years alone. In doing so, we’re penetrating territories, clearing forests, draining wetlands, hunting for pleasure, reducing overall biodiversity, making it difficult for others to survive, while there are more and more of us. Fortunately for all of us, the first four human-adapted coronaviruses were merely the cause of common colds. No one considered them a serious threat to public health.
3. Were SARS and MERS a serious threat?
SARS (severe acute respiratory syndrome) and MERS (Middle Eastern acute respiratory syndrome) were a real and big surprise for scientists and experts. Specifically, these were respiratory viruses from the coronavirus family, the fifth and sixth that were able to pass over to humans. Surprisingly, instead of colds, they could have caused very severe, fatal pneumonia. In addition, the death rate among those infected with both diseases was truly frightening. Both could have caused a horrible amount of death of humans if, by chance, it had spread to the world’s entire population.
The coronavirus that caused SARS had its reservoir in bats, which hibernate in caves in winter. Then, no one hunts or consumes them. However, it did manage to transfer over to an animal from the cat family, a civet. It was also contracted by a man, a farmer in Guangdong province, in late 2002, from a civet. SARS then spread to more than twenty countries and infected more than 8,000 people, with every tenth person confirmed to be infected. It was the fifth human coronavirus, but it was the first to kill humans.
Ten years later, in 2012, the MERS coronavirus appeared in Saudi Arabia. It was passed on to humans from the camels in the desert. It has also spread to more than twenty countries, infecting about 2500 people and every third infected person died. So, MERS had a really scary mortality rate. The advent of MERS showed us that SARS was not some isolated incident with a coronavirus that we can just forget, but that coronaviruses have become our most significant potential enemy. If SARS or MERS had spread around the world and infected billions of people, it would have been a catastrophe unlike anything from the last century or two, that is, in popular culture, it would’ve been called the “zombie apocalypse.”
4. How did MERS and SARS manage to be dealt with so quickly considering the fact that they were so dangerous?
In those two cases, we were actually very lucky. Namely, a completely new virus that tries to transfer over to the human species can spread in humans in three basic ways. These ways depend on our ability to deal with epidemic surveillance. Once the virus enters the human body, it begins to multiply in the kind of specialised cells that it has been able to bind to. In the case of coronaviruses, these are the cells of the respiratory system. It multiplies in them by “hacking” its cellular genetic instruction and using that “machinery” to build proteins.
This multiplication of the virus destroys the cells, which is why there are symptoms characteristic of problems with the respiratory system: such as a sore throat and cough. In the first mode of the spread, the virus spreads from the infected person to other people only after the onset of symptoms.
It is easiest to stop such an epidemic because the sick person no longer leaves home. Therefore, it mainly infects only their household members. It’s also relatively easy to identify who was in contact with the person after the onset of symptoms and also put those people in isolation. We were fortunate that both SARS and MERS spread to other people only after the onset of the symptoms of the disease, so we were able to suppress the epidemics by isolating those infected and all their contacts after the onset of the symptoms. This is the most important reason why SARS and MERS didn’t manage to kill an incredible number of people.
It’s much more difficult to stop an epidemic if the virus spreads from the infected to the healthy during the period of the so-called incubation, which lasts from the entry of the virus into the body until the onset of the first symptoms. Then, the infected person can transmit the virus by contact to a significantly larger number of people in the days before they get any symptoms. That’s the situation with this new COVID-19 pandemic. But even then, it’s at least possible for every new patient to determine from whom he or she has previously contracted the infection. Namely, they had to meet somewhere, so it’s possible to follow the whole chain of movement of the virus from person to person.
Due to this, intensive isolation measures of all those exposed to those already infected can significantly slow down the spread of the virus. This was done in Wuhan. That’s why quarantines are justified and that’s why they give good results.
A nightmare for any epidemiologist, however, is a third possibility for the virus to spread. In such a variant, people become infected and transmit the virus, but they themselves never show any symptoms. Scientists are currently looking for such possible spreads of contagion with this new COVID-19 pandemic. That’s why such persons are occasionally mentioned in the media.
Namely, because of such infected people, cases are beginning to emerge among the population that can’t be linked to any of the already infected people. When people are circulating in the population without symptoms but passing the virus on to others, it’s very difficult for epidemiologists to do anything to prevent it from spreading among humans. Such an epidemic has the potential to spread over time, mainly due to such transmitters or carriers who show no symptoms.
5. What makes the new COVID-19 outbreak different from the previous six coronaviruses?
When something has happened six times in a system as complex as the Earth’s ecosystem, then it’s no surprise that it’s happened for the seventh time. Another coronavirus is trying to make itself at home now in the human species. In this case, the primary reservoirs were probably bats again, because the genetic sequence of this new coronavirus coincides with that found in hibernating bats in about 96 percent. This time, instead of a civet, a smaller mammal or bird has served as coronavirus’ transitional reservoir.
It’s possible that it was a shellfish, because in one of them, a coronavirus that matched to the human form in as much as 99 percent of the sequence was found, although this isn’t completely definite either. Sequence matching is not the only important factor when it comes to transfering to humans. What’s also important is how many individuals in the species that serve as the transient reservoir are infected and how often the species comes into contact with humans. Sometimes these factors are more important, so they can bridge the gap of 2 percent or 3 percent of the genome difference, because bats are a protected species and can’t be eaten.
Thus, in the Chinese province of Hubei, in the City of Wuhan, which has a population of eleven million, at around the end of 2019, the number of patients with unusual and very dangerous type of pneumonia began to increase around the fish market. It was soon discovered that this disease was spreading very quickly. Each infected person managed to successfully further infect as many as two to three people. Such a degree of infectivity is very high and leads to rapid growth of the epidemic. We had the misfortune of COVID-19 apparently managing to spread even during the incubation period, probably by touch.
This incubation period lasts about five days on average, and it becomes very tricky when it lasts longer. However, an incubation period of up to two weeks isn’t that unusual, and incubation cases of up to four weeks seem to occur. During all this time, the infected person may spread the virus before the onset of any symptoms. If there are also infected people who don’t develop symptoms, it will be extremely difficult to completely reverse this pandemic until we develop a vaccine for it. In conclusion, infectivity, ie, the ability to move from the infected to the uninfected, was significantly higher in COVID-19 than it was with SARS and MERS. But that’s why we now know for sure that the COVID-19 mortality rate is still significantly lower than that of SARS and MERS.
6. What is the death rate among those infected with the COVID-19 epidemic, and why is there so much ambiguity about it in the media?
First, I will clarify that in this text, for ease of reference, I use the term “death rate” instead of the term “lethality” or “case-fatality rate” and to distinguish it from the term “mortality rate”, which would refer to the term “mortality”. In order to answer this rather complicated question, it must first be said that nowadays, the registered number of infected persons and the number of deaths can be monitored online.
When the registered number of infected people was divided by the number of deaths at the beginning of the pandemic, a figure of about 2 percent would be obtained. From this, one could apparently conclude that this coronavirus is new and so nobody is immune to it, which means that it will spread throughout the world over time and infect us all. If it kills 2 percent of all people, then it’s not hard to calculate that out of 7.5 billion people, about 150 million will die from it. And it’s difficult for anyone who is not a specialist in this field to understand how such an outcome can now be prevented at all, because a vaccine against this virus doesn’t yet exist, nor do medicines.
The question of the death rate among those infected with COVID-19 indicated a general misunderstanding of the epidemiology profession in the public and in the media. From the very beginning of this pandemic, there were people who claimed that the new coronavirus was a disease milder than even the flu, but also those who believed it was significantly more dangerous. In recent days, this issue has finally caught the attention of all the world’s media as the World Health Organisation reported “that about 3.4 percent of those infected with coronavirus have died.” That sounded terrifying to the media and the public.
But then US President Donald Trump also made a public statement saying the number released by the WHO was “wrong.” He said he’d talked to people who knew something about it and that his impression was that the number was certainly below 1 percent, if not significantly less. In my guest appearance on Sunday at 2 (Croatian TV show), I made my estimate of the death rate of 0.5 to 1 percent, with the possibility that it would be smaller.
However, both Trump and WHO are actually right, each in their own way, which shows best and how difficult it is for many people to keep track of what is really going on because of their ignorance of this profession.
In the beginnings of every viral epidemic, the virus still has to transfer over to humans, and that can be difficult. Therefore, they will choose those with a weakened immune system, who will have a harder time rejecting it. Because of this, the first patients are often people who are either older or already have some underlying illnesses that make them more vulnerable. They end up in a hospital, where at that point no one doubts the epidemic potential of their pneumonia.
They then become infected by other hospital patients, and by some healthcare professionals. The latter then spread the disease to other patients in the hospital – very sensitive people, the elderly, patients being treated for serious illnesses. For this reason, the proportion of deaths among all COVID-19 patients was initially very high. That’s how it started out in Wuhan, and in exactly the same way in Italy – they died of infections in hospitals, and they were mostly very old and sick people.
In the meantime, the virus has started to spread among the general population, those outside of hospital situations. It has infected many people who are otherwise healthy and has as such better adapted. A large number of these people thought they had a cold, or the flu, and maybe even a more severe flu, which they were just letting run its course, resting at home. Considering that it was flu season in Wuhan at the time of the outbreak, and it was reported that something strange was happening in hospitals and that people were dying on a larger scale, it is now understood that many with the coronavirus stayed home and treated themselves.
Few people wanted to go to the hospital to have tests for the flu because of coronavirus, when a seemingly very deadly epidemic was brewing there. Only the few who have struggled with fevers and symptoms for more than eight or nine days sought help from Wuhan hospitals.
In China, there is typically no primary health care and family medicine as we know it, but there are huge hospitals in their huge cities where patients report directly. That’s why the death rate among patients at Wuhan hospitals at the beginning of the epidemic was so frighteningly high.
7. Is the infection of the most vulnerable in Wuhan hospitals early on in the epidemic the sole reason for the high initial death rate of COVID-19?
It isn’t. The epidemic seemed even more dangerous at first, as it created a great deal of pressure on hospital intensive care units, which were unprepared for this infection. As a result, all severely ill patients could not receive intensive care. This further increased the mortality rate at the beginning of the epidemic. That’s why the Chinese have started building new hospitals – to have sufficient capacities to be able to provide intensive care and to move all those infected with COVID-19 away from other seriously ill people who are sick because of other diseases, who are at the highest risk of dying if they do become infected.
Based on this, it should be understood that the total number of those infected with COVID-19 in Wuhan was much higher than what was confirmed by health statistics. Specifically, only those with coronaviruses who were eventually admitted to the hospital were confirmed to be infected and were tested for the new virus there. They are by no means representative of all those infected with the new coronavirus in Wuhan.
Their mortality rates cannot, therefore, be mapped even in terms of the population of the total number of those infected with coronavirus in Wuhan, let alone the entire population of Wuhan – ie, all infected and uninfected people. Therefore, it’s completely wrong to look at the number of confirmed infected and the number of deaths on the Internet and divide the number of deaths by the number of confirmed infected people and draw any conclusions from that.
8. Why does the number of infected and deceased people on the Internet, which is constantly being updated, give a wrong impression about the death rate of COVID-19?
If the deaths are divided by the confirmed number of infected people, then both the numerator and the denominator are completely wrong when it comes to calculating the actual death rate. Even deaths in the numerator are wrong because if we monitor the confirmed infected and those who have died in real time, that is, day by day, it can be understood that a great many infected people haven’t even had a chance to either recover or die.
People in intensive care will die for days, weeks, maybe months, which is why the death toll in numbers will increase over time. In doing that, some future number of registered deaths, as the numerator, will increasingly correspond to the current number of registered infected persons, as the denominator. The mortality rate of “deaths through confirmed infection” will then no longer be 2 percent or 3 percent, but may increase over time, perhaps to 6 percent or 7 percent.
Therefore, to say that “3 percent or 4 percent of those confirmed to have been infected so far have died” isn’t really wrong in itself, which is what the World Health Organisation did. But what it missed is explaining that this mortality rate among confirmed infected people is quite unrepresentative of the mortality rate among those infected, which is much lower. It wouldn’t surprise me, as an epidemiologist, if it is up to ten times smaller, maybe more. This could ultimately make COVID-19 a less deadly and dangerous disease even than the common flu.
9. Can you be sure that the total number of infected people is much higher than the number of registered infected people, is there any evidence for this?
Given that the virus is new and unknown, this is a key question. Unfortunately, the possibility that this virus is quite different from known ones must also be allowed. It may be that the rate of deaths among confirmed infected people is only 3 to 5 times lower than the death rate among the number of all infected people, and not ten or thirty times lower. The only sure thing is that the number of confirmed infected people certainly didn’t quite equal the number of infected in Wuhan. The current global totals for COVID-19 are still largely determined by what happened in Wuhan at the beginning of the epidemic, since about two-thirds of cases worldwide still originate in Wuhan to this day.
That’s why I’ve already explained on Sunday at 2 that the mortality rate among confirmed infected people is not so important to us because it’s a subset of the most severe patients. You should know the mortality rate among the total infected people. However, no one can know that at this time, because at least 100,000 Wuhan residents would need to be tested for this and then the presence of antibodies against coronaviruses should be detected.
Accordingly, we’d also know the proportion of people who got over it without ever even seeing a doctor. So far, no one has conducted these studies because the health system was preoccupied with the diagnosis of coronavirus in hospitals and even struggled with it. It’s now known that during some days of the outbreak, while it was spreading, there were not enough tests for all those who had symptoms.
However, the first additional evidence is beginning to emerge. The first is the report of an international panel of experts who visited China. They concluded that when looking at just about all cases across China that were reported after February the 1st, when the identification of all those infected was significantly improved, and hospitals were better prepared for the epidemic, the mortality rate of all cases that came under health surveillance and were tested dropped to 0.7 percent.
For all those skeptical of China’s data, we’ve also received reports from South Korea. In that country, the authorities have really done their best to aggressively test people, seek out all those infected and isolate them and treat them. In their analyses to date, the death rate of all infected people has been slightly above 0.6 percent. Both of these figures could increase slightly, but not really significantly, if they also included those who could die over time, and are currently counted as infected, but at such a low rate of death, there won’t be as many. It’s more likely that many infected people remain undiagnosed and the rate is actually even lower.
Another interesting recent new source is the study of more than 1000 COVID-19 patients followed up right up until the end of the infection, collected from over 500 Chinese hospitals, published in a top scientific journal. It showed their mortality rate of 1.4 perent. However, it was not all those infected again, but those who requested hospital treatment, and therefore it should still be at least two to three times less among all those infected.
Thus, it appears that data from very different and increasingly reliable sources are starting to converge to the values I predicted on Sunday at 2 a week ago, i.e. 0.5 percent to 1 percent. Because of all of the above, US President Donald Trump is most likely right to say that number is certainly less than 1 percent, and he believes it could be well below 1 percent. Everything we know about epidemiology and previous pandemics gives us hope that this could be the case.
10. Can anyone in a country be infected with a coronavirus? If so, would the death rate of 0.5 percent or 1 percent be applicable to the whole population then?
The virus will not succeed in infecting just about everyone in Croatia for a variety of reasons. The front line of defense is currently anti-epidemic measures. All those who may be infected are being tested, and then COVID-19 patients and all their contacts are isolated.
These measures significantly slow down and prevent the spread of the virus in Croatia and buy us some time. It’s of utmost importance that the number of patients doesn’t increase too quickly, in order to enable the staff of our health care system to provide quality care to all patients, and if necessary – intensive care. In the absence of these measures, there would be an exponential increase in the number of infected people, which would soon become intolerable for the health system. We’re also protected by our geographical dispersion, ie, there are many people living in smaller towns and settlements. A large number of them will probably never be entered by an infected person.
Furthermore, as people become infected and get over it, they should become immune to the virus. As a result, there will be fewer and fewer people the virus can transfer to. At some point, the number of new people that infected people can spread coronavirus to will decrease to an average of less than one. This will limit and stop the epidemic itself. That’s the reason we vaccinate – to disable the virus, even if it infects some unvaccinated people, it has less options for further spread. Specifically, some people will already be immune to the virus and their bodies will reject it if the virus tries to get into them. Many processes in nature are self-limiting in a similar way – forest fires and epidemics.
Furthermore, in the Sunday at 2 broadcast, I also explained why the finally determined death rate among all those infected should not be directly mapped to the entire population of a country, in order to estimate the possible death toll. The first reason is that the virus mainly affects the elderly. That’s why this established rate of death among all those infected can be projected only on the elderly, but not on young people and children. Young people and children rarely get sick and their death rates are much, much lower. This further contributes to the diminishing potential of the virus to cause a very high number of COVID-19 casualties.
11. Should we then fear the COVID-19 pandemic, and if so, how much?
The situation should be taken seriously and people should be cautious, but there’s no reason to be overly afraid, there’s especially no reason to panic. I understand that many people are afraid of this pandemic because they probably think we’re in a completely unfamiliar situation, so anything could happen. But it’s unlikely that much could happen for which science could not find explanations and answers, and the epidemiological services responded in a timely manner. Although it’s not good for a serious scientist to try to predict anything about the spread of a completely new and unknown virus to the entire human population in the world and to predict each individual event, we have in recent weeks collected enough information about the new COVID-19 virus for at least some predictions.
If the new coronavirus completely spreads across Croatia over time and manages to circumvent the many prevention measures currently in place, its casualties should be at least roughly comparable to the deaths from flu or road accidents in the same period. This means that some healthy caution is advisable. This caution is reasonable as long as it is on the same level as the fear you may feel when sitting in a car and preparing for a longer trip, or when you hear on the news that a more severe form of influenza has arrived in Croatia.
But many wonder why coronavirus is written so much about and why it attracts such a level of attention. This is because flu has been a well-known disease for decades, it comes back every year and we have experience with its manifestation in tens of millions of patients worldwide, we know how to develop vaccines against it in advance, and we’ve started to get the first somewhat effective drugs on the market. Unlike the flu, the new coronavirus is unknown to us and we’re most cautious about not being unpleasantly surprised. At the same time, the most vulnerable among us, who are already seriously ill or very old, aren’t vaccinated, as is the case with the flu, so this new disease can kill more easily.
12. Is it now quite clear that COVID-19 is a significantly more dangerous virus than the flu?
This question has constantly been being raised since the beginning because many are looking at various figures without a deeper understanding of their background and are comparing the incomparable.
First of all, the general public underestimates how dangerous and serious the flu actually is, especially for the most vulnerable, the elderly and the already ill. In the world, influenza causes between 250,000 and 650,000 deaths annually, depending on the strain of the circulating virus. Different strains can cause milder or more severe symptoms, and the virus mutates year after year. However, we try to prepare those most vulnerable before the flu season begins.
Therefore, the number of deaths from influenza is reduced by preventive health intervention, ie, vaccination, and this can’t be done with the spread of COVID-19. This is the first reason why the flu seems less dangerous, but it may be no less dangerous, it’s just that we protect the most vulnerable. In addition, flu vaccinations make it more difficult for it to spread among the population because there are fewer options for it to transfer to the uninfected. Due to the slower spread, new cases are slower to emerge and the health care system has time to deal with them properly, especially if they require intensive care.
Another reason is that the number of deaths directly from the flu is several times lower than the number of deaths indirectly from the flu. Influenza is often not cited as a direct cause in statistics on the causes of death, if it has merely led to the exacerbation of some of the long-present chronic, underlying disease. These chronic diseases are then cited as the primary cause of death, and not influenza. Therefore, the actual role of influenza in total annual mortality is often significantly underestimated. It could also be several times higher if the cause of death were reclassified at the end of each year, given the increase in deaths from chronic diseases during the flu season.
The third reason is that we have a much better idea of the total number of people truly infected with the flu than we do with coronavirus. This is because influenza is a disease that is typically managed around the world within primary care, after which patients are referred to home care and only the most serious cases end up in hospital.
Due to the obligation to report to the central registry, as well as for sick leave, the total number of people infected with influenza in the population, ie, the denominator for death rates, is much better known to us than the coronavirus. COVID-19 has so far been diagnosed and treated exclusively in hospitals for severe cases. Their estimates of death rates include patients suffering from ”hospital outbreaks”, which have spread to the elderly, the sick and the immunocompromised.
From all of this, it should be concluded that the rates of death from influenza, as a very dangerous viral disease, have been mathematically reduced compared to the current reports of death rates for coronaviruses for the three reasons I mentioned. The first is to vaccinate those most vulnerable to the flu before the flu arrives. Another reason is that health statistics don’t record the majority of flu deaths as deaths from influenza, but because of the exacerbation of pre-existing underlying illnesses such as cardiovascular disease, diabetes, malignant tumors and other things.
The third is that the denominator we use to calculate the death rates from influenza is much closer to the total population actually infected, while the denominator for coronaviruses is not yet known with sufficient certainty. Epidemiologists, from experience with other respiratory viruses, know that all events in hospitals that affect among the most vulnerable, should by no means be mapped and placed alongside the healthy. However, the general public who is not in the profession cannot have a good sense of this huge difference. That’s why all death rates from the number of people infected with the flu are not currently comparable to all the death rates of coronaviruses currently being managed.
While the general public, on the one hand, underestimates the risk of influenza for three reasons, it is also easy to overestimate the risk of the new coronavirus due to its intense media focus. If influenza in Croatia was monitored in this way each year to report on each infected person and their influenza testing, almost every day at least one person in Croatia would die directly from the flu during the winter months, and three or four more would die indirectly. Then the public would realise how dangerous the flu really is and how reasonable it is to be vaccinated against it.
Therefore, it still doesn’t seem possible to me, at least at this stage of the pandemic, to decisively state which of the two diseases is inherently more dangerous to humans or which will cause more deaths this year. Flu will, at least apparently, cause fewer deaths because the most vulnerable go for vaccinations, and many of the deaths it causes are not attributed to it in health statistics. COVID-19, in turn, will cause fewer deaths than it could due to epidemiological surveillance, the prevention of its spread and possible severe quarantine, and it may also have seasonal characteristics and simply disappear with the arrival of late spring.
13. Are such strict quarantines justified?
When we have no other means of defending ourselves against the new virus, all we can really do is retreat indoors and prevent the virus from travelling from infected to healthy individuals. People generally don’t have an intuitive sense of exponential growth.
If each newly infected person infects just one more person each day, the number of newly infected people will increase from 2 to 16 during the early phase, which doesn’t seem like a big increase. A little later, it will jump to 1024 infected people from 128 over the next three days, and that doesn’t sound so terrible either. But there will also come four days in which the number of newly infected people will increase from 100,000 to 800,000.
When China saw that the COVID-19 epidemic was out of control and entered that explosive phase, it immediately cut off Wuhan and then fifteen other cities from the rest of the country. In addition, it ordered that the population within these cut-off areas stay in their apartments and not leave. It was an unprecedented measure in human history – tens of millions of people were quarantined for weeks. Everything stopped.
However, this measure produced excellent results and China could stop the death toll of less than 5,000, although the epidemic found it unprepared and the virus spread to just about every province. A recent report from a World Health Organisation commission made up of 25 international experts visiting China concluded the following:
“The very bold Chinese approach to preventing the rapid spread of this new respiratory virus has changed the course of a then rapidly escalating and deadly epidemic. Faced with an unknown virus, China has implemented probably the most ambitious, agile and aggressive effort to combat infectious diseases – ever. This uncompromising and rigorous non-pharmaceutical measure of ordinary quarantine in curbing the transmission of COVID-19 virus in multiple contexts is now providing us with key lessons in planning a global response.”
14. What happened on the Diamond Princess ship, which is also isolated? It appears to have a death rate of more than 1 percent for those infected. Isn’t that very informative for scientists?
I can only say that this may be because, on these large ships, people are mostly older, because one should look at the age and gender structure of passengers, which, I believe, would explain at least something more. Also, it is quite possible that a mutated version of the virus, which is somewhat more dangerous, also enters into such a pocket, and such isolated groups emerge in which the disease actually ran a more severe course. This is not impossible, but it also isn’t likely that it can be mapped to the entire population of a country.
The virus, now spreading through the human species, continues to mutate in order to adapt to us as quickly as possible. According to previous epidemiological experiences, many of these mutations should make it less dangerous for our health, as they will be better adapted to us in this way. However, some random mutations could make it more dangerous, and we need to be on our guard until we get better acquainted with it and the pandemic is over. It’s unlikely that the new coronavirus will mutate to become significantly more dangerous than it is now, but we’ll only be able to assert that for sure when the pandemic is over.
15. What’s happening in Italy and Iran? Does COVID-19 behave differently there than it does in other countries? Could the development of a mutated, more dangerous variant of the virus be the reason?
These are very difficult questions to answer until we get more quality data from both countries. In principle, it’s possible that the first entry of the virus into a new country may be in the body of an infected person, in which the virus has mutated into some more severe form. If all further cases come from this mutant and a more dangerous virus, then in these countries, the situation may initially seem more difficult than elsewhere, until other carriers emerge. In population genetics this development is known as the so-called “founder effect” – the effect of the founder. However, both of these countries may also have different explanations.
The reason why the rate of deaths among infected people in Italy appears to be very high is because even there, the disease spread in small-town hospitals which were completely unprepared for the epidemic, and among the elderly who are at much greater risk of dying if they become infected.
The death rates in hospital outbreaks among older, sick, and possibly immunocompromised people will be much higher than those in the community, among healthy and younger people. Among the top 100 deaths in Italy, almost all people were over 60 years of age and had underlying illnesses. That’s why the mortality rate seems so high there, but it just isn’t representative of the entire population. Seasonal flu would probably have done similar damage if many had not been vaccinated against it. But it’s also possible that there are many more cases in the population than previously thought because the virus has been spreading for a long time. In Iran, however, the situation is unclear so far. The most likely explanation, too, is that there are already significantly more cases of infection than was imagined among the population.
16. Is it possible that coronavirus may surprise us and ultimately prove significantly more dangerous than seasonal influenza and kill more than one million people in the world, or even several million?
If COVID-19 proves to be significantly more dangerous than seasonal influenza, then one million deaths worldwide could indeed be expected, perhaps significantly more. Unfortunately, such a scenario is still possible in principle with a virus that is new and unknown to us, for a variety of reasons. Because of this, all experts in the field, including myself, are constantly urging people to take caution, but without the unnecessary panic.
In which scenarios could the situation become much more difficult? Firstly, most epidemiologists, based on their experience with previous epidemics and pandemics, expect the COVID-19 mortality rate to fall well below 1 percent when the death toll begins to be shared with a better estimate of all infected people. However, the virus is new, so it’s possible in principle for this specific virus that the number of infected individuals not registered may not be as large as epidemiologists would expect. This would come as a surprise to science and would indicate a different nature of this virus.
The new coronavirus causing COVID-19 is somewhat similar to that caused by SARS. The SARS pathogen, however, had an extremely high death rate among all those infected. If the total population infected is found to be higher than the registered infected population by only two or three times, and not by at least ten times, then the death rate of those infected with COVID-19 could be significantly higher than the flu.
Combined with the lack of a vaccination, because we don’t have vaccines for it, it would lead to a significantly higher number of deaths than the flu. However, such an event will be prevented by measures of isolation of the patients and their contacts, as well as by quarantines, which aren’t applied to the flu. We also hope that the passage of winter and the arrival new seasons will become our allies, which will slow down or completely hinder the further spread of the virus.
Furthermore, the virus could spread to infected people in some of its more dangerous forms, as well as in milder forms. Previous experiences with epidemics have shown that mutation into milder forms is more likely, but mutation into more dangerous forms, or those that are more easily spread, isn’t impossible either. In some countries, such a variant would increase the death rate locally compared to other countries or accelerate infection.
This would put their health systems in a really difficult situation as intensive care units would soon become overloaded. With poorer care available, the death rate of all those infected would increase further, with the collapse of part of the health system. It’s also a very tricky scenario in which many healthcare professionals would become infected over time in providing care to patients, which would make the situation worse.
Therefore, currently, perhaps the most important citizens of Croatia are all those healthcare professionals who work in hospitals for infectious diseases, especially in their intensive care units. They should be protected from work overload but also from coronavirus infection by their patients. With the increasing number of infected people, the demand for quality intensive care, respirators and ECMO devices for extracorporeal oxygen enrichment and the doctors and nurses in these wards will become the “bottleneck” of the health care system, which should be amplified and further strengthened before they come under increased pressure.
The worst-case scenario imaginable to epidemiologists right now is the entry of some more dangerous, mutated version of coronavirus into one of the very poor countries in the world with a poor health system. Such countries cannot implement satisfactory quality epidemiological surveillance measures. Then, a more dangerous version of the virus would infect a large percentage of the country’s population relatively quickly. Panic would ensue, probably also a black market for the transport of migrants to other countries. Then COVID-19 would start to expand uncontrollably and in a whole new way.
In the event of any of these unfavourable developments, which are all unfortunately possible, though not likely, we’d need a completely new protection strategy. Each country will have its own approach. When the death toll in each of the affected countries begins to rise so much as to cause fear among the population, people will become more willing to take much stricter measures. In such a case, more and more countries will resort to a “Chinese” solution that has proven effective in Wuhan – declaring large, very strict quarantines. It’s essential to buy time in such quarantines so that health systems don’t become overburdened and to anticipate the end of winter and the possible seasonality of this virus, which could then begin to spread in a weakened manner or disappear altogether, at least until next winter.
17. With these reasons for caution and adverse scenarios, is there any reason for possible optimism?
There are at least several reasons for optimism. First of all, epidemiological surveillance and “front lines of defense” are currently in place throughout the European Union. If it works well in most countries, it’s possible that their outbreaks will be controlled and not go into a phase of exponential growth in the number of cases. In the most favourable scenario, with this retention, this coronavirus would show seasonality and slowly disappear from circulation with changes in nature characteristic of late spring and summer. However, this is the most favourable scenario, in which the final death toll would be much lower than that already caused by the flu this year.
However, if the front line of defense and epidemiological surveillance is broken through by the virus, then governments will resort to strict measures to ban assemblies and organise quarantines, as the Chinese did. Several models done in recent weeks indicate that strict quarantine should completely suppress the spread of this coronavirus within three months. This is exactly what we’ve already seen in China. That’s why it seems to me that one great positive lesson of this pandemic is that humanity today would be able to survive even more dangerous infectious diseases than COVID-19 with strict quarantine, in which people would remain until scientists developed vaccines. This is really a new situation that has shown us this.
Finally, the tireless work of numerous scientists currently testing over a hundred drugs against this virus, as well as at least eleven experimental vaccines, should be noted. It is also impossible to get recommendations on the use of medicines in the foreseeable future, and vaccines should become available over time. In this unusual situation, these are all unknowns that could at some point become important and make a significant difference.
18. With the effectiveness of quarantine in China, can we draw any lessons from this pandemic?
We should always strive to find something good in all the bad things that are currently happening to us. I hope from this that many people will finally realise how dangerous flu is and start to get vaccinated against it. Each year, the flu kills between 250,000 and 650,000 people worldwide.
In China, which is one-sixth of the world’s population, the death toll from COVID-19 could be stopped below 5000 by the Wuhan quarantine. If all other countries could implement anti-epidemic measures like China, then the death toll from COVID -19 could be at most six times higher, ie, up to 30,000. That would be ten times fewer deaths than the total number of deaths caused annually by seasonal influenza. Unfortunately, many countries will not be able to follow China’s example closely and will have uncontrolled outbreaks if the warmer season doesn’t stop the spread of the virus.
Furthermore, if the virus continues to spread throughout 2020, it will demonstrate in a very cruel way how well the public health systems of individual countries function. It will be possible to produce performance charts for each country in controlling this new infectious disease, given the population size and age structure. These will be very important lessons to learn in preparation for a future pandemic, which could be even more dangerous.
Additionally, the virus generally spreads by contact. This means that it’s good to be reminded that hands should be regularly and properly washed during epidemics, you should avoid touching surfaces that many people touch (knobs, handrails, ATMs), avoid shaking hands, keep at least two steps away from people who have symptoms of respiratory infections, and it’s also advisable to regularly ventilate your living quarters. It’s also helpful to work to strengthen your personal immunity with sufficient sleep, exercise and good nutrition.
19. Are there any real surprises for science related to this pandemic, at least for now?
Very few [surprises], I’d say. I explained why it’s no surprise that after the previous six coronaviruses, the seventh has now manifested in a human. Nor is its spread rate a surprise, as there are both significantly more infectious and much less infectious respiratory viruses. It would be somewhat surprising for epidemiologists if the number of the total infected people in the population wasn’t significantly higher than the number of registered infected people, which would raise the death rate significantly above that of the flu. We continue to await the information of well-conducted studies on this.
Perhaps the biggest surprises are related to the clinical course of COVID-19 rather than the epidemiology itself. For now, clinicians in China have reported that registered infected people report to the hospital rather late, on average after as many as 9-12 days of home care. This may be a reflection of their fear of being admitted to the hospital during an epidemic, but it may also be an interesting feature of infections with slow development over other respiratory infections. Furthermore, fever doesn’t appear to accompany other symptoms of the disease in the first few days, making it difficult to locate cases by controlling people’s temperatures.
The media has also reported on the possible return of the virus after suffering from the infection in some cases. For now, it’s hard to know how common these cases are, and how many exceptions there are. Many viral respiratory infections always need to be “rested”, that is, to allow the body to recover for a day or two after the infection has ended, as it is unknown whether or not these infections can return if the immune system has not completely removed the virus from the body. But with all new and unknown viruses such surprises are possible, so one should be careful until the pandemic is over.
20. What are your closing messages?
In all the answers I have offered in this article, I’ve endeavored to convey an insight into the most likely scientific explanations for the abundant information that is published about COVID-19 in the domestic and international media. Over time, some of the likely scientific explanations may need to be modified in the light of new information. One shouldn’t forget that this is a new virus, so surprises and deviations from the expected scenarios are in principle possible. That’s why I emphasise that caution is needed, but not panic. I will monitor the further development of the pandemic.
Obviously, we need to prepare for a serious flu-like illness against which no one will be able to be vaccinated. Therefore, elderly people and those with underlying illnesses should be extremely careful because the infection is very dangerous to them. Having gained our first knowledge of COVID-19, we now need to concentrate on preventing the spread of the virus in Croatia and buying our time in regard to the weather until the arrival of warmer days, when we might be lucky enough to slowly stop the virus from circulating due to seasonality. Unfortunately, we can’t know that right now. From everything written, it should be understood that all measures of active searching and the isolation of patients and their contacts are justified.
These also include bans on gathering together larger groups of people, as well as possible quarantine if the epidemic starts to elude control. Particularly, older people should be looked after because the probability of a bad outcome increases significantly with age. In addition, those with heart disease, diabetes, or undergoing cancer treatment should take special care.”
This text was written by Igor Rudan and translated by Lauren Simmonds
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