COVID-19 Italian epidemic: quarantine with continuous spillover.

Background. In December 2019, an epidemic started in China caused by a new coronavirus (SARS-CoV-2), probably derived from bats. The Italian COVID-19 epidemic begins on February 21, 2020. Methods. We have collected and analyzed the data produced daily by the Civil Protection. We cataloged this data and produced tables and graphs to obtain dynamic curves for certain parameters. In addition, we also calculated the change in active cases with the following formula: (newly infected) - (new deaths) - (new recoveries). Findings. The number of total cases increased by about 40 times in the period 2-20 March (from 2,036 to 80,539). In the same period, the active cases increased by about 21 times (from 1,835 to 37,860). Active cases do not close quickly and remain open for a long time because those who enter in intensive care do not recover before 2-3 weeks. On March 19 Italy’s death toll surpasses China’s, becoming the country with the highest number of coronavirus deaths in the world. On March 26 the deaths in Italy are more than the double of those of China (8,215 deaths in Italy, vis 3,287 deaths in China). Conclusion. Poor management of medium cases, in accordance with WHO guidelines, inevitably leads to overload of intensive care units. The progression of clusters in Southern Italy is more pronounced in Campania, Puglia and Sicily. The main cause of the high mortality would be attributable to the collapse of the Italian health system.


Introduction
In December 2019, an epidemic started in China caused by a new coronavirus (SARS-CoV-2), probably derived from bats.Severe acute respiratory syndrome-coronavirus (SARS-CoV) enters the human cells expressing the ACE2 receptor which is a transmembrane protein with its catalytic site located outside the cell [1].ACE2 receptors are expressed in various human tissues, including lung and brain [2].COVID-19 disease is caused by SARS-CoV-2 and has a certain degree of lethality.Although the main cause of death from COVID-19 is severe pneumonia, which often leads to acute respiratory distress syndrome (ARDS), which requires hospitalization in an intensive care unit, the virus is neurotropic and the brain of patients affected from COVID-19 can become infected [3].It has been shown that in brain sections from SARS patients, the virus was detected almost exclusively in neurons [4,5].In addition, human neurons express ACE2 receptors [6].In studies conducted in mice it has been seen that the virus enters the brain via the olfactory bulb and can cause extensive neuronal infection which can lead to death due to damage of neurons located in cardiorespiratory centers [3].Furthermore, during the Chinese epidemic from COVID-19 it has been shown that some subjects could have an impairment of the cardiorespiratory centers and that the virus could access the central nervous system through the synaptic connections of the mechanoreceptors and chemoreceptors of the lung and lower airways [7].In Italy mortality is very high and cannot be justi ed by a different ACE2 expression, even if ACE2 expression increases with age [8].
In this paper, we presented a series of data relating to the Italian epidemic, and we analyzed some trends.Furthermore, we have identi ed and listed a series of errors and risks related to a not perfect management of the recent epidemic which is still in full evolution.In addition, we compared the four epidemic management models implemented by the UK, China, Italy and South Korea.They are management models that have critical points, and that deserve careful analysis.

Materials And Methods
We have collected and analyzed the data produced daily by the Civil Protection.We cataloged this data and produced tables and graphs to obtain dynamic curves for certain parameters.In addition, we also calculated the change in active cases with the following formula: (newly infected) -(new deaths) -(new recoveries).

Results
Progression of total cases.The total number of cases in the period between 2 and 8 March have more than tripled.In the period between 8 and 14 March the number of cases have still tripled, but they are 10 times those that have been registered on the 2nd March.In the period between 14 and 20 March, the total number of cases have more than doubled, and the number of cases that have been registered was 23 times the number of cases The progression of clusters in Southern Italy is more pronounced in Campania, Puglia and Sicily (Fig. 4).
Since the great exodus of people coming from the Northern and going to the Southern Italy occurred on March 7, and a similar exodus, but of smaller proportions occurred on March 14, it is still early to verify if the "measures of social distancing", suggested by the Italian government, have produced effects in terms of slowing the spread of the infection down.

Discussion
Before describing the characteristics of the Italian epidemic, we will describe the characteristics of four different management models.There are four different models that have been used to combat the COVID-19 epidemic.On our point of view, at present, the model that has been proven most effective is the one used by South Korea, followed by the Chinese totalitarian model.The other two models, the Italian and the English ones, are bad models not to be used in other countries, due to the critical issues they present, and which we will explain.

South Korean management
South Korea has been able to slow the progression of the epidemic down.In fact, on March 26, there were 9,241 total cases with 131 deaths, 4,144 recovered, 4,966 active cases, and 59 serious cases.They used a large testing program (tested more than 270,000 people) and they were able to isolate infected people and track contacts in order to quarantine them.New legislation has made it possible to overcome the limitations imposed by privacy laws (which exist in democracies) by giving health authorities the opportunity to reconstruct the movements of test positive subjects.Then, particular applications managed on social media allowed individual subjects to check whether they had contact with infected people [9].

Chinese totalitarian model
The military closure of the province of Hubei, the isolation of Wuhan city, the identi cation of cases and contacts, their mandatory quarantine and the environmental remediation systems in order to prevent the non-human spread, have made it possible to control the epidemic in about 4 months.
The English model: Herd Immunity or Herd Mortality?English prime minister's initial idea, supported by a team of scientists, was to not take any measure to contain the SARS-CoV-2 infection.This was not only a serious political mistake compared to a pandemic, but above all it was a defeat of science.In fact, only children have a great number of natural killer (NK) lymphocytes with adequate cytotoxic capacity, and with an ability to kill cells infected by the virus [10], without a preliminary presentation of foreign proteins by antigen-presenting cells (APC).In addition, these lymphocytes produce several cytokines that regulate the immune system [11], and the NK lymphocytes have immunological memory, like the T-and B-lymphocytes [12].
On march 22, 2020, the citizens of the UK gave a bad test of the perception of the danger, invading beaches and public parks.On march 23, UK Prime Minister Boris Johnson has announced that the country will go into a complete lockdown: Britons will be allowed to leave home only if essential.
The Italian model: quarantine with continuous spillover On February 19, the deaths in Italy exceeded those in China, even though the total number of positivity to the SARS-CoV-2 in Italy was about a half of the ones in China.This unusual virulence at the moment has no plausible explanations and we do not know if it can be related to the characteristics of the coronaviruses circulating in Italy and / or to certain characteristics of the people affected by COVID-19.However, on March 26 the deaths in Italy are more than the double of those in China (8,215 deaths in Italy, vis 3,287 deaths in China).

Clusters in Southern Italy
On March 8, a decree law is produced by the Italian government that limits traveling on Italian territory, but this announcement is made on the mass media one day before the publication of the same decree.This announcement completes a mass exodus towards Southern Italy that would have brought more than 100,000 citizens out of the Regions with the highest viral transmission.These citizens arrived at their destination on March 8 when in the 5 Regions of Southern Italy there were only 207 cases of test positivity for SARS-CoV-2 (Table 1).).This spillover changes the epidemiology and all the prediction models of the Italian epidemic trend, because it inserts a new variable, which on the one hand, leads to the expansion of the viral transmission, and on the other it shortens the duration times of epidemic, because it increases the number of citizens infected by unit of time, and the territories affected by the same viral transmission.In fact, a prediction model of the estimate of the number of patients [13] who could be affected as of March 15, led to an error in the estimate of about 23% (estimated about 32,000 infected patients, vis really infected 24,747).
According to ISTAT data, updated to 01/01/2019, the population of Southern Italy was represented by over 17 million inhabitants [14].Based on population density, Campania is at a higher risk of spreading the infection, while the risk of spreading is halved in Puglia and then decreases in other Regions, as indicated in Table 2.If the positive cases identi cation measures will work (number of tests), and contacts will be traced and placed in quarantine, the supplementary measures of "social distancing" will slow down the spread of the infection.
However, on March 26, the size of the clusters of Campania differ for a little from those of Puglia (1,310 vis 1,182) and this could be a bad sign for Puglia (Table 1).Since the duration of the disease in hospitalized patients is very long (about 2-3 weeks), the possibility of admitting all the people who need it to the existing intensive care units does no longer exists.Hence, many patients who have died of COVID-19 will not enter on o cial case series.For this reason, the real mortality is much higher than the current one which is already the highest in the world.

Italian mistakes
The rst news of Italian COVID-19 disease, in Northern Italy, were reported on 21st February 2020.Genomic investigation estimates that SARS-CoV-2 had started to circulate in the Northern Italian territories between mid-December 2019 and 30th January 2020.This research estimates that in Italy there have been different kinds of introductions of SARS-CoV-2, through people who travelled along the peninsula, and people who live in Italy.The phylogenetic investigations have established that one of the rst introductions, in the territory of Northern Italy, took place through a traveler from Germany.It can be reasonable to think that it took, at least, one month from the start of SARS-CoV-2 circulation in Italy and the rst communication of the case.In this length of time, virus transmission had no containment.

Genomic sequencing
Unfortunately, the failure to control genomic sequences by the Istituto Superiore di Sanità (ISS) has led to serious scienti c, political and economic consequences since everyone thought that Italy was the source of widespread contagion, while it was only the territory of multiple viral introductions that derived from infected subjects in many parts of the rest of the world and which essentially transited the territory of Northern Italy.This surveillance would also have served other countries to become aware that their citizens were infected and also circulated outside of Italy.
Andersen et al. [19] claim that SARS-CoV-2 is not a laboratory construct, in fact the receptor binding domain (RBD) in the spike protein (S) of SARS-CoV has ~ 96% identity with a coronavirus present in the bat Rhinolophus a nis.Spike protein binds to the extracellular part of the enzyme ACE2 (angiotensin converting enzyme 2) which is present in many tissues, including the lung and nervous system.In addition, SARSCoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1 / S2 subunits that sets this virus apart from others SARS-CoV [20].
The possible intermediate host has not been identi ed even if the primitive zoonotic event occurred in the bat.As of 11 March 2020, the sequences of 35 samples connected to the Italian COVID-19 epidemic are available in some databases.Only 2 of these sequences were produced by Italy [21].The rst sequence was produced by the Spallanzani Institute in Rome, and belonged to a Chinese woman infected in China; while the second was published by the Istituto Superiore di Sanità, in early March 2020, and derived from a sample obtained from an Italian subject.Before this publication, the genomes of two Brazilian citizens who fell ill on their return and made a trip to Italy had been sequential.The phylogenetic analysis conducted on these two sequences allows Brazilian scientists to hypothesize that there have been multiple virus introductions to Northern Italy [22].
Subsequently, the genome from the rst Nigerian patient with COVID-19 who arrived from Italy was sequenced.The phylogenetic tree shows that this genome was introduced in Northern Italy by some persons who came from Germany [23].Now, we think that the viral genome sequencing, from biological samples obtained from young subjects who fell ill with COVID-19, is necessary.

Environmental Stability of SARS-CoV-2
SARS-CoV-2 remains stable on plastic and stainless steel surfaces, while it is less stable on copper and cardboard.The viral titer drops over time [24].This work con rms that it is necessary to break down the non-human transmission of SARS-CoV-2, as they did in Asia.It is possible that one of the causes of the sustained transmission of the virus in Northern Italy is due to particulate matter.In fact, this territory is home of strong environmental pollution and there is poor air circulation, and in the particulates the viral particles can be adsorbed.If they remain in the particulates, they easily reach the lungs with the breath.

COVID-19: an easy diagnosis complicated and delayed by WHO standards
The WHO of 29 January 2020 do not allow early detection of COVID-19 disease, because the de nition of a suspect case is no longer valid during a pandemic [25].Since pneumonia due to SARS-CoV-2 infection develops about 8 days after the onset of symptoms, it is di cult to think that a suspect case is subjected to a speci c test the rst few days of illness, when the transmission of the viral load is maximum.In addition, other cases of illness can occur within 8 days of the contagion of any contacts due to the short incubation period (3-5 days).Furthermore, within these rst 8 days of illness this neurotropic virus can enter the central nervous system and produce damage to the bulbar and pontine cardio-respiratory centers.
Rather, attention should also be paid to the loss of the sense of smell and taste, which are symptoms reported by Italian patients in the early stages of the disease.

Misinterpretation of the rst tests
of February 26, some countries have published the number of tests and positivity rate for SARS-CoV-2.Our mass media said that we were the best of all in Europe to nd out the cases because we did more tests than the others.Table 3 reports these data.However, what we didn't understand, and the French imitated us, that the positivity rates were alarming.In fact, we had 5% positivity rate of the tests and the French had 2.2% positivity rate.Even the USA (3.1% positivity rate) did not understand that this percentage of positivity signaled a widespread circulation of SARS-CoV-2 in those areas subjected to tests.The negative role of Italian scientists on public opinion Many people were alarmed when the World Health Organization announced in March that COVID-19 has killed 3.4% of the people who have caught it so far a mortality rate far higher than not only the seasonal u, but also higher than earlier COVID-19 mortality estimates, which were around 2% [27].Some Italian scientists continue to say in the mass media that seasonal u is more deadly, even in the presence of over 200 deaths a day [28].O cial data on u mortality in the 2018-2019 season report 205 deaths [29].
On the single day of 13 there were 250 deaths from COVID-19 [30].Then, they say that the virus mainly affects the elderly, while about 60% of infections develop in the age group under 70 years.Even today, some scientists claim that this infection is like a common cold.These facts have heavily affected the civic sense of the population who, by trusting these experts, have exposed themselves to the infection, by not adopting the behaviors useful to avoid it.

Deleterious role of mass
To all of these negative factors we could add the disastrous communication, which has trivialized the harmfulness of this virus, like the typical phrase: "It is just a silly cold", followed by the phrase: "Death with the virus and not because of the virus", and to nish: "I will stay home".To promote all these slogans many guests, believed to be experts (who were not), had been interviewed on TV shows.In this way, the Italian population moved on from the slogan: "It is just a silly cold" to "The Italian quarantine", and while all of this was happening the damaging: "Death with the virus and not because of the virus" was being promoted.To still trivialize people's death, they proclaimed that only the elderly having previous illnesses dies.It happened to be believed that who died was actually "of a certain age".In other words, the age of death of the elderly from COVID-19 really corresponded to completion of life expectancy of the Italian population.But, we know that the virus is extremely virulent and it also infects young people who are in excellent health, and then nd themselves in acute respiratory distress syndrome (ARDS) and have to be admitted to intensive care.On March 25, the mass media, instead of focusing on the deaths caused by COVID-19, resume a television report from 3 years ago (RAI television) which concerned a scienti c article.Aided by a number of Italian scientists, they rushed to show that the SARS-CoV2 virus was not a laboratory construct.The work of Andersen et al.[19] had already been clear enough about the laboratory construct hypothesis, but in Italy nothing is ever certain.Menachery et al. [31], had just done an experiment using an SARS-CoV infectious clone to generate a chimeric virus that expressing the spike of bat coronavirus SHC014 in a mouse adapted SARS-CoV backbone.These authors had demonstrated that group 2b viruses encoding the SHC014 spike in a wild type backbone can e ciently utilize multiple ACE2 receptor orthologs, replicated e ciently in primary human airway cells, and achieve in vitro titers equivalent to epidemic strains of SARS-CoV.The relevant discovery made by these authors was not understood by the mass media and their experts, but they had told us 4 years in advance that a new SARS-CoV beta can use ACE2 receptors to enter human airway cells.

Political mistakes
Each political error is the result of one or more scienti c errors.Since in Italy there is no totalitarian regime like that of China, political decisions are suggested by scientists who occupy national health institutions, which in turn have been nominated by politicians.Public opinion is then heavily conditioned by groups of scientists who are often not informed about the speci c case, but constantly appear on talk shows.They are these groups that invented some slogans that distorted the perception of danger in the population and destroyed the already weak civic sense.Many scienti c exponents have close relationships with politics and often condition it directly, and indirectly because of the massive media exposure.So we used opinion leaders to harm us, and we hurt ourselves badly.
The only valid political decision to curb the infection was the military closure of Lombardy and Veneto, starting on February 22nd.But all this has not been done.Furthermore, an environmental remediation has not been completed to bring down the non-human transmission of SARS-CoV-2.In addition, the most serious fact is the "spillover quarantine" which implanted the COVID-19 clusters in Southern Italy, which will soon be the site of a new epidemic.
Dr Girolamo Giannotta, had done some interviews and participated in two talk shows and had produced some serious alarms that politics and health authorities have ignored.He had warned in advance that the spillover would produce the new COVID-19 clusters in Southern Italy, which has now happened.In addition, he raised the problem of eld hospitals that were to be built to house the mass of COVID-19 patients who would later be produced and could not be hospitalized in existing intensive care units [32][33][34].

Conclusion
Active cases grow consistently over time.This long stay in the intensive care unit does not allow all other patients, who fell ill, afterwards, to be hospitalized at the appropriate time, because there are no vacancies in these intensive care units.Poor management of medium cases, in accordance with WHO guidelines, inevitably leads to overload of intensive care units.The progression of clusters in Southern Italy is more pronounced in Campania, Puglia and Sicily.Since the great exodus of people coming from the Northern and going to the Southern Italy occurred on March 7, and a similar exodus, but of smaller proportions occurred on March 14, it is still early to verify if the "measures of social distancing", suggested by the Italian government, have produced effects in terms of slowing the spread of the infection down.The main cause of the high mortality would be attributable to the collapse of the Italian health system.Many subjects died without a diagnosis, they were not hospitalized and they did not have a diagnostic test while they were still alive.Many health workers have become infected due to a lack of personal protective equipment, in the exercise of their activity.The best management system was the Korean one.The biggest mistake made by the Italian, French and American governments is to not have understood that the percentage of test positivity was too high and indicative of an imminent health disaster.The British government has deliberately put itself in a losing position, and a 15-day advantage cannot be given to the SARS-CoV-2 virus.It is a failure to rely on the

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Figure 2 Distribution
Figure 2

Table 1
Total number of test positivity for SARS-CoV-2.

Table 2
[17]lation and inhabitants density in Southern Italy.Italian population, as of March 17, was 7.2%, much higher than in China (2.3%), and still higher than the one observed in other countries.The fatality rate was de ned as number of deaths in persons who tested positive for SARS-CoV-2 divided by number of SARS-CoV-2 cases[15], but the resulting number does not represent the true case fatality rate (CFR) and might be off by orders of magnitude.In other words, in just 7 days in Italy, the patients who died of COVID-19 are more than the ones who died in China in 4 months epidemic.If the two epidemics, Chinese and Italian, had ended on March 26, we could have calculated the CFR (the proportion of cases who eventually die from a disease) with the formula: deaths / cases.On March 26, China would have had a CFR value of 4.04% (3,287 total deaths: 81,285 total cases = 4.04); while Italy would have had a CFR of 10.19% (8,215 total deaths: 80,589 total cases = 10.19).In the absence of raw data, we cannot do any veri cation and we must rely on what the Italian health authorities publish.The collapse of the Italian health systemThe National Health System (SSN) is very well organized and provides free assistance to all Italian citizens from birth to end of life.There is a national territorial network where children are assisted by a series of pediatricians who can have 800 patients at the most, and can assist them until they reach the age of 16.Adults also have their own general doctors and have a maximum assisted limit of 1,500 people.Then, there is a territorial network of outpatient specialists and a Hospital network that works more e ciently in Central and Northern Italy.In addition, in the 12 night hours there is a territorial medical guard service for all citizens.On March 25, 40 doctors have died because of COVID-19[16].13generaldoctors in Lombardy have died (about 20,000 patients have been left without medical assistance), others are in quarantine (thousands more patients are without medical assistance) as the epidemic progresses.On march 25, There are 6,205 health-care workers positive to SARS-CoV-2 test[17].The main effect produced by the infection of medical personnel is the failure to diagnose COVID-19 disease, which associated with the di culty and / or impossibility of performing the necessary tests (staff not su cient compared to the gigantic requests), also due to the coronavirus positivity of the health personnel assigned to perform the tests, leads to death in a non quanti ed number of subjects without the suspicion of diagnosis, diagnosis and therapy for COVID-19 disease.The WHO guidelines state that patient with mild COVID-19 should only be treated with antipyretics[18].A case of medium disease not treated with chloroquine or hydroxychloroquine may evolve towards spontaneous healing or may aggravate, contract interstitial pneumonia and end up in an intensive care unit, if there is a possibility, otherwise it will die.This losing strategy increases stress on intensive care units, and increases otherwise avoidable mortality to a great extent.This is what happens in Northern Italy.But the primary cause of this collapse is political, because human resources lost over time have not been replaced.
The Istituto Superiore di Sanità (ISS) states that mortality in persons with con rmed COVID-19, in the 2-On March 26 the dead in Italy are more than double those of China (8,215 deaths in Italy, vis 3,287 deaths in China).