Jul 30, 2020

A Half-Year Summary of COVID-19 Pandemic – Spread, Course, Comparing Countries, Handling in the World, SARS-Cov-2 Virus and Its Origin, Consequences, and the Way Out

Spreading of the epidemic over the globe – at one look
The WHO started to report about the coronavirus on 21 January 2020, when 309 cases were allegedly diagnosed in China, including 6 deaths; no cases in other countries were reported by then. The numbers of diagnosed cases in 15 selected countries over the first half of the year 2020 are presented in Table 1, which further includes the numbers of new daily cases, the sum of deaths  and  new  daily  deaths  (extracted   from   the  WHO  web  here), as well as  the  number  of  tests  (extracted from the
WORLDOMETERS web here). The values per million people and some other parameters have been calculated for the table. The values are given in two-week intervals from Feb 4 till May 26, and later in one-month intervals till July 21. The countries are arranged according to the increasing number of positive cases per million people found by June 23. TABLE 1 SHOWS NEARLY ALL ABOUT THE 2020 PANDEMIC AT ONE LOOK.

The first cases outside China were reported on January 25, wherein the U.S., Asian and European countries reported between 1 and 20 cases in February 4. The maximal growth rates can be seen in the following dates: from February 4 to February 18 in Singapore; from February 18 to March 3 in Korea, Japan and Italy; and from March 3 to March 17 in Australia, Spain, Germany, France, Britain, Switzerland, Israel, Czechia, US, and Sweden. The fortnight maximal growth rates comprise between 4 fold and 100 fold jumps. The highest rate values are probably affected by a sudden increase of the available tests, and the lowest rate values result from the applied protection measures. The first deaths were reported in various countries with delays corresponding to the spread course, somewhere between February 18 and March 3, and even as late as on March 17 or March 31.

The disease is called COVID‑19 (COrona VIrus Disease starting in 2019). The virus is called SARS‑CoV‑2 (Severe Acute Respiratory Syndrome caused by Corona Virus, 2nd epidemics after the 2002 first SARS epidemics). Both the virus and the disease may be shortly called corona.

Viruses and coronavirus
Virus is a submicroscopic entity that replicates inside the cells of its specific host. It consists of one or more molecules of nucleic acid bearing the genetic information and protective proteins, forming a particle (virion) having dimensions usually between 20 and 1000 nm, sometimes enveloped with a lipid layer derived from its host. The viruses have probably coexisted and coevolved with all cellular living forms since the beginning 3.8 billion years ago and, as with all parasites, their harmfulness had to be kept at reasonable levels not to wipe out their hosts. Some viruses have been incorporated into the genomes of the hosts, and the incorporated DNA has sometimes acquired important functions in the host; about 8% of the human genome DNA originates from viruses. All living organisms have their specific viruses, from bacteria to plants and animals.

Viruses are divided into groups according to the type of their nucleic acid, which can be RNA or DNA, single-stranded or double-stranded (see Table 2); the Table concisely describes the properties of the viruses and the history of important discoveries. Coronaviridae is a family of single-stranded RNA viruses, positive-sense (it means that the RNA can directly serve as a messenger RNA to make proteins), enveloped, having one RNA molecule 26,000 to 32,000 bases long; their spherical virion is decorated with conspicuous protein projections which look like the solar corona in electron micrographs.

Coronaviruses, particularly betacoronaviruses, cause 10-30% cases of common cold-like symptoms and respiratory infection symptoms, caused also by rhinoviruses, influenza viruses, adenoviruses, human respiratory syncytial virus, and parainfluenza viruses (here, here, here). Newly appeared coronaviruses strains caused epidemics of severe acute respiratory syndrome (SARS) in 2002-2004 and in 2019, the virus of the former epidemic being now called SARS-CoV-1 (shortly Cov-1) and of the latter SARS-CoV-2 (shortly CoV-2). Virus CoV-2 differs from CoV-1 in 20% RNA sequences, and from common cold-like coronavirus HCoV-OC43 in 35% RNA sequences, but from the closest known coronaviruse, bat CoV RaTG13, only in 4% RNA sequences. Coronaviruses infect many mammals, like bats or cattle, and rarely pass to humans, but in the case of both SARS epidemics, as well as the MERS epidemic of 2012, the virus emerged from an animal reservoir, comprising in some stages the bats.

RNA viruses mutate quite quickly, usually collecting at least about 4×10−4 substitutions per site per year (here, here, here, here), which for coronavirus of 30,000 bases makes at least 12 changed bases per genome per year (one mutation per month), resulting in 4% RNA sequence change within 100 years. However, CoV-2 seems to mutate at least twice as quickly, but strangely the reports mostly note that CoV-2 mutates relatively slowly (here), or slower than influenza virus; however, two fold higher mutation was reported (here), or even four fold higher mutation rate has been shown (i.e. 4 per months, here). The combinations of various mutations make hundreds of existing strains, reflecting the history of their spread over the globe. Some mutations are believed to affect the pathogenicity or infectivity and other viral properties (here, here, here), so that differences in the disease course in various countries might be partially explained this way.

High RNA sequence variability may reduce the danger of cross-reactions with other corona species during testing, but may increase the danger of more false negative results. Also, the immunization against the new CoV-2 by previous corona infections seems less probable for the same reason.

As for the stability of the coronaviruses outside the human body, the virus can remain infectious for human lung cells even after 5 days on common non-biocidal surfaces (not hot or dry or sunny), including PTFE, PVC, ceramic tiles, glass, silicone rubber, and stainless steel (here).

Diagnosis, symptoms, treatment
Cov-2 is diagnosed by RT-PCR tests, which identify the viral RNA in a swab taken from patient’s nose or throat within several days after the infection till about two weeks; the enzyme reverse transcriptase (RT) firstly converts the viral RNA to complementary DNA and then multiplies the DNA by polymerase chain reaction (PCR) to enable its detection. During the first months of 2020, the tests were hardly available and great logistic problems were met in most countries. The numbers of performed tests started to be available for most countries from April (WORLDOMETERS).

The number of positively tested (see Table 1) surely reflected the increasing number of available test kits. Immunoassay detecting antibodies against CoV-2 proteins can reveal the previous infection. The sensitivity and specificity of all above tests are reported to be between 70-100%, usually at least 90%, depending on their origin (here, here). Chest CT was reported as a reliable diagnostic tool at the beginning of the epidemic, stating 98% sensitivity versus 71% sensitivity of an RT-PCR test (here). 
About 80% infected people have no symptoms or do not realize any symptoms (here, here, here). The patients having symptoms exhibit at least one of fever, cough, shortness of breath, and fatigue. In rare cases, blood clots formation is reported. Opacities on chest CT scans are observed. More serious reactions are observed mainly in patients with underlying conditions, including cancer, hypertension, pulmonary diseases, diabetes, obesity, or in immunocompromised patients and elderly patients. The reactions include acute respiratory syndrome, cytokine storm and lung injury. In a group of deceased patients, it was reported that 49% of them had 3 other underlying conditions, 25% had 2 other conditions, while 25% had 1 other condition, and only 1% did not suffer from a known other condition (here).

Treatment of serious cases includes blood clots prevention (e.g. by heparin) and improving oxygen saturation (ventilation), while measuring, among others, blood D-dimer and CRP; steroids (e.g. dexamethasone) or IL6 inhibitors for treating cytokine storm are employed, and antivirals are attempted, including remdesivir or hydroxychloroquine. About 2600 clinical studies associated with COVID-19 ran by July 16 (here), and more than a hundred companies have been developing a vaccine against CoV-2.

Person to person spreading rate
Table 1 nicely shows the exponential growth of the case numbers within the fortnight periods, when the tests were already available but yet without strong protective measures in effect; the growth seems to have an exponent of about 10 (see, for example, Australian case numbers between March 3 and March 31, being 33, 375, 4359). Tenfold increase of the cases within 14 days would approximately correspond to one patient infecting three people in one week if no restrictions are imposed (√10 = cca 3.2), which is a reasonable assumption in view of about one-week long infectivity. This is also supported by the spreading rate observed in Ecuador, where the first case woman arrived on Feb 14, being detected on Feb 29, and dead on March 13, resulting in 1595 cases on March 27 (here); if she was the only arrived case, we can calculate the number of people onto which one infected person passed the virus during the chain action there („reproduction number“) within one week, as we know that 1595 were infected within 6 weeks (15 days in Feb + 27 days in Mar = 42 d = 6 weeks); if one infects x people in one week, it will be x6 in 6 weeks (x6 = 1595), providing x = 3.4 (close to the above value 3.2), so that again one person would infect about 3 persons in a week without applied restrictions. The value of 3 people being infected by one person within a week, derived from Table 1, is in a good accordance with the generally estimated value of the reproduction number of about 3 for SARS-CoV-2 (e.g. here and here). After introducing protecting measures, the jumps in the total number of infected people within a fortnight period decreased to 4 or 2 or even less (see Table 1), corresponding to a reduced reproduction number of (√2=1,4=) between 1 and 2. For comparison, measles has a reproduction number of 15 in a non-immunized population, influenza between 1 and 2 (here).

Morbidity, mortality, lethality, infected population fraction (IPF)
The number of afflicted by a disease per million people (or per 100,000, or per hundred = %) is called morbidity, the number of deceased per million people is called mortality, the fraction of afflicted who die (in %) is called lethality. When there are clear symptoms, the said parameters can be simply determined. For example, the smallpox morbidity in the 1950th was 20 000 per million (= 2% world population), the mortality being about 12 000 per million, and the lethality being about (12000 /20000 =) 60% of the infected. However, corona seems to result in noticeable symptoms only in 20% infected people, so that the the reported number of positively diagnosed people is at least five times lower than the number of really infected people; the difference would be still higher since many even symptomatic people do not come to be tested, not speaking about up to 30% infected people who may be falsely diagnosed as negative (see here). From the beginning of the current epidemic, the real number of the infected (real morbidity) has seemed to be 10 to 100 times higher (here, here, here, here), usually about 30 times higher, than the number of positively diagnosed.

The population fraction in % which has been infected (sometimes called infection rate) is called here IPF for brevity (Infected Population Fraction). IPF is the sum of real morbidity in % and mortality in %, but IPF approximately equals to the real morbidity %, as mortality can be neglected relatively to morbidity in case of COVID-19. The value of IPF can be assessed from antibodies measurements, as they approximately show the population fraction having been exposed to COVID-19 from the beginning of the epidemics to about ten days before the measurement (it takes about ten days to form the antibodies). The few published antibody survey values, roughly corresponding to IPF, are incorporated in Table 1 (blue-marked “morbidity % by antibody survey” in the penultimate column); they are affected by a great error (and seems to hold only for a part of the country in some cases), ranging in various countries between 0.2% and 30% in April-May (the more updated IPF values can be estimated from the previous ones by increasing them proportionally to the increased apparent morbidity). Dividing these “real” morbidity values by the “apparent” morbidity values for the same date yielded a ratio (pink values M in the table, placed in the line of June 23) of between 2 and 93 for various countries, mostly between 10 and 50, which is consistent with the above approximation of 30 for the ratio of the real morbidity and apparent morbidity.

Table 1 gives, for selected countries, the numbers of positively diagnosed cases per million people (blue values in the 4th column), corresponding to the apparent morbidity; for example on June 23, the values range from about 140 per million (= 0.01% population) in Japan to about 7,000 per million (= 0.7% population) in the U.S. The apparent % morbidity should be multiplied by a factor of at least 10 to get a more precise assessment of IPF, as explained above, and in most cases even by a factor of 30. The numbers of positive cases per 100 tests (yellow numbers in the next to last column in Table 1) provide a closer estimation of IPF than the apparent morbidity (and approach the real value of IPF as the number of performed tests increases). The number of positive cases per 100 tests within the last month (red numbers in the next to last column) may also delimit the IPF estimation (after multiplying by the number of previous one-month measurement periods, as the value reflects only the last month infections). Of course, the more people have been tested, the closer the apparent morbidity in %, as well as the number of positive cases per 100 tests, is to the real morbidity. If employing the factor of 30, the real morbidities would be about 6000 per million (=0.6%=IPF) in Japan and about 340,000 per million (=34%=IPF) in the U.S. by July 21

Table 1 gives the numbers of deaths with corona for said countries, the mortality ranging from less than 4 to about 600 per million on June 23; the corresponding apparent lethality, called also crude lethality (= mortality/ apparent morbidity), ranges from 0.1% in Singapore to as high as 19% in France (black numbers in the next to last column). However, real lethality, L, is lower, as the real morbidity (really infected) is higher than the apparent morbidity as mentioned: L = apparent lethality/M. The estimated values of L are presented in Table 1 (bold black values in the last column). In most cases, the real lethality values fall into a range of 0.1% to 1%.

Measuring the fraction of people exhibiting RT-PCR positive test (fresh infection) and anti-corona antibody positive test (previous infection) in random population samples would provide a more accurate picture of the epidemic course. However, incomprehensibly and irrationally, all countries have hindered well-controlled, systematic and repeated population testing in random samples during the epidemic’ first half of year.

Herd immunity
It is supposed that the infection provides protection (immunity) against next infection for some time at least (here, here, here), even though the stability of the protective immunoglobulins remains to be determined (here). A sufficiently high fraction of the immunized people in the population, 60-90%, is supposed to render the population with “herd immunity”, as the disease spreading slows down and the disease eventually peters out due to the decreasing amount of susceptible people, in accordance with the spreading kinetics (here).

Roughly, the increase of the fraction of infected people with time (spreading rate), dP/Pdt, is proportional to the fraction of people that still can be infected, 1 - P/K (P is the number of infected people, K is the maximum number of people that can be infected):
dP/dt = P * R * (1 - P/K),
wherein the proportionality constant R, called growth rate, corresponds to the above reproduction number, if no protective measures are taken and at the beginning of the epidemic (about 3 for corona). If zero people are infected, P=0, the disease spreading rate is R; if half of the susceptible people are infected (IPF = 50%), the spread rate decreases to half; if all susceptible are infected, P=K, the spread stops; if a great part of the susceptible people are infected, for example 2/3 of them (IPF = 67%), the spreading rate will be 1/3*R, which for corona is (3/3=) about 1, and the disease is supposed to peter out (one person will infect only another one or less).

Despite dramatic news from Spain in May, only about 5% population seem to have been infected by then (here). As of July, the herd immunity has not been achieved in Britain either (here). Even the most liberal protective measures in Sweden have not resulted in more than 6% infected in April (here), but the value may have increased to 40% in the and of July. Iran reports about a third of the population infected on July 18 (it would be 93 times more than found by testing, i.e. M = 93, here). The results published on June 8 from Italian Bergamo show over half of people there having the antibodies against SARS-CoV-2 (here), which may explain the slowdown in the infection rate and possibly also the recently observed weaker disease course (here, here).

Excess deaths
It can be assumed that 1% of the population die in the developed countries every year, since people can be divided approximately into 100 age groups from 1 to 100 years old, and one of the group (the oldest) dies every year. Annual mortality observed in various countries indeed approximates 1000 per 100,000, i.e. 1% (here, here). For example in Italy, 600 000 people should die every year, which is 50 000 per month and 1600 every day. At the maximum, 917 people died with COVID-19 on March 27, which was about a half of the usual daily deaths; from March to July, during four months, 35,000 died with corona in Italy, giving a rate of 287 daily, which was one fifth of the usual daily deaths. It may be hypothesized that most of the deceased had underlying conditions and would die even without corona within several months, but this can be verified only in the future, by comparing the annual death rates.

When comparing the current weekly death rates with the death rates from the previous years, excess deaths have been observed in more countries, including England in regard to 65+ year old (here), the U.S. with observed 30% increase of weekly deaths (here), New York with 100% increase of monthly deaths (here), Europe with 50% increase of weekly deaths (here), Spain with 32% deaths increase during March-April (here), Germany with 40% increase in March (here), and Italy with 17% to 294% deaths increase in various Lombardy cities in March (here).

Many physicians have observed that the reduced service given in the emergency units and all other clinics during the corona epidemic have led to many excessive deaths. Some elderly have died because of the severed contacts with their families. The statistics will show whether it was coronavirus or these associated problems that will have caused more excessive deaths.

Age of the deceased
From the beginning, it was reported that the mortality sharply increases with age (here, here), while more than 70% dead are above 65 years, and less than 3% are without underlying conditions, so that less than 1% dead are younger than 65 without known conditions (here). The mean age of the deceased was reported between 80 and 86 in Europe and U.S. (here). I recalculated the mortality values per million of people in the age intervals for the Czech republic; it can be seen that the mortality increases approximately exponentially, with a common ratio of about 3 for the increased mortality per every 10 years of increased age (Table 3).

Comparison with influenza
As said above, the infection by COVID-19 results in about 80% asymptomatic or nearly asymptomatic cases; according to a British study, around 75% of flu infections in England in 2014 were symptom-free or so mild that they weren't identified through weekly questioning (here). According to the same study, influenza had been usually infecting 18% of unvaccinated people each winter, based on levels of antibodies in the blood; in May 2020, COVID-19 had infected 17% Londoners (here].

Both conditions are more dangerous for the elderly, ages 65+. However, while flu may be dangerous for small children (here), COVID-19 does not affect children (here); for example, more than 200 children up to 5 years old died in the Italian flu season of 2016 (here). Speaking of Italy, both flu of 2016 and CoV-2 of 2020 showed a higher excess mortality in Italy compared to other European countries (here). By July 21, COVID-19 claimed 245,000 diagnosed and 35,000 dead in Italy, providing apparent lethality of 14%. When correcting the value for the real number of infected (IPF), which has recently seemed to be at least 20% population (here), the lethality value would be 0.3%. The influenza season of 2016 in Italy afflicted 5.4 million people and took lives of 43,336 (here), corresponding to the lethality of 0.8%. In New York, 20% have been infected and 20,000 have died with CoV-2, which makes 1% lethality, versus 0.1-0.2% for flu (here).

The flu lethality is usually given in the range of 0.01 to 1%, the COVID-19 lethality values of many countries are mostly in the same range, as shown in in Table 1 (bold black in the last column).

For further comparison, the flu pandemic of 2009 infected between 700 and 1400 million people with 150-600 thousand deaths (cca 0.03% lethality); by the end of July, COVOD-19 has infected about (17 million confirmed x 30=) cca 500 million with 660 thousand deaths (0.1% lethality).

So far, the current corona epidemic does not seem to result in more serious consequences than recent flu epidemics, except for enormous economic damages

Comparing CoV-2 course and handling in various countries

Different reporting attitudes
It is generally accepted that people die rather with corona than due to corona, and mostly due to additional serious conditions. It is not clear how the death with corona is determined, and how the tested people are chosen, and different local rules have surely contributed to some differences. But the morbidity ranking is similar to the mortality ranking in Table 1, which shows to similar treatment of this issue in various countries (for example Switzerland is 7th in both parameters, and Israel is 10th in both parameters on June 23).  Singapore differs in this respect, being the first in morbidity and the 14th in mortality. Singapore may be more restrictive than other countries in defining and reporting the death with corona, but other factors may be involved. 

Non-democratic and developing countries started to report later than democratic countries, and probably did not have the same means and will to report real or precise data.

Protective measures and strategies
Restrictions were introduced in all countries, usually starting in the middle of March in many countries (see the 1st column of Table 1). In the countries closer to China, protective measures were initiated earlier, as these countries are more distrustful of the Communist China and more closely follow up what is happening there. The state borders were closed in many countries. Public gathering sites were closed in most countries at some stages, including restaurants, various shops, and sport facilities. Free movement of people was restricted to the essential activities, while introducing compulsory masks and distancing. Going to work was often restricted and working from home was encouraged. Lockdowns were implemented in several countries. Schools were closed, for some time at least, in most countries. Attending work and school was not much limited in, for example, Australia or Korea,  but the disease courses in these countries seemed to be better than in many other countries anyway. No closures were implemented in Sweden, but the numbers of ill or dead per million has not been much different there from Spain, Italy or Britain, who implemented stricter measures (see Table 1). Austria, Finland, Norway, Singapore have all reopened their schools earlier and none of those countries have seen an explosion of cases linked to schools; in Denmark, schools have been open since late April, masks have not been required, but the number of infected children has steadily declined (here).

Most countries started to test suspected patients by the RT-PCR tests, which were obtained only with difficulties in the beginning. The website WORLDOMETERS reported the numbers of performed tests around the world from the beginning of April. The measures further included quarantining the positively tested, as well as the persons coming to contact with them, and the persons returning from abroad.

No country (except for Sweden) defined any clear strategy, while the responsible politicians or experts tried to imitate the measures employed elsewhere. The plans usually mentioned “flattening the curve”, which meant spreading the infection to a broader time interval to avoid eventual shortage of hospital equipment and personnel; the measures, sometimes called “clever quarantine”, including following the citizens' movement and contacts, aimed at interrupting the infection chain in most countries (see for example "Strategic Objectives" of WHO, here). “Unnecessary” use of the PCR tests was discouraged in most countries, including for example Japan and Germany. The elderly and vulnerable were to be particularly protected, for example by limiting visits in the elderly homes.

In providing the protective means like masks or tests, defective products were often obtained from Chinese or other sources (here, here).

Different disease courses
A group of 34 mostly democratic countries are ranked in Table 4 according to several parameters characterizing the corona situation and its handling, including apparent morbidity (the placing of the country shows parameter a in Table 4), mortality (parameter b), apparent lethality (parameter c), and the inverted number of performed tests per million people (parameter d), the countries being arranged from the least afflicted to the most afflicted, and from the highest test number to the lowest. The countries have been also ranked by combining morbidity with mortality (parameter e), and by combining morbidity, mortality and inverted number of tests (parameter f). Table 4 shows the countries arranged according to parameter f (few ill and dead with many tests go first). Hong Kong has ended as the luckiest country or the most successful, Spain as the least lucky or successful in the table.

The ratings of a country according to morbidity, mortality and lethality (parameters a, b, c, e) often correlate with each other, as expected; some deviations can be seen, for example, in case of Hungary, Bulgaria, Iceland, and the above mentioned Singapore, indicating eventual different attitudes in characterizing the ill or dead. Also as expected, the number of tests does not correlate with the mortality.

Generally, Eastern hemisphere countries have come out better off in the current epidemic, even though being closer to the disease source, including Australia, New Zealand, Japan, Korea, Taiwan, and even Hong Kong. Also in the rest of the world, the Eastern countries, including Eastern Europe with Baltic states, are usually in better situation than Western Europe and America. Better preparedness of Hong Kong, Taiwan, Japan, Korea, and Singapore may be explained by their distrust toward their big brother, by earlier information, and by their traditional use of the respiration masks.

Some differences among the countries may be explained by different “inoculation”, i.e. by greater number of visitors from the afflicted areas, for example Italy having many Chinese workers and tourists. Some differences can be explained by calculating the real morbidities. For example, on June 23 Germany had the same apparent morbidity as Israel, and three times higher mortality (see Table 1), but when corrected for higher exposure fraction in Germany (higher real morbidity), probably caused by higher initial inoculation, the real lethality was similar in both countries, 0.05% and 0.1% for Germany and Israel, respectively. An analogous difference between France and Germany, who show the same apparent morbidities while France has 4.5 times higher mortality, is difficult to explain, but it may at least partially comprise more discipline and less hugging in Germany.

It was suggested that less extensive testing in Italy and other countries might be masking a number of cases with mild symptoms, compared to Germany, thereby overestimating the lethality in those countries (here); further, different testing methods are employed, in Germany elderly people who die are not necessarily given postmortem examinations for coronavirus, while in Italy reportedly everyone who dies is tested. Moreover, the elderly in Germany often do not live in larger families. In addition, the average age of those infected was lower in Germany than in many other countries; many of the early patients caught the virus in Austrian and Italian ski resorts and were relatively young and healthy, the average age of contracting the disease was relatively low in Germany as of April, at 49, compared to 62 in France and Italy. Germany has further one of the highest levels of intensive care beds per capita in Europe – 29 per 100,000 residents compared to 13 in Italy, 12 in France, 10 in Spain and 7 in UK (here, here), wherein the medical staff are regularly tested to prevent spread by them, eventually doing block tests which check swabs of 10 employees at a time and following up with individual tests only if there is a positive result (here).

Political factors might have contributed as well. One of them is the dismissive attitude of some leftist politicians, like Belgian Prime Minister Charles Michel (today's European Council president) who decided to destroy Belgium's entire "strategic stock" of 63 million protective face-masks in 2015 to use the stock space for accommodating migrants (here); Belgium now exhibits a morbidity between Spain and Britain, but its mortality is the highest in he world. In another case, the Spanish leftist government organized broad celebrations and a march on the Stalinist holiday of International Women Day in March, despite the corona danger (here). In February, the Florence mayor, social democrat Dario Nardella, encouraged the residents to hug Chinese people in the streets to “encourage them in their fight against the novel coronavirus” (here).

The CoV-2 virus mutates quickly, and many strains circulate around the world, surely contributing to the differences in the disease courses.

Different CoV-2 strains
Despite contradicting media reports, spread by the WHO (here), and possibly also supported by vaccine developers (here), the CoV-2 virus does not mutate slower than expected (see the paragraph "Viruses and coronaviruses" above). 

Coronavirus mutation rate and diversity have been studied, showing for example that a single base substitution can increase the mutation rate 20 fold (here). It is known that changed regulation sequences can accelerate the coronavirus transcription 100-1000 fold (here). Although thousands of known CoV-2 genomes have been sequenced from all around the world, clear links between the virus RNA sequence and its different behaviors in various countries have not been shown (see the below paragraph "Origin of SARS-CoV-2"). We are still waiting for comparisons of strains prevailing in various countries, including the differences in the RNA sequences and their effects on the virus properties

Inaccurate data
The reported values comprise some inconsistencies, seen also in Table 1 (question marks), sometimes caused by late or inconsistent reporting, and sometimes by other reasons.  Of 15 countries in Table 1, China exhibits the lowest number of both ill and dead (16th place in the table both in morbidity and mortality), in spite of being the first country in the pandemic chain. In the beginning, People’s Republic of China (PRC) reported some cases from its whole area, including the giant cities of Shanghai and Beijing (here). However, after the initial growth, the number of reported ill and dead people soon stopped and remained strikingly lower than in other countries, for example several times lower than in Japan or Korea, and by several orders lower than in the Western countries. China has later not related to the situation in other big cities except for Wuhan, and the reported values look improbable (and nearly impossible, see the nearly constant values of morbidity and mortality in Table 1); moreover, no information has been available about the number of Chinese tests till the end of June. China may have suffered by many orders more ill and dead people than reported, according to indirect signs (here). The data provided by PRC are not reliable, similarly to the data of other non-democratic countries, as was obvious in their values provided to the WHO. 

Origin of SARS-CoV-2
For years, the Chinese scientists have studied the bat coronaviruses (here). In 2015, the leading Wuhan coronavirus scientist, Dr. Shi Zheng-Li, together with several US scientists modified a harmless bat coronavirus to be capable of infecting the human cells (here); the work was strongly criticized (here) as a dangerous “gain-of-function” experiment.

In 2017, a Nature article reported about a laboratory in Wuhan cleared to work with the world’s most dangerous pathogens (Institute of Virology); the lab being part of a plan to build between five and seven biosafety level-4 labs across the Chinese mainland by 2025 (here). The Wuhan lab was built with the capacity to withstand a magnitude 7 earthquake, but the Western scientists worried that viruses could easily escape even without any earthquake in view of known repeated escapes from high-level containment facilities in China, including in Beijing. The article notes that transparency is the basis of the work in such labs, but it is missing in China, and the labs even raise worries about potential development of bioweapons.

In 2018, the U.S. Embassy in Beijing took the unusual step of repeatedly sending U.S. science diplomats to the Wuhan Institute of Virology (WIV), and then they dispatched diplomatic cables warning to Washington about safety and management weaknesses at the WIV lab, mentioning the lab’s work on bat coronaviruses and their potential human transmission representing a risk of a new SARS-like pandemic (here and here). During interactions with scientists at the WIV laboratory, the Americans noted the new lab has a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory; they also met with Shi Zheng-Li, the head of the research project (later called “Bat woman” by the media); her research was designed to prevent the next SARS-like pandemic by anticipating how it might emerge, but other scientists questioned whether Shi’s team was taking unnecessary risks already in 2015; in October 2014, the U.S. government had imposed a moratorium on funding any research that makes a virus more deadly or contagious, known as “gain-of-function” experiments.

Strangely, in September 2019, the Global Preparedness Monitoring Board of the WHO, comprising mostly Western scientists including Anthony Fauci, published a first “Annual report on global preparedness for health emergencies”, dramatically named “A WORLD AT RISK”, in which they “prophetically” warned about having to be prepared for the worst in a possible rapidly spreading, lethal respiratory pathogen pandemic. They wrote: “In addition to a greater risk of pandemics from natural pathogens, scientific developments allow for disease-causing microorganisms to be engineered or recreated in laboratories. Should countries, terrorist groups, or scientifically advanced individuals create or obtain and then use biological weapons that have the characteristics of a novel, high-impact respiratory pathogen, the consequences could be as severe as, or even greater, than those of a natural epidemic, as could an accidental release of epidemic-prone microorganisms” (here). It turns out that the epidemics started much earlier than admitted by the Chinese authorities, possibly already in August and September 2019 (here, here). It can be hypothesized that the above “prophetical” Annual report might have been inspired by first indirect indications. 

Incredible sloppiness of the work in the Wuhan lab was indicated by the reports about experimental animal appearing on the local meat market as some Chinese researchers are in the habit of selling the laboratory animals to street vendors after they have finished experimenting on them instead of properly disposing of infected animals by cremation, as the law requires, to make an extra cash; one Beijing researcher, now in jail, allegedly made a million dollars selling his monkeys and rats on the live animal market, where they eventually wound up in someone’s stomach (here). Wuhan scientists allegedly “did absolutely crazy things to alter coronavirus and enabled it to infect humans”, according to Prof. Petr Chumakov of Russia (here). Even Dr. Shi Zheng-Li inadevertantly admitted, in her interview for Scientic American in February 2020, that she had wondered whether the new virus could not originate from her laboratory (the interview was published in June, see here, line 20).

When rumors about a new virus started to circulate toward the end of 2019, Chinese scientists quickly published its whole sequence, its properties and its relatedness to other coronaviruses in two articles submitted to Nature (here and here). The first of the articles (received in Nature on January 7) managed to identify and totally characterize the “unknown agent“ of an unknown disease (the new coronavirus) in one patient within six days. The second article (received in Nature on January 20), co-authored by Zheng-Li Shi of Wuhan, analyzed several patients, and the authors searched for a new coronavirus, which they found and totally characterized within two weeks. Strangely, the second article also announces the existence of a bat virus, called CoV RaTG13 (known to them but not published since 2013), which has 96% homology with the newly discovered CoV-2.

The Chinese government tried to attract attention to the local meat market as to possible animal source of the new virus, in which the virus would have evolved naturally, mentioning snakes, bats, and pangolins (for example in both above Nature articles). The “natural origin” of the new virus was generally supported by the mainstream media and establishment from the beginning, an example being condemnation of any attempts to look for an artificial origin in Guardian on 20 February 2020: “Experts fear false rumours could harm Chinese cooperation on coronavirus” (here). The scientific establishment tries to reject the laboratory origin of COVID-19 too; for example, Nature in January 2020 (by retroactive adding their note to an old article, here), or Nature on 17 March 2020 (here). For example, Lancet of 7 March 2020 states that “We stand together to strongly condemn conspiracy theories suggesting that COVID-19 does not have a natural origin” (here). However, a research scientist of University of California at Berkeley, Xiao Qiang, said: “I don’t think it’s a conspiracy theory. I think it’s a legitimate question that needs to be investigated and answered... To understand exactly how this originated is critical knowledge for preventing this from happening in the future” (here and here).

Cov-2 virus comprises unique structural features. The RNA segment coding for the spike protein, which binds to the human receptor ACE2, was found to have an insertion of 12-nucleotides resulting in four extra amino acids in positions 681-684 of the spike protein (here); the authors believe these four extra residues, entirely unique to this human virus and not found in any other species, may have improved contagiousness of the virus. Additional elements may contribute to the virus properties; for example, the envelope protein E is very conservative in other coronaviruses, but in CoV-2 it seems different (here).

It is known, that a one-base change can increase the mutation rate of a coronavirus 20 fold (here); it is also known that changes in the regulation sequence could accelerate the coronavirus transcription 100-1000 fold (here). For example, the importance of the 5'-UTR for the coronavirus replication is known (here), even though I have not managed to find unexpected diversity in 5'-UTR of CoV-2 in comparison with other coronaviruses (here). However, changes in several other CoV-2 parts of genome might explain the virus's behavior. An ever increasing number of reports search for the links between various mutations and the new behavior features of the virus (here, here, here). The present day technology enables not only to radically change an existing virus, but even to synthesize a new virus entirely from scratch (here).

The origin of SARS-CoV-2 has not been explained so far, the same as the origin of SARS-CoV-1. The CoV-2 genome may have been artificially edited or not, but its escape from one of the Wuhan labs seems hardly refutable. Many publications relate to the mysterious origin of the virus (for example, here, here, here, here, here), and while not supporting a possible artificial intervention in its structure, their findings do not disprove such intervention, and still less an eventual lab escape. Hopefully, the non-intimidated scientists outside or inside China will eventually explain the origin of CoV-2 and make the Chinese government admit its errors (here). 

The attitude of politicians, media, and experts
As outlined above in the paragraph about strategies, leaders around the world took overcautious attitudes and have rather imitated the measures from elsewhere than prepared clear and efficient plans with local experts. Some politicians hurried to be the first in closing borders and restricting the movement of their citizens, others to introduce masks and distancing, and most copied at least something from abroad, while enjoying the role of saviors of their nations. Some countries decided to go for as broad testing as possible (but illogically without random sampling), others decided (illogically) to save on the tests. The rulers in nondemocratic countries preferred to ignore the epidemic, at least in the beginning. Experts who were invited to participate in the decision making seemed to be rather opportunists than scientists with broad horizons. Only a few countries tried to take a different course, particularly Sweden, by not insisting on too restrictive measures, but even they were not well prepared and underestimated increased mortality. With all the different attitudes, no clear correlation between any measures and results can be given, and it seems that it was the virus itself that decided the course of events everywhere.

In all countries it was logical and necessary to employ a part of the numerous tests for random population testing to determine the extent of infection, to know the fraction of the people who have already been infected (have antibodies) and also the fraction of people who are active (PCR positive). Any planning is possible only when knowing how many people are infected and still can be infected – but all the leaders and all the officials responsible for handling corona everywhere tried to avoid this random testing for ridiculous reasons. Nearly all countries had the goal of “flattening the curve”, i.e. to retard the disease spread and keep the number of hospitalized low, while possibly also interrupting the chain of infection (“clever quarantine”); however, no goals can be planned or checked without exact values obtained by random testing. The only reasonable preventive measure, with or without testing, has been protecting the vulnerable; all other restrictions were harmful; the damages caused to the economy are immense, but the social and psychological consequences of the lockdown are incalculable as well, including the forced isolation of the old people from their families, often resulting in premature death.

Nowhere in the world, the media employ intelligent people with technical education or at least with solid general knowledge, so that nowhere could the citizens hear any reasonable opinions, having to rely on what their politicians wished to babble – similarly in democratic and nondemocratic countries. Naturally, citizens in all countries took very seriously the frightening news about helpless Italian doctors and their dying patients, and so they obediently complied with all requirements, at least in the beginning. Media workers enjoyed playing experts and passing to the public the threatening news – together with many fake news. All kinds of experts also flooded the citizens with ever altering views, for example one day the coronavirus mutated quickly, another day slowly. Even the state leading experts usually turned out to be totally confused (Sweden, Czech Republic, Israel, etc.).

Only occasionally, dissenting opinions could be heard. One of the scientists who warned of hysteria was  pneumologist Dr. Wolfgang Wodarg, former Bundestag member, who spoke about “corona hype which, without due epidemiological evidence, caused damages to our freedom and personal rights through frivolous and unjustified quarantine measures and restrictions, employing the mainstream of fear mongers in labs, media, and ministries” (here). Similar tone was heard, for example, from a former Israeli Health Ministry director, Prof. Yoram Lass (here). They correctly noted that many scientists swam along, needing money, and showing their contribution and importance, while ignoring the facts about similar effects of seasonal flu infections.

As mentioned in the paragraph “Different disease courses”, while the pandemic started to spread in Italy, the leftist Italian politicians absurdly appealed to the people to show love for the Chinese and hug them in the streets wherever they meet them (here). Similar signs of love for the Chinese and the will to help them occurred in many countries, including Europe, U.S., and Israel (here). People’s Republic of China returned these signs of friendship by accusing the U.S. of bringing the new virus to Wuhan (here). A part of the material help, which had been provided to China at the beginning of the pandemic, was later sold back to the helping countries for exaggerated prices (here).

Who is WHO?
World Health Organization (WHO) has been publishing contradicting proclamations and recommendations, starting with arguing about the use of the term “pandemic”. Their texts are confused and confusing, e.g. mixing mortality with lethality (here), or showing many mutants around the world while stating that the virus is not mutating (here). When the only reasonable measure turned out to be wearing masks, the WHO decided against the masks (here, here).

For years, the World Health Organization (WHO) was managed by the representative of China, a country taking the 144th place of 190 in the list of countries arranged according to the quality of healthcare, followed by the last three years during which the WHO has been managed by the representative of Ethiopia – a country which takes the 180th place of 190 in the list (here). The WHO’s general secretary, Tedros Adhanom Ghegreyesus, used to be the leader of the terrorist organization Tigray People's Liberation Front (here); he is also known for covering up cholera epidemics in Ethiopia when serving as the health minister there (here). Although the budget of the WHO is paid by developed and democratic countries (22% is paid by the U.S. and 10% by Japan), developing or nondemocratic countries direct its politics.

China has special powers in WHO, which is indicated also by the fact that an important developed and democratic country like Taiwan has no place in the WHO. Not surprisingly, the WHO and its leader Adhanom decided that the most important element in the strategy against corona is to find all infected and isolate them (here), despite the fact that finding the infected is hardly possible when 80% people have no symptoms, and when most countries test only a small part of the population; so the mask-less strategy of the WHO would clearly result in more infected people who, however, cannot be located, so that lockdown of the Western world would last forever, and its economy would eventually collapse. This would be the result of the strategy promoted by Mr. Adhanom – a great friend of People’s Republic of China.

The status in the end of July
As of the end of July 2020, the 1st place in the number of CoV-2 cases per million people in the list of all countries was Qatar (39,000 = 3.9% population have been diagnosed positive), followed by (only the developed and democratic countries are shown, the numbers are rounded): USA (10th with 13,000 cases per million), Luxembourg (16th with 10,000), Sweden (18th with 8,000), Spain (22nd with 6,800), Israel (23rd with 6,700), Belgium (27th with 5,700), Iceland (32nd with 5,400), Ireland (33rd with 5,200), Portugal (36th with 4,900), Britain (40th with 4,400), Italy (44th with 4,100), Switzerland (46th with 4,000), Netherland (56th with 3,100), Canada (57th with 3,000), France (63rd with 2,800), Germany (69th with 2,500), Denmark (74th with 2,300), and Austria (75th with 2,300). In absolute numbers of the diagnosed cases, the 1st is US with 4.5 million, 2nd Brazil with 2.5 million, and 3rd India with 1.5 million (around July 27).

The case number for the whole world is between the values for the 79th and 80th countries (2,100 cases per million), showing that the developing countries have lower morbidity due to less intense travelling, and/or due to lower testing. For example, India, having 1,4 billion population, is 99th with 1,000 cases; China, where the pandemics started, having also 1,4 billion population, is 193rd with merely 58 cases per million (all the values are from WORLDOMETERS).

The list of countries according to the decreasing number of deaths per million (July 27) goes as follows: the 1st is San Marino with 1,240 (= 0.1% population), followed by: Belgium (2nd with 850), Britain (3rd with 680), Spain (5th with 610), Italy (6th with 580), Sweden (7th with 560), France (10th with 460), USA (11th with 450), Netherland (13th with 360), Ireland (14th with 360), Canada (22nd with 240), Switzerland (23rd with 230), Luxembourg (30th with 180), Portugal (31st with 170), Germany (39th with 110), Denmark (41st with 110), etc. The mean value for the world is 83 deaths per million and is placed between the 47th and 48th countries in the list. The biggest countries, India and China, are 99th with 23 and 163rd with 3 dead per million, respectively. In absolute numbers of the deaths, the 1st is US with about 150,000, 2nd  Brazil with about 90,000, and the 3rd is UK with about 45,000.

The most throughout tested are citizens of Monaco (97% of all people), followed by Luxembourg (3rd with 63%), Iceland (9th with 35%), UK (13th with 21%), Israel (18th with 17%), USA (22nd with 16%), Italy (34th with 11%), Czechia (57th with 6%), France (78th with 5%), Korea (97th with 3%), India (136th with 1%), Japan (159th with 0.6%), Taiwan (172nd with 0.3%), etc.

Assessments of the IPF values (as outlined in the paragraph "Morbidity, mortality, lethality, IPF")
provide the following estimation ranges for the infected population fractions in various countries by the end of July: 25-50% in Sweden, 15-30% in U.S., 10-30% in Italy (supposing that the reported values of 30-50% related rather to Northern Italy), 5-15% in Germany, 6-10% in Israel, 5-10% in United Kingdom, 5-8% in Spain, 5-8% in France, 3-5% in Singapore, 2-4% in Czechia, 0.5-3% in Japan, 0.5-2% in Korea, 0.5-1% in Australia. The data for China would suggest only 0.05-0.2% infected, again absurdly placing the PRC as the least afflicted country in the whole world.

If using the above IPF ranges for recalculating the lethality values, the following real lethality values are estimated (the red values of mortality per million from the 7th column of Table 1 are divided by the mean value of said above ranges and divided by 100): 0.3% in Sweden, 0.2% in U.S., 0.3% in Italy, 0.05% in Israel, 1% in Spain, 0.7% in France, 0.1% in Germany, 1.0% in United Kingdom, 0.1% in Czechia, 0.01% in Singapore, and 0.05% in Japan, Korea and Australia. Again, the lethality values by July are between 0.1 and 1%, not much differing for the values for flu.

In all countries (except for China, where the values are different from all other countries), the numbers of positively diagnosed people (apparent morbidities, see the blue values in the 4th column in Table 1) stopped the exponential increase by April-May, and continued to increase in a rather linear way, manifested as stagnating or decreasing increments of the new daily cases. In some of the initially worst corona-explosion centers, like Italy, Spain and Britain, the situation after the first half of the year seems to have slowly stabilized. However, the public pressure toward releasing restrictions seems to have resulted in the increased new cases, for example in the U.S. and Israel (called “a second wave”).

Everywhere the apparent lethality (black values in the last but one column in Table 1), as well as the numbers of new deaths, reached a maximum (in April for the number of new deaths and in May for the mortality) and started to decrease. Decreasing deaths may result from the improved intensive care (the personnel have learned to better provide ventilation and medication to difficult patients); it is also possible that the most vulnerable people started to protect themselves better, and further that the virus lowered its virulence (the most virulent strains of CoV-2 may have killed their hosts, and the most susceptible people have already been infected); lower motivation of the authorities to report the deaths cannot be excluded either. In any case, the virulence of CoV-2 seems to fade since June, at least in Italy (here).

In various countries, the disease infected between 1% and 50% people, mostly far from reaching the herd immunity. The available measures cannot eradicate the disease and, moreover, the restrictions will have to be moderated, in order to prevent economic collapse, so that the disease will continue in most countries in a similar way for many months to come. As of the end of July, the business starts slowly to return to its speed, even though many restrictions go on, including the movement restrictions between the countries (flights, tourism). The recession in the developed countries will comprise more than 10% decrease in the employment and the same decrease in the GDP within the first corona year.

Preliminary conclusions
An unexpected global problem of a pandemic, less lethal than most of known diseases, has demonstrated that neither the united Western world, nor any of the developed countries alone, are able to efficiently cope with new problems. No capable leader has appeared in any country; no existing political or scientific national or international body has come with usable ideas; no scientist or a scientific body sounded a reasonable plan sufficiently aloud so as to be transferred by the mainstream media to the public. As expected, the nondemocratic countries have even not been able to acknowledge what was happening.

No systematic population random sampling has been performed, as if an invisible hand of chaos worked against the Western society. The hospitals have reduced their activities, the elderly homes prevented contacts with family members, people have been dying for many reasons other than corona. The media have not provided scientific information but only frightened and confused the public (possibly except for Sweden). The politicians around the world showed incompetence, and even stupidity, for example when being surprised by trivial and expectable events, such as increased cases with increased testing or renewed CoV spread with released restrictions, or when they wondered "why to test people who are not ill".

The Western culture was able to eliminate hunger on Earth and to bring the man to the Moon, but it has not been able to face a mild disease that has spread out of China. This case will have to be studied well, since the humankind will hardly be able to face challenges like a global earthquake, a big asteroid strike, or a global Ebola-like epidemic, if the developed countries will not learn to optimally utilize the best science and technology in common actions.

Whereas the Chinese scientists were allegedly able to completely solve the enigma of a novel disease by examining several patients within six days (see their article in Nature here), millions of the world scientists have not been able to come with some concrete conclusions, even though having detailed information from millions patients, including thousands of CoV-2 genome sequences.

Only in war times were people locked in homes. But never during the whole history have people gone through a global lockdown, with state borders closed. Even the greatest political terrors have not banned on visiting parents and grandparents. Prayers in churches and synagogues have not been stopped for thousands years, even in the darkest ages.

Minimal economic damages may be estimated at 5,000 billion dollars (if taking the Western annual production as worth of about 100,000 billion dollars, and if considering the losses only as 5% during the first corona year). This minimal damage estimation equals 1/3 of the Chinese GDP, and should be claimed in reparations from the PRC, together with appropriate explanations and apologies.

Way out
The authorities anywhere in the world have not presented any real plan, only waiting for some changes in some parameters and imitating proclamations of others. Real plan will not wait for anything before being presented clearly to the public. For example, the following principles may hold immediately, either in individual countries or internationally:
(1) Vulnerable people, as defined by healthcare authorities (e.g. suffering from cancer, hypertension, pulmonary diseases, diabetes, obesity), will protect themselves, or will be protected by their families, or by responsible institutes (like retired homes) with families’ consent in order to reduce the probability of contracting CoV-2 (masks, special attention to contacts with the others);
(2) all businesses, big and small, and all activities will immediately start to function as before the current epidemics; and
(3) a scientific committee or board will be established, consisting of the best scientists, to evaluate the course of the disease (including regular antibody and RT-PCR random sampling), to plan the necessary research, and to regularly inform the public.

The herd immunity will be considered, together with developing vaccines and/or medicaments, in parallel. No good plan can afford to freeze the society’s life, or to wait for the herd immunity (here, here, here, here, here, here, here). The infection chain cannot be easily interrupted either, since 80% people have no symptoms, and too many people are infected. The fact is that the infection spreads surprisingly quickly in closed groups of people without restrictions (here, here). Even if locating and isolating all infected people in one country (which would be feasible by quick testing the whole population), new cases will be brought from abroad, so that global eradication would be necessary. But similar viruses may appear any time again from nature, or they can be constructed by terrorists or hostile governments and spread around the world again. The plan must consider all scenarios.

The strains of sequenced viruses from the victims around the world should be compared, and samples of the blood donors around the world should be retroactively checked for SARS-CoV-2 for the periods of the whole year 2019, to trace the origin of the epidemic, and to entirely understand it. The scientific and political conclusions will have to be drawn from the COVID-19 epidemic.

The Western society should start promoting technical education and exact sciences over pure humanities and politics. The West should further strengthen its independence on, and its upper hand over, the non-democratic countries. Critically, China must be pushed toward more openness and democracy

No comments:

Post a Comment