Meeting and parting are constant in this inconstant world,
Were joy and sadness alternate like night and day;
Officials come and go, but justice and righteounsess remain,
And unchangeable remains forever the imperial way.

The Chinese Gold Murders
Robert van Gulik

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At the heart of COVID-19

For COVID-19 note that the figures provided were purely indicative and changing fast.

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arrow 29 april 2020. The virus circulating in France in January differs from that in Wuhan and in Italy.
A virus causing severe cases of atypical pneumonia already existed in mid-December 2019 in China, possibly even in Italy, in France, and in the USA in January 2020 not initially ascribed to COVID-19. It could well be that early ancestors of SARS-CoV-2, producing asymptomatic infections had already spread before causing clinical—COVID-19—disease. Severe unusual cases appear sporadically in children. Several features of the disease may suggest a course where a first benign infection may trigger a severe paradoxical response upon secondary infection by a virus with related antigenic markers (as is the case for dengue fever). Before placing much hope in vaccines it is important to remember that a first infection is not always protective, but, in contrast, may create a negative sensitisation reaction. This explains why it has not been yet possible to create a completely safe dengue vaccine.
arrow 27 april 2020. The discrepancy between countries in the way they manage COVID-19 gets more prominent.
We have now 3,000,000 identified cases in the world, with 1,000,000 in the USA. But New Zealand reports to be free of the virus, while Hong Kong reports several days without new cases. Wuhan has been declared free of the virus yesterday. By contrast Singapore has now more than 14,000 cases, but reports its 11th death today, a remarkably low figure. This may be explained by the fact that most of the cases are reported from dormitories of migrant workers, who are young. But this may emphasize again the considerable bias for fatalities for people aged 60 or more. Together with several unusual symptoms of the severe cases—including attack of the blood vessels epithelium—this displays symptoms worryingly similar to those of dengue fever. Comparing the severe cases of SARS and COVID-19 it is as if people born before 1960 had frequently met with a disease that left scars in their immune system, which then triggers the severe form of COVID-19. This hypothesis should be studied in priority because it may mean that people with benign symptoms today might be affected by severe symptoms in a next epidemic of a related virus.
arrow 25 april 2020. "Muller's ratchet" is engaged and the evolving landscape of the virus is shrinking.
Muller had shown how, in the absence of possibility of recombination, the evolutionary landscape of a species whose genome mutates over time is reduced, and leads to its demise. For a virus, this is the basis for its attenuation. Yet this is on condition that it cannot recombine. It is therefore absolutely necessary to avoid clusters of cases, which would inevitably lead to go backwards and resurrect the virus' virulence. The situation in Brazil is becoming of great concern as this country is the host of many cults, with no social distancing, while the head of the state denies the importance of COVID-19, letting the health system be overwhelmed by severe cases.
arrow 24 april 2020. Because the nose mucosa has an important number of receptors of the virus, wearing masks is likely to be protective.
It is difficult to know how reliable are the figures provided by Chinese authorities. However the fact that the country is progressively coming out of lockdown is a demonstration that something, in the recommendations of the authorities did work. Wearing masks in all public circumstances might indeed have considerably alleviated the burden of the epidemic by lowering the R0 contagion factor. The lesson does not appear to have been understood in most of the western world. In a parallel unfortunate demonstration of gullibility, the treatment using hydroxychloroquine begins to make victims and the FDA issued a warning to dissuade people to use it for applications other than its standard recommendation (in particular rhumatoid arthritis and related diseases).
arrow 23 april 2020. Most countries in the Western world failed to manage the epidemic properly.
Hong Kong and South Korea are counterexamples. This differences combines the general attitude of the public and lack of insightful governments. The South China Morning Post summarizes the situation in a vivid picture.
arrow 22 april 2020. Yet another cruise ship, in Japan again, as a cluster source of COVID-19.
Taking into account the role of clusters in the spread of the diseases looks essential, as the Costa Atlantica is being repaired in Nagasaki, with at least 30 crew members infected by SARS-CoV-2. It will be interesting to follow what happens as it seems that some of the crew had left the restricted area of the harbour. The virus keeps evolving, in particular following the selection pressure against its cytosine content.
arrow 20 april 2020. A Tale of Two Cities: Hong Kong and Singapore.
No new case in Hong Kong today, while Singapore reports 1,426 new cases of COVID-19. Germany begins to alleviate lockdown conditions, while France has a rate of deaths from the disease 6 times higher than the former. How can we account for these discrepancies?
arrow 19 april 2020. The way COVID-19 propagates follows several paths.
The vast majority of models of the epidemic (which did not really succeed in anticipating what is now happening) considers one type of transmission of the SARS-CoV-2 virus, from person to person, with some variation in the contaminating routes. Yet, looking back at the notes taken since january 1st we find that there is a scenario that repeats itself, contagion occurs in clusters: cult meetings, celebration dinners, sport events, group tourism, dormitories for migrant workers and what not. As a rule, these events subsequently spread the disease not only locally but in a way that has features of an explosion: tourists go back to their countries of origin, cult worshippers try to convince others to follow their creed, workers go to their work, etc. This feature must now be seriously taken into account. It may explain the huge difference between Hong Kong and Singapore, the latter being at pain to contain the epidemic which now reached more than 6,000 cases, six times the number in Hong Kong. In the same way some practices lead to a considerable increase in contagion: running without a mask implies shedding fomites very far away, so that standard social distancing is not enough. The same would be true for singing, for example, but this is not a general practice, except in some quarters.
arrow 18 april 2020. A need for scientific rationality.
This is the time of fake news, rumors and primitive irrational reactions, with complete lack of understanding of what science is
. Here are a few rules to check whether you can read any of the « information » which is dumped on you:
1. If you read « famous », « leading », or « prestigious » journal or author, stay away, there are good chances that the content of what is written is at best unproven and that it will sometimes be retracted. If one needs to make an impression, this means that one tries to mislead you. The content of any scientific news should be self-sufficient scientifically, with no emotion.
2. Read the content of the source of information, not its title or summary. Beware of predatory journals. They go by the thousands. Their content has nothing to do with science.
3. Ask yourself common sense questions: is the information plausible? Essentially, does it provide you with means to check its sources, the way it is performed. Beware of results extracted from arcane techniques. Beware of information that rests on data supplied as images that may be photoshopped.
4. Remember that statistics require hypotheses that are generally not stated by the people using these approaches. Remember Bertrand's paradox.
5. At this point, you can build up an idea of the rational behind interpretations of the topic which is of interest to you. It is time to try and make a list of unanswered questions, so that you will be ready when yet another surprise makes the catch titles of mass media and is relayed by people exchanging with you.
arrow 16 april 2020. While COVID-19 is almost under control in South Korea a number of mostly young patients become reinfected.
n yet another surprising turn it seems that immunity against the SARS-CoV-2 virus is unstable (or that it may survive as persister viruses for some time). This is worrying as this casts doubt on the fast production of a vaccine. By contrast big pharmas try to restart studies based on antivirals with known efficacy. This is against viruses other than the present one, but several leads may be rewarding. Remember however the Hippocratic primum non nocere, as many drugs have dangerous side effects that can only be detected in the long term (such as carcinogenicity). 
To place things in perspective here are the data of the flu season as compared to COVID-19 in Switzerland, a country that did better than other European countries (but less well than Germany, at this point). This shows that the epidemic is clearly more severe than flu in standard conditions. Only one new case of COVID-19 in Hong Kong today (1,017). A general studies reveals a paradoxical effect of the disease: smokers seem to be less affected and there may be a protecting effect of nicotine but this should be taken with great caution as other studies give the exact opposite information.
arrow 15 april 2020. The role of temperature  in the spread of the virus is difficult to assay as air conditioning appears to be a significant source of contamination.
In warm and humid countries public space is submitted to omnipresent air conditioning with a temperature set at a very cool level. Furthermore air blows often directly on people
and this has a confounding effect when connecting the spread of the disease and the weather in warm climate countries. In the same way, the role of total lockdown of people is challenged by the spread of the disease in countries such as South Korea, and, in Europe, Sweden. It will be interesting to see the spread of the disease at a moment the number of cases remained approximately constant over the last couple of weeks there, with a death rate at present 4 times lower than that in Spain. The difference between countries could also be linked to the understanding and application of hygiene measures in hospitals. Political authorities are not selected on their intelligence, they are often very vulnerable to fake news and bad science. They resist to understand how bad a situation can be and follow fashion, after lay persons vote (sic) for treatments or approaches. This makes that despite the difficulties in making vaccines, they bet on the rapid production of a vaccine to take their political decisions. We should however remember that, as found with dengue fever, immunity can sometimes make the course of a disease much worse, and one of the phenotypes of SARS-CoV-2 infection goes unfortunately in this worrying direction.
arrow 14 april 2020. Now that the official number of COVID-19 cases reaches two millions the stark constrast between the behaviour of different countries becomes prominent.
Comparing Hong Kong (1,010 cases and 5 deaths) and Singapore (where wearing masks has become compulsory as of today,
3,252 cases and 9 deaths) is a case in point. We should note however that the death rate at both places is extremely low as compared to the situation in Europe. The situation in Germany and in Northern Europe countries (except perhaps Sweden) is considerably better than in other European countries, with ten times less death cases per million people than in Spain, for example (6 times less than in France). This is highly telling about their socio-political background and the level of their governing bodies. China is progressively reopening schools but university students are requested to stay on campus until further notice in order to prevent massive movements across the country. A few studies suggest that the HLA polymorphism impacts the contagion and severity of the disease, with the B*46:01 allele more vulnerable (as was shown during the SARS episode). By contrast the B*15:03 allele would be more protective. Many vaccine protocols are ongoing, but work with variants of SARS-CoV-2 suggest that the virus may rapidly escape vaccination, as does the flu virus. A remarkable side effect of the present epidemic is that it is observed, world wide that the rate of cardiac infarction as well as stroke has sharply decreased. This is only, in part, associated to some increase in sudden death. This certainly deserves careful analysis of the consequences of the type of stress induced by an epidemic.
arrow 13 april 2020. An outbreak of Decapod Iridescent Virus (DIV1) infection in prawn farms threatens freshwater polyculture systems.
Since the beginning of February the virus, naturally present in the wild and known since the middle of the 1980s, is invading aquaculture farms in southeast Asia, Indonesia and the Philippines. The disease has already infected a quarter of the shrimp farms in Guangdong province in China, killing most crustaceans there.
arrow 12 april 2020. The enigmatic origin of SARS-CoV-2 and asymptomatic cases.
We still do not know where the virus emerged. In parallel there are many asymptomatic cases, but their number seems to vary in wide proportions from place to place. This suggests that the many forms of the virus do not have exactly the same pattern of contagion and virulence. It may well be that during the autumn of 2019 a totally innocuous SARS-CoV began to spread in the population, possibly world-wide. It triggered sporadic cases of severe asymptomatic pneumonia, and the patients spread the disease to the health personnel taking care of them and to their families. The disease thus spread unseen until, after some mutations, possibly differing in different places of the world modified the virus into a more pathogenic form, starting COVID-19 as we now know it. This would explain the apparently « explosive » nature of the epidemic, once started. Hong Kong passed the threshold of 1,000 cases. While COVID-19 is certainly a serious outbreak it is essential to put the epidemic in perspective. The French National Centre of Demographic statistics, INSEE, collects mortality data in France in detail, and for the month of March 2020 there is an excess mortality in France compared to 2019, but overall this does not yet reach the figure for 2018, but is at some places significantly higher. However the present slope of mortality suggests that the trend is on the increase.
arrow 11 april 2020. The enthusiasm for nucleoside analogs should be tuned down as many are dangerous mutagens or carcinogens.
There is a lot of advertisements for using  analogs of the building blocks of the virus. Yet one must remember that SARS-CoV-2 is a mimic of a standard mRNA of the host cell so that any interference will also affect the cell. This is why it is so difficult to make relevant drugs. A further matter of concern is that it seems that investigators are seldom aware of the fact that the analog they propose is a strong mutagen.
This is the case, for example, of derivatives of N4-hydroxy-cytidine, which have been know for almost half a century to be strong mutagens, because of the tautomerisation of the base. Remember that most clinical assays cannot tell whether a molecule is carcinogenic or not.
arrow 10 april 2020. The « One Health »  international research program is essential to understand what happens to us, but we look elsewhere.
It has long been known that emerging infectious diseases come from the way we interact with animals. Tearing apart the habitat of animals long adapted to their specific environment changes the equilibrium of pathogens that have evolved towards commensalism or mutualism and, when reaching the human host evolve rapidly back to a highly virulent state. We are the ultimate cause of our woes. The Chinese government may have begun to understand this situation and is regulating the trade of wild animals. Whether this will be effective is an open question because it is a multibillion dollars activity.
arrow 9 april 2020. The origins (plural) of the virus remain enigmatic.
We do not have any real idea of the time when the epidemic started, nor even of its place(s) of birth. Because we tend to be « adamists » we always think that there is one origin to things. This is a wrong view as we can see when investigating how Homo sapiens appeared on Earth, knowing that our closest ape cousins have 48 chromosomes, while we have 46 (our chromosome 2 is a gross genetic accident, the head-to-tail fusion of two ancestral chromosomes). This initial chromosomal accident had to spread over many generations in a
group of social primates in order to build up a community with a sizeable number of individuals with 47 chromosomes (a genetically unstable situation, because meiosis produces two types of gametes, with 23 chromosomes or 24 as in the parental « normal » gametes). It took many generations for an homogeneous population of individuals with 46 chromosomes to build up.   As a consequence, there is no date of origin of H. sapiens. In the same way, the virus may be the result of a ménage à trois: a host and two CoVs that later recombined, spread and evolved by adjusting their genome to their hosts over a long period (which may have lasted several months and have taken place in several places). This view suggests that it will be extremely important to monitor biological parameters of the largest possible number of patients with atypical pneumonia in the world before December 15th 2019.
arrow 8 april 2020. Marco Ferrari, the head of the European Research Council resigns.
President of the ERC since January 1st Marco Ferrari said that was disappointed of the European Union response to the COVID-19 epidemic. However, this could be related to serious conflicts of interests. Travel to and from Wuhan is now open, but this implies that China has completely shut up its borders to foreigners in order to stop a second wave of the epidemic. The border with Russia is severely controlled after 25 new were imported from Russia by Chinese nationals. The problem is that this cannot be a long term solution. All countries which will alleviate confinement will face the same hurdle. It is therefore extremely urgent to find efficient antiviral drugs. Following what happens for the second wave in Hong Kong (now 960 cases, 4 deaths) and in Singapore (1,623 cases, 7 deaths) may tell us what is to be expected. A reason for the uncontrolled spread of COVID-19: among the 885 infections reported in China between March 31 and April 7, 601 had no symptoms. This is a limited data set but quite revealing.
arrow 7 april 2020. The number of cases in Pakistan is exploding.
The Tablighi Jamaat religious gathering in Lahore assembled more than 100,000 many of the attendees infected by the SARS-CoV-2 and then disseminated across the country. More than half of the 5,000 cases or so registered by the authorities have attended the event. Also, the symptoms of severe COVID-19 look like some of those of severe dengue fever (without haemorrhagy) and this is a matter of great concern as this would preclude an easy route to a vaccine.
arrow 6 april 2020. Triggering a likely second wave of the epidemic, people tend to return to their previous behaviour as lockdown is lifted.
It seems unfortunate that people return to old habits when lockdown conditions are alleviated. This explains why a second wave of COVID-19 is on its way in Hong Kong and in Singapore, starting with cases due to the coming back of citizens from infected countries. Again, the situation in South Korea should be monitored carefully as the country returns to normal: social distancing, and, at a time when it is not possible to know who is a carrier, wearing masks is essential. To cheer us up, and better than chloroquine, a Chinese study is developing a clinical study using Viagra® as an anti SARS-CoV-2!
arrow 5 april 2020. Investigating human polymorphism becomes a critical question to understand the future of the disease.
Many proteins exposed at the surface of membranes and envelopes are modified by sugar (carbohydrate) tags. These modifications result from the action of enzymes, glycosyltransferases, of a variety of types. These enzymes are encoded by genes of the host (and sometimes of the pathogen), so that there may be variations between individuals (polymorphism) who get a type or another type, and, sometimes mutants inactivating these genes. The so-called H antigen is a complex carbohydrate that tags a variety of proteins, in particular in the blood. When unmodified it corresponds to the O group. With different modifications it gives the A or B groups as well as other variants.
H antigen
These tags are used for adressing proteins or cells to proper targets, and they are recognized, directly or indirectly, by viruses to help them enter their hosts. This explains why susceptibility to infection may be different with different polymorphic markers. Many other markers have evolved during animal—man in particular—evolution. Secretions, for example, are tagged with another carbohydrate (fucose) that makes the « Lewis secretory system ». In the same way, the large polymorphism in the so-called HLA system (Human Leukocyte Antigen) explains why it is difficult to find « compatible » donors for organ grafts. It will be essential that a large number of patients infected by SARS-CoV-2 are tested so that we could understand the nature of the polymorphism that increases or decreases susceptibility to the disease. In a surprising turn of things mass tourism exploded in China after lockdown stopped. Thousands of people, of course without any hint of social distancing, flocked to the famous Yellow mountains (Huang Shan) in Anhui province. This is highly telling about the lack of understanding of the general population and sends a very negative message for the future of the epidemic.
arrow 4 april 2020. The New York Times gives an excellent summary of what is know on SARS-CoV-2 at this time.
A reason for the apparent lack of preparation of the world to the present epidemic is that an overstated reaction happened during the H1N1 « swine flu » in april 2009. At the time we already had somewhat effective drugs, and the pipeline for a vaccine could be activated rapidly, as another isolate of this flu type was recognized by seasonal vaccines. By the end of that year it was obvious that the disease would be mild. This however triggered stockpiling resources, so that, later on, authorities thought better and discarded their stores, forgetting that a really serious epidemic might happen later on. Crying wolf is always dangerous. A most puzzling feature of the serious cases of the disease is that it unfolds in two steps, the second, severe one following an apparent remission with some symptoms reminiscent of severe dengue (without haemorrhagy however). Proselytic sects of all religions have been and still are a major source of the epidemic because they are meant to spread people communicating with other people.
arrow 3 april 2020. After the departure of the last cruise ships, Australia's authorities think they can suppress COVID-19.
There is still 19 cruise ships in Australia's waters, but they are all leaving. We are at the beginning of autumn in the southern hemisphere where weather conditions might increase the probability of contagion of respiratory viruses. Epidemics there return to the northern hemisphere the following  year. It is a sign of hope that Australia might be able to stop contagion before it has a sizeable amount of cases. Google is now monitoring people's mobility world-wide, using data collected for people accepted to be localized when using websites. Among the puzzling features of the epidemic is the difference between Spain and Portugal, ten times more fatalities in the former country as compared to the latter.
arrow 2 april 2020. The slow return to normal in China has to be monitored carefully.
Movements are allowed in some places in China, with people returning to work. However the authorities fear that a second wave of COVID-19 will start the epidemic again despite the fact that only few local cases are still recorded. Yesterday Jia county, near the city of Pingdingshan, in Henan province has been completely locked down presumably because of recording one or several unexpected cases of the disease in a nearby hospital. Moving to work requires special permits and testing. From today, China includes asymptomatic carriers in its official daily figures of the disease. In Laos 200,000 migrant workers came back from neighbouring countries, some heavily contaminated such as Thailand, and the local government is worrying about a surge of cases in a country with very little upscale medical facilities and ancestral unvalidated medical traditions (as shown here by Paul Brey).
In this context it is also very worrying that China has authorized the absurd use of bear's bile as a cure against coronaviruses. 1,000,000 recorded cases of COVID-19 are recorded.
arrow 1 april 2020. Knowledge, alas, is not contagious, and transparency is a way to promote incompetence.
Why are governments so often unable to come rapidly about good decisions? Transparency means visibility. The history of disasters likes to tell us that heroes had a unique role for the common good. Unfortunately, the dark side of humanity rests on competition for resources among which glory (and the venal prizes linked to it) plays a key role. How, then, can well tell the bad from the good? One way is to look for improbable associations that place together people who, previously, were competing and suddenly found a way to share the ultimate prizes, while they had only anecdotal competence in a narrow domain of knowledge. Universals and anecdotes in times of emergencies: Some stand alone and some try to get people team up to be in the limelight and, who knows? get big prizes. We note, again, the surprising lack of incentive to discover the true origin of the infecting virus. Exactly as was the case for the HKU-Pasteur Research Centre Ltd, rapidly dismantled, there was no real support for the Institut Pasteur du Laos, and his remarkable director, Paul Brey, who kept telling that an essential effort in the domain of in situ virology, entomology and parasitology was lacking. All this happens when a deluge of publications floods the newspapers, but always with the fashion lamppost effect (looking where light shines, instead of producing interesting hypotheses). Singapore's cases rise to 1,000 with 74 new cases with only 20 imported. Two clusters have been found at a dormitory and at an Old Age Home. This is an indication that a second wave of local transmission has been masked by asymptomatic cases.