Concerns, variants and Covid-19: photograph of the epidemic in mid-February

0). The strange course of the Covid-19 pandemic that began in January 2020 keeps getting even stranger. Take a good look at the media and the tone of the health comments, you will see that variants have gradually invaded the media space. People in the know keep talking about the British B117 variant and the two exotic variants, from Brazil and South Africa. The coronavirus is rather facetious. The influenza virus is more serious. It is spreading in the southern hemisphere, the labs study it to produce the vaccines intended to protect the patients when the flu reaches the North after winter arrives. The coronavirus respects nothing. The variants circulating in the summer in the southern hemisphere invite themselves at the same time in the North in the middle of the winter season.

1) Incernable Pandemic. The monitoring of the case and death curves reveals large-scale chronological and geographical disparities. No country follows a generic pattern. It should be noted that it is not the virus that creates the pandemic but the infected patients who manufacture the virus and transmit it in a space regulated by social distances specific to each country to which are added the climatic rules. This remark explains the disparities in contagion, spread and virulence. India, which has ceased confinement for a few months, sees the epidemic dying out. In the Scandinavian countries, the second wave is on the decline. In the UK, the States and Brazil, the epidemic is weakening only slightly and remains at a high death threshold. In Asia it’s different. Island countries like Taiwan, New Zealand, Australia, are getting off temporarily. China is in political trouble. Demographic and epigenetic factors are also invited to disrupt the statistics, not to mention the health status of populations. From Japan to the rich western countries, we go from 5% of overweight people to 30 or 40%. Ambient temperature and humidity seem to influence the course of epidemics. In short, the Covid escapes any attempt at modeling accompanied by projections. In addition, the variants seem to produce variations in epidemic kinetics, at least in Manaus and England.

2) Clades et variants. If the theory of species evolution is solid on its conceptual basis, with the generic concept of the clade, virology had better not draw too much inspiration from evolutionism. Two concepts are necessary, the gain of function and the variation. The gain of function characterizes a change in infectious dynamism for a virus, modification of tropism, for a species or a tissue, increase in contagiousness. Variation designates a change in the genomic sequence of the virus, with point mutations, more or less large deletions, insertions, recombinations. As the influenza virus is segmented, gene exchanges are possible and produce reassortments. This is what happened with the emergence of H1N1 in 2009.

SARS-CoV-2 has only varied and sometimes variations become dominant. Either the mutation is beneficial and the virus spreads faster, or a mutation takes the lead over the others in favor of an outbreak that explodes and spreads. The early D614G mutation became dominant. It is not appropriate to speak of viral clades but rather of branches listed on the phylogenetic tree which now contains hundreds of branches from the first coronavirus recorded in Wuhan.

B.1.1.7, code name of the British variant, whose formula is:

aa:orf1ab:T1001I

aa: orf1ab: A1708D

aa:orf1ab:I2230T

from: 11288: 9

from: 21765: 6

from: 21991: 3

aa:S:N501Y

aa:S:A570D

aa:S:P681H

aa:S:T716I

aa:S:S982A

aa:S:D1118H

aa: Orf8: Q27 *

aa: Orf8: R52I

aa: Orf8: Y73C

aa: N: D3L

aa: N: S235F

This variant has 17 alterations making it distinct from the ancestral virus. If it is apparently more contagious, virologists explain it with the N501Y mutation affecting the spicule, which would allow the virus to attach more easily to the membrane receptor ACE2. The Brazilian B.1.1.28 and African B.1.351 variants also have an E484K mutation also located on the binding domain of the spike, which would make it, like its British counterpart, more affine for the receptor. Nevertheless, an enigma emerges; the mutation in 484 was recorded from April to September in Galicia, England, Sweden, California, without spreading. The accelerated release of the South African variant began around November 2020 and December for the Brazilian variant, which was spotted in Argentina and other countries. It is the same configuration for mutation 501, recorded twice in April, then repeatedly in Australia (B.1.1.136) during June, at the end of August in the United States, with notification B1. Viruses sequenced before fall 2020 were not the variants recorded since November; they did not have all the mutations that we observe and which keep increasing so that it becomes improper to speak of an English variant but rather of a multitude of variants generated by the addition of mutations additional. FYI, the English variant registered as a clade has a divergence of 24 nucleotide mutations (producing 17 aa changes) while its descendants now have a divergence of between 30 and 40.

3) Epidemiologists speak of an epidemic within the epidemic, or even a second epidemic or a new epidemic as indicated by Didier Raoult without wanting to worry. In France, the English variant is spreading, in Brittany, in IdF, in Dunkirk, without one note a runaway figures of contamination, percentages of positivity, admissions in hospital care. “The epidemic is receding and the variants are spreading” headlines the media. Does this calm herald the next storm predicted by Inserm? Unless the virus calms down by some sort of physiological or seasonal or cosmological explanation? Variants create the epidemic, say scientists. And if it was the opposite, the epidemic which is progressing and favoring the spread of variants? Or even a declining epidemic combined with a spread of the variant. Denmark is the country with the most English variant, 1600 as of February 15. However, this country of 6M inhabitants has detected less than 500 daily contaminations for two weeks, with a threshold in view of 300. And less than 10 deaths per day for a week. It is to understand nothing there.

4) Inserm modeled the epidemic by integrating the dissemination of variants. A peak estimated at the highest 25,000 weekly admissions was projected for March 22, more than double the current figure, stabilized for four weeks with just over 11,000 admissions. If proportionality is respected, there should be more than 7000 resuscitations. The peak of the first wave would then be exceeded. And the white plan has just been triggered, as a precaution. In reality, nothing is certain except one thing, when a result is worrying it is widely publicized in the media. The history of this epidemic shows that the projections are not reliable and that there are no deterministic laws making it possible to predict the health evolution.

5) anything is possible, a moderate increase, stabilization and even a slow attenuation. The course of the epidemic in India and other countries indicates an enigmatic attenuation so that the optimistic scenario is just as possible as the alarmist forecasts of Inserm. If the epidemic eases, the clinical gap will once again require scientific investigations into this emerging pathology which represents a real challenge for science and its four mobilized disciplines. Theepidemiology faced with the strange course of propagation in populations and over time. The clinique faced with the multiple symptoms and especially the emergence of long-lasting Covid, a not so exceptional event since it occurs with other infections but quite unexpected for a coronavirus, although the feedback on cases of first SARS infection may have been also highlight long-term pathologies. The autoimmune track is privileged for the sustainable Covid, hoping that it does not become chronic. Theimmunology is mobilized to understand how immunity is failing against SARS-CoV-2 with interference with signaling pathways, MAPK, JAK, etc … and the virologie must explain how these viruses are generated and why they acquire a gain of function, with sometimes advantageous mutations and variants whose diffusion seems to be linked to a selective advantage becoming visible after a few weeks.

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Annex. Count of the English variant per country as of February 16, 2020

United Kingdom 63088, Denmark 1614, France 847, United States of America 756, Belgium 693, Spain 594, Ireland 507, Italy 495, Switzerland 488, Netherlands 471, Israel 221, Portugal 205, Sweden 148, Turkey 142, Austria 140, Finland 97, Australia 93, Germany 92, Nigeria 75, Slovakia 70, Ghana 62, Singapore 53, Norway 51, Jordan 42, Canada 41, Romania 35, India 34, Luxembourg 32, New Zealand 26, United Arab Emirates 21, Iceland 20, Brazil 19, Czech Republic 17, Sri Lanka 15, South Korea 13, Poland 11, Saint Lucia 9, Thailand 7, Ecuador 6, Mexico 5, Macedonia 5, Hungary 5, Latvia 5, Slovenia 4, Greece 4, Hong Kong 4, Jamaica 4, Barbados 3, Bangladesh 3, Gambia 3, Cayman Islands 2, Malaysia 2, Democratic Republic of the Congo 2, Pakistan 2, Peru 1, Iran 1, Argentina 1, Oman 1, Kuwait 1, Dominican Republic 1, Trinidad and Tobago 1, South Africa 1, Bosnia and Herzegovina 1, Taiwan 1

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