End of Year notes, by Prof. H. Fleury
by Prof. Hervé Fleury, MD-PhD | Ventum Biotech Scientific Board Member
Omicron in Great Britain
COVID-19: Omicron Daily Overview
Our English friends being ahead of the European continent regarding the dissemination of Omicron, the study of their data is important to try to anticipate our own situation.
The data analyzed here is from the UK Health Security Agency website.
The figure above refers to the number of infections from November1 to December 28, 2021
In green, we identify the Delta variant; in purple, a variant is identified that has an amplification deficit on the S gene in diagnostic PCR; it is Omicron.
We see how Omicron gets the better of Delta.
The figure above gives the percentages of Delta and Omicron according to the regions of the United Kingdom; if we consider the curve at the top right, it indicates that in London, 97.2% of infections are related to Omicron.
The table above shows the percentage of hospitalized patients with Omicron infection who are unvaccinated. In London, this percentage is 41.2% while the Omicron strain represents 97.2% of the circulating virus.
You may see a significant discrepancy between Omicron's dominance in the population and the percentage of patients requiring Omicron-related hospitalization.
In total, data that indicate that Omicron is less pathogenic than previous variants; The ideal would be that this variant becomes a banal coronavirus as we know 4 in children and that it circulates freely in winter by inducing protection against other coronaviruses ... But it is a hypothesis at this stage.
Be careful and my best wishes anticipated for the year 2022.
Omicron pathogenicity in an animal model
SARS-CoV-2 Omicron-B.1.1.529 Variant leads to less severe disease than Pango B and Delta variants strains in a mouse model of severe COVID-19
Eleanor G Bentley, Adam Kirby, Parul Sharma, Anja Kipar, Daniele F Mega, Chloe Bramwell, Rebekah Penrice-Randal, Tessa Prince, Jonathan C Brown, Jie Zhou, Gavin R Screaton, Wendy S Barclay, Andrew Owen, Julian Alexander Hiscox, James P Stewart
Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK.
Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, University of Zurich, Switzerland.
Department of Infectious Disease, Imperial College London, London, UK
Welcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Department of Pharmacology and Therapeutics, Centre of Excellence in Long-acting Therapeutics (CELT), University of Liverpool, UK.
Department of Preventive Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
Infectious Diseases Horizontal Technology Centre (HTC ID), A*STAR, Singapore.
Department of Infectious Disease, University of Georgia, Georgia, USA.
Article posted online in BioRxiv on December 28 awaiting trial by a peer-reviewed journal
Given the teams involved in this work and who have an international reputation, it seems reasonable to comment on this study even before its "official" publication.
The authors used a line of transgenic mice whose epithelial cells exhibit the human SARS CoV2 receptor (hACE2)
These mice were respiratorily infected with identical doses of 3 strains of SARS CoV2: Pango B (an initial strain of the outbreak in England), Delta and Omicron.
The clinical status and viral production of the mice were monitored for 6 days.
Mouse weight loss was less pronounced with Omicron; as for the viral load it was lower with Omicron in all samples and especially in the nasal and pulmonary tissues (figure below).
Legend of the figure: amount of viral RNA (PCR); B: nasal tissue; C: lung tissue
Blue: Pango B; green: Delta; red: Omicron
The histological study of the lungs shows less inflammation (objectified among other things by the dark red spans) in mice infected with Omicron compared to that observed in mice infected with Pango B and Delta.
In total, the authors conclude that there is less pathogenicity in the mouse model.
SARS CoV2: what hope for 2022? Antiviral drugs!
An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19 – Owen et Coll, Science – Nov 2021
It is very surprising that our media andpoliticianstalk all the time about the variationsof SARS-CoV2, successive waves andvaccine epidemics without almost ever talking about antiviral drugs.
At a time when the issue of multiple vaccine boosters (4th injection in Israel)is being addressed, the fundamental issue of antiviral drugs must be addressed. After the conflict of chloroquine, it is necessary to clarify that research in this field has not ceased especially in the United States, which dominates world scientific research.
A very recent article by a Pfizer team describes a protease inhibitor that, when used orally, reduces viral replication.
In a previous note, I presented you with a diagram of the SARS CoV2 virus by pointing out that its proteins must be cleaved to be functionally active. This cleavage is carried out with the help of specialized enzymes, proteases of which there are several types. The one that interests us here can therefore be inhibited by the Pfize drugr PF-07321332.
The figure above allows you in "D" to appreciate the antiviral activity in cells of the drug PF-07321332 on SARS CoV2 but also on SARS CoV1 (epidemic of 2003 especially in Hong Kong), MERS (MiddleEast Respiratory Syndrome)CoV (epidemic in progress in the Middle East and in particular in Saudi Arabia) and 229 E (a coronavirus raging in children in winter and associated with minor respiratory infections). We note the 100% efficiency of the molecule for a concentration around 100 nM (nanomolar) and activity against all coronaviruses tested.
The drug was then evaluated in humanized mice infected with SARS-CoV 2 nasally; viral titers were determined in the lungs, particularly with a significant reduction in treated mice/untreated mice. The histological study of the lungs was conducted as can be seen in the figure below; especially at the "E" level we can note the accumulation of viral particles (red/brown cluster) in the lungs of untreated mice (0) with a reduction in treated mice to 300mg/kg and an absence when the concentration is higher (1000).
The kinetics of the drug were then evaluated in rats, monkeys and human volunteers with results in line with expectations. This drug will now move on to an efficacy trial in infected humans.
The treatment of infected patients must become a priority for 2022 without relaxing a vaccination effort that may be insufficient to control theepidemic. Remember that HIV infection is treated with associated drugs (including anti-proteases) without a vaccine being developed almost 40 years after the discovery of the virus.
Admittedly, the arrival of anti-SARS CoV2 drugs will also be associated with problems of diffusion on the European and other markets as well as problems of licenses and prices.
But the emergence of these antiviral drugs must be part of the wishes we can express for 2022.
