rogespeed, we're in uncharted waters. I don't know if the new variant Omicron is more virulent. There is nothing in the mutations to which we can point and say "Ah, marker of increased virulence" - but there is nothing in the mutations to which we can point to say that it's NOT more virulent. This is something we'll only discover with epidemiological evidence, and the urgent studies already underway to test the key aspects. It's too early at this stage to even begin to predict increased severity of disease and increased likelihood of death. But... worryingly, it's not too early to predict increased likelihood of transmissibility and increased ability to evade the human immune system (based on some of the mutations which have been seen in earlier variants).
The number of mutations in this variant is insane. More than 50 mutations have been identified, and more than 30 of those are in the spike protein. Of those, a staggering 15 of the mutations are on the “receptor binding domain” aka RBD (that binds to human ACE2 receptors, which is how the virus gains access to the cells) with 10 of those specifically on the receptor binding motif aka RBM (an insertion to the RBD which contains short β5-6 strands; it's the bit that contains most of the contact residues, and is in contrast to the RBD's other structural region, a core which is relatively conserved/non-variable).
Some of the mutations are familiar to us (from previous variants) but many are not.
Quoting Prof Lawrence Young, Virologist and Professor of Molecular Oncology, Warwick Medical School, University of Warwick:
“This new variant of the COVID-19 virus is very worrying. It is the most heavily mutated version of the virus we have seen to date. This variant carries some changes we’ve seen previously in other variants but never all together in one virus. It also has novel mutations that we’ve not seen before. Some of the mutations that are similar to changes we’ve seen in other variants of concern are associated with enhanced transmissibility and with partial resistance to immunity induced by vaccination or natural infection.”
Here's a diagram of the B.1.1.529 lineage report, from the genome sequencing done in South Africa.
(Please click on the image to enlarge it.)
I draw your attention in particular to the purple section in the Omicron lineage report above. That illustrates the Receptor Binding Motif (RBM) region. 10 mutations there alone; by comparison, Delta had 2 in that region.
- Multiple RBD and NTD mutations associated with resistance to neutralising antibodies (and therapeutic monoclonal antibodies)
- Cluster of mutations (H655Y + N679K + P681H) adjacent to Sa/S2 furin cleavage site - associated with more efficient cell entry ➔ enhanced transmissibility
- nsp6 deletion (Δ105-107) - similar to deletion to Alpha, Beta, Gamma, Lambda - may be associated with evasion of innate immunity (interferon antagonism) ➔ could also enhance transmissibility
- R203K+G204R mutations in nucleocapsid - seen in Alpha, Gamma, Lambda - associated with increased infectivity
So... this variant may be able to evade our immune system in more ways than just being able to resist antibodies (from previous infection or from vaccination). IFNs (interferons) are vital to mounting a strong defence against viral infections. There are urgent studies RIGHT NOW looking at antibody neutralisation of Omicron and also with interactions with T cells - but these are going to take several weeks.
Another image to show the mutations, deletions, insertions of the Omicron variant. Again, please click to enlarge it.
This variant's unprecedented number of mutations is far more than one would normally see, given the observed rate of genetic shift/drift in this virus. A likely explanation is that it mutated within a person who had long-term infection - i.e., chronic infection, possibly in an immunocompromised host.
Quoting Professor Ravi Gupta, Professor of Clinical Microbiology, University of Cambridge,
“B.1.1.529 has signatures of cumulative mutation indicating that it emerged in a chronic infection.”
I also quote Professor Sharon Peacock, Director of COG-UK Genomics UK Consortium, and Professor of Public Health and Microbiology, University of Cambridge:
“The genetic difference of B.1.1.529 has led to the hypothesis that this may have evolved in someone who was infected but could then not clear the virus, giving the virus the chance to genetically evolve (the equivalent of an evolutionary gym).”
I'm also posting a YouTube video of the information release meeting (Zoom) released by the South Africa Ministry of Health and some of the scientists involved in the sequencing and identification, etc. It took place on the 25th, before the WHO had named the B.1.1.529 variant Omicron. (By the way, South Africa has acted with astonishing speed on this - in picking up that there was a new variant rather than just emerging clusters, in the genomic sequencing showing that there was indeed a new variant, and in releasing the information immediately. They deserve enormous praise.)
(There's a lot of fluffing around - technical problems and so on - until about just before 9 minutes in, so you should start watching from that point.)
