New Emerging SARS-CoV-2 Variants And Sub-lineages Such As BQ1.1.10, XBB.3, BA.4.6.3 and CH.1.1 Are Taking Immune Evasion To A Newer Level!

COVID-19 News: Researchers are sounding alarms that while the SARS-CoV-2 coronavirus is evolving rapidly and spawning a variety of variants and sub-lineages, some of these such as the BQ1.1.10, XBB.3, BA.4.6.3 and CH.1.1 sub-lineages are literally taking immune evasion to a whole new level. It is warned that it is only a matter of time before any form of natural immunity or immunity induced by any of the prevailing vaccines and also any known monoclonal antibodies will have no neutralizing effects against the emerging variants and sub-lineages.


 
Dr Yunlong Cao from the Biomedical Pioneering Innovation Center (BIOPIC) at Peking University, Beijing, - China and his study team are warning that imprinted SARS-CoV-2 humoral immunity is inducing rapid convergent Omicron RBD evolution.
 
According to the study team, “Continuous evolution of Omicron has led to a rapid and simultaneous emergence of numerous variants that display growth advantages over BA.5. Despite their divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots. The driving force and destination of such convergent evolution and its impact on humoral immunity remain unclear.”
 
The study team demonstrated that these convergent mutations can cause striking evasion of neutralizing antibody (NAb) drugs and convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2 binding capability.
 
According to the study team, BQ.1.1.10, BA.4.6.3, XBB, and CH.1.1 are the most antibody-evasive strain tested, even exceeding SARS-CoV-1 level.
 
In order to delineate the origin of the convergent evolution, the study team determined the escape mutation profiles and neutralization activity of monoclonal antibodies (mAbs) isolated from BA.2 and BA.5 breakthrough-infection convalescents.
 
Importantly, due to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection caused significant reductions in the epitope diversity of NAbs and increased proportion of non-neutralizing mAbs, which in turn concentrated humoral immune pressure and promoted convergent evolution.
 
The study findings also showed that the convergent RBD mutations could be accurately inferred by integrated deep mutational scanning (DMS) profiles, and the evolution trends of BA.2.75/BA.5 subvariants could be well-simulated through constructed convergent pseudovirus mutants.
 
The study finding suggest current herd immunity and BA.5 vaccine boosters may not provide good protection against infection. Broad-spectrum SARS-CoV-2 vaccines and NAb drugs development should be highly prioritized, and the constructed mutants could help to examine their effectiveness in advance.
 
The study findings were published on a preprint server and are currently being peer reviewed. https://www.biorxiv.org/content/10.1101/2022.09.15.507787v4
 
Readers should however note that there is no correlation to date between the more immune evasive variants and sub-lineages and increased risk disease severity and mortality.
 
Most COVID-19 News outlets around the wo rld have not reported about any increase in COVID-19 deaths or increase in disease severity although hospitalizations have been increasing….. but again, most health authorities around the world are claiming that these increase in COVID-19 hospitalizations have nothing to do with increased disease severity and are often using statistical comparison between the Delta surge and the current surges to play down any disease severity associated with these new variants or sub-lineages!
 
However, we can expect more breakthrough infections and reinfections even in shorter intervals and those in the vulnerable groups such as the aged, the young, the obese, the immunocompromised, those with existing comorbidities and those with certain genetic makeups ill be more susceptible to the worse effects of an infection or reinfection.
 
Also, it should be noted that while all these immune evasive strategies are being picked up by the new variants and sub-lineages, they are actually being ‘groomed’ for longer viral persistence in the human host while also displaying some changes in their pathogenesis.
 
Hence, we can expect to see more long- term health issues and even more serious Long COVID complications and we can also expect to see more incidences of heart failures, strokes, CVST events, organ failures and sepsis, often with fatal outcomes. We can also expect to witness more secondary opportunistic infections and also an increase in various types of cancers and also new forms of medical conditions never seen before.


Though we were initially worried about the BQ.1.1 variant or the recombinant variant XBB, we know the BQ.1.1.10 which shows more evasion (than BQ.1.1) after 3 CoronaVac shots plus a BA.5 breakthrough infection. There’s also XBB.1, XBB.3 and many new sub-lineages, along with BA.4.6.3, CH.1.1, that similarly take immune evasion to a higher level than what we’ve previously seen.
https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?aaMutations=S%3AY144-&nucMutations=T16413C&nextcladePangoLineage=BQ.1.1*
 
https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?nextcladePangoLineage=XBB.1*
 
https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?nextcladePangoLineage=XBB.2*
 
https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?nextcladePangoLineage=XBB.3*
 
https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?aaMutations=S%3AQ677R&nextcladePangoLineage=XBB*
 
https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?aaMutations=Orf1a%3AG963C%2CS%3AK444N%2CS%3AN460K&nextcladePangoLineage=BA.4.6*
 
https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?nextcladePangoLineage=CH.1.1*
 
It is being reported that the growth advantage compared with BA.5 is substantial, such that for each of the convergent mutations that the swarm of variants are accruing, the growth advantage increases.

Alarmingly, in the early phase of this rapid evolution that was seen around 7 to 8 months ago, by monitoring the converging mutations seen in the new variants, it was mostly 4 or 5 mutations per emerging variant or sub-lineage, but now these new variants and sub-lineages are spotting up to even 8 or 9 mutations with almost doubling of the growth advantage vs BA.5.


 
To date however, there are no observed clinical impacts such as increased disease severity or increased mortality.
 
Singapore that recently witnessed an XBB surge and is now in descent, did not have a major corresponding spike in hospitalizations or deaths. XBB is also dominant in other countries like Bangladesh and India, which have not shown any spike in cases or deaths either.
 
It should be noted however that the vaccination and booster rate in Singapore is extremely high (boosters were the original, not bivalent).
 
It is also hard to assess whether the BQ.1.1 variant also increases disease severity or increased mortality as most countries have not reached a point yet where BQ.1.1 is the predominant circulating variant. France is the closest but has yet to exhibit an increase in cases or hospitalizations.
 
In will be interesting to see what happens as the BQ.1.1 variant starts increasing in dominance in Europe and also in Northern America. It is projected that it will take between 4 to 8 weeks before it accounts for >50% of new cases. It isn’t yet clear how well cross-reactivity with BA.5 or prior Omicron lineages (BA.1, BA.2, BA.2.12.1, BA.4.6) will help provide protection vs BQ.1.1x or even how the boosters will perform.
 
However, the coming Winter surge in Europe and Northern America will be fun to watch considering the large number of emerging SARS-CoV-2 variants and sub-lineages at play.
https://cov-spectrum.org/collections/24
 
It will also be interesting to see if co-infections involving two or more variants or sub-lineages become the next new norm and also to see what the effects of such co-infections will bring.
 
But for sure we will see more breakthrough infections and reinfections with much shorter intervals and we will also see excess deaths rising especially from strokes, heart failures, organ failures and sepsis.
https://www.med.hku.hk/en/news/press/20221027-increase-in-young-stroke
 
https://jamanetwork.com/journals/jama/article-abstract/2795026
 
https://www.dicardiology.com/content/covid-19-surges-linked-spike-heart-attacks
 
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