#17,210
The CDC had been reporting on a related strain (XBB) in the United States for about a month, and while it was gaining on BQ.1/BQ.1.1, it was climbing at a far more leisurely pace than XBB.1.5.
While data on XBB.1.5 is limited, we have seen risk assessments on BQ.1 and XBB suggesting that they may be among the most transmissible, and immune evasive, variants we've seen to date.
This assessment looks at 3 characteristics of these variants (Growth advantage, Immune Escape, and Infection Severity) and found with moderate confidence that in two out of three categories (marked in red), these variants are `worse than BA.5'.
They also found (albeit with low confidence) that for the third characteristic - infection severity - these two new variants remain comparable to BA.5.
While we are seeing hospitalization rates begin to climb in New York State, a region heavily impacted by XBB.1.5, it is not yet year whether this new variant produces any greater severity of infection than previous Omicron variants.
All of which brings us to a new preprint, published yesterday in bioRxiv by researchers from China, that finds that XBB.1.5 not only has enhanced antibody evasion compared to XBB and BQ.1, it also appears to have a substantially increased hACE2-binding affinity as well.
Enhanced transmissibility of XBB.1.5 is contributed by both strong ACE2 binding and antibody evasionCan Yue, Weiliang Song, Lei Wang, Fanchong Jian, Xiaosu Chen, Fei Gao, Zhongyang Shen, Youchun Wang, Xiangxi Wang, Yunlong Richard Caodoi: https://doi.org/10.1101/2023.01.03.522427
Abstract
SARS-CoV-2 recombinant subvariant XBB.1.5 is growing rapidly in the United States, carrying an additional Ser486Pro substitution compared to XBB.1 and outcompeting BQ.1.1 and other XBB sublineages. The underlying mechanism for such high transmissibility remains unclear.
Here we show that XBB.1.5 exhibits a substantially higher hACE2-binding affinity compared to BQ.1.1 and XBB/XBB.1. Convalescent plasma samples from BA.1, BA.5, and BF.7 breakthrough infection are significantly evaded by both XBB.1 and XBB.1.5, with XBB.1.5 displaying slightly weaker immune evasion capability than XBB.1.
Evusheld and Bebtelovimab could not neutralize XBB.1/XBB.1.5, while Sotrovimab remains its weak reactivity and notably, SA55 is still highly effective. The fact that XBB.1 and XBB.1.5 showed comparable antibody evasion but distinct transmissibility suggests enhanced receptor-binding affinity would indeed lead to higher growth advantages.
The strong hACE2 binding of XBB.1.5 could also enable its tolerance of further immune escape mutations, which should be closely monitored.
(SNIP)
With stronger immune escape ability than BQ.1.1 but limited by weaker ACE2 binding affinity, XBB and XBB.1 have only prevailed in a few countries, such as Singapore and India, in the past few months, while BQ.1.1 has quickly become the global dominant strain.
Given its enhanced hACE2-binding affinity but comparable antibody evasion, the prevalence of XBB.1.5 demonstrates that receptor-binding affinity will substantially affect the transmissibility, but the underlying mechanism still needs further investigation. Also, whether the increased receptor-binding affinity would cause a difference in pathogenicity compared to XBB is unclear and requires immediate research 8 .
Moreover, the strong affinity to hACE2 may allow XBB.1.5 to acquire additional immune-escape mutations, similar to the evolution trend of BA.2.75, when met with substantial immune pressure 9 . Therefore, the circulation of XBB.1.5 needs to be closely monitored, and the development of effective neutralizing antibodies and vaccines against XBB.1.5 is urgently needed.
The ability of SARS-CoV-2 to reinvent itself is why we are entering our 4th year of COVID, with no end in sight. Vaccines, which were initially very protective, have become far less so as the virus mutates, and monoclonal antibodies that were once deemed `game-changers', are now nearly useless.
Many seem to want to blame `immune pressure' from the vaccine as the culprit driving COVID's rapid evolution. This is a possibility we've discussed previously (see UK Sage: International Vaccination: Potential impact on Viral Evolution and UK), but it is far from the only potential driver of viral evolution.
Post-infection immunity also deprives the virus of susceptible hosts, and helps drive its evolution, as can the infection of immunocompromised individuals, who may not clear the virus for weeks or months (see EID: Highly Divergent SARS-CoV-2 Alpha Variant in Chronically Infected Immunocompromised Person) allowing the virus extra time to mutate and adapt.
SARS-CoV-2 can also mutate via recombination - which can occur when a host is infected by 2 or more COVID strains (see A COVID Recombination Review). The XBB subvariant is a prime example, as it is recombinant of BA.2.10.1 and BA.2.75 sublineages.
We've also seen ample evidence that SARS-CoV-2 infection of non-human hosts can lead to new mutations, and we've seen several instances where those mutated viruses have spilled back into the human population.
Nature: Divergent SARS-CoV-2 Variant Emerges in White-tailed Deer with Deer-to-Human Transmission (Revisited)
Preprint: Wildlife Exposure to SARS-CoV-2 Across a Human Use Gradient
CDC: Investigating Possible Mink-To-Human Transmission Of SARS-CoV-2 In The United States
Denmark Orders Culling Of All Mink Following Discovery Of Mutated Coronavirus
For more on this, see Maryn McKenna's Wired article Where Did Omicron Come From? Maybe Its First Host Was Mice.
How often SARS-CoV-2 infects animals in the wild is largely unknown, but the spillover of the virus into other species is increasingly viewed as a serious threat (see WHO/FAO/OIE Joint Statement On Monitoring SARS-CoV-2 In Wildlife & Preventing Formation of Reservoirs).
And lastly, SARS-CoV-2 is a single-stranded RNA virus and is therefore subject to `duplication errors' during replication (see Mechanisms of Viral Mutation).
Those who point to the vaccine and blame it for COVID's rapid mutation rate are simply cherry-picking, and demonizing, one of many potential causes.
Even if vaccines can be blamed for some of COVID's rapid evolution, they have also undoubtedly saved millions of lives.
I'll close by repeating what I wrote in the summer of 2021, when we looked at this possibility:
There are no foolproof battle plans for this (or any) pandemic. Global public health outbreaks are complicated and messy, and our responses to them are often confused or sub-optimal. While science should guide us, it doesn't always give us definitive answers at the moment we need them.
In those cases, the best we can do is pick what appears to be the right course at the time, and be ready to pivot if things don't go as planned. Not everything we will try will work. Some may even backfire.
But in a pandemic - as in any crisis - we can't let the fear of failure paralyze us into doing nothing.
