SARS-CoV-2 Delta AY.122 Subvariant: China Imposes Urgent Stringent Lockdown In City Of Baise Near Vietnam Border

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Chinese authorities over the last 24 hours imposed an urgent and stringent lockdown in the city of Baise in the southern Guangxi region that is home to more than 3.6 million people due to a new surge that is being caused by the SARS-CoV-2 Delta subvariant AY.122 and also sub-lineages that the AY.122 is also spawning.

The AY.122 subvariant has been causing a massive surge in Vietnam and also in Russia and is more severe than the Omicron.

Infections with the AY.122 variant has shown to be more severe and often needs hospitalization and also the mortality risk is increased especially for the elderly and those with existing comorbidities.

To date more than 70 cases have been confirmed over the last 3 days but hundreds more of symptomatic individuals are awaiting test results according to local health authorities.
It was reported that China is the only major world economy that still sticking to a staunch zero-COVID policy.
 
The country is also on high alert for any outbreaks as it hosts the Beijing Winter Olympics.
 
Health officials in the city of Baise in the southern Guangxi region announced late Sunday that no one would be allowed to leave the city, while residents of some districts would be confined to their homes.
 
Vice-mayor for Baise, Gu Junyan told local media, “Citywide traffic controls will be implemented. In principle, vehicles and people cannot enter or leave the city and personnel control strictly enforced to ensure no unnecessary movement of people.”
 
He added that residents of some neighborhoods in smaller rural cities and counties under Baise’s jurisdiction have been placed under strict home confinement, while others cannot leave their district.
 
The city of Baise, located about 100 kilometers (62 miles) from the Vietnamese border, on Friday discovered its first local case ie a traveler who had returned home for the week-long Lunar New Year holiday from Vietnam, according to local Chinese officials.
 
China has built a heavily enforced wire mesh fence along its southern border to keep out illegal migrants from Vietnam and Myanmar ever since the pandemic started as well as potential COVID-19 infections.

The AY.122 lineage was frequent in Russia among Delta samples from the start, and has not increased in frequency in other countries where it has been observed, suggesting that its high prevalence in Russia has probably resulted from a random founder effect.

The presence of the nsp2:K81N mutation puts these 92.4% of Russian Delta samples in the recently designated AY.122 pango lineage.

The nsp2:K81N+ORF7a:P45L combination is rare among GISAID Delta samples worldwide (2.3%); outside Russia, its frequency is the highest in Moldova (100%; 9 out of 9 samples), followed by Ecuador (86%; 76 out of 89 samples), Kazakhstan (76%; 32 out of 42 samples) and Latvia (73%; 52 out of 71 samples).

The Omicron has not been able to displace the Delta AY.122 subvariant that seems to in fact working in the opposite direction and is now the predominant variant in both countries and gradually spreading to other countries. 

https://www.medrxiv.org/content/10.1101/2021.12.02.21267168v1

The success of the AY.122+ORF7a:P45L combination is probably not due to increased fitness
To explain the success of the nsp2:K81N+ORF7a:P45L combination in Russia, we hypothesized that it could arise from fitness advantage conferred by these two mutations.

The identity of these mutations does not lend strong support to this hypothesis. nsp2 is a rapidly evolving non-structural protein which was found to be localized to endosomes and viral replication-transcription complexes. Based on structural analysis and affinity purification mass spectrometry, it is thought to interact with multiple host proteins and mitochondrial RNA, and its suggested functions are engagement of mitochondria to viral replication sites and modulation of cellular endosomal pathway [37].

No signs of either positive or negative selection were found at site 81 of nsp2 (https://observablehq.com/@spond/evolutio[email protected]spond/sars-cov-2) using FEL and MEME algorithms of HyPhy [38].

ORF7a has been shown to suppress BST2 protein that restricts the egress of viral particles from the cell [39]. It was also shown to bind to CD14+ monocytes, which reduces their antigen representation capacity and triggers the production of proinflammatory cytokines [40]. Nonsynonymous mutations in ORF7a contribute to SARS-CoV-2 clade success [18].

C-terminal truncations of ORF7a are frequent and were shown to affect viral replication [41]. Nevertheless, a lineage characterized by a frameshifting deletion in ORF7a has spread rapidly in Australia [42]. Site ORF7a:45 experiences episodic diversifying selection (according to MEME algorithm of HyPhy) and increase of non-reference amino acid in frequency according to (https://observablehq.com/@spond/evolutio[email protected]spond/sars-cov-2). It has also been predicted to be included in the B-cell epitope [43].

Moreover, the dynamics of the nsp2:K81N + ORF7a:P45L combination outside Russia also doesn’t support its increased fitness. To show this, we estimated the logistic growth rates of this combination in those countries where it has been frequent (with >15 days with samples carrying this combination both before and after July 1).

While this lineage has been growing in most countries before July 1 (Fig. S7), this growth was due to the weakness of competition from non-Delta variants; no systematic growth compared with other Delta lineages was observed (Fig. S8).

The lack of a systematic fitness advantage of this lineage across the globe suggests that the selection that favors this variant, if it exists, is weak.


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