Thursday, February 17, 2022

Preprint: Virological characteristics of SARS-CoV-2 BA.2 variant


CDC Nowcast Tracking 3 Omicron Variants (B.1.1.529, BA.1.1 & BA.2)

#16,577

Although we saw a welcomed reduction in the severity of COVID infection with the arrival of the Omicron (B.1.1.529) variant late last year, we've also seen a concurrent increase in its transmissibility.  As a result, hospitals and emergency services remain stressed, and deaths remain fairly high. 

Over the past 3 months several subvariants of Omicron have also emerged (BA.1, BA.1.1, BA.2 & BA.3), and while evidence is limited, some are clearly more transmissible than B.1.1.529. 

In some parts of the world BA.2 is already the dominant strain, while in others BA.1 is dominant, but BA.2 is showing signs of catching up. Two days ago (see CDC Nowcast: Now Tracking 3 Omicron Variants), the CDC estimated BA.1.1 to comprise > 73% of all cases, while BA.2 only represented 3.9%. 

But BA.2 is estimated to have more than doubled over the past week in the United States, and given its performance elsewhere in the world, may erode BA.1.1's current dominance in the weeks ahead. 

Over the past 90 days we've seen the COVID world rocked 3 times by new variants; B.1.1.529 which gave way to BA.1, which now appears to be giving way to BA.2 (at least in some parts of the world). 

While another variant could always emerge to rock the boat, right now the battle for king of the COVID hill appears to be between BA.1 (including BA.1.1) and BA.2.

Although not a lot is known about BA.1.1, and even less about BA.3, we are starting to get a better handle on the capabilities of BA.2.  Today we have a preprint, which suggests BA.2 probably has what it takes to overtake BA.1, and become the dominant strain. 

The authors also suggest that BA.2 may be more pathogenic (at least in hamsters) than BA.1, and therefore may pose a greater threat to global health. 

The two big caveats here being that this is a preprint, and is not a peer-reviewed study, and greater pathogenicity in hamsters may not directly translate to pathogenicity in humans. 

Every risk assessment we've seen so far (see below) has been quick to say there is "No evidence of increase in severity of BA.2 relative to BA.1", and so far, we've yet to see any obvious signals of increased severity in countries where BA.2 is already dominant. 


Still, this report's findings are sobering, and require further study. This is a long (52-page), highly technical report, and I've only reproduced the abstract and excerpts from the summary below (bolding mine). 

You'll want to follow the link to read it in its entirety.  I'll have a brief postscript when you return. 


Virological characteristics of SARS-CoV-2 BA.2 variant

Daichi Yamasoba, Izumi Kimura, Hesham Nasser, Yuhei Morioka, Naganori Nao, Jumpei Ito, Keiya Uriu, Masumi Tsuda, Jiri Zahradnik, Kotaro Shirakawa, Rigel Suzuki, Mai Kishimoto, Yusuke Kosugi, Kouji Kobiyama, Teppei Hara, Mako Toyoda, Yuri L Tanaka, Erika P Butlertanaka, Ryo Shimizu, Hayato Ito, Lei Wang, Yoshitaka Oda, Yasuko Orba, Michihito Sasaki, Kayoko Nagata, Kumiko Yoshimatsu, Hiroyuki Asakura, Mami Nagashima, Kenji Sadamasu, Kazuhisa Yoshimura, Jin Kuramochi, Motoaki Seki, Ryoji Fujiki, Atsushi Kaneda, Tadanaga Shimada, Taka-aki Nakada, Seiichiro Sakao, Takuji Suzuki, Takamasa Ueno, Akifumi Takaori-Kondo, Ken J Ishii, Gideon Schreiber, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Hirofumi Sawa, Akatsuki Saito, Takashi Irie, Shinya Tanaka, Keita Matsuno, Takasuke Fukuhara, Terumasa Ikeda, Kei Sato

doi: https://doi.org/10.1101/2022.02.14.480335


Abstract

Soon after the emergence and global spread of a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron lineage, BA.1, another Omicron lineage, BA.2, has initiated outcompeting BA.1. Statistical analysis shows that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralisation experiments show that the vaccine-induced humoral immunity fails to function against BA.2 like BA.1, and notably, the antigenicity of BA.2 is different from BA.1.

Cell culture experiments show that BA.2 is more replicative in human nasal epithelial cells and more fusogenic than BA.1. Furthermore, infection experiments using hamsters show that BA.2 is more pathogenic than BA.1. Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1.

          (SNIP)

Discussion 

Although BA.2 is considered as an Omicron variant, its genomic sequence is heavily different from BA.1, which suggests that the virological characteristics of BA.2 is different from that of BA.1. Here, we elucidated the virological characteristics of BA.2, such as its higher effective reproduction number, higher fusogenicity, higher pathogenicity when compared to BA.1.

Moreover, we   demonstrated that BA.2 is resistant to the BA.1-induced humoral immunity. Our data indicate that BA.2 is virologically different from BA.1 and raise a proposal that BA.2 should be given a letter of the Greek alphabet and be distinguished from BA.1, a commonly recognized Omicron variant.

(SNIP) 

Third, it would be most critical for global health that BA.2 exhibits higher pathogenicity than BA.1. Although clinical researches on the BA.2 pathogenicity are needed, our investigations using a hamster model showed that the pathogenicity of BA.2 is similar to that of an ancestral B.1.1 and higher than that  of BA.1. 

More importantly, the viral RNA load in the lung periphery and histopathological disorders of BA.2 were more severe than those of BA.1 and even B.1.1. Together with a higher effective reproduction number and pronounced immune resistance of BA.2, it is evident that the spread of BA.2 can be a serious issue for global health in the near future. 

In summary, our data suggest the possibility that BA.2 would be the most concerned variant to global health. Currently, both BA.2 and BA.1 are recognised together as Omicron and these are almost undistinguishable. Based on our findings, we propose that BA.2 should be recognised as a unique variant of concern, and this SARS-CoV-2 variant should be monitored in depth.

          (Continue.  . . )

The lesson of the last 3 months is that COVID continues to evolve at a rapid pace, and today's dominant variant can easily become extinct - or at least irrelevant - over a matter of weeks or months.  

Until this rapid-replacement cycle slows markedly, predictions about what the pandemic will do in the months ahead are more guesswork than science.