BA.2系統は、従来のBA.1系統よりも伝播力も病原性も高い可能性

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東大の佐藤佳准教授が主催する『The SATO Laboratory』のツイートと、今回の佐藤ラボの論文を紹介した倉持仁医師のツイートより

 

◆Virological characteristics of SARS-CoV-2 BA.2 variant
【bioRxiv　2022年2月15日】
https://www.biorxiv.org/content/10.1101/2022.02.14.480335v1.full

Soon after the emergence and global spread of a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron lineage, BA.1 (ref1, 2), 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.

 

 

◆BREAKING! Japanese Study Alarmingly Reveals That Omicron BA.2 Variant Is A Major Health Threat As It Is More Fusogenic, Pathogenic And Causes Severe Outcomes! – Thailand Medical News
【Thailand Medical News　2022年2月16日】

A new detailed study on the characteristics of the Omicron BA.2 variant by Japanese researchers from the University of Tokyo, Kobe University, Kumamoto University, Hokkaido University and Kyoto University has alarmingly found that the new variant is completely different from the initial Omicron BA.1 variant and is far more fusogenic and pathogenic and poses a serious health threat as it now spreading globally at an exponential rate due to its increased transmissibility.

The study findings also indicate that BA.2 is more rapidly and efficiently spread in the lung tissues than BA.1!

The study was also supported by experts from Weizmann Institute of Science-Israel and the Suez Canal University-Egypt.

Statistical analysis shows that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1.

Neutralization experiments show that the vaccine-induced humoral immunity fails to function against BA.2 variant like BA.1, and notably, the antigenicity of BA.2 is different from BA.1.

The study findings involving cell culture experiments showed that showed that BA.2 is more replicative in human nasal epithelial cells and more fusogenic than BA.1.

Worryingly, infection experiments using hamsters show that BA.2 is more pathogenic than BA.1.

The study findings suggest that the risk of BA.2 for global health is potentially far higher than that of BA.1.

The study findings were published on a preprint server and are currently being peer reviewed. https://www.biorxiv.org/content/10.1101/2022.02.14.480335v1

The study findings showed that although the growth of BA.1 and BA.2 was comparable in VeroE6/TMPRSS2 cells, BA.2 was more replicative than BA.1 in Calu-3 cells and primary human nasal epithelial cells.

Notably, the morphology of infected cells was different; BA.2 formed significantly (1.52-fold) larger syncytia than BA.1. Whereas the plaque size in VeroE6/TMPRSS2 cells infected with BA.1 and BA.2 was significantly smaller than those of cells infected with B.1.1, the plaques formed by BA.2 infection are significantly (1.27-fold) larger than those by BA.1 infection.

Moreover, the coculture of S-expressing cells with HEK293-ACE2/TMPRSS2 cells showed that BA.2 S induces significantly (2.9-fold) larger multinuclear syncytia formation when compared to BA.1.

These study findings suggest that BA.2 is more fusogenic than BA.1.

To further address this possibility, the study team analyzed the fusogenicity of the S proteins of BA.2 S by a cell-based fusion assay. The expression level of BA.2 S on the cell surface was significantly lower than that of BA.1 S.

The fusion assay using VeroE6/TMPRSS2 cells and Calu-3 cells showed that BA.2 S is significantly more fusogenic than BA.1 S.

The study team then analyzed the binding affinity of BA.2 S receptor binding domain (RBD) to ACE2 by a yeast surface display assay. Although the binding affinity of BA.1 S RBD to ACE2 is controversial, our yeast surface display showed that the binding affinity of the RBD of BA.1 and BA.2 is comparable.

These study findings suggest that BA.2 is more rapidly and efficiently spread in the lung tissues than BA.1.

In order to investigate the pathogenicity of BA.2, the right lungs of infected hamsters were collected at 1, 3, and 5 d.p.i. and were used for haematoxylin and eosin (H&E) staining and histopathological analysis.

All histopathological parameters including bronchitis/bronchiolitis, haemorrhage, alveolar damage, and the levels of type II pneumocytes, of BA.2-infected hamsters were significantly higher than those in BA.1.

The score indicating haemorrhage including congestive edema of BA.2 was significantly higher than that of B.1.1.

Hyperplastic large type II pneumocytes suggesting the severity of inflammation were observed in all infected hamsters at 5 d.p.i., and particularly, the area of large type II pneumocytes in BA.2-infected hamsters was significantly larger than those in B.1.1- and BA.1-infected hamsters!

Total histology score of BA.2 was significantly higher than that of BA.1. Furthermore, in the BA.2- and B.1.1-infected lungs, the inflammation with type II alveolar pneumocyte hyperplasia was found in each lobe especially frontal/upper and accessary lobes.

These study findings show that the BA.2 variant can cause extensive lung damage and also cause disease severity in those that are infected and is definitely is not as mild as the initial Omicron BA.1 variant.

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, the study findings suggest the possibility that BA.2 would be the most concerned variant to global health. Currently, both BA.2 and BA.1 are recognized together as Omicron and these are almost undistinguishable.

Based on the study findings, the study team proposes that BA.2 should be recognized as a unique variant of concern, and this SARS-CoV-2 variant should be monitored in depth.