Why BA.2 Variant Is A Major Health Threat?


A new detailed study on the characteristics of the Omicron BA.2 variant by Japanese researchers 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, reports Thailand Medical News.

What are the outcomes of the study?

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

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 risk of BA.2 for global health 

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.

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.

Impact on lungs 

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.

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.

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Source: Thailand Medical News


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