BA.5 Disrupts Respiratory Epithelial And Endothelial Barriers More Efficiently

A new study involving the comparative pathogenicity of SARS-CoV-2 Omicron subvariants including 1 BA.1, BA.2, and BA.5 by Japanese researchers from Hokkaido University, The University of Tokyo, Kobe University and  Kyoto University has found that the SARS-CoV-2 Ba.5 variant is more fusogenic and disrupts respiratory epithelial and endothelial barriers more efficiently and is more inflammatory

The study findings were publsihed on a preprint server and are currently being peer reviewed.
https://www.biorxiv.org/content/10.1101/2022.08.05.502758v1

In recent months, multiple omicron sub-lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged¹ and impose continually public concerns for COVID-19 control measurement.

The subvariants named BA.4/BA.5 are firstly isolated in South Africa². Now they have been detected in dozens of countries worldwide, with a combined frequency of over 50% in recent weeks at the time of writing the initial manuscript of this study in July 2022.

As of August 2022, BA.5 has outcompeted the original BA.2 and becomes dominant variant in the world. The raising cases of COVID-19 by BA.4/BA.5 indicate that they acquire the enhanced transmission ability compared to the sister linages, BA.1 and BA.2.

Indeed, as shown in a recent report from Portugal where outbreak by BA.5 was occurred³, morbidity of BA.5 is higher than that of BA.1 variants.

To answer potential urgency for COVID-19 wave, the several groups conducted the ability of immunoprophylaxis conferred by vaccination or infection with previous variants. The recent reports showed that BA.4/BA.5 substantially escape from neutralizing antibodies induced by vaccination or infection^4-8.

By genome sequencing and evolutionary analyses, BA.4 and BA.5 are more similar to BA.2 than to the BA.1 strain that surged in late last year. We have been shown that viral spike protein is one of the major virulence determinants^9-12.

BA.4 and BA.5 have identical spike protein and carry their own unique mutations, including L452R that exhibited the enhanced fusogenic activity and pose resistant to the immunity induced by the infection with early variants¹³.

This observation is consistent with the series of our studies using the recombinant viruses replacing the spike protein gene from the ancestral early pandemic variants. However, virological characters of BA.5 strain isolated from COVID-19 patients has not yet fully defined.

Here, we employed the indicated omicron subvariants (BA.1 lineage, strain TY38-873, GISAID ID: EPI_ISL_7418017; BA.2 lineage, strain TY40-385, GISAID ID: EPI_ISL_9595859; BA.5 lineage, strain TKYS14631, GISAID ID: EPI_ISL_12812500)¹⁴ for investigating virological characters in vitro and in vivo model.