TY - JOUR T1 - Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5 JF - bioRxiv DO - 10.1101/2022.08.05.502758 SP - 2022.08.05.502758 AU - Tomokazu Tamura AU - Daichi Yamasoba AU - Yoshitaka Oda AU - Jumpei Ito AU - Tomoko Kamasaki AU - Naganori Nao AU - Rina Hashimoto AU - Yoichiro Fujioka AU - Rigel Suzuki AU - Lei Wang AU - Hayato Ito AU - Izumi Kimura AU - Isao Yokota AU - Mai Kishimoto AU - Masumi Tsuda AU - Hirofumi Sawa AU - Kumiko Yoshimatsu AU - Yusuke Ohba AU - Yuki Yamamoto AU - Tetsuharu Nagamoto AU - Jun Kanamune AU - The Genotype to Phenotype Japan (G2P-Japan) Consortium AU - Keita Matsuno AU - Kazuo Takayama AU - Shinya Tanaka AU - Kei Sato AU - Takasuke Fukuhara Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/08/05/2022.08.05.502758.abstract N2 - Unremitting emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants imposes us to continuous control measurement. Given the rapid spread, new Omicron subvariant named BA.5 is urgently required for characterization. Here we analyzed BA.5 with the other Omicron variants BA.1, BA.2, and ancestral B.1.1 comprehensively. Although in vitro growth kinetics of BA.5 is comparable among the Omicron subvariants, BA.5 become much more fusogenic than BA.1 and BA.2. The airway-on-a-chip analysis showed that the ability of BA.5 to disrupt the respiratory epithelial and endothelial barriers is enhanced among Omicron subvariants. Furthermore, in our hamster model, in vivo replication of BA.5 is comparable with that of the other Omicrons and less than that of the ancestral B.1.1. Importantly, inflammatory response against BA.5 is strong compared with BA.1 and BA.2. Our data suggest that BA.5 is still low pathogenic compared to ancestral strain but evolved to induce enhanced inflammation when compared to prior Omicron subvariants.Competing Interest StatementYuki Yamamoto and Tetsuharu Nagamoto are founders and shareholders of HiLung, Inc. Jun Kanamune is an employee of HiLung, Inc. Yuki Yamamoto is a co-inventor of patents (PCT/JP2016/057254; "Method for inducing differentiation of alveolar epithelial cells", PCT/JP2016/059786, "Method of producing airway epithelial cells"). The other authors declare that no competing interests exist. ER -