RT Journal Article SR Electronic T1 Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.08.05.502758 DO 10.1101/2022.08.05.502758 A1 Tomokazu Tamura A1 Daichi Yamasoba A1 Yoshitaka Oda A1 Jumpei Ito A1 Tomoko Kamasaki A1 Naganori Nao A1 Rina Hashimoto A1 Yoichiro Fujioka A1 Rigel Suzuki A1 Lei Wang A1 Hayato Ito A1 Izumi Kimura A1 Isao Yokota A1 Mai Kishimoto A1 Masumi Tsuda A1 Hirofumi Sawa A1 Kumiko Yoshimatsu A1 Yusuke Ohba A1 Yuki Yamamoto A1 Tetsuharu Nagamoto A1 Jun Kanamune A1 The Genotype to Phenotype Japan (G2P-Japan) Consortium A1 Keita Matsuno A1 Kazuo Takayama A1 Shinya Tanaka A1 Kei Sato A1 Takasuke Fukuhara YR 2022 UL http://biorxiv.org/content/early/2022/08/05/2022.08.05.502758.abstract AB 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.