Abstract

The unremitting emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants necessitates ongoing control measures. Given its rapid spread, the new Omicron subvariant BA.5 requires urgent characterization. Here, we comprehensively analyzed BA.5 with the other Omicron variants BA.1, BA.2, and ancestral B.1.1. Although in vitro growth kinetics of BA.5 was comparable among the Omicron subvariants, BA.5 was much more fusogenic than BA.1 and BA.2. Airway-on-a-chip analysis showed that, among Omicron subvariants, BA.5 had enhanced ability to disrupt the respiratory epithelial and endothelial barriers. Furthermore, in our hamster model, in vivo pathogenicity of BA.5 was slightly higher than that of the other Omicron variants and less than that of ancestral B.1.1. Notably, BA.5 gains efficient virus spread compared with BA.1 and BA.2, leading to prompt immune responses. Our findings suggest that BA.5 has low pathogenicity compared with the ancestral strain but enhanced virus spread /inflammation compared with earlier Omicron subvariants.

The virological and pathological features of Omicron subvariants are compared in in vitro cellular and airway-on-a-chip and in vivo hamster models.

Details

Title
Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5
Author
Tamura, Tomokazu 1   VIAFID ORCID Logo  ; Yamasoba, Daichi 2 ; Oda, Yoshitaka 3 ; Ito, Jumpei 4   VIAFID ORCID Logo  ; Kamasaki, Tomoko 5 ; Nao, Naganori 6 ; Hashimoto, Rina 7   VIAFID ORCID Logo  ; Fujioka, Yoichiro 5 ; Suzuki, Rigel 1 ; Wang, Lei 8   VIAFID ORCID Logo  ; Ito, Hayato 9 ; Kashima, Yukie 10 ; Kimura, Izumi 4 ; Kishimoto, Mai 11 ; Tsuda, Masumi 8   VIAFID ORCID Logo  ; Sawa, Hirofumi 12   VIAFID ORCID Logo  ; Yoshimatsu, Kumiko 13   VIAFID ORCID Logo  ; Yamamoto, Yuki 14 ; Nagamoto, Tetsuharu 14 ; Kanamune, Jun 14 ; Suzuki, Yutaka 10   VIAFID ORCID Logo  ; Ohba, Yusuke 5   VIAFID ORCID Logo  ; Suzuki, Saori 1 ; Kato, Marie 3 ; Ferdous, Zannatul 3 ; Mouri, Hiromi 3 ; Shishido, Kenji 3 ; Misawa, Naoko 4 ; Uriu, Keiya 4 ; Kosugi, Yusuke 4 ; Fujita, Shigeru 4 ; Suganami, Mai 4 ; Chiba, Mika 4 ; Yoshimura, Ryo 4 ; Nakagawa, So 15 ; Wu, Jiaqi 15 ; Takaori-Kondo, Akifumi 16 ; Shirakawa, Kotaro 16 ; Nagata, Kayoko 16 ; Kazuma, Yasuhiro 16 ; Nomura, Ryosuke 16 ; Horisawa, Yoshihito 16 ; Tashiro, Yusuke 16 ; Kawai, Yugo 16 ; Hashiguchi, Takao 16 ; Suzuki, Tateki 16 ; Kimura, Kanako 16 ; Sasaki, Jiei 16 ; Nakajima, Yukari 16 ; Sakamoto, Ayaka 16 ; Yasuhara, Naoko 16 ; Irie, Takashi 17 ; Kawabata, Ryoko 17 ; Ikeda, Terumasa 18 ; Nasser, Hesham 18 ; Shimizu, Ryo 18 ; Begum, Monira 18 ; Takahashi, Otowa 18 ; Ichihara, Kimiko 18 ; Ueno, Takamasa 18 ; Motozono, Chihiro 18 ; Toyoda, Mako 18 ; Saito, Akatsuki 19 ; Tanaka, Yuri L. 19 ; Butlertanaka, Erika P. 19 ; Shofa, Maya 19 ; Tabata, Kaori 20 ; Yokota, Isao 21   VIAFID ORCID Logo  ; Matsuno, Keita 22   VIAFID ORCID Logo  ; Takayama, Kazuo 23   VIAFID ORCID Logo  ; Tanaka, Shinya 8   VIAFID ORCID Logo  ; Sato, Kei 24   VIAFID ORCID Logo  ; Fukuhara, Takasuke 25   VIAFID ORCID Logo 

1  Hokkaido University, Department of Microbiology and Immunology, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Institute for Vaccine Research and Development, HU-IVReD, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
2  The University of Tokyo, Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); Kobe University, Faculty of Medicine, Kobe, Japan (GRID:grid.31432.37) (ISNI:0000 0001 1092 3077) 
3  Hokkaido University, Department of Cancer Pathology, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
4  The University of Tokyo, Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
5  Hokkaido University, Department of Cell Physiology, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Global Station for Biosurfaces and Drug Discovery, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Japan Agency for Medical Research and Development (AMED), AMED-CREST, Tokyo, Japan (GRID:grid.480536.c) (ISNI:0000 0004 5373 4593) 
6  Hokkaido University, Institute for Vaccine Research and Development, HU-IVReD, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Division of International Research Promotion, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, One Health Research Center, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
7  Kyoto University, Center for iPS Cell Research and Application (CiRA), Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
8  Hokkaido University, Department of Cancer Pathology, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
9  Hokkaido University, Department of Microbiology and Immunology, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
10  The University of Tokyo, Graduate School of Frontier Sciences, Kashiwa, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
11  Hokkaido University, Division of Molecular Pathobiology, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
12  Hokkaido University, Institute for Vaccine Research and Development, HU-IVReD, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Division of International Research Promotion, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, One Health Research Center, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Division of Molecular Pathobiology, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, International Collaboration Unit, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
13  Hokkaido University, Institute for Genetic Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
14  HiLung Inc, Kyoto, Japan (GRID:grid.39158.36) 
15  Tokai University School of Medicine, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626) 
16  Kyoto University, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
17  Hiroshima University, Hiroshima, Japan (GRID:grid.257022.0) (ISNI:0000 0000 8711 3200) 
18  Kumamoto University, Kumamoto, Japan (GRID:grid.274841.c) (ISNI:0000 0001 0660 6749) 
19  University of Miayzaki, Kumamoto, Japan (GRID:grid.274841.c) 
20  Kyushu University, Kumamoto, Japan (GRID:grid.177174.3) (ISNI:0000 0001 2242 4849) 
21  Hokkaido University, Department of Biostatistics, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
22  Hokkaido University, Institute for Vaccine Research and Development, HU-IVReD, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, One Health Research Center, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, International Collaboration Unit, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Division of Risk Analysis and Management, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
23  Japan Agency for Medical Research and Development (AMED), AMED-CREST, Tokyo, Japan (GRID:grid.480536.c) (ISNI:0000 0004 5373 4593); Kyoto University, Center for iPS Cell Research and Application (CiRA), Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
24  The University of Tokyo, Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); The University of Tokyo, Graduate School of Medicine, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); The University of Tokyo, Graduate School of Frontier Sciences, Kashiwa, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); The University of Tokyo, International Research Center for Infectious Diseases, The Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); The University of Tokyo, International Vaccine Design Center, The Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); Kumamoto University, Collaboration Unit for Infection, Joint Research Center for Human Retrovirus Infection, Kumamoto, Japan (GRID:grid.274841.c) (ISNI:0000 0001 0660 6749); Japan Science and Technology Agency, CREST, Kawaguchi, Japan (GRID:grid.419082.6) (ISNI:0000 0004 1754 9200) 
25  Hokkaido University, Department of Microbiology and Immunology, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Institute for Vaccine Research and Development, HU-IVReD, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Japan Agency for Medical Research and Development (AMED), AMED-CREST, Tokyo, Japan (GRID:grid.480536.c) (ISNI:0000 0004 5373 4593); Osaka University, Laboratory of Virus Control, Research Institute for Microbial Diseases, Suita, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971) 
Pages
772
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-023-05081-w
ProQuest document ID
2841215145
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.