Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5

Tomokazu Tamura; Daichi Yamasoba; Yoshitaka Oda; Jumpei Ito; Tomoko Kamasaki; Naganori Nao; Rina Hashimoto; Yoichiro Fujioka; Rigel Suzuki; Lei Wang; Hayato Ito; Yukie Kashima; Izumi Kimura; Mai Kishimoto; Masumi Tsuda; Hirofumi Sawa; Kumiko Yoshimatsu; Yuki Yamamoto; Tetsuharu Nagamoto; Jun Kanamune; Yutaka Suzuki; Yusuke Ohba; Genotype to Phenotype Japan (G2P-Japan) Consortium; Isao Yokota; Keita Matsuno; Kazuo Takayama; Shinya Tanaka; Kei Sato; Takasuke Fukuhara

doi:10.1038/s42003-023-05081-w

Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5

Commun Biol. 2023 Jul 24;6(1):772. doi: 10.1038/s42003-023-05081-w.

Authors

Tomokazu Tamura^#^{1

2}, Daichi Yamasoba^#^{3

4}, Yoshitaka Oda^#⁵, Jumpei Ito^#³, Tomoko Kamasaki^#^{6

7

8}, Naganori Nao^#^{2

9

10}, Rina Hashimoto^#¹¹, Yoichiro Fujioka^{6

7

8}, Rigel Suzuki^{1

2}, Lei Wang^{5

12}, Hayato Ito¹, Yukie Kashima¹³, Izumi Kimura³, Mai Kishimoto¹⁴, Masumi Tsuda^{5

12}, Hirofumi Sawa^{2

9

10

14

15}, Kumiko Yoshimatsu¹⁶, Yuki Yamamoto¹⁷, Tetsuharu Nagamoto¹⁷, Jun Kanamune¹⁷, Yutaka Suzuki¹³, Yusuke Ohba^{6

7

8}; Genotype to Phenotype Japan (G2P-Japan) Consortium; Isao Yokota¹⁸, Keita Matsuno^{19

20

21

22}, Kazuo Takayama^{23

24}, Shinya Tanaka^{25

26}, Kei Sato^{27

28

29

30

31

32

33}, Takasuke Fukuhara^{34

35

36

37}

Collaborators

Genotype to Phenotype Japan (G2P-Japan) Consortium:
Saori Suzuki, Marie Kato, Zannatul Ferdous, Hiromi Mouri, Kenji Shishido, Naoko Misawa, Keiya Uriu, Yusuke Kosugi, Shigeru Fujita, Mai Suganami, Mika Chiba, Ryo Yoshimura, So Nakagawa, Jiaqi Wu, Akifumi Takaori-Kondo, Kotaro Shirakawa, Kayoko Nagata, Yasuhiro Kazuma, Ryosuke Nomura, Yoshihito Horisawa, Yusuke Tashiro, Yugo Kawai, Takao Hashiguchi, Tateki Suzuki, Kanako Kimura, Jiei Sasaki, Yukari Nakajima, Ayaka Sakamoto, Naoko Yasuhara, Takashi Irie, Ryoko Kawabata, Terumasa Ikeda, Hesham Nasser, Ryo Shimizu, Monira Begum, Otowa Takahashi, Kimiko Ichihara, Takamasa Ueno, Chihiro Motozono, Mako Toyoda, Akatsuki Saito, Yuri L Tanaka, Erika P Butlertanaka, Maya Shofa, Kaori Tabata

Affiliations

¹ Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
² Institute for Vaccine Research and Development, HU-IVReD, Hokkaido University, Sapporo, Japan.
³ Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
⁴ Faculty of Medicine, Kobe University, Kobe, Japan.
⁵ Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
⁶ Department of Cell Physiology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
⁷ Global Station for Biosurfaces and Drug Discovery, Hokkaido University, Sapporo, Japan.
⁸ AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.
⁹ Division of International Research Promotion, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
¹⁰ One Health Research Center, Hokkaido University, Sapporo, Japan.
¹¹ Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
¹² Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Japan.
¹³ Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.
¹⁴ Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
¹⁵ International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
¹⁶ Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
¹⁷ HiLung Inc, Kyoto, Japan.
¹⁸ Department of Biostatistics, Faculty of Medicine, Hokkaido University, Sapporo, Japan. [email protected].
¹⁹ Institute for Vaccine Research and Development, HU-IVReD, Hokkaido University, Sapporo, Japan. [email protected].
²⁰ One Health Research Center, Hokkaido University, Sapporo, Japan. [email protected].
²¹ International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan. [email protected].
²² Division of Risk Analysis and Management, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan. [email protected].
²³ AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan. [email protected].
²⁴ Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan. [email protected].
²⁵ Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan. [email protected].
²⁶ Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Japan. [email protected].
²⁷ Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. [email protected].
²⁸ Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. [email protected].
²⁹ Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan. [email protected].
³⁰ International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. [email protected].
³¹ International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. [email protected].
³² Collaboration Unit for Infection, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan. [email protected].
³³ CREST, Japan Science and Technology Agency, Kawaguchi, Japan. [email protected].
³⁴ Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo, Japan. [email protected].
³⁵ Institute for Vaccine Research and Development, HU-IVReD, Hokkaido University, Sapporo, Japan. [email protected].
³⁶ AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan. [email protected].
³⁷ Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Suita, Japan. [email protected].

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
COVID-19*
Cricetinae
Inflammation
SARS-CoV-2
Virulence

Supplementary concepts

SARS-CoV-2 variants