2. Academic Validation
  3. The viral fitness and intrinsic pathogenicity of dominant SARS-CoV-2 Omicron sublineages BA.1, BA.2, and BA.5

The viral fitness and intrinsic pathogenicity of dominant SARS-CoV-2 Omicron sublineages BA.1, BA.2, and BA.5

  • EBioMedicine. 2023 Aug 12;95:104753. doi: 10.1016/j.ebiom.2023.104753.
Huiping Shuai 1,  Jasper Fuk-Woo Chan 2,  Bingjie Hu 1,  Yue Chai 1,  Chaemin Yoon 1,  Huan Liu 1,  Yuanchen Liu 1,  Jialu Shi 1,  Tianrenzheng Zhu 1,  Jing-Chu Hu 3,  Ye-Fan Hu 3,  Yuxin Hou 1,  Xiner Huang 1,  Terrence Tsz-Tai Yuen 1,  Yang Wang 1,  Jinjin Zhang 1,  Yao Xia 1,  Lin-Lei Chen 1,  Jian-Piao Cai 1,  Anna Jinxia Zhang 4,  Shuofeng Yuan 5,  Jie Zhou 4,  Bao-Zhong Zhang 6,  Jian-Dong Huang 3,  Kwok-Yung Yuen 2,  Kelvin Kai-Wang To 7,  Hin Chu 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • 2 State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, China; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China; Academician Workstation of Hainan Province, Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, Hainan, China; and The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, China; Guangzhou Laboratory, Guangdong Province, China.
  • 3 School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • 4 State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China.
  • 5 State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, China; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China.
  • 6 CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong Province, China.
  • 7 State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, China; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China; Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, China; Guangzhou Laboratory, Guangdong Province, China.
  • 8 State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, China; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China. Electronic address: [email protected].
PMID: 37579626 DOI: 10.1016/j.ebiom.2023.104753
Abstract

Background: Among the Omicron sublineages that have emerged, BA.1, BA.2, BA.5, and their related sublineages have resulted in the largest number of infections. While recent studies demonstrated that all Omicron sublineages robustly escape neutralizing antibody response, it remains unclear on whether these Omicron sublineages share any pattern of evolutionary trajectory on their replication efficiency and intrinsic pathogenicity along the respiratory tract.

Methods: We compared the virological features, replication capacity of dominant Omicron sublineages BA.1, BA.2 and BA.5 in the human nasal epithelium, and characterized their pathogenicity in K18-hACE2, A129, young C57BL/6, and aged C57BL/6 mice.

Findings: We found that BA.5 replicated most robustly, followed by BA.2 and BA.1, in the differentiated human nasal epithelium. Consistently, BA.5 Infection resulted in higher viral gene copies, infectious viral titres and more abundant viral antigen expression in the nasal turbinates of the infected K18-hACE2 transgenic mice. In contrast, the Omicron sublineages are continuously attenuated in lungs of infected K18-hACE2 and C57BL/6 mice, leading to decreased pathogenicity. Nevertheless, lung manifestations remain severe in Omicron sublineages-infected A129 and aged C57BL/6 mice.

Interpretation: Our results suggested that the Omicron sublineages might be gaining intrinsic replication fitness in the upper respiratory tract, therefore highlighting the importance of global surveillance of the emergence of hyper-transmissive Omicron sublineages. On the contrary, replication and intrinsic pathogenicity of Omicron is suggested to be further attenuated in the lower respiratory tract. Effective vaccination and other precautions should be in place to prevent severe infections in the immunocompromised populations at risk.

Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Keywords

Animal models; BA.5; COVID-19; Evolution trajectory; Mice; Omicron; Pathogenicity; Replication; SARS-CoV-2; Spike.

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