Divergent trajectory of replication and intrinsic pathogenicity of SARS-CoV-2 Omicron post-BA.2/5 subvariants in the upper and lower respiratory tract

Bingjie Hu, Jasper Fuk Woo Chan, Yuanchen Liu, Huan Liu, Yan Xia Chen, Huiping Shuai, Ye Fan Hu, Madeline Hartnoll, Li Chen, Yao Xia, Jing Chu Hu, Terrence Tsz Tai Yuen, Chaemin Yoon, Yuxin Hou, Xiner Huang, Yue Chai, Tianrenzheng Zhu, Jialu Shi, Yang Wang, Yixin HeJian Piao Cai, Jie Zhou, Shuofeng Yuan, Jinxia Zhang, Jian Dong Huang, Kwok Yung Yuen, Kelvin Kai Wang To, Bao Zhong Zhang, Hin Chu

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Background: Earlier Omicron subvariants including BA.1, BA.2, and BA.5 emerged in waves, with a subvariant replacing the previous one every few months. More recently, the post-BA.2/5 subvariants have acquired convergent substitutions in spike that facilitated their escape from humoral immunity and gained ACE2 binding capacity. However, the intrinsic pathogenicity and replication fitness of the evaluated post-BA.2/5 subvariants are not fully understood. Methods: We systemically investigated the replication fitness and intrinsic pathogenicity of representative post-BA.2/5 subvariants (BL.1, BQ.1, BQ.1.1, XBB.1, CH.1.1, and XBB.1.5) in weanling (3–4 weeks), adult (8–10 weeks), and aged (10–12 months) mice. In addition, to better model Omicron replication in the human nasal epithelium, we further investigated the replication capacity of the post-BA.2/5 subvariants in human primary nasal epithelial cells. Findings: We found that the evaluated post-BA.2/5 subvariants are consistently attenuated in mouse lungs but not in nasal turbinates when compared with their ancestral subvariants BA.2/5. Further investigations in primary human nasal epithelial cells revealed a gained replication fitness of XBB.1 and XBB.1.5 when compared to BA.2 and BA.5.2. Interpretation: Our study revealed that the post-BA.2/5 subvariants are attenuated in lungs while increased in replication fitness in the nasal epithelium, indicating rapid adaptation of the circulating Omicron subvariants in the human populations. Funding: The full list of funding can be found at the Acknowledgements section.

Original languageEnglish
Article number104916
Number of pages17
JournalEBioMedicine
Volume99
DOIs
Publication statusPublished - Jan 2024
Externally publishedYes

Fingerprint

Dive into the research topics of 'Divergent trajectory of replication and intrinsic pathogenicity of SARS-CoV-2 Omicron post-BA.2/5 subvariants in the upper and lower respiratory tract'. Together they form a unique fingerprint.

Cite this