Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G

Zigui Chen; Rita Way Yin Ng; Grace Lui; Lowell Ling; Agnes S. Y. Leung; Chit Chow; Siaw Shi Boon; Wendy C. S. Ho; Maggie Haitian Wang; Renee Wan Yi Chan; Albert Martin Li; David Shu Cheong Hui; Paul Kay Sheung Chan

doi:10.1016/j.virs.2024.01.010

April 2024

. doi: 10.1016/j.virs.2024.01.010

Citation: Zigui Chen, Rita Way Yin Ng, Grace Lui, Lowell Ling, Agnes S. Y. Leung, Chit Chow, Siaw Shi Boon, Wendy C. S. Ho, Maggie Haitian Wang, Renee Wan Yi Chan, Albert Martin Li, David Shu Cheong Hui, Paul Kay Sheung Chan. Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G .VIROLOGICA SINICA, 2024, 39(2) : 218-227. http://dx.doi.org/10.1016/j.virs.2024.01.010

严重急性呼吸系统综合症冠状病毒2型（SARS-CoV-2）Omicron BA.2变异株和非关注D614G变异株（non-VOC-D614G）亚基因组RNA的定量和定性研究

陈子桂 ^a ,
吴炜燕 ^a ,
雷颂恩 ^b ,
凌若崴 ^c ,
梁诗彦 ^d ,
周捷 ^e ,
温晓诗 ^a ,
何静诗 ^a ,
王海天 ^f ,
陈韵怡 ^d ,
李民瞻 ^d ,
许树昌 ^b,g ,
陈基湘 ^a,g,,

a. 香港中文大学医学院微生物学系;
b. 香港中文大学医学院内科及药物治疗学系;
c. 香港中文大学医学院微生物学系麻醉及深切治疗学系;
e. 香港中文大学医学院病理解剖及细胞学系;
f. 香港中文大学医学院赛马会公共衞生及基层医疗学院;
g. 香港中文大学医学院何鸿燊防治传染病研究中心

通讯作者： 陈基湘, paulkschan@cuhk.edu.hk
收稿日期： 2023-10-18
录用日期： 2024-01-31

摘要

严重急性呼吸系统综合症冠状病毒2型（SARS-CoV-2）欧密克戎（Omicron）变异株因其高传播性而臭名昭著，但对其亚基因组RNA（sgRNA）的表达知之甚少。本研究应用RNA高通量测序技术描绘了118例欧密克戎BA.2变异株（Omicron BA.2）和338例非关注D614G变异株（non-VOC-D614G）的典型sgRNA的定量和定性特征。结果显示，无论患者的性别、年龄以及是否患有肺炎，Omicron BA.2和non-VOC-D614G均表现出由9个典型sgRNA相对丰度组成的独特特征定量表达谱。这种表达谱在病毒载量低时会消失，表明sgRNA模式有可能用于指示特定时间点患者的病毒活性。对Omicron BA.2和non-VOC-D614G典型sgRNA的特征定性表达谱的描述发现，所有9个典型sgRNA均表达的模式与病毒载量具一致相关性（AUC = 0.91，95% CI 0.88 - 0.94），其中的sgRNA ORF7b可被视为最佳替代标志物，用于检测患者个体化感染状况。sgRNA在疫苗和抗病毒药物开发中的应用潜力值得进一步挖掘。
- 严重急性呼吸系统综合症冠状病毒2型
- , 欧密克戎BA.2变异株
- , 非关注D614G变异株
- , 亚基因组RNA
- , RNA高通量测序

Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G

a. Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China;
b. Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China;
c. Department of Anaesthesia and Intensive Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China;
d. Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China;
e. Department of Anatomical and Cellular Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China;
f. Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China;
g. Stanley Ho Centre for Emerging Infectious Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China

Corresponding author: Paul Kay Sheung Chan, paulkschan@cuhk.edu.hk
Received Date: 18 October 2023
Accepted Date: 31 January 2024

Abstract

The SARS-CoV-2 Omicron variants are notorious for their transmissibility, but little is known about their subgenomic RNA (sgRNA) expression. This study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern (non-VOC)-D614G. A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOC-D614G regardless of host gender, age and presence of pneumonia. Remarkably, such profile was lost in samples with low viral load, suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point. A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and non-VOC-D614G. The presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load (AUC = 0.91, 95% CI 0.88–0.94), and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual patient. Further potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.
- Coronavirus
- , SARS-CoV-2
- , Omicron BA.2
- , Non-VOC-D614G
- , RNA-seq
- , Subgenomic RNA(sgRNA)

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