Transcriptome analysis of COVID-19 patient nasopharyngeal samples and SARS-CoV-2 Virus-Like-Particle (VLP) infected cells. COVID-19 patient nasopharyngeal samples and SARS-CoV-2 Virus-Like-Particle (VLP)

In this work, we performed a comparative transcriptomic analysis of COVID-19 patients infected with KR-mutant SARS-CoV-2 (KR-patients n = 39) or wildtype SARS-CoV-2 (RG-patients n = 39) compared to healthy controls (Healthy n = 34). Our data demonstrate noticeable disparities in host transcriptional responses, especially the immune response, between the KR-patients and RG-patients. The impact of KR mutation on immune response was further characterized experimentally in cell lines using the VLP approach. By transcriptomic profiling of VLP infected cells, we identified and validated our observed association of enhanced immune response in the KR variant. These findings reveal an unprecedented link between the nucleocapsid KR mutations (R203K/G204R) in SARS-CoV-2 and a clinically significant hyper-immune phenotype of COVID-19.

本研究针对感染KR突变型严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的新型冠状病毒肺炎（COVID-19）患者（KR组，39例）、感染野生型SARS-CoV-2的COVID-19患者（RG组，39例），以及健康对照组（34例健康个体）开展了比较转录组学分析。研究数据显示，KR组与RG组患者的宿主转录应答，尤其是免疫应答，存在显著差异。本研究进一步通过病毒样颗粒（Virus-like Particle, VLP）实验方法，在细胞系中对KR突变对免疫应答的影响进行了实验表征。通过对VLP感染细胞进行转录组分析，本研究鉴定并验证了KR突变株免疫应答增强的相关关联。上述研究结果揭示了SARS-CoV-2核衣壳KR突变（R203K/G204R）与COVID-19临床意义显著的超免疫表型之间前所未有的关联。