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

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.