Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Authors: Sohn et al. 

Journal/ Pre-PrintbioRxiv 

Tags: Immunology/Immunity, Inflammation, Transcriptomics 

Research Highlights 

  1. PBMCs of mild & severe COVID-19 patients showed upregulation of genes involved in cytokine-cytokine receptor interaction and NFκB signalling. 

  1. The expression of TLR4 (receptor for LPS, S100 proteins) was increased in patient PBMC compared to healthy control PBMC, whereas the expression of TLR7 and TLR8 (receptors for viral ssRNA) was unchanged. 

  1. No differential gene expression of immune genes between mild & severe patients was identifiedpossibly due to large heterogeneity within groups.  

Summary 

This paper describes 20 mild/moderate COVID-19 patients, 8 severe patients, and 20 healthy controls. RNA-sequencing of PBMC samples was performed with Nanostring nCounter Human Immunology gene expression assays. Differential PBMC counts are not described, making it unclear whether the detected changes in gene expression are related to transcriptional changes or to shifts in the PBMC composition. Many components of the NFκB signalling pathway were upregulated in COVID-19 patients. This pathway lies downstream of TLRs and the IL-1β receptor, amongst others, indicating inflammatory signalling in PBMCs of patients. 

Impact for SARS-CoV2/COVID19 research efforts 

Understand the immune response to SARS-CoV2/COVID19  

Study Type 

  • Patient Case study; descriptive transcriptomics of 28 patients 

Strengths and limitations of the paper 

Novelty:  

Standing in the field:Considering existing literature, it is surprising that there is no difference at all in immune gene expression between mild and severe patients, but this is likely a consequence of low statistical power.  

Appropriate statistics: Yes, but the entire PCA (Fig. 1B) is dominated by 1 outlier, and the thresholds for differential expression are lenient. 

Viral model used:none (SARS-CoV-infected patients) 

Translatability:No direct translational potential. 

Main limitations: > The authors conclude that the upregulation in NFκB signalling pathway components is related to TLR4 signalling but don’t provide mechanistic evidence for this. This important pathway can also be triggered by other immune receptors. 

> It is mentioned that part of the mild/moderate patient group was asymptomatic but it is unclear how many patients and if there are any differences in their transcriptomic profile. 

> Only immune genes were checked, and only at the mRNA level.