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Authors:Lieberman et al. 

Journal/ Pre-Print:Bioarchives  

Tags: Bioinformatics, Clinical, Immunology/Immunity, Inflammation 

Research Highlights 

  1. This transcriptional study, using nasopharyngeal swabs (NS) from 430 SARS-CoV-2-infected (PCR+) individuals, identified viral load (VL) as major determinant of host responses. 

  1. In silico analysis suggests immune cell infiltration and cytokine production may vary with age and sex, but the data appear somewhat preliminary.  

  1. Longitudinal analysis shows a reduction of the IFN response, recovery of translational machinery and initiation of wound healing and humoral responses. 

Summary 

Lieberman et al. examine the transcriptome of 430 SARS-CoV-2-infected individuals by RNA sequencing using nasopharyngeal swabs, and correlate gene expression data with VL, age and sex. 83 differentially expressed genes were identified upon infectionof which 19 were also differentially expressed in a Human Airway Epithelial (HAE) cell line upon in vitro infectionIn silico analysis points to a differential infiltration of immune cells depending on VLAnalysis of sex and age found males to have reduced B and NK cell-specific transcripts, and age to correlate with CTL or NK dysfunctionHost responses are mainly linked to VL, that correlates with higher interferon and inflammatory responses as well as a downregulation of the metabolic machinery.  

Impact for SARS-CoV2/COVID19 research efforts  

Understand the immune response to SARS-CoV2/COVID19  

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19 based on VL, age and sex differences 

Study Type  

  • In silico study / bioinformatics study 

  • In vitro study 

  • In vivo study (e.g. mouse, NHP) 

Strengths and limitations of the paper 

Novelty: Large sequencing data set from human patients that links VL, more than age or sex, as the prominent factor inducing a differential host gene expression dominated by an IFN response.  

Standing in the field:Findings are in line with current literature 

Appropriate statistics:  yes 

Viral model used:Clinical samples and icSARS-CoV-2-mNG 

Translatability:This paper dose not focus on therapeutics 

Main limitations:  

  • The study does not discuss disease severity status. 

  • As with many large data sets many different angles are covered but no clear narrative formed; hard to asses validity of each stand-alone finding.   

  • The samples obtained from NS may grasp the response on the upper respiratory track only and may have low sequencing depth. 

  • The paper widely reasons differences in cytokines and cell infiltrates are responsible for increased SARS-CoV2 infection in males and elderly. This cannot be proven without in vitro and in vivo work.