In vivo antiviral host response to SARS-CoV-2 by viral load, sex, and age
bioinformatics clinical immunology/immunity inflammation
Authors:Lieberman et al.
Link to paper: https://www.biorxiv.org/content/10.1101/2020.06.22.165225v1
Tags: Bioinformatics, Clinical, Immunology/Immunity, Inflammation
This transcriptional study, using nasopharyngeal swabs (NS) from 430 SARS-CoV-2-infected (PCR+) individuals, identified viral load (VL) as a major determinant of host responses.
In silico analysis suggests immune cell infiltration and cytokine production may vary with age and sex, but the data appear somewhat preliminary.
Longitudinal analysis shows a reduction of the IFN response, recovery of translational machinery and initiation of wound healing and humoral responses.
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 infection, of which 19 were also differentially expressed in a Human Airway Epithelial (HAE) cell line upon in vitro infection. In silico analysis points to a differential infiltration of immune cells depending on VL. Analysis of sex and age found males to have reduced B and NK cell-specific transcripts, and age to correlate with CTL or NK dysfunction. Host 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
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
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.