Upper airway gene expression differentiates COVID-19 from other acute respiratory illnesses and reveals suppression of innate immune responses by SARS-CoV-2
bioinformatics clinical immunology/immunity
Authors: Mick et al.
Journal/ Pre-Print: MedRxiv
Tags: Immunology/Immunity, Bioinformatics, Clinical/ Diagnostics
1. SARS-CoV-2 infection is specifically associated with a diminished innate immune response in naso/oropharyngeal (NP/OP) samples due to a decreased expression of genes involved in toll-like receptor and interleukin signaling, chemokine binding, neutrophil degranulation, and interactions with lymphoid cells.
2. SARS-CoV-2 infection also specifically affects the proportions of immune cells in NP/OP samples, with a reduction of neutrophils and macrophages, and an increase in goblet, dendritic, and B-cells.
3. Identification of a set of genes (3, 10, or 26) specifically induced in SARS-CoV-2 in comparison to other viral or non-viral acute respiratory illnesses (ARIs), which could be used to complement the SARS-CoV-2 PCR assay.
This study analyzes the host/viral metagenomic transcriptomes of NP/OP swabs from 238 acute respiratory infection (ARI) patients, including 94 SARS-CoV-2 positive, 41 positive for other viral ARIs, and 103 without viral infections. COVID19, in comparison to other ARIs, was associated with diminished innate immune response (including reduced expression of toll-like receptor and interleukin signaling genes) and changes in predicted immune cell counts (reduction in neutrophils and macrophages, increase in goblet, dendritic, and B-cells). The authors also identified predictive models using host gene expression (26, 10, or 3 genes) that differentiate SARS-CoV-2 infection from other ARIs, which they suggest could be used be used along with the SARS-CoV-2 PCR assay to reduce false positives.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19
Understand the virology and/or cell biology of SARS-CoV2/COVID19
Develop diagnostic tools for SARS-CoV2/COVID19
· In silico study / bioinformatics study
· Patient Case study
Strengths and limitations of the paper
Novelty: The authors identified a set of genes induced specifically by SARS-CoV-2, when compared to other viral or non-viral ARIs, which could be used for developing a complementary diagnostic tool, based on the host transcriptional response, for SARS-CoV-2.
Standing in the field: The transcriptomic results, induction by SARS-CoV-2 of ACE2, IFI6, IFI44L, IFI27 and OAS2 and a milder induction of the interferon response, are in agreement with the literature. For the proportions of immune cells, some differences with the literature is observed. In lung bronchoalveolar lavage fluid, Chen et al (MedrXiv, 2020) observed by single-cell RNA-seq an increase in neutrophil count, in T and NK cell activation and a decrease in macrophages. A decrease in macrophages is observed in both studies but a difference is observed for neutrophils (decreased in this study), which could be due to the different origin of the samples (naso/oropharyngeal vs lung bronchoalveolar).
Appropriate statistics: Yes.
Viral model used: SARS-CoV-2 patient data.
Translatability: Identification of a set of genes (3, 10, or 26) specifically induced in SARS-CoV-2 in comparison to other viral or non-viral ARIs, which could be used to complement the SARS-CoV-2 PCR assay.
Main limitations: The study has been performed on naso/oropharyngeal swabs, which might not represent what happened in other tissues/organs known to be infected by SARS-CoV-2. The set of genes specifically induced by SARS-CoV-2 has been identified by comparing patients with single infections, and therefore they might not work for patients with co-infections. The observations on the proportions of immune cells in patients is predicted based on bulk RNA-seq, not single cell RNA-seq or FACS, and might therefore not be correct. This method may only be a suitable diagnostic for critical patients and not diagnose mild or asymptomatic patients.