Upper airway gene expression reveals suppressed immune responses to SARS-CoV-2 compared with other respiratory viruses.

Nature Communications
Eran MickCharles Langelier

Abstract

SARS-CoV-2 infection is characterized by peak viral load in the upper airway prior to or at the time of symptom onset, an unusual feature that has enabled widespread transmission of the virus and precipitated a global pandemic. How SARS-CoV-2 is able to achieve high titer in the absence of symptoms remains unclear. Here, we examine the upper airway host transcriptional response in patients with COVID-19 (n = 93), other viral (n = 41) or non-viral (n = 100) acute respiratory illnesses (ARIs). Compared with other viral ARIs, COVID-19 is characterized by a pronounced interferon response but attenuated activation of other innate immune pathways, including toll-like receptor, interleukin and chemokine signaling. The IL-1 and NLRP3 inflammasome pathways are markedly less responsive to SARS-CoV-2, commensurate with a signature of diminished neutrophil and macrophage recruitment. This pattern resembles previously described distinctions between symptomatic and asymptomatic viral infections and may partly explain the propensity for pre-symptomatic transmission in COVID-19. We further use machine learning to build 27-, 10- and 3-gene classifiers that differentiate COVID-19 from other ARIs with AUROCs of 0.981, 0.954 and 0.885, respectivel...Continue Reading

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Citations

Dec 19, 2020·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Benjamin M Liu, Harry R Hill
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Sep 17, 2021·The Indian Journal of Medical Research·Madhu Chhanda MohantyMevis Minin Fernandes

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Datasets Mentioned

BETA
MN908947.3

Methods Mentioned

BETA
PCR
single-cell sequencing
RNA-seq

Software Mentioned

R package MASS
ENSEMBL
REACTOME
R package tximport
Kraken2
kallisto 48
limma
R package glmnet
GSEA
R package fgsea

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