Comparative Upper Respiratory Tract Transcriptomic Profiling Reveals a Potential Role of Early Activation of Interferon Pathway in Severe COVID-19

Abstract

Infection with SARS-CoV-2 results in Coronavirus disease 2019 (COVID-19) is known to cause mild to acute respiratory infection and sometimes progress towards respiratory failure and death. The mechanisms driving the progression of the disease and accumulation of high viral load in the lungs without initial symptoms remain elusive. In this study, we evaluated the upper respiratory tract host transcriptional response in COVID-19 patients with mild to severe symptoms and compared it with the control COVID-19 negative group using RNA-sequencing (RNA-Seq). Our results reveal an upregulated early type I interferon response in severe COVID-19 patients as compared to mild or negative COVID-19 patients. Moreover, severely symptomatic patients have pronounced induction of interferon stimulated genes (ISGs), particularly the oligoadenylate synthetase (OAS) family of genes. Our results are in concurrence with other studies depicting the early induction of IFN-I response in severe COVID-19 patients, providing novel insights about the ISGs involved.

A deficient immune response to SARS-CoV-2 in the nasopharynx is associated with severe COVID-19 pneumonia

“…The univariate analysis also found that IFN-β expression levels increased with increasing pneumonia severity. Since IFN-β induces the expression of ISGs [18 , 19] , the low expression of RIG-I, ISG15, CCL5 , and CXCL10 seems contradictory. However, Sposito et al .…”

Epigenetic liquid biopsies reveal elevated vascular endothelial cell turnover and erythropoiesis in asymptomatic COVID-19 patients

“…(iv) Heightened interferon response. SARS-Cov-2 infection causes a massive elevation in the expression of interferon-stimulated genes, as measured in leukocytes and in material from invasive biopsies (35)(36)(37). The identification of an interferon response in cell-free chromatin underscores the potential of epigenetic liquid biopsies to reveal gene expression program in cells prior to their death.…”