SARS-CoV-2 variants induce increased inflammatory gene expression but reduced interferon responses and heme synthesis as compared with wild type strains

Mariam Merchant, Javaria Ashraf, Kiran Iqbal Masood, Maliha Yameen, Rabia Hussain, Asghar Nasir, Zahra Hasan

Research output: Contribution to journalArticlepeer-review

Abstract

SARS-CoV-2 variants of concern (VOC) have been associated with increased viral transmission and disease severity. We investigated the mechanisms of pathogenesis caused by variants using a host blood transcriptome profiling approach. We analysed transcriptional signatures of COVID-19 patients comparing those infected with wildtype (wt), alpha, delta or omicron strains seeking insights into infection in Asymptomatic cases. Comparison of transcriptional profiles of Symptomatic and Asymptomatic COVID-19 cases showed increased differentially regulated gene (DEGs) of inflammatory, apoptosis and blood coagulation pathways, with decreased T cell and Interferon stimulated genes (ISG) activation. Between SARS-CoV-2 strains, an increasing number of DEGs occurred in comparisons between wt and alpha (196), delta (1425) or, omicron (2313) infections. COVID-19 cases with alpha or, delta variants demonstrated suppression transcripts of innate immune pathways. EGR1 and CXCL8 were highly upregulated in those infected with VOC; heme biosynthetic pathway genes (ALAS2, HBB, HBG1, HBD9) and ISGs were downregulated. Delta and omicron infections upregulated ribosomal pathways, reflecting increased viral RNA translation. Asymptomatic COVID-19 cases infected with delta infections showed increased cytokines and ISGs expression. Overall, increased inflammation, with reduced host heme synthesis was associated with infections caused by VOC infections, with raised type I interferon in cases with less severe disease.

Original languageEnglish
Article number25734
JournalScientific Reports
Volume14
Issue number1
DOIs
Publication statusPublished - Dec 2024

Keywords

  • ALAS2
  • Delta variant
  • EGR1
  • ISG
  • SARS-CoV-2
  • Variants of concern

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