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Analysis of blood and nasal epithelial transcriptomes to identify mechanisms associated with control of SARS-CoV-2 viral load in the upper respiratory tract

Marjaneh et al., Journal of Infection, doi:10.1016/j.jinf.2023.10.009
Oct 2023  
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Blood and nasal epithelial transcriptomic analysis suggesting potential benefits of several treatments including:
Vitamin E: transcriptomic analysis revealed that the AIPL1 module, which contains genes connected to vitamin E (α-tocopherol), negatively correlated with SARS-CoV-2 viral load. Vitamin E has antioxidant properties and is known to enhance immune cell functions like natural killer cell activity. The enrichment of the α-tocopherol degradation pathway in this module suggests vitamin E may aid viral control.
NSAIDs: transcriptomic analysis revealed that increased expression of inflammation-related genes, including those involved in prostanoid synthesis, was associated with higher SARS-CoV-2 viral loads. NSAIDs including ibuprofen, indomethacin, and aspirin can inhibit prostanoid production by blocking cyclooxygenase enzymes. By suppressing these inflammatory prostanoids that may enhance viral replication, NSAID treatment could potentially restrict SARS-CoV-2 viral load in the upper respiratory tract.
Study covers indomethacin, ibuprofen, and aspirin.
Marjaneh et al., 18 Oct 2023, peer-reviewed, 21 authors. Contact: m.moradi@imperial.ac.uk, a.cunnington@imperial.ac.uk.
This PaperIndomethacinAll
Analysis of blood and nasal epithelial transcriptomes to identify mechanisms associated with control of SARS-CoV-2 viral load in the upper respiratory tract
Mahdi Moradi Marjaneh, Joseph D Challenger, Antonio Salas, Alberto Gómez-Carballa, Abilash Sivananthan, Irene Rivero-Calle, Gema Barbeito-Castiñeiras, Cher Y Foo, Yue Wu, Felicity Liew, Heather R Jackson, Dominic Habgood-Coote, Giselle D’souza, Samuel J Nichols, Victoria J Wright, Michael Levin, Myrsini Kaforou, Ryan S Thwaites, Lucy C Okell, Federico Martinón-Torres, Aubrey J Cunnington
Journal of Infection, doi:10.1016/j.jinf.2023.10.009
Objectives: The amount of SARS-CoV-2 detected in the upper respiratory tract (URT viral load) is a key driver of transmission of infection. Current evidence suggests that mechanisms constraining URT viral load are different from those controlling lower respiratory tract viral J o u r n a l P r e -p r o o f mechanisms, including likely roles for NK cells, granulysin, prostanoids and interferon alpha-14. Inhibition of prostanoid production, and administration of interferon alpha-14 may be attractive transmission-blocking interventions.
accession E-MTAB-12791. NanoString nCounter data and corresponding metadata are available at https://github.com/MahdiMoradiMarjaneh/COVID19_viral_load. Codes used in the analyses can be accessed on the same GitHub repository. Competing interests The authors declare that they have no competing interests. -0 .69 1 How many days after symptom onset the viral load was measured. 2 Cycle threshold value 3 Relative to the days of illness at the time of viral load measurement (see Figure 2D ) * These two samples are from the same subject The number of genes involved in each module. 2 Genes with the absolute value of module membership (the correlation between the module eigengene and gene expression values) > 0.9. Genes with negative module membership are marked with an asterisk. 3 No genes had module membership higher than 0.9 or lower than -0.9 Authors' contributions Conceptualization Declarations of interest: None. Graphical
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