tetano
Editor, Senior Moderator
Clin Immunol
. 2023 Oct 16:109808.
doi: 10.1016/j.clim.2023.109808. Online ahead of print. Multi-omic profiling reveals early immunological indicators for identifying COVID-19 Progressors
Katherine A Drake[SUP] 1 [/SUP], Dimitri Talantov[SUP] 2 [/SUP], Gary J Tong[SUP] 1 [/SUP], Jack T Lin[SUP] 1 [/SUP], Simon Verheijden[SUP] 2 [/SUP], Samuel Katz[SUP] 1 [/SUP], Jacqueline M Leung[SUP] 1 [/SUP], Benjamin Yuen[SUP] 1 [/SUP], Vinod Krishna[SUP] 2 [/SUP], Michelle J Wu[SUP] 1 [/SUP], Alex Sutherland[SUP] 1 [/SUP], Sarah A Short[SUP] 1 [/SUP], Pouya Kheradpour[SUP] 1 [/SUP], Maxwell Mumbach[SUP] 1 [/SUP], Kate M Franz[SUP] 1 [/SUP], Vladimir Trifonov[SUP] 2 [/SUP], Molly V Lucas[SUP] 2 [/SUP], James Merson[SUP] 2 [/SUP], Charles C Kim[SUP] 3 [/SUP]; PRESCO Study Group
Collaborators, Affiliations
We sought to better understand the immune response during the immediate post-diagnosis phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by identifying molecular associations with longitudinal disease outcomes. Multi-omic analyses identified differences in immune cell composition, cytokine levels, and cell subset-specific transcriptomic and epigenomic signatures between individuals on a more serious disease trajectory (Progressors) as compared to those on a milder course (Non-progressors). Higher levels of multiple cytokines were observed in Progressors, with IL-6 showing the largest difference. Blood monocyte cell subsets were also skewed, showing a comparative decrease in non-classical CD14[SUP]-[/SUP]CD16[SUP]+[/SUP] and intermediate CD14[SUP]+[/SUP]CD16[SUP]+[/SUP] monocytes. In lymphocytes, the CD8[SUP]+[/SUP] T effector memory cells displayed a gene expression signature consistent with stronger T cell activation in Progressors. These early stage observations could serve as the basis for the development of prognostic biomarkers of disease risk and interventional strategies to improve the management of severe COVID-19. BACKGROUND: Much of the literature on immune response post-SARS-CoV-2 infection has been in the acute and post-acute phases of infection. TRANSLATIONAL SIGNIFICANCE: We find differences at early time points of infection in approximately 160 participants. We compared multi-omic signatures in immune cells between individuals progressing to needing more significant medical intervention and non-progressors. We observed widespread evidence of a state of increased inflammation associated with progression, supported by a range of epigenomic, transcriptomic, and proteomic signatures The signatures we find support other findings at later time points and serve as the basis for prognostic biomarker development or inform interventional strategies.
Keywords: COVID19; Early infection; Multi-omic analysis; SARS-CoV-2; Systems immunology.
. 2023 Oct 16:109808.
doi: 10.1016/j.clim.2023.109808. Online ahead of print. Multi-omic profiling reveals early immunological indicators for identifying COVID-19 Progressors
Katherine A Drake[SUP] 1 [/SUP], Dimitri Talantov[SUP] 2 [/SUP], Gary J Tong[SUP] 1 [/SUP], Jack T Lin[SUP] 1 [/SUP], Simon Verheijden[SUP] 2 [/SUP], Samuel Katz[SUP] 1 [/SUP], Jacqueline M Leung[SUP] 1 [/SUP], Benjamin Yuen[SUP] 1 [/SUP], Vinod Krishna[SUP] 2 [/SUP], Michelle J Wu[SUP] 1 [/SUP], Alex Sutherland[SUP] 1 [/SUP], Sarah A Short[SUP] 1 [/SUP], Pouya Kheradpour[SUP] 1 [/SUP], Maxwell Mumbach[SUP] 1 [/SUP], Kate M Franz[SUP] 1 [/SUP], Vladimir Trifonov[SUP] 2 [/SUP], Molly V Lucas[SUP] 2 [/SUP], James Merson[SUP] 2 [/SUP], Charles C Kim[SUP] 3 [/SUP]; PRESCO Study Group
Collaborators, Affiliations
- PMID: 37852344
- DOI: 10.1016/j.clim.2023.109808
We sought to better understand the immune response during the immediate post-diagnosis phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by identifying molecular associations with longitudinal disease outcomes. Multi-omic analyses identified differences in immune cell composition, cytokine levels, and cell subset-specific transcriptomic and epigenomic signatures between individuals on a more serious disease trajectory (Progressors) as compared to those on a milder course (Non-progressors). Higher levels of multiple cytokines were observed in Progressors, with IL-6 showing the largest difference. Blood monocyte cell subsets were also skewed, showing a comparative decrease in non-classical CD14[SUP]-[/SUP]CD16[SUP]+[/SUP] and intermediate CD14[SUP]+[/SUP]CD16[SUP]+[/SUP] monocytes. In lymphocytes, the CD8[SUP]+[/SUP] T effector memory cells displayed a gene expression signature consistent with stronger T cell activation in Progressors. These early stage observations could serve as the basis for the development of prognostic biomarkers of disease risk and interventional strategies to improve the management of severe COVID-19. BACKGROUND: Much of the literature on immune response post-SARS-CoV-2 infection has been in the acute and post-acute phases of infection. TRANSLATIONAL SIGNIFICANCE: We find differences at early time points of infection in approximately 160 participants. We compared multi-omic signatures in immune cells between individuals progressing to needing more significant medical intervention and non-progressors. We observed widespread evidence of a state of increased inflammation associated with progression, supported by a range of epigenomic, transcriptomic, and proteomic signatures The signatures we find support other findings at later time points and serve as the basis for prognostic biomarker development or inform interventional strategies.
Keywords: COVID19; Early infection; Multi-omic analysis; SARS-CoV-2; Systems immunology.