Preprint A 50-gene high-risk profile predictive of COVID & pulmonary fibrosis mortality from molecular imbalance in monocyte & T-cell subsets, 2023, Tourki +

Discussion in 'Long Covid research' started by SNT Gatchaman, Oct 25, 2023.

  1. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    A 50-gene high-risk profile predictive of COVID-19 and Idiopathic Pulmonary Fibrosis mortality originates from a molecular imbalance in monocyte and T-cell subsets that reverses in survivors with post-COVID-19 Interstitial Lung Disease
    Bochra Tourki; Minxue Jia; Theodoros Karampitsakos; Iset M Vera; Alyssa Arsenault; Krystin Marlin; Carole Y Perrot; Dylan Allen; Forouzandeh Farsaei; David Rutenberg; Debabrata Bandyopadhyay; Ricardo Restrepo; Muhammad R. Qureshi; Kapilkumar Patel; Argyrios Tzouvelekis; Maria Kapetanaki; Brenda Juan-Guardela; Kami Kim; Panayiotis V Benos; Jose Herazo-Maya

    Background: We aim to study the source of circulating immune cells expressing a 50-gene signature predictive of COVID-19 and IPF mortality.

    Methods: Whole blood and Peripheral Blood Mononuclear cells (PBMC) were obtained from 231 subjects with COVID-19, post-COVID-19-ILD, IPF and controls. We measured the 50-gene signature (nCounter, Nanostring), interleukin 6 (IL6), interferon gamma;-induced protein (IP10), secreted phosphoprotein 1 (SPP1) and transforming growth factor beta (TGF-beta) by Luminex. PCR was used to validate COVID-19 endotypes. For single-cell RNA sequencing (scRNA-seq) we used Chromium Controller (10X Genomics). For analysis we used the Scoring Algorithm of Molecular Subphenotypes (SAMS), Cell Ranger, Seurat, Propeller, Kaplan-Meier curves, CoxPH models, Two-way ANOVA, T-test, and Fisher exact.

    Results: We identified three genomic risk profiles based on the 50-gene signature, and a subset of seven genes, associated with low, intermediate, or high-risk of mortality in COVID-19 with significant differences in IL6, IP10, SPP1 and TGFβ-1. scRNA-seq identified Monocytic-Myeloid-Derived Suppressive cells (M-MDSCs) expressing CD14+HLA DRlowCD163+ and high levels of the 7-gene signature (7Gene-M-MDSC) in COVID-19. These cells were not observed in post-COVID-19-ILD or IPF. The 43-gene signature was mostly expressed in CD4 T and CD8 T cell subsets. Increased expression of the 43 gene signature was seen in T cell subsets from survivors with post-COVID-19-ILD. The expression of these genes remained low in IPF.

    Conclusion: A 50-gene, high-risk profile in COVID-19 is characterized by a genomic imbalance in monocyte and T-cell subsets that reverses in survivors with post-COVID-19 Interstitial Lung Disease.


    Link | PDF (Preprint: BioRxiv)
     
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  2. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    They're looking at interstitial lung disease (ILD) / pulmonary fibrosis as a phenotype of long Covid (non-ME). Comparing to acute Covid, recovered convalescents and idiopathic pulmonary fibrosis (IPF). This is analogous to looking at LC as ME/CFS post SARS-2 infection vs generic ME/CFS from any cause.
     
    Last edited: Oct 25, 2023
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  3. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Selected summary quotes —

     
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