التفاصيل البيبلوغرافية
| العنوان: |
Integrated longitudinal multi-omics study identifies immune programs associated with COVID-19 severity and mortality in 1152 hospitalized participants. |
| المؤلفون: |
Gygi JP, Maguire C, Patel RK, Shinde P, Konstorum A, Shannon CP, Xu L, Hoch A, Jayavelu ND, Network I, Haddad EK, Reed EF, Kraft M, McComsey GA, Metcalf J, Ozonoff A, Esserman D, Cairns CB, Rouphael N, Bosinger SE, Kim-Schulze S, Krammer F, Rosen LB, van Bakel H, Wilson M, Eckalbar W, Maecker H, Langelier CR, Steen H, Altman MC, Montgomery RR, Levy O, Melamed E, Pulendran B, Diray-Arce J, Smolen KK, Fragiadakis GK, Becker PM, Augustine AD, Sekaly RP, Ehrlich LIR, Fourati S, Peters B, Kleinstein SH, Guan L |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2023 Nov 06. Date of Electronic Publication: 2023 Nov 06. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
Hospitalized COVID-19 patients exhibit diverse clinical outcomes, with some individuals diverging over time even though their initial disease severity appears similar. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity. In this study, we carried out deep immunophenotyping and conducted longitudinal multi-omics modeling integrating ten distinct assays on a total of 1,152 IMPACC participants and identified several immune cascades that were significant drivers of differential clinical outcomes. Increasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, NETosis, and T-cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma immunoglobulins and B cells, as well as dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to the failure of viral clearance in patients with fatal illness. Our longitudinal multi-omics profiling study revealed novel temporal coordination across diverse omics that potentially explain disease progression, providing insights that inform the targeted development of therapies for hospitalized COVID-19 patients, especially those critically ill. |
| التعليقات: |
Update in: J Clin Invest. 2024 May 1;134(9):e176640. doi: 10.1172/JCI176640. (PMID: 38690733) |
| معلومات مُعتمدة: |
U19 AI125357 United States AI NIAID NIH HHS; R01 AI132774 United States AI NIAID NIH HHS; U19 AI118608 United States AI NIAID NIH HHS; U19 AI089992 United States AI NIAID NIH HHS; U19 AI167891 United States AI NIAID NIH HHS |
| تواريخ الأحداث: |
Date Created: 20231121 Latest Revision: 20240810 |
| رمز التحديث: |
20240812 |
| مُعرف محوري في PubMed: |
PMC10659275 |
| DOI: |
10.1101/2023.11.03.565292 |
| PMID: |
37986828 |
| قاعدة البيانات: |
MEDLINE |
