| Literature DB >> 33713619 |
Can Liu1, Andrew J Martins2, William W Lau3, Nicholas Rachmaninoff1, Jinguo Chen4, Luisa Imberti5, Darius Mostaghimi2, Danielle L Fink6, Peter D Burbelo7, Kerry Dobbs8, Ottavia M Delmonte8, Neha Bansal2, Laura Failla2, Alessandra Sottini5, Eugenia Quiros-Roldan9, Kyu Lee Han4, Brian A Sellers4, Foo Cheung4, Rachel Sparks2, Tae-Wook Chun10, Susan Moir10, Michail S Lionakis8, Camillo Rossi11, Helen C Su8, Douglas B Kuhns6, Jeffrey I Cohen12, Luigi D Notarangelo8, John S Tsang13.
Abstract
COVID-19 exhibits extensive patient-to-patient heterogeneity. To link immune response variation to disease severity and outcome over time, we longitudinally assessed circulating proteins as well as 188 surface protein markers, transcriptome, and T cell receptor sequence simultaneously in single peripheral immune cells from COVID-19 patients. Conditional-independence network analysis revealed primary correlates of disease severity, including gene expression signatures of apoptosis in plasmacytoid dendritic cells and attenuated inflammation but increased fatty acid metabolism in CD56dimCD16hi NK cells linked positively to circulating interleukin (IL)-15. CD8+ T cell activation was apparent without signs of exhaustion. Although cellular inflammation was depressed in severe patients early after hospitalization, it became elevated by days 17-23 post symptom onset, suggestive of a late wave of inflammatory responses. Furthermore, circulating protein trajectories at this time were divergent between and predictive of recovery versus fatal outcomes. Our findings stress the importance of timing in the analysis, clinical monitoring, and therapeutic intervention of COVID-19.Entities:
Keywords: CITE-seq; COVID-19; exhaustion; immune juncture; mixed-effect statistical modeling; single cell multi-omics; time-resolved
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Year: 2021 PMID： 33713619 PMCID： PMC7874909 DOI： 10.1016/j.cell.2021.02.018
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582