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Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19.

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 CD56^dimCD16^hi 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.

SUBMITTER: Liu C

PROVIDER: S-EPMC7874909 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19.

Liu Can C Martins Andrew J AJ Lau William W WW Rachmaninoff Nicholas N Chen Jinguo J Imberti Luisa L Mostaghimi Darius D Fink Danielle L DL Burbelo Peter D PD Dobbs Kerry K Delmonte Ottavia M OM Bansal Neha N Failla Laura L Sottini Alessandra A Quiros-Roldan Eugenia E Han Kyu Lee KL Sellers Brian A BA Cheung Foo F Sparks Rachel R Chun Tae-Wook TW Moir Susan S Lionakis Michail S MS Rossi Camillo C Su Helen C HC Kuhns Douglas B DB Cohen Jeffrey I JI Notarangelo Luigi D LD Tsang John S JS

Cell 20210210 7

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 ...[more]

PMID: 33713619

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Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19.

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Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19.

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