Journal
CELL
Volume 184, Issue 7, Pages 1836-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2021.02.018
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Funding
- NIAID OCICB (Office of Cyber Infrastructure and Computational Biology) and its Bioinformatics and Computational Biosciences [HHSN316201300006W/HHSN27200002]
- Intramural Research Program of the NIAID
- Intramural Research Program of NIDCR
- NIH supporting the NIH Center for Human Immunology, Regione Lombardia (project Immune response in patients with COVID-19 and co-morbidities'')
- federal funds from the National Cancer Institute, NIH [HHSN261200800001E]
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This study longitudinally assessed various factors in single peripheral immune cells of COVID-19 patients and identified primary correlates of disease severity and outcome. Timing was emphasized as crucial in the analysis, clinical monitoring, and therapeutic intervention of COVID-19.
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(dim)CD16(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.
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