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Please cite this article as: Liu, C., Martins, A.J., Lau, W.W., Rachmaninoff, N., Chen, J., Imberti, L., Mostaghimi, D., Fink, D.L., Burbelo, P.D., Dobbs, K., Delmonte, O.M., Bansal, N., Failla, L., Sottini, A., Quiros-Roldan, E., Lee Han, K., Sellers, B.A., Cheung, F., Sparks, R., Chun, T.-W., Moir, S., Lionakis, M.S., NIAID COVID Consortium, COVID Clinicians, Rossi, C., Su, H.C., Kuhns, D.B., Cohen, J.I., Notarangelo, L.D., Tsang, J.S., Time-resolved Systems Immunology Reveals a Late Juncture Linked to Fatal COVID-19, Cell (2021),
doi: https://doi.org/10.1016/j.cell.2021.02.018.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published
in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
SUMMARY
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 IL-15. CD8+ T cell activation was apparent without signs of exhaustion. While 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-fatal outcomes. Our findings stress the importance of timing in the analysis, clinical monitoring, and therapeutic intervention of COVID-19.
Please cite this article as: Liu, C., Martins, A.J., Lau, W.W., Rachmaninoff, N., Chen, J., Imberti, L., Mostaghimi, D., Fink, D.L., Burbelo, P.D., Dobbs, K., Delmonte, O.M., Bansal, N., Failla, L., Sottini, A., Quiros-Roldan, E., Lee Han, K., Sellers, B.A., Cheung, F., Sparks, R., Chun, T.-W., Moir, S., Lionakis, M.S., NIAID COVID Consortium, COVID Clinicians, Rossi, C., Su, H.C., Kuhns, D.B., Cohen, J.I., Notarangelo, L.D., Tsang, J.S., Time-resolved Systems Immunology Reveals a Late Juncture Linked to Fatal COVID-19, Cell (2021),
doi: https://doi.org/10.1016/j.cell.2021.02.018.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published
in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
SUMMARY
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 IL-15. CD8+ T cell activation was apparent without signs of exhaustion. While 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-fatal outcomes. Our findings stress the importance of timing in the analysis, clinical monitoring, and therapeutic intervention of COVID-19.