Abstract

Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. Validation was performed in two independent cohorts of COVID-19 patients. Severe COVID-19 was characterized by an increase of proliferating, metabolically hyperactive plasmablasts. Coinciding with critical illness, we also identified an expansion of interferon-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signaling. Megakaryocyte- and erythroid-cell-derived co-expression modules were predictive of fatal disease outcome. The study demonstrates broad cellular effects of SARS-CoV-2 infection beyond adaptive immune cells and provides an entry point toward developing biomarkers and targeted treatments of patients with COVID-19.

Cite as

Mishra, N., Tran, F., Bahmer, T., Best, L., Bordoni, D., Franzenburg, J., Geisen, U., Josephs-Spaulding, J., Köhler, P., Künstner, A., Rosati, E., Bacher, P., Baran, N., Boysen, T., Brandt, B., Bruse, N., Dörr, J., Dräger, A., Elke, G., Ellinghaus, D., Fischer, J., Forster, M., Franke, A., Franzenburg, S., Frey, N., Friedrichs, A., Fuß, J., Glück, A., Hamm, J., Hinrichsen, F., Imm, S., Junker, R., Kaiser, S., Knoll, R., Lange, C., Laue, G., Lier, C., Lindner, M., Marinos, G., Markewitz, R., Nattermann, J., Noth, R., Pickkers, P., Renz, A., Röcken, C., Rupp, J., Schaffarzyk, A., Scheffold, A., Schulte-Schrepping, J., Schunk, D., Skowasch, D., Ulas, T., Wandinger, K., Wittig, M., Zimmermann, J., Busch, H., Kaleta, C., Heyckendorf, J., Kox, M., Rybniker, J., Schreiber, S., Rosenstiel, P., Network, H., (DeCOI), D., Bernardes, J., Blase, J., Aschenbrenner, A., Hoeppner, M., Kan, Y., Rabe, K., Hoyer, B. & Schultze, J. 2020, 'Longitudinal multi-omics analyses identify responses of megakaryocytes, erythroid cells, and plasmablasts as hallmarks of severe COVID-19', Immunity, 53(6), pp. 1296-1314, article no: e9. http://dx.doi.org/10.1016/j.immuni.2020.11.017

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Last updated: 27 August 2025
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