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.
- Bernardes, J. P.
- Mishra, N.
- Tran, F.
- Bahmer, T.
- Best, L.
- Blase, J. I.
- Bordoni, D.
- Franzenburg, J.
- Geisen, U.
- Josephs-Spaulding, J.
- Köhler, P.
- Künstner, A.
- Rosati, E.
- Aschenbrenner, A. C.
- 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.
- Hoeppner, M. P.
- Imm, S.
- Junker, R.
- Kaiser, S.
- Kan, Y. H.
- Knoll, R.
- Lange, C.
- Laue, G.
- Lier, C.
- Lindner, M.
- Marinos, G.
- Markewitz, R.
- Nattermann, J.
- Noth, R.
- Pickkers, P.
- Rabe, K. F.
- Renz, A.
- Röcken, C.
- Rupp, J.
- Schaffarzyk, A.
- Scheffold, A.
- Schulte-Schrepping, J.
- Schunk, D.
- Skowasch, D.
- Ulas, T.
- Wandinger, K. P.
- Wittig, M.
- Zimmermann, J.
- Busch, H.
- Hoyer, B. F.
- Kaleta, C.
- Heyckendorf, J.
- Kox, M.
- Rybniker, J.
- Schreiber, S.
- Schultze, J. L.
- Rosenstiel, P.
Keywords
- Adult
- Aged
- Aged, 80 and over
- Biomarkers
- Blood Circulation
- COVID-19/immunology/*metabolism
- Cells, Cultured
- Cohort Studies
- Disease Progression
- Erythroid Cells/*pathology
- Female
- Gene Expression Profiling
- Humans
- Male
- Megakaryocytes/*physiology
- Middle Aged
- Plasma Cells/*physiology
- Proteomics
- SARS-CoV-2/*physiology
- Sequence Analysis, RNA
- Severity of Illness Index
- Single-Cell Analysis
- *covid-19
- *RNA-seq
- *acute respiratory distress
- *blood
- *disease trajectory
- *immune response
- *infectious disease
- *methylation
- *scRNA-seq
- *virus