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Title (Primary) Longitudinal multi-omics analyses identify responses of megakaryocytes, erythroid cells, and plasmablasts as hallmarks of severe COVID-19
Author 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.; Banovich, N.E.; Desai, T.; Eickelberg, O.; Haniffa, M.; Horvath, P.; Kropski, J.A.; Lafyatis, R.; Lundeberg, J.; Meyer, K.; Nawijn, M.C.; Nikolic, M.; Montanes, J.O.; Pe’er, D.; Tata, P.R.; Rawlins, E.; Regev, A.; Reyfman, P.; Samakovlis, C.; Schultze, J.; Shalek, A.; Shepherd, D.; Spence, J.; Teichmann, S.; Theis, F.; Tsankov, A.; van den Berge, M.; von Papen, M.; Whitsett, J.; Zaragosi, L.E.; Angelov, A.; Bals, R.; Bartholomäus, A.; Becker, A.; Bezdan, D.; Bonifacio, E.; Bork, P.; Clavel, T.; Colme-Tatche, M.; Diefenbach, A.; Dilthey, A.; Fischer, N.; Förstner, K.; Frick, J.-S.; Gagneur, J.; Goesmann, A.; Hain, T.; Hummel, M.; Janssen, S.; Kalinowski, J.; Kallies, R.; Kehr, B.; Keller, A.; Kim-Hellmuth, S.; Klein, C.; Kohlbacher, O.; Korbel, J.O.; Kurth, I.; Landthaler, M.; Li, Y.; Ludwig, K.; Makarewicz, O.; Marz, M.; McHardy, A.; Mertes, C.; Nöthen, M.; Nürnberg, P.; Ohler, U.; Ossowski, S.; Overmann, J.; Peter, S.; Pfeffer, K.; Poetsch, A.R.; Pühler, A.; Rajewsky, N.; Ralser, M.; Rieß, O.; Ripke, S.; Nunes da Rocha, U.; Saliba, A.-E.; Sander, L.E.; Sawitzki, B.; Schiffer, P.; Schulte, E.-C.; Sczyrba, A.; Stegle, O.; Stoye, J.; Vehreschild, J.; Vogel, J.; von Kleist, M.; Walker, A.; Walter, J.; Wieczorek, D.; Ziebuhr, J.;
Journal Immunity
Year 2020
Department UMB;
Volume 53
Issue 6
Language englisch;
POF III (all) T41;
Supplements https://ars.els-cdn.com/content/image/1-s2.0-S1074761320305045-mmc1.pdf
https://ars.els-cdn.com/content/image/1-s2.0-S1074761320305045-mmc2.xlsx
https://ars.els-cdn.com/content/image/1-s2.0-S1074761320305045-mmc3.xlsx
https://ars.els-cdn.com/content/image/1-s2.0-S1074761320305045-mmc4.pdf
Keywords COVID-19; RNA-seq; acute respiratory distress; blood; disease trajectory; immune response; infectious disease; methylation; scRNA-seq; virus
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.
ID 24204
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=24204
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., Banovich, N.E., Desai, T., Eickelberg, O., Haniffa, M., Horvath, P., Kropski, J.A., Lafyatis, R., Lundeberg, J., Meyer, K., Nawijn, M.C., Nikolic, M., Montanes, J.O., Pe’er, D., Tata, P.R., Rawlins, E., Regev, A., Reyfman, P., Samakovlis, C., Schultze, J., Shalek, A., Shepherd, D., Spence, J., Teichmann, S., Theis, F., Tsankov, A., van den Berge, M., von Papen, M., Whitsett, J., Zaragosi, L.E., Angelov, A., Bals, R., Bartholomäus, A., Becker, A., Bezdan, D., Bonifacio, E., Bork, P., Clavel, T., Colme-Tatche, M., Diefenbach, A., Dilthey, A., Fischer, N., Förstner, K., Frick, J.-S., Gagneur, J., Goesmann, A., Hain, T., Hummel, M., Janssen, S., Kalinowski, J., Kallies, R., Kehr, B., Keller, A., Kim-Hellmuth, S., Klein, C., Kohlbacher, O., Korbel, J.O., Kurth, I., Landthaler, M., Li, Y., Ludwig, K., Makarewicz, O., Marz, M., McHardy, A., Mertes, C., Nöthen, M., Nürnberg, P., Ohler, U., Ossowski, S., Overmann, J., Peter, S., Pfeffer, K., Poetsch, A.R., Pühler, A., Rajewsky, N., Ralser, M., Rieß, O., Ripke, S., Nunes da Rocha, U., Saliba, A.-E., Sander, L.E., Sawitzki, B., Schiffer, P., Schulte, E.-C., Sczyrba, A., Stegle, O., Stoye, J., Vehreschild, J., Vogel, J., von Kleist, M., Walker, A., Walter, J., Wieczorek, D., Ziebuhr, J. (2020):
Longitudinal multi-omics analyses identify responses of megakaryocytes, erythroid cells, and plasmablasts as hallmarks of severe COVID-19
Immunity 53 (6), 1296 - 1314