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Title (Primary) Severe COVID-19 is marked by a dysregulated myeloid cell compartment
Author Schulte-Schrepping, J.; Reusch, N.; Paclik, D.; Baßler, K.; Schlickeiser, S.; Zhang, B.; Krämer, B.; Krammer, T.; Brumhard, S.; Bonaguro, L.; De Domenico, E.; Wendisch, D.; Grasshoff, M.; Kapellos, T.S.; Beckstette, M.; Pecht, T.; Saglam, A.; Dietrich, O.; Mei, H.E.; Schulz, A.R.; Conrad, C.; Kunkel, D.; Vafadarnejad, E.; Xu, C.-J.; Horne, A.; Herbert, M.; Drews, A.; Thibeault, C.; Pfeiffer, M.; Hippenstiel, S.; Hocke, A.; Müller-Redetzky, H.; Heim, K.-M.; Machleidt, F.; Uhrig, A.; Bosquillon de Jarcy, L.; Jürgens, L.; Stegemann, M.; Glösenkamp, C.R.; Volk, H.-D.; Goffinet, C.; Landthaler, M.; Wyler, E.; Georg, P.; Schneider, M.; Dang-Heine, C.; Neuwinger, N.; Kappert, K.; Tauber, R.; Corman, V.; Raabe, J.; Kaiser, K.M.; Vinh, M.T.; Rieke, G.; Meisel, C.; Ulas, T.; Becker, M.; Geffers, R.; Witzenrath, M.; Drosten, C.; Suttorp, N.; von Kalle, C.; Kurth, F.; Händler, K.; Schultze, J.L.; Aschenbrenner, A.C.; Li, Y.; Nattermann, J.; Sawitzki, B.; Saliba, A.-E.; Sander, L.E.; Angelov, A.; Bals, R.; Bartholomäus, A.; Becker, A.; Bezdan, D.; Bonifacio, E.; Bork, P.; Clavel, T.; Colome-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.; 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.; Rosenstiel, P.; Schiffer, P.; Schulte, E.-C.; Sczyrba, A.; Stegle, O.; Stoye, J.; Theis, F.; Vehreschild, J.; Vogel, J.; von Kleist, M.; Walker, A.; Walter, J.; Wieczorek, D.; Ziebuhr, J.;
Journal Cell
Year 2020
Department UMB;
Volume 182
Issue 6
Language englisch;
POF III (all) T41;
Keywords COVID-19; SARS-CoV-2; dysfunctional neutrophils; emergency myelopoiesis; immune profiling; mass cytometry; monocytes; neutrophils; scRNA-seq.
Abstract Coronavirus disease 2019 (COVID-19) is a mild to moderate respiratory tract infection, however, a subset of patients progress to severe disease and respiratory failure. The mechanism of protective immunity in mild forms and the pathogenesis of severe COVID-19 associated with increased neutrophil counts and dysregulated immune responses remain unclear. In a dual-center, two-cohort study, we combined single-cell RNA-sequencing and single-cell proteomics of whole-blood and peripheral-blood mononuclear cells to determine changes in immune cell composition and activation in mild versus severe COVID-19 (242 samples from 109 individuals) over time. HLA-DRhiCD11chi inflammatory monocytes with an interferon-stimulated gene signature were elevated in mild COVID-19. Severe COVID-19 was marked by occurrence of neutrophil precursors, as evidence of emergency myelopoiesis, dysfunctional mature neutrophils, and HLA-DRlo monocytes. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.
ID 24202
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=24202
Schulte-Schrepping, J., Reusch, N., Paclik, D., Baßler, K., Schlickeiser, S., Zhang, B., Krämer, B., Krammer, T., Brumhard, S., Bonaguro, L., De Domenico, E., Wendisch, D., Grasshoff, M., Kapellos, T.S., Beckstette, M., Pecht, T., Saglam, A., Dietrich, O., Mei, H.E., Schulz, A.R., Conrad, C., Kunkel, D., Vafadarnejad, E., Xu, C.-J., Horne, A., Herbert, M., Drews, A., Thibeault, C., Pfeiffer, M., Hippenstiel, S., Hocke, A., Müller-Redetzky, H., Heim, K.-M., Machleidt, F., Uhrig, A., Bosquillon de Jarcy, L., Jürgens, L., Stegemann, M., Glösenkamp, C.R., Volk, H.-D., Goffinet, C., Landthaler, M., Wyler, E., Georg, P., Schneider, M., Dang-Heine, C., Neuwinger, N., Kappert, K., Tauber, R., Corman, V., Raabe, J., Kaiser, K.M., Vinh, M.T., Rieke, G., Meisel, C., Ulas, T., Becker, M., Geffers, R., Witzenrath, M., Drosten, C., Suttorp, N., von Kalle, C., Kurth, F., Händler, K., Schultze, J.L., Aschenbrenner, A.C., Li, Y., Nattermann, J., Sawitzki, B., Saliba, A.-E., Sander, L.E., Angelov, A., Bals, R., Bartholomäus, A., Becker, A., Bezdan, D., Bonifacio, E., Bork, P., Clavel, T., Colome-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., 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., Rosenstiel, P., Schiffer, P., Schulte, E.-C., Sczyrba, A., Stegle, O., Stoye, J., Theis, F., Vehreschild, J., Vogel, J., von Kleist, M., Walker, A., Walter, J., Wieczorek, D., Ziebuhr, J. (2020):
Severe COVID-19 is marked by a dysregulated myeloid cell compartment
Cell 182 (6), 1419 - 1440