Early IFN-a signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19
Supplemental tables of the publication "Early IFN-a signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19" Benjamin Krämer et al., 2021. Sup. Table S1: Cohort details [related to all Figures] Sup. Table S2: marker for NK selection and NK subtype marker gene list from the scRNA-seq analyses cohort 1 [related to Figure 2A+D+C and S2A] Sup. Table S3: Module marker gene list and function analysis from the scRNA-seq analyses cohort 1 [related to Figure 2B] Sup. Table S4: Module marker gene list, function analysis, TF and ligand prediction from the scRNA-seq analyses cohort 1 [related to Figure 3C] Sup. Table S5: List of antibodies used for multi-color flow cytometry [related to Figures 1, S1, 2, S2, 3, S3, S4 S6, 7, S7] Sup. Table S6: Number of donors, samples and cells by experiment [related to all figures] Sup. Table S7: Oligo-Primer sequences [related to STAR methods] Benjamin Krämer, Rainer Knoll, Lorenzo Bonaguro, Michael ToVinh, Jan Raabe, Rosario Astaburuaga-García, Jonas Schulte-Schrepping, Kim Melanie Kaiser, Gereon J. Rieke, Jenny Bischoff, Malte B. Monin, Christoph Hoffmeister, Stefan Schlabe, Elena De Domenico, Nico Reusch, Kristian Händler, Gary Reynolds, Nils Blüthgen, Gudrun Hack, Claudia Finnemann, Hans D. Nischalke, Christian P. Strassburg, Emily Stephenson, Yapeng Su, Louis Gardner, Dan Yuan, Daniel Chen, Jason Goldman, Philipp Rosenstiel, Susanne V. Schmidt, Eicke Latz, Kevin Hrusovsky, Andrew J. Ball, Joe M. Johnson, Paul-Albert Koenig, Florian I. Schmidt, Muzlifah Haniffa, James R. Heath, Beate M. Kümmerer, Verena Keitel, Björn Jensen, Paula Stubbemann, Florian Kurth, Leif E. Sander, Birgit Sawitzki, Deutsche COVID-19 OMICS Initiative (DeCOI), Anna C. Aschenbrenner, Joachim L. Schultze, Jacob Nattermann Summary Longitudinal analyses of the innate immune system including earliest time points are essential to understand the immunopathogenesis and clinical course of COVID-19. Here, we performed a detailed characterization of natural killer cells in 205 patients (403 samples, day 2-41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated IFN-α plasma levels in early severe COVD-19 alongside increased NK cell expression of ISGs and genes involved in IFN-α signaling, while upregulation of TNF-induced genes was observed in moderate disease. NK cells exert anti-SARS-CoV-2 activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates prolonged IFN-α-induced NK cell response with poorer disease outcome.