%0 Journal Article %1 noauthororeditor2021complement %A Georg, Philipp %A Astaburuaga-García, Rosario %A Bonaguro, Lorenzo %A Brumhard, Sophia %A Michalick, Laura %A Lippert, Lena J %A Kostevc, Tomislav %A Gäbel, Christiane %A Schneider, Maria %A Streitz, Mathias %A Demichev, Vadim %A Gemünd, Ivana %A Barone, Matthias %A Tober-Lau, Pinkus %A Helbig, Elisa Theresa %A Stein, Julia %A Dey, Hannah-Philine %A Paclik, Daniela %A Mülleder, Michael %A Aulakh, Simran Kaur %A Mei, Henrik E %A Schulz, Alex R %A Hippenstiel, Stefan %A Max Corman, Victor %A Beule, Dieter %A Wyler, Emanuel %A Landthaler, Markus %A Obermayer-Wasserscheid, Benedikt %A Boor, Peter %A Demir, Münevver %A Wesselmann, Hans %A Suttorp, Norbert %A Uhrig, Alexander %A Müller-Redetzky, Holger %A Nattermann, Jacob %A M. Kuebler, Wolfgang M %A Meisel, Christian %A Ralser, Markus %A Schultze, Joachim L %A Aschenbrenner, Anna C %A Thibeault, Charlotte %A Kurth, Florian %A Sander, Leif-Erik %A Blüthgen, Nils %A Sawitzki, Birgit %D 2021 %J Med Rx IV %K COVID-19 T-cell complement severity %R 10.1101/2021.06.08.2125848 %T Complement activation induces excessive T cell cytotoxity in severe COVID-19 %U https://www.medrxiv.org/content/10.1101/2021.06.08.21258481v1 %X Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathogenesis, and it remains unclear if T cells also contribute to disease pathology. Here, we combined single-cell transcriptomics and proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated, CD16+ T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16+ T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16+ T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Age-dependent generation of C3a in severe COVID-19 induced activated CD16+ cytotoxic T cells. The proportion of activated CD16+ T cells and plasma levels of complement proteins upstream of C3a correlated with clinical outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.

@article{noauthororeditor2021complement, abstract = {Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathogenesis, and it remains unclear if T cells also contribute to disease pathology. Here, we combined single-cell transcriptomics and proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated, CD16+ T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16+ T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16+ T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Age-dependent generation of C3a in severe COVID-19 induced activated CD16+ cytotoxic T cells. The proportion of activated CD16+ T cells and plasma levels of complement proteins upstream of C3a correlated with clinical outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.}, added-at = {2021-08-20T15:11:39.000+0200}, author = {Georg, Philipp and Astaburuaga-García, Rosario and Bonaguro, Lorenzo and Brumhard, Sophia and Michalick, Laura and Lippert, Lena J and Kostevc, Tomislav and Gäbel, Christiane and Schneider, Maria and Streitz, Mathias and Demichev, Vadim and Gemünd, Ivana and Barone, Matthias and Tober-Lau, Pinkus and Helbig, Elisa Theresa and Stein, Julia and Dey, Hannah-Philine and Paclik, Daniela and Mülleder, Michael and Aulakh, Simran Kaur and Mei, Henrik E and Schulz, Alex R and Hippenstiel, Stefan and Max Corman, Victor and Beule, Dieter and Wyler, Emanuel and Landthaler, Markus and Obermayer-Wasserscheid, Benedikt and Boor, Peter and Demir, Münevver and Wesselmann, Hans and Suttorp, Norbert and Uhrig, Alexander and Müller-Redetzky, Holger and Nattermann, Jacob and M. Kuebler, Wolfgang M and Meisel, Christian and Ralser, Markus and Schultze, Joachim L and Aschenbrenner, Anna C and Thibeault, Charlotte and Kurth, Florian and Sander, Leif-Erik and Blüthgen, Nils and Sawitzki, Birgit}, biburl = {https://www.bibsonomy.org/bibtex/20a39923c2a12a72b3fce44cb6ef11856/bellao}, doi = {10.1101/2021.06.08.2125848}, interhash = {0945e15bea9ddbe4b26caf5c2aeee946}, intrahash = {0a39923c2a12a72b3fce44cb6ef11856}, journal = {Med Rx IV}, keywords = {COVID-19 T-cell complement severity}, language = {English}, month = {June }, timestamp = {2022-04-24T11:08:01.000+0200}, title = {Complement activation induces excessive T cell cytotoxity in severe COVID-19}, url = {https://www.medrxiv.org/content/10.1101/2021.06.08.21258481v1}, year = 2021 }