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Human small intestinal infection by SARS-CoV-2 is characterized by a mucosal infiltration with activated CD8+ T cells.
Lehmann, Malte; Allers, Kristina; Heldt, Claudia; Meinhardt, Jenny; Schmidt, Franziska; Rodriguez-Sillke, Yasmina; Kunkel, Désirée; Schumann, Michael; Böttcher, Chotima; Stahl-Hennig, Christiane; Elezkurtaj, Sefer; Bojarski, Christian; Radbruch, Helena; Corman, Victor M; Schneider, Thomas; Loddenkemper, Christoph; Moos, Verena; Weidinger, Carl; Kühl, Anja A; Siegmund, Britta.
  • Lehmann M; Medical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
  • Allers K; Medical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
  • Heldt C; Medical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
  • Meinhardt J; Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Schmidt F; Flow & Mass Cytometry Core Facility, Berlin Institute of Health at Charité - Universitä̈tsmedizin Berlin, Berlin, Germany.
  • Rodriguez-Sillke Y; Medical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
  • Kunkel D; Flow & Mass Cytometry Core Facility, Berlin Institute of Health at Charité - Universitä̈tsmedizin Berlin, Berlin, Germany.
  • Schumann M; Flow & Mass Cytometry Core Facility, Berlin Institute of Health at Charité - Universitä̈tsmedizin Berlin, Berlin, Germany.
  • Böttcher C; Medical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
  • Stahl-Hennig C; Klinik für Psychiatrie und Psychotherapie, Campus Mitte, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Elezkurtaj S; German Primate Center, 37077, Göttingen, Germany.
  • Bojarski C; Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Radbruch H; Medical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
  • Corman VM; The Transregio 241 IBDome Consortium, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Schneider T; Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Loddenkemper C; Institute of Virology and German Centre for Infection Research, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Moos V; Berlin Institute of Health Charité Clinician Scientist Program, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Weidinger C; Medical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
  • Kühl AA; PathoTres, Gemeinschaftspraxis für Pathologie und Neuropathologie, Teltowkanalstr. 2, 12247, Berlin, Germany.
  • Siegmund B; Medical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
Mucosal Immunol ; 14(6): 1381-1392, 2021 11.
Article in English | MEDLINE | ID: covidwho-1366810
ABSTRACT
The SARS-CoV-2 pandemic has so far claimed over three and a half million lives worldwide. Though the SARS-CoV-2 mediated disease COVID-19 has first been characterized by an infection of the upper airways and the lung, recent evidence suggests a complex disease including gastrointestinal symptoms. Even if a direct viral tropism of intestinal cells has recently been demonstrated, it remains unclear, whether gastrointestinal symptoms are caused by direct infection of the gastrointestinal tract by SARS-CoV-2 or whether they are a consequence of a systemic immune activation and subsequent modulation of the mucosal immune system. To better understand the cause of intestinal symptoms we analyzed biopsies of the small intestine from SARS-CoV-2 infected individuals. Applying qRT-PCR and immunohistochemistry, we detected SARS-CoV-2 RNA and nucleocapsid protein in duodenal mucosa. In addition, applying imaging mass cytometry and immunohistochemistry, we identified histomorphological changes of the epithelium, which were characterized by an accumulation of activated intraepithelial CD8+ T cells as well as epithelial apoptosis and subsequent regenerative proliferation in the small intestine of COVID-19 patients. In summary, our findings indicate that intraepithelial CD8+ T cells are activated upon infection of intestinal epithelial cells with SARS-CoV-2, providing one possible explanation for gastrointestinal symptoms associated with COVID-19.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Lymphocyte Activation / CD8-Positive T-Lymphocytes / Immunity, Mucosal / Duodenum / Intraepithelial Lymphocytes / SARS-CoV-2 / COVID-19 / Intestinal Diseases / Intestinal Mucosa Subject: Lymphocyte Activation / CD8-Positive T-Lymphocytes / Immunity, Mucosal / Duodenum / Intraepithelial Lymphocytes / SARS-CoV-2 / COVID-19 / Intestinal Diseases / Intestinal Mucosa Type of study: Observational study / Prognostic study / Risk factors Language: English Journal: Mucosal Immunol Year: 2021

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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Lymphocyte Activation / CD8-Positive T-Lymphocytes / Immunity, Mucosal / Duodenum / Intraepithelial Lymphocytes / SARS-CoV-2 / COVID-19 / Intestinal Diseases / Intestinal Mucosa Subject: Lymphocyte Activation / CD8-Positive T-Lymphocytes / Immunity, Mucosal / Duodenum / Intraepithelial Lymphocytes / SARS-CoV-2 / COVID-19 / Intestinal Diseases / Intestinal Mucosa Type of study: Observational study / Prognostic study / Risk factors Language: English Journal: Mucosal Immunol Year: 2021
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