Human small intestinal infection by SARS-CoV-2 is characterized by a mucosal infiltration with activated CD8+ T cells

• Published in: Mucosal immunology Vol. 14; no. 6; pp. 1381 - 1392
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2021; Nature Publishing Group
• Subjects: Adult; Aged; Allergology; Animals; Antibodies; Apoptosis; Biomedical and Life Sciences; Biomedicine; Biopsy; Case-Control Studies; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Cell Proliferation; Chlorocebus aethiops; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - pathology; COVID-19 - virology; Cytometry; Duodenum - immunology; Duodenum - pathology; Duodenum - virology; Epithelial cells; Epithelium; Female; Gastroenterology; Gastrointestinal tract; Host-Pathogen Interactions; Humans; Immunity, Mucosal; Immunohistochemistry; Immunology; Infections; Intestinal Diseases - immunology; Intestinal Diseases - pathology; Intestinal Diseases - virology; Intestinal Mucosa - immunology; Intestinal Mucosa - pathology; Intestinal Mucosa - virology; Intraepithelial Lymphocytes - immunology; Intraepithelial Lymphocytes - virology; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Male; Mucosal immunity; Nucleocapsids; Pandemics; Re-Epithelialization; SARS-CoV-2 - immunology; SARS-CoV-2 - pathogenicity; Severe acute respiratory syndrome coronavirus 2; Small intestine; Tropism; Vero Cells; Viral Load
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/s41385-021-00437-z

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.