A new analysis of SARS-CoV-2, the virus that causes COVID-19, reveals that the pathogen can infect and replicate in cells that line the inside of the human intestines. The results show that the intestines are a target organ for the virus and could explain why some patients with COVID-19 experience gastrointestinal symptoms. As the COVID-19 pandemic continues to unfold across the world, scientists have prioritized understanding how exactly SARS-CoV-2 infects and damages human cells. Studies have shown that the virus enters epithelial cells in the lungs by exploiting an enzyme called ACE2, allowing the virus to replicate and spread further. The ensuing damage results in some of the respiratory symptoms that COVID-19 is known for, which can range from coughing and shortness of breath to pneumonia in more severe cases. Preliminary observations suggest that the virus may also infect cells in the gut: patients sometimes show gastrointestinal symptoms like diarrhea, and researchers know that gut epithelial cells also harbor ACE2. Mart Lamers and colleagues generated 3D structures that display all cell types of the human small intestinal epithelium and grew them in four different culture conditions. The human small intestinal organoids grown in different conditions expressed varying amounts of ACE2 and could be infected with SARS-CoV-2. Using electron microscopy, the authors discovered that the virus infected both mature and progenitor enterocytes, which are intestinal absorptive epithelial cells that line the inner surface of the intestines. They also found that the virus provoked the activity of genes involved with antiviral responses. Notably, the rates of infection were similar across the organoid models, indicating that even low quantities of ACE2 may be enough for the virus to infect epithelial cells. Lamers et al. suggest that human organoid models will offer a useful resource for researchers studying the basic biology of SARS-CoV-2 and other coronaviruses.
