SARS-CoV-2 infection of the intestinal tract modelled in human pluripotent stem cell-derived intestinal organoids

The COVID-19 pandemic, caused by beta-corona-virus SARS-CoV-2, has spread to over 180 countries worldwide and poses a severe health risk to the global population. While the most common symptoms are fever, cough and in severe cases pneumonia, about 10 % of patients also show a variety of gastrointestinal symptoms like diarrhoea, vomiting and abdominal pain. Additionally, high titers of the virus can be detected in faeces of patients, even long after nasopharyngeal swabs are tested negative. It is therefore of high interest to not only investigate the viral effects on the lung, but also to take a closer look at the effects of SARS-CoV-2 in the gastrointestinal tract. Immune histological stainings of different tissues and organs of the GI tract showed strong expression of the viral entry receptor ACE2 especially in the small intestine. To investigate whether the virus is able to infect and replicate in intestinal tissue, human stem cell derived intestinal organoids were used. Compared to intestinal cell lines cultivated in monolayer, organoids have the advantage of forming complex 3D structures with different compartments and generating not only one but all cell types of the intestine. Just like in primary tissue, a strong expression of ACE2 was detectable in intestinal organoids. Organoids were infected with wildtype SARS-CoV-2 and analysed after different time points for infection. 24 h after infection, viral spike protein was already detectable in the organoids, however only in a small proportion of cells. After 48 h the virus had spread throughout around 70 % of the cells, indicating that it cannot only infect but also successfully replicate in intestinal organoids. Infected cells showed signs of cell death and the morphology of organoids was visibly disturbed by the presence of the virus. The data suggest that intestinal organoids can be used as a tool to investigate the effects of SARS-CoV-2 infection in the gastrointestinal tract in vitro and to test potential compounds and inhibitors that might be able to inhibit viral infection or replication.

Publication History

Article published online:
08 September 2020