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dcyphr | Infection of bat and human intestinal organoids by SARS-CoV-2
3
Contributors
Leanna Zelle

I am a pre medical student at Missouri S...

Janet Hsu

Hi! I am a Molecular, Cellular, and Deve...

Abstract

Based on genetics, SARS-CoV-2 is similar to SARS-related coronaviruses seen in horseshoe bats. This study tests small live tissue samples, called organoids, in horseshoe bats. The organoids in this study were made to mimic the intestines. These organoids can be infected with SARS-CoV-2. This shows that COVID-19 can affect the digestive system, not the respiratory system alone. This study compared stool samples and intestinal organoids from bats and humans, and found live virus in both. This suggests that SARS-CoV-2 can be spread through stool, not respiratory droplets alone.


Introduction

It is common for bats to carry RNA viruses that cause severe disease in humans and other animals. Even though the outbreak of SARS-CoV in 2003 has increased our knowledge of coronaviruses in bats, many of the viruses we know about have not been studied well. This is because it is hard to study live bats in the wild. So, researchers can use stem cells to grow miniature tissues that mimic whole organs. These are called organoids. This is the first study to create successful bat organoids. Most organoid studies are done with human tissue.

Methods

The research team used stem cells from the intestines of bats to grow the organoids. To grow them, they incubated the samples in different shaped containers and cell mediums to get the right shape and cell types. Medium is a liquid mix of different nutrients that help the cells grow. The researchers let the human and bat organoids mature. Then they were infected using a nasal swab from a COVID-19 positive patient. The researchers used PCR to see if their organoids were infected.


Results

The intestinal organoids of humans and bats were both infected by SARS-CoV-2. The researchers then looked at how the different coronaviruses typically enter cells, and tested three of those potential methods. The three methods of cell entry they looked at were angiotensin-converting enzyme 2 (ACE2), transmembrane cellular protease human (TMPRSS2), and human endosomal protease cathepsin L (CTSL). They found ACE2 and TMPRSS2 at high levels in the organoids. CTSL was at lower levels than usual, which was expected for this test. The CTSL method is usually used by SARS-CoV and MERS-CoV, not SARS-CoV-2.


Then the researchers look at how fast SARS-CoV-2 infected the organoids. In the bat small intestine organoid, infection rate was slower than the human small intestine organoid. The researchers also tested a human organoid that mimicked the large intestine, and this had the fastest rate of infection.


The researchers also found that the cells called enterocytes had the highest level of infection. Enterocytes are the cells in the small intestine that line the inside of the intestine and absorb food. There was a test done to see which inflammation causing molecules were present in the organoids, but more research is needed to understand this data.


The researchers isolated the virus from a COVID-19 positive stool sample to see if the virus in the stool still had the ability to infect other people. Live virus was found, suggesting that stool can infect people with SARS-CoV-2.


Discussion

This study was able to make the first stable small intestine organoids of bats. This may make it easier to study other bat viruses in the future. Even though digestive issues are not the most common symptoms of COVID-19, they are still present. Some stool samples have contained live virus, even after the respiratory tests have come back negative and the patient was feeling better. Based on the results of this study, COVID-19 is more than a respiratory illness. It can also infect the digestive system and spread through stool.