Bad News – Coronavirus SARS-CoV-2 Infects Cells of the Intestine and Multiplies There

Intestinal Organoids Infected With Coronavirus SARS-CoV-2

Intestinal organoids, the right one infected with coronavirus SARS-CoV-2. The coronavirus is colored white, the organoids themselves are colored blue and green. Credit: Joep Beumer, copyright Hubrecht Institue

Researchers from the Hubrecht Institute in Utrecht, Erasmus MC University Medical Center Rotterdam, and Maastricht University in the Netherlands have found that the coronavirus SARS-CoV-2, which causes COVID-19, can infect cells of the intestine and multiply there. Using state-of-the-art cell culture models of the human intestine, the researchers have successfully propagated the virus in vitro, and monitored the response of the cells to the virus, providing a new cell culture model for the study of COVID-19. These findings could explain the observation that approximately one third of COVID-19 patients experience gastrointestinal symptoms such as diarrhea, and the fact that the virus often can be detected in stool samples. The results of this study were published in the scientific journal Science on the 1st of May 2020.

Patients with COVID-19 show a variety of symptoms associated with respiratory organs – such as coughing, sneezing, shortness of breath, and fever – and the disease is transmitted via tiny droplets that are spread mainly through coughing and sneezing. One third of the patients however also have gastrointestinal symptoms, such as nausea and diarrhea. In addition, the virus can be detected in human stool long after the respiratory symptoms have been resolved. This suggests that the virus can also spread via so-called “fecal-oral transmission.”

Coronavirus SARS-CoV-2 Intestinal Cell

Illustration of a villus in the intestine with a zoom-in to an electron microscopy image of coronavirus SARS-CoV-2 (dark circles) at the edge of an intestinal cell. Credit: Kèvin Knoops, Raimond Ravelli and Maaike de Backer, copyright: Maastricht University

Though the respiratory and gastrointestinal organs may seem very different, there are some key similarities. A particularly interesting similarity is the presence of the ACE2 receptor, the receptor through which the COVID-19 causing SARS-CoV-2 virus can enter the cells. The inside of the intestine is loaded with ACE2 receptors. However, until now it was unknown whether intestinal cells could actually get infected and produce virus particles.

Intestinal organoids

Researchers from the Hubrecht Institute, Erasmus MC and Maastricht University set out to determine whether the SARS-CoV-2 virus can directly infect the cells of the intestine, and if so, whether it can replicate there as well. They used human intestinal organoids: tiny versions of the human intestine that can be grown in the lab. Hans Clevers (Hubrecht Institute): “These organoids contain the cells of the human intestinal lining, making them a compelling model to investigate infection by SARS-CoV-2.”

Infection of intestinal cells

When the researchers added the virus to the organoids, they were rapidly infected. The virus enters a subset of the cells in the intestinal organoids, and the number of cells that are infected increases over time. Using electron microscopy, an advanced way to visualize different components of the cell in great detail, the researchers found virus particles inside and outside the cells of the organoids. Peter Peters (Maastricht University): “Due to the lockdown, we all studied virtual slides of the infected organoids remotely from home.”

Intestinal Organoid Infected With Coronavirus SARS-CoV-2

Intestinal organoid infected with coronavirus SARS-CoV-2. The coronavirus is colored white, the organoids themselves are colored blue and green. Credit: Joep Beumer, copyright: Hubrecht Institute

The researchers investigated the response of the intestinal cells to the virus with RNA sequencing, a method to study which genes are active in the cells. This revealed that so-called interferon stimulated genes are activated. These genes are known to combat viral infection. Future work will focus on these genes more carefully, and on how they could be used to develop new treatments.

The researchers also cultured the organoids in different conditions that result in cells with higher and lower levels of the ACE2 receptor, through which SARS-CoV-2 can enter the cells. To their surprise, they found that the virus infected cells with both high and low levels of the ACE2 receptor. Ultimately, these studies may lead to new ways to block the entry of the virus into our cells.

Implications

Bart Haagmans (Erasmus MC): “The observations made in this study provide definite proof that SARS-CoV-2 can multiply in cells of the gastrointestinal tract. However, we don’t yet know whether SARS-CoV-2, present in the intestines of COVID-19 patients, plays a significant role in transmission. Our findings indicate that we should look into this possibility more closely.” The current study is in line with other recent studies that identified gastrointestinal symptoms in a large fraction of COVID-19 patients and virus in the stool of patients free of respiratory symptoms. Special attention may be needed for those patients with gastrointestinal symptoms. More extensive testing using not only nose and throat swabs, but also rectal swabs or stool samples may thus be needed.

In the meantime, the researchers are continuing their collaboration to learn more about COVID-19. They are studying the differences between infections in the lung and the intestine by comparing lung and intestinal organoids infected with SARS-CoV-2.

Reference: “SARS-CoV-2 productively Infects Human Gut Enterocytes” by Mart M. Lamers, Joep Beumer, Jelte van der Vaart, Kèvin Knoops, Jens Puschhof, Tim I. Breugem, Raimond B.G. Ravelli, J. Paul van Schayck, Anna Z. Mykytyn, Hans Q. Duimel, Elly van Donselaar, Samra Riesebosch, Helma J.H. Kuijpers, Debby Schipper, Willine J. van de Wetering, Miranda de Graaf, Marion Koopmans, Edwin Cuppen, Peter J. Peters, Bart L. Haagmans and Hans Clevers, 1 May 2020, Science.
DOI: 10.1126/science.abc1669

This study was a collaboration between the Hubrecht Institute in Utrecht, the Erasmus MC University Medical Center Rotterdam, Maastricht University, the UMC Utrecht and Single Cell Discoveries in the Netherlands. The microscopy data are publicly available via the Image Data Resource (idr0083 – with help from the University of Dundee and the European Bioinformatics Institute) and the genomic data are publicly available via the Gene Expression Omnibus (GSE149312), to ensure efficient sharing of data related to COVID-19 between researchers all across the world.

Hans Clevers is principal investigator at the Hubrecht Institute and the Princess Máxima Center for Pediatric Oncology, professor of Molecular Genetics at the UMC Utrecht and Utrecht University, and Oncode Investigator.

Bart Haagmans is a principal investigator at the Viroscience department at the Erasmus MC University Medical Center Rotterdam.

Peter Peters is director and principal investigator at the Maastricht Multimodal Molecular Imaging Institute (M4i) and professor of Nano Biology at the Maastricht University and Maastricht University Medical Center.

8 Comments on "Bad News – Coronavirus SARS-CoV-2 Infects Cells of the Intestine and Multiplies There"

  1. Rosa Fasching | May 4, 2020 at 8:16 am | Reply

    Do this intestinal organoids contain gut bacteria?

  2. Yes it does contain bacteria, but that’s irrelevant to the virus attacking epithelium cells of the gut lining. I haven’t seen any indication microbiome alters the virus binding.

  3. Could this be how to “vaccinate” (not a real vaccine) against COVID-19? If an infection starts in the gut (either ingested or introduced through the other end) that gives your immune system a head start on recognizing and fighting it before it ever makes it to the respiratory tract. It may not be pleasant, but unlike having it in your lungs it doesn’t sound like this kills people, so maybe it’s a way to give people protective immunity that will last a few years until we come up with another less-unpleasant vaccination method?

  4. Michele Ditrani | May 4, 2020 at 6:47 pm | Reply

    I’m absolutely sure I had this virus in my intestines for sure ! Long story short! Went grocery shopping on March 12 Thursday! A lady in line was talking to me I actually felt her breath go down my throat. Not a sneeze or a cough just her breath! 2 weeks to the day I suddenly had the worst diarrhea of my life that lasted 10 days. Couldn’t sleep eat drink I paced the floors all night then after the 10 days still had some diarrhea but stomach was gurgling out of control I was deathly sick didn’t want to go to a doctor because we were in lock down. It lasted a total of just about 5 weeks ! After reading this I really think I maybe had the virus !! Any thoughts ??

  5. Ervin Faulmann | May 4, 2020 at 7:53 pm | Reply

    The activation of interferon stimulated genes in the infected cells in the absence of typical interferon-producing cells (is this true in your organoid system?) provides evidence of these cells as additional sources for the extreme cytokine release seen in many COVID-19 patients.

  6. George DeCarlo | May 4, 2020 at 9:07 pm | Reply

    Test these, forget the drugs.

    The hunt for BIGPHARMA PROFIT MAKING treatments is on and pockets of governments and supposed medical authorities. I just gave my PERSONAL plan which is

    All these may be taken together: zinc 30-40mg + quercitin 500-1,000mg and/or EGCG 600-700mg – these were shown as effective as quinine drugs in 2014; BHT which disturbs lipid coats of such viruses rendering them open to the immune system; mega doses of Vitamin C – I take 5,000mg a day but would take up to 20,000 or more if ill. Linus Pauling had done extensive initial research; and in a medical office since some simple equipment is used by a nurse would be photoluminescence (UV light) therapy. Deadly and quite effective on microbes. These would deal quite nicely with the manifesting illness. Oh, with an advanced medical office if they had hyperbaric oxygen chambers, I would be pleased to lie in one for 45 minutes as oxygen is deeply saturated into the body. Such levels help with other conditions but are deadly to viruses. All this is more than enough.

  7. Que Sera Sera | May 5, 2020 at 7:11 am | Reply

    In Feb I came back from a business trip to Singapore. At the time it was still not so serious here in Malaysia. I had diarrhea for about 4 days after and I was wondering what happened. Then I watched a prominent Dr from Singapore on tv saying that if you have diarrhea, this could be a symptom but not many people have said this. After that I felt fine and I still wonder if I had caught the virus while I was in Singapore without realizing it.

  8. Jennifer S | May 5, 2020 at 6:17 pm | Reply

    @ George DeCarlo

    You’re correct about Linus Pauling research. However, everyone should keep the following in mind, especially now with the corona scamdemic going on: there are many bogus voices around who strive to distract the public from the value of vitamin C therapy and the fact that Pauling’s VALID work with vitamin C supplementation has been “falsified” by data distortions and lies, and he as a person (a double Nobel laureate) has been slandered as some deluded idiot by the criminal medical establishment and its countless quackwatch shills, lackeys, ignoramuses, and trolls for decades and it continues today — search for the scholarly report “2 Big Lies: No Vitamin Benefits & Supplements Are Very Dangerous” by Rolf Hefti (a published author of the Orthomolecular Medicine News organization).

    But you can’t discredit the facts with lies. That only exposes and discredits the liars (see citation above).

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