COVID-19 is still affecting many people worldwide. The precautions to be taken are well known to the society by now. Across the globe, the governments are hard at work establishing the physical infrastructure to fight the pandemic. At the same time, many laboratories across the world are working on clinical trials evaluating potential treatments. Researchers at MIT, the Ragon Institute of MGH, and Harvard along with colleagues from around the world have identified specific types of cells that appear to be the targets of the coronavirus, which is causing the Covid-19 pandemic. Using existing data on the RNA found in different types of cells, the researchers were able to search for cells that express the two proteins that help the SARS-CoV-2 virus enter human cells. They found subsets of cells in the lung, the nasal passages, and the intestine that express RNA for both of these proteins much more than other cells. Alex K. Shalekfrom MIT and Jose Ordovas-Montanes, a former MIT postdoc who now runs his lab at Boston Children's Hospital, are the senior authors of the study, which appears today in the scientific journal Cell. "Our goal is to get information out to the community and to share data as soon as is humanly possible so that we can help accelerate ongoing efforts in the scientific and medical communities," says Alex K. Shalek, Associate Professor of Chemistry affiliated to MIT’s Institute for Medical Engineering and Science (IMES).
Not long after the SARS-CoV-2 outbreak began, scientists discovered that the viral "spike" protein binds to a receptor on human cells known as angiotensin-converting enzyme 2 (ACE2). Another human protein, an enzyme called TMPRSS2, helps to activate the coronavirus spike protein, to allow for cell entry. The combined binding and activation allows the virus to get into host cells. Prof. Shalek's lab, and many other labs around the world, have performed large-scale studies of tens of thousands of human, nonhuman primate, and mouse cells, in which they use single-cell RNA sequencing technology to determine which genes are turned on in a given cell type. Since last year, researchers at MIT have been building a database with partners at the Broad Institute to store a huge collection of these datasets in one place, allowing researchers to study potential roles for particular cells in a variety of infectious diseases. Much of the data came from labs that belong to the Human Cell Atlas project, whose goal is to catalog the distinctive patterns of gene activity for every cell type in the human body. The datasets that the MIT team used for this study included hundreds of cell types from the lungs, nasal passages, and intestine. The researchers chose those organs for the Covid-19 study because previous evidence had indicated that the virus can infect each of them. They then compared the results to cell types from unaffected organs. In the nasal passages, the researchers found that goblet secretory cells, which produce mucus, express RNAs for both of the proteins that SARS-CoV-2 uses to infect cells. In the lungs, they found the RNAs for these proteins mainly in cells called type II pneumocytes. These cells line the alveoli (air sacs) of the lungs and are responsible for keeping them open. In the intestine, they found that cells called absorptive enterocytes, which are responsible for the absorption of some nutrients, express the RNAs for these two proteins more than any other intestinal cell type. "This may not be the full story, but it paints a much more precise picture than where the field stood before," Prof. Ordovas-Montanes says. "Now we can say with some level of confidence that these receptors are expressed on these specific cells in these tissues." "It's hard to make any broad conclusions about the role of interferon against this virus. The only way we'll begin to understand that is through carefully controlled clinical trials," Prof. Shalek says. "What we are trying to do is put information out there, because there are so many rapid clinical responses that people are making. We're trying to make them aware of things that might be relevant." Prof. Shalek now hopes to work with collaborators to profile tissue models that incorporate the cells identified in this study. Such models could be used to test existing antiviral drugs and predict how they might affect SARS-CoV-2 infection. The MIT team and their collaborators have made all the data they used in this study available to other labs who want to use it. Much of the data used in this study were generated in collaboration with researchers around the world, who were very willing to share it, Prof. Shalek says. The researchers hope that their findings will help guide scientists who are working on developing new drug treatments or testing existing drugs that could be repurposed for treating Covid-19.
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