Goblet cells and ciliated epithelium in the nose contain a particularly large number of the vulnerable receptor proteins that SARS-CoV-2 uses to get into our cells. But the heart also has a high density of these receptors.
Explanation for high transmission rate of COVID-19
Two types of cells in the nose are probably the first entry points for the new coronavirus. Using data from the Human Cell Atlas, researchers have discovered particularly many of the vulnerable receptor proteins in goblet cells and ciliated epithelium in the nose that SARS-CoV-2 uses to get into our cells. After the body has been infected, the heart appears to be particularly at risk.
This first publication with the Lung Biological Network is part of the ongoing international efforts to use the data from the Human Cell Atlas to understand infection and disease, the scientists reported in the journal “Nature Medicine”. In addition, the publication showed that in addition to the nose, cells in the eye and in some other organs such as the heart also have these entry points for the viruses. These findings are u. a. important to possibly develop a drug that could make transmission of the virus more difficult.
COVID-19 mainly affects the lungs and the respiratory tract. The symptoms of the patients can therefore be flu-like, with fever, cough and sore throat, while other people do not notice any symptoms but can still transmit viruses. In the worst cases, the virus causes pneumonia, which can lead to death. It is currently believed that the virus spreads through droplets that occur when an infected person coughs or sneezes, making it very easy to transmit.
Which cell types are involved in the infection?
Scientists around the world want to understand exactly how this virus works to prevent transmission and develop a vaccine. SARS-CoV-2 is known to infect cells through a mechanism similar to that of a related coronavirus that caused the SARS epidemic in 2003. However, the exact types of cells involved in the nose had not previously been determined.
The researchers therefore analyzed various data sets from the Human Cell Atlas (HCA) consortium that had been obtained from single-cell RNA sequencing of more than 20 different tissues of uninfected people. This included cells from the lungs, nasal cavity, eye, intestine, heart, kidney and liver. The researchers investigated which of the individual cells express the two most important entry proteins that the virus uses for the infection.
Dr. Waradon Sungnak, lead author of the Wellcome Sanger Institute study, said: “The receptor protein – ACE2 – and the TMPRSS2 protease, which can help SARS-CoV-2 to enter, are expressed in the cells of various organs, including the cells on the inside of the nose. We have shown that of all cells, the mucus-producing goblet cells and cilia in the nose have the highest concentrations of these two proteins. This makes these cells the most likely primary infection site for the virus. ”
The cells of the nose are easy for the virus to reach
Dr. Martijn Nawijn from the University Hospital Groningen in the Netherlands said for the HCA Lung Biological Network: “These special cells in the nose have now been linked to COVID-19 for the first time. Of course, there are many factors that affect the transmissibility of the virus. But ours The results go well with the rapid infection rates of the virus that have been observed to date. The location of these cells on the surface of the inside of the nose makes them easily accessible to the virus and can help transmission to other people. ”
The two most important entry proteins ACE2 and TMPRSS2 can also be found in the corneal cells of the eye and in the intestinal mucosa. This suggests another possible route of infection via the eye or lacrimal glands and reveals the potential for fecal-oral transmission. In individual cases, both have already been observed in a few patients worldwide and discussed as possible contagion routes.
When cells are damaged or fight infection, various immune genes are also activated. The study showed that the production of the ACE2 receptor in the nasal cells is likely to be activated simultaneously with these other immunogens.
ACE2 can also be found in the heart
Up to 20% of COVID-19 patients treated in the hospital also suffer damage to the heart muscle up to heart failure. It was therefore crucial to map the gene expression of the SARS-CoV-2 receptor and the helping protease for the heart as well. “We analyzed more than 500,000 individual cells from 14 human hearts. We identified the cellular areas that express this portal of entry: These are pericytes – cells that belong to the fine capillary system of the heart – cardiac muscle cells and fibroblasts that contribute to to give the heart its structure, “said Dr. Michela Noseda of the National Heart & Lung Institute of the Imperial College in London: “Knowing exactly which cells in the heart the virus is targeting is the basis for understanding the mechanisms of the damage and deciding on a treatment.”
“We can rely on unique data sets from single cell sequencing,” said Professor Norbert Hübner, who heads the “Genetics and Genomics of Cardiovascular Diseases” working group at the Max Delbrück Center for Molecular Medicine (MDC) and additional projects at the German Center for Cardiovascular Research (DZHK ) and at the Berlin Institute of Health (BIH). Together with Jonathan Seidman, Bugher Professor of Cardiovascular Genetics at Harvard Medical School, he coordinates a team of 13 scientists from Germany, Great Britain and the USA who want to understand the human heart cell by cell.
Michela Noseda and Sarah Teichmann also belong to this group: “We found the ACE2 receptor especially in the pericytes. The receptor probably plays a fundamental role in maintaining the blood flow in the body. Its role in the heart problems of COVID- 19 patients is a different matter. We don’t know yet whether the virus itself causes damage to the heart or whether it is a secondary effect. ”
Use the Human Cell Atlas to understand COVID-19
Dr. Sarah Teichmann, a senior author of the study from the Wellcome Sanger Institute and co-chair of the HCA organizing committee, added: “While we are building the Human Cell Atlas, it is already being used to understand COVID-19 and to help cells Identify those that are critical to initial infection and portability. This information can be used to better understand the spread of coronavirus. Knowing the exact cell types that are important for virus transmission provides a basis for potential therapies develop and reduce the spread of the virus. ”
The global HCA Lung Biological Network continues to analyze the data. The network wants to gain further clues to cells and targets that are likely to be involved in COVID-19 and to compare them with the characteristics of patients.
Professor Sir Jeremy Farrar, director of Wellcome, concluded: “By determining the characteristics of each cell type, the Human Cell Atlas helps scientists diagnose, monitor and treat diseases like COVID-19 in a completely new way. Researchers around the world are working at an unprecedented pace to deepen our understanding of COVID-19, and this new work is testament to this: Cross-border collaboration and open exchange of research results are critical to the rapid development of effective diagnostics, therapies and Vaccines and to make sure no country is left behind. ”
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