Which cells does SARS-CoV-2 attack?

Scientists at the Berlin Institute of Health (BIH), Charité-Universitätsmedizin Berlin, and the Chest Clinic at Heidelberg University Hospital are looking at non-viral samples, sponsored by the German Lung Research Center (DZL) Patients infected to determine which cells of the lung and bronchi are targets for novel coronavirus (SARS-CoV-2) infection. They found that the coronavirus receptor was abundantly expressed in certain progenitor cells. These cells develop into airway cells, usually lined with hairy projections called cilia, which clear mucus and bacteria from the lungs.

Professor Roland Eils of Thorax Clinic in Heidelberg and his colleagues initially intended to study why lung cancer sometimes occurs in people who have never smoked. They started by analyzing samples from 12 lung cancer patients. These samples were obtained from the Heidelberg Lung Biobank and were taken from both the cancerous part of the lung and the surrounding healthy lung tissue. They also studied cells from the airways of healthy patients that were collected minimally invasively during bronchoscopy performed to rule out lung cancer. The rapidly spreading coronavirus has prompted researchers to review these existing, but not previously published, data. “I was convinced that the data collected from these non-coronavirus-infected patients provided important information to understand the virus infection,” said Roland Eils, founding director of the BIH Digital Health Center. I am.

Infection requires receptors and cofactors

“We wanted to find specific cells that the coronavirus attacks,” explains Christian Conrad, a professor at the BIH Digital Health Center. Scientists have shown from research by Professor Christian Drosten BIH, director of the Virus Institute at Campus Charité, that Mitte, and others, have found that viral spike proteins are attached to cell surface ACE2 receptors. is showing. In addition, one or more cofactors are required for the virus to enter cells. But which cells have such receptors and cofactors? Which cells in which part of the respiratory system are particularly susceptible to SARS-CoV-2 infection? Eils and his colleagues at BIH and Charité. We are currently using single-cell sequencing technology to examine cells in Heidelberg samples.

60,000 single cells sequenced

“After that, we analyzed a total of nearly 60,000 cells to determine if they activated the genes for the receptor and potential cofactors. ” EMBO Journal. “Genes transcripts of ACE2 and the cofactor TMPRSS2 were found in very few cells, and only a few.” Lukasen and his four co-authors, Robert Lorenzture, Timothrefzer, Nicholas C. Kern, Mark A. Schneider discovered that certain progenitor cells of the bronchi are primarily involved in the production of coronavirus receptors. These progenitor cells develop into airway cells, usually lined with hairy processes called cilia, which clear mucus and bacteria from the lungs. “Knowing which cells are being attacked has allowed us to develop targeted therapies,” said Michael Kreuter, a clinic clinic at Heidelberg University Hospital.

Why do infections progress so differently?

An interesting additional finding of this study is that ACE2 receptor density on cells increased with age and was generally higher in men than in women. “This was just a trend, but it may explain why SARS-CoV-2 transmitted more men than women,” says Eils. However, he pointed out, “Our sample size is still too small to be conclusive and we need to repeat the study in a larger patient cohort.”

“These results show that the virus acts very selectively and that the virus relies on certain human cells to spread and replicate,” Eils explains. “The better we understand the interaction between the virus and its host, the better we can develop an effective counter strategy.” COVID 19 patients will be studied to see if they have been infected. “We want to understand why infections follow a benign course in some patients and cause severe disease in others,” says Eils. “Therefore, we will also look into immune cells in infected tissues.”

High-tech companies provide expertise

Based on high-performance technology solutions designed by Dell, Dell has developed a hardware and system architecture that reduces the processing time required to sequence 60,000 single cells. According to Hannes Schwaderer, Country Manager for Intel Germany:

BIH supports COVID-19 research

The Berlin Health Institute (BIH) is working on a new coronavirus, SARS-CoV-2, through a targeted program. Professor Axel R. Please, Interim Chairman and Dean of the BIH Board, Caritez University-Faculty of Medicine emphasizes: Scientific knowledge to understand the virus and its infection strategy, and disease progression in COVID-19 patients. Only that can identify high-risk patients and develop new treatments and vaccines. Every contribution to this effort makes a difference. “

reference: Lukassen, S. (2020). SARS-CoV-2 receptors ACE2 and TMPRSS2 are mainly expressed in bronchial transient secretory cells. EMBO Journal. https://doi.org/doi:10.15252/embj.20105114

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