A new study finds out what cell types may be infected with SARS-CoV-2 as a result of their viral entry factors. The study also suggests that increased gene expression of these viral entry factors in some individuals partly explains the differences of COVID-19 anxiety reported in terms of age, sex, and smoking status. .
The study came from the Human Atlas Cell Lung Biological Network with key contributions from Helmholtz Zentrum München, the MIT and Harvard Broad Institute, the Wellcome Sanger Institute and the University of Groningen Medical Center.
COVID-19 does not affect everyone in the same way. While the coronavirus SARS-CoV-2 appears in the lung, it can also infect other organs. Clinical observations throughout the pandemic also indicate that some population groups – such as the elderly, men and smokers – tend to be more susceptible to the disease. To date, the molecular reasons for this have not been described.
Previous studies had shown that, in order to induce human cells, SARS-CoV-2 must contain specific viral genetic entry factors in the cell – namely ACE2 receptor and protease (TMPRSS2 or CTSL). Thus we would know which cell types express both ACE2 and protease information about the cells that may be infected with SARS-CoV-2.
The Atlas of Human Cells (HCA) consortium aims to map all cell types in the human body, changing our understanding of biology and disease. Within this, researchers from the HCA Lung Biological Network came together to augment and interpret gene expression data from individual cells. Together, they analyzed more than 100 data sets of single-cell gene expression of healthy individuals, to see which cell types express both ACE2 and protease.
The analysis showed that specific cell types in the epithelium of the lungs and airways, but also in the liver, colon, and eye are rich in viral genetic entry factors (= high expression of ACE2 receptor and protease) – and therefore the molecules are essential for the release of SARS-CoV-2 infection.
In addition, the researchers found that the expression of genes underlying the viral entry factors is increased in elderly cells and slightly in men compared to women. In addition, cells from smokers (especially airway cells) express more SARS-CoV-2 entry factors than from non-smokers.
These results match differences in reported disease depth for COVID-19 patients in these population groups and thus offer a molecular explanation for this difference (alongside other undiagnosed factors). studied in this study such as weaker immune system).
Big data for biomedical analysis
“Fighting the pandemic, we cannot rely on decisions that are limited to just a few ideas. Instead, we have to rely on robust analysis of big data. For example , to determine whether the ACE2 receptor required for virus entry is more abundant in cells of the elderly, we need a robust representation of many diverse individuals in our dataset.
Using data from the Human Cell Atlas, we were able to model how genetic viral entry factors in cells are expressed across the population. “
Malte Lücken, Study Co-authored author and computer biologist, Helmholtz Zentrum Munich
“A key aspect of this large study was the age range of samples we were able to study. This study included data from human development stages, samples from children and young adults, as well as samples from old people.
This gave us a special power to assess changes that are happening over people’s lives. The large size of the data allowed us to see molecular differences with age, sex and smoking status, ”said Kerstin Meyer, author of the paper from the Wellcome Sanger Institute.
“This study was a prime example of a whole range coming together. Within the Atlas Human Cell consortium everyone who generated data on healthy human lungs submitted their data, both published and unpublished. , to enable our analysis.
When we then reached outside the consortium, more data laboratories added to the effort. It is only through these contributions that our analysis has been made possible, “says Fabian Theis, Director of the Institute of Computational Biology at Helmholtz Zentrum München.
Strengths and limitations
The study examined the cells most likely to be infected with SARS-CoV-2. The results partially explain how disease depth may differ between population groups due to the molecular profile of cells.
This provides a target for further intervention research. Moving forward, the findings may help to better understand the spread of the corona virus throughout the body. The association between viral entry factor expression and increased infectivity or depth of disease has been shown in mice and in the laboratory, but further confirmation is needed in humans.
Source:
Helmholtz Zentrum München – German Research Center for Environmental Health
Magazine Reference:
Muus, C., et al. (2021) One-cell meta-analysis of SARS-CoV-2 entry genes across nappies and demographics. Nature’s cure. doi.org/10.1038/s41591-020-01227-z.