Single Cell Atlas of COVID-19 Affected Cells Created to Help Future Research

Single Cell Atlas of COVID-19 Affected Cells Created to Help Future Research
3D Rendering,COVID-19 virus infection of human lungs

A large collaboration of U. S. scientists, led by the Broad Institute, has created a single cell atlas to represent the impact severe COVID-19 can have on different cell types around the body.

They hope that by collating this information and allowing other researchers to access it that it will help in the quest to develop new treatments and understand the disease better.

“We knew people were passing away from COVID-related pneumonia and extrapulmonary complications,” said Alexandra-Chloé Villani, Ph.D., a principal investigator at Mass General and assistant professor at Harvard Medical School, who is also affiliated to the Broad Institute.

“Before this study, we had limited knowledge of the cellular and molecular mechanisms that were involved in driving a patient’s demise.”

The team was given permission to collect tissue samples from 17 individuals who died from COVID-19 and were hospitalized at Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, and Massachusetts General Hospital.

The researchers collected cell samples from the lungs, heart, liver, kidneys, as well as from some other organs, which were then analyzed using single cell RNA sequencing. The team also created a spatial atlas of the lungs. The cell analysis was also carried out on healthy cells for comparison purposes.

As reported in the journal Nature, the researchers found evidence of multiple failed regeneration attempts in the lung tissue. Alveolar type 2 (AT2) differentiation into AT1 cells failed and fibroblast cells failed to expand as they would normally. TP63+ intrapulmonary basal-like progenitor cells, which are produced under severe injury conditions to repair lung tissue, also appeared to be defective. High amounts of viral RNA were also found in certain types of lung cells.

Significant signs of cellular and genetic damage were also seen in the heart cells, but very little viral RNA. “Whether that means the virus had already been cleared, or that the heart was collateral damage is an area for further research,” said Aviv Regev, Ph.D., co-senior author of the study and a core institute member at the Broad Institute of MIT and Harvard (currently based at Genentech) when the study began.

As well as characterizing cells and building a 420-specimen biobank that other researchers can use, the team also assessed gene expression across the different cell types. They confirmed links with various genes previously discovered to have links to risk for severe COVID-19 including OAS3 in lung AT2 and club cells and SLC4A7 in lung CD8 T cells.

“We created a foundational resource for other researchers to use in the future to ask specific questions,” said Orit Rozenblatt-Rosen, Ph.D., co-senior author and an institute scientist and the scientific director of the Klarman Cell Observatory at the Broad when the study began (currently based at Genentech). “Hopefully our findings will allow people to find better therapeutics for COVID-19.”

A second companion study describing the impact on lung cells in more detail was also published in Nature by collaborators based at Columbia University.