Scientists from several hospitals and research centers have shown what happens in individual cells of patients who died of COVID-19. In a study published in Nature, the researchers describe how infected cells from multiple organs exhibited a range of molecular and genomic changes. They also saw signs of multiple, unsuccessful attempts by the lungs to repair themselves in response to respiratory failure, which is the leading cause of death in COVID-19 patients.
"You really feel the tragedy of the disease when you see that result," said Aviv Regev, co-senior author of the study and a core institute member at the Broad Institute of MIT and Harvard when the study began. "The lung tries everything at its disposal, and it still can't fix itself. This was a very emotional study. We are grateful to the patients and families who agreed to donate tissue for COVID-19 research to help advance understanding of this devastating disease."
The researchers studied tissue obtained at autopsies of 17 individuals who succumbed to COVID-19 and were cared for at Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, and Massachusetts General Hospital.
The team investigated how the SARS-CoV-2 virus interferes with the function of cells and their genetic programs. They used single-cell RNA sequencing data from tissue samples taken from 11 organ systems--including the lungs, heart, liver, and kidneys--to build a comprehensive "cell atlas" of hundreds of thousands of individual cells showing how COVID-19 can lead to organ failure and death.
"We knew people were passing away from COVID-related pneumonia and extrapulmonary complications," said Alexandra-Chloé Villani, an associate member of the Broad, a principal investigator at Mass General, an assistant professor of medicine at Harvard Medical School, and co-senior author on the study. "Before this study, we had limited knowledge of the cellular and molecular mechanisms that were involved in driving a patient's demise."
The study details the results of a collaboration of researchers from the Broad Institute, Mass General, the Ragon Institute of MGH, MIT and Harvard, MIT, Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Columbia University Irving Medical Center, and other institutions. A team led by the Columbia collaborators co-authored a companion study that is also published in Nature.
The team's cell atlas is freely and openly available for other scientists to explore. They also created a 420-specimen biobank from the autopsy samples that can be used for other COVID-19 studies. "We created a foundational resource for other researchers to use in the future to ask specific questions," said Orit Rozenblatt-Rosen, co-senior author and an institute scientist and the scientific director of the Klarman Cell Observatory at the Broad when the study began. "Hopefully our findings will allow people to find better therapeutics for COVID-19."
Novel techniques for a novel virus
To learn about cellular mechanisms underlying organ failure caused by COVID-19, the researchers knew they needed to study the organs themselves. For that, they would need samples from autopsies.
Working with autopsy samples is challenging under normal circumstances. To deal with samples that might carry a novel, highly contagious pathogen, the researchers developed new tissue collection and processing protocols compatible with requirements for a Biosafety Level 3 lab.
"We wanted to ensure we could learn and share as much as humanly possible to help prevent future deaths, while prioritizing the safety and well-being of all involved. This was no small feat, given COVID-related restrictions and all the surrounding uncertainties. It was amazing to see dozens of scientists and medical professionals from several institutes come together as a collaborative partnership to carefully design and coordinate our ex...
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