New single-cell technologies help scientists understand COVID-19 disease progression

Today, the Chan Zuckerberg Initiative (CZI) announced $750,000 in funding to support five distinct projects studying how COVID-19 progresses in patients at the level of individual cells and tissues. This work will generate some of the first single-cell biology datasets from donors infected by SARS-CoV2 and provide critical insights into how the virus infects humans, which cell types are involved, and how the disease progresses.

The COVID-19 Cell Atlas, supported in part by CZI grants, has provided the most comprehensive resource to date for exploring cell-type specific expression of SARS-CoV2-linked genes. These data have informed our understanding of which cell types are susceptible to viral infection. The five new projects will use similar approaches to profile cells in infected tissues and the immune system in COVID-19 patients.

“Single-cell technologies provide a powerful platform for researchers to understand the cellular basis of any disease — including COVID-19,” said CZI Head of Science Cori Bargmann. “CZI’s support of the Human Cell Atlas has already enabled valuable insights into COVID-19 — including identifying cells in the nose that may be entry points for the virus — and we’re proud to continue supporting this fundamental resource and increase our collective ability to address the coronavirus pandemic.”

The new grants will support projects led by investigators at Harvard Medical School, Massachusetts General Hospital, MIT’s Ragon Institute, the Broad Institute of MIT & Harvard, Columbia University, VIB-UGent, the Wellcome Sanger Institute, and the Josep Carreras Research Institute, with funding allocated equally among the five projects. All data generated by these grants will quickly be made available to the scientific community via open access datasets and portals, including CZI’s cellxgene tool, which allows scientists to explore and visualize high dimensional single-cell transcriptomics datasets. CZI recently launched a new version of cellxgene and is working to support the single-cell biology community in sharing COVID-19 data, compiled by the global Human Cell Atlas effort, in an interactive and scalable way.

The funded projects are as follows:

Broad Institute of MIT and Harvard

• Researchers will investigate the host immune and cellular response associated with COVID-19 infection, symptoms, and lethality. This project is being done in close collaboration with several investigators and clinicians at the Massachusetts General Hospital and the Brigham and Women’s Hospital to use single-cell genomic pipelines to analyze 500 longitudinal blood samples from COVID-19 patients collected in the hospital setting, as well as tissue samples (lung, heart, liver) from 10 deceased patients. Data will be rapidly shared as de-identified datasets with the biomedical community, and researchers will work closely with experts to analyze the results to inform disease outcomes in COVID-19 patients.
  • Project Leads: Alexandra-Chloe Villani and Orit Rozenblatt-Rosen
• Researchers will study how the airways of pediatric patients respond to SARS-CoV-2 and common respiratory viruses to better understand COVID-19 disease in children. This project involves integral collaboration with clinicians at Boston Children’s Hospital, and will profile 20 SARS-CoV-2 patients, 20 influenza patients, and 20 asymptomatic pediatric patients using computational tools to identify cells infected by these viruses. Determining what causes protective and detrimental cellular responses in infected patients may have an immediate impact on pediatric and adult health.
  • Project Leads: Alex K. Shalek and Jose Ordovas-Montanes

Columbia University

• This project will explore the possibility that immune responses in respiratory cells of COVID-19 patients with active SARS-CoV2 infection will be distinct from immune responses in the blood, and will vary in clinical severity during the course of the disease. To investigate, researchers will use longitudinal sampling and single-cell analysis of paired blood and tissue samples.
  • Project Lead: Donna Farber

VIB-UGent 

• Researchers will collect samples from COVID-19 patients and perform a single-cell proteogenomics study to gain a better understanding of virus-host interactions and potential immunotherapy targets to treat COVID-19 patients. Scientists will work to identify surface markers of the pathogenic immune cells and map the intracellular signaling circuits that drive the cytokine storm in COVID-19 patients.
  • Project Lead: Niels Vandamme

Wellcome Sanger Institute and Josep Carreras Research Institute

• In order to better understand immune response and progression of SARS-CoV2 infection, researchers will study samples from up to 50 COVID-19 patients using single-cell transcriptomics methods. Patients will include those with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and multiple sclerosis, as well as immunodeficient patients diagnosed with common variable immunodeficiency. In addition, autoimmune/immunodeficiency patients without COVID-19 and COVID-19 patients without any pre-existing immunodeficiency will serve as controls.
  • Project Leads: Roser Vento-Tormo (Sanger Institute) and Esteban Ballestar (Josep Carreras Institute)

“We are deeply appreciative for CZI’s support of this international effort, and look forward to rapidly sharing critical data with the community to help in the battle against COVID-19,” said Alex Shalek, a member of the Broad Institute of MIT and Harvard, the Pfizer-Laubach Career Development Assistant Professor at MIT, as well as a core member of the Institute for Medical Engineering and Science, an assistant professor of chemistry at MIT, and an extramural member of the Koch Institute for Integrative Cancer Research.

“We are tremendously grateful to the Chan Zuckerberg Initiative for supporting this translational effort that may result in important insights in understanding why there is such a large range of immune response associated with severe disease in COVID-19 patients and provide clues for mechanisms determining the outcome of infection with SARS-CoV-2 that could offer new therapeutic avenues. It is truly inspiring to see our healthcare professionals, medical, and scientific community all coming together selflessly to try to find solutions to better care for patients infected with SARS-CoV-2,” said Alexandra-Chloé Villani, a member of the Broad Institute of MIT and Harvard, Assistant Professor of Medicine at Harvard Medical School, as well as Director of the Single-Cell Genomics Program at the Massachusetts General Hospital Center for Immunology and Inflammatory Diseases.

“Studying hundreds of thousands of individual immune cells in respiratory samples from COVID-19 patients throughout the course of their disease may allow us to identify markers of disease severity and potential treatments,” said Donna Farber, George H. Humphreys, II Professor of Surgical Sciences and professor of microbiology and immunology at Columbia University Vagelos College of Physicians and Surgeons, who is conducting the work with Peter Sims, MD, assistant professor of systems biology and chemistry and of molecular biophysics at Columbia. “Pairing these findings with evidence from immune cells in blood samples may give us insight into both local and systemic immune response.”

“For this COVID-19 CZI research project we have formed a multidisciplinary team composed of virologists, pulmonary doctors, immunologists, single-cell technology experts and computational scientists from the Ghent University Hospital, VIB and the Weizmann Institute. Applying cutting-edge single-cell technologies to characterize this unique type of lung inflammation will undoubtedly lead to novel therapeutic avenues,” said Niels Vandamme, Staff Scientist at the VIB-UGent Center for Inflammation Research, who is conducting this work with Bart Lambrecht, Linos Vandekerckhove, Yvan Saeys, Martin Guilliams, and Ido Amit.

Roser Vento-Tormo, Group Leader at the Wellcome Sanger Institute, said, “I’m delighted that the Chan Zuckerberg Initiative is supporting this single-cell work. Our study will characterize the immune response of COVID-19 patients with pre-existing immune conditions. Creating a cell atlas of these immune cells will help understand how the immune system reacts to the virus, and the host susceptibility to SARS-CoV-2 infection.”

For more information about how CZI and our grant partners are responding to COVID-19, visit our website.

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About the Chan Zuckerberg Initiative

Founded by Dr. Priscilla Chan and Mark Zuckerberg in 2015, the Chan Zuckerberg Initiative (CZI) is a new kind of philanthropy that’s leveraging technology to help solve some of the world’s toughest challenges — from eradicating disease, to improving education, to reforming the criminal justice system. Across three core Initiative focus areas of Science, Education, and Justice & Opportunity, we’re pairing engineering with grant-making, impact investing, and policy and advocacy work to help build an inclusive, just and healthy future for everyone. For more information, please visit www.chanzuckerberg.com.