COVID-19 patients have a spectrum of immunological responses, ranging from asymptomatic SARS-CoV-2 infection to death. Researchers discovered underlying metabolic alterations that influence how immune cells respond to the disease after analysing blood samples from nearly 200 COVID-19 patients. These changes are related to the severity of the disease and may be used to predict patient survival. Nature Biotechnology published the findings.

“We know that COVID-19 induces a variety of immunological responses, but the molecular mechanisms underlying those responses remain unknown,” said co-first author Jihoon Lee, a graduate student at the Fred Hutchinson Cancer Research Center. “We investigated thousands of biological markers associated with the metabolic pathways that underpin the immune system and discovered some clues about the immuno-metabolic alterations that may be critical in severe disease. Our goal is that these studies of immune function will aid in the deciphering of the body’s reaction to COVID-19 by others. The increased understanding gained here may someday result in more specific medicines that target the most troublesome immunological or metabolic alterations.”

The researchers took 374 blood samples from patients — two per patient during the first week following diagnosis of SARS-CoV-2 infection — and studied their plasma and single immune cells. The investigation includes 1,387 genes and 1,050 plasma metabolites implicated in metabolic pathways.

The scientists discovered that greater COVID-19 severity is connected with metabolite changes in plasma, implying enhanced immune-related activity. Additionally, researchers discovered that each major immune cell type has a specific metabolic profile by single-cell sequencing.

“We discovered metabolic reprogramming that is highly specific to specific immune cell classes (e.g., “killer” CD8+ T cells, “helper” CD4+ T cells, antibody-secreting B cells, etc.) and even cell subtypes, and that the immune system’s complex metabolic reprogramming is associated with the plasma global metabolome and is predictive of disease severity and even patient death,” said co-first and co-authors. “Without improved single-cell multi-omic research, such in-depth and clinically relevant insights into sophisticated metabolic reprogramming inside our varied immune systems would be unattainable.”

“This research contributes significantly to the development of more effective treatments for COVID-19. Additionally, it constitutes a significant technological barrier “Dr. Jim Heath, ISB’s president and a professor and a co-corresponding author on the article, stated. “Numerous data sets derived from these patients measure extremely disparate elements of the disease and are evaluated in isolation. Naturally, one would prefer for these disparate perspectives to contribute to a more complete picture of the patient. The technique proposed here enables the aggregate of the many data sets to be far bigger than the sum of the individual data sets, allowing for a much richer interpretation of the disease.”

ISB, the Fred Hutchinson Cancer Project Center, Stanford University, Swedish Medical Center St. John’s Cancer Institute at Saint John’s Health Center, the University of Washington, and the Howard Hughes Medical Institute collaborated on the research.

Merck and the Biomedical Advanced Research and Development Authority (BARDA), the Wilke Family Foundation, the MJ Murdock Charitable Trust, the Swedish Medical Center Foundation, the Parker Institute for Cancer Immunotherapy, Gilead, Amazon Web Services, and the National Institutes of Health have all contributed funding to this project.

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Materials provided by Institute for Systems Biology


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