Metabolic changes in plasma and immune cells associated with COVID-19 severity, can predict patient survival

Date:
September 6, 2021
Source:
Institute for Systems Biology
Summary:
After examining the blood samples from nearly 200 COVID-19 patients,
researchers have uncovered underlying metabolic changes that
regulate how immune cells react to the disease. These changes
are associated with disease severity and could be used to predict
patient survival.



FULL STORY ========================================================================== COVID-19 patients have differing immune responses that lead to disease
outcomes ranging from asymptomatic SARS-CoV-2 infection to death. After examining the blood samples from nearly 200 COVID-19 patients, researchers
have uncovered underlying metabolic changes that regulate how immune
cells react to the disease. These changes are associated with disease
severity and could be used to predict patient survival. The findings
were published in the journal Nature Biotechnology.


==========================================================================
"We know that there are a range of immune responses to COVID-19, and the biological processes underlying those responses are not well understood,"
said co-first author Jihoon Lee, a graduate student at Fred Hutchinson
Cancer Research Center. "We analyzed thousands of biological markers
linked to metabolic pathways that underlie the immune system and found
some clues as to what immune-metabolic changes may be pivotal in severe disease. Our hope is that these observations of immune function will
help others piece together the body's response to COVID-19. The deeper understanding gained here may eventually lead to better therapies that can
more precisely target the most problematic immune or metabolic changes."
The researchers collected 374 blood samples -- two draws per patient
during the first week after being diagnosed with SARS-CoV-2 infection --
and analyzed their plasma and single immune cells. The analysis included
1,387 genes involved in metabolic pathways and 1,050 plasma metabolites.

In plasma samples, the team found that increased COVID-19 severity
is associated with metabolite alterations, suggesting increased
immune-related activity. Furthermore, through single-cell sequencing, researchers found that each major immune cell type has a distinct
metabolic signature.

"We have found metabolic reprogramming that is highly specific to
individual immune cell classes (e.g. "killer" CD8+ T cells, "helper" CD4+
T cells, antibody-secreting B cells, etc.) and even cell subtypes, and the complex metabolic reprogramming of the immune system is associated with
the plasma global metabolome and are predictive of disease severity and
even patient death," said co-first and co-corresponding author Dr. Yapeng
Su, a research scientist at Institute for Systems Biology. "Such deep and clinically relevant insights on sophisticated metabolic reprogramming
within our heterogeneous immune systems are otherwise impossible to
gain without advanced single-cell multi-omic analysis." "This work
provides significant insights for developing more effective treatments
against COVID-19. It also represents a major technological hurdle,"
said Dr. Jim Heath, president and professor of ISB and co-corresponding
author on the paper. "Many of the data sets that are collected from
these patients tend to measure very different aspects of the disease,
and are analyzed in isolation. Of course, one would like these different
views to contribute to an overall picture of the patient. The approach described here allows for the sum of the different data sets to be much
greater than the parts, and provides for a much richer interpretation
of the disease." The research was conducted by scientists from ISB,
Fred Hutchinson Cancer Research Center, Stanford University, Swedish
Medical Center St. John's Cancer Institute at Saint John's Health Center,
the University of Washington, the Howard Hughes Medical Institute.

Funding for this project comes from 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.

========================================================================== Story Source: Materials provided by Institute_for_Systems_Biology. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jihoon W. Lee, Yapeng Su, Priyanka Baloni, Daniel Chen, Ana Jimena
Pavlovitch-Bedzyk, Dan Yuan, Venkata R. Duvvuri, Rachel H. Ng,
Jongchan Choi, Jingyi Xie, Rongyu Zhang, Kim Murray, Sergey
Kornilov, Brett Smith, Andrew T. Magis, Dave S. B. Hoon, Jennifer
J. Hadlock, Jason D. Goldman, Nathan D. Price, Raphael Gottardo,
Mark M. Davis, Leroy Hood, Philip D.

Greenberg, James R. Heath. Integrated analysis of plasma and
single immune cells uncovers metabolic changes in individuals
with COVID-19.

Nature Biotechnology, Sept. 6, 2021; DOI: 10.1038/s41587-021-01020-4 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210906111320.htm

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