09/28/2026
Breaking: PolyBio Funds Spatial Metabolomic Mapping of Long COVID Tissues
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Medford, MA — September 28, 2026 — PolyBio Research Foundation has funded a new project using advanced mass spectrometry imaging to map metabolic and mitochondrial abnormalities directly within tissues from people with Long COVID. The study aims to uncover localized changes in energy production, lipid metabolism, oxidative stress, and other biochemical pathways that may contribute to Long COVID symptoms and disease progression.
The project is led by Elizabeth K. Neumann, PhD, Assistant Professor of Chemistry at the University of California, Davis, in collaboration with Timothy J. Henrich, MD, Professor of Medicine and Director of the Center for Infectious Disease and Molecular Imaging at the University of California, San Francisco.
The team will apply matrix-assisted laser desorption/ionization mass spectrometry imaging, or MALDI MSI, to colorectal tissue, bone marrow, muscle, cerebrospinal fluid, and paired blood or plasma samples collected through the UCSF LIINC cohort and other PolyBio-supported studies. Samples will include those from people with Long COVID, carefully matched individuals who fully recovered from SARS-CoV-2 infection, and participants in certain interventional clinical trials.
Long COVID has been associated with abnormalities in energy metabolism, mitochondrial function, lipid regulation, and oxidative stress. However, most metabolomic studies analyze molecules extracted from blood or homogenized tissue. These approaches can identify broad biochemical differences but eliminate the spatial information needed to determine where abnormalities occur, which cells and tissue structures are affected, and whether distinct metabolic changes coexist within the same samples.
MALDI MSI addresses this limitation by measuring large numbers of molecular species directly within intact tissue sections. A chemical matrix is applied to the tissue and stimulated with a laser, allowing hundreds of lipids and metabolites to be identified by mass spectrometry and mapped back to their original locations.
“Metabolic and mitochondrial dysfunction are increasingly implicated in Long COVID, but we still have a limited understanding of how these abnormalities manifest within affected tissues,” said Amy Proal, PhD, President and Research Director of PolyBio Research Foundation. “This technology will allow the team to identify localized biochemical changes that may be missed when an entire tissue sample is analyzed in bulk. The resulting maps could reveal important pathways driving symptoms and point toward new biomarkers and treatment targets.”
The investigators expect to detect approximately 200 distinct lipids and 150 metabolites in each tissue sample. Because the approach is label-free and does not require researchers to select a limited set of molecular targets in advance, it can generate an unbiased view of the biochemical pathways altered in Long COVID.
The MALDI MSI findings will also be integrated with spatial multiomic analyses performed on adjacent tissue sections. These analyses include measurements of immune activity, host responses, and single- and double-stranded SARS-CoV-2 RNA. This complementary information will help the investigators interpret the metabolic findings within a broader biological context and determine how altered biochemical pathways relate to other features of Long COVID pathology.
The Neumann laboratory has previously demonstrated the power of this approach by using MALDI trapped-ion mobility mass spectrometry imaging to localize low-abundance polystyrene particles across mouse tissues while simultaneously identifying organ-specific changes in lipid metabolism. The study detected distinct molecular alterations in the stomach, liver, and heart, showing that the technology can connect tissue exposures with surrounding biochemical changes.
In the new Long COVID study, the investigators will additionally examine whether MALDI MSI can detect and characterize extracellular vesicles in paired plasma and cerebrospinal fluid samples. Extracellular vesicles are small membrane-bound particles released by cells that carry proteins, lipids, nucleic acids, and other molecular cargo into accessible biofluids.
By comparing tissue-level metabolic abnormalities with extracellular vesicle signals in blood or cerebrospinal fluid, the researchers may identify accessible biomarkers that reflect mitochondrial or metabolic dysfunction occurring within less accessible tissues. Such biomarkers could ultimately help distinguish biological subgroups of Long COVID, identify patients most likely to benefit from specific therapies, and monitor treatment responses during clinical trials.
The project advances PolyBio’s broader strategy of combining direct tissue analysis with next-generation biofluid diagnostics.
Read more on the study's background: https://polybio.org/polybio-funds-spatial-metabolomic-mapping-of-long-covid-tissues/
