The SARS-CoV-2 beta coronavirus is the etiological driver of COVID-19 disease, which is
primarily characterized by shortness of breath, persistent dry cough, and fever. Because they transport
oxygen, red blood cells (RBCs) may play a role in the severity of hypoxemia in COVID-19 patients.
The present study combines state-of-the-art metabolomics, proteomics, and lipidomics
approaches to investigate the impact of COVID-19 on RBCs from 23 healthy subjects and 29
molecularly-diagnosed COVID-19 patients. RBCs from COVID-19 patients had increased levels of
glycolytic intermediates, accompanied by oxidation and fragmentation of ankyrin, spectrin beta, and
the N-terminal cytosolic domain of band 3 (AE1). Significantly altered lipid metabolism was also
observed, especially short and medium chain saturated fatty acids, acyl-carnitines, and sphingolipids.
Nonetheless, there were no alterations of clinical hematological parameters, such as RBC count,
hematocrit, and mean corpuscular hemoglobin concentration, with only minor increases in mean
corpuscular volume. Taken together, these results suggest a significant impact of SARS-CoV-2
infection on RBC structural membrane homeostasis at the protein and lipid levels. Increases in RBC
glycolytic metabolites are consistent with a theoretically improved capacity of hemoglobin to offload
oxygen as a function of allosteric modulation by high-energy phosphate compounds, perhaps to
counteract COVID-19-induced hypoxia. Conversely, because the N-terminus of AE1 stabilizes
deoxyhemoglobin and finely tunes oxygen off-loading and metabolic rewiring towards the hexose
monophosphate shunt, RBCs from COVID-19 patients may be less capable to respond to
environmental variations in hemoglobin oxygen saturation/oxidant stress when traveling from the
lungs to peripheral capillaries and vice versa.
[doi:10.25345/C5548G]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: SARS-CoV-2 ; erythrocyte ; band 3 ; AE1 ; metabolomics ; proteomics ; lipidomics
Principal Investigators: (in alphabetical order) |
Angelo D'alessandro, University of Colorado - Anschutz Medical Campus, USA |
Submitting User: | rchill14 |
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Owner | Reanalyses | |
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