Background

Affectation of the red blood cells (RBCs) in COVID-19 has been associated to severe disease evolution, including changes in hemoglobin levels and RBC shape and renovation. We aim to identify specific association between altered metabolic pathways in RBCs and unfavorable outcomes in hospitalized COVID-19 patients.

Methods

Patients were stratified into moderate or severe outcomes (acute respiratory failure, acute myocardial injury, acute kidney failure, ICU admission or death). We analyzed the metabolic profile of RBCs using Nuclear Magnetic Resonance spectroscopy. The resulting profiles were then compared, performing multivariate PLS-DA analysis between groups.

Results

We identified several metabolites specifically altered in patients with severe outcomes related with different pathways, including an affectation of glutathione redox system and the pentose phosphate pathway (necessary for NADPH production). Based on the RBCs profile, we identified two subgroups of severe patients (those who presented or not acute myocardial injury, DIC, acidosis, and death) in whom the Luebering-Rapoport pathway, that regulates oxygen release from hemoglobin and delivery to tissues, seemed to be altered, as well as glycolysis.

Conclusions

Our study allowed the identification of specific alterations in RBC metabolism related with pathways that regulate the response to oxidative stress and the release of oxygen to the tissues that are associated with a worse evolution in COVID-19 patients.Our results open new avenues in the identification of novel prognostic factors and potential therapeutical targets based on the metabolic profile of RBCs in this patients.

Funded: MSD Investigators Study Program MISP 60614