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Hyperglycemia, Reduced Hematopoietic Stem Cells, and Outcome of COVID-19

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posted on 21.01.2022, 16:21 by Benedetta Maria Bonora, Paola Fogar, Jenny Zuin, Daniele Falaguasta, Roberta Cappellari, Annamaria Cattelan, Serena Marinello, Anna Ferrari, Angelo Avogaro, Mario Plebani, Daniela Basso, Gian Paolo Fadini
Admission hyperglycemia has emerged worldwide as a predictor of poor COVID-19 outcome. Hyperglycemia leads to a defect in circulating hematopoietic stem/progenitor cells (HSPCs) which, in turn, predicts diabetic complications. Here, we explored whether reduced HSPCs mediated at least part of the prognostic effect of hyperglycemia on COVID-19 outcome. We found that patients with COVID-19 (n=100) hospitalized in a non-intensive setting displayed dramatically (50-60%) reduced levels of HSPCs measured by flow cytometry as CD34+, CD34+CD45dim or CD34+CD133+ cells, compared with controls (n=595). This finding was highly significant (all p<10-10) after multivariable adjustment, or manual 1:1 patient match, or propensity score matching. Admission hyperglycemia (≥7.0 mmol/l) was present in 45% of patients, was associated with a significant further ~30% HSPCs reduction and predicted a 2.6-fold increased risk of the primary outcome of adverse COVID-19 course (admittance to the intensive care unit or death). Low HSPCs were also associated with advanced age, higher peak C-reactive protein and neutrophil/lymphocyte ratio. Independently from confounders, one standard deviation lower CD34+ HSPCs was associated with a >3-fold higher risk of adverse outcome. Upon formal analysis, reduction of HSPCs was a significant mediator of the admission hyperglycemia on COVID-19 outcome, being responsible for 28% of its prognostic effect.

Funding

Supported by the Department of Medicine, University of Padova (Fondazione CARIPARO, COVIDIMED project) and by the Italian Ministry of Education, University and Research, 2020 PRIN call (202077EYN7).

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