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

Admission hyperglycemia has emerged worldwide as a predictor of poor coronavirus disease 2019 (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 nonintensive setting displayed dramatically (50-60%) reduced levels of HSPCs measured by flow cytometry as CD34(+), CD34(+)CD45(dim), or CD34(+)CD133(+) cells, compared with control subjects (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 similar to 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-to-lymphocyte ratio. Independently from confounders, 1 SD lower CD34(+) HSPCs was associated with a more than threefold 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.