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Halil Yildiz,1,&ast; Diego Castanares-Zapatero,2,&ast; Guillaume Pierman,1 Lucie Pothen,1 Julien De Greef,1 Frank Aboubakar Nana,3 Hector Rodriguez-Villalobos,4 Leila Belkhir,1 Jean Cyr Yombi1 1Department of Internal Medicine and Infectious Diseases, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (UCLouvain), Brussels, Belgium; 2Department of Intensive Care Unit, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium; 3Department of Pneumology, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium; 4Department of Microbiology, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium&ast;These authors contributed equally to this workCorrespondence: Halil YildizDepartment of Internal Medicine and Infectious Diseases, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, 10 avenue hippocrate, Brussels, BelgiumTel +3227641902Fax +3227641046Email halil.yildiz@uclouvain.beIntroduction: The neutrophil-to-lymphocyte ratio (NLR) could be a predictive factor of severe COVID-19. However, most relevant studies are retrospective, and the optimal NLR cut-off point has not been determined. The objective of our research was identification and validation of the best NLR cut-off value on admission that could predict high in-hospital mortality in COVID-19 patients.Methods: Medical files of all patients admitted for COVID-19 pneumonia in our dedicated COVID-units between March and April 2020 (derivation cohort) and between October and December 2020 (validation cohort) were reviewed.Results: Two hundred ninety-nine patients were included in the study (198 in the derivation and 101 in the validation cohort, respectively). Youden’s J statistic in the derivation cohort determined the optimal cut-off value for the performance of NLR at admission to predict mortality in hospitalized patients with COVID-19. The NLR cut-off value of 5.94 had a sensitivity of 62% and specificity of 64%. In ROC curve analysis, the AUC was 0.665 [95% CI 0.530– 0.801, p= 0.025]. In the validation cohort, the best predictive cut-off value of NLR was 6.4, which corresponded to a sensitivity of 63% and a specificity of 64% with AUC 0.766 [95% CI 0.651– 0.881, p < 0.001]. When the NLR cut-off value of 5.94 was applied in the validation cohort, there was no significant difference in death and survival in comparison with the derivation NLR cut-off. Net reclassification improvement (NRI) analysis showed no significant classification change in outcome between both NLR cut-off values (NRI:0.012, p=0.31).Conclusion: In prospective analysis, an NLR value of 5.94 predicted high in-hospital mortality upon admission in patients hospitalized for COVID-19 pneumonia.Keywords: neutrophil-to-lymphocyte ratio, coronavirus disease, SARS-CoV-2 infection, COVID-19, risk factors, laboratory markers