Citation: Coco¸ s, R.; Mahler, B.; Turcu-Stiolica, A.; Stoichit , ˘ a, A.; Ghinet, A.; Shelby, E.-S.; Bohîlt , ea, L.C. Risk of Death in Comorbidity Subgroups of Hospitalized COVID-19 Patients Inferred by Routine Laboratory Markers of Systemic Inflammation on Admission: A Retrospective Study. Viruses 2022, 14, 1201. https:// doi.org/10.3390/v14061201 Academic Editors: Amilcar Tanuri and Luciana Jesus Costa Received: 9 May 2022 Accepted: 28 May 2022 Published: 31 May 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). viruses Article Risk of Death in Comorbidity Subgroups of Hospitalized COVID-19 Patients Inferred by Routine Laboratory Markers of Systemic Inflammation on Admission: A Retrospective Study Relu Coco¸ s 1,2, * ,† , Beatrice Mahler 1,3,† , Adina Turcu-Stiolica 4, * , Alexandru Stoichit , ă 1,5 , Andreea Ghinet 1 , Elena-Silvia Shelby 6 and Laurent , iu Camil Bohîlt , ea 2 1 Institute of Pneumophtisiology “Marius Nasta”, 050159 Bucharest, Romania; beatrice.mahler@umfcd.ro (B.M.); alexandru.stoichita@drd.umfcd.ro (A.S.); andreea_bc15@yahoo.com (A.G.) 2 Department of Medical Genetics, University of Medicine and Pharmacy “Carol Davila”, 020032 Bucharest, Romania; gen_og@yahoo.com 3 Pneumology Department (II), University of Medicine and Pharmacy “Carol Davila”, 020021 Bucharest, Romania 4 Department of Pharmacoeconomics, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania 5 Department of Cardiology, University of Medicine and Pharmacy “Carol Davila”, 020021 Bucharest, Romania 6 Scientific Research Nucleus, Dr. Nicolae Robanescu National Clinical Centre for Children’s Neurorecovery, 041408 Bucharest, Romania; silviajdx@yahoo.com * Correspondence: relu.cocos@umfcd.ro (R.C.); adina.turcu@umfcv.ro (A.T.-S.) These authors contributed equally to this work. Abstract: Our study objective was to construct models using 20 routine laboratory parameters on admission to predict disease severity and mortality risk in a group of 254 hospitalized COVID-19 patients. Considering the influence of confounding factors in this single-center study, we also retro- spectively assessed the correlations between the risk of death and the routine laboratory parameters within individual comorbidity subgroups. In multivariate regression models and by ROC curve analysis, a model of three routine laboratory parameters (AUC 0.85; 95% CI: 0.79–0.91) and a model of six laboratory factors (AUC 0.86; 95% CI: 0.81–0.91) were able to predict severity and mortality of COVID-19, respectively, compared with any other individual parameter. Hierarchical cluster analysis showed that inflammatory laboratory markers grouped together in three distinct clusters including positive correlations: WBC with NEU, NEU with neutrophil-to-lymphocyte ratio (NLR), NEU with systemic immune-inflammation index (SII), NLR with SII and platelet-to-lymphocyte ratio (PLR) with SII. When analyzing the routine laboratory parameters in the subgroups of comorbidities, the risk of death was associated with a common set of laboratory markers of systemic inflammation. Our results have shown that a panel of several routine laboratory parameters recorded on admission could be helpful for early evaluation of the risk of disease severity and mortality in COVID-19 patients. Inflammatory markers for mortality risk were similar in the subgroups of comorbidities, suggesting the limited effect of confounding factors in predicting COVID-19 mortality at admission. Keywords: COVID-19; severity predictors; comorbidity; model; inflammatory markers 1. Introduction Since the first reported case of coronavirus disease 2019 (COVID-19) in Hubei province, China, in December 2019, this disease, which was initially described as a cluster of pneumo- nia cases with unknown viral etiology, spread quickly into an ongoing and evolving pan- demic that caused millions of infections and deaths worldwide despite the implemented containment measures [1]. Shortly after, the causative agent of the current COVID-19 pandemic, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified and sequenced [2]. Viruses 2022, 14, 1201. https://doi.org/10.3390/v14061201 https://www.mdpi.com/journal/viruses