Objective Evidence-based characterization of the diagnostic and prognostic value of the hematological and immunological markers related to the epidemic of Coronavirus Disease 2019 (COVID-19) is critical to understand the clinical course of the infection and to assess in development and validation of biomarkers. Methods Based on systematic search in Web of Science, PubMed, Scopus, and Science Direct up to April 22, 2020, a total of 52 eligible articles with 6,320 laboratory-confirmed COVID-19 cohorts were included. Pairwise comparison between severe versus mild disease, Intensive Care Unit (ICU) versus general ward admission and expired versus survivors were performed for 36 laboratory parameters. The pooled standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using the DerSimonian Laird method/random effects model and converted to the Odds ratio (OR). The decision tree algorithm was employed to identify the key risk factor(s) attributed to severe COVID-19 disease. Results Cohorts with elevated levels of white blood cells (WBCs) (OR = 1.75), neutrophil count (OR = 2.62), D-dimer (OR = 3.97), prolonged prothrombin time (PT) (OR = 1.82), fibrinogen (OR PLOS ONE

Background: Coronavirus disease-2019 (COVID-19) has a deleterious effect on several systems, including the cardiovascular system. We aim to systematically explore the association of COVID-19 severity and mortality rate with the history of cardiovascular diseases and/or other comorbidities and cardiac injury laboratory markers. Methods: The standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CIs) were applied to estimate pooled results from the 56 studies. The prognostic performance of cardiac markers for predicting adverse outcomes and to select the best cutoff threshold was estimated by receiver operating characteristic curve analysis. Decision tree analysis by combining cardiac markers with demographic and clinical features was applied to predict mortality and severity in patients with COVID-19.

Objective Evidence-based characterization of the diagnostic and prognostic value of the hematological and immunological markers related to the epidemic of Coronavirus Disease 2019 (COVID-19) is critical to understand the clinical course of the infection and to assess in development and validation of biomarkers. Methods Based on systematic search in Web of Science, PubMed, Scopus, and Science Direct up to April 22, 2020, a total of 52 eligible articles with 6,320 laboratory-confirmed COVID-19 cohorts were included. Pairwise comparison between severe versus mild disease, Intensive Care Unit (ICU) versus general ward admission, and expired versus survivors were performed for 36 laboratory parameters. The pooled standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using the DerSimonian Laird method/random effects model and converted to Odds ratio (OR). The decision tree algorithm was employed to identify the key risk factor(s) attributed to severe COVID-19 disease. Results Cohorts with elevated levels of white blood cells (WBCs) (OR=1.75), neutrophil count (OR=2.62), D-dimer (OR=3.97), prolonged prothrombin time (PT) (OR=1.82), fibrinogen (OR=3.14), erythrocyte sedimentation rate (OR=1.60), procalcitonin (OR=4.76), IL-6 (OR=2.10), and IL-10 (OR=4.93) had higher odds of progression to severe phenotype. Decision tree model (sensitivity=100%, specificity=81%) showed the high performance of neutrophil count at a cut-off value of more than 3.74 x109/L for identifying patients at high risk of severe COVID‐19. Likewise, ICU admission was associated with higher levels of WBCs (OR=5.21), neutrophils (OR=6.25), D-dimer (OR=4.19), and prolonged PT (OR=2.18). Patients with high IL-6 (OR=13.87), CRP (OR=7.09), D-dimer (OR=6.36), and neutrophils (OR=6.25) had the highest likelihood of mortality. Conclusions Several hematological and immunological markers, in particular neutrophilic count, could be helpful to be included within the routine panel for COVID-19 infection evaluation to ensure risk stratification and effective management.

Multilineage-differentiating stress-enduring (Muse) cells are endogenous nontumorigenic stem cells collectable as stage-specific embryonic antigen 3 (SSEA-3) + from various organs including the bone marrow and are pluripotent-like. The potential of human bone marrow-derived Muse cells to commit to cardiac lineage cells was evaluated. We found that (1) initial treatment of Muse cells with 5′-azacytidine in suspension culture successfully accelerated demethylation of cardiac marker Nkx2.5 promoter; (2) then transferring the cells onto adherent culture and treatment with early cardiac differentiation factors including wingless-int (Wnt)-3a, bone morphogenetic proteins (BMP)-2/4, and transforming growth factor (TGF) β1; and (3) further treatment with late cardiac differentiation cytokines including cardiotrophin-1 converted Muse cells into cardiomyocyte-like cells that expressed α-actinin and troponin-I with a striation-like pattern. MLC2a expression in the final step suggested differentiation of the cells into an atrial subtype. MLC2v, a marker for a mature ventricular subtype, was expressed when cells were treated with Dickkopf-related protein 1 (DKK-1) and Noggin, inhibitors of Wnt3a and BMP-4, respectively, between steps (2) and (3). None of the steps included exogenous gene transfection, making induced cells feasible for future clinical application.