Monocyte Distribution Width (MDW) as novel inflammatory marker with prognostic significance in COVID-19 patients

Giovanni Riva,Sara De Biasi,Jovana Milić,Stefano Busani,Cristina Mussini,Beatrice Lusenti,Massimo Girardis,Andrea Cossarizza,Giovanni Guaraldi,Tommaso Trenti,Enrico Tagliafico,Lara Gibellini,Rossella Manfredini,Mario Luppi,Anna Maria Ottomano,Giuliano Bergonzini,Ambra Paolini,Sara Castellano,Vincenzo Nasillo

doi:10.1038/s41598-021-92236-6

Abstract

Monocyte Distribution Width (MDW), a new cytometric parameter correlating with cytomorphologic changes occurring upon massive monocyte activation, has recently emerged as promising early biomarker of sepsis. Similar to sepsis, monocyte/macrophage subsets are considered key mediators of the life-threatening hyper-inflammatory disorder characterizing severe COVID-19. In this study, we longitudinally analyzed MDW values in a cohort of 87 COVID-19 patients consecutively admitted to our hospital, showing significant correlations between MDW and common inflammatory markers, namely CRP (p < 0.001), fibrinogen (p < 0.001) and ferritin (p < 0.01). Moreover, high MDW values resulted to be prognostically associated with fatal outcome in COVID-19 patients (AUC = 0.76, 95% CI: 0.66–0.87, sensitivity 0.75, specificity 0.70, MDW threshold 26.4; RR = 4.91, 95% CI: 1.73–13.96; OR = 7.14, 95% CI: 2.06–24.71). This pilot study shows that MDW can be useful in the monitoring of COVID-19 patients, as this innovative hematologic biomarker is: (1) easy to obtain, (2) directly related to the activation state of a fundamental inflammatory cell subset (i.e. monocytes, pivotal in both cytokine storm and sepsis immunopathogenesis), (3) well correlated with clinical severity of COVID-19-associated inflammatory disorder, and, in turn, (4) endowed with relevant prognostic significance. Additional studies are needed to define further the clinical impact of MDW testing in the management of COVID-19 patients.

Highlights

Monocyte Distribution Width (MDW), a new cytometric parameter correlating with cytomorphologic changes occurring upon massive monocyte activation, has recently emerged as promising early biomarker of sepsis
Based on the laboratory dataset available for our cohort of 87 COVID-19 patients with at least one MDW measurement, we performed repeated measures correlation analysis to compare MDW with main inflammatory markers frequently tested in this setting, as part of routine laboratory monitoring
We observed a good association between MDW values and body temperatures (p < 0.05), further indicating that high MDW values may be associated with inflammatory syndromes, often including fever

Summary

Introduction

Monocyte Distribution Width (MDW), a new cytometric parameter correlating with cytomorphologic changes occurring upon massive monocyte activation, has recently emerged as promising early biomarker of sepsis. High MDW values resulted to be prognostically associated with fatal outcome in COVID-19 patients (AUC = 0.76, 95% CI: 0.66–0.87, sensitivity 0.75, specificity 0.70, MDW threshold 26.4; RR = 4.91, 95% CI: 1.73–13.96; OR = 7.14, 95% CI: 2.06–24.71) This pilot study shows that MDW can be useful in the monitoring of COVID-19 patients, as this innovative hematologic biomarker is: (1) easy to obtain, (2) directly related to the activation state of a fundamental inflammatory cell subset (i.e. monocytes, pivotal in both cytokine storm and sepsis immunopathogenesis), (3) well correlated with clinical severity of COVID19-associated inflammatory disorder, and, in turn, (4) endowed with relevant prognostic significance. In these studies, the area under the curve (AUC) for ESId test ranges 0.73–0.87, with remarkable negative predictive values (NPV, 93–97%)[9,10,11,12]

Methods

Results

Discussion

Conclusion