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

Abstract

Background: Monocyte Distribution Width (MDW), a new cytometric parameter correlating with cytomorphologic changes occurring during massive monocyte activation, has recently been described as promising early biomarker of sepsis. Similar to sepsis, in SARS-CoV-2-associated disease (COVID-19) monocyte/macrophage subsets are considered key mediators of the life-threatening hyper-inflammatory disorder –commonly defined as ‘cytokine storm’– which is part of the complex infection-associated immune dysregulation observed in severe COVID-19 cases (possibly constituting a kind of viral sepsis). Therefore, in this work, we aimed at investigating, for the first time, possible roles of MDW testing in the monitoring of COVID-19 patients.Methods: We longitudinally measured MDW values (readily available along with automated blood cell count) in a cohort of 87 patients with COVID-19 diagnosis, consecutively admitted to our clinics in early 2020, due to aggravation of their clinical status. Statistical analyses were then applied to correlate MDW values with inflammatory markers, disease severity, clinical trajectories and final outcome.Results: We initially found significant direct correlations between MDW and different inflammatory markers routinely assessed during hospitalization, namely CRP (p<0.001), fibrinogen (p<0.001) and ferritin (p<0.01). Moreover, high MDW values resulted remarkably associated with fatal outcome of severe 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). Furthermore, when evaluating MDW dynamics in COVID-19 cases with longer follow-up, we frequently observed progressive MDW increment in patients with worsening inflammation, while clinical recovery was consistently associated with MDW decrease. Of note, MDW evaluation may also help to assess the response to immunomodulatory treatments, such as tocilizumab. Conclusions: Our pilot study shows that MDW can be useful in the monitoring of COVID-19 patients, as this innovative hematologic biomarker is (i) easy and rapid to obtain, (ii) directly related to the activation state of a fundamental inflammatory cell subset (i.e. monocytes, pivotal in both cytokine storm and sepsis immunopathogenesis), (iii) well correlated with clinical severity of COVID-19-associated inflammatory disorder, and, in turn, (iv) 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.

Molecular and cellular immune features of aged patients with severe COVID-19 pneumonia

“…The presence of higher levels of PD-1 and PD-L1 on monocytes from severe COVID-19 has been linked to metabolic dysfunctions, even if altered mitochondrial ultrastructure are unable to impair their ability to produce pro-in ammatory cytokines 13 . Other than ultrastructure, cytomorphologic changes have been described, and indeed the monocyte distribution width (MDW) can now be considered a novel cytometry-based marker of disease severity with a relevant prognostic signi cance 54 . If several evidences con rm that a hyperin ammatory signature characterizes monocytes from COVID-19 patients, other data prove that an immunosuppressive signature, de ned by downregulation of HLA-DRA, ALOX5AP, and RETN, also exists.…”

Retrospective study on the efficacy of monocyte distribution width (MDW) as a screening test for COVID-19

“…This study was conducted after being approved by the ethics committee of National Hospital Organization Omuta National Hospital (Approval No. : [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19].…”

“…In severe infections such as sepsis, cytokine storm and activation of WBC are known to occur [ 9-13 ], and morphological change of monocytes [14] and cytokine storm have been reported in COVID-19, which is an infectious disease [15][16]. Therefore, the usefulness of MDW as an index of COVID-19 has been reported [17][18][19].…”

Circulating histones contribute to monocyte and MDW alterations as common mediators in classical and COVID-19 sepsis

“…Among common laboratory biomarkers shared by SARS-CoV-2 and Sepsis infections [7,11], the modification of the hematological parameter Monocyte Distribution Width (MDW) predicts both multiorgan failure and increased mortality rate in Sepsis conditions [11]. MDW index (FDA-approved, EC-marked early Sepsis indicator of monocyte heterogeneity upon massive inflammatory activation [11]) is further recognized as diagnostic/prognostic marker for COVID-19 severity and clinical outcomes, as a kind of novel viral Sepsis biomarker [12][13][14].…”