Elevated monocyte distribution width in COVID-19 patients: The contribution of the novel sepsis indicator

Ognibene, Agostino; Lorubbio, Maria; Magliocca, Pasqualino; Tripodo, Emanuela; Vaggelli, Guendalina; Iannelli, Giovanni; Feri, Marco; Scala, Raffaele; Tartaglia, Alessandro Polcini; Galano, Angelo; Pancrazzi, Alessandro; Tacconi, Danilo

doi:10.1016/j.cca.2020.06.002

Cited by 48 publications

(55 citation statements)

References 11 publications

(11 reference statements)

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“…In particular, we showed that high MDW values, identi ed by using 26.4 as threshold, can be associated with elevated mortality risk (about one third) in COVID-19 patients. Possibly in line with this nding, in a series of 41 COVID-19 patients tested once for MDW at the time of ED admission, MDW mean value was 28.8 in very critical patients (admitted to ICU after ED triage), while mean value of 25.4 was observed in patients with milder symptoms [25], thus supporting the idea that severe clinical conditions can be associated with higher MDW values. Moreover, in the original studies describing ESId test, based on two wide cohorts of consecutive patients admitted to ED [9][10][11], MDW values of 20 and 20.5 were identi ed as best thresholds to consider the test positive.…”

Section: Discussionsupporting

confidence: 67%

“…While other reports have recently started to describe the performance of MDW as diagnostic marker for COVID-19 [25,32], in this work we focused on the use of MDW in the monitoring of hospitalized patients diagnosed with COVID-19, and we disclosed, for the rst time, the potentials of MDW as prognostic marker during COVID-19 course. Our study suggests that virtually all COVID-19 in-patients present at least one positive value (>20.5) of MDW, which actually constitutes a novel sepsis biomarker.…”

Section: Discussionmentioning

confidence: 99%

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

Riva

Castellano

Nasillo

et al. 2021

Preprint

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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.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

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

Riva

Castellano

Nasillo

et al. 2021

Preprint

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“…In this proof of concept study, we have demonstrated that both lymph index and the MDW were significantly increased in COVID-19 patients. These observations were supported by a recent study that showed also elevated MDW in COVID-19 patients 10. Elevated lymph index and the monocyte volumetric parameters indicate increased overall cell sizes with greater cell size variations among circulating lymphocyte and monocyte populations.…”

supporting

confidence: 78%

Monocyte volumetric parameters and lymph index are increased in SARS‐CoV‐2 infection

Zeng

Xing

Yan

et al. 2020

Int J Lab Hematology

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“…CSS is an aberrant overactivation of cytokine signaling that leads to a toxic excessive immune response [ 37 – 40 ]. There is evidence that monocytes play a key role in COVID-19 induced CSS [ 38 , 41 ]. We demonstrated that ex vivo exposure to SARS-CoV-2 S protein leads to an initial increase in CD14hi monocytes.…”

Section: Discussionmentioning

confidence: 99%

Human Hematopoietic Stem, Progenitor, and Immune Cells Respond Ex Vivo to SARS-CoV-2 Spike Protein

Ropa

Cooper

Capitano

et al. 2020

Stem Cell Rev and Rep

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Despite evidence that SARS-CoV-2 infection is systemic in nature, there is little known about the effects that SARS-CoV-2 infection or exposure has on many host cell types, including primitive and mature hematopoietic cells. The hematopoietic system is responsible for giving rise to the very immune cells that defend against viral infection and is a source of hematopoietic stem cells (HSCs) and progenitor cells (HPCs) which are used for hematopoietic cell transplantation (HCT) to treat hematologic disorders, thus there is a strong need to understand how exposure to the virus may affect hematopoietic cell functions. We examined the expression of ACE2, to which SARS-CoV-2 Spike (S) protein binds to facilitate viral entry, in cord blood derived HSCs/HPCs and in peripheral blood derived immune cell subtypes. ACE2 is expressed in low numbers of immune cells, higher numbers of HPCs, and up to 65% of rigorously defined HSCs. We also examined effects of exposing HSCs/HPCs and immune cells to SARS-CoV-2 S protein ex vivo. HSCs and HPCs expand less effectively and have less functional colony forming capacity when grown with S protein, while peripheral blood monocytes upregulate CD14 expression and show distinct changes in size and granularity. That these effects are induced by recombinant S protein alone and not the infectious viral particle suggests that simple exposure to SARS-CoV-2 may impact HSCs/HPCs and immune cells via S protein interactions with the cells, regardless of whether they can be infected. These data have implications for immune response to SARS-CoV-2 and for HCT. Graphical Abstract • Human HSCs, HPCs, and immune cells express ACE2 on the cell surface, making them potentially susceptible to SARS-CoV-2 infection. • SARS-CoV-2 S protein, which binds to ACE2, induces defects in the colony forming capacity of human HPC and inhibits the expansion of HSC/HPC subpopulations ex vivo . These effects can be at least partially neutralized by treatment with SARS-CoV-2 targeting antibody, recombinant human ACE2, or Angiotensin1–7. • S protein also induces aberrant morphological changes in peripheral blood derived monocytes ex vivo . • Thus, there are many different manners in which SARS-CoV-2 virus may impact the functional hematopoietic system, which has important implications for hematological manifestations of COVID-19 (i.e. thrombocytopenia and lymphopenia), immune response, and hematopoietic stem cell transplant in the era of COVID-19. Electronic supplementary material The online version of this article (10.1007/s12015-020-10056-z) contains supplementary material, which is available to authorized users.

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Elevated monocyte distribution width in COVID-19 patients: The contribution of the novel sepsis indicator

Cited by 48 publications

References 11 publications

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

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

Monocyte volumetric parameters and lymph index are increased in SARS‐CoV‐2 infection

Human Hematopoietic Stem, Progenitor, and Immune Cells Respond Ex Vivo to SARS-CoV-2 Spike Protein

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