Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19

Carissimo, Guillaume; Xu, Weili; Kwok, Immanuel; Abdad, Mohammad Yazid; Chan, Yi Hao; Fong, Siew‐Wai; Puan, Kia Joo; Lee, Cheryl Yi‐Pin; Yeo, Nicholas Kim‐Wah; Amrun, Siti Naqiah; Chee, Rhonda Sin Ling; How, Wilson; Chan, Sui Yung; Fan, Bingwen Eugene; Andiappan, Anand Kumar; Lee, Bernett; Rötzschke, Olaf; Young, Barnaby Edward; Leo, Yee Sin; Lye, David C.; Rénia, Laurent; Ng, Lai Guan; Larbi, Anis; Ng, Lisa F. P.

doi:10.1038/s41467-020-19080-6

Cited by 156 publications

(207 citation statements)

References 76 publications

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“… 43 , 44 CD169 has been found on circulating monocytes in mild COVID-19 patients. 20 , 42 , 45 Furthermore, CD169 + monocytes have been shown to have a strong ISG signature in single-cell RNA sequencing (scRNA-seq) data, which is consistent with the induction of ISGs observed in our study, including CD64, CD38, and IDO. We find that this phenotype can also be present in severe COVID-19.…”

Section: Discussionsupporting

confidence: 91%

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A distinct innate immune signature marks progression from mild to severe COVID-19

Chevrier

Zurbuchen

Cervia

et al. 2021

Cell Reports Medicine

121

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Section: Discussionsupporting

confidence: 91%

“…Among the phenotype changes occurring early upon SARS-CoV-2 infection, we identified a decrease in non-activated classical monocytes, a depletion of non-activated intermediate and non-classical monocytes, and a surge of CD169 + activated monocytes as well as low-density neutrophils. 42 …”

Section: Discussionmentioning

confidence: 99%

A distinct innate immune signature marks progression from mild to severe COVID-19

Chevrier

Zurbuchen

Cervia

et al. 2021

Cell Reports Medicine

121

123

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“…Moreover, by considering the important prognostic role of T-cell lymphopenia in COVID-19 [28], an innovative parameter combining these two cytometric values (putatively called "MDW-to-lymphocyte ratio") could worthily be investigated. This suggestion seems consistent with COVID-19 studies highlighting the predictive role of neutrophils-to-lymphocyte ratio (NLR) and other similar cell ratios, based on combination of myeloid and lymphoid subsets [29][30][31]. Very recently, a diagnostic test using NLR and MDW has been demonstrated to accurately distinguish COVID-19 from in uenza and common upper respiratory tract infections in patients with suspected symptoms (AUC: 0.84; MDW threshold, ≥20) [32].…”

Section: Discussionsupporting

confidence: 84%

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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“…The increased neutrophil frequency was associated with a decreased expression of surface markers of maturation including CD11b, HLA-DR and CD15. COVID-19 is associated with accumulation of peripherally circulating immature low-density neutrophils (LDN) 14 , previously characterized to have low-to-intermediate surface expression of CD11b 13 and HLA-DR 13,14,15 . Similarly, CD15 is a marker of neutrophil antimicrobial function, with decreased CD15 expression being associated with high TB microbial burden and treatment failure 31 .…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of the Leukocyte Signaling Landscape during Acute COVID-19

Turnbull¹,

Fuchs²,

Remy³

et al. 2021

Preprint

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The global COVID-19 pandemic has claimed the lives of more than 450,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated local tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction in COVID-19 we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry. COVID-19 is associated with wholesale activation of a broad set of signaling pathways across myeloid and lymphoid cell populations. STAT3 phosphorylation predominated in both monocytes and T cells and was tightly correlated with circulating IL-6 levels. High levels of STAT3 phosphorylation was associated with decreased markers of myeloid cell maturation/activation and decreased ex-vivo T cell IFN-gamma production, demonstrating that during COVID-19 dysregulated cellular activation is associated with suppression of immune effector cell function. Collectively, these data reconcile the systemic inflammatory response and functional immunosuppression induced by COVID-19 and suggest STAT3 signaling may be the central pathophysiologic mechanism driving immune dysfunction in COVID-19.

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Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19

Cited by 156 publications

References 76 publications

A distinct innate immune signature marks progression from mild to severe COVID-19

A distinct innate immune signature marks progression from mild to severe COVID-19

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

Dysregulation of the Leukocyte Signaling Landscape during Acute COVID-19

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