Kinetics of peripheral blood neutrophils in severe coronavirus disease 2019

Metzemaekers, Mieke; Cambier, Seppe; Blanter, Marfa; Vandooren, Jennifer; Carvalho, Ana Carolina de; Malengier‐Devlies, Bert; Vanderbeke, Lore; Jacobs, Cato; Coenen, Samuel; Martens, Erik; Pörtner, Noëmie; Vanbrabant, Lotte; Mol, Pierre Van; Herck, Yannick Van; Aerde, Nathalie Van; Hermans, Greet; Gunst, Jan; Borin, Alexandre; Pereira, Bruna Toledo Nunes; Gomes, Arilson Bernardo SP; Muraro, Stéfanie Primon; Souza, Gabriela Fabiano de; Farias, Alessandro S.; Proença-Módena, José Luiz; Vinolo, Marco Aurélio Ramirez; Marques, Pedro Elias; Wouters, Carine; Wauters, Els; Struyf, Sofie; Matthys, Patrick; Opdenakker, Ghislain; Marques, Rafael Elias; Wauters, Joost; Gouwy, Mieke; Proost, Paul; Wilmer, Alexander; Meersseman, Philippe; Lambrechts, Diether; Casaer, Michaël P; Rex, Steffen; Lorent, N; Thevissen, Karin; Martinod, Kim

doi:10.1002/cti2.1271

Cited by 38 publications

(54 citation statements)

References 57 publications

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“…3 C , we detected a wide set of interactions between monocyte-derived (but also CD4 + T cell-derived) chemokines (i.e., CCL3, CXCL1, CXCL2, and CXCL8) binding CCR3 and CXCR1/2 on neutrophil subsets, particularly evident in patients with severe COVID-19 ( Fig. 3 G ) ( 38 ). Patients with mild COVID-19 displayed a marked interaction between neutrophil and plasmablasts through BAFF (TNFSF13B) and BAFF receptors (encoded by TNFRSF13C, TNFRSF13B, or TNFRSF17) ( Fig.…”

Section: Resultsmentioning

confidence: 93%

High-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19

Lourda

Dzidic

Hertwig

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Since the outset of the COVID-19 pandemic, increasing evidence suggests that the innate immune responses play an important role in the disease development. A dysregulated inflammatory state has been proposed as a key driver of clinical complications in COVID-19, with a potential detrimental role of granulocytes. However, a comprehensive phenotypic description of circulating granulocytes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)−infected patients is lacking. In this study, we used high-dimensional flow cytometry for granulocyte immunophenotyping in peripheral blood collected from COVID-19 patients during acute and convalescent phases. Severe COVID-19 was associated with increased levels of both mature and immature neutrophils, and decreased counts of eosinophils and basophils. Distinct immunotypes were evident in COVID-19 patients, with altered expression of several receptors involved in activation, adhesion, and migration of granulocytes (e.g., CD62L, CD11a/b, CD69, CD63, CXCR4). Paired sampling revealed recovery and phenotypic restoration of the granulocytic signature in the convalescent phase. The identified granulocyte immunotypes correlated with distinct sets of soluble inflammatory markers, supporting pathophysiologic relevance. Furthermore, clinical features, including multiorgan dysfunction and respiratory function, could be predicted using combined laboratory measurements and immunophenotyping. This study provides a comprehensive granulocyte characterization in COVID-19 and reveals specific immunotypes with potential predictive value for key clinical features associated with COVID-19.

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Section: Resultsmentioning

confidence: 93%

High-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19

Lourda

Dzidic

Hertwig

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…A possible mechanism for neutrophil activation may be attributable to CXCR2 and C5aR down-regulation. In addition, in patients with severe COVID-19, increased concentrations of neutrophil elastase, gelatinolytic activity, and TIMP-1/MMP-9 complexes were found [ 22 ]. In our study, patients requiring IMV upon ICU admission had higher mean values for immature granulocytes compared with patients not on IPPV.…”

Section: Discussionmentioning

confidence: 99%

“…NLR is the most studied hematological index in COVID-19 patients and higher values were correlated with disease severity and progression [ 12 , 13 , 23 , 24 , 25 ], death [ 13 , 14 , 22 , 24 , 26 ], and treatment response [ 27 ]. Our observations are in agreement for NLR but also for PLR, MLR, SII, and dNLR and are correlated with results from other studies [ 11 , 12 , 13 , 14 , 15 , 23 , 24 , 25 , 26 , 28 , 29 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…In our study, at admission, there were no differences for the studied indices between patients with these associated diseases and those without these conditions, or between patients on low-dose and patients on high-dose dexamethasone at 48 h. Although in the case of methylprednisolone therapy at 48 h there were significant differences for NLR, dNLR, and SII, as we reported in the results section, these differences were also significant at ICU admission (before methylprednisolone initiation) and may have represented only a trend maintenance over time. Moreover, corticosteroids do not seem to change neutrophil phenotype and polarization in severe COVID-19 patients [ 22 ]. Even with these results, we must make two observations: (1) unfortunately, data about corticosteroid therapy administered previously to ICU admission was not available and (2) data about precise corticosteroid dosage was available only for 165 patients out of 272.…”

Section: Discussionmentioning

confidence: 99%

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Dynamic Changes of the Neutrophil-to-Lymphocyte Ratio, Systemic Inflammation Index, and Derived Neutrophil-to-Lymphocyte Ratio Independently Predict Invasive Mechanical Ventilation Need and Death in Critically Ill COVID-19 Patients

et al. 2021

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Background: Hematological indices can predict disease severity, progression, and death in patients with coronavirus disease-19 (COVID-19). Objectives: To study the predictive value of the dynamic changes (first 48 h after ICU admission) of the following ratios: neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), monocyte-to-lymphocyte (MLR), systemic inflammation index (SII), and derived neutrophil-to-lymphocyte (dNLR) for invasive mechanical ventilation (IMV) need and death in critically ill COVID-19 patients. Methods: Observational, retrospective, and multicentric analysis on 272 patients with severe or critical COVID-19 from two tertiary centers. Hematological indices were adjusted for confounders through multivariate analysis using Cox regression. Results: Patients comprised 186 males and 86 females with no difference across groups (p > 0.05). ΔNLR > 2 had the best independent predictive value for IMV need (HR = 5.05 (95% CI, 3.06–8.33, p < 0.0001)), followed by ΔSII > 340 (HR = 3.56, 95% CI 2.21–5.74, p < 0.0001) and ΔdNLR > 1 (HR = 2.61, 95% CI 1.7–4.01, p < 0.0001). Death was also best predicted by an NLR > 11 (HR = 2.25, 95% CI: 1.31–3.86, p = 0.003) followed by dNLR > 6.93 (HR = 1.89, 95% CI: 1.2–2.98, p = 0.005) and SII > 3700 (HR = 1.68, 95% CI: 1.13–2.49, p = 0.01). Conclusions: Dynamic changes of NLR, SII, and dNLR independently predict IMV need and death in critically ill COVID-19 patients.

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“…Neutrophils are able to internalize viruses bound to antibodies or opsonized by complement, and express PRRs such as TLR7, TLR8 and MDA5 that would be activated upon binding of viral genomes, depending on genome composition and structure [ 41 ]. Neutrophils are not target cells in the majority of viral infections, being either impervious to infection or nonpermissive of viral replication [ 29 , 43 ]. Few exceptions include the infection of neutrophils by alphavirus and evidence that hepatitis C virus can replicate in PMN cells [ 44 ], but the contribution of this event to viremia and disease development is unknown.…”

Section: Participation Of Neutrophils In Immune Responses Against Virusesmentioning

confidence: 99%

Neutrophil Recruitment and Participation in Severe Diseases Caused by Flavivirus Infection

Fontoura

Rocha

Marques

2021

Life

Self Cite

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Neutrophils are first-line responders to infections and are recruited to target tissues through the action of chemoattractant molecules, such as chemokines. Neutrophils are crucial for the control of bacterial and fungal infections, but their role in the context of viral infections has been understudied. Flaviviruses are important human viral pathogens transmitted by arthropods. Infection with a flavivirus may result in a variety of complex disease manifestations, including hemorrhagic fever, encephalitis or congenital malformations. Our understanding of flaviviral diseases is incomplete, and so is the role of neutrophils in such diseases. Here we present a comprehensive overview on the participation of neutrophils in severe disease forms evolving from flavivirus infection, focusing on the role of chemokines and their receptors as main drivers of neutrophil function. Neutrophil activation during viral infection was shown to interfere in viral replication through effector functions, but the resulting inflammation is significant and may be detrimental to the host. For congenital infections in humans, neutrophil recruitment mediated by CXCL8 would be catastrophic. Evidence suggests that control of neutrophil recruitment to flavivirus-infected tissues may reduce immunopathology in experimental models and patients, with minimal loss to viral clearance. Further investigation on the roles of neutrophils in flaviviral infections may reveal unappreciated functions of this leukocyte population while increasing our understanding of flaviviral disease pathogenesis in its multiple forms.

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Kinetics of peripheral blood neutrophils in severe coronavirus disease 2019

Cited by 38 publications

References 57 publications

High-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19

High-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19

Dynamic Changes of the Neutrophil-to-Lymphocyte Ratio, Systemic Inflammation Index, and Derived Neutrophil-to-Lymphocyte Ratio Independently Predict Invasive Mechanical Ventilation Need and Death in Critically Ill COVID-19 Patients

Neutrophil Recruitment and Participation in Severe Diseases Caused by Flavivirus Infection

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