sTREM-1 Predicts Disease Severity and Mortality in COVID-19 Patients: Involvement of Peripheral Blood Leukocytes and MMP-8 Activity

Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients (n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.

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Critical Role of Nitric Oxide During the Apoptosis of Peripheral Blood Leukocytes from Patients with AIDS

Molecular Medicine ◽

10.1007/bf03401994 ◽

1999 ◽

Vol 5 (12) ◽

pp. 812-819 ◽

Cited By ~ 13

Author(s):

M. Djavad Mossalayi ◽

Pierre-André Becherel ◽

Patrice Debré

Keyword(s):

Nitric Oxide ◽

Peripheral Blood ◽

Critical Role ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes

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Prognostic value of sTREM-1 in COVID-19 patients: a biomarker for disease severity and mortality

10.1101/2020.09.22.20199703 ◽

2020 ◽

Author(s):

Pedro V da Silva Neto ◽

Jonatan C S de Carvalho ◽

Vinicius E Pimentel ◽

Malena M Perez ◽

Ingryd Carmona-Garcia ◽

...

Keyword(s):

Disease Severity ◽

Clinical Characteristics ◽

Early Recognition ◽

Severe Disease ◽

Critical Role ◽

Critical Groups ◽

Receiver Operating Curve ◽

Mild Disease ◽

Clinical Scores ◽

Novel Coronavirus

Background: The uncontrolled inflammatory response plays a critical role in the novel coronavirus disease (COVID-19) and triggering receptor expressed on myeloid cells-1 (TREM-1) is thought to be intricate to inflammatory signal amplification. This study aims to investigate the association between soluble TREM-1 (sTREM-1) and COVID-19 as a prognostic biomarker to predict the disease severity, lethality and clinical management.Methods: We enrolled 91 patients with COVID-19 in domiciliary care (44 patients) or in hospital care (47 patients), who were classified after admission into mild, moderate, severe and critical groups according to their clinical scores. As non-COVID-19 control, 30 healthy volunteers were included. Data on demographic, comorbidities and baseline clinical characteristics were obtained from their medical and nurse records. Peripheral blood samples were collected at admission and after hospitalization outcome to assess cytokine profile and sTREM-1 level by specific immunoassays Results: Within COVID-19 patients, the highest severity was associated with the most significant elevated plasma levels sTREM-1. Using receiver operating curve analysis (ROC), sTREM-1 was found to be predictive of disease severity (AUC= 0.988) and the best cut-off value for predicting in-hospital severity was ≥ 116.5 pg/mL with the sensitivity for 93.3% and specificity for 95.8%. We also described the clinical characteristics of these patients and explored the correlation with markers of the disease aggravation. The levels of sTREM-1 were positively correlated with IL-6, IL-10, blood neutrophils counts, and critical disease scoring (r= 0.68, p<0.0001). On the other hand, sTREM-1 level was significantly negative correlated with lymphocytes counting, and mild disease (r= -0.42, p<0.0001). Higher levels of sTREM-1 were related to poor outcome and death, patients who received dexamethasone tended to have lower sTREM-1 levels. Conclusion: Our results indicated that sTREM-1 in COVID-19 is associated with severe disease development and a prognostic marker for mortality. The use of severity biomarkers such as sTREM-1 together with patients clinical scores could improve the early recognition and monitoring of COVID-19 cases with higher risk of disease worsening. Key words: COVID-19; sTREM-1; Inflammation; Biomarker; Severity; Mortality.

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Analysis of an association of TNF –308G>A polymorphism with a risk for pulmonary sarcoidosis in the Russian population of the Republic of Karelia

Terapevticheskii arkhiv ◽

10.17116/terarkh201789361-64 ◽

2017 ◽

Vol 89 (3) ◽

pp. 61-64

Author(s):

I E Malysheva ◽

L V Topchieva ◽

E L Tikhonovich ◽

O Yu Barysheva

Keyword(s):

Peripheral Blood ◽

Inflammatory Responses ◽

Clinical Manifestations ◽

Pulmonary Sarcoidosis ◽

Russian Population ◽

Control Group ◽

Mrna Levels ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes ◽

The Republic

Aim. To analyze an association of TNF –308G>A polymorphism with a risk for pulmonary sarcoidosis (PS) in the Russian population of the Republic of Karelia Subjects and methods. 84 patients with persistent PS and 96 donors without clinical manifestations of this disease (a control group) were examined. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to identify alleles and genotypes by the marker of TNF –308G>A polymorphism. The level of transcripts of the above gene in the peripheral blood leukocytes of healthy and sick people was determined by real-time PCR. Results. There were no significant differences in the distribution of allelic and genotypic frequencies by the marker of TNF –308G>A polymorphism between the control and PS patient groups. There was a significant increase in the number of TNF gene transcripts in the peripheral blood leukocytes of patients with PS compared to the controls. At the same time, there were no marked differences in mRNA expression levels in the above gene in the carriers of different genotypes by the marker of TNF –308G>A polymorphism in all the examined groups. Conclusion. The marker of TNF –308G>A polymorphism is unassociated with the risk of PS in the Russian population of the Republic of Karelia. No differences in TNF mRNA levels in the carriers of different genotypes by the above marker may suggest that the found elevated level of transcripts in the above gene in patients with diagnosed with PS is due to the development of the body’s inflammatory responses in this disease.

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Lymphopenia and DMTs for relapsing forms of MS

Neurology Clinical Practice ◽

10.1212/cpj.0000000000000567 ◽

2019 ◽

Vol 9 (1) ◽

pp. 53-63 ◽

Cited By ~ 8

Author(s):

Edward J. Fox ◽

Guy J. Buckle ◽

Barry Singer ◽

Vibhuti Singh ◽

Aaron Boster

Keyword(s):

Peripheral Blood ◽

Immune Surveillance ◽

Drug Efficacy ◽

Peripheral Blood Leukocyte ◽

Patient Characteristics ◽

Blood Leukocytes ◽

Leukocyte Counts ◽

Absolute Lymphocyte Counts ◽

Blood Leukocyte

Purpose of reviewTo provide neurologists with an update on the proposed mechanisms of action (MOAs) of disease-modifying therapies (DMTs) for the treatment of relapsing MS, and their effect on peripheral blood leukocytes, in order to inform treatment decisions.Recent findingsDMTs have vastly differing MOAs, including effects on peripheral blood leukocyte counts, particularly lymphocytes. The clinical implications of changes in lymphocyte counts need to be understood in the context of the underlying MOAs of each respective DMT, with treatment tailored to individual patient needs.SummaryDMTs can alter lymphocyte counts, subsets, activation, and distribution, and thus can influence immune surveillance. Serial monitoring of total leukocytes and absolute lymphocyte counts (ALCs) is advisable in patients receiving DMTs. ALCs should be interpreted regarding expected immunologic changes and individual patient characteristics. Any decision to switch DMTs should consider these factors, along with drug efficacy, safety, and effect on quality of life.

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Determining molecular and genetic markers for severe EBV-mononucleosis

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-dma-1271 ◽

2020 ◽

Vol 10 (4) ◽

pp. 707-716

Author(s):

E. N. Filatova ◽

N. A. Sakharnov ◽

O. V. Utkin ◽

E. A. Kulova

Keyword(s):

Genetic Markers ◽

Infectious Mononucleosis ◽

Peripheral Blood ◽

Severe Disease ◽

Severe Form ◽

Immunocompetent Cells ◽

Blood Leukocytes ◽

Healthy Donors ◽

Custom Made ◽

Apparently Healthy

Epstein—Barr virus (EBV) is one of the etiological agents causing infectious mononucleosis. A severe form of the disease can result in developing serious complications, which risk might also depend on the state of patient’s immune system. To date, no specific tests for assessing a risk of developing severe disease form are available. Our study was aimed at identifying molecular genetic markers of severe EBV-infectious mononucleosis (EBV-IM) in immunocompetent peripheral blood cells. Expression of 483 genes and gene transcripts regulating apoptosis, proliferation and differentiation of immunocompetent cells was measured in the peripheral blood leukocytes from patients with severe and moderate EBV-IM as well as apparently healthy donors. A DNA-microarray designed by us and subsequent data processing were carried out by using custom-made “MiDA” software. To identify markers of a severe form of the pathology, expression of each gene and transcript was compared in EBV-IM patients and apparently healthy donors. For each gene and transcript, the level of expression fold change and significance for binary classification were determined. Genes and transcripts, characterized by the maximum values of two determined parameters while comparing patients with severe infection and healthy donors, as well as patients with severe and moderate EBV-IM forms, were selected as markers of severe EBV-IM. Genes and transcripts with differed expression in patients with moderate EBV-IM and healthy donors, were excluded from the list of markers. In addition, sex- and age-linked markers with differed expression were excluded as well. The markers for severe EBV-IM consisted of apoptosis regulators (BCL2L11, BIRC3 genes and XIAP.NM_001167 transcript) and splicing factors (CELF6 gene and SF1.NM_201995 transcript). Compared with donors and patients with a moderate form of the disease, a decreased expression of BCL2L11, BIRC3 genes, transcripts SF1.NM_201995 and XIAP.NM_001167, as well as increased expression of the CELF6 gene were detected in the blood of patients with severe EBV-IM. The functional role of identified molecular markers suggests that severe EBV-IM is characterized by suppressed mitochondrial and activated TRAF-dependent apoptosis pathways in immunocompetent cells. The expression pattern for select markers is specific for severe EBV-MI, not associated with patient sex and age. Thus, study data may be used to develop specific tools for assessing a risk of developing complications of EBV mononucleosis.

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