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

Neto, Pedro Vieira da Silva; Carvalho, Jonatan C. S. de; Pimentel, Vinícius E.; Pérez, Malena M.; Toro, Diana Mota; Fraga-Silva, Thais F. C.; Fuzo, Carlos Alessandro; Oliveira, Camilla Narjara Simão; Rodrigues, Lílian Cataldi; Argolo, Jamille Guedes Malta; Carmona‐Garcia, Ingryd; Neto, Nicola T; Souza, Camila Oliveira Silva; Fernandes, Talita Morais; Bastos, Víctor Alexandre Félix; Degiovani, Augusto M.; Constant, Leticia F.; Ostini, Fátima M.; Feitosa, Marley Ribeiro; Parra, Rogério Serafim; Vilar, Fernando Crivelenti; Gaspar, Gilberto Gambero; Rocha, José Joaquim Ribeiro da; Féres, Omar; Frantz, Fabiani Gai; Gerlach, Raquel Fernanda; Maruyama, Sandra Regina; Russo, Elisa Maria de Sousa; Lettiere-Viana, Angelina; Fernandes, Ana Paula; Santos, Isabel M.; Bonato, Vânia L D; Boechat, Antônio Luiz; Malheiro, Adriana; Sadikot, Ruxana T.; Dias‐Baruffi, Marcelo; Cardoso, Cristina Ribeiro de Barros; Faccioli, Lúcia Helena; Sorgi, Carlos Artério; Group, On Behalf Of The Imunocovid Study

doi:10.3390/v13122521

Cited by 36 publications

(41 citation statements)

References 46 publications

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“…Corroborating this hypothesis, previous data from our group has shown an association between SNPs in TLR3 and TNFα involved in the decrease of antiviral immune response, with CZS occurrence and severity 19 . In contrast, higher levels of sTREM-1 have been described as indicative of poor prognosis in early stages of DENV arbovirus infection 46 , and recently, on the outcomes of SARS-CoV-2 infections 47 .…”

Section: Discussionmentioning

confidence: 99%

Association between genetic variants in TREM1, CXCL10, IL4, CXCL8 and TLR7 genes with the occurrence of congenital Zika syndrome and severe microcephaly

Santos

Magalhães

Fonseca

et al. 2023

Sci Rep

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Congenital Zika syndrome (CZS) is a cluster of malformations induced by Zika virus (ZIKV) infection and the underline mechanisms involved in its occurrence are yet not fully understood. Along with epidemiological and environmental factors, the genetic host factors are suggested as important to the CZS occurrence and development, however, few studies have evaluated this. This study enrolled a total of 245 individuals in a case–control association study compound a cohort of high specific interest constituted by 75 mothers who had delivered CZS infants, their 76 infants, and 47 mothers that had delivered healthy infants, and their 47 infants. Sixteen single-nucleotide polymorphisms on TREM1, CXCL10, IL4, CXCL8, TLR3, TLR7, IFNR1, CXCR1, IL10, CCR2 and CCR5 genes were genotyped to investigate their association as risk factors to CZS. The results show an association between C allele at TREM1 rs2234246 and C allele at IL4 rs224325 in mothers infected with ZIKV during pregnancy, with the increased susceptibility to CZS occurrence in their infants and the SNP CXCL8 rs4073 and the G allele at CXCL10 rs4508917 with presence of CZS microcephaly in the infants. Furthermore, the T allele at CXCL8 rs4073 and TRL7 rs179008 SNPs were associated with the severity of microcephaly in children with CZS. These results suggest that these polymorphisms in genes of innate immune responses addressed here are associated to increased risk of occurrence and severity of CZS in pregnant mothers infected with ZIKV and their CZS infants.

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Section: Discussionmentioning

confidence: 99%

Association between genetic variants in TREM1, CXCL10, IL4, CXCL8 and TLR7 genes with the occurrence of congenital Zika syndrome and severe microcephaly

Santos

Magalhães

Fonseca

et al. 2023

Sci Rep

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“…Matrix metalloproteinases (MMPs) are prominent mediators of tissue destruction and immune activity, whose importance has also been noted in the development of COVID-19 [7]. Increased activities of matrix metalloproteinase 9 (MMP-9), as well as matrix metalloproteinase 8 (MMP-8), were reported in patients with severe form of COVID-19 [8,9]. MMP-9 is a zinc-metalloproteinase (collagenase type IV; gelatinase B) that could alternate for primed neutrophils, while MMP-8 (neutrophil collagenase) degrades type I, II and III collagen of extracellular matrix.…”

Section: Introductionmentioning

confidence: 99%

MMP-9/BDNF ratio predicts more severe COVID-19 outcomes

Savić¹,

Stevanović²,

Mihajlović³

et al. 2022

Int. J. Med. Sci.

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COVID-19 clinically manifests from asymptomatic to the critical range. Immune response provokes the pro-inflammatory interactions, which lead to the cytokines, reactive oxygen/nitrogen species, peptidases, and arachidonic acid metabolites enlargement and activation of coagulation components. Matrix metalloproteinases (MMPs) contribute to tissue destruction in the development of COVID-19. Due to the endothelial, systemic course of the disease, VEGF A participates actively in COVID-19 development, while neurotrophic and metabolic effects of BDNF recommends for the prediction of complications in COVID-19 patients. Searching for a marker that would improve and simplify the ranking in COVID-19, the study intended to evaluate the relationship of MMP-9 with VEGF A, BDNF, and MMP-8 with the COVID-19 severity. Upon admission to the hospital and before the therapy administration, 77 patients were classified into a mild, moderate, severe, or critical group. Due to the inflammatory stage in COVID-19, a comparison between groups showed related differences in leukocytes, neutrophils, lymphocytes, and platelets counts as anticipated. Only in seriously ill patients, there is a significant increase in the serum concentration of MMP-9, MMP-8, and VEGF A, while BDNF values did not show significant variations between groups. However, all those parameters positively correlated with each other. The ratio of MMP-9/BDNF markedly decreased in the severe and critically patients compared to the mild group. Testing the capability of this ratio to predict the COVID-19 stage by ROC curves, we found the MMP-9/BDNF could be a suitable marker for differentiating stages I/II (AUC 0.7597), stage I/III (AUC 0.9011), and stage I/IV (AUC 0.7727). Presented data describe for the first time the high-level systemic MMP-9/BDNF ratio in patients with COVID-19. This parameter could contribute to a more precise determination of the phase of the disease.

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“…Several lines of evidence support the role of HLA-G in COVID-19 pathogenesis, including (i) the increased levels of sHLA-G molecules in patients exhibiting various clinical manifestations of the disease [ 14 , 15 , 16 , 17 , 18 ], (ii) the increased number of immune system cells expressing HLA-G [ 16 , 19 ], (iii) the association of the HLA-G 3′untranslated region polymorphism with susceptibility to the disease [ 18 ], (iv) the increased tissue expression of HLA-G in case reports [ 20 , 21 ], and (v) the induction of the expression of hub genes, including HLA-G , in lung tissue infected by SARS-CoV-2 [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

The Severity of COVID-19 Affects the Plasma Soluble Levels of the Immune Checkpoint HLA-G Molecule

Cordeiro

Fernandes

Toro

et al. 2022

IJMS

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The non-classical histocompatibility antigen G (HLA-G) is an immune checkpoint molecule that has been implicated in viral disorders. We evaluated the plasma soluble HLA-G (sHLA-G) in 239 individuals, arranged in COVID-19 patients (n = 189) followed up at home or in a hospital, and in healthy controls (n = 50). Increased levels of sHLA-G were observed in COVID-19 patients irrespective of the facility care, gender, age, and the presence of comorbidities. Compared with controls, the sHLA-G levels increased as far as disease severity progressed; however, the levels decreased in critically ill patients, suggesting an immune exhaustion phenomenon. Notably, sHLA-G exhibited a positive correlation with other mediators currently observed in the acute phase of the disease, including IL-6, IL-8 and IL-10. Although sHLA-G levels may be associated with an acute biomarker of COVID-19, the increased levels alone were not associated with disease severity or mortality due to COVID-19. Whether the SARS-CoV-2 per se or the innate/adaptive immune response against the virus is responsible for the increased levels of sHLA-G are questions that need to be further addressed.

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

Cited by 36 publications

References 46 publications

Association between genetic variants in TREM1, CXCL10, IL4, CXCL8 and TLR7 genes with the occurrence of congenital Zika syndrome and severe microcephaly

Association between genetic variants in TREM1, CXCL10, IL4, CXCL8 and TLR7 genes with the occurrence of congenital Zika syndrome and severe microcephaly

MMP-9/BDNF ratio predicts more severe COVID-19 outcomes

The Severity of COVID-19 Affects the Plasma Soluble Levels of the Immune Checkpoint HLA-G Molecule

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