Role of triggering receptor expressed on myeloid cells-1 (TREM-1) in COVID-19 and other viral pneumonias: a systematic review and meta-analysis of clinical studies

Oliveira, Yrna Lorena Matos de; Resende, Aimara da Cunha; Martins-Filho, Paulo Ricardo; Moura, Tatiana Rodrigues de

doi:10.1007/s10787-022-00972-6

Cited by 9 publications

(6 citation statements)

References 41 publications

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“…Increased levels of sTREM-1 have been found in patients with COVID-19 compared to healthy controls [123], and in patients with severe disease compared to moderate disease and control groups [124]. sTREM-1 has been proposed as a strong predictive biomarker of COVID-19 severity, and has been related to worse outcomes and death [125].…”

Section: Ephrin-a1 and Ephrin Type-a Receptormentioning

confidence: 99%

Endotheliopathy in Acute COVID-19 and Long COVID

Vassiliou

Vrettou

Keskinidou

et al. 2023

IJMS

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The pulmonary endothelium is a highly regulated organ that performs a wide range of functions under physiological and pathological conditions. Since endothelial dysfunction has been demonstrated to play a direct role in sepsis and acute respiratory distress syndrome, its role in COVID-19 has also been extensively investigated. Indeed, apart from the COVID-19-associated coagulopathy biomarkers, new biomarkers were recognised early during the pandemic, including markers of endothelial cell activation or injury. We systematically searched the literature up to 10 March 2023 for studies examining the association between acute and long COVID-19 severity and outcomes and endothelial biomarkers.

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Section: Ephrin-a1 and Ephrin Type-a Receptormentioning

confidence: 99%

Endotheliopathy in Acute COVID-19 and Long COVID

Vassiliou

Vrettou

Keskinidou

et al. 2023

IJMS

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“…We also observed upregulation of the chemokine signaling pathway with age. The role of TREM-1 in viral-associated complications, including pneumonia, is increasingly gaining prominence [ 52 – 55 ]. TREM-1 is a pattern recognition receptor that amplifies inflammatory responses by inducing the release of proinflammatory cytokines and chemokines, including CXCL-8.…”

Section: Discussionmentioning

confidence: 99%

Changes in the innate immune response to SARS-CoV-2 with advancing age in humans

Agrawal,

Tran,

Jennings

et al. 2024

Immun Ageing

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Background Advancing age is a major risk factor for respiratory viral infections. The infections are often prolonged and difficult to resolve resulting hospitalizations and mortality. The recent COVID-19 pandemic has highlighted this as elderly subjects have emerged as vulnerable populations that display increased susceptibility and severity to SARS-CoV-2. There is an urgent need to identify the probable mechanisms underlying this to protect against future outbreaks of such nature. Innate immunity is the first line of defense against viruses and its decline impacts downstream immune responses. This is because dendritic cells (DCs) and macrophages are key cellular elements of the innate immune system that can sense and respond to viruses by producing inflammatory mediators and priming CD4 and CD8 T-cell responses. Results We investigated the changes in innate immune responses to SARS-CoV-2 as a function of age. Our results using human PBMCs from aged, middle-aged, and young subjects indicate that the activation of DCs and monocytes in response to SARS-CoV-2 is compromised with age. The impairment is most apparent in pDCs where both aged and middle-aged display reduced responses. The secretion of IL-29 that confers protection against respiratory viruses is also decreased in both aged and middle-aged subjects. In contrast, inflammatory mediators associated with severe COVID-19 including CXCL-8, TREM-1 are increased with age. This is also apparent in the gene expression data where pathways related host defense display an age dependent decrease with a concomitant increase in inflammatory pathways. Not only are the inflammatory pathways and mediators increased after stimulation with SARS-CoV-2 but also at homeostasis. In keeping with reduced DC activation, the induction of cytotoxic CD8 T cells is also impaired in aged subjects. However, the CD8 T cells from aged subjects display increased baseline activation in accordance with the enhanced baseline inflammation. Conclusions Our results demonstrate a decline in protective anti-viral immune responses and increase in damaging inflammatory responses with age indicating that dysregulated innate immune responses play a significant role in the increased susceptibility of aged subjects to COVID-19. Furthermore, the dysregulation in immune responses develops early on as middle-aged demonstrate several of these changes. Graphical abstract

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“…In addition, TREM-1 has been consistently investigated in inflammatory and infectious diseases, since its main function is to amplify inflammatory responses [ 31 , 32 , 59 ]. TREM-1 expression and the expression of haptoglobin-hemoglobin scavenger receptor (CD163) on monocytes and HLA-DR on HD neutrophils were also positively associated with red blood parameters in the OB group, which may indicate activation related to the endothelial damage.…”

Section: Discussionmentioning

confidence: 99%

“…In the absence of any infection, obesity has been reported to be associated with the dysregulation of immunometabolism and skewed functions of monocytes, macrophages, neutrophils, and natural killer (NK) cells [ 24 , 25 , 27 , 28 , 29 , 30 ]. Complementarily, among several immunological markers, TREM-1, a receptor expressed mainly on the neutrophil’s surface, has also been studied in COVID-19 and other chronic inflammatory diseases as an important target contributing to hyperinflammation [ 31 , 32 , 33 ]. Moreover, TREM-1 has been previously associated with inflammation in obesity, insulin resistance and other obesity-associated comorbidities [ 34 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Obesity in Severe COVID-19 Patients Has a Distinct Innate Immune Phenotype

et al. 2023

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Obesity alters the capacity of effective immune responses in infections. To further address this phenomenon in the context of COVID-19, this study investigated how the immunophenotype of leukocytes was altered in individuals with obesity in severe COVID-19. This cross-sectional study enrolled 27 ICU COVID-19 patients (67% women, 56.33 ± 19.55 years) that were assigned to obese (BMI ≥ 30 kg/m2, n = 9) or non-obese (BMI < 30kg/m2, n = 18) groups. Monocytes, NK, and both Low-Density (LD) and High-Density (HD) neutrophils were isolated from peripheral blood samples, and surface receptors’ frequency and expression patterns were analyzed by flow cytometry. Clinical status and biochemical data were additionally evaluated. The frequency of monocytes was negatively correlated with BMI, while NK cells and HD neutrophils were positively associated (p < 0.05). Patients with obesity showed a significant reduction of monocytes, and these cells expressed high levels of PD-L1 (p < 0.05). A higher frequency of NK cells and increased expression of TREM-1+ on HD neutrophils were detected in obese patients (p < 0.05). The expression of receptors related to antigen-presentation, phagocytosis, chemotaxis, inflammation and suppression were strongly correlated with clinical markers only in obese patients (p < 0.05). Collectively, these outcomes revealed that obesity differentially affected, and largely depressed, innate immune response in severe COVID-19.

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Role of triggering receptor expressed on myeloid cells-1 (TREM-1) in COVID-19 and other viral pneumonias: a systematic review and meta-analysis of clinical studies

Cited by 9 publications

References 41 publications

Endotheliopathy in Acute COVID-19 and Long COVID

Endotheliopathy in Acute COVID-19 and Long COVID

Changes in the innate immune response to SARS-CoV-2 with advancing age in humans

Obesity in Severe COVID-19 Patients Has a Distinct Innate Immune Phenotype

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