Early suPAR levels as a predictor of COVID-19 severity: A new tool for efficient patient triage

Infectious Diseases Now, Journal Year: 2025, Volume and Issue: 55(4), P. 105058 - 105058

Published: March 16, 2025

Language: Английский

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Endotheliopathy in Acute COVID-19 and Long COVID

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8237 - 8237

Published: May 4, 2023

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

Language: Английский

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T cell perturbations persist for at least 6 months following hospitalization for COVID-19

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 8, 2022

COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of disease on immune cells. The different arms system are interlinked, with humoral responses production high-affinity antibodies largely dependent T cell immunity. Here, we longitudinally explored effect has populations virus-specific cells, as well neutralizing antibody responses, for 6-7 months following hospitalization. CD8 + TEMRA exhausted CD57 cells were markedly affected elevated levels that lasted long into convalescence. Further, markers associated activation upregulated at inclusion, in case CD69 CD4 this all through study duration. expressing negative checkpoint molecules increased patients sustained a prolonged duration recovery. Within 2-3 weeks after symptom onset, developed anti-nucleocapsid IgG spike-neutralizing SARS-CoV-2-specific responses. In addition, found alterations follicular helper (TFH) populations, such enhanced TFH-TH2 recovery from COVID-19. Our revealed significant key events pathogenesis.

Language: Английский

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Modulation of Cellular Function by the Urokinase Receptor Signalling: A Mechanistic View

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: April 8, 2022

Urokinase-type plasminogen activator receptor (uPAR or CD87) is a glycosyl-phosphatidyl-inositol anchored (GPI) membrane protein. The uPAR primary ligand the serine protease urokinase (uPA), converting into plasmin, broad spectrum protease, active on most extracellular matrix components. Besides uPA, binds specifically also to protein vitronectin and, therefore, regarded as an adhesion receptor. Complex formation of with diverse transmembrane proteins, including integrins, formyl peptide receptors, G protein-coupled receptors and epidermal growth factor results in intracellular signalling. Thus, multifunctional coordinating surface-associated pericellular proteolysis signal transduction, thereby affecting physiological pathological mechanisms. uPAR-initiated signalling leads remarkable cellular effects, that include increased cell migration, adhesion, survival, proliferation invasion. Although this beyond scope review, uPA/uPAR system great interest cancer research, it associated aggressive cancers poor patient survival. Increasing evidence links axis epithelial mesenchymal transition, highly dynamic process, by which cells can convert phenotype. Furthermore, many reports indicate involved maintenance stem-like phenotype differentiation process different types. Moreover, levels anchor-less, soluble form uPAR, respond variety inflammatory stimuli, tumorigenesis viral infections. Finally, role virus infection has received increasing attention, view Covid-19 pandemics new information becoming available. In we provide mechanistic perspective, via detailed examination consolidated recent studies responses multiple activities.

Language: Английский

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suPAR: An Inflammatory Mediator for Kidneys

Kidney Diseases, Journal Year: 2022, Volume and Issue: 8(4), P. 265 - 274

Published: Jan. 1, 2022

<b><i>Background:</i></b> Inflammation is a common feature of many kidney diseases. The implicated inflammatory mediators and their underlying molecular mechanisms however are often not clear. <b><i>Summary:</i></b> suPAR the soluble form urokinase-type plasminogen activator receptor (uPAR), associated with inflammation immune activation. It has evolved into unique circulating disease factor over last 10 years. In particular, multiple looks due to enzymatic cleavage alternative transcriptional splicing uPAR gene. Most recently, emerged as systemic mediator for COVID-19 infection, lung well dysfunction. Like membrane-bound uPAR, could interact integrins (e.g., αvβ3 integrin) on podocytes, providing basis some glomerular addition, there have been numerous studies suggesting that connects acute injury chronic special risk factor. Moreover, implication levels in transplantation plasmapheresis only indicates its relevance monitoring recurrence but also implies possible therapeutic target. fact, concept manipulating function evidenced several experimental models. <b><i>Key Messages:</i></b> years research established kidneys. While open questions remain deserve additional studies, modulating may represent promising novel strategy disease.

Language: Английский

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Comparison of C-reactive protein with distinct hyperinflammatory biomarkers in association with COVID-19 severity, mortality and SARS-CoV-2 variants

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: June 14, 2023

C-reactive protein (CRP) has been one of the most investigated inflammatory-biomarkers during ongoing COVID-19 pandemics caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The outcome among patients with SARS-CoV-2 infection is closely related to cytokine storm and hyperinflammation responsible for distress multiple organ failure. It still remains a challenge determine which hyperinflammatory biomarkers cytokines are best predictors disease severity mortality in patients. Therefore, we evaluated compared prediction efficiencies between CRP, recently reported inflammatory modulators (suPAR, sTREM-1, HGF), classical (MCP-1, IL-1β, IL-6, NLR, PLR, ESR, ferritin, fibrinogen, LDH) confirmed at hospital admission. Notably, had higher serum levels suPAR, HGF mild moderate cases. Our data also identified all analytes, discriminate non-severe forms disease, while LDH, sTREM-1 proved be excellent Importantly, suPAR emerged as key molecule characterizing Delta variant infections.

Language: Английский

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Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 4, 2023

Introduction After more than two years the Coronavirus disease-19 (COVID-19) pandemic continues to burden healthcare systems and economies worldwide, it is evident that effects on immune system can persist for months post-infection. The activity of myeloid cells such as monocytes dendritic (DC) essential correct mobilization innate adaptive responses a pathogen. Impaired levels DC severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) likely be driving force behind dysregulation characterizes COVID-19. Methods Here, we followed cohort COVID-19 patients hospitalized during early waves 6-7 months. phenotypes circulating monocyte subsets were assessed determine both long-term SARS-CoV-2 infection. Results We found increased persisted months, mostly attributed elevated classical monocytes. Myeloid derived suppressor also over this period. While most recovered from an initial decrease, cDC2/cDC3 at month timepoint. Analysis functional markers revealed sustained reduction in program death ligand 1 (PD-L1) expression but CD86 across almost all cell types examined. Finally, C-reactive protein (CRP) correlated positively intermediate negatively recovery subsets. Conclusion By exploring compartments, show here alterations landscape remain 6 after COVID-19, which could indicative ongoing healing and/or persistence viral antigens.

Language: Английский

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Considering innate immune responses in SARS-CoV-2 infection and COVID-19

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 22(8), P. 465 - 470

Published: July 4, 2022

Language: Английский

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RAGE pathway activation and function in chronic kidney disease and COVID-19

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: Aug. 9, 2022

The multi-ligand receptor for advanced glycation end-products (RAGE) and its ligands are contributing factors in autoimmunity, cancers, infectious disease. RAGE activation is increased chronic kidney disease (CKD) coronavirus 2019 (COVID-19). CKD may increase the risk of COVID-19 severity also develop form long COVID. expressed essentially all cell types. Increased production isoforms during promotes activity. downstream effects include cellular dysfunction, tissue injury, fibrosis, inflammation, which turn contribute to a decline function, hypertension, thrombotic disorders, cognitive impairment. In this review, we discuss forms mechanisms COVID-19. Because various small molecules antagonize activity animal models, targeting RAGE, co-receptors, or offer novel therapeutic approaches slowing halting progressive disease, current therapies often inadequate.

Language: Английский

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Circulating suPAR associates with severity and in‐hospital progression of COVID‐19

European Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 52(7)

Published: April 18, 2022

COVID-19 disease progression is characterized by hyperinflammation and risk stratification may aid in early aggressive treatment advanced planning. The aim of this study was to assess whether suPAR other markers measured at hospital admission can predict the severity COVID-19.The primary outcome measure international, multi-centre, prospective, observational with adult patients hospitalized primarily for association WHO Clinical Progression Scale (WHO-CPS) suPAR, ferritin, CRP, albumin, LDH, eGFR, age, procalcitonin, interleukin-6. Admission plasma levels were determined using suPARnostic® ELISA Turbilatex assays.Seven hundred sixty-seven patients, 440 (57.4%) males 327 (42.6%) females, included a median age 64 years. Log-suPAR significantly correlated WHO-CPS score, each doubling increasing score one point (p < .001). All also score. lower survivors (7.10 vs. 9.63, 95% CI 1.47-3.59, p A linear model (SALGA) including serum lactate dehydrogenase, best estimate survival. Combining all five parameters SALGA improve accuracy discrimination an AUC 0.80 (95% CI: 0.759-0.836).suPAR point. serve as quick tool predicting survival admission.

Language: Английский

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