Clinical Utility of Circulating Pentraxin 3 as a Prognostic Biomarker in Coronavirus Disease 2019: A Systematic Review and Meta-analysis.

INTRODUCTION: Pentraxin 3 (PTX3) is involved in inflammation regulation and has a certain association with infectious diseases. However, its specific correlation with infectious diseases remains controversial. This study aimed to analyze the association between them and explore the possible role of PTX3 in the prognosis of coronavirus disease 2019 (COVID-19). METHODS: Five databases (PubMed, Cochrane Library, Embase, Clinicaltrials.gov, and gray literature) were searched. Outcomes were expressed as a standardized mean difference (SMD) and 95% confidence intervals (CI). The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of included articles. Stata 12 and Meta-DiSc were applied to analyze the pooled data. Receiver operating characteristic (ROC) curves were conducted to determine the prognostic value of PTX3 for mortality. RESULTS: Six articles met the inclusion criteria. Circulating PTX3 levels had a nonsignificant difference between intensive care unit (ICU) and non-ICU patients with COVID-19 [SMD 1.37 (-0.08, 2.81); I2 = 93.9%, P < 0.01], while the PTX3 levels in nonsurvival COVID-19 patients was significantly lower than those in survival patients [SMD -1.41 (-1.92, -0.91); I2 = 66.4%, P = 0.051]. Circulating PTX3 had good mortality prediction ability (area under ROC curve, AUC = 0.829) in COVID-19. Funnel plots and Egger's tests showed low probabilities of publication bias. Through sensitivity analysis, the results of this study were robust. CONCLUSION: This study found that PTX3 was differentially expressed between survival and nonsurvival patients with COVID-19, while there was no significant difference between ICU and non-ICU patients. Meanwhile, circulating PTX3 may be a good biomarker for monitoring the prognosis of COVID-19, which may provide new ideas and directions for clinical and scientific research.

This study focuses on the relationship between circulating pentraxin 3 (PTX3) and coronavirus disease 2019 (COVID-19). COVID-19 can initiate the inflammatory reaction of the body, trigger a series of immune mechanisms, and cause death in severe cases. PTX3 is a soluble pattern recognition molecule (PRM) belonging to the humoral innate immune system, which may be increasingly deemed as an independent strong prognostic indicator in severe infectious diseases, such as COVID-19. Five databases (Pubmed, Cochrane Library, EMBASE, Clinicaltrials.gov, and gray literature) were searched for six keywords. There was no significant difference in circulating PTX3 levels between intensive care unit (ICU) and non-ICU patients with COVID-19, while the PTX3 levels of nonsurvival patients with COVID-19 was significantly lower than those of survival patients. Circulating PTX3 may indicate good diagnostic value in predicting the mortality of COVID-19, which may be useful as an indicator for monitoring.

The Prognostic Value of Pentraxin-3 in COVID-19 Patients: A Systematic Review and Meta-Analysis of Mortality Incidence.

Over the last three years, humanity has been facing one of the most serious health emergencies due to the global spread of Coronavirus disease (COVID-19). In this scenario, the research of reliable biomarkers of mortality from COVID-19 represents a primary objective. Pentraxin 3 (PTX3), a highly conserved protein of innate immunity, seems to be associated with a worse outcome of the disease. Based on the above, this systematic review and meta-analysis evaluated the prognostic potential of PTX3 in COVID-19 disease. We included 12 clinical studies evaluating PTX3 in COVID-19 patients. From our research, we found increased PTX3 levels compared to healthy subjects, and notably, PTX3 was even more augmented in severe COVID-19 rather than non-severe cases. Moreover, we performed a meta-analysis to establish if there were differences between ICU and non-ICU COVID-19 patients in PTX3-related death. We combined 5 studies for a total of 543 ICU vs. 515 non-ICU patients. We found high significative PTX3-related death in ICU COVID-19 hospitalized individuals (184 out of 543) compared to non-ICU (37 out of 515), with an overall effect OR: 11.30 [2.00, 63.73]; p = 0.006. In conclusion, we probed PTX3 as a reliable marker of poor outcomes after COVID-19 infection as well as a predictor of hospitalized patients' stratification.

Diagnostic performance of serum pentraxin-3 in pediatric acute appendicitis: a prospective diagnostic validation study.

INTRODUCTION: Pediatric acute appendicitis (PAA) is a pathology with a high rate of diagnostic error. The search for new diagnostic tools is justified by the high morbidity and healthcare costs associated with diagnostic error. METHODS: We designed a prospective study to validate serum pentraxin-3 (PTX3) as a diagnostic tool in PAA. Participants were divided into three groups: (1) patients with no underlying pathology (2) patients with non-surgical abdominal pain and (3) patients with a confirmed diagnosis of PAA. For further analyses, patients in group 3 were divided into complicated or uncomplicated PAA. Quantitative variables were expressed as medians and interquartile ranges and categorical variables as percentages. Quantitative variables were compared using the Kruskal-Wallis test and the Mann-Whitney U test. Diagnostic performance was evaluated with ROC curves. RESULTS: This study included 215 patients divided into group 1 (n = 63), group 2 (n = 53) and group 3 (n = 99). Median serum PTX3 values were 2.54 (1.70-2.95) ng/mL, 3.29 (2.19-7.64) ng/mL and 8.94 (6.16-14.05) in groups 1, 2 and 3, respectively (p = 0.001). Patients with complicated PAA showed significantly higher values than patients with uncomplicated PAA (p = 0.04). The AUC (group 2 vs. 3) was 0.77 (95% CI 0.69-0.85) and the best cut-off point was at 7.28 ng/mL, with a sensitivity of 61.3% and a specificity of 73.1%. The AUC (complicated vs. uncomplicated PAA) was 0.65 (95% CI 0.54-0.77) and the best cut-off point was 12.33 ng/mL, with a sensitivity of 51.72% and a specificity of 72.73%. CONCLUSIONS: The diagnostic ability of serum PTX3 in PAA is only moderate and therefore it cannot be considered a definitive diagnostic test. The discriminatory ability of PTX3 between complicated and uncomplicated PAA is poor. These findings, which contrast with those reported to date, should be validated with future properly designed prospective studies.

Long pentraxin 3 (PTX3) levels predict death, intubation and thrombotic events among hospitalized patients with COVID-19.

Background: PTX3 is an important mediator of inflammation and innate immunity. We aimed at assessing its prognostic value in a large cohort of patients hospitalized with COVID-19. Methods: Levels of PTX3 were measured in 152 patients hospitalized with COVID-19 at San Gerardo Hospital (Monza, Italy) since March 2020. Cox regression was used to identify predictors of time from admission to in-hospital death or mechanical ventilation. Crude incidences of death were compared between patients with PTX3 levels higher or lower than the best cut-off estimated with the Maximally Selected Rank Statistics Method. Results: Upon admission, 22% of the patients required no oxygen, 46% low-flow oxygen, 30% high-flow nasal cannula or CPAP-helmet and 3% MV. Median level of PTX3 was 21.7 (IQR: 13.5-58.23) ng/ml. In-hospital mortality was 25% (38 deaths); 13 patients (8.6%) underwent MV. PTX3 was associated with risk of death (per 10 ng/ml, HR 1.08; 95%CI 1.04-1.11; P<0.001) and death/MV (HR 1.04; 95%CI 1.01-1.07; P=0.011), independently of other predictors of in-hospital mortality, including age, Charlson Comorbidity Index, D-dimer and C-reactive protein (CRP). Patients with PTX3 levels above the optimal cut-off of 39.32 ng/ml had significantly higher mortality than the others (55% vs 8%, P<0.001). Higher PTX3 plasma levels were found in 14 patients with subsequent thrombotic complications (median [IQR]: 51.4 [24.6-94.4] versus 21 [13.4-55.2]; P=0.049). Conclusions: High PTX3 levels in patients hospitalized with COVID-19 are associated with a worse outcome. The evaluation of this marker could be useful in prognostic stratification and identification of patients who could benefit from immunomodulant therapy.

Association of polymorphisms in long pentraxin 3 and its plasma levels with COVID-19 severity.

COVID-19 is an infectious respiratory disease caused by SARS-CoV-2. Pentraxin 3 (PTX3) is involved in the activation and regulation of the complement system, demonstrating an important role in the pathogenesis of COVID-19. The aim was to evaluate the association of single nucleotide polymorphisms in PTX3 and its plasma levels with the severity of COVID-19. This is a retrospective cohort study, carried out between August 2020 and July 2021, including patients with confirmed COVID-19 hospitalized in 2 hospitals in the Northeast Region of Brazil. Polymorphisms in PTX3 (rs1840680 and rs2305619) were determined by real-time PCR. PTX3 plasma levels were measured by ELISA. Serum levels of interleukin (IL)-6, IL-8, and IL-10 were determined by flow cytometry. A multivariate logistic regression model was used to identify parameters independently associated with COVID-19 severity. P values < 0.05 were considered significant. The study included 496 patients, classified as moderate (n = 267) and severe (n = 229) cases. The PTX3 AA genotype (rs1840680) was independently associated with protection against severe COVID-19 (P = 0.037; odds ratio = 0.555). PTX3 plasma levels were significantly associated with COVID-19 severity and mortality (P < 0.05). PTX3 levels were significantly correlated with IL-6, IL-8, IL-10, C-reactive protein, total leukocytes, neutrophil-to-lymphocyte ratio, urea, creatinine, ferritin, length of hospital stay, and higher respiratory rate (P < 0.05). Our results revealed a protective effect of the PTX3 AA genotype (rs1840680) on the development of severe forms of COVID-19. Additionally, PTX3 plasma levels were associated with the severity of COVID-19. The results of this study provide evidence of an important role of PTX3 in the immunopathology of COVID-19.

Molecular insight into pentraxin-3: Update advances in innate immunity, inflammation, tissue remodeling, diseases, and drug role.

Pentraxin-3 (PTX3) is the prototype of the long pentraxin subfamily, an acute-phase protein consisting of a C-terminal pentraxin domain and a unique N-terminal domain. PTX3 was initially isolated from human umbilical vein endothelial cells and human FS-4 fibroblasts. It was subsequently found to be also produced by synoviocytes, chondrocytes, osteoblasts, smooth muscle cells, myeloid dendritic cells, epithelial cells, and tumor cells. Various modulatory factors, such as miRNAs, cytokines, drugs, and hypoxic conditions, could regulate the expression level of PTX3. PTX3 is essential in regulating innate immunity, inflammation, angiogenesis, and tissue remodeling. Besides, PTX3 may play dual (pro-tumor and anti-tumor) roles in oncogenesis. PTX3 is involved in the occurrence and development of many non-cancerous diseases, including COVID-19, and might be a potential biomarker indicating the prognosis, activity,and severity of diseases. In this review, we summarize and discuss the potential roles of PTX3 in the oncogenesis and pathogenesis of non-cancerous diseases and potential targeted therapies based on PTX3.

Pan-Cancer Analysis of Pentraxin 3: A Potential Biomarker of COVID-19.

Pentraxin 3 (PTX3), a potential biomarker of the severity and mortality of COVID-19 patients, is aberrantly expressed in human tumors. However, a comprehensive pan-cancer analysis of PTX3 remains to be elucidated. PTX3 data profiles and clinical information in TCGA cancers were obtained from different public databases to clarify the expression levels, genetic alterations, prognostic significance, underlying mechanisms, and the predicted role in immunotherapy of PTX3 across TCGA cancers. Our analyses showed that PTX3 was aberrantly expressed in most tumors and was significantly related to prognosis and tumor stage. Interaction network and enrichment analyses revealed that PTX3 participated in tumor immuno-related progression. In addition, PTX3 levels were critically associated with immune cell components and immune scores, and PTX3 strongly coexpressed with immune-related genes in TCGA cancers. Meanwhile, PTX3 expression was associated with immune checkpoint genes, and immunotherapy potential biomarkers in multiple cancers, predicting special immunotherapy responses in different tumor types. In kidney renal clear cell carcinoma (KIRC), PTX3 emerged as an independent prognostic factor through multivariable Cox regression analyses. Blocking PTX3 with siRNA could suppress the growth of KIRC cells and invasion. Conclusively, our study shows a comprehensive bioinformatic analysis of PTX3, which might serve as a pan-cancer prognostic biomarker.

A 'Multiomic' Approach of Saliva Metabolomics, Microbiota, and Serum Biomarkers to Assess the Need of Hospitalization in Coronavirus Disease 2019.

BACKGROUND AND AIMS: The SARS-CoV-2 pandemic has overwhelmed the treatment capacity of the health care systems during the highest viral diffusion rate. Patients reaching the emergency department had to be either hospitalized (inpatients) or discharged (outpatients). Still, the decision was taken based on the individual assessment of the actual clinical condition, without specific biomarkers to predict future improvement or deterioration, and discharged patients often returned to the hospital for aggravation of their condition. Here, we have developed a new combined approach of omics to identify factors that could distinguish coronavirus disease 19 (COVID-19) inpatients from outpatients. METHODS: Saliva and blood samples were collected over the course of two observational cohort studies. By using machine learning approaches, we compared salivary metabolome of 50 COVID-19 patients with that of 270 healthy individuals having previously been exposed or not to SARS-CoV-2. We then correlated the salivary metabolites that allowed separating COVID-19 inpatients from outpatients with serum biomarkers and salivary microbiota taxa differentially represented in the two groups of patients. RESULTS: We identified nine salivary metabolites that allowed assessing the need of hospitalization. When combined with serum biomarkers, just two salivary metabolites (myo-inositol and 2-pyrrolidineacetic acid) and one serum protein, chitinase 3-like-1 (CHI3L1), were sufficient to separate inpatients from outpatients completely and correlated with modulated microbiota taxa. In particular, we found Corynebacterium 1 to be overrepresented in inpatients, whereas Actinomycetaceae F0332, Candidatus Saccharimonas, and Haemophilus were all underrepresented in the hospitalized population. CONCLUSION: This is a proof of concept that a combined omic analysis can be used to stratify patients independently from COVID-19.

Eosinophil count, neutrophil-to-lymphocyte ratio, and pentraxin-3 level as predictors of clinical severity in SARS-CoV-2 patients

Background: New biomarkers are urgently needed to predict the severity of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Eosinophil count and neutrophil-to-lymphocyte ratio (NLR) are new biomarkers for the severity of viral infection. Pentraxin 3 (PTX3) is a natural humoral immune mediator that can bind to viruses, complement, and apoptotic cells, and can trigger T-helper type 1 (Th1) to produce pro-inflammatory cytokines and their levels increase depending on the severity of the disease. Materials and Methods: This was a case-control study consisting of 66 patients infected with SARS-CoV-2 who were divided into critical patients (Group C) and noncritical patients (Group N). We obtained lab samples from the subjects upon admission. We then analyzed the data using the Mann-Whitney U test, receiving operator characteristic (ROC) analysis, and chi-square test with odds ratio (OR) to test the hypothesis. Results: Median eosinophil count, NLR, and PTX3 levels in Group C were 0 ×10 3 /μL, 13.53 and 608.73 pg/mL, compared to 0.11 ×10 3 /μL, 1.94 and 28.50 pg/mL in Group N. The ROC analysis showed good predictive ability for eosinophil count, NLR, and PTX3 with area under the curve (AUC) of 0.913, 0.988, and 0.942 to predict coronavirus disease-2019 (COVID-19) severity. At the cutoff eosinophil count of 0.035 × 10 3 /μL, NLR 4.13 and PTX3 114.51 pg/mL, the OR values were 17.5, 320, and 72.5 (P 0.05) with a sensitivity of 84.8%, 97.0%, and 90.9% and specificity 75.8%, 90.9%, and 87.9%. Conclusions: Eosinophil count, NLR, and PTX3 levels can be used as predictors of clinical severity in SARS-CoV-2. Eosinophil count of 0.035 ×10 3 /μL, NLR 4.13, and PTX3 level 114.51 pg/mL are risk factors for critical conditions for COVID-19. © ESO 2022.

Prediction of Respiratory Failure and Mortality in COVID-19 Patients Using Long Pentraxin PTX3.

The course of COVID-19 is unpredictable, ranging from asymptomatic to respiratory failure and death. Prognostic biomarkers are urgently needed. We hypothesized that long pentraxin PTX3 could be a valuable plasma biomarker due to its essential role in inflammatory processes. In a prospective hospitalized COVID-19 derivation cohort (n = 126) during the spring of 2020, we measured PTX3 within 4 days of admission. The predictive value of mechanical ventilation (MV) and 30-day mortality compared with clinical parameters and other markers of inflammation were assessed by logistic regression analysis and expressed as odds ratio (OR) with 95% confidence interval (CI). Analyses were repeated in a prospective validation cohort (n = 112) of hospitalized patients with COVID-19 treated with remdesivir and dexamethasone. Thirty-day mortality in the derivation cohort was 26.2%. In patients who died, the median PTX3 concentration upon admission was 19.5 ng/mL (IQR: 12.5-33.3) versus 6.6 ng/mL (IQR 2.9-12.3) (p < 0.0001) for survivors. After adjustment for covariates, the odds of 30-day mortality increased two-fold for each doubling of PTX3 (OR 2.03 [95% CI: 1.23-3.34], p = 0.006), which was also observed in the validation cohort (OR 1.70 [95% CI: 1.09-2.67], p = 0.02). Similarly, PTX3 levels were associated with MV. After adjustment for covariates, OR of MV was 2.34 (95% CI: 1.33-4.12, p = 0.003) in the derivation cohort and 1.64 (95% CI: 1.03-2.62, p = 0.04) in the validation cohort. PTX3 appears to be a useful clinical biomarker to predict 30-day respiratory failure and mortality risk in COVID-19 patients treated with and without remdesivir and dexamethasone.

Fetuin-A Deficiency but Not Pentraxin 3, FGF-21, or Irisin, Predisposes to More Serious COVID-19 Course.

Analysis of liver biopsy specimens showed that SARS-CoV-2 might have led to liver damage. This study aimed to evaluate the role of selected hepatokines and myokines in the development and progression of COVID-19. Seventy patients with laboratory-confirmed COVID-19 and 20 healthy volunteers were enrolled in the study. Irisin, pentraxin 3, fetuin-A, and FGF-21 serum concentrations and biochemical parameters were assessed using an immunoenzymatic method with commercially available enzyme immunoassay (EIA) or enzyme-linked immunosorbent assay (ELISA) kits. Serum fetuin-A concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers. The serum concentration of FGF-21 was significantly increased in obese COVID-19 patients compared to overweight ones. Moreover, the FGF-21 level was higher in COVID-19 patients diagnosed with metabolic syndrome than in patients without metabolic syndrome. PTX3 concentration was higher in COVID-19 patients with higher HOMA-IR values than those with lower HOMA-IR values. COVID-19 patients with HOMA-IR ≤ 3 and >3 had significantly lower fetuin-A levels than the control group. Irisin concentration was significantly decreased in the HOMA-IR ≤ 3 COVID-19 subgroup when comparing with the control group. Lower levels of fetuin-A observed in COVID-19 patients despite higher HOMA-IR, CRP, and ferritin levels, pneumonia, patients requiring ICU care suggests that fetuin-A deficiency predisposes to more severe COVID-19 course. Upregulated pentraxin 3 may be used as a potential predictor of COVID-19 severity.