Pentraxin 3: Potential prognostic role in SARS-CoV-2 patients admitted to the emergency department.

Coronavirus disease 2019 (COVID‐19) was caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) and spread all over the world. Patterns of hematologic, biochemical, inflammatory, and immune biomarker abnormalities have been identified in patients with severe disease compared to mild systemic disease and differently combined in risk stratification models. Current clinical practice suggests determining IL-6, D-dimer, lactate dehydrogenase (LDH), and transaminases in addition to routine laboratory tests, in order to identify patients at risk of fatal complications. However, several biomarkers have been investigated as a possible role for prognosis outcome, like Presepsin (PSP) that in a recent analysis has emerged as a potential prognostic marker in SARS‐CoV‐2 patients. We read with interest a recent manuscript by Hansen C et al. that evaluated the role of complement related pattern recognition molecules, including C-reactive protein (CRP) and Pentraxin 3 (PTX3), as markers of short-term mortality in intensive care patients. PTX3 and CRP are the well-known, prototypic short and long pentraxin, respectively, differing for gene organization, protein oligomerization and expression pattern. CRP is produced by the liver, whereas PTX3 is an inflammatory mediator produced by various cells in peripheral tissues. CRP is a typical acute phase biomarker since it is produced as a result of systemic inflammatory responses. Conversely, PTX3 defines early and local acute phases, being rapidly produced and released by mononuclear phagocytes, neutrophils, fibroblasts, and epithelial and endothelial cells in response to primary inflammatory signals (e.g. IL-1 and TNF-α). In patients with community-acquired pneumonia (CAP), the plasma concentration of PTX3, but not CRP, was correlated with the severity of CAP based on the pneumonia severity index (PSI), CURB-65, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, and the length of hospital stay. In order to evaluate the potential prognostic value of PTX3 and its correlation with the severity of SARS‐CoV‐2, measurement of PTX3 in serum samples of patients (n = 75, male/female 47/28, age 69 years (median) 59–75 years (IQR)) with COVID-19 microbiology proven infection (from March to May 2020) was carried out using an enzyme-linked immunosorbent assay (ELISA) (DSX, Technogenetics srl, Milano, Italy), in addition to routine laboratory tests performed at admission. Forty patients were admitted in the intensive care unit (ICU), 35 patients in infectious disease division or in pneumology division (nICU). According to the severity and the evolution of the disease, 37 ICU patients died and 3 were moved to nICU divisions for improved clinical conditions. In our cohort, routine laboratory tests showed an increase of CRP (Dimension Vista, Siemens Healthcare Diagnostics Inc, Tarrytown USA), D-dimer (CS 5100, Siemens Healthcare Diagnostics Inc), PSP (Pathfast, Chemical Medience Corporation, Tokyo, Japan), Procalcitonin (PCT) and Interleukin-6 (IL-6) (Cobas 8000 system, Roche Diagnostics, GmbH, Mannheim, Germany), in line with other studies. , In particular 85% of patients showed CRP >10 mg/L, 73% D-dimer >500 ug/L, 66% LDH >241 U/L, 88% PSP >250 pg/mL, 26% PCT >0.5 ng/ml, and 82% IL-6 >7 pg/mL. PTX3 was measured at the admission of patients in emergency covid room and values higher than the cut-off suggested by the manufacturer (2000 pg/mL) were observed in patients who died (median; IQR =13,589; 11,734–15,000) as well as in patients who survived (median; IQR =5729; 3362–9470). According to ROC curve analysis of all biomarkers considered in our study, the AUC of PTX3 values in predicting the mortality was 0.93 (95% CI: 0.86–0.99) reaching a sensitivity of 89% and a specificity of 92% at the threshold level of 10,792 (Fig. 1 ). The AUC resulting from the combination of PTX3, IL-6 and PCT was significantly higher than that of PTX3 alone (0.95, 95% CI: 0.90–1.0). Fig. 2 shows the median values of PTX3 between patients who died and those who survived (p < 0.001). Moreover, PTX3 correlated (Spearman test) with some inflammation biochemical parameters commonly evaluated in SARS‐CoV‐2 patients, in particular with IL-6 (r = 0.69, p < 0.001), PCT (r = 0.52, p < 0.001), PSP (r = 0.52, p < 0.001), LDH (r = 0.62, p < 0.001), CRP (r = 0.59, p < 0.001), and D-dimer (r = 0.43, p < 0.001). Furthermore, a multivariate logistic regression analysis, using all considered variables, confirmed the independent prognostic role of PTX3 with an OR = 1.001 (95% CI: 1.000–1.001, p = 0.005). Taken together, data obtained from our preliminary study suggest a potential prognostic role of PTX3 in SARS‐CoV‐2 patients, with higher levels associated with poor outcome. Moreover, we observed that the combination of PTX3 with IL-6 and PCT associated with COVID-19 disease progression improves the accuracy of prognosis prediction. As such, PTX3, peaking within 6 to 8 hours of the inflammatory stimulus, might have important implications for the clinical management of patients with COVID-19 allowing to identify, at admission, the patients headed for adverse outcomes. Our study presents some limitations, namely the limited number of patients. Then, PTX3 concentrations should be assessed during the hospitalization period to better estimate the prognostic role of this biomarker. If further studies will confirm our preliminary findings, the manufacturer could be encouraged to improve the current diagnostic method in order to reduce the analytic turnaround time (TAT) according to clinical needs. Interestingly, PTX3 is not only present in blood samples but can also be found in other biofluids, including pleural fluid. It is hence possible to hypothesize that PTX3 concentration measurement in bronchoalveolar lavage fluid correlates with disease severity in SARS‐CoV‐2 patients presenting frequent pulmonary complications such as acute lung injury.

Fig. 1

ROC curve for serum level of PTX3, IL-6, PCT, LDH, PSP, D-dimer, PCT, and combination of PTX3 with IL-6 and PCT, detected at admission in relation to mortality in SARS-CoV-2 patients. (AUC: area under curve).

Fig. 2

Relationship between pentraxin 3 values and mortality (A), and survival analysis based on PTX3 values (B).

Author contributions

All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

Ethical approval

The study has been cleared by the local Ethical Committee (AOU Policlinico Consorziale of Bari; No. 6388 COVID19 DOM - protocol number 0034687/12-05-2020).

Declaration of Competing Interest

Authors state no conflict of interest.