Introduction: Pentraxin (PTX-3) is an acute phase protein, which has significant functions in humoral innate immunity, such as regulation of inflammatory responses, control of complement pathways, tissue repair. Purpose: A systematic literature review was performed to better define the prognostic role of PTX3 in COVID-19 disease. This study also Aims to analyse PTX-3 levels in our cohort of healthcare workers, belonging to the A.O.U. "G.Martino", who have or have not contracted the infection in their lifetime, after anti-SARS-CoV-2 vaccination (Pfizer/BioNTech Comirnaty). Materials and Methods: The PubMed database (MEDLINE) was searched using the keywords PTX-3 and COVID-19, considering observational studies, case-control studies, cross-sectional studies, cohorts. Data extraction for this systematic update was performed by two independent reviewers. The cohort analysed consisted of workers vaccinated and supervised by the Hospital Hygiene Unit. A personal and family medical history was taken and an objective examination of the individual participants was carried out, who underwent blood sampling. Serum aliquots obtained after centrifugation were stored at -20°C. Subjects enrolled in the study were divided into 2 groups: SARS-CoV-2 positive (n=40); SARS-CoV-2 negative (n=40). Using commercially available kits, serum PTX-3 concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). Results: We included 11 studies in the systematic review. PTX-3 was evaluated in COVID-19 patients versus non-infected subjects and in COVID-19 patients in ICU versus COVID-19 patients not in ICU. For the healthcare workers in the study, demographic, clinical, laboratory characteristics were collected and reported in a dedicated database and associated with PTX-3 levels. Preliminary data showed variability in PTX-3 levels in healthy subjects correlated with sex, age, BMI, comorbidities and genetic characteristics. Discussion and Conclusions: The results to date support the hypothesis that PTX3 levels can be considered a useful biomarker of the inflammatory response and could have a relevant clinical impact on COVID-19 disease outcomes.