The long Pentraxin PTX3 serves as an early predictive biomarker of co-infections in COVID-19Research in context
Francesco Scavello,
Enrico Brunetta,
Sarah N. Mapelli,
Emanuele Nappi,
Ian David García Martín,
Marina Sironi,
Roberto Leone,
Simone Solano,
Giovanni Angelotti,
Domenico Supino,
Silvia Carnevale,
Hang Zhong,
Elena Magrini,
Matteo Stravalaci,
Alessandro Protti,
Alessandro Santini,
Elena Costantini,
Victor Savevski,
Antonio Voza,
Barbara Bottazzi,
Michele Bartoletti,
Maurizio Cecconi,
Alberto Mantovani,
Paola Morelli,
Federica Tordato,
Cecilia Garlanda
Affiliations
Francesco Scavello
IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Enrico Brunetta
Infectious Diseases Unit, Hospital Health Direction, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Sarah N. Mapelli
IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Emanuele Nappi
IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Milan, Italy
Ian David García Martín
Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Milan, Italy
Marina Sironi
IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Roberto Leone
IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Simone Solano
IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Giovanni Angelotti
Artificial Intelligence Center, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Domenico Supino
IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Silvia Carnevale
IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Hang Zhong
IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Milan, Italy
Elena Magrini
IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Matteo Stravalaci
IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Alessandro Protti
Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Milan, Italy; Department of Anesthesia and Intensive Care, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Alessandro Santini
Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Milan, Italy; Department of Anesthesia and Intensive Care, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Elena Costantini
Department of Anesthesia and Intensive Care, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Victor Savevski
Artificial Intelligence Center, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Antonio Voza
Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Milan, Italy; Emergency Department, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Barbara Bottazzi
IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Michele Bartoletti
Infectious Diseases Unit, Hospital Health Direction, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Milan, Italy
Maurizio Cecconi
Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Milan, Italy; Department of Anesthesia and Intensive Care, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Alberto Mantovani
IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Milan, Italy; The William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK
Paola Morelli
Infectious Diseases Unit, Hospital Health Direction, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Federica Tordato
Infectious Diseases Unit, Hospital Health Direction, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
Cecilia Garlanda
IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Milan, Italy; Corresponding author. IRCCS Humanitas Research Hospital, via Manzoni 56, 20089, Rozzano, Milan, Italy.
Summary: Background: COVID-19 clinical course is highly variable and secondary infections contribute to COVID-19 complexity. Early detection of secondary infections is clinically relevant for patient outcome. Procalcitonin (PCT) and C-reactive protein (CRP) are the most used biomarkers of infections. Pentraxin 3 (PTX3) is an acute phase protein with promising performance as early biomarker in infections. In patients with COVID-19, PTX3 plasma concentrations at hospital admission are independent predictor of poor outcome. In this study, we assessed whether PTX3 contributes to early identification of co-infections during the course of COVID-19. Methods: We analyzed PTX3 levels in patients affected by COVID-19 with (n = 101) or without (n = 179) community or hospital-acquired fungal or bacterial secondary infections (CAIs or HAIs). Findings: PTX3 plasma concentrations at diagnosis of CAI or HAI were significantly higher than those in patients without secondary infections. Compared to PCT and CRP, the increase of PTX3 plasma levels was associated with the highest hazard ratio for CAIs and HAIs (aHR 11.68 and 24.90). In multivariable Cox regression analysis, PTX3 was also the most significant predictor of 28-days mortality or intensive care unit admission of patients with potential co-infections, faring more pronounced than CRP and PCT. Interpretation: PTX3 is a promising predictive biomarker for early identification and risk stratification of patients with COVID-19 and co-infections. Funding: Dolce & Gabbana fashion house donation; Ministero della Salute for COVID-19; EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT) and MUR PNRR Italian network of excellence for advanced diagnosis (Project no. PNC-E3-2022-23683266 PNC-HLS-DA); EU MSCA (project CORVOS 860044).
