Interferon gamma-induced protein 10 (IP-10) for the early prognosis of the risk for severe respiratory failure and death in COVID-19 pneumonia
Charilaos Samaras, Evdoxia Kyriazopoulou, Garyphallia Poulakou, Eran Reiner, Maria Kosmidou, Ioanna Karanika, Vasileios Petrakis, George Adamis, Nikolaos Gatselis, Archontoula Fragkou, Aggeliki Rapti, Eleonora Taddei, Ioannis Kalomenidis, George Chrysos, Giulia Bertoli, Ilias Kainis, Zoi Alexiou, Francesco Castelli, Francesco Saverio Serino, Petros Bakakos, Emanuele Nicastri, Vassiliki Tzavara, Evangelos Kostis, Lorenzo Dagna, Sofia Koukidou, Glykeria Tzatzagou, Maria Chini, Matteo Bassetti, Christina Trakatelli, George Tsoukalas, Carlo Selmi, Michael Samarkos, Athina Pyrpasopoulou, Aikaterini Masgala, Emmanouil Antonakis, Aikaterini Argyraki, Karolina Akinosoglou, Styliani Sympardi, Periklis Panagopoulos, Haralampos Milionis, Symeon Metallidis, Konstantinos N. Syrigos, Alon Angel, George Ν. Dalekos, Mihai G. Netea, Evangelos J. Giamarellos‐Bourboulis
Abstract
OBJECTIVES: Elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict progression to severe respiratory failure (SRF) or death among patients with COVID-19 pneumonia and guide early anakinra treatment. As suPAR testing may not be routinely available in every health-care setting, alternative biomarkers are needed. We investigated the performance of C-reactive protein (CRP), interferon gamma-induced protein-10 (IP-10) and TNF-related apoptosis-inducing ligand (TRAIL) for predicting SRF or death in COVID-19. METHODS: Two cohorts were studied; one discovery cohort with 534 patients from the SAVE-MORE clinical trial; and one validation cohort with 364 patients from the SAVE trial including also 145 comparators. CRP, IP-10 and TRAIL were measured by the MeMed Key® platform in order to select the biomarker with the best prognostic performance for the early prediction of progression into SRF or death. RESULTS: IP-10 had the best prognostic performance: baseline concentrations 2000 pg/ml or higher predicted equally well to suPAR (sensitivity 85.0 %; negative predictive value 96.6 %). Odds ratio for poor outcome among anakinra-treated participants of the SAVE-MORE trial was 0.35 compared to placebo when IP-10 was 2,000 pg/ml or more. IP-10 could divide different strata of severity for SRF/death by day 14 in the validation cohort. Anakinra treatment decreased this risk irrespective the IP-10 concentrations. CONCLUSIONS: IP-10 concentrations of 2,000 pg/ml or higher are a valid alternative to suPAR for the early prediction of progression into SRF or death the first 14 days from hospital admission for COVID-19 and they may guide anakinra treatment. CLINICALTRIALS: gov, NCT04680949 and NCT04357366.