Interferon gamma-induced protein 10 (IP-10) for the early prognosis of the risk for severe respiratory failure and death in COVID-19 pneumonia

Samaras, C.; Kyriazopoulou, E.; Poulakou, G.; Reiner, E.; Kosmidou, M.; Karanika, I.; Petrakis, V.; Adamis, G.; Gatselis, N. K.; Fragkou, A.; Rapti, A.; Taddei, E.; Kalomenidis, I.; Chrysos, G.; Bertoli, G.; Kainis, I.; Alexiou, Z.; Castelli, F.; Saverio Serino, F.; Bakakos, P.; Nicastri, E.; Tzavara, V.; Kostis, E.; Dagna, L.; Koukidou, S.; Tzatzagou, G.; Chini, M.; Bassetti, M.; Trakatelli, C.; Tsoukalas, G.; Selmi, C.; Samarkos, M.; Pyrpasopoulou, A.; Masgala, A.; Antonakis, E.; Argyraki, A.; Akinosoglou, K.; Sympardi, S.; Panagopoulos, P.; Milionis, H.; Metallidis, S.; Syrigos, K. N.; Angel, A.; Dalekos, G. N.; Netea, M. G.; Giamarellos-Bourboulis, E. J.

doi:10.1016/j.cyto.2022.156111

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. Trial registration. ClinicalTrials.gov, NCT04680949 and NCT04357366.

Interferon gamma-induced protein 10 (IP-10) for the early prognosis of the risk for severe respiratory failure and death in COVID-19 pneumonia / Samaras, C.; Kyriazopoulou, E.; Poulakou, G.; Reiner, E.; Kosmidou, M.; Karanika, I.; Petrakis, V.; Adamis, G.; Gatselis, N. K.; Fragkou, A.; Rapti, A.; Taddei, E.; Kalomenidis, I.; Chrysos, G.; Bertoli, G.; Kainis, I.; Alexiou, Z.; Castelli, F.; Saverio Serino, F.; Bakakos, P.; Nicastri, E.; Tzavara, V.; Kostis, E.; Dagna, L.; Koukidou, S.; Tzatzagou, G.; Chini, M.; Bassetti, M.; Trakatelli, C.; Tsoukalas, G.; Selmi, C.; Samarkos, M.; Pyrpasopoulou, A.; Masgala, A.; Antonakis, E.; Argyraki, A.; Akinosoglou, K.; Sympardi, S.; Panagopoulos, P.; Milionis, H.; Metallidis, S.; Syrigos, K. N.; Angel, A.; Dalekos, G. N.; Netea, M. G.; Giamarellos-Bourboulis, E. J.. - In: CYTOKINE. - ISSN 1043-4666. - 162:(2023), p. 156111. [10.1016/j.cyto.2022.156111]