Immune and inflammatory responses to SARS-CoV-2 contribute to disease severity of COVID-19. However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity, and assessed type-I IFN-, type-II IFN-, and NF-κB-dependent whole blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and non-hematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type-I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients' first samples revealed 12 biomarkers (CCL2, IL-15, sST2, NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and two additional biomarkers (lactoferrin, CXCL9) that were significantly associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.

Abers, M., Delmonte, O., Ricotta, E., Fintzi, J., Fink, D., de Jesus, A., et al. (2021). An immune-based biomarker signature is associated with mortality in COVID-19 patients. JCI INSIGHT, 6(1 (11 January 2021)) [10.1172/jci.insight.144455].

An immune-based biomarker signature is associated with mortality in COVID-19 patients

Biondi, Andrea;Bettini, Laura R;D'Angio', Mariella;Bonfanti, Paolo;
2021

Abstract

Immune and inflammatory responses to SARS-CoV-2 contribute to disease severity of COVID-19. However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity, and assessed type-I IFN-, type-II IFN-, and NF-κB-dependent whole blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and non-hematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type-I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients' first samples revealed 12 biomarkers (CCL2, IL-15, sST2, NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and two additional biomarkers (lactoferrin, CXCL9) that were significantly associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.
Articolo in rivista - Articolo scientifico
COVID-19; Chemokines; Cytokines; Immunology;
English
Abers, M., Delmonte, O., Ricotta, E., Fintzi, J., Fink, D., de Jesus, A., et al. (2021). An immune-based biomarker signature is associated with mortality in COVID-19 patients. JCI INSIGHT, 6(1 (11 January 2021)) [10.1172/jci.insight.144455].
Abers, M; Delmonte, O; Ricotta, E; Fintzi, J; Fink, D; de Jesus, A; Zarember, K; Alehashemi, S; Oikonomou, V; Desai, J; Canna, S; Shakoory, B; Dobbs, K; Imberti, L; Sottini, A; Quiros-Roldan, E; Castelli, F; Rossi, C; Brugnoni, D; Biondi, A; Bettini, L; D'Angio', M; Bonfanti, P; Castagnoli, R; Montagna, D; Licari, A; Marseglia, G; Gliniewicz, E; Shaw, E; Kahle, D; Rastegar, A; Stack, M; Myint-Hpu, K; Levinson, S; Dinubile, M; Chertow, D; Burbelo, P; Cohen, J; Calvo, K; Tsang, J; Su, H; Gallin, J; Kuhns, D; Goldbach-Mansky, R; Lionakis, M; Notarangelo, L
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/295880
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