1. An immune-based biomarker signature is associated with mortality in COVID-19 patients
- Author
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Michael S. Abers, Ottavia M. Delmonte, Emily E. Ricotta, Jonathan Fintzi, Danielle L. Fink, Adriana A. Almeida de Jesus, Kol A. Zarember, Sara Alehashemi, Vasileios Oikonomou, Jigar V. Desai, Scott W. Canna, Bita Shakoory, Kerry Dobbs, Luisa Imberti, Alessandra Sottini, Eugenia Quiros-Roldan, Francesco Castelli, Camillo Rossi, Duilio Brugnoni, Andrea Biondi, Laura Rachele Bettini, Mariella D’Angio’, Paolo Bonfanti, Riccardo Castagnoli, Daniela Montagna, Amelia Licari, Gian Luigi Marseglia, Emily F. Gliniewicz, Elana Shaw, Dana E. Kahle, Andre T. Rastegar, Michael Stack, Katherine Myint-Hpu, Susan L. Levinson, Mark J. DiNubile, Daniel W. Chertow, Peter D. Burbelo, Jeffrey I. Cohen, Katherine R. Calvo, John S. Tsang, NIAID COVID-19 Consortium, Helen C. Su, John I. Gallin, Douglas B. Kuhns, Raphaela Goldbach-Mansky, Michail S. Lionakis, Luigi D. Notarangelo, 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, and Notarangelo, L
- Subjects
Male ,0301 basic medicine ,Chemokine ,Azithromycin ,Chemokine CXCL9 ,Severity of Illness Index ,0302 clinical medicine ,Adrenal Cortex Hormones ,Medicine ,Enzyme Inhibitors ,Chemokine CCL2 ,Interleukin-15 ,biology ,Lactoferrin ,NF-kappa B ,General Medicine ,Middle Aged ,Prognosis ,Anti-Bacterial Agents ,Interleukin-10 ,Matrix Metalloproteinase 9 ,Receptors, Tumor Necrosis Factor, Type I ,030220 oncology & carcinogenesis ,Interferon Type I ,Cytokines ,Biomarker (medicine) ,CXCL9 ,Female ,Chemokines ,Research Article ,Hydroxychloroquine ,Adult ,Immunology ,CCL2 ,Antibodies, Monoclonal, Humanized ,Antiviral Agents ,S100A9 ,COVID-19 ,Interferon-gamma ,03 medical and health sciences ,Immune system ,Lipocalin-2 ,Calgranulin B ,Humans ,Immunologic Factors ,Cytokine ,Aged ,Vascular Endothelial Growth Factor Receptor-1 ,Interleukin-6 ,SARS-CoV-2 ,business.industry ,Gene Expression Profiling ,Interleukin-1 Receptor-Like 1 Protein ,Ferritin ,030104 developmental biology ,Case-Control Studies ,Ferritins ,Multivariate Analysis ,biology.protein ,Interleukin-2 ,business ,Biomarkers - Abstract
Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (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 nonhematopoietic 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, soluble ST2 [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 2 additional biomarkers (lactoferrin, CXCL9) that were substantially 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.
- Published
- 2021