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

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.

• Authors: 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
• Journal: JCI insight (JCI Insight) Vol. 6 Issue 1 (01 11 2021) ISSN: 2379-3708 [Electronic] United States
• PMID: 33232303 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Adrenal Cortex Hormones
• Anti-Bacterial Agents
• Antibodies, Monoclonal, Humanized
• Antiviral Agents
• Biomarkers
• CCL2 protein, human
• CXCL9 protein, human
• Calgranulin B
• Chemokine CCL2
• Chemokine CXCL9
• Enzyme Inhibitors
• IL10 protein, human
• IL15 protein, human
• IL1RL1 protein, human
• IL2 protein, human
• IL6 protein, human
• Immunologic Factors
• Interferon Type I
• Interleukin-1 Receptor-Like 1 Protein
• Interleukin-15
• Interleukin-2
• Interleukin-6
• LCN2 protein, human
• LTF protein, human
• Lipocalin-2
• NF-kappa B
• Receptors, Tumor Necrosis Factor, Type I
• S100A9 protein, human
• TNFRSF1A protein, human
• Interleukin-10
• canakinumab
• Hydroxychloroquine
• Interferon-gamma
• Azithromycin
• Ferritins
• Vascular Endothelial Growth Factor Receptor-1
• Lactoferrin
• MMP9 protein, human
• Matrix Metalloproteinase 9
• tocilizumab

Topics

• Adrenal Cortex Hormones (therapeutic use)
• Adult
• Aged
• Anti-Bacterial Agents (therapeutic use)
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antiviral Agents (therapeutic use)
• Azithromycin (therapeutic use)
• Biomarkers
• COVID-19 (genetics, immunology, mortality, therapy)
• Calgranulin B (genetics, immunology)
• Case-Control Studies
• Chemokine CCL2 (genetics, immunology)
• Chemokine CXCL9 (genetics, immunology)
• Enzyme Inhibitors (therapeutic use)
• Female
• Ferritins (genetics, immunology)
• Gene Expression Profiling
• Humans
• Hydroxychloroquine (therapeutic use)
• Immunologic Factors (therapeutic use)
• Interferon Type I (genetics, immunology)
• Interferon-gamma (genetics, immunology)
• Interleukin-1 Receptor-Like 1 Protein (genetics, immunology)
• Interleukin-10 (genetics, immunology)
• Interleukin-15 (genetics, immunology)
• Interleukin-2 (genetics, immunology)
• Interleukin-6 (genetics, immunology)
• Lactoferrin (genetics, immunology)
• Lipocalin-2 (genetics, immunology)
• Male
• Matrix Metalloproteinase 9 (genetics, immunology)
• Middle Aged
• Multivariate Analysis
• NF-kappa B (genetics, immunology)
• Prognosis
• Receptors, Tumor Necrosis Factor, Type I (genetics, immunology)
• SARS-CoV-2
• Severity of Illness Index
• Vascular Endothelial Growth Factor Receptor-1 (genetics, immunology)