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

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 6...

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Veröffentlicht in:	JCI insight Jg. 6; H. 1
Hauptverfasser:	Abers, Michael S., Delmonte, Ottavia M., Ricotta, Emily E., Fintzi, Jonathan, Fink, Danielle L., de Jesus, Adriana A. Almeida, Zarember, Kol A., Alehashemi, Sara, Oikonomou, Vasileios, Desai, Jigar V., Canna, Scott W., Shakoory, Bita, Dobbs, Kerry, Imberti, Luisa, Sottini, Alessandra, Quiros-Roldan, Eugenia, Castelli, Francesco, Rossi, Camillo, Brugnoni, Duilio, Biondi, Andrea, Bettini, Laura Rachele, D’Angio’, Mariella, Bonfanti, Paolo, Castagnoli, Riccardo, Montagna, Daniela, Licari, Amelia, Marseglia, Gian Luigi, Gliniewicz, Emily F., Shaw, Elana, Kahle, Dana E., Rastegar, Andre T., Stack, Michael, Myint-Hpu, Katherine, Levinson, Susan L., DiNubile, Mark J., Chertow, Daniel W., Burbelo, Peter D., Cohen, Jeffrey I., Calvo, Katherine R., Tsang, John S., Su, Helen C., Gallin, John I., Kuhns, Douglas B., Goldbach-Mansky, Raphaela, Lionakis, Michail S., Notarangelo, Luigi D.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States American Society for Clinical Investigation 11.01.2021 American Society for Clinical investigation
Schlagworte:	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 Blood levels Calgranulin B - genetics Calgranulin B - immunology Case-Control Studies Chemokine CCL2 - genetics Chemokine CCL2 - immunology Chemokine CXCL9 - genetics Chemokine CXCL9 - immunology Clinical outcomes Comorbidity Coronaviruses COVID-19 COVID-19 - genetics COVID-19 - immunology COVID-19 - mortality COVID-19 - therapy Diabetes Discordance Enzyme Inhibitors - therapeutic use Female Ferritin Ferritins - genetics Ferritins - immunology Gelatinase B Gene Expression Profiling Hospitalization Humans Hydroxychloroquine - therapeutic use Immunologic Factors - therapeutic use Immunology Infections Inflammation Interferon Type I - genetics Interferon Type I - immunology Interferon-gamma - genetics Interferon-gamma - immunology Interleukin 10 Interleukin 15 Interleukin 2 Interleukin-1 Receptor-Like 1 Protein - genetics Interleukin-1 Receptor-Like 1 Protein - immunology Interleukin-10 - genetics Interleukin-10 - immunology Interleukin-15 - genetics Interleukin-15 - immunology Interleukin-2 - genetics Interleukin-2 - immunology Interleukin-6 - genetics Interleukin-6 - immunology Lactoferrin Lactoferrin - genetics Lactoferrin - immunology Lipocalin-2 - genetics Lipocalin-2 - immunology Male Matrix Metalloproteinase 9 - genetics Matrix Metalloproteinase 9 - immunology Middle Aged Monocyte chemoattractant protein 1 Mortality Multivariate Analysis Neutrophils NF-kappa B - genetics NF-kappa B - immunology NF-κB protein Patients Pneumonia Prognosis Receptors, Tumor Necrosis Factor, Type I - genetics Receptors, Tumor Necrosis Factor, Type I - immunology SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Severity of Illness Index Steroids Vascular Endothelial Growth Factor Receptor-1 - genetics Vascular Endothelial Growth Factor Receptor-1 - immunology Italy COVID-19 Immunology Cytokines Chemokines
ISSN:	2379-3708, 2379-3708
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Authorship note: MSA, OMD, EER, and JF contributed equally to this work. JIG, DBK, RGM, MSL, and LDN contributed equally to this work.
ISSN:	2379-3708 2379-3708
DOI:	10.1172/jci.insight.144455