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JCI Insight ; 6(1)2021 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-33232303

RESUMEN

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.


Asunto(s)
COVID-19/inmunología , COVID-19/mortalidad , Corticoesteroides/uso terapéutico , Adulto , Anciano , Antibacterianos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , Biomarcadores , COVID-19/genética , COVID-19/terapia , Calgranulina B/genética , Calgranulina B/inmunología , Estudios de Casos y Controles , Quimiocina CCL2/genética , Quimiocina CCL2/inmunología , Quimiocina CXCL9/genética , Quimiocina CXCL9/inmunología , Inhibidores Enzimáticos/uso terapéutico , Femenino , Ferritinas/genética , Ferritinas/inmunología , Perfilación de la Expresión Génica , Humanos , Hidroxicloroquina/uso terapéutico , Factores Inmunológicos/uso terapéutico , Interferón Tipo I/genética , Interferón Tipo I/inmunología , Interferón gamma/genética , Interferón gamma/inmunología , Proteína 1 Similar al Receptor de Interleucina-1/genética , Proteína 1 Similar al Receptor de Interleucina-1/inmunología , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-15/genética , Interleucina-15/inmunología , Interleucina-2/genética , Interleucina-2/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Lactoferrina/genética , Lactoferrina/inmunología , Lipocalina 2/genética , Lipocalina 2/inmunología , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/inmunología , Persona de Mediana Edad , Análisis Multivariante , FN-kappa B/genética , FN-kappa B/inmunología
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