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.
【저자키워드】 COVID-19, immunology, Cytokines, chemokines, 【초록키워드】 coronavirus disease, SARS-CoV-2, Coronavirus disease 2019, coronavirus, Biomarker, Biomarkers, Mortality, Hospitalization, IL-6, severity, disease severity, ferritin, outcome, severe acute respiratory syndrome Coronavirus, immune, Clinical outcome, Protein, cells, Patient, trajectory, CXCL9, type I IFNs, lactoferrin, IL-10, respiratory, utility, disease, Critical, predict, Blood, IL-2, IL-15, Inflammatory response, Analysis, Inflammatory, Type I IFN, acute respiratory syndrome, Activation, Discordance, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, CCL2, type I, multivariable analysis, multivariate, multivariate analyses, IL-1α, S100A9, IFNA2, type II IFN, Cell, transcriptional, produced, analyzed, died, contribute, transcript level, Italian patient, ST2, with COVID-19, 【제목키워드】 Mortality, COVID-19 patient, biomarker signature,