Article ; Online: An immune-based biomarker signature is associated with mortality in COVID-19 patients.
JCI insight
2021 Volume 6, Issue 1
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 ... ...
| 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. |
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| MeSH term(s) | 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 ; COVID-19/immunology ; COVID-19/mortality ; COVID-19/therapy ; Calgranulin B/genetics ; Calgranulin B/immunology ; Case-Control Studies ; Chemokine CCL2/genetics ; Chemokine CCL2/immunology ; Chemokine CXCL9/genetics ; Chemokine CXCL9/immunology ; Enzyme Inhibitors/therapeutic use ; Female ; Ferritins/genetics ; Ferritins/immunology ; Gene Expression Profiling ; Humans ; Hydroxychloroquine/therapeutic use ; Immunologic Factors/therapeutic use ; Interferon Type I/genetics ; Interferon Type I/immunology ; Interferon-gamma/genetics ; Interferon-gamma/immunology ; 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/genetics ; Lactoferrin/immunology ; Lipocalin-2/genetics ; Lipocalin-2/immunology ; Male ; Matrix Metalloproteinase 9/genetics ; Matrix Metalloproteinase 9/immunology ; Middle Aged ; Multivariate Analysis ; NF-kappa B/genetics ; NF-kappa B/immunology ; Prognosis ; Receptors, Tumor Necrosis Factor, Type I/genetics ; Receptors, Tumor Necrosis Factor, Type I/immunology ; SARS-CoV-2 ; Severity of Illness Index ; Vascular Endothelial Growth Factor Receptor-1/genetics ; Vascular Endothelial Growth Factor Receptor-1/immunology |
| Chemical Substances | 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 (130068-27-8) ; canakinumab (37CQ2C7X93) ; Hydroxychloroquine (4QWG6N8QKH) ; Interferon-gamma (82115-62-6) ; Azithromycin (83905-01-5) ; Ferritins (9007-73-2) ; Vascular Endothelial Growth Factor Receptor-1 (EC 2.7.10.1) ; Lactoferrin (EC 3.4.21.-) ; MMP9 protein, human (EC 3.4.24.35) ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; tocilizumab (I031V2H011) |
| Language | English |
| Publishing date | 2021-01-11 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Intramural |
| ISSN | 2379-3708 |
| ISSN (online) | 2379-3708 |
| DOI | 10.1172/jci.insight.144455 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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