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

  1. Author:
    Abers, Michael S
    Delmonte, Ottavia M
    Ricotta, Emily E
    Fintzi, Jonathan
    Fink,Dani
    de Jesus, Adriana A
    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 R
    D'Angio', Mariella
    Bonfanti, Paolo
    Castagnoli, Riccardo
    Montagna, Daniela
    Licari, Amelia
    Marseglia, Gian Luigi
    Gliniewicz, Emily
    Shaw, Elana R
    Kahle, Dana
    Rastegar, Andre T
    Stack, Michael A
    Myint-Hpu, Katherine
    Levinson, Susan L
    DiNubile, Mark J
    Chertow, Daniel W
    Burbelo, Peter
    Cohen, Jeffrey I
    Calvo, Katherine R
    Tsang, John S
    Su, Helen C
    Gallin, John I
    Kuhns,Doug
    Goldbach-Mansky, Raphaela
    Lionakis, Michail S
    Notarangelo, Luigi D

  2. Author Address

    Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, United States of America., Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, United States of America., Neutrophil Monitoring Laboratory, Frederick National Laboratory for Cancer Research, Frederick, United States of America., Children 39;s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, United States of America., CREA Laboratory, Diagnostic Department, ASST Spedali Civili di Brescia, Milan, Italy., Department of Infectious and Tropical Diseases, University of Brescia and ASST Spedali di Brescia, Brescia, Italy., ASST Spedali Civili, Brescia, Italy., Laboratorio Analisi Chimico-Cliniche, ASST Spedali Civili, Brescia, Italy., Pediatric Department and Centro Tettamanti, University of Milano-Bicocca-Fondazione MBBM-Ospedale San Gerardo, Milano, Italy., Department of Infectious Diseases, University of Milano-Bicocca-Fondazione MBBM-Ospedale San Gerardo, Monza, Italy., Department of Pediatrics, University of Pavia, Pavia, Italy., Laboratory of Immunology and Transplantation, University of Pavia, Pavia, Italy., BioAegis Therapeutics, Inc., North Brunswick, United States of America., Ciritical Care Medicine Department, NIH Clinical Center, National Institutes of Health, bethesda, United States of America., National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, United States of America., Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, United States of America., Hematology Section, Department of Laboratory Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, United States of America., Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, Bethesda, United States of America.,
    1. Year: 2021
    2. Date: Jan 11
    3. Epub Date: 2020 11 24
  2. Journal: JCI insight
    1. 6
    2. 1
    3. Pages: pii: 144455
  4. Type of Article: Article
  5. Article Number: e144455
  6. ISSN: 2379-3708
  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 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-kappa B-dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-a2a 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-1a 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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External Sources

  1. View Full Text
  2. DOI: 10.1172/jci.insight.144455
  3. PMID: 33232303
  4. View record in Web of Science®
  5. WOS: 000607653800016
  6. PII : 144455

Library Notes

  1. Fiscal Year: FY2020-2021
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