ArticleJCI insight2021
An immune-based biomarker signature is associated with mortality in COVID-19 patients.
Registry-linked trialOpen access · goldAbstract read
In one paragraph
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04953312 (Calprotectin Involvement in Emergency Hematopoiesis Observed in Severe COVID-19), which is not on this map. Cited by 229 papers, 5 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
229citing papers in PubMed, 5 pooled it
7.5field-weighted citation impact, top 2% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Calprotectin Involvement in Emergency Hematopoiesis Observed in Severe COVID-19
Who cites it
229 citing papers in PubMed, 5 syntheses or guidelines pooled it, 365 citations in OpenAlex.
- Aortic dissection and Covid-19; a comprehensive systematic review.Current problems in cardiology · 2023Pooled it
- Identification of Parameters Representative of Immune Dysfunction in Patients with Severe and Fatal COVID-19 Infection: a Systematic Review and Meta-analysis.Clinical reviews in allergy & immunology · 2023Pooled it
- Innate immunity to SARS-CoV-2 infection: a review.Epidemiology and infection · 2022Pooled it
- T-Cell Subsets and Interleukin-10 Levels Are Predictors of Severity and Mortality in COVID-19: A Systematic Review and Meta-Analysis.Frontiers in medicine · 2022Pooled it
- Adaptive immunity to SARS-CoV-2 infection: A systematic review.Frontiers in immunology · 2022Pooled it
- A Phase 1, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Escalation Study for the Evaluation of the Safety, Tolerability, and Pharmacokinetics of Recombinant Human Plasma Gelsolin (rhu-pGSN) Following Intravenous Administration to Healthy Volunteers.Clinical pharmacology in drug development · 2026Trial
- Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Trial
- Spleen tyrosine kinase inhibition restores myeloid homeostasis in COVID-19.Science advances · 2023Trial
- Matrix metalloproteinases (MMP) 3 and 9 as biomarkers of severity in COVID-19 patients.Scientific reports · 2022Trial
- Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology.Journal of hematology & oncology · 2022Trial
- Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial.The Lancet. Respiratory medicine · 2021Trial
- Immune-Based Cytokine Signatures of Prolonged Pandemic-Associated Chilblains.The Journal of infectious diseases · 2026Article
- Association of Plasma Biomarkers of Immunothrombosis With Death in Patients With Coronavirus Disease 2019 on Extracorporeal Membrane Oxygenation.The Journal of infectious diseases · 2026Article
- Autoantibodies to IL-1Ra and PGRN in severe COVID-19 are associated with inflammation-induced hyperphosphorylated antigen isoforms.Nature communications · 2026Article
- The Open Reading Frame 7b of the SARS-CoV-2 Disperse Trans-Golgi and Activate the NLRP3 Inflammasome.Journal of medical virology · 2026Article
- Association of gender and main comorbidities with expression of lncRNAs and mRNAs in COVID-19 patients.Journal, genetic engineering & biotechnology · 2026Article
- Monocyte chemoattractant protein-1 (MCP-1/CCL2) and matrix metalloproteinase-9 (MMP-9) as biomarkers of disease severity in COVID-19 patients.Biochemistry and biophysics reports · 2026Article
- Serum Calprotectin in Hospitalized Patients with COVID-19 in Relation to High-Dimensional Serum Proteomic Patterns.International journal of molecular sciences · 2026Observational
- Abnormal Serum Albumin, Alanine Aminotransferase, and Blood Urea Nitrogen are Associated with Higher Risks for Mechanical Ventilation and In-Hospital Mortality in COVID-19 Positive US Veterans.Biomarker insights · 2026Article
- Article
169 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
47 authors at 9 institutions in 2 countries.
Michael S AbersLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Ottavia M DelmonteLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Emily E RicottaLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Jonathan FintziBiostatistics Research Branch, NIAID, NIH, Bethesda, Maryland, USA.
Danielle L FinkNeutrophil Monitoring Laboratory, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Adriana A Almeida de JesusLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Kol A ZaremberLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Sara AlehashemiLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Vasileios OikonomouLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Jigar V DesaiLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Scott W CannaChildren's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Bita ShakooryLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Kerry DobbsLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Luisa ImbertiCREA Laboratory, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.
Alessandra SottiniCREA Laboratory, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.
Eugenia Quiros-RoldanDepartment of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, Brescia, Italy.
Francesco CastelliDepartment of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, Brescia, Italy.
Camillo RossiDirezione Sanitaria, ASST Spedali Civili di Brescia, Italy.
Duilio BrugnoniLaboratorio Analisi Chimico-Cliniche, ASST Spedali Civili, Brescia, Italy.
Andrea BiondiPediatric Department and Centro Tettamanti-European Reference Network on Paediatric Cancer, European Reference Network on Haematological Diseases, and European Reference Network on Hereditary Metabolic Disorders-University of Milano-Bicocca-Fondazione MBBM, Monza, Italy.
Laura Rachele BettiniPediatric Department and Centro Tettamanti-European Reference Network on Paediatric Cancer, European Reference Network on Haematological Diseases, and European Reference Network on Hereditary Metabolic Disorders-University of Milano-Bicocca-Fondazione MBBM, Monza, Italy.
Mariella D'Angio'Pediatric Department and Centro Tettamanti-European Reference Network on Paediatric Cancer, European Reference Network on Haematological Diseases, and European Reference Network on Hereditary Metabolic Disorders-University of Milano-Bicocca-Fondazione MBBM, Monza, Italy.
Paolo BonfantiDepartment of Infectious Diseases, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
Riccardo CastagnoliDepartment of Pediatrics and.
Daniela MontagnaLaboratory of Immunology and Transplantation, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Amelia LicariDepartment of Pediatrics and.
Gian Luigi MarsegliaDepartment of Pediatrics and.
Emily F GliniewiczLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Elana ShawLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Dana E KahleLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Andre T RastegarLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Michael StackLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Katherine Myint-HpuLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Susan L LevinsonBioAegis Therapeutics, Inc, North Brunswick, New Jersey, USA.
Mark J DiNubileBioAegis Therapeutics, Inc, North Brunswick, New Jersey, USA.
Daniel W ChertowCritical Care Medicine Department, NIH Clinical Center, NIH, Bethesda, Maryland, USA.
Peter D BurbeloNational Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, USA.
Jeffrey I CohenLaboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA.
Katherine R CalvoHematology Section, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, Maryland, USA.
John S TsangLaboratory of Immune System Biology and Clinical Genomics Program, NIAID, NIH, Bethesda, Maryland, USA.
NIAID COVID-19 Consortium
Helen C SuLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
John I GallinLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Douglas B KuhnsNeutrophil Monitoring Laboratory, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Raphaela Goldbach-ManskyLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Michail S LionakisLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Luigi D NotarangeloLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
National Institutes of Health · USAzienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia · ITUniversity of Milano-Bicocca · ITIo Therapeutics (United States) · USLeidos (United States) · USChildren's Hospital of Pittsburgh · USNational Institute of Dental and Craniofacial Research · USNational Institutes of Health Clinical Center · USUniversity of Pavia · IT
Funding
Integrative analysis and modeling of human immune responses and pathologiesZIAAI001152 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI TSANG, JOHN · 2011 to 2022
$14.1MHost factors contributing to susceptibility to COVID-19 diseaseZIAAI001265 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, HELEN CHUN-HUI · 2020 to 2025
$9.5MClinical Studies Of Abnormal Host DefenseZIAAI000155 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI GALLIN, JOHN I · 2009 to 2022
$3.1MSystems Immunology of COVID-19ZIAAI001266 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI TSANG, JOHN · 2020 to 2022
$1.2MCharacterization of host immune responses to SARS-CoV-2ZIAAI001270 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI NOTARANGELO, LUIGI · 2020 to 2025
$1.2MSerologic studies of persons with COVID-19 infectionZIAAI001258 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI COHEN, JEFFREY · 2020 to 2025
$411kThe pathogenesis of COVID-19ZIAAI001318 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LIONAKIS, MICHAIL · 2020 to 2023
$290kLongitudinal IFN signature response and cytokine profiling in patients with severe COVID infectionsZIAAI001303 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI GOLDBACH-MANSKY, RAPHAELA · 2020 to 2023
$137kThe Role of microRNA in Hematologic MalignanciesZIACL090025 · CLC · CLINICAL CENTER · PI CALVO, KATHERINE · 2010 to 2025
$0kClinical and Molecular Features of Coronavirus Disease 2019ZIACL090070 · CLC · CLINICAL CENTER · PI CHERTOW, DANIEL S · 2020 to 2025
$0kCCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001E
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.
Indexed as
Adrenal Cortex HormonesAdultAgedAnti-Bacterial AgentsAntibodies, Monoclonal, HumanizedAntiviral AgentsAzithromycinBiomarkersCalgranulin BCase-Control StudiesChemokine CCL2Chemokine CXCL9COVID-19Enzyme InhibitorsFemaleFerritinsAdrenal Cortex HormonesAnti-Bacterial AgentsAntibodies, Monoclonal, HumanizedAntiviral AgentsAzithromycinBiomarkersCalgranulin BcanakinumabCCL2 protein, humanChemokine CCL2Chemokine CXCL9CXCL9 protein, humanEnzyme InhibitorsFerritinsHydroxychloroquineIL10 protein, humanIL15 protein, humanIL1RL1 protein, humanIL2 protein, humanIL6 protein, humanImmunologic FactorsInterferon-gammaInterferon Type IInterleukin-10Interleukin-15Interleukin-1 Receptor-Like 1 ProteinInterleukin-2Interleukin-6LactoferrinLCN2 protein, humanLipocalin-2LTF protein, humanMatrix Metalloproteinase 9MMP9 protein, humanNF-kappa BReceptors, Tumor Necrosis Factor, Type IS100A9 protein, humanTNFRSF1A protein, humantocilizumabVascular Endothelial Growth Factor Receptor-1ChemokinesCOVID-19CytokinesImmunology
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Read underepoch 390
Registered trials
NCT04953312ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.