Characterization of the cytokine storm reflects hyperinflammatory endothelial dysfunction in COVID-19

Autor: Brian J. Nickoloff, Silvia Ottaviani, Jonathan T. Sims, Nicoletta Bivi, Richard E. Higgs, Ajay Nirula, Venkatesh Krishnan, George H. Rodgers, Giacomo Casalini, Robert J. Benschop, Anabela Cardoso, Justin Stebbing, Mario Corbellino, Sarah M. Engle, Ching Yun Chang, Robert J. Konrad, Stephanie de Bono
Přispěvatelé: British Society for Antimicrobial Chemotherapy
Rok vydání: 2021
Předmět:
Male
Proteomics
SCF
Stem cell factor
0301 basic medicine
Allergy
medicine.medical_treatment
Poly (ADP-Ribose) Polymerase-1
Disease
030204 cardiovascular system & hematology
Cardiovascular
Pathogenesis
0302 clinical medicine
Baricitinib
MCP
Monocyte chemoattractant protein
GDF-2
Growth/differentiation factor 2
Immunology and Allergy
IL
Interleukin
Endothelial dysfunction
COVID-19
Coronavirus disease 2019
IFN
Interferon
ICU
Intensive care unit
Cytokine
1107 Immunology
Cytokines
Biomarker (medicine)
CXCL9
Female
Cytokine Release Syndrome
JAK
Janus kinase
Adult
MMP
Matrix metalloproteinase
Ordinal Scale
Immunology
Article
03 medical and health sciences
PEA
Proximity extension array
medicine
Humans
CXCL10
tSNE
T-distributed stochastic neighbor embedding
Inflammation
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
SARS-CoV-2
STAT
Signal transducer and activator of transcription
business.industry
PTX3
Pentraxin-related protein 3
COVID-19
medicine.disease
030104 developmental biology
business
Cytokine storm
Biomarkers
Zdroj: The Journal of Allergy and Clinical Immunology
Journal of Allergy and Clinical Immunology
ISSN: 0091-6749
Popis: Background Physicians treating COVID-19 patients increasingly believe that the hyperinflammatory acute stage of COVID-19 results in a cytokine storm. The circulating biomarkers seen across the spectrum of COVID-19 have not been characterized compared to healthy controls, but such analyses are likely to yield insights into the pursuit of interventions that adequately reduce the burden of these cytokine storms. Objective To identify and characterize the host inflammatory response to SARS-CoV-2 infection, we assessed levels of proteins related to immune responses and cardiovascular disease, in patients stratified as mild, moderate, and severe, versus matched healthy controls. Methods Blood samples from adult patients hospitalized with COVID-19 were analyzed using high-throughput and ultrasensitive proteomic platforms and compared with age- and sex-matched healthy controls to provide insights into differential regulation of 185 markers. Results Results indicate a dominant hyperinflammatory milieu in the circulation and vascular endothelial damage markers within COVID-19 patients, and strong biomarker association with patient response as measured by Ordinal scale. As patients progress, we observe statistically significant dysregulation of IFNγ, IL-1RA, IL-6, IL-10, IL-19, MCP-1, -2, -3, CXCL9, CXCL10, CXCL5, ENRAGE and PARP-1. Furthermore, in a limited series of patients who were sampled frequently confirming reliability and reproducibility of our assays, we demonstrate that intervention with baricitinib attenuates these circulating biomarkers associated with the cytokine storm. Conclusion These wide-ranging circulating biomarkers show an association with increased disease severity and may help stratify patients and selection of therapeutic options. They also provide insights into mechanisms of SARS-CoV-2 pathogenesis and the host response.
Capsule Summary: This detailed analysis of plasma biomarkers in COVID-19 patients provides definitive understanding of the cytokine storm and changes in vascular endothelial markers that may inform us of the changes in the Ordinal scale for COVID-19.
Databáze: OpenAIRE
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