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Updated: Dec 9, 2025
Author Spotlight: Unveiling the Polyfunctionality and Heterogeneity in Immune Responses
Published on: March 8, 2024
Characterization of the cytokine storm reflects hyperinflammatory endothelial dysfunction in COVID-19
Jonathan T Sims1, Venkatesh Krishnan1, Ching-Yun Chang1
1Eli Lilly and Company, Indianapolis, Ind.
Insights
Researchers identified key circulating biomarkers in COVID-19 patients, revealing a hyperinflammatory state and vascular damage. These markers correlate with disease severity and can be attenuated by baricitinib, offering insights into cytokine storm interventions.
Area of Science:
- Immunology
- Virology
- Proteomics
Background:
- COVID-19 (coronavirus disease 2019) is associated with a hyperinflammatory acute stage, often termed a cytokine storm.
- Characterizing circulating biomarkers in COVID-19 patients compared to healthy individuals is crucial for developing targeted interventions.
Purpose of the Study:
- To identify and characterize host inflammatory responses to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection.
- To assess protein levels related to immune and cardiovascular responses in patients with varying COVID-19 severity.
Main Methods:
- Utilized high-throughput and ultrasensitive proteomic platforms to analyze blood samples from hospitalized COVID-19 patients and matched healthy controls.
- Compared differential regulation of 185 markers across mild, moderate, and severe COVID-19 cases.
Main Results:
- Observed a dominant hyperinflammatory milieu and vascular endothelial damage markers in COVID-19 patients.
- Identified significant dysregulation of numerous cytokines (e.g., IFN-γ, IL-6, IL-10) and chemokines (e.g., MCP-1, CXCL10) correlating with disease progression.
- Demonstrated that baricitinib treatment attenuates these cytokine storm-associated biomarkers.
Conclusions:
- The identified circulating biomarkers are associated with increased COVID-19 severity and can aid in patient stratification and therapeutic selection.
- These findings provide valuable insights into the pathogenesis of SARS-CoV-2 and the host's inflammatory response.
Background:
Physicians treating patients with coronavirus disease 2019 (COVID-19) 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 with 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 severe acute respiratory syndrome coronavirus 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 patients with COVID-19, and strong biomarker association with patient response as measured by Ordinal Scale. As patients progress, we observe statistically significant dysregulation of IFN-γ, IL-1RA, IL-6, IL-10, IL-19, monocyte chemoattractant protein (MCP)-1, MCP-2, MCP-3, CXCL9, CXCL10, CXCL5, ENRAGE, and poly (ADP-ribose) polymerase 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.
Conclusions:
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 severe acute respiratory syndrome coronavirus 2 pathogenesis and the host response.
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