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Cytokine profiles dynamics in COVID-19 patients: a longitudinal analysis of disease severity and outcomes

Sara Ghaffarpour1, Tooba Ghazanfari2,3, Sussan Kaboudanian Ardestani1,4

  • 1Immunoregulation Research Center, Shahed University, Tehran, Iran.

Scientific Reports
|April 24, 2025
PubMed

Insights

The immune response in COVID-19 varies by severity. An imbalance in interleukin-1 beta (IL-1β) and interferon-alpha (IFN-α) indicates severe disease, with higher IL-1β/IFN-α ratios linked to better outcomes.

Area of Science:

  • Immunology
  • Virology
  • Infectious Diseases

Background:

  • The immune response's outcome hinges on inflammatory mediators, timing, and duration.
  • Coronavirus disease 2019 (COVID-19) patients exhibit diverse disease severity.
  • Understanding immune response variations across COVID-19 severity is crucial for elucidating disease mechanisms.

Purpose of the Study:

  • To serially analyze cytokine profiles in 809 patients with mild to critical COVID-19.
  • To identify cytokine patterns associated with different COVID-19 disease severities.
  • To determine if specific cytokine ratios can distinguish between mild and critical COVID-19 cases.

Main Methods:

  • Serial analysis of cytokine profiles in 809 COVID-19 patients.
  • Principal Component Analysis (PCA) to identify components associated with disease severity.
  • Spearman correlation analysis to compare cytokine relationships between mild and critical patients.

Main Results:

  • Elevated levels of IL-1β, IL-1Ra, TNF-α, IL-6, IL-2, IL-8, and IL-18, with impaired IFN-α and -β production observed overall.
  • Early rises in IL-1Ra, IL-6, and IL-2, and long-term rises in multiple cytokines were linked to worse outcomes.
  • A component including IL-1β, TNF-α, IFN-α, and IL-12 correlated with disease severity, with distinct IL-1β/IFN-α ratios between mild and critical patients.

Conclusions:

  • An imbalance in the IL-1β/IFN-α ratio contributes to hyperinflammation in COVID-19.
  • The IL-1β/IFN-α ratio serves as a potential criterion for distinguishing critical from mild COVID-19.
  • Higher IL-1β/IFN-α ratios correlate with improved outcomes in COVID-19 patients.

Keywords:
COVID-19Cytokine profileLongitudinal studyPrinciple component analysis.SARS-CoV-2

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