Distinct cytokine profiles associated with COVID-19 severity and mortality

Area of Science:

• Immunology
• Virology
• Critical Care Medicine

Background:

• Patients with coronavirus disease 2019 (COVID-19) exhibit elevated proinflammatory cytokines and impaired type-I interferon responses.
• Understanding these immune responses is crucial for predicting COVID-19 severity and outcomes.

Purpose of the Study:

• To investigate the association between specific cytokine profiles and COVID-19 severity and mortality.
• To identify cytokine patterns that can predict patient outcomes based on respiratory support needs.

Main Methods:

• Serum cytokine concentrations and SARS-CoV-2 antigen levels were measured in hospitalized COVID-19 patients (N=115) categorized by respiratory support: no mechanical ventilatory support (No-MVS), mechanical ventilatory support (MVS), and extracorporeal membrane oxygenation (ECMO).
• Principal-component analysis was employed to define cytokine profiles linked to severity and mortality, with validation in an independent cohort (N=86).

Main Results:

• ECMO patients showed a dominant proinflammatory response (TNF-α, IL-6, IL-8, IL-10), while No-MVS patients had elevated type-I interferons (IFN-α, IFN-β). MVS patients displayed both profiles.
• Mortality was associated with specific cytokine profiles depending on support modality: proinflammatory cytokines in ECMO, type-I interferons in No-MVS, and a combination in MVS patients, achieving 88.5% prediction accuracy.
• SARS-CoV-2 antigen levels correlated with type-I interferons and mortality but not with proinflammatory responses or severity.

Conclusions:

• Distinct cytokine profiles correlate with COVID-19 severity and differentially predict mortality based on oxygen support.
• Cytokine profiling offers a pathway for personalized treatment strategies in COVID-19 patients.