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Association of IL-1β, IL-6, IL-8, IL-12, TNF-α, and IFN-α With Severe Pediatric COVID-19 and Multisystem Inflammatory
Kateryna Kozak1, Halyna Pavlyshyn1
1Department of Pediatrics No. 2,I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine.
Insights
Cytokine levels can help assess severe pediatric COVID-19 and multisystem inflammatory syndrome in children (MIS-C). This study identified specific cytokine thresholds and patterns for these conditions, aiding in diagnosis and understanding inflammatory responses.
Area of Science:
- Immunology
- Pediatrics
- Infectious Diseases
Background:
- Cytokine profiles offer insights into inflammatory responses during infectious diseases like SARS-CoV-2.
- Thresholds and patterns of cytokines linked to severe pediatric COVID-19 and MIS-C require further characterization.
Purpose of the Study:
- To evaluate serum levels and threshold concentrations of specific cytokines (IL-1β, IL-6, IL-8, IL-12, TNF-α, IFN-α) in pediatric COVID-19 and MIS-C.
- To characterize distinct cytokine patterns across various clinical presentations of SARS-CoV-2 infection in children.
Main Methods:
- A cohort study involving 200 children with SARS-CoV-2 infection (mild, moderate, severe), 40 with MIS-C, and 45 controls.
- Serum cytokine concentrations were measured within 24 hours of hospitalization using immunoenzymatic assays.
- Random Forest analysis was employed to determine the importance of cytokines in classifying COVID-19 severity.
Main Results:
- Specific cytokine cut-off values were identified for severe COVID-19 and MIS-C.
- IL-1β and IL-8 demonstrated the highest importance in Random Forest models for classifying COVID-19 severity.
- Cytokine profiles showed adequate discriminatory performance for identifying MIS-C.
Conclusions:
- Cytokine profiling can enhance the evaluation of hyperinflammatory responses in pediatric SARS-CoV-2 infections.
- Further validation in larger, independent pediatric cohorts is necessary to establish the clinical utility of cytokine profiling beyond standard markers.
Background:
The cytokine profile may provide clinically relevant information for assessing the inflammatory response in infectious diseases, including SARS-CoV-2. However, the threshold concentrations of cytokines associated with severe pediatric COVID-19 and cytokine patterns related to multisystem inflammatory syndrome in children (MIS-C), remain insufficiently characterized.
Objectives:
This study aimed to evaluate serum levels and exploratory threshold concentrations of IL-1β, IL-6, IL-8, IL-12, TNF-α, and IFN-α associated with severe pediatric COVID-19 and MIS-C, and to characterize cytokine patterns across different clinical forms of SARS-CoV-2 infection in children.
Design:
The cohort study included 200 children with laboratory-confirmed SARS-CoV-2 infection, including mild COVID-19 (n=106), moderate COVID-19 (n=72), and severe COVID-19 (n= 22), 40 children diagnosed with MIS-C, and 45 children with negative PCR and ELISA results for SARS-CoV-2. Participants were aged 1 month to 17 years (6.47±5.53 years), and none had received a COVID-19 vaccine at the time of inclusion.
Methods:
Serum concentrations of IL-1β, IL-6, IL-8, IL-12, TNF-α, and IFN-α were measured within the first 24 hours of hospitalization, before treatment initiation, using immunoenzymatic assays.
Results:
Cytokines associated with severe COVID-19 included IL-1β (cut-off 6.96 pg/mL), IL-6 (cut-off 68.37 pg/mL), IL-12 (cut-off 34.53 pg/mL), TNF-α (cut-off 60.63 pg/mL), and IFN-α (cut-off 26.96 pg/mL). All measured cytokines demonstrated adequate discriminatory performance for identifying MIS-C: IL-1β (cut-off 7.28 pg/mL), IL-6 (cut-off 100.64 pg/mL), IL-8 (cut-off 16.93 pg/mL), IL-12 (cut-off 34.91 pg/mL), TNF-α (cut-off 80.19 pg/mL), and IFN-α (cut-off 30.56 pg/mL). Random Forest analysis identified IL-1β and IL-8 as variables with the highest model-derived importance for COVID-19 severity classification, whereas age and sex showed lower model-derived importance than cytokine biomarkers.
Conclusion:
Cytokine profiling may support a more nuanced evaluation of hyperinflammatory immune responses in pediatric SARS-CoV-2-associated disease. However, its additional clinical value beyond routine clinical and laboratory markers requires validation in larger independent pediatric cohorts.
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