AUTHOR=Koyou Haily Liduin , Ramachandran Vasudevan , Salleh Mohd Nazil , Wan Sulaiman Wan Aliaa , Mohamed Mohd Hazmi , Mohd Badrin Mohd Jaamia Qaadir , Jelemie Caroline Satu 
  
TITLE=S100 Protein and Interleukin Biomarkers Among COVID-19 Subjects With and Without Pneumonia: A Systematic Review and Meta-Analysis
  
JOURNAL=British Journal of Biomedical Science
  
VOLUME=Volume 82 - 2025
  
YEAR=2026
  
URL=https://www.frontierspartnerships.org/journals/british-journal-of-biomedical-science/articles/10.3389/bjbs.2025.15355
  
DOI=10.3389/bjbs.2025.15355
  
ISSN=2474-0896
  
ABSTRACT=BackgroundThe global spread of COVID-19, caused by SARS-CoV-2, has resulted in a wide spectrum of clinical manifestations, ranging from asymptomatic cases to severe complications, such as pneumonia, acute respiratory distress syndrome (ARDS), and multiple organ failure. Identifying effective biomarkers is essential for predicting disease severity and improving patient management.ObjectivesThis meta-analysis aims to assess the significance of S100 proteins (S100A4, S100A8, S100A9, S100A12, S100B, S100P) and interleukins (IL) (IL-6, IL-8, IL-10, IL-17, IL-1β) in COVID-19 patients, comparing those with and without pneumonia or organ failure.MethodsA systematic literature search was conducted on different databases, yielding 47 relevant studies published between 2020 and 2024. Data on the prevalence of IL and S100 protein levels were extracted and analyzed using pooled standardized mean differences (SMD) and heterogeneity (I2) to evaluate their associations with disease severity.ResultsIL-6 and IL-10 levels were significantly elevated in COVID-19 patients suffering from pneumonia or organ failure. IL-6 levels were notably higher in pneumonia patients compared to those without (SMD = 0.34 [95% CI: 0.17, 0.52], I2 = 29%). Similarly, elevated S100B levels were observed in severe cases (SMD = 0.51 [95% CI: 0.19, 0.83], I2 = 0%). While IL-10 levels showed high variability (I2 = 90%), they remained consistently linked with worse outcomes.ConclusionThis meta-analysis underscores the potential of IL-6, IL-10, and S100 proteins as important biomarkers in evaluating COVID-19 severity, offering valuable insights to help clinical management.