The Clinical Significance of GRP78 in COVID-19 Pneumonia Across Two Regional Cohorts

COVID-19 pneumonia remains a major driver of morbidity and mortality worldwide, with outcomes influenced by demographic, clinical, and systemic factors. Glucose-regulated protein 78 (GRP78) has emerged as a potential biomarker of disease severity, but its clinical significance across different populations remains underexplored. We conducted a retrospective cohort study including 83 hospitalized COVID-19 patients from General Hospital "Sv. Georgi", Plovdiv, Bulgaria, and 97 from Denizli, Türkiye. Pneumonia diagnosis was based on clinical, laboratory, and radiological criteria. Patient demographics and biomarkers (CRP, D-dimer, oxygen saturation, lymphocyte count, and serum GRP78) were compared between cohorts. Statistical analyses included Mann-Whitney U, <i>t</i>-tests, and logistic regression. Pneumonia prevalence was 48.8% in patients from General Hospital "Sv. Georgi", Plovdiv and 58.8% in Denizli. Patients in Plovdiv were older and exhibited higher CRP, D-dimer, and GRP78 levels, alongside lower oxygen saturation and lymphocyte counts. Logistic regression demonstrated that GRP78 significantly predicted pneumonia in both cohorts, with robust discriminative performance on ROC analysis. This study highlights significant regional differences in COVID-19 pneumonia presentation between Bulgaria and Türkiye. Elevated GRP78 levels were strongly associated with pneumonia and other severity markers, underscoring its potential as a clinically valuable biomarker for early risk stratification. These findings emphasize the importance of both localized epidemiological analyses and biomarker-based approaches to optimize COVID-19 management.