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

Petrov et al., International Journal of Molecular Sciences, doi:10.3390/ijms262110312, Oct 2025
https://c19early.org/petrov2.html
Retrospective 180 hospitalized COVID-19 patients showing elevated GRP78 protein levels associated with pneumonia development and disease severity.
Petrov et al., 23 Oct 2025, retrospective, Bulgaria, peer-reviewed, 7 authors. Contact: martina.bozhkova@mu-plovdiv.bg (corresponding author), steliyan.petrov@mu-plovdiv.bg, stanislava.popova@mu-plovdiv.bg, mariela.geneva@mu-plovdiv.bg, tanya.deneva@mu-plovdiv.bg, iturkcuer@pau.edu.tr, akoseler@pau.edu.tr.
The Clinical Significance of GRP78 in COVID-19 Pneumonia Across Two Regional Cohorts
Steliyan Petrov, Martina Bozhkova, Stanislava Popova-Belova, Mariela Geneva-Popova, Tanya Deneva, İbrahim Türkçüer, Aylin Köseler
International Journal of Molecular Sciences, doi:10.3390/ijms262110312
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, t-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.
Author Contributions: Conceptualization, A.K.; methodology, A.K., M.B. and S.P.; software, A.K., S.P.; validation, A.K., M.B. and S.P.; formal analysis, A.K. and S.P.; investigation, A.K. and S.P.; resources, S. Conflicts of Interest: The authors declare no conflicts of interest. Abbreviations The following abbreviations are used in this manuscript: COVID-19 Coronavirus disease 2019 SARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2 GRP78 Glucose-regulated protein 78 CRP C-reactive protein ICU Intensive Care Unit
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DOI record: { "DOI": "10.3390/ijms262110312", "ISSN": [ "1422-0067" ], "URL": "http://dx.doi.org/10.3390/ijms262110312", "abstract": "<jats:p>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, t-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.</jats:p>", "alternative-id": [ "ijms262110312" ], "author": [ { "ORCID": "https://orcid.org/0000-0003-0522-5682", "affiliation": [ { "name": "Department of Medical Microbiology and Immunology—“Prof. Dr. Elissay Yanev”, Medical University-Plovdiv, 4002 Plovdiv, Bulgaria" } ], "authenticated-orcid": false, "family": "Petrov", "given": "Steliyan", "sequence": "first" }, { "ORCID": "https://orcid.org/0000-0003-4230-3299", "affiliation": [ { "name": "Department of Medical Microbiology and Immunology—“Prof. Dr. Elissay Yanev”, Medical University-Plovdiv, 4002 Plovdiv, Bulgaria" } ], "authenticated-orcid": false, "family": "Bozhkova", "given": "Martina", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Propedeutics of Internal Diseases “Anton Mitov”, Medical University-Plovdiv, General Hospital “Sv. 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