GBP2 Expression Inversely Linked to COVID-19 Severity

In a retrospective cross-sectional study published in BMC Infectious Diseases, researchers identified a strong inverse association between the expression of the interferon-stimulated gene GBP2 and the clinical severity of COVID-19. The study, conducted by Abdullah Yücel Baba and Bahadır Feyzioğlu, analyzed archived whole-blood samples from adults with RT-PCR-confirmed SARS-CoV-2 infection. The central finding indicates that as disease severity increased from mild to critical, GBP2 mRNA expression decreased in a stepwise manner, suggesting a potential link between host immune response markers and disease progression.

The research team aimed to evaluate the relationship between the expression of guanylate-binding proteins, specifically GBP2 and GBP5, and clinical outcomes in patients with SARS-CoV-2. Guanylate-binding proteins are GTPases that are induced by interferon responses and have been shown to restrict SARS-CoV-2 by interfering with the furin-mediated processing of the viral spike protein. While the role of host interferon responses in determining COVID-19 outcomes is increasingly recognized, the specific relationship between these gene expressions and clinical severity had not been extensively studied. The investigators used GBP5 as a comparator gene to test whether any observed associations were specific to GBP2 or representative of a broader class of interferon-stimulated genes.

The study design was retrospective and cross-sectional, utilizing archived whole-blood samples collected between November 2020 and February 2021. The cohort consisted of 150 adults with confirmed SARS-CoV-2 infection, categorized into four severity groups based on WHO and national criteria: 37 mild, 32 moderate, 46 severe, and 35 critical. Additionally, the study included 50 SARS-CoV-2-negative controls. The researchers measured GBP2 and GBP5 mRNA levels using quantitative reverse transcription polymerase chain reaction (qRT-PCR). To ensure accurate quantification, the expression levels were normalized to the housekeeping gene GAPDH using the 2−ΔΔCt method.

Statistical analysis involved comparing gene expression levels across the five study groups using one-way analysis of variance (ANOVA) with Tukey post-hoc testing. To account for potential variances and ensure robustness, the team also performed variance-robust and log2-scale sensitivity analyses. Demographic factors such as age, sex, and comorbidity were assessed using Spearman correlation and regression models.

The results demonstrated that GBP2 expression differed significantly across the five study groups, with an F-statistic of 288.27 and a p-value less than 0.001. Relative to the control group, GBP2 expression decreased stepwise from the mild group, which showed a 4.76-fold change, to the critical group, which showed a 0.60-fold change. All ten pairwise comparisons between the groups were statistically significant on the fold-change scale. On the log2 scale, nine of the ten comparisons remained significant using Tukey’s Honestly Significant Difference (HSD) test, with the exception of the comparison between mild and moderate groups, which yielded a p-value of 0.205. When using the Games–Howell test, all ten pairwise comparisons were significant, further supporting the graded nature of the association.

In contrast, GBP5 expression showed a much weaker and non-graded pattern across the severity groups. The F-statistic for GBP5 was 3.31 with a p-value of 0.012, indicating a statistically significant but less pronounced difference compared to GBP2. Specifically, GBP5 expression was higher in critical patients (1.35-fold) than in controls (1.00-fold), but it did not follow the stepwise decrease observed in GBP2. The lack of a graded pattern in GBP5 reinforces the specificity of the GBP2 finding.

Further analysis revealed that GBP2 expression was inversely correlated with age, with a correlation coefficient of r = −0.57 and a p-value less than 0.001. However, clinical severity remained an independent predictor of GBP2 expression after adjusting for age, sex, and comorbidity. The p-value for each severity group was less than 0.001 in the adjusted models. Sex and comorbidity were not independently associated with GBP2 expression. Age reached statistical significance only on the log2 scale, with a conventional p-value of 0.045 and an HC3 p-value of 0.020.

The authors conclude that GBP2 expression is inversely associated with COVID-19 severity in this cohort, characterized by a strong graded relationship across severity strata. The study highlights the importance of GBP2 as a potential marker of disease severity, while emphasizing that the findings represent an observed cross-sectional association rather than a causal relationship. The limitations of the study include the measurement of only two interferon-stimulated genes, which precludes inferences about the broader class of such genes.

Subject of Research: Association of GBP2 and GBP5 expression with COVID-19 severity

Article Title: Association of GBP2 and GBP5 expression with COVID-19 severity: a retrospective cross-sectional study

Article References: Baba, A. Y., & Feyzioğlu, B. (2026). Association of GBP2 and GBP5 expression with COVID-19 severity: a retrospective cross-sectional study. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14793-3

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14793-3

Keywords: GBP2, GBP5, COVID-19, SARS-CoV-2, Interferon-stimulated genes, mRNA expression, Clinical severity, Retrospective study, Biomarkers, Immune response, Association, expression