Soluble HLA-G (sHLA-G) molecules are considered potent immunomodulators, and their dysregulated expression has been implicated in several pathological conditions, including coronavirus disease 19 (COVID-19). Therefore, a case-control study (103 COVID-19 patients and 105 controls) was performed to determine sHLA-G role in severity of COVID-19. Results revealed that median levels of sHLA-G were significantly increased in serum of patients compared to controls (19.3 vs . 12.7 ng/mL; p < 0.001). When patients and controls were stratified by age group, gender, body mass index, chronic disease, or ABO and Rh blood groups, the sHLA-G level did not show a significant difference in each stratum. Logistic regression analysis demonstrated that the up-regulated expression of sHLA-G was associated with an elevated risk of developing COVID-19. Receiver operating characteristic curve analysis showed that sHLA-G was a very good predictor of COVID-19, and at a cut-off value of 15.4 ng/mL, the sensitivity and specificity of sHLA-G were 79.6 and 79.0%, respectively. Spearman rank correlation analysis revealed that sHLA-G was positively correlated with age, erythrocyte sedimentation rate, white blood cell count, and random blood glucose, while a negative correlation was recorded with vitamin D. In conclusion, up-regulated expression of sHLA-G was indicated in patients with severe COVID-19.

Antimicrobial peptides (AMPs) have recently been proposed as significant immunological factors involved in pathogenesis of coronavirus disease 19 (COVID-19). Human β-defensins (hBDs) are among these AMPs, but the evidence is not well detailed. Therefore, this case-control study analyzed levels of hBD1, hBD2, hBD3 and hBD4 in serum of 103 patients with severe COVID-19 and 105 healthy controls. Most patients were older than 45 years (80.6%), and more than 50% suffered from chronic diseases (cardiovascular and diabetes). Results revealed that median levels of hBD1 and hBD3 did not show significant differences between patients and controls. On the contrary, HBD2 levels were significantly decreased in patients compared to controls (1036 vs . 1289 ng/L; p < 0.001), while HBD4 levels were significantly increased (4.04 vs . 2.43 ng/L; p < 0.001). Receiver operating characteristic curve analysis demonstrated the predictive significance of hBD2 (area under the curve [AUC] = 0.795; 95% confidence interval [CI] = 0.729–0.861; p < 0.001) and hBD4 (AUC = 0.816; 95% CI = 0.756–0.876; p < 0.001) in discriminating between COVID-19 patients and controls. Logistic regression analysis (adjusted for age, gender and body mass index) confirmed the significance of hBD2 (odds ratio [OR] = 0.996; corrected p = 0.004) and hBD4 (OR = 4.948; corrected p < 0.001) in susceptibility to COVID-19. In conclusion, the study indicated that hBD2 showed low levels in serum of patients infected with severe COVID-19, while hBD4 showed elevated levels. These differences in HBDs were not influenced by age, gender, body mass index, or chronic disease.

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A cross-sectional observational study was conducted on 213 patients with COVID-19 who did not have a clinical history of diabetes at hospital admission. One week after hospitalization, they were stratified by random blood glucose levels. It was found that 25.4, 22.5 and 52.1% of COVID-19 patients were classified as normoglycemia, prediabetes and diabetes, respectively. The study indicated that diabetes may be a risk factor for COVID-19 or the disease may be associated with an increased risk of developing diabetes.