Clinical and Prognostic Significance of Baseline Serum Vitamin D Levels in Hospitalized Egyptian Covid-19 Patients.

Background and Aim: Vitamin D is a hormone with essential roles in both cellular metabolism and immunity. It controls calcium homeostasis and modulates innate and adaptive immune system responses. Many studies suggested an association between vitamin D deficiency and clinical outcomes of covid-19 infection, while others failed to document such a relation. The present study aimed to evaluate the clinical and prognostic significance of baseline vitamin D levels in hospitalized Egyptian covid-19 patients. Patients and Methods: The present retrospective study included 300 hospitalized covid-19 patients. Patients were submitted to standard clinical, laboratory, and radiological assessment. According to vitamin D levels, patients were classified to have normal levels (≥30), insufficient levels (20-29) or deficient levels (<20). Results: According to their vitamin D levels, patients were classified into those with normal vitamin D (n=135), others with vitamin D insufficiency (n=114), and a third group with vitamin D deficiency (n=51). Patients with normal vitamin D levels and vitamin D insufficiency are significantly younger [median (IQR): 49.0 (39.0-57.0) versus 51.0 (40.0-61.0) and 55.0 (43.0-62.0) years, respectively, p=0.012] and had less frequency of severe disease (24.4% versus 40.4% and 51.0%, respectively) when compared with those with vitamin D deficiency. Moreover, they had significantly lower levels of D dimer [median (IQR): 1.5 (0.9-2.5) versus 1.8 (0.9-3.1) and 2.0 (1.0-3.2)], CRP [median (IQR): 58.0 (30.0-120.0) versus 76.0 (42.5-160.0) and 105.0 (74.0-208.0), respectively, p<0.001], ferritin [median (IQR): 458.0 (240.0-759.0) versus 606.0 (433.8-897.8) and 820.0 (552.0-1087.0), respectively, p<0.001], and procalcitonin [median (IQR): 290.0 (152.0-394.0) versus 372.5 (227.0-530.5) and 443.0 (272.0-575.0), respectively, p<0.001]. Only lower vitamin D levels were significant predictors of mortality in multivariate analysis [OR (95% CI): 0.88 (0.84-0.92), p<0.001]. Conclusion: Low vitamin D levels are related to exaggerated inflammatory response, disease severity, and poor clinical outcome in hospitalized covid-19 patients.

Cytotoxic T Cell Expression of Leukocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1) in Viral Hepatitis C-Mediated Hepatocellular Carcinoma.

Virus-related hepatocellular carcinoma (HCC) pathogenesis involves liver inflammation, therefore, despite successful treatment, hepatitis C virus (HCV) may progress to HCC from initiated liver cirrhosis. Cytotoxic T cells (Tcs) are known to be involved in HCV-related cirrhotic complications and HCC pathogenesis. The inhibitory checkpoint leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is expressed on Tcs. Therefore, we aimed to determine whether the Tc expression level of LAIR-1 is associated with HCC progression and to evaluate LAIR-1 expression as a noninvasive biomarker for HCC progression in the context of liver cirrhosis related to HCV genotype 4 (G4) in Egyptian patients' peripheral venous blood liquid biopsy. A total of 64 patients with HCC and 37 patients with liver cirrhosis were enrolled in this case-controlled study, and their LAIR-1 expression on Tc related to the progression of liver cirrhosis was examined and compared to that of the apparently healthy control group (n = 20). LAIR-1 expression was analyzed using flow cytometry. Results: The HCC group had significantly higher LAIR-1 expression on Tc and percentage of Tc positive for LAIR-1 (LAIR-1+Tc%) than the HCV G4-related liver cirrhosis group. LAIR-1+Tc% was correlated with the HCC surrogate tumor marker AFP (r = 0.367, p = 0.001) and insulin resistance and inflammation prognostic ratios/indices. A receiver operating characteristic (ROC) curve revealed that adding LAIR-1+Tc% to AFP can distinguish HCC transformation in the Egyptian patients' cohort. Upregulated LAIR-1 expression on Tc could be a potential screening noninvasive molecular marker for chronic inflammatory HCV G4 related liver cirrhosis. Moreover, LAIR-1 expression on Tc may be one of the players involved in the progression of liver cirrhosis to HCC.

T-Natural Killers and Interferon Gamma/Interleukin 4 in Augmentation of Infection in Foot Ulcer in Type 2 Diabetes.

BACKGROUND: The link between immune system and type 2 diabetes mellitus (T2DM) pathogenesis attracted attention to demonstrate the role of immune cells and their secreted cytokines in T2DM development and its subsequent foot complications. OBJECTIVE: To investigate the relation between T Natural killer cell (TNK) %, Interleukin 4 (IL4) and Interferon gamma (IFN-γ) and diabetic foot infection (DFI) development in patients with diabetic foot ulcer (DFU). PATIENTS AND METHODS: Ninety patients with diabetes were included in this work, divided as T2DM group (n=30), DFU group (n=30), and DFI group (n=30). TNK% was detected using flow cytometry. Serum IL4 and IFN-γ were measured by ELISA. Diabetes biochemical parameters were also analyzed. RESULTS: Significant decrease was detected in TNK% and IFN-γ in DFI group compared to other 2 groups (P<0.001). Significant decrease was detected in serum levels of IL4 in DFI group compared to T2DM group (P=0.006). IFN-γ/IL4 was significantly decreased in DFI compared to DFU group (P=0.020). There was a significant correlation of TNK% with both IL4 and IFN-γ (r=0.385, P<0.001; r=0.534, P<0.001, respectively). Significant negative correlation of TNK% with HbA1c and LDL was revealed (r=-0.631, P<0.001; and r=-0.261, P=0.013, respectively), while a positive correlation was seen with HDL (r=0.287, P=0.006). A significant negative correlation of IL4 with HbA1c  was found (r=-0.514, P<0.001;. As for IFN-γ, a significant negative correlation with HbA1c and LDL was detected (r=-0.369, P< 0.001; r=-0.229, P=0.030). TNK % and IFN-γ level showed negative correlations with disease duration/year (r=-0.546, P< 0.001; r=-0.338, P=0.001,respectively). CONCLUSION: Decline in TNK frequency has essential role in T2DM pathogenesis and subsequent foot complications. Downregulation of TNK% and IFN-γ level have potential roles in predicting infection of diabetic ulcer and are correlated with disease duration.