Molecular Determination of Tumor Necrosis Factor-alpha, Interleukin-8, Interleukin-10, and C-X-C Chemokine Receptor-2 Genetic Variations and their Association with Disease Susceptibility and Mortality in COVID-19 Patients.

Background: Altered cytokine levels have been associated with poor outcomes among COVID-19 patients. TNF-α, IL-8 and IL-10 are key cytokines in COVID-19 pathogenesis, and CXCR-2 is a major chemokine receptor involved in inflammatory response. Polymorphisms in the genes of these proteins are proposed to influence disease outcomes. In this study, we aimed to find out the association of genetic polymorphisms in TNF-α, IL-8, IL-10 and CXCR-2 genes with susceptibility to and mortality of COVID-19. Methods: The present case-control study was conducted on 230 subjects, among whom 115 were clinically diagnosed and RT-PCR-confirmed COVID-19 patients and 115 healthy control subjects. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), CXCR2 +785 C>T (rs2230054) genes were detected by ARMS -PCR assay whereas for IL-10 (-1082 G>A), rs1800896 G>A allele-specific PCR assay was used and their association with COVID-19 susceptibility and mortality was estimated by multivariate analysis. The results were analyzed for risk of infection and mortality through different inheritance models. Results: Frequencies of TNF-α rs1800629 GA, AA, IL-8 rs4073 TA, AA, IL-10 (-1082 G>A), rs1800896 GA and GG, and CXCR2 rs2230054 CT genotypes were significantly higher in COVID-19 patients compared to the control group (p < 0.05). Furthermore, COVID-19 patients had a higher frequency of the polymorphic A allele of TNF-α, the A allele of IL-8, the G allele of IL-10, and the T allele of CXCR2. The risk of susceptibility to COVID-19 was significantly associated with TNF-α rs1800629 GA, GA+AA genotypes and the A allele, IL-8 rs4073 TA, AA genotypes and A allele, IL-10 rs1800872 GA and CC genotypes and C allele, and CXCR2 rs2230054 CT and CT+CC genotypes. TNF-α-GA and AA genotypes and A allele, IL-8 TA and AA genotypes and A allele and CXCR-2 CC and CT genotypes have significant associations with mortality risk in COVID-19 patients, while GA and GG genotypes of the IL-10 are shown to confer significant protection against mortality from COVID-19. Conclusion: The findings of this study provide important insights into the COVID-19 disease and susceptibility risk. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), IL-10 (-1082 G>A), rs1800896 and CXCR2 +785 C>T (rs2230054) are associated with the risk of susceptibility to COVID-19 and with mortality in COVID-19 patients. Further studies with larger sample sizes are necessary to confirm our findings.

IL-2 and IL-1ß Patient Immune Responses Are Critical Factors in SARS-CoV-2 Infection Outcomes.

BACKGROUND: Immune dysregulation has been linked to morbidity and mortality in COVID-19 patients. Understanding the immunology of COVID-19 is critical for developing effective therapies, diagnostics, and prophylactic strategies to control the disease. AIM: The aim of this study was to correlate cytokine and chemokine serum levels with COVID-19 disease severity and mortality. SUBJECTS AND METHODS: A total of 60 hospitalized patients from the Tabuk region of Saudi Arabia with confirmed COVID-19 were included in the study. At hospital admission, the IL-1 ß, IL-2, IL-8, IL-10, LT-B4, and CCL-2 serum levels were measured. The cytokine levels in COVID-19 patients were compared to the levels in 30 healthy matched control subjects. RESULTS: The IL-1 ß, IL-2, LTB-4, CCL-2, and IL-8 levels (but not IL-10) were significantly higher in all COVID-19 patients (47 survivors and 13 non-survivors) compared with the levels in the healthy control group. In the non-survivor COVID-19 patients, patients' age, D-dimer, and creatinine kinase were significantly higher, and IL-1 ß, IL-2, and IL-8 were significantly lower compared with the levels in the survivors. CONCLUSION: Mortality rates in COVID-19 patients are associated with increased age and a failure to mount an effective immune response rather than developing a cytokine storm. These results warrant the personalized treatment of COVID-19 patients based on cytokine profiling.

Detection of Epstein-Barr virus in breast carcinoma in Egyptian women.

BACKGROUND: The association of oncogenic EBV with breast carcinoma (BC) is still in controversy. AIM OF WORK: Assess the association of EBV with BC in Egyptian women and find possible relationship between prognostic factors of BC and EBV detection. SUBJECTS AND METHODS: Paraffin-embedded sections from 40 female patients with primary invasive BC; ductal (n=32) and lobular (n=8) and breast tissues from patients with fibrocystic disease (n=20) as control were screened for presence of EBV by EBV nuclear antigen-1 (EBNA-1) immunostaining and by PCR for EBV-DNA. RESULTS: 10/40 (25%) of the BC specimens stained positively for EBNA-1; EBNA-1 expression was restricted to a fraction 5%-60% of tumor epithelial cells. EBV-DNA was detected in 8/10 of BC specimens positive for EBNA-1. Control specimens were negative by both techniques. 7/8 (87.5%) of EBV-DNA positive tumors were associated with >3 lymph nodes involvement. CONCLUSION: EBV is associated with some invasive BC in Egyptian females and may play a role in their etiology.

Antiproliferative effect of hepatitis C virus on mitogen-stimulated peripheral blood mononuclear cells: potential role in viral persistence in Egyptian patients.

OBJECTIVES: We aimed to study the effect of hepatitis C virus (HCV) and sera of chronic HCV patients on phytohemagglutinin (PHA)-stimulated normal donor PBMCs and to study the effect of chronic HCV infection on some cytokine profile. SUBJECTS AND METHODS: (3)H-Thymidine uptake was utilized to study effect of pelleted virus and patients sera on PBMCs proliferation in vitro. The study included 337 Egyptian chronic liver patients from Ain Shams University Hospitals and 90 healthy control subjects. The patients' group included chronic hepatitis C (250 subjects), and other chronic liver diseases (87 subjects). All subjects' sera were subjected to RT-PCR for HCV RNA detection, IL-4, IL-1beta, and TNF-alpha measurement by EIA, and biochemical measurement of ALT and albumin. RESULTS: Treatment of PHA-stimulated normal donor PBMCs with pelleted virus led to decrease (dose response) in their rate of proliferation. This was partially reversed after addition of HCV RNA positive patients' sera. HCV RNA positive patients were significantly higher in IL-4 and ALT, and lower in IL-1beta and albumin than HCV RNA negative patients. CONCLUSION: HCV infection suppresses early immune response. This leads to increased IL-4 Th2 cytokine.