RESUMO
Aim: The study aimed to assess the relationships between serum cytokine levels and pulmonary dysfunctions in individuals with COVID-19. These correlations may help to suggest strategies for prevention and therapies of coronavirus disease. Patients and methods: Fifty healthy participants and one hundred COVID-19 patients participated in this study. COVID-19 participants were subdivided into moderate and severe groups based on the severity of their symptoms. In both patients and healthy controls, white blood cells (WBCs) and lymphocytes counts and serum C-reactive protein (CRP), interleukin (IL)-1, IL-4, IL-6, IL-18, and IL-35 levels were estimated. All the patients were examined by chest computed tomography (CT) and the COVID-19 Reporting and Data System (CO-RADS) score was assessed. Results: All COVID-19 patients had increased WBCs count and CRP, IL-1ß, IL-4, IL-6, IL-18, and IL-35 serum levels than healthy controls. Whereas WBCs, CRP, and cytokines like IL-6 showed significantly higher levels in the severe group as compared to moderate patients, IL-4, IL-35, and IL-18 showed comparable levels in both disease groups. Lymphocytes count in all patient groups exhibited a significant decrease as compared to the heathy controls and it was significantly lower in severe COVID-19 than moderate. Furthermore, CO-RADS score was positively connected with WBCs count as well as CRP and cytokine (IL-35, IL-18, IL-6, IL-4 and IL-1ß) levels in both groups. CO-RADS score, also demonstrated a positive correlation with lymphocytes count in the moderate COVID-19 patients, whereas it demonstrated a negative correlation in the severe patients. The receiver operator characteristic (ROC) curve analysis indicated that IL-1ß, IL-4, IL-18, and IL-35 were fair (acceptable) predictors for COVID-19 in moderate cases. Whereas IL-6 was good predictor of COVID-19 in severe cases (AUC > 0.800), IL-18 and IL-35 were fair. Conclusion: Severe COVID-19 patients, compared to individuals with moderate illness and healthy controls, had lower lymphocyte counts and increased CRP with greater WBCs counts. In contrast to moderate COVID-19 patients, severe COVID-19 patients had higher levels of IL-6, but IL-4, IL-18, and IL-35 between both illness categories were at close levels. IL-6 level was the most potent predictor of COVID-19 progress and severity. CO-RADS 5 was the most frequent category in both moderate and severe cases. Patients with a typical CO-RADS involvement had a higher CRP and cytokine (IL-1ß, IL-6, IL-4, IL-18, and IL-35) levels and WBCs count with a lower lymphocyte number than the others. Cytokine and CRP levels as well as WBCs and lymphocyte counts were considered surrogate markers of severe lung affection and pneumonia in COVID 19 patients.
RESUMO
Aim: The study evaluated the correlations between cytokine levels, liver function markers, and neuropilin-1 (NRP-1) expression in patients with COVID-19 in Egypt. The study also aimed to evaluate the accuracy sensitivity, specificity, and area under the curve (AUC) of the tested laboratory parameters in identifying COVID-19 infection and its severity. Patients and Methods: Fifty healthy subjects and 100 confirmed patients with COVID-19 were included in this study. COVID-19 patients were separated into two groups based on the severity of their symptoms. Serum ALT, AST, albumin, C-reactive protein (CRP), interleukin (IL)-1ß, IL-4, IL-6, IL-18, IL-35, prostaglandin E2 (PGE2), and thromboxane A2 (TXA2) were estimated. We measured the gene expression for nuclear factor-kappa B p50 (NF-κB p50) and nuclear factor-kappa B p65 (NF-κB p65) and NRP-1 in blood samples using quantitative real-time polymerase chain reaction (qRT-PCR). AUC and sensitivity and specificity for cytokine levels and NF-κB p50 and NF-κB p65 and NRP-1 in identifying COVID-19 infection were also determined in both moderate and severe patient groups using receiver-operating characteristic curve (ROC) analysis. Results: All patients with COVID-19 showed higher serum activities of liver enzymes, levels of CRP, IL-1ß, IL-4, IL-6, IL-18, IL-35 PGE2, and TXA2, and mRNA expression of NF-κB p50, NF-κB p65, and NRP-1 than healthy subjects. The severe group exhibited a significant increase in serum ALT, AST and IL-6 and a significant decrease in albumin, IL-1ß, TXA2, and NF-κB p65 levels compared to the moderate group. In all patients (moderate and severe), all cytokines were positively correlated with NF-κB p50, NF-κB p65 and NRP-1 expression levels. Serum ALT and AST were positively correlated with CRP, cytokines (IL-4, IL-6, IL-18, IL-35 and TXA2), and NF-κB p50 and NF-κB p65 expression levels in both moderate and severe groups. They were also positively correlated with serum IL-1ß level in the severe COVID-19 patient group and with NRP-1 expression in the moderate group. Using the logistic regression analysis, the most important four statistically significant predictors associated with COVID-19 infection in the study were found to be IL-6, TAX2, NF-κB p50 and NF-κB p65. ROC analysis of these variables revealed that three of them had AUC > 0.8. In moderate cases, AUC of the serum TXA2 level and NF-κB p65 expression were 0.843 (95% CI 0.517−0.742, p < 0.001) and 0.806 (95% CI 0.739−0.874, p < 0.001), respectively. In the severe group, AUC of serum IL-6 level was 0.844 (95% CI 0.783−0.904, p < 0.001). Moreover, Il-6 had a sensitivity of 100% in both moderate and severe groups. Conclusions: This study concluded that liver injury in patients with COVID-19 may be strongly attributed to the cytokines storm, especially IL-6, which was positively correlated to NF-κB p50, NF-κB p65 and NRP-1 mRNA expression levels. Moreover, ROC analysis revealed that IL-6, TXA2, and NF-κB p65 could be useful in predicting the possibility of infection with COVID-19, and IL-6 could be of possible significance as a good predictor of the severity and disease progress. However, RT-qPCR for SARS-CoV-2 detection is essential to confirm infection and further clinical studies are required to confirm this elucidation.