Correlations between Kidney and Heart Function Bioindicators and the Expressions of Toll-Like, ACE2, and NRP-1 Receptors in COVID-19

Sultan, Rabab Hussain; Elesawy, Basem H.; Ali, Tarek M.; Abdallah, Maged; Assal, Hebatallah Hany; Ahmed, Amr E.; Ahmed, Osama M.

doi:10.3390/vaccines10071106

Cited by 13 publications

(9 citation statements)

References 64 publications

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“…Upregulated NRP-1 is related to deterioration of renal function. This was verified by the significant correlation between NRP-1 expression and serum creatinine and urea levels in severe COVID-19 patients ( 32 , 77 ). The consumption of NRP-1 after infection may lead to impaired podocyte function and aggravate DKD ( 78 ).…”

Section: Dkd and Covid-19mentioning

confidence: 63%

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An update on the interaction between COVID-19, vaccines, and diabetic kidney disease

Yang

Zou

2022

Front. Immunol.

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Up to now, coronavirus disease 2019 (COVID-19) is still affecting worldwide due to its highly infectious nature anrapid spread. Diabetic kidney disease (DKD) is an independent risk factor for severe COVID-19 outcomes, and they have a certain correlation in some aspects. Particularly, the activated renin–angiotensin–aldosterone system, chronic inflammation, endothelial dysfunction, and hypercoagulation state play an important role in the underlying mechanism linking COVID-19 to DKD. The dipeptidyl peptidase-4 inhibitor is considered a potential therapy for COVID-19 and has similarly shown organ protection in DKD. In addition, neuropilin-1 as an alternative pathway for angiotensin-converting enzyme 2 also contributes to severe acute respiratory syndrome coronavirus 2 entering the host cells, and its decreased expression can affect podocyte migration and adhesion. Here, we review the pathogenesis and current evidence of the interaction of DKD and COVID-19, as well as focus on elevated blood glucose following vaccination and its possible mechanism. Grasping the pathophysiology of DKD patients with COVID-19 is of great clinical significance for the formulation of therapeutic strategies.

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Section: Dkd and Covid-19mentioning

confidence: 63%

“…Sultan et al. reported that both expressions of TLR2, TLR4 mRNA, and NRP-1 were elevated in moderate and severe COVID-19 patients, and the NRP-1 level was positively correlated with TLR2 and TLR4 ( 77 ). Upregulated NRP-1 is related to deterioration of renal function.…”

Section: Dkd and Covid-19mentioning

confidence: 99%

An update on the interaction between COVID-19, vaccines, and diabetic kidney disease

Yang

Zou

2022

Front. Immunol.

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“…In addition, the clinical symptoms of COVID-19 infection were confirmed by the Physician. The confirmed COVID-19 patients were categorized into two groups, moderate and severe, according to the guidelines for diagnosis and management of COVID-19 released by National Health Commission of China [ 25 ] and also according to our previous publications [ 14 , 15 ]. Patients in the group had symptoms such as fever and respiratory tract symptoms and pneumonia manifestation, which were seen in imaging.…”

Section: Methodsmentioning

confidence: 99%

“…NRP-1 is implicated in several aspects of a SARS-CoV-2 infection, including possible spread through the olfactory bulb and into the central nervous system (CNS) and increased NRP-1 RNA expression in lungs of severe COVID-19 [ 13 ]. Recently, it was found that impairment of renal and cardiac function biomarkers in serum might be the result of a cytokine storm and an increase in the expression of ACE-2 and NRP-1 in COVID-19 patients [ 14 , 15 ]. Understanding how SARS-CoV-2 enters and spreads throughout human organs is important for developing preventative and therapy measures.…”

Section: Introductionmentioning

confidence: 99%

Correlations between Cytokine Levels, Liver Function Markers, and Neuropilin-1 Expression in Patients with COVID-19

et al. 2022

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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)-1β, 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-1β, 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-1β, 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-1β 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.

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“…The COVID-19 patients were split into two groups in accordance with the seventh edition of the Guidelines on the Diagnosis and Cure of COVID-19 published by the National Health Commission of China [ 10 ] and according our previous publications [ 9 , 11 , 12 ]. Thus, the study population include three groups (each of 50 individuals), which are healthy control, moderate COVID-19 and severe COVID-19 groups.…”

Section: Methodsmentioning

confidence: 99%

Relation between Cytokine Levels and Pulmonary Dysfunction in COVID-19 Patients: A Case-Control Study

Kazafy

Fouad

Said

et al. 2022

JPM

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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-1β, 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-1β) 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-1β, 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-1β, 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.

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Correlations between Kidney and Heart Function Bioindicators and the Expressions of Toll-Like, ACE2, and NRP-1 Receptors in COVID-19

Cited by 13 publications

References 64 publications

An update on the interaction between COVID-19, vaccines, and diabetic kidney disease

An update on the interaction between COVID-19, vaccines, and diabetic kidney disease

Correlations between Cytokine Levels, Liver Function Markers, and Neuropilin-1 Expression in Patients with COVID-19

Relation between Cytokine Levels and Pulmonary Dysfunction in COVID-19 Patients: A Case-Control Study

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