The Pivotal Role of Galectin-3 in Viral Infection: A Multifaceted Player in Host-Pathogen Interactions.

Galectin-3 (Gal-3), a beta-galactoside-binding lectin, plays a pivotal role in various cellular processes, including immune responses, inflammation, and cancer progression. This comprehensive review aims to elucidate the multifaceted functions of Gal-3, starting with its crucial involvement in viral entry through facilitating viral attachment and catalyzing internalization. Furthermore, Gal-3 assumes significant roles in modulating immune responses, encompassing the activation and recruitment of immune cells, regulation of immune signaling pathways, and orchestration of cellular processes such as apoptosis and autophagy. The impact of Gal-3 extends to the viral life cycle, encompassing critical phases such as replication, assembly, and release. Notably, Gal-3 also contributes to viral pathogenesis, demonstrating involvement in tissue damage, inflammation, and viral persistence and latency elements. A detailed examination of specific viral diseases, including SARS-CoV-2, HIV, and influenza A, underscores the intricate role of Gal-3 in modulating immune responses and facilitating viral adherence and entry. Moreover, the potential of Gal-3 as a biomarker for disease severity, particularly in COVID-19, is considered. Gaining further insight into the mechanisms and roles of Gal-3 in these infections could pave the way for the development of innovative treatment and prevention options for a wide range of viral diseases.

Increased Pro Th1 And Th17 Transcriptional Activity In Patients With Severe COVID-19.

Background: COVID-19 is known to disrupt immune response and induce hyperinflammation that could potentially induce fatal outcome of the disease. Until now, it is known that interplay among cytokines is rather important for clinical presentation and outcome of COVID-19. The aim of this study was to determine transcriptional activity and functional phenotype of T cells and the relationship between pro- and anti-inflammatory cytokines and clinical parameters of COVID-19 severity. Methods: All recruited patients met criteria for COVID-19 are were divided in four groups according to disease severity. Serum levels of IL-12, IFN-γ, IL-17 and IL-23 were measured, and flow cytometry analysis of T cells from peripheral blood was performed. Results: Significant elevation of IL-12, IFN-γ, IL-17 and IL-23 in stage IV of the disease has been revealed. Further, strong intercorrelation between IL-12, IFN-γ, IL-17 and IL-23 was also found in stage IV of the disease, marking augmented Th1 and Th17 response. Analyses of T cells subsets indicate a noticeable phenotype change. CD4+, but not CD8+ T cells expressed increased transcriptional activity through increased expression of Tbet and RORγT, accompanied with increased percentage of IFN-γ and IL-17 producing T cells. Conclusion: Our results pose a novel hypothesis of the underlying mechanism behind deteriorating immune response in severe cases of COVID-19.

Galectin-3 as an important prognostic marker for COVID-19 severity.

Galectin-3 (Gal-3), multifunctional protein plays important roles in inflammatory response, infection and fibrosis. The goal of study was to determine the association of Gal-3, immune response, clinical, biochemical, and radiographic findings with COVID-19 severity. Study included 280 COVID-19 patients classified according to disease severity into mild, moderate, severe and critical group. Cytokines, clinical, biochemical, radiographic data and peripheral blood immune cell make up were analyzed. Patients in critical group had significantly higher serum level of Gal-3, IL-1ß, TNF-α, IL-12, IL-10 compared to the patients in less severe stages of disease. Strong positive correlation was detected between Gal-3 and IL-1ß, moderate positive correlation between Gal-3, TNF-α and IL-12, moderate negative correlation between Gal-3, IL-10/IL-1ß and IL-10/TNF-α. Moderate positive correlation noted between Gal-3 and urea, D dimer, CXR findings. Strong negative correlation detected between Gal-3 and p02, Sa02, and moderate negative correlation between Gal-3, lymphocyte and monocyte percentage. In the peripheral blood of patients with more severe stages of COVID-19 we detected significantly increased percentages of CD56- CD3+TNF-α+T cells and CD56- CD3+Gal-3+T cells and increased expression of CCR5 in PBMCs. Our results predict Gal-3 as an important marker for critical stage of COVID-19. Higher expression of Gal-3, TNF-α and CCR5 on T cells implicate on promoting inflammation and more severe form of disease.

Galectin-1 as the new player in staging and prognosis of COVID-19.

A new virus from the group of coronaviruses was identified as the cause of atypical pneumonia and called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and disease called Corona Virus Disease (COVID-19). During the cytokine storm, the main cause of the death, proinflammatory cytokines are released which stimulate further tissue destruction. Galectin-1 (Gal-1) is a pleiotropic cytokine involved in many immune and inflammatory processes and its role in COVID-19 is still unknown. The aim of this study was to determine systemic values of Gal-1 and correlations between Gal-1 and proinflammatory cytokines and clinical parameters during COVID-19 progression. This is observational and cross-sectional study. 210 COVID-19 patients were included and divided into mild, severe or critical group according to COVID-19 severity. Serum levels of IL-1ß, IL-6, IL-10, IL-23, IL-33 and Gal-1 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Systemic levels of IL-1ß, IL-6, IL-10, IL-23, IL-33 and Gal-1 were significantly higher in stage III of COVID-19 patients compared to stage I and II. There were no significant differences in the ratio between Gal-1 and IL-10 with proinflammatory cytokines. Positive correlation was detected between Gal-1 and IL-1ß, IL6, IL-10, IL-23 and IL-33. Gal-1 positively correlated with chest radiographic finding, dry cough and headache and negatively correlated with normal breathing sound. Linear regression model and ROC curve analysis point on Gal-1 as significant predictor for COVID-19 severity. Presented results implicate on Gal-1 and IL-10 dependent immunomodulation. The precise mechanism of Gal-1 effect in COVID-19 and its potential as a stage marker of disease severity is still to be clarified.

IL 33 Correlates With COVID-19 Severity, Radiographic and Clinical Finding.

Objective: The increased level of interleukin (IL)-33 is considered as a predictor of severe coronavirus disease 2019 (COVID-19) infection, but its role at different stages of the disease is still unclear. Our goal was to analyze the correlation of IL-33 and other innate immunity cytokines with disease severity. Methods: In this study, 220 patients with COVID-19 were included and divided into two groups, mild/moderate and severe/critical. The value of the cytokines, clinical, biochemical, radiographic data was collected and their correlation with disease severity was analyzed. Results: Most patients in the severe/critical group were male (81.8%) and older (over 64.5 years). We found a statistically significant difference (p < 0.05) in these two groups between clinical features (dyspnea, dry cough, fatigue, and auscultatory findings); laboratory [(neutrophil count, lymphocyte count, monocyte count, hemoglobin, plasma glucose, urea, creatinine, total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), albumin (ALB), lactate dehydrogenase (LDH), creatinine kinase (CK), D-dimer, C-reactive protein (CRP), procalcitonin (PCT), Fe, and Ferritin)], arterial blood gases (oxygen saturation-Sa02, partial pressure of oxygen -p02), and chest X-rays (CXR) lung findings (p = 0.000). We found a significantly higher serum concentration (p < 0.05) of TNF-α, IL-1ß, IL-6, IL-12, IL-23, and IL-33 in patients with COVID-19 with severe disease. In the milder stage of COVID-19, a positive correlation was detected between IL-33 and IL-1ß, IL-12 and IL-23, while a stronger positive correlation between the serum values of IL-33 and TNF-α, IL-1ß, IL-6, and IL-12 and IL-23 was detected in patients with COVID-19 with severe disease. A weak negative correlation (p < 0.05) between pO2 and serum IL-1ß, IL-12, and IL-33 and between SaO2 and serum IL-33 was noted. The positive relation (p < 0.05) between the serum values of IL-33 and IL-12, IL-33 and IL-6, and IL-6 and IL-12 is proven. Conclusion: In a more progressive stage of COVID-19, increased IL-33 facilitates lung inflammation by inducing the production of various innate proinflammatory cytokines (IL-1ß, IL-6, TNF-α, IL-12, and IL-23) in several target cells leading to the most severe forms of the disease. IL-33 correlates with clinical parameters of COVID-19 and might represent a promising marker as well as a therapeutic target in COVID-19.