Increases in expression of carbohydrate sulfotransferases CHST11 and CHST15 and decline in N-acetylgalactosamine-4-sulfatase (Arylsulfatase B, ARSB) require phospho-p38-MAPK following exposure to SARS-CoV-2 spike protein receptor binding domain in human a

Objective: Immunohistochemistry of post-mortem lung tissue from Covid-19 patients with diffuse alveolar damage demonstrated marked increases in chondroitin sulfate and CHST15 and decline in N-acetylgalactosamine-4-sulfatase. Studies were undertaken to identify the mechanisms involved in these effects. Method(s): Human primary small airway epithelial cells (PCS 301-010;ATCC) were cultured and exposed to the SARSCoV- 2 spike protein receptor binding domain (SPRBD;AA: Lys310-Leu560;Amsbio). Expression of the spike protein receptor, angiotensin converting enzyme 2 (ACE2), was enhanced by treatment with Interferon-beta. Promoter activation, DNA-binding, RNA silencing, QPCR, Western blots, ELISAs, and specific enzyme inhibitors were used to elucidate the underlying molecular mechanisms. Result(s): Treatment of the cultured cells by the SPRBD led to increased CHST15 and CHST11 expression and decline in ARSB expression. Sulfotransferase activity, total chondroitin sulfate, and sulfated glycosaminoglycan (GAG) content were increased. Phospho-T180/T182-p38-MAPK and phospho- S423/S425-Smad3 were required for the activation of the CHST15 and CHST11 promoters. Inhibition by SB203580, a phospho-p38 MAPK inhibitor, and by SIS3, a Smad3 inhibitor, blocked the CHST15 and CHST11 promoter activation. SB203580 reversed the SPRBD-induced decline in ARSB expression, but SIS3 had no effect on ARSB expression or promoter activation. Phospho-p38 MAPK was shown to reduce retinoblastoma protein (RB) S807/S811 phosphorylation and increase RB S249/T252 phosphorylation. E2F-DNA binding declined following exposure to SPRBD, and SB203580 reversed this effect. This indicates a mechanism by which SPRBD, phospho-p38 MAPK, E2F, and RB can regulate ARSB expression and thereby impact on chondroitin 4-sulfate and dermatan sulfate and molecules that bind to these sulfated GAGs, including Interleukin-8, bone morphogenetic protein-4, galectin-3 and SHP-2 (Src homology region 2-containing protein tyrosine phosphatase 2). Conclusion(s): The enzyme ARSB is required for the degradation of chondroitin 4-sulfate and dermatan sulfate, and accumulation of these sulfated GAGs can contribute to lung pathophysiology, as evident in Covid-19. Some effects of the SPRBD may be attributable to unopposed Angiotensin II, when Ang1-7 counter effects are diminished due to binding of ACE2 with the SARS-CoV-2 spike protein and reduced production of Ang1-7. Aberrant cell signaling and activation of the phospho-p38 MAPK and Smad3 pathways increase CHST15 and CHST11 production, which can contribute to increased chondroitin sulfate in infected cells. Decline in ARSB may occur as a consequence of effects of phospho-p38 MAPK on RB phosphorylation and E2F1 availability. Decline in ARSB and the resulting impaired degradation of sulfated GAGs have profound consequences on cellular metabolic, signaling, and transcriptional events. Funding is VA Merit Award.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Alzheimer's disease and COVID-19.

In elderly patients with COVID-19 cognitive functions decline;it has been suggested that SARS-CoV-2 infection may lead to the development of Alzheimer's disease (AD) and other long-term neurological consequences. We review several parallels between AD and COVID-19 in terms of pathogenetic mechanisms and risk factors. Possible mechanisms through which COVID-19 can initiate AD are discussed. These include systemic inflammation, hyperactivation of the renin-angiotensin system, innate immune activation, oxidative stress, and direct viral damage. It has been shown that increased expression of angiotensin-renin receptors (ACE2) may be a risk factor for COVID-19 in patients with AD. When entering the central nervous system, the SARS-CoV-2 virus can directly activate glial cell-mediated immune responses, which in turn can lead to the accumulation of beta-amyloid and the subsequent onset or progression of current AD. The involvement of inflammatory biomarkers, including interleukins (IL): IL6, IL1, as well as galectin-3, as a link between COVID-19 and AD is discussed. The rationale for the use of memantine (akatinol memantine) in patients with COVID-19 in order to prevent the development of cognitive deficits is discussed. Memantine has been shown to have a positive effect on neuroinflammatory processes in the onset or exacerbation of cognitive deficits, in reducing cerebral vasospasm and endothelial dysfunction in viral infections. Memantine therapy may improve everyday activity and reduce the risk of severe SARS-CoV-2 infection.Copyright © 2022 Ima-Press Publishing House. All rights reserved.

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.

Alzheimer's disease and COVID-19

In elderly patients with COVID-19 cognitive functions decline;it has been suggested that SARS-CoV-2 infection may lead to the development of Alzheimer's disease (AD) and other long-term neurological consequences. We review several parallels between AD and COVID-19 in terms of pathogenetic mechanisms and risk factors. Possible mechanisms through which COVID-19 can initiate AD are discussed. These include systemic inflammation, hyperactivation of the renin-angiotensin system, innate immune activation, oxidative stress, and direct viral damage. It has been shown that increased expression of angiotensin-renin receptors (ACE2) may be a risk factor for COVID-19 in patients with AD. When entering the central nervous system, the SARS-CoV-2 virus can directly activate glial cell-mediated immune responses, which in turn can lead to the accumulation of beta-amyloid and the subsequent onset or progression of current AD. The involvement of inflammatory biomarkers, including interleukins (IL): IL6, IL1, as well as galectin-3, as a link between COVID-19 and AD is discussed. The rationale for the use of memantine (akatinol memantine) in patients with COVID-19 in order to prevent the development of cognitive deficits is discussed. Memantine has been shown to have a positive effect on neuroinflammatory processes in the onset or exacerbation of cognitive deficits, in reducing cerebral vasospasm and endothelial dysfunction in viral infections. Memantine therapy may improve everyday activity and reduce the risk of severe SARS-CoV-2 infection.Copyright © 2022 Ima-Press Publishing House. All rights reserved.

Alzheimer's disease and COVID-19.

In elderly patients with COVID-19 cognitive functions decline;it has been suggested that SARS-CoV-2 infection may lead to the development of Alzheimer's disease (AD) and other long-term neurological consequences. We review several parallels between AD and COVID-19 in terms of pathogenetic mechanisms and risk factors. Possible mechanisms through which COVID-19 can initiate AD are discussed. These include systemic inflammation, hyperactivation of the renin-angiotensin system, innate immune activation, oxidative stress, and direct viral damage. It has been shown that increased expression of angiotensin-renin receptors (ACE2) may be a risk factor for COVID-19 in patients with AD. When entering the central nervous system, the SARS-CoV-2 virus can directly activate glial cell-mediated immune responses, which in turn can lead to the accumulation of beta-amyloid and the subsequent onset or progression of current AD. The involvement of inflammatory biomarkers, including interleukins (IL): IL6, IL1, as well as galectin-3, as a link between COVID-19 and AD is discussed. The rationale for the use of memantine (akatinol memantine) in patients with COVID-19 in order to prevent the development of cognitive deficits is discussed. Memantine has been shown to have a positive effect on neuroinflammatory processes in the onset or exacerbation of cognitive deficits, in reducing cerebral vasospasm and endothelial dysfunction in viral infections. Memantine therapy may improve everyday activity and reduce the risk of severe SARS-CoV-2 infection.Copyright © 2022 Ima-Press Publishing House. All rights reserved.

Galectin-3 as a Marker for Increased Thrombogenicity in COVID-19.

Galectin-3 is a beta-galactoside-binding lectin involved in inflammation and lung fibrosis and postulated to enhance thrombosis. In COVID-19, it is considered to be a prognostic marker of severity. The aim of this study was to evaluate whether galectin-3 is associated with thrombogenicity in COVID-19. Patients with moderate-to-severe COVID-19 (COVpos; n = 55) and patients with acute respiratory diseases, but without COVID-19 (COVneg; n = 35), were included in the study. We measured the amount of galectin-3, as well as other platelet and coagulation markers, and correlated galectin-3 levels with these markers of thrombogenicity and with the SOFA Score values. We found that galectin-3 levels, as well as von Willebrand Factor (vWF), antithrombin and tissue plasminogen activator levels, were higher in the COVpos than they were in the COVneg cohort. Galectin-3 correlated positively with vWF, antithrombin and D-dimer in the COVpos cohort, but not in the COVneg cohort. Moreover, galactin-3 correlated also with clinical disease severity, as measured by the SOFA Score. In patients with acute respiratory diseases, galectin-3 can be considered as a marker not only for disease severity, but also for increased hypercoagulability. Whether galectin-3 might be a useful therapeutic target in COVID-19 needs to be assessed in future studies.

Galectin-3 as a possible marker for increased thrombogenicity in COVID-19

Background: Galectin-3 is a beta-galactoside-binding lectin that has been described to be overexpressed in inflammation, atherosclerosis, and in myocardial fibrosis. In COVID-19, galectin-3 has been proposed as an important regulator of the inflammatory response and fibrosis processes. The role of galectin-3 as a platelet activator and thrombosis enhancer has been also recently described. However, the role of galectin-3 in the thrombotic risk in COVID-19 hasn't been studied extensively. Method(s): Patients with moderate to severe COVID-19 were included in the study. Hospitalized patients with acute respiratory diseases without COVID-19 were examined as controls. We compared the levels of galectin- 3, soluble ST2, tissue factor and tissue factor activity (TFa) as well as several other markers of increased thrombogenicity in both groups. The correlations between galectin-3 and coagulation as well as inflammation markers were assessed. The SOFA score was used as a marker for the clinical outcome. Result(s): 93 patients were included into the study of which 56 were SARS-CoV-2 positive (COV+) and 37 were SARS-CoV-2 negative controls (COV-). Galectin-3 levels were higher in the COV+ group (median 7.10 ng/ml [IQR 4.61-9.81] vs. 5.47 ng/ml [3.63-6.66] p=0.016) as well as the TFa (median 334.48 pM [115.19-632.58] vs. 134.02 pM [86.92- 206.66]) and the ST2 levels (median 5.49 ng/ml [2.40-9.28] vs. 2.19 ng/ml [0.66-3.91] p<0.001). We also observed a positive correlation between galectin-3 and IL-6 (r=0.559, p<0.001), ST2 (r=0.332, p=0.005), SOFA score (r=0.441, p=0.003), von Willebrand factor (r=0.401, p<0.001), plasminogen (r=0.361, p=0.001), antithrombin (r=0.453, p<0.001), and Ddimer (r=0.377, p=0.001). Conclusion(s): In patients with acute respiratory diseases, especially with COVID-19, galectin-3 is a marker for increased hypercoagulability and worse clinical outcome. Galactin-3 might be a useful therapeutic target for patients with COVID-19.

Evaluation of Salivary Galectin-3 Level and its Potential Role in Increasing the Severity of COVID-19 Infection in Patients with Periodontitis

Aim: To evaluate and compare the salivary galectin-3 (Gal-3) level in chronic periodontitis patients, coronavirus disease 2019 (COVID-19) patients, and patients with COVID-19 + periodontitis and thus determining the risk of periodontitis in increasing the severity of COVID-19 infection. Materials and methods: For the present study, a total of 77 participants were recruited to the study with 20 healthy controls (group I), 20 patients with chronic generalized periodontitis (group II), 19 COVID-19 patients (group III), and 18 with COVID-19 and periodontitis (group IV). Demographic characteristics and periodontal clinical parameters like plaque index (PI), probing pocket depth (PPD), and clinical attachment level (CAL) were recorded for all patients. Saliva samples were collected and Gal-3 levels were assessed using enzyme-linked immunosorbent assay (ELISA) kit. One-way analysis of variance (ANOVA) analysis and Tukey's honest significant difference post hoc tests were carried out for data analysis. Results: Group IV patients had a higher concentration of salivary Gal-3 (15.50 ng/mL) than that of group III (10.247 ng/mL) and group II (12.340 ng/mL), and the mean difference in Gal-3 level was statistically significant with the p-value 0.000. The mean PPD, CAL, and PI were significantly high in groups II and IV compared to groups I and II with a p-value of 0.000. Conclusion: The result of the present study showed that patients with periodontitis and periodontitis + COVID-19 presented significant higher salivary Gal-3 levels in comparison with COVID-19 patients and healthy subjects. Thus periodontitis can be a risk factor in increasing the severity of COVID-19 infection. Clinical significance: This study was carried out to evaluate whether periodontitis is a risk factor for increasing the severity of COVID-19 infection. This study also highlights the importance of maintaining good oral hygiene and periodontal health in preventing COVID-19 severity. © The Author(s). 2023.

An Oral Galectin Inhibitor in COVID-19-A Phase II Randomized Controlled Trial.

BACKGROUND: SARS-CoV-2 vaccines play an important role in reducing disease severity, hospitalization, and death, although they failed to prevent the transmission of SARS-CoV-2 variants. Therefore, an effective inhibitor of galectin-3 (Gal-3) could be used to treat and prevent the transmission of COVID-19. ProLectin-M (PL-M), a Gal-3 antagonist, was shown to interact with Gal-3 and thereby prevent cellular entry of SARS-CoV-2 in previous studies. AIM: The present study aimed to further evaluate the therapeutic effect of PL-M tablets in 34 subjects with COVID-19. METHODS: The efficacy of PL-M was evaluated in a randomized, double-blind, placebo-controlled clinical study in patients with mild to moderately severe COVID-19. Primary endpoints included changes in the absolute RT-PCR Ct values of the nucleocapsid and open reading frame (ORF) genes from baseline to days 3 and 7. The incidence of adverse events, changes in blood biochemistry, inflammatory biomarkers, and levels of antibodies against COVID-19 were also evaluated as part of the safety evaluation. RESULTS: PL-M treatment significantly (p = 0.001) increased RT-PCR cycle counts for N and ORF genes on days 3 (Ct values 32.09 ± 2.39 and 30.69 ± 3.38, respectively) and 7 (Ct values 34.91 ± 0.39 and 34.85 ± 0.61, respectively) compared to a placebo treatment. On day 3, 14 subjects in the PL-M group had cycle counts for the N gene above the cut-off value of 29 (target cycle count 29), whereas on day 7, all subjects had cycle counts above the cut-off value. Ct values in placebo subjects were consistently less than 29, and no placebo subjects were RT-PCR-negative until day 7. Most of the symptoms disappeared completely after receiving PL-M treatment for 7 days in more patients compared to the placebo group. CONCLUSION: PL-M is safe and effective for clinical use in reducing viral loads and promoting rapid viral clearance in COVID-19 patients by inhibiting SARS-CoV-2 entry into cells through the inhibition of Gal-3.

GALACTIC-1: Galectin-3 inhibition in idiopathic pulmonary fibrosis (IPF) - rationale, objectives and design of a 52-week, Phase IIb study of GB0139

Availability of well-tolerated novel agents that can slow or stop disease progression and improve quality of life remain an unmet medical need in IPF management. GB0139, a novel inhaled galectin-3 inhibitor, has shown good tolerability and antifibrotic potential via changes in biomarkers associated with IPF progression in an animal model (Delaine, T. et al. Chembiochem 2016;17:1759-70) and a Phase I study (Hirani, N. et al. Eur Respir J 2021;57(5):2002559) in healthy participants and IPF patients. We report the design of a Phase IIb study of GB0139 in IPF. This randomised, double-blind, placebo-controlled, parallel-group, multicentre study (NCT03832946) was initiated in April 2019. The primary endpoint is rate of decline in forced vital capacity (FVC) over 52 weeks. Key secondary endpoints are proportion of participants with an absolute decline from baseline in FVC % predicted of <=10%, change from baseline in St. George's Respiratory Questionnaire total score, time to first respiratory-related hospitalisation, and time to death (all-causes). Systemic GB0139 pharmacokinetics are included as an exploratory endpoint. Despite the COVID-19 pandemic, study recruitment has continued in ~100 centres across 15 countries, with over 400 participants randomised as of February 2022. Initially, participants treated with or without standard of care (SOC) were included. Following a protocol amendment in 2021, the current target is to randomise 141 participants who are not treated with SOC, with study completion in mid-2023.

Distribution of sequelae in post-covid patients according to previous need of respiratory support

Introduction: "Long COVID" is defined by the persistence of symptoms after 4-12 weeks from COVID-19 disease. Data comparing different clinical phenotypes according to COVID-19 severity are still scanty. Aims and objectives: We aimed to identify different clinical phenotypes of post-COVID syndrome according to the level of respiratory support used. Method(s): We enrolled 309 patients who previously suffered from COVID-19 disease. All patients performed routine blood tests, arterial blood gas analysis, 6 minute walking test and body plethysmography. Then, we assigned each patient to a "severity group" according to the respiratory support needed during COVID-19 disease. Severity group 0: no respiratory support needed Severity group 1: oxygen only Severity group 2: positive airway pressure (CPAP or NIV) Severity group 3: Invasive Mechanical Ventilation (IMV) Results: Patients belonging to Group 0 experienced less fatigue (p=0.004) and mood disorders (p=0.007) compared to the other groups. Group 0 and 3 reported less frequently insomnia (p<0.0001). Hospitalized patients developed sleep and mood disorders during hospitalization due to several factors (fear, acoustic/visual triggers ect.). Patients who underwent IMV, instead, were completely sedated for the entire course of the acute phase of the disease, not being exposed to these triggers. Among blood markers, only Galectin-3 (p=0.004) and IL6 (p=0.004) had significant lower serum concentrations in patients belonging to Group 0, confirming their lower inflammatory status Conclusion(s): Awake hospitalization seems to deeply affect post-COVID sequelae in several patients.

90K/Mac-2 BP Is a New Predictive Biomarker of Response to Infliximab Therapy in IBD Patients.

Inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and Ulcerative Colitis (UC), are multifactorial disorders characterized by a chronic inflammatory status with the secretion of cytokines and immune mediators. Biologic drugs targeting pro-inflammatory cytokines, such as infliximab, are broadly used in the treatment of IBD patients, but some patients lose responsiveness after an initial success. The research into new biomarkers is crucial for advancing personalized therapies and monitoring the response to biologics. The aim of this single center, observational study is to analyze the relationship between serum levels of 90K/Mac-2 BP and the response to infliximab, in a cohort of 48 IBD patients (30 CD and 18 UC), enrolled from February 2017 to December 2018. In our IBD cohort, high 90K serum levels were found at baseline in patients who then developed anti-infliximab antibodies at the fifth infusion (22 weeks after the first), becoming non-responders (9.76 ± 4.65 µg/mL compared to 6.53 ± 3.29 µg/mL in responder patients, p = 0.005). This difference was significant in the total cohort and in CD, but not significant in UC. We then analyzed the relationship between serum levels of 90K, C-reactive protein (CRP), and Fecal calprotectin. A significant positive correlation was found at baseline between 90K and CRP, the most common serum inflammation marker (R = 0.42, p = 0.0032). We concluded that circulating 90K could be considered a new non-invasive biomarker for monitoring the response to infliximab. Furthermore, 90K serum level determination, before the first infliximab infusion, in association with other inflammatory markers such as CRP, could assist in the choice of biologics for the treatment of IBD patients, thereby obviating the need for a drug switch due to loss of response, and so improving clinical practice and patient care.

An Inhaled Galectin-3 Inhibitor in COVID-19 Pneumonitis (DEFINE): A Phase Ib/IIa Randomised Controlled Trial.

RATIONALE: High circulating galectin-3 is associated with poor outcomes in patients with COVID-19. We hypothesised that GB0139, a potent inhaled thiodigalactoside galectin-3 inhibitor with anti-inflammatory and antifibrotic actions, would be safely and effectively delivered in COVID-19 pneumonitis. OBJECTIVES: Primary outcomes were safety and tolerability of inhaled GB0139 as an add-on therapy for patients hospitalised with COVID-19 pneumonitis. METHODS: We present the findings of two arms of a phase Ib/IIa randomised controlled platform trial in hospitalised patients with confirmed COVID-19 pneumonitis. Patients received standard of care (SoC) or SoC plus 10 mg inhaled GB0139 twice daily for 48 hours, then once daily for up to 14 days or discharge. RESULTS: Data are reported from 41 patients, 20 of which were assigned randomly to receive GB0139. PRIMARY OUTCOMES: the GB0139 group experienced no treatment-related serious adverse events. Incidences of adverse events were similar between treatment arms (40 with GB0139+SoC vs 35 with SoC). SECONDARY OUTCOMES: plasma GB0139 was measurable in all patients after inhaled exposure, and demonstrated target engagement with decreased circulating galectin (overall treatment effect post-hoc ANCOVA over days 2-7: p=0.0099 vs SoC). Plasma biomarkers associated with inflammation, fibrosis, coagulopathy and major organ function were evaluated. CONCLUSIONS: In COVID pneumonitis, inhaled GB013 was well-tolerated, achieved clinically relevant plasma concentrations with target engagement. The data support larger clinical trials to determine clinical efficacy. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT04473053. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Exercise modulation in inflammation and metabolic hormonal disorders of COVID-19 to decrease risk factors in coronary heart disease.

OBJECTIVES: Sedentary life style separated during COVID-19 pandemic. Patients with cardiovascular diseases (CVD) are vulnerable with sedentary life style. Therefore, the aim of this study was to investigate the effect of 8 weeks of combined and high intensity interval training (HIIT) on C Reactive protein, galectin-3, leptin, fibrinogen and insulin resistance index in coronary heart disease after COVID-19. METHODS: Thirty-six cardiovascular patients (55.14 ± 1.4 years, 78.6 ± 5.1 kg) were divided into three groups of combined exercise (n=13), HIIT (n=12) and control group (n=11). Combined exercise consisted of aerobic (4 weeks) and aerobic + HIIT exercise (4 weeks), three sessions per weeks. The protocol of the HIIT group included performing high intensity interval training, three sessions per weeks for 8 weeks. Blood samples were taken 24 h before the first training session and 48 h after the last training. C Reactive protein (CRP), galectin-3, leptin, fibrinogen measured with ELISA kit. RESULTS: CRP, galectin-3 and fibrinogen decreased significantly after 8 weeks of combined training and HIIT (compare to pre-test). Also, insulin resistance index after 8 weeks of combined exercise showed a significant decrease compare to pre-test (p<0.05). After 8 weeks, CRP, galectin-3 and insulin resistance significantly decreased compare to control group (p<0.05). CONCLUSIONS: In the patient with CVD, combined exercise training may be more effective than HIIT in reducing metabolic and heart risk factors after an epidemic such as COVID-19. However, change of leptin need to more studies.

Efficacy of serum apelin and galectin-3 as potential predictors of mortality in severe COVID-19 patients.

Apelin is a cardioprotective biomarker while galectin-3 is a pro-inflammatory and profibrotic biomarker. Endothelial dysfunction, hyperinflammation, and pulmonary fibrosis are key mechanisms that contribute to the development of adverse outcomes in Coronavirus disease 2019 (COVID-19) infection. This study aims to analyze the prognostic value of serum apelin and galectin-3 levels to early predict patients at high risk of mortality in patients hospitalized for severe COVID-19 pneumonia. The study included 78 severe COVID-19 patients and 40 healthy controls. The COVID-19 patients were divided into two groups, survivors and nonsurvivors, according to their in-hospital mortality status. Basic demographic and clinical data of all patients were collected, and blood samples were taken before treatment. In our study, serum apelin levels were determined to be significantly lower in both nonsurvivor and survivor COVID-19 patients compared to the control subjects (for both groups, p < 0.001). However, serum apelin levels were similar in survivor and nonsurvivor COVID-19 patients (p > 0.05). Serum galectin-3 levels were determined to be higher in a statistically significant way in nonsurvivors compared to survivors and controls (for both groups; p < 0.001). Additionally, serum galectin-3 levels were significantly higher in the survivor patients compared to the control subjects (p < 0.001). Positive correlations were observed between galectin-3 and age, ferritin, CK-MB and NT-proBNP variables (r = 0.32, p = 0.004; r = 0.24, p = 0.04; r = 0.24, p = 0.03; and r = 0.33, p = 0.003, respectively) while a negative correlation was observed between galectin-3 and albumin (r = -0.31, p = 0.006). Multiple logistic regression analysis revealed that galectin-3 was an independent predictor of mortality in COVID-19 patients (odds ratio [OR] = 2.272, 95% confidence interval [CI] = 1.106-4.667; p = 0.025). When the threshold value for galectin-3 was regarded as 2.8 ng/ml, it was discovered to predict mortality with 80% sensitivity and 57% specificity (area under the curve = 0.738, 95% CI = 0.611-0.866, p = 0.002). Galectin-3 might be a simple, useful, and prognostic biomarker that can be utilized to predict patients who are at high risk of mortality in severe COVID-19 patients.

Complement and endothelial cell activation in COVID-19 patients compared to controls with suspected SARS-CoV-2 infection: A prospective cohort study.

Background: Thromboinflammation may influence disease outcome in COVID-19. We aimed to evaluate complement and endothelial cell activation in patients with confirmed COVID-19 compared to controls with clinically suspected but excluded SARS-CoV-2 infection. Methods: In a prospective, observational, single-center study, patients presenting with clinically suspected COVID-19 were recruited in the emergency department. Blood samples on presentation were obtained for analysis of C5a, sC5b-9, E-selectin, Galectin-3, ICAM-1 and VCAM-1. Results: 153 cases and 166 controls (suffering mainly from non-SARS-CoV-2 respiratory viral infections, non-infectious inflammatory conditions and bacterial pneumonia) were included. Hospital admission occurred in 62% and 45% of cases and controls, respectively. C5a and VCAM-1 concentrations were significantly elevated and E-selectin concentrations decreased in COVID-19 out- and inpatients compared to the respective controls. However, relative differences in outpatients vs. inpatients in most biomarkers were comparable between cases and controls. Elevated concentrations of C5a, Galectin-3, ICAM-1 and VCAM-1 on presentation were associated with the composite outcome of ICU- admission or 30-day mortality in COVID-19 and controls, yet more pronounced in COVID-19. C5a and sC5b-9 concentrations were significantly higher in COVID-19 males vs. females, which was not observed in the control group. Conclusions: Our data indicate an activation of the complement cascade and endothelium in COVID-19 beyond a nonspecific inflammatory trigger as observed in controls (i.e., "over"-activation).

Galectin-3 as a Potential Prognostic Biomarker for COVID-19 Disease: A Case-Control Study.

Background Recent studies have investigated the importance of Galetin-3 in inflammation, fibrosis, cell proliferation, cardiac disease, diabetes, and tumor formation. Aims This study aims to investigate the role of the Galectin-3 level in the diagnosis of COVID-19 pneumonia and the value of the Galectin-3 level in predicting the clinical course of the patient. Methods This study employed a prospective, case-control study design and was conducted at Bakircay University Cigli Training and Research Hospital. A total of 100 patients (40 had moderate and 60 had severe/critical COVID-19 disease according to World Health Organisation guidelines) and 50 non-symptomatic healthy volunteers participated in the study. Blood samples were taken from patients at the time of hospital admission, after which serum was isolated. Following the isolation of serum, Galectin-3 levels were evaluated using the enzyme-linked immunosorbent assay (ELISA) method.  Results The serum Galectin-3 level was measured as 13.57 (10.9-16.4) ng/mL in the control group, 13.52 (10.69-16.6) ng/mL in the moderate disease group, and 11.65 (6.09-14.33) ng/mL in the severe/critical disease group. Serum Galectin-3 levels were significantly lower in the severe/critical disease group compared to the control and moderate disease groups (p=0.001 and p=0.019, respectively). Using ROC analysis, a larger area under the curve (AUC) for the serum Galectin-3 levels of the control group (AUC=0.622, 95% CI =0.529-0.714; p=0.015) was calculated compared to the COVID-19 patient group for the diagnosis of COVID-19 disease. The Galectin-3 level was found to be 75% sensitive and 50% specific at a cut-off level of 11.3 ng/mL in predicting the need for ICU treatment. Conclusion Galectin-3 levels may be a beneficial biomarker in predicting the clinical severity of COVID-19 disease when used in conjunction with other known biomarkers, at the time of admission to the emergency department (ED).

Contributing Factors to Increased Left Ventricular End-Diastolic Volume in COVID-19 ICU Patients in Sanglah Hospital: A Study on Galectin-3

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory disease that has become the largest pandemic and also could put the heart at risk of dysfunction. Galectin-3 is involved in the inflammatory process that continues with remodeling and eventually fibrosis. Using galectin-3 examination, we could predict the possible worsening of heart function and evaluate data on influencing factors for increased left ventricular end-diastolic volume (LVEDV) which could later progress to heart failure. METHOD(S): This is an observational prospective analytic study in the COVID-19 ICU of Sanglah Hospital, Bali, Indonesia. The study was conducted from June to October 2021. All research subjects had their blood samples taken for galectin-3 levels examination using enzyme-linked immunosorbent assay (ELISA). Subjects were also evaluated for left ventricular end-diastolic volume (LVEDV) with echocardiography, SOFA scores, and troponin I levels. Subjects were treated with COVID-19 standard protocol established by the Ministry of Health. After 72 h post-admission, subjects were re-examined for galectin-3 levels and LVEDV. Data were analyzed using STATATM. RESULT(S): A total of 45 research subjects were analyzed. Bivariate analysis of the difference of galectin-3 and LVEDV was shown to be insignificant (r = 0.08), no correlation was found between galectin-3 level and LVEDV on ICU admission (r = 0.191), and no correlation found between galectin-3 level and LVEDV after 72 h of hospitalization (r=0.197). Multivariate analysis also showed that none of the variables, namely, difference of galectin-3 level, age, gender, troponin I, SOFA, and Charlson scores had statistically significant correlation with LVEDV (p < 0.05). CONCLUSION(S): No significant correlation was found between galectin-3 level and an increase in LVEDV. Copyright © 2022 Marilaeta Cindryani Lolobali, I. M. G. Widnyana, Ni Made Ayu Wulansari, Ida Bagus Rangga Wibhuti, Made Wiryana, Rudyanto Sedono, Aldy Heriwardito.