Association of COVID-19 Vaccines ChAdOx1-S and BNT162b2 with Circulating Levels of Coagulation Factors and Antithrombin.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is associated with increased risk of thrombosis and thromboembolism. Exposure to COVID-19 vaccines is also associated with immune thrombotic thrombocytopenia, ischemic stroke, intracerebral haemorrhage, and cerebral venous thrombosis, and it is linked with systemic activation of coagulation. METHODS: We assess the circulating levels of coagulation factors (factors XI, XII, XIII, and prothrombin) and antithrombin in individuals who completed two doses of either ChAdOx1-S or BNT162b2 COVID-19 vaccine, within the timeframe of two months, who had no previous history of COVID-19. RESULTS: Elevated levels of factors XI, XII, XIII, prothrombin, and antithrombin were seen compared to unvaccinated controls. Levels of coagulation factors, antithrombin, and prothrombin to antithrombin ratio were higher with BNT162b2 compared to ChAdOx1-S vaccine. CONCLUSIONS: The clinical significance of such coagulation homeostasis disruption remains to be elucidated but it is worthy of global scientific follow-up effort.

GALNT2 rs4846914 SNP Is Associated with Obesity, Atherogenic Lipid Traits, and ANGPTL3 Plasma Level.

N-Acetylgalactosaminyltransferase 2 (GALNT2) is associated with serum lipid levels, insulin resistance, and adipogenesis. Additionally, angiopoietin-like (ANGPTL) proteins have emerged as regulators of lipoprotein lipase and lipid metabolism. In this study, we evaluated the association between GALNT2 rs4846914 variant, known for its association with lipid levels in European cohorts, with plasma levels of ANGPTL proteins, apolipoproteins, lipids, and obesity traits in individuals of Arab ethnicity. GALNT2 rs4846914 was genotyped in a cohort of 278 Arab individuals from Kuwait. Plasma levels of ANGPTL3 and ANGPTL8 were measured by ELISA and apolipoproteins by Luminex multiplexing assay. Allele-based association tests were performed with Bonferroni-corrected p-value thresholds. The GALNT2 rs4846914_G allele was associated with increased ANGPTL3 (p-values ≤ 0.05) but not with ANGPTL8 plasma levels. The allele was associated significantly with higher BMI and weight (p-values < 0.003), increased ApoC1 levels (p-values ≤ 0.006), and reduced HDL levels (p-values ≤ 0.05). Individuals carrying the GG genotype showed significantly decreased HDL and increased BMI, WC, ApoC1, and TG. Interactions exist between (AG+GG) genotypes and measures of percentage body fat, ApoA1A, ApoC1, and ApoB48-mediated HDL levels. GALNT2 is confirmed further as a potential link connecting lipid metabolism and obesity and has the potential to be a drug target for treating obesity and dyslipidemia.

Robust Antibody Levels in Both Diabetic and Non-Diabetic Individuals After BNT162b2 mRNA COVID-19 Vaccination.

The emergence of effective vaccines for COVID-19 has been welcomed by the world with great optimism. Given their increased susceptibility to COVID-19, the question arises whether individuals with type-2 diabetes mellitus (T2DM) and other metabolic conditions can respond effectively to the mRNA-based vaccine. We aimed to evaluate the levels of anti-SARS-CoV-2 IgG and neutralizing antibodies in people with T2DM and/or other metabolic risk factors (hypertension and obesity) compared to those without. This study included 262 people (81 diabetic and 181 non-diabetic persons) that took two doses of BNT162b2 (Pfizer-BioNTech) mRNA vaccine. Both T2DM and non-diabetic individuals had a robust response to vaccination as demonstrated by their high antibody titers. However, both SARS-CoV-2 IgG and neutralizing antibodies titers were lower in people with T2DM. The mean ( ± 1 standard deviation) levels were 154 ± 49.1 vs. 138 ± 59.4 BAU/ml for IgG and 87.1 ± 11.6 vs. 79.7 ± 19.5% for neutralizing antibodies in individuals without diabetes compared to those with T2DM, respectively. In a multiple linear regression adjusted for individual characteristics, comorbidities, previous COVID-19 infection, and duration since second vaccine dose, diabetics had 13.86 BAU/ml (95% CI: 27.08 to 0.64 BAU/ml, p=0.041) less IgG antibodies and 4.42% (95% CI: 8.53 to 0.32%, p=0.036) fewer neutralizing antibodies than non-diabetics. Hypertension and obesity did not show significant changes in antibody titers. Taken together, both type-2 diabetic and non-diabetic individuals elicited strong immune responses to SARS-CoV-2 BNT162b2 mRNA vaccine; nonetheless, lower levels were seen in people with diabetes. Continuous monitoring of the antibody levels might be a good indicator to guide personalized needs for further booster shots to maintain adaptive immunity. Nonetheless, it is important that people get their COVID-19 vaccination especially people with diabetes.

Previous COVID-19 Infection and Antibody Levels After Vaccination.

Background: The emergence of new COVID-19 variants of concern coupled with a global inequity in vaccine access and distribution has prompted many public health authorities to circumvent the vaccine shortages by altering vaccination protocols and prioritizing persons at high risk. Individuals with previous COVID-19 infection may not have been prioritized due to existing humoral immunity. Objective: We aimed to study the association between previous COVID-19 infection and antibody levels after COVID-19 vaccination. Methods: A serological analysis to measure SARS-CoV-2 immunoglobulin (Ig)G, IgA, and neutralizing antibodies was performed on individuals who received one or two doses of either BNT162b2 or ChAdOx1 vaccines in Kuwait. A Student t-test was performed and followed by generalized linear regression models adjusted for individual characteristics and comorbidities were fitted to compare the average levels of IgG and neutralizing antibodies between vaccinated individuals with and without previous COVID-19 infection. Results: A total of 1,025 individuals were recruited. The mean levels of IgG, IgA, and neutralizing antibodies were higher in vaccinated subjects with previous COVID-19 infections than in those without previous infection. Regression analysis showed a steeper slope of decline for IgG and neutralizing antibodies in vaccinated individuals without previous COVID-19 infection compared to those with previous COVID-19 infection. Conclusion: Previous COVID-19 infection appeared to elicit robust and sustained levels of SARS-CoV-2 antibodies in vaccinated individuals. Given the inconsistent supply of COVID-19 vaccines in many countries due to inequities in global distribution, our results suggest that even greater efforts should be made to vaccinate more people, especially individuals without previous COVID-19 infection.

Increased Expression of Meteorin-Like Hormone in Type 2 Diabetes and Obesity and Its Association with Irisin.

Type 2 diabetes (T2D) is a growing pandemic associated with metabolic dysregulation and chronic inflammation. Meteorin-like hormone (METRNL) is an adipomyokine that is linked to T2D. Our objective was to evaluate the changes in METRNL levels in T2D and obesity and assess the association of METRNL levels with irisin. Overall, 228 Arab individuals were enrolled. Plasma levels of METRNL and irisin were assessed using immunoassay. Plasma levels of METRNL and irisin were significantly higher in T2D patients than in non-diabetic patients (p < 0.05). When the population was stratified based on obesity, METRNL and irisin levels were significantly higher in obese than in non-obese individuals (p < 0.05). We found a significant positive correlation between METRNL and irisin (r = 0.233 and p = 0.001). Additionally, METRNL and irisin showed significant correlation with various metabolic biomarkers associated with T2D and Obesity. Our data shows elevated METRNL plasma levels in individuals with T2D, further exacerbated with obesity. Additionally, a strong positive association was observed between METRNL and irisin. Further studies are necessary to examine the role of these proteins in T2D and obesity, against their ethnic background and to understand the mechanistic significance of their possible interplay.

Increased Level of Angiopoietin Like Proteins 4 and 8 in People With Sleep Apnea.

Objective: Obstructive sleep apnea (OSA) is a sleep disorder caused by the complete or partial obstruction of the upper airways. The worldwide prevalence of OSA is increasing due to its close association with obesity epidemic and multiple health complications, such as hypertension, cardiovascular disease, and Type 2 diabetes. Angiopoietin-like protein (ANGPTL)-4 and ANGPTL8 (betatrophin) have been suggested to play a role in the development of these diseases through their role in regulating the metabolism of plasma lipid molecules. This study was designed to evaluate ANGPTL4 and 8 levels in an OSA group and a control group to clarify the effect of OSA on ANGPTL4 and 8 levels. Methods: In total, 74 subjects were enrolled in this study, including 22 age- and body mass index (BMI)-matched controls with the Apnea Hypopnea Index (AHI) score of <5 events/h and 52 subjects with an AHI score of >5 events/h. Sleep apnea was assessed using a portable sleep test. ANGPTL4 and 8 levels were measured in plasma samples using enzyme-linked immunosorbent assay. Results: Mean AHI score (2.5 ± 1.6) in the control group was significantly lower than that in the OSA group (22.9 ± 17.9; p < 0.0001). Leptin, interleukin-(IL) 6, insulin, and HOMA-IR values were higher in the OSA group than in the control group. ANGPTL8 level was higher in the OSA group (1130.0 ± 108.61 pg/mL) than in the control group (809.39 ± 108.78 pg/mL; p = 0.041). Similarly, ANGPTL4 was higher in the OSA group (179.26 ± 12.89 ng/mL) than in the control group (142.63 ±7.99 ng/mL; p = 0.018). Conclusion: Our findings demonstrate that ANGPTL4 and 8 levels were increased in subjects with OSA, suggesting that the upregulation of these lipid metabolism regulators might play a role in lipid dysregulation observed in people with OSA.

Increased plasma and adipose tissue levels of ANGPTL8/Betatrophin and ANGPTL4 in people with hypertension.

BACKGROUND: Hypertension is a risk factor for both cardiovascular diseases (CVDs) and type 2 diabetes (T2D). Angiopoietin-like proteins (ANGPTLs), mainly ANGPTL3, ANGPTL4 and ANGPTL8, are associated with increased plasma lipid content due to their role in regulating the activity of lipoprotein lipase, a key enzyme in metabolism of the lipoprotein in circulation. Dyslipidaemia is a risk factor for hypertension development; however, the roles of ANGPTL3, ANGPTL4 and ANGPTL8 in subjects with hypertension have not yet been established. This study compared the plasma and adipose tissue levels of ANGPTL3, ANGPTL4 and ANGPTL8 in age- and body mass index-matched subjects with and without hypertension. METHODS: A total of 119 subjects, including 69 hypertensive and 50 non-hypertensive subjects, were enrolled. ANGPTL3, ANGPTL4 and ANGPTL8 plasma levels were measured by ELISA, whereas their levels in adipose tissue were assessed via real-time PCR. RESULTS: We found that ANGPTL4 (202.49 ± 17.44 ng/mL vs. 160.64 ± 10.36 ng/mL, p = 0.04) and ANGPTL8 levels (2310.96 ± 194.88 pg/mL vs. 1583.35 ± 138.27 pg/mL, p = 0.001) were higher in hypertensive subjects than non-hypertensive subjects. However, ANGPTL3 levels were not significantly different between the two populations. Similarly, ANGPTL4 and ANGPTL8 levels were also elevated in subjects with T2D and hypertension than in those with T2D but not hypertension. Additionally, people with highest tertiles of ANGPTL8 had higher odds of having hypertension (odd ratio [OR] = 3.8, 95% confidence interval [CI] = (1.5-9.8), p-Value = 0.005. Similar to its plasma levels, ANGPTL4 and ANGPTL8 were higher in adipose tissue. CONCLUSIONS: In conclusion, our data illustrate that ANGPTL4 and ANGPTL8 levels in both plasma and adipose tissues are increased in subjects with hypertension. The elevated levels of ANGPTL4 and ANGPTL8 in hypertensive subjects highlight their potential involvement, their potential role as biomarkers for hypertension and their therapeutic value in hypertension given their roles in regulating lipid metabolism.

Novel G6B gene variant causes familial autosomal recessive thrombocytopenia and anemia.

OBJECTIVE: To characterize the underlying genetic and molecular defects in a consanguineous family with lifelong blood disorder manifested with thrombocytopenia (low platelets count) and anemia. METHODS: Genetic linkage analysis, exome sequencing, and functional genomics were carried out to identify and characterize the defective gene. RESULTS: We identified a novel truncation mutation (p.C108*) in chromosome 6 open reading frame 25 (C6orf25) gene in this family. We also showed the p.C108* mutation was responsible for destabilizing the encoded truncated G6B protein. Unlike the truncated form, wild-type G6B expression resulted in enhanced K562 differentiation into megakaryocytes and erythrocytes. C6orf25, also known as G6B, is an effector protein for the key hematopoiesis regulators, Src homology region 2 domain-containing phosphatases SHP-1 and SHP-2. CONCLUSION: G6B seems to act through an autosomal recessive mode of disease transmission in this family and regarded as the gene responsible for the observed hematological disorder. This inference is well supported further by in vivo evidence where similar outcomes were reported from G6b-/- and SHP1/2 DKO mouse models.

Circulating ANGPTL8/Betatrophin Is Increased in Obesity and Reduced after Exercise Training.

OBJECTIVE: ANGPTL8 is a liver and adipose tissue produced protein that regulates the level of triglyceride in plasma as well as glucose homeostasis. This study was designed to evaluate the level of ANGPTL8 in obese and non-obese subjects before and after exercise training. METHODS: A total of 82 non-obese and 62 adult obese were enrolled in this study. Subjects underwent a three months of exercise training. Both full length and C-terminal 139-198 form of ANGPTL8 were measured by ELISA. RESULTS: Our data show that the full length ANGPTL8 level was increased in obese subjects (1150.04 ± 108.10 pg/mL) compared to non-obese (775.54 ± 46.12) pg/mL (p-Value = 0.002). C-terminal 139-198 form of ANGPTL8 was also increased in obese subjects 0.28 ± 0.04 ng/mL vs 0.20 ± 0.02 ng/mL in non-obese (p-value = 0.058). In obese subjects, the levels of both forms were reduced after three months of exercise training; full length was reduced from 1150.04 ± 108.10 pg/mL to 852.04 ± 51.95 pg/mL (p-Values 0.015) and c-terminal form was reduced from 0.28 ± 0.04 ng/mL to 0.19 ± 0.03 ng/mL (p-Value = 0.058). Interestingly, full length ANGPTL8 was positively associated with fasting blood glucose (FBG) in non-obese (r = 0.317, p-Value = 0.006) and obese subjects (r = 0.346, p-Value = 0.006) C-terminal 139-198 form of ANGPTL8 on the other hand, did not show any correlation in both groups. CONCLUSION: In conclusion, our data demonstrate that ANGPTL8 was increased in obesity and reduced after exercise training supporting the potential therapeutic benefit of reducing ANGPTL8. The various forms of ANGPTL8 associated differently with FBG suggesting that they have different roles in glucose homeostasis.