ABSTRACT
COVID-19 has severely affected the population of patients with end stage renal disease. Current data have proved a two-dose vaccination schedule against SARS-CoV-2 to be effective among dialyzed patients. There are limited data on the longevity and modulating factors of humoral response after vaccination. We performed a prospective longitudinal cohort study to determine longevity of the humoral response after SARS-CoV-2 vaccine. The study included 191 adult patients on hemodialysis and peritoneal dialysis. All participants had been vaccinated with three doses, either with BNT162b2 (Pfizer-BioNTech) (n = 109) or mRNA-1273 (Moderna) (n = 82). Anti-spike protein receptor-binding domain antibodies (anti-S IgG) were assessed using SARS-CoV-2 (RBD) IgG ELISA EIA-6150 IVD assay at baseline, on the 21st day and 43rd day, before a booster dose and two weeks thereafter. We found that before vaccination, 37.7% of the cohort had anti-S IgG titres concordant with seroconversion. After two-dose vaccination, seroconversion occurred in 97% of patients. The booster dose evoked a ~12-fold increase in antibody level. Obesity increased more than two-fold the odds for a decrease in anti-S IgG. Previous COVID-19 infection enhanced longevity of the humoral response following vaccination. In patients with previous COVID-19 infection, the BNT162b2 vaccine was associated with a higher odds of anti-S IgG waning compared to the mRNA-1273 vaccine. In conclusion, we report that obesity predisposes patients to protective antibody waning, hybrid immunity enhances odds for higher anti-S IgG concentrations and vaccine efficacy may be influenced by previous SARS-CoV-2 infection. The results might provide a rationale for vaccination protocol design.
ABSTRACT
Sclerostin (Scl) is implicated in vascular calcification and angiogenesis and localizes within vasculature. Its molecule incorporates a heparin-binding site that implies also binding to endothelial glycocalyx. We preliminary tested whether intravenous (IV) low-molecular-weight heparin enoxaparin can stimulate intravascular release of this calcification inhibitor in humans. Sixteen male volunteers were injected with a bolus of 1 mg/kg body weight of enoxaparin. After 10 minutes, plasma immunoreactive Scl levels increased uniformly by a mean of 184% versus baseline level of 0.56 ± 0.17 ng/mL ( P = .0004). Plasma Scl levels were found still elevated after 2 and 6 hours (with a median of 20.9% and 8.69%, respectively) and became normal after 24 hours. The percentage of increase (Δ) in plasma Scl after 10 minutes was directly correlated with enoxaparin dose per kg/m2 of body mass index (ρ = 0.587, P = .017) and strongly inversely correlated with the preinjection Scl levels (ρ = -0.747, P = .0008). A robust negative association between the ΔScl increase after 10 minutes and the ΔScl decrease after 2 hours versus 10 minutes was observed (ρ = -0.835, P < .0001). Complementary in vitro spiking experiment showed no effects of enoxaparin addition and whole blood incubation on plasma Scl levels when measured with the immunoassay. This study shows that enoxaparin has a stimulating effect on the intravascular release of calcification inhibitor Scl in healthy men. This novel pharmacological action of the popular anticoagulant drug seems important in cardiovascular medicine.
