The aim of this investigation was to determine the effect of SARS-Cov-2 vaccination in hemodialysis patients, search for risk factors for non- or low-response, and to measure the effect of a third booster vaccination in non- or low-responders. Methods SARS-CoV-2 IgG antibodies and the virus-neutralizing capacity were measured 4–5 weeks after a full standard vaccination in 95 chronic hemodialysis patients and 60 controls. IgG titers > 30 AU/mL served to classify participants as responders. Multivariable binary logistic regression analysis was used to search for risk factors of reduced vaccination success. Patients with vaccination failure were offered a third booster dosage. Results 82.1% of the patient cohort as compared to 98.3% of the healthy control group were able to mount SARS-CoV-2 titers above 30 AU/mL after two standard vaccine doses. Mean IgG antibody titers were lower in hemodialysis patients than controls (78 ± 35 vs. 90 ± 20 AU/mL, p = 0.002). Multivariable binary logistic regression analysis showed age and immunosuppressive medication as major risk factors for vaccination failure with a decreased probability of successful vaccination of −6.1% (95% CI −1.2 to −10.9) per increase in age of one year and −87.4% (95% CI −98.0 to −21.5) in patients on immunosuppressive therapy (crude odds ratio for vaccination failure for immunosuppressive therapy 6.4). Ten out of 17 patients with non-response to vaccination were offered a third dose. Booster vaccination after the second dose induced an increase in effective antibody titers of >30 AU/mL in seven out of ten patients 4–5 weeks later (70%). Conclusion Standard SARS-CoV-2 vaccination schemes are highly effective in mounting protective neutralizing IgG antibodies in chronic hemodialysis patients. Nevertheless, response to vaccination is diminished as compared to a healthy control group. Major risk factors for vaccination failure are older age and immunosuppressive therapy. In non- or low-responders to standard vaccination a third booster vaccination was able to induce effective antibody titers in about 70% of patients, indicating that a third booster vaccination might be preferable to decreasing immunosuppressive therapy.

The aim of this study is to determine the effect of repeated vaccinations on neutralizing SARS-CoV-2 IgG antibody titers, evaluate risk factors for immunological non-response, and to report breakthrough infections in chronic hemodialysis patients. Methods: A prospective, multi-center cohort study in 163 chronic hemodialysis patients was conducted. Antibody titers were measured three months after second, third, and fourth (10 pts) booster vaccinations. SARS-CoV-2 neutralizing antibody titers in BAU/mL and % inhibition were divided into three categories (<216, 216–433, >433 and <33, 33–66, and >66%). Somers’s test, paired t-test, and univariable and multivariable logistic regression analysis were applied to evaluate differences in antibody levels and search for risk factors for vaccination failure defined as neutralizing titers <50% and/or need for repeated booster vaccinations. Furthermore, we report on a case series to describe characteristics of patients after four vaccinations (n = 10) and breakthrough infections (n = 20). Results: Third dose boosters resulted in higher proportions of patients with neutralizing antibody levels >66% as compared to after the second dose (64.7% after second dose vs. 88.9% after third dose, p = 0.003), as well as in a respective increase in neutralizing titer levels in % from 68 ± 33% to 89 ± 24 (p < 0.001). The proportion of patients with IgG-titers below 216 BAU/mL decreased from 38.6 to 10.5% (p ≤ 0.001). Age (p = 0.004, OR 1.066, 95% CI 1.020–1.114) and presence of immunosuppressive medications (p = 0.002, OR 8.267, 95% CI 2.206–30.975) were identified as major risk factors for vaccination failure. Repeated booster vaccinations ≥4 times were effective in 8 out of 10 former low-responders (80%) without any side effects or safety concerns. Breakthrough infections showed a clinically mild course but were associated with prolonged viral shedding on PCR-testing ranging 7–29 (mean 13) days. Conclusions: Third and fourth mRNA-based booster vaccinations resulted in higher and longer lasting SARS-CoV-2 antibody levels as compared to after two dosages. The presence of immunosuppressive medication and repeat vaccinations are major potentially modifiable measures to increase antibody levels in non-or low-responders. Breakthrough infections with SARS-CoV-2 Omicron were associated with prolonged viral shedding but clinically mild disease courses.

634th MEETING, BATH 963 tions in the pattern o f newly synthesized and secreted proteins. There appeared t o be three main modulations under the influence of the fucopolysaccharide. One occurred o n SDS/PAGE in the area o f low molecular mass proteins (below 46 kDa) and two alterations occurred in the area of high molecular mass proteins of 220 kDa and 180 kDa. These two proteins were identified as fibronectin and thrombospondin. lmmunoprecipitation and quantification revealed that the synthesis of fibronectin is reduced under the influence of fucoidan, whereas thrombospondin synthesis was increased (Fig. 1). The effect of fibronectin was not shared by heparin. Moreover, it could bc shown that desulphation of native fucoidan abolished the observed modulation o n fibronectin and thrombospondin. The effect o f fucoidan on the synthesis of the two extracellular matrix proteins is an early time event after addition of the fucopolysaccharide t o growth-stimulated smooth muscle cells. This argues for a connection between the observed influence o n cell proliferation and the modulation of the composition o f the extracellular matrix of smooth muscle cells.The observed differences in the modulation of extracellular matrix proteins by fucoidan compared with heparin suggest different pathways of the action o f both sulphatcd polysaccharides on smooth muscle cells. This investigation was supported by the Ikutsche Forschungsgemeinschaft (SFH 3 10). I . Clowes. A. & Karnovsky, M. J. ( 1977) Notrtri, ( I m i d o r i ) 265, 2. Castellot. Itisriliit fiir A rterioskIer~)sef~~rsc.hiiti~, Domrigksirrrsse 3, D-44M) Miitisler, I;. R. G.Much interest has been focused on endothelial and smooth muscle cells of the blood vessel wall. because the development of several pathogenic vascular diseases like thrombosis and atherosclerosis is closely connected with metabolic changes in these cells [ I ] . The glycoconjugate metabolism of thesc cells is only poorly understood. In an earlier investigation, we have reported on the biosynthesis o f N-acetelyneuraminic acid in cultured arterial wall cells [2]. In the present work. wc have investigated the metabolism of Lfucose in aortic tissue and cultured arterial wall cells.Two different pathways are known for the formation of GDP-fucose. The pathway for L-fucose synthesis de t m ' o uses GDP-mannose as a precursur t o form GDP-fucosc, whereas in the second pathway, a specific kinasc acts o n free fucose t o form fucose I-phosphate, which is further converted t o GDP-fucose. Both pathways have been invcstigated and the enzymes involved characterized in cultured endothelial and smooth muscle cells. Arterial wall cells were isolated from porcine aortas and cultured as described previously [ 31. Fucokinase ( E C 2.7.1 . 5 2 ) activity was estimated by measuring the rate of formation o f L-[ "Clfucose-1phosphate from I--[ lJC]fucose. For the estimation of G T P fucose-I -phosphate guanyltransferase (EC 2.7.7.30) ITlabelled fucose-1 -phosphate was prepared from GDP-fucose by enzymic conversion with pho...