Coronavirus disease 2019 (COVID-19) poses an increased risk for severe illness and suboptimal vaccination responses in patients with kidney disease, in which oxidative stress may be involved. Oxidative stress can be reliably measured by determining circulating free thiols (R–SH, sulfhydryl groups), since R–SH are rapidly oxidized by reactive species. In this study, we aimed to examine the association between serum free thiols and the ability to mount a humoral immune response to SARS-CoV-2 vaccination in kidney patients. Serum free thiol concentrations were measured in patients with chronic kidney disease stages 4/5 (CKD G4/5) ( = 46), on dialysis ( = 43), kidney transplant recipients (KTR) ( = 73), and controls ( = 50). Baseline serum free thiol and interferon-γ-induced protein-10 (IP-10) – a biomarker of the interferon response – were analyzed for associations with seroconversion rates and SARS-CoV-2 spike (S1)-specific IgG concentrations after two doses of the mRNA-1273 vaccine. Albumin-adjusted serum free thiol concentrations were significantly lower in patients with CKD G4/5 ( < 0.001), on dialysis ( < 0.001), and KTR ( < 0.001), as compared to controls. Seroconversion rates after full vaccination were markedly reduced in KTR (52.1%) and were significantly associated with albumin-adjusted free thiols (OR = 1.76, = 0.033). After adjustment for MMF use, hemoglobin, and eGFR, this significance was not sustained (OR = 1.49, = 0.241). KTR show suboptimal serological responses to SARS-CoV-2 vaccination, which is inversely associated with serum R–SH, reflecting systemic oxidative stress. Albeit this association was not robust to relevant confounding factors, it may at least partially be involved in the inability of KTR to generate a positive serological response after SARS-CoV-2 vaccination.

中文翻译：

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全身氧化应激可能与接种疫苗的肾移植受者中针对 SARS-CoV-2 的 IgG 抗体滴度降低有关：RECOVAC-IR 观察性研究的事后分析

2019 年冠状病毒病 (COVID-19) 会增加肾病患者患严重疾病和疫苗接种反应欠佳的风险，其中可能涉及氧化应激。由于 R-SH 会被活性物质快速氧化，因此可以通过测定循环游离硫醇（R-SH、巯基）来可靠地测量氧化应激。在这项研究中，我们旨在研究肾脏患者血清游离硫醇与对 SARS-CoV-2 疫苗接种产生体液免疫反应的能力之间的关系。测量了慢性肾病 4/5 期 (CKD G4/5) ( = 46) 患者、透析患者 ( = 43)、肾移植受者 (KTR) ( = 73) 和对照组 ( = 50) 的血清游离硫醇浓度）。分析基线血清游离硫醇和干扰素 γ 诱导蛋白 10 (IP-10)（干扰素反应的生物标志物）与两次给药后血清转化率和 SARS-CoV-2 尖峰 (S1) 特异性 IgG 浓度的关系mRNA-1273 疫苗。与对照组相比，CKD G4/5 (< 0.001)、透析患者 (< 0.001) 和 KTR (< 0.001) 患者的白蛋白调整血清游离硫醇浓度显着较低。 KTR 中完全疫苗接种后的血清转化率显着降低（52.1%），并且与白蛋白调整的游离硫醇显着相关（OR = 1.76，= 0.033）。在调整 MMF 使用、血红蛋白和 eGFR 后，这种显着性不再持续（OR = 1.49，= 0.241）。 KTR 对 SARS-CoV-2 疫苗接种表现出次优的血清学反应，这与血清 R-SH 呈负相关，反映了全身氧化应激。尽管这种关联对于相关混杂因素而言并不稳健，但它可能至少部分涉及 KTR 在 SARS-CoV-2 疫苗接种后无法产生阳性血清学反应。