Abstract：
Immunocompromised individuals are at significantly elevated risk for severe courses of coronavirus disease 2019 (COVID-19). In addition to vaccination, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies (nAbs) have been applied throughout the pandemic, with time of treatment onset and potency against the currently prevailing virus variant identified as relevant factors for medical benefit. Using data from the European Society for Immunodeficiencies (ESID) registry, the present study evaluated COVID-19 cases in three groups of patients with inborn errors of immunity (IEI; 981 agammaglobulinemia patients on immunoglobulin replacement therapy (IGRT); 8960 non-agammaglobulinemia patients on IGRT; 14 428 patients without IGRT), and the neutralizing capacity of 1100 immunoglobulin lots against SARS-CoV-2 (\"Wuhan\" and Omicron strains), throughout 3 years. From the first (2020/2021) to the second (2021/2022) cold season, i.e., during the virus drift to the more contagious Omicron variants, an increase in case numbers was recorded that was comparable (~2- to 3-fold) for all three study groups. During the same period, immunoglobulin lots showed a profound nAb increase against the archetypal SARS-CoV-2 strain, yet only low levels of Omicron nAbs. Notably, shortly before the third (2022/2023) cold season, Omicron-neutralizing capacity of released immunoglobulin lots had plateaued at high levels. From the second to the third cold season, COVID-19 cases dropped markedly. While a ~6-fold case reduction was recorded for the groups of non-agammaglobulinemia patients on IGRT and IEI patients not receiving IGRT, the decline was ~30-fold for the group of agammaglobulinemia patients on IGRT. These findings suggest a substantial COVID-19-protective effect of IGRT, at least for distinct groups of antibody-deficient patients.
摘要：
免疫功能低下的个体患2019年冠状病毒病严重病程的风险显著升高(COVID-19)。除了接种疫苗，严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）中和抗体（nAbs）已在整个大流行中应用，随着治疗的开始时间和对目前流行的病毒变体的效力被确定为医疗利益的相关因素。使用来自欧洲免疫缺陷学会（ESID）注册表的数据，本研究评估了三组先天性免疫缺陷患者的COVID-19例(IEI；981例接受免疫球蛋白替代疗法(IGRT)的丙种球蛋白血症患者；8960例非丙种球蛋白血症患者；14428例非IGRT患者)，1100批免疫球蛋白对SARS-CoV-2（\“武汉\”和Omicron菌株）的中和能力，整整3年。从第一个（2020/2021）到第二个（2021/2022）寒冷季节，即，在病毒漂移到更具传染性的Omicron变种的过程中，在所有三个研究组中,病例数的增加是相当的(~2-3倍).在同一时期,免疫球蛋白批次显示针对原型SARS-CoV-2株的nAb大幅增加，然而只有低水平的Omicron单克隆抗体。值得注意的是,在第三个（2022/2023）寒冷季节前不久，释放的免疫球蛋白批次的Omicron中和能力已稳定在高水平。从第二个到第三个寒冷的季节，COVID-19病例明显下降。虽然IGRT组非无球蛋白血症患者和未接受IGRT的IEI患者的病例减少了约6倍，IGRT无丙种球蛋白血症患者组的下降幅度约为30倍。这些发现表明IGRT具有实质性的COVID-19保护作用，至少对于不同的抗体缺乏患者群体。
