Institute of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Institute of Physiology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
J Infect Public Health. 2023 Mar;16(3):384-392. doi: 10.1016/j.jiph.2023.01.016. Epub 2023 Jan 21.
Age represents the major risk factor for fatal disease outcome in coronavirus disease (COVID-19) due to age-related changes in immune responses. On the one hand lymphocyte counts continuously decline with advancing age, on the other hand somatic hyper-mutations of B-lymphocytes and levels of class-switched antibodies diminish, resulting in lower neutralizing antibody titers. To date the impact of age on immunoglobulin G (IgG) production in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. Therefore, we investigated the impact of age on the onset of IgG production and its association with outcome, viral persistence, inflammatory and thrombotic markers in consecutive, hospitalized COVID-19 patients admitted to the Clinic Favoriten (Vienna, Austria) between April and October 2020 that fulfilled predefined inclusion criteria. Three different IgGs against SARS-CoV-2 (spike protein S1, nucleocapsid (NC), and the spike protein receptor binding domain (RBD)) were monitored in plasma of 97 patients upon admission and three times within the first week followed by weekly assessment during their entire hospital stay. We analyzed the association of clinical parameters including C-reactive protein (CRP), D-dimer levels and platelet count as well as viral persistence with the onset and concentration of different anti-SARS-CoV-2 specific IgGs. Our data demonstrate that in older individuals anti-SARS-CoV-2 IgG production increases earlier after symptom onset and that deceased patients have the highest amount of antibodies against SARS-CoV-2 whereas intensive care unit (ICU) survivors have the lowest titers. In addition, anti-SARS-CoV-2 IgG concentrations are not associated with curtailed viral infectivity, inflammatory or thrombotic markers, suggesting that not only serological memory but also other adaptive immune responses are involved in successful viral killing and protection against a severe COVID-19 infection.
年龄是导致冠状病毒病 (COVID-19) 致命疾病结局的主要危险因素，这是由于免疫反应随年龄相关变化所致。一方面，随着年龄的增长，淋巴细胞计数持续下降；另一方面，B 淋巴细胞的体细胞超突变和类别转换抗体水平降低，导致中和抗体滴度降低。迄今为止，年龄对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染后免疫球蛋白 G (IgG) 产生的影响尚不清楚。因此，我们研究了年龄对 IgG 产生的影响及其与结局、病毒持续存在、炎症和血栓形成标志物的关系，纳入了 2020 年 4 月至 10 月期间连续入住奥地利维也纳 Clinic Favoriten 的符合预定义纳入标准的 COVID-19 住院患者。在入院时和第 1 周内的 3 次随访中，监测了 97 例患者血浆中针对 SARS-CoV-2 的 3 种不同 IgG（刺突蛋白 S1、核衣壳 (NC) 和刺突蛋白受体结合域 (RBD)），随后在整个住院期间每周评估一次。我们分析了包括 C 反应蛋白 (CRP)、D-二聚体水平和血小板计数在内的临床参数以及病毒持续存在与不同抗 SARS-CoV-2 特异性 IgG 的产生和浓度之间的关联。我们的数据表明，在年龄较大的个体中，症状出现后抗 SARS-CoV-2 IgG 的产生更早开始，死亡患者对 SARS-CoV-2 的抗体数量最多，而重症监护病房 (ICU) 幸存者的抗体滴度最低。此外，抗 SARS-CoV-2 IgG 浓度与病毒传染性、炎症或血栓形成标志物无关，这表明不仅是血清学记忆，其他适应性免疫反应也参与了成功的病毒杀伤和对严重 COVID-19 感染的保护。
