Antibody development after COVID-19 vaccination in patients with autoimmune diseases in the Netherlands: a substudy of data from two prospective cohort studies.
Antibody development after COVID-19 vaccination in patients with autoimmune diseases in the Netherlands: a substudy of data from two prospective cohort studies.
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DOI：
10.1016/s2665-9913(21)00222-8
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发表时间：
2021-11
期刊：
影响因子：
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通讯作者：
Wolbink G
中科院分区：
文献类型：
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作者：
Boekel L;Steenhuis M;Hooijberg F;Besten YR;van Kempen ZLE;Kummer LY;van Dam KPJ;Stalman EW;Vogelzang EH;Cristianawati O;Keijzer S;Vidarsson G;Voskuyl AE;Wieske L;Eftimov F;van Vollenhoven R;Kuijpers TW;van Ham SM;Tas SW;Killestein J;Boers M;Nurmohamed MT;Rispens T;Wolbink G
关于COVID-19疫苗在自身免疫性疾病患者中的免疫原性的数据很少，这些患者通常接受免疫抑制药物治疗。我们旨在研究不同免疫抑制药物对自身免疫性疾病患者接种COVID-19疫苗后抗体产生的影响。在这项研究中，我们使用了从荷兰两项正在进行的前瞻性队列研究中纳入的自身免疫性疾病患者和健康对照者中收集的血清样本。如果参与者通过荷兰国家疫苗计划接种了任何COVID-19疫苗，则有资格入选本子研究，当时荷兰国家疫苗计划优先考虑老年人接种。在第一次或第二次COVID-19疫苗接种后收集样本。未采集系列样本。血清转换率和IgG抗体滴度对受体结合结构域的SARS-CoV-2刺突蛋白进行了测量。使用逻辑和线性回归分析来研究疫苗接种时和至少直到采样时的药物使用、血清转换率和IgG抗体滴度之间的相关性。收集数据的研究已在荷兰试验注册中心（试验ID NL 8513）和ClinicalTrials.org（NCT 04498286）注册。在2020年4月26日至2021年3月1日期间，招募了3682例风湿性疾病患者，546例多发性硬化症患者和1147例健康对照参与两项前瞻性队列研究。在第一次（507例患者和239例对照）或第二次（125例患者和50例对照）COVID-19疫苗接种后，从自身免疫性疾病患者（n=632）和健康对照（n=289）中采集样本。患者和对照组的平均年龄为63岁（SD 11），632例自身免疫性疾病患者中有423例（67%）为女性，289例对照组中有195例（67%）为女性。在既往无SARS-CoV-2感染的参与者中，首次接种疫苗后患者的血清转化率显著低于对照组（432例患者中210例[49%] vs 210例对照中154例[73%];校正比值比0.33 [95%CI 0.23 - 0.48]; p<0.0001），主要是由于接受甲氨蝶呤或抗CD 20治疗的患者血清转化率较低。第二次接种后，所有患者治疗亚组的血清转化率均超过80%，但接受抗CD 20治疗的患者除外（7例患者中有3例[43%]）。我们观察到，既往感染过SARS-CoV-2的患者接受过单剂疫苗接种后，血清转换和IgG抗体滴度没有差异（75例患者中的72例[96%]，中位IgG滴度127 Au/mL [IQR 27-300]）和既往未感染SARS-CoV-2但接受过两次疫苗接种的患者（106例患者中的97例[92%]，中位IgG滴度49 Au/mL [17-134]）。我们的数据表明，在接受特定免疫抑制药物治疗的老年患者中，首次COVID-19疫苗接种后的血清转化延迟，但第二次或重复暴露于SARS-CoV-2，无论是通过感染还是疫苗接种，都可以改善接受免疫抑制药物治疗的患者的体液免疫。因此，在接受免疫抑制药物的患者中，应避免延迟第二次接种COVID-19疫苗。未来的研究，包括年轻的患者需要做，以确认我们的结果的普遍性。ZonMw、里德基金会和阿姆斯特丹MS中心。
Data are scarce on immunogenicity of COVID-19 vaccines in patients with autoimmune diseases, who are often treated with immunosuppressive drugs. We aimed to investigate the effect of different immunosuppressive drugs on antibody development after COVID-19 vaccination in patients with autoimmune diseases. In this study, we used serum samples collected from patients with autoimmune diseases and healthy controls who were included in two ongoing prospective cohort studies in the Netherlands. Participants were eligible for inclusion in this substudy if they had been vaccinated with any COVID-19 vaccine via the Dutch national vaccine programme, which at the time was prioritising vaccination of older individuals. Samples were collected after the first or second COVID-19 vaccination. No serial samples were collected. Seroconversion rates and IgG antibody titres against the receptor-binding domain of the SARS-CoV-2 spike protein were measured. Logistic and linear regression analyses were used to investigate the association between medication use at the time of vaccination and at least until sampling, seroconversion rates, and IgG antibody titres. The studies from which data were collected are registered on the Netherlands Trial Register, Trial ID NL8513, and ClinicalTrials.org, NCT04498286. Between April 26, 2020, and March 1, 2021, 3682 patients with rheumatic diseases, 546 patients with multiple sclerosis, and 1147 healthy controls were recruited to participate in the two prospective cohort studies. Samples were collected from patients with autoimmune diseases (n=632) and healthy controls (n=289) after their first (507 patients and 239 controls) or second (125 patients and 50 controls) COVID-19 vaccination. The mean age of both patients and controls was 63 years (SD 11), and 423 (67%) of 632 patients with autoimmune diseases and 195 (67%) of 289 controls were female. Among participants without previous SARS-CoV-2 infection, seroconversion after first vaccination were significantly lower in patients than in controls (210 [49%] of 432 patients vs 154 [73%] of 210 controls; adjusted odds ratio 0·33 [95% CI 0·23–0·48]; p<0·0001), mainly due to lower seroconversion in patients treated with methotrexate or anti-CD20 therapies. After the second vaccination, seroconversion exceeded 80% in all patient treatment subgroups, except among those treated with anti-CD20 therapies (three [43%] of seven patients). We observed no difference in seroconversion and IgG antibody titres between patients with a previous SARS-CoV-2 infection who had received a single vaccine dose (72 [96%] of 75 patients, median IgG titre 127 AU/mL [IQR 27–300]) and patients without a previous SARS-CoV-2 infection who had received two vaccine doses (97 [92%] of 106 patients, median IgG titre 49 AU/mL [17–134]). Our data suggest that seroconversion after a first COVID-19 vaccination is delayed in older patients on specific immunosuppressive drugs, but that second or repeated exposure to SARS-CoV-2, either via infection or vaccination, improves humoral immunity in patients treated with immunosuppressive drugs. Therefore, delayed second dosing of COVID-19 vaccines should be avoided in patients receiving immunosuppressive drugs. Future studies that include younger patients need to be done to confirm the generalisability of our results. ZonMw, Reade Foundation, and MS Center Amsterdam.