Department of Nephrology and Hypertension, Inselspital University Hospital Bern, Bern, Switzerland.
Division of Nephrology, Department of Internal Medicine, Neuchâtel Hospital Network, Neuchâtel, Switzerland.
RMD Open. 2022 Feb;8(1). doi: 10.1136/rmdopen-2021-002036.
Immune responses on SARS-CoV-2 vaccination in patients receiving anti-CD20 therapies are impaired but vary considerably. We conducted a systematic review and meta-analysis of the literature on SARS-CoV-2 vaccine induced humoral and cell-mediated immune response in patients previously treated with anti-CD20 antibodies.
We searched PubMed, Embase, Medrxiv and SSRN using variations of search terms 'anti-CD20', 'vaccine' and 'COVID' and included original studies up to 21 August 2021. We excluded studies with missing data on humoral or cell-mediated immune response, unspecified methodology of response testing, unspecified timeframes between vaccination and blood sampling or low number of participants (≤3). We excluded individual patients with prior COVID-19 or incomplete vaccine courses. Primary endpoints were humoral and cell-mediated immune response rates. Subgroup analyses included time since anti-CD20 therapy, B cell depletion and indication for anti-CD20 therapy. We used random-effects models of proportions.
Ninety studies were assessed. Inclusion criteria were met by 23 studies comprising 1342 patients. Overall rate of humoral response was 0.40 (95% CI 0.35 to 0.47). Overall rate of cell-mediated immune responses was 0.71 (95% CI 0.57 to 0.87). A time interval >6 months since last anti-CD20 therapy was associated with higher humoral response rates with 0.63 (95% CI 0.53 to 0.72) versus <6 months 0.2 (95% CI 0.03 to 0.43); p=0<01. Similarly, patients with circulating B cells more frequently showed humoral responses. Anti-CD20-treated kidney transplant recipients showed lower humoral response rates than patients with haematological malignancies or autoimmune disease.
Patients on anti-CD20 therapies can develop humoral and cell-mediated immune responses after SARS-CoV-2 vaccination, but subgroups such as kidney transplant recipients or those with very recent therapy and depleted B cell are at high risk for non-seroconversion and should be individually assessed for personalised SARS-CoV-2 vaccination strategies. Potential limitations are small patient numbers and heterogeneity of studies included.
This study was funded by Bern University Hospital.
接受抗 CD20 治疗的患者对 SARS-CoV-2 疫苗的免疫反应受损，但差异很大。我们对先前接受过抗 CD20 抗体治疗的患者接种 SARS-CoV-2 疫苗后产生的体液和细胞介导免疫反应的文献进行了系统评价和荟萃分析。
我们使用“抗 CD20”、“疫苗”和“COVID”的变体在 PubMed、Embase、Medrxiv 和 SSRN 上进行了搜索，并纳入了截至 2021 年 8 月 21 日的原始研究。我们排除了未报告体液或细胞介导免疫反应数据、未明确反应检测方法、疫苗接种和采血之间的时间框架不明确或参与者数量较少（≤3）的研究。我们还排除了既往患有 COVID-19 或未完成疫苗接种的个别患者。主要终点是体液和细胞介导免疫反应率。亚组分析包括抗 CD20 治疗的时间、B 细胞耗竭和抗 CD20 治疗的适应症。我们使用了比例的随机效应模型。
评估了 90 项研究。纳入标准符合 23 项研究，共纳入 1342 例患者。体液反应总率为 0.40（95%CI 0.35 至 0.47）。细胞介导免疫反应的总率为 0.71（95%CI 0.57 至 0.87）。与 6 个月内末次抗 CD20 治疗相比，末次抗 CD20 治疗后 >6 个月时体液反应率更高，分别为 0.63（95%CI 0.53 至 0.72）和 0.2（95%CI 0.03 至 0.43）；p=0<01。同样，有循环 B 细胞的患者更常出现体液反应。与血液系统恶性肿瘤或自身免疫性疾病患者相比，接受抗 CD20 治疗的肾移植受者的体液反应率较低。
接受抗 CD20 治疗的患者在接种 SARS-CoV-2 疫苗后可以产生体液和细胞介导的免疫反应，但亚组（如肾移植受者或最近接受治疗且 B 细胞耗竭的患者）发生非血清转化的风险较高，应单独评估个体化的 SARS-CoV-2 疫苗接种策略。潜在的局限性是患者数量较少和纳入研究的异质性。
本研究由伯尔尼大学附属医院资助。
