Abstract：
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.
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.
摘要：
在接受抗CD20治疗的患者中，SARS-CoV-2疫苗接种的免疫反应受损，但差异很大。我们对以前用抗CD20抗体治疗的患者中SARS-CoV-2疫苗诱导的体液和细胞介导的免疫应答的文献进行了系统回顾和荟萃分析。
我们搜索了PubMed,Embase,Medrxiv和SSRN使用搜索词“anti-CD20”的变体，“疫苗”和“COVID”，包括截至2021年8月21日的原始研究。我们排除了缺乏体液或细胞介导的免疫反应数据的研究，未指明的响应测试方法，疫苗接种和血液采样之间的时间范围不明或参与者人数少（≤3）。我们排除了既往有COVID-19疫苗疗程或未完成疫苗疗程的个体患者。主要终点是体液和细胞介导的免疫应答率。亚组分析包括抗CD20治疗以来的时间，B细胞耗竭和抗CD20治疗的适应症。我们使用比例的随机效应模型。
评估了90项研究。23项研究符合纳入标准，包括1342名患者。总体体液反应率为0.40(95%CI0.35至0.47)。细胞介导的免疫反应的总比率为0.71（95％CI0.57至0.87）。自上次抗CD20治疗以来的时间间隔>6个月与较高的体液反应率相关，分别为0.63（95％CI0.53至0.72）和<6个月0.2（95％CI0.03至0.43）；p=0<01。同样，循环B细胞的患者更频繁地表现出体液反应。抗CD20治疗的肾移植受者的体液反应率低于血液恶性肿瘤或自身免疫性疾病患者。
接受抗CD20治疗的患者在接种SARS-CoV-2疫苗后可产生体液和细胞介导的免疫反应，但肾移植受者或最近接受治疗且B细胞耗竭的患者等亚组存在非血清转换的高风险,应针对个性化的SARS-CoV-2疫苗接种策略进行单独评估.潜在的局限性是患者人数少和研究的异质性。
这项研究由伯尔尼大学医院资助。
我们搜索了PubMed,Embase,Medrxiv和SSRN使用搜索词“anti-CD20”的变体，“疫苗”和“COVID”，包括截至2021年8月21日的原始研究。我们排除了缺乏体液或细胞介导的免疫反应数据的研究，未指明的响应测试方法，疫苗接种和血液采样之间的时间范围不明或参与者人数少（≤3）。我们排除了既往有COVID-19疫苗疗程或未完成疫苗疗程的个体患者。主要终点是体液和细胞介导的免疫应答率。亚组分析包括抗CD20治疗以来的时间，B细胞耗竭和抗CD20治疗的适应症。我们使用比例的随机效应模型。
评估了90项研究。23项研究符合纳入标准，包括1342名患者。总体体液反应率为0.40(95%CI0.35至0.47)。细胞介导的免疫反应的总比率为0.71（95％CI0.57至0.87）。自上次抗CD20治疗以来的时间间隔>6个月与较高的体液反应率相关，分别为0.63（95％CI0.53至0.72）和<6个月0.2（95％CI0.03至0.43）；p=0<01。同样，循环B细胞的患者更频繁地表现出体液反应。抗CD20治疗的肾移植受者的体液反应率低于血液恶性肿瘤或自身免疫性疾病患者。
接受抗CD20治疗的患者在接种SARS-CoV-2疫苗后可产生体液和细胞介导的免疫反应，但肾移植受者或最近接受治疗且B细胞耗竭的患者等亚组存在非血清转换的高风险,应针对个性化的SARS-CoV-2疫苗接种策略进行单独评估.潜在的局限性是患者人数少和研究的异质性。
这项研究由伯尔尼大学医院资助。
