Humoral and cellular immune responses upon SARS-CoV-2 vaccines in patients with anti-CD20 therapies: A systematic review and meta-analysis of 1342 patients

Background Immune responses upon 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. Methods We searched PubMed, EMBASE, Medrxiv and SSRN using variations of search terms 9anti-CD209, 9vaccine9 and 9COVID9 and included original studies up to August 21st,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 (n 6 months), time point of response testing after vaccination ( 4 weeks) and disease entity (autoimmune vs cancer vs renal transplant). We used random-effects models of proportions. Findings Ninety studies were assessed. Inclusion criteria were met by 23 studies comprising 1342 patients. Overall rate of humoral response was 0.41 (95% CI 0.35-0.47). Overall rate of cell-mediated immune responses was 0.71 (95% CI 0.47-0.90). Longer time interval since last anti-CD20 therapy was associated with higher humoral response rates > 6 months 0.63 (95% CI 0.53-0.72) vs < 6 months 0.2 (95% CI 0.03-0.43); p = 0.001. Compared to patients with haematological malignancies or autoimmune diseases, anti-CD20 treated kidney transplant recipients showed the lowest vaccination response rates. Interpretation 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 B-cell depleting therapy are at high risk for non-seroconversion and should be individually assessed for personalized SARS-CoV-2 vaccination strategies. Potential limitations are small patient numbers, heterogeneous diseases and assays used. Funding This study was funded by Bern University Hospital.