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

Abstract

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 'anti-CD20', 'vaccine' and 'COVID' 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<=3). We excluded individual patients with prior SARS-CoV-2 infection or incomplete vaccine courses. Primary endpoints were humoral and cell-mediated immune response rates. Pre-specified subgroups were time of vaccination after anti-CD20 therapy (< vs > 6 months), time point of response testing after vaccination (< vs > 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.

Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy

“…In the initial RituxiVac study, we showed that in a mixed population of patients with kidney transplant, autoimmune disease or cancer, only 49% of patients produce a humoral immune response after mRNA vaccination against SARS-CoV-2 3. Our recent meta-analysis revealed similar results by several studies, with some differences depending on the types of patient populations 4…”

“…Others have further discriminated CMI after two SARS-CoV-2 vaccines in this patient population: vaccine-driven CD4 responses were more impaired than CD8+ cell responses, with severe impairment of circulating T follicular helper cell subpopulations in anti-CD20-treated patients, and vaccine-driven CD8 responses were absent in patients with low CD4 count 19 27. Overall, CMI in anti-CD20-treated patients may be diminished or at least very heterogeneous after 2 or 3 SARS-CoV-2 vaccinations, depending on patient population or comedication 4. Together with the ubiquitously reported impaired humoral responses to SARS-CoV-2 vaccines in anti-CD20-treated patients, the consequence is undoubtedly an increased risk of severe breakthrough infections in this population, as reported from two potentially overlapping study populations 28 29…”

COVID-19 vaccine response and safety in patients with cancer: An overview of systematic reviews

“…By title/abstract screening, 188 articles were identified for fulltext view. Finally, 18 systematic reviews (15 with meta-analyses and 3 without meta-analyses) were identified which fulfilled the eligibility criteria (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). The study flow was depicted according to the PRISMA guidelines in Figure 2.…”