Convalescent Plasma Treatment of B-cell Depleted Patients with COVID-19: Systematic Review and Individual Participant Data Meta-Analysis

Background: COVID-19 convalescent plasma (CCP) is obtained from people recently recovered from COVID-19 and contains viral-neutralizing antibodies. Because such treatment is safe and effective against SARS-CoV-2, the US Food and Drug Administration (FDA) has recently authorized the use of CCP for COVID-19 patients with immunodeficiencies. Currently available CCP is a ″hybrid″ product with antibodies from individuals who had both infection and vaccination (vaccine-boosted CCP). In this context, there is growing interest in CCP treatment outcomes in specific groups of immunocompromised patients. Specifically, B-cell depleted patients are at risk of not producing antibodies after either infection or vaccination. Hence, B-cell depleted patients are conceivably among those who would benefit the most from CCP. We thus conducted a systematic review and individual patient data meta-analysis to assess characteristics associated with 60-day survival in B-cell depleted patients transfused with CCP. Methods: The last search was April 2nd, 2024, and included all studies using CCP in B-cell depleted patients. Whenever not available in the publication, we requested individual participant data from corresponding authors of eligible studies. Risk of bias was assessed using Joanna Briggs Institute Critical Appraisal Tools. Data were analyzed using conditional logistic regression. Results: We describe individual patient data extracted from 85 studies and synthesized into a cohort of 570 patients. The overall 60-day survival rate was 86.5%. Of patients with information available, 70.1% achieved SARS-CoV-2 clearance, and 64.3% had clinical improvement within 5 days of CCP transfusion. After controlling for age, sex, calendar year of infection and World Health Organization (WHO) disease severity, we found a significant association between 60-day survival and days since last anti-CD20 dose (OR=1.16 per 10-day increase; 95% CI 1.04 to 1.29; p=0.007) and transfusion of vaccine-boosted CCP (OR=9.49; 95% CI 2.01 to 44.82; p=0.005), but not with concomitant remdesivir treatment (OR=1.31; 95% CI 0.66 to 2.61; p=0.440). Discussion: Our study is limited to individual participant data analysis, with a majority of the studies included being case series and case reports. Overall survival in our cohort of B-cell depleted patients was consistent with prior meta-analysis of randomized controlled trials on survival of immunocompromised patient transfused with CCP (~84%). A novel finding from this analysis is that vaccine-boosted CCP with a presumably higher content of neutralizing antibodies is associated with a high survival benefit. Registration: The protocol for this systematic review and individual participant data meta-analysis was registered with PROSPERO (CRD42024516513) on March 1st, 2024. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement The authors report no funding beyond support from their home institutions. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used openly available participant data from included studies. The study was determined by the Mayo Clinic Institutional Review Board as exempt. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data presented in the study are available upon reasonable request to the authors.