COVID-19 Convalescent Plasma for B-cell Depleted Patients: A Systematic Review and Individual Patient Data Meta-analysis

Solomiia Zaremba¹Daniele Focosi²Wyatt W. Pruter¹Massimo Franchini³Diana B. Collantes Hoyos¹Mario Cruciani³Alex J. Miller¹Juan G. Ripoll¹Arturo Casadevall⁴Sidna M. Tulledge-Scheitel¹Nathalie Rufer^5,6Thomas Hueso⁷Justin E. Juskewitch¹Camille M. van Buskirk¹Petros Ioannou^8,9Francesco Lanza^10,11Raymund Razonable¹Ferenc Magyari¹²László Imre Pinczés¹²Ravindra Ganesh¹Claudia M. Denkinger^13,14Ryan T. Hurt¹Maike Janssen¹³James Stubbs¹Carsten Müller- Tidow^13,15Jeffrey Winters¹Karin Holm¹⁶Sameer A. Parikh¹Gordana Simeunovic¹⁷Neil E. Kay, M.D.¹Bart Rijnders¹⁸R. Scott Wright¹Nahema Issa¹⁹Hélѐne Chaussade¹⁹Rickey Carter¹Darrell R. Schroeder¹Jonathon W. Senefeld^20*Michael Joyner^1*

• ¹Mayo Clinic, Rochester, United States
• ²Pisa University Hospital, Pisa, Italy
• ³Hospital Carlo Poma, Mantua, Italy
• ⁴Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States
• ⁵Interregional Blood Transfusion SRC, Epalinges, Switzerland
• ⁶Universite de Lausanne, Lausanne, Switzerland
• ⁷Gustave Roussy, Villejuif, France
• ⁸University of Crete, Heraklion, Greece
• ⁹University Hospital of Heraklion, Heraklion, Greece
• ¹⁰Ravenna Hospital, Ravenna, Italy
• ¹¹University of Bologna, Bologna, Italy
• ¹²University of Debrecen, Debrecen, Hungary
• ¹³Heidelberg University Hospital, Heidelberg, Germany
• ¹⁴German Center for Infection Research, Heidelberg, Germany
• ¹⁵National Center for Tumor Diseases, Heidelberg, Germany
• ¹⁶Lunds Universitet, Lund, Sweden
• ¹⁷Corewell Health West/Michigan State University College of Human Medicine, Grand Rapids, United States
• ¹⁸Erasmus MC, Rotterdam, Netherlands
• ¹⁹CHU Bordeaux, Bordeaux, France
• ²⁰University of Illinois Urbana-Champaign, Urbana, United States

Abstract COVID-19 convalescent plasma (CCP) obtained from recently recovered people is safe and effective against SARS-CoV-2. Currently available CCP is a "hybrid" product with antibodies from individuals who had both infection and vaccination (vaccine-boosted CCP). B-cell depleted patients are at risk of not producing antibodies after either infection or vaccination, hence conceivably among those who would benefit the most from CCP. We thus conducted a systematic review and individual participant data meta-analysis to assess characteristics associated with 60-day survival in B-cell depleted patients transfused with CCP. The protocol was registered with PROSPERO (CRD42024516513) on March 1st, 2024. The last search was on April 2nd, 2024, and included all studies using CCP in B-cell depleted patients. Whenever not available, 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. The overall 60-day survival rate was 86.5% in our cohort of 570 patients (85 included studies). 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 transfusion of vaccine-boosted CCP (OR=9.49; 95% CI 2.01 to 44.82; p=0.005). 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 is associated with a high survival benefit.