Immunogenicity and Safety of SARS-CoV-2 Vaccines and Breakthrough Infections Among Solid Organ Transplant Recipients: Systematic Review and Meta-Analysis

ABSTRACT

Purpose: The SARS-CoV-2 pandemic has had a significant impact on the field of solid organ transplant(SOT). Immunization against SARS-CoV-2 is globally available since 2021. SOT recipients represent a vulnerable group with a higher risk of infection and worse outcomes from COVID-19 compared with the general population. There is a concern for the efficacy of SARS-CoV-2 vaccination amongst SOT recipients. We aimed to assess immunogenicity, safety and breakthrough infections after SARS-CoV-2 vaccination. Method(s) We conducted a systematic review and a meta-analysis using articles from 8 databases published from January 1,2020 to July 13,2021. We included studies reporting data regarding SOT and SARS-CoV-2 post vaccine antibody response or cellular response;safety of vaccination;and SARS-CoV-2 infection after at least one vaccine dose. A meta-analysis of postvaccine antibody response and death in breakthrough infections was conducted using a random-effects model. Result(s) Initially, we identified 572 potential studies. After careful review, we included 64 studies for systematic review and 46 studies for meta-analysis. We identified 6,710 SOT recipients. Pooled incidence of antibody positivity after completion of any vaccine schedule was 28.3% (95% confidence interval[CI] 22.5-34.8%). Pooled incidence of antibody positivity after messenger RNA vaccination with 2 doses and 3 doses were 29.3%(95%CI 23.58%-35.74%) and 57.4%(95%CI 48.63-65.78%), respectively. Twelve reports on interferon-gamma response to SARS-CoV-2 spike antigen peptides showed a positivity between 30.4% and 55.0% after messenger RNA vaccines. The most common side effect after vaccination was site pain. Only 5 cases developed rejection but no graft loss. The pooled incidence of death in breakthrough infections was 17.1%(95%CI 10.2%-27.2%). Conclusion(s) Our findings show that only 29% of SOT recipients could mount antibodies after 2 doses of messenger RNA vaccines, with an improved response seen after 3 doses (57%). Even with 3 doses, the immunogenicity is still suboptimal and further studies to investigate the optimal vaccination strategies in this population are needed.