The Evolution of Evidence on COVID-19 Vaccination in Solid Organ Transplant Recipients: A Living Systematic Review and Network Meta-Analysis

Abstract

Background: The impact of COVID-19 vaccination on clinical outcomes in solid organ transplant (SOT) recipients remains unclear. This living systematic review and network meta-analysis sought to assess the effectiveness of COVID-19 vaccination in SOT recipients and to evaluate the evolution of evidence in this population over time. Methods: We searched six databases from inception to March 1st, 2024 for randomized controlled trials (RCTs) and observational studies evaluating different COVID-19 vaccination strategies (i.e., number of doses, type of vaccine) in SOT recipients. Based on patient-important outcomes, we performed frequentist random-effects pairwise meta-analyses and NMAs, separating RCTs and observational studies, and used the GRADE approach to assess certainty in the evidence. We compared the body evidence identified at four timepoints (October 1st, 2022, March 1st, 2023, July 1st, 2023, and March 1st, 2024). Results: We included 6 RCTs (N=814) and 42 observational studies (N=125,101). We identified a dose-response relationship between the number of COVID-19 vaccines received and a reduction in the risk of COVID-19 infection. The evidence evaluating the number of doses on other patient-important outcomes, including mortality, hospitalization, and ICU admission, and the evidence investigating the impact of the type of COVID-19 vaccine demonstrated low to very low certainty. Across the four iterations of this living systematic review, the conclusions drawn from the evidence supported by randomized data largely remained unchanged; however, half of the conclusions drawn from the evidence supported by observational data changed in certainty or direction. Conclusion: Throughout the COVID-19 pandemic, clinicians and SOT recipients worked with minimal evidence with variable certainty in relation to COVID-19 vaccines in this population. In the instance of future public health emergencies, clinicians and researchers should collaborate closely with patient partners to ensure there is adequate evidence in the transplant population on patient-important outcomes.