Serological Responses after a Fourth Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis

The humoral immune response and safety of the fourth dose of the coronavirus disease 2019 (COVID-19) vaccine in solid organ transplant (SOT) recipients need to be fully elucidated. We conducted a systematic review and meta-analysis to assess the efficacy and safety associated with this additional dose of the COVID-19 vaccine in the SOT recipients. A comprehensive search was conducted to identify studies on SOT patients without prior natural SARS-CoV-2 infection who received the fourth dose of the COVID-19 vaccine. Serological antibody responses following vaccination were synthesized by a meta-analysis of proportions. The proportions for each outcome were integrated by using a random-effects model. Approximately 56-92% of the SOT patients developed a humoral immune response, and the pooled seroprevalence rate was 75% (95% confidence interval [CI], 62-82%) after administering the third vaccine dose. Following the fourth dose of vaccination, approximately 76-95% of the patients developed a humoral immune response. The pooled seroprevalence rate after the fourth dose was 85% (95% CI, 79-91%). Of the patients who initially tested seronegative after the second dose, approximately 22-76% of patients subsequently became seropositive after the third dose. The pooled seroconversion rate for the third dose was 47% (95% CI, 31-64%). Among the patients who were seronegative after the third dose, approximately 25-76% turned seropositive after the fourth dose. The pooled seroconversion rate after the fourth dose was 51% (95% CI, 40-63%). Safety data were reported in three studies, demonstrating that adverse effects following the fourth dose were generally mild, and patients with these adverse effects did not require hospitalization. No transplant rejection or serious adverse events were observed. A fourth dose of the COVID-19 vaccine in SOT recipients was associated with an improved humoral immune response, and the vaccine was considered relatively safe.