Attenuated immunogenicity of SARS-CoV-2 vaccines and risk factors in stem cell transplant recipients: a meta-analysis

Immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is diminished in hematopoietic stem cell transplant (HSCT) recipients. To summarize current evidence and identify risk factors for attenuated responses, 5 electronic databases were searched since database inceptions through 12 January 2023 for studies reporting humoral and/or cellular immunogenicity of SARS-CoV-2 vaccination in the HSCT population. Using descriptive statistics and random-effects models, extracted numbers of responders and pooled odds ratios (pORs) with 95% confidence intervals (CIs) for risk factors of negative immune responses were analyzed (PROSPERO: CRD42021277109). From 61 studies with 5906 HSCT recipients, after 1, 2, and 3 doses of messenger RNA (mRNA) SARS-CoV-2 vaccines, the mean antispike antibody seropositivity rates (95% CI) were 38% (19-62), 81% (77-84), and 80% (75-84); neutralizing antibody seropositivity rates were 52% (40-64), 71% (54-83), and 78% (61-89); and cellular immune response rates were 52% (39-64), 66% (51-79), and 72% (52-86). After 2 vaccine doses, risk factors (pOR; 95% CI) associated with antispike seronegativity were male recipients (0.63; 0.49-0.83), recent rituximab exposure (0.09; 0.03-0.21), haploidentical allografts (0.46; 0.22-0.95), <24 months from HSCT (0.25; 0.07-0.89), lymphopenia (0.18; 0.13-0.24), hypogammaglobulinemia (0.23; 0.10-0.55), concomitant chemotherapy (0.48; 0.29-0.78) and immunosuppression (0.18; 0.13-0.25). Complete remission of underlying hematologic malignancy (2.55; 1.05-6.17) and myeloablative conditioning (1.72; 1.30-2.28) compared with reduced-intensity conditioning were associated with antispike seropositivity. Ongoing immunosuppression (0.31; 0.10-0.99) was associated with poor cellular immunogenicity. In conclusion, attenuated humoral and cellular immune responses to mRNA SARS-CoV-2 vaccination are associated with several risk factors among HSCT recipients. Optimizing individualized vaccination and developing alternative COVID-19 prevention strategies are warranted.