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

Abstract

Immunogenicity of 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 from database inceptions through January 12, 2023, for studies reporting humoral and/or cellular immunogenicity of SARS-CoV-2 vaccination in 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 5,906 HSCT recipients, after 1, 2, and 3 doses of mRNA SARS-CoV-2 vaccines, the mean (95% CI) antispike antibody seropositivity rates 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), time from HSCT <24 months (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.