Immunologic responses to the third and fourth doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in cell therapy recipients: a systematic review and meta-analysis

Abstract

Background: Multiple studies have provided evidence of suboptimal or poor immune responses to SARS-CoV-2 vaccines in recipients of hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor-T (CAR-T) cell therapy compared to healthy individuals. Given the dynamic nature of SARS-CoV2, characterized by the emergence of many viral variations throughout the general population, there is ongoing discussion regarding the optimal quantity and frequency of additional doses required to sustain protection against SARS-CoV2 especially in this susceptible population. This systematic review and meta-analysis investigated the immune responses of HSCT and CAR-T cell therapy recipients to additional doses of the SARS-CoV-2 vaccines.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the study involved a comprehensive search across PubMed, Scopus, Web of Science Core Collection, Embase, and Cochrane Biorxiv and medRxiv, focusing on the serological responses to the third and fourth vaccine doses in HSCT and CAR-T cell patients.

Results: This study included 32 papers, with 31 qualifying for the meta-analysis. Results showed that after the third dose, the seroconversion rate in HSCT and CAR-T cell therapy recipients who didn't respond to the second dose was 46.10 and 17.26%, respectively. Following the fourth dose, HSCT patients had a seroconversion rate of 27.23%. Moreover, post-third-dose seropositivity rates were 87.14% for HSCT and 32.96% for CAR-T cell therapy recipients. Additionally, the seropositive response to the fourth dose in the HSCT group was 90.04%.

Conclusion: While a significant portion of HSCT recipients developed antibodies after additional vaccinations, only a minority of CAR-T cell therapy patients showed a similar response. This suggests that alternative vaccination strategies are needed to protect these vulnerable groups effectively. Moreover, few studies have reported cellular responses to additional SARS-CoV-2 vaccinations in these patients. Further studies evaluating cellular responses are required to determine a more precise assessment of immunogenicity strength against SARS-CoV-2 after additional doses.

Keywords: COVID-19 vaccine additional dose; Chimeric antigen receptor-T cell therapy; Hematopoietic stem cell transplantation; Immunologic response; SARS-CoV-2 vaccine.

Fig. 1

Research selection procedure flowchart in accordance with the PRISMA criteria

Fig. 2

Forest plot of seroconversion after third dose in HSCT recipients

Fig. 3

Forest plot of seroconversion after fourth dose in HSCT recipients

Fig. 4

Prevalence of seroconversion after the third dose in CAR-T cell therapy recipients, which is significantly lower than in the HSCT group

Fig. 5

Prevalence of humoral response rate after third dose in HSCT recipients

Fig. 6

Prevalence of humoral response rate after the fourth dose in HSCT recipients. The patients exhibited enhanced antibody response after the second additional dose

Fig. 7

Prevalence of humoral response rate after the third dose in CAR-T cell therapy recipients. Nearly one-third of the patients showed a positive humoral response after the third dose

Fig. 8

Forest plot of seroconversion after third dose in HSCT recipients by type of cell therapy received

Fig. 9

Doi plot with minor asymmetry represents the low probability of publication bias