Serologic response and safety of COVID-19 vaccination in HSCT or CAR T-cell recipients: a systematic review and meta-analysis

Abstract

Background: Patients receiving hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR T-cell) therapy are immunocompromised and at high risk of viral infection, including SAR2-CoV-2 infection. However, the effectiveness and safety of COVID-19 vaccines in these recipients is not well characterized. The present meta-analysis evaluated the serologic response and safety of COVID-19 vaccines in these population.

Methods: Literature databases (MEDLINE, EMBASE, Web of Science, MedRvix and BioRvix) were searched for original studies with serologic response post COVID-19 vaccination in HSCT or CAR T-cell recipients published until July 14, 2022. The analysis included 27 observational studies with a total of 2899 patients receiving allogeneic HSCT (2506), autologous HSCT (286) or CAR T-cell therapy (107), and 683 healthy participants with serologic response data. Random effects models were used to pool the rate of serologic response to COVID-19 vaccination in HSCT or CAR T-cell recipients and odds ratio comparing with healthy controls.

Results: The pooled seropositivity rates in HSCT and CAR T-cell recipients were 0.624 [0.506-0.729] for one dose, 0.745 [0.712-0.776] for two doses. The rates were significantly lower than those in healthy controls (nearly 100%). In subgroup analysis, CAR T-cell recipients exhibited an even lower seroconversion rate (one dose: 0.204 [0.094-0.386]; two doses: 0.277 [0.190-0.386]) than HSCT counterparts (one dose: 0.779 [0.666-0.862]; two doses: 0.793 [0.762-0.821]). The rates were comparable between autologous and allogeneic HSCT recipients. Other possible impact factors related to seropositivity were time interval between therapy and vaccination, use of immunosuppressive drugs and immune cell counts. Most vaccine-related adverse effects were mild and resolvable, comparable to general population.

Conclusions: This analysis revealed a diminished response to COVID-19 vaccines in HSCT or CAR T-cell recipients. Our findings may inform regular COVID-19 vaccination at appropriate intervals after HSCT or CAR T-cell therapy.

Keywords: COVID-19; Chimeric antigen receptor T cell therapy; Hematopoietic stem cell transplantation; Meta-analysis; Vaccine.

Fig. 1

PRISMA flow diagram summarizing the process for study identification. 4993 articles were identified through the literature search. 4966 were excluded after the screening. 27 articles met eligibility criteria and were included for the analysis. HSCT: hematopoietic stem cell transplantation; CAR T-cell therapy: chimeric antigen receptor T-cell therapy

Fig. 2

Serologic response after COVID-19 vaccination. The seroconversion rates after one dose (A), two doses (B) or three doses (C) of COVID-19 vaccine were plotted. The solid circles indicates the seropositivity rates, and the horizontal lines mean the 95% confidence interval (CI). The diamonds indicate the pooled estimate, and the lateral tips of the diamonds mean the 95% CIs. The event rate, lower limit, upper limit and relative weight were analyzed using the random effects models. The heterogenicity of each subgroup was represented by Q, I² and P values as described in Methods

Fig. 3

Comparison of seropositive rates between patients receiving HSCT or CAR T-cell therapy and healthy controls. The comparison of seropositive rates between HSCT or CAR T-cell recipients and healthy controls after one dose (A), two doses (B) or three doses (C) of COVID-19 vaccine were plotted. The solid circles indicates the odds ratio, and the horizontal lines mean the 95% CIs. The diamonds indicate the pooled estimate, and the lateral tips of the diamonds mean the 95% CIs. The event rate, lower limit, upper limit and relative weight were analyzed using the random effects models. The heterogenicity of each subgroup was represented by Q, I² and P values as described in Methods

Fig. 4

Effect of time interval between therapy to vaccination on seroconversion rate. The studies were categorized into different subgroups based on time interval between HSCT and the vaccination, referring to the classification of the time interval in the original studies. The studies included in this figure contained individuals with one or two doses vaccines and were annotated in the figure. Two studies set 6 months as the cut-off (< 6 months and > 6 months) while three studies set 12 months as the cut-off (< 12 months and > 12 months). The event rate, lower limit, upper limit and relative weight were analyzed using the random effects models. The heterogenicity of each subgroup was represented by Q, I² and P values as described in Methods