SARS-CoV-2-reactive antibody waning, booster effect and breakthrough SARS-CoV-2 infection in hematopoietic stem cell transplant and cell therapy recipients at one year after vaccination

Abstract

The kinetics of SARS-CoV-2 reactive IgG antibodies after full vaccination and booster in allogeneic and autologous stem cell transplantation (allo-HSCT, ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) are of utmost importance for estimating risk of infection. A prospective multicenter registry-based cohort study, conducted from December 2020 to July 2022 was used to analyze antibody waning over time, booster effect and the relationship of antibody response and breakthrough infection in 572 recipients (429 allo-HSCT, 121 ASCT and 22 CAR-T cell therapy). A significant decline in antibody titers was observed at 3 and 6 months after full vaccination in recipients without pre-vaccine SARS-CoV-2 infection, whereas recipients infected prior to vaccination showed higher and stable antibody titers over time. In poor responders, a booster dose was able to increase antibody titers in 83% of allo-HSCT and 58% of ASCT recipients but not in CART-T cell recipients [0%] ( p < 0.01). One-year cumulative incidence of breakthrough infection was 15%, similar among cell therapy procedures. Immunosuppressive drugs at the time of vaccination [hazard ratio (HR) 1.81, p = 0.0028] and reduced intensity conditioning (HR 0.49, p = 0.011) were identified as the only conditions associated with different risk of breakthrough infection in allo-HSCT recipients. Antibody titers were associated with breakthrough infection and disease severity. No death was observed among the 72 breakthrough infections. Antibody level decay after the first two vaccine doses was common except in recipients with pre-vaccination SARS-CoV-2 infection. Poorly responding allo-HSCT recipients showed a response advantage with the booster as compared to ASCT and, especially, the null response found in CAR-T cell recipients. Antibody titers were positively correlated with the risk of breakthrough SARS-CoV-2 infection which was mainly driven by the immunosuppression status.

COVID‐19 in hematopoietic stem‐cell transplant recipients: A systematic review and meta‐analysis of clinical characteristics and outcomes

“…COVID‐19 clinical characteristics, medication used, and lethality are reported in Table 3. From the studies that reported symptomatic rate 7,11,15,21–26 we found 79.4% of symptomatic disease ( n = 624/785, range: 50.0% 26 to 100% 15,23 ). The hospitalization rate varied from 9.2% 26 to 74.0% 10 and the median duration of hospital stay from 14 7 to 8 11 days.…”

“…The most frequent hematological underline disease was acute myeloid leukemia in eight (50.0%) articles 7,10,15,19,22,23,25,26 . Allogeneic HSCT patients were the majority in most studies, 7,10,15,18,19,21–26 with a total of 861 patients (72.5%).…”

“…Piñana et al 26 . conducted their prospective multicenter study in Spain from December 2020 to July 2022.…”

“…The conditions associated with breakthrough were use of immunosuppressive drugs at the time of vaccination (HR 1.81, p = 0.0028) and reduced intensity conditioning (HR 0.49, p = 0.011). No death was reported 26 …”

“…The pooled prevalence of death for the entire population was 17% (95% CI 0.13–0.22; I 2 = 76%; n = 221/1117), 17% (95% CI 0.12–0.23; I 2 = 67%; n = 152/822) for allogeneic‐HSCT 7,9,10,15–23,25,26 and 14% (95% CI 0.08–0.22; I 4 = 65%; n = 48/293) for autologous‐HSCT 9–11,15–21,25,26 (Figure 3–5).…”