Anti‐SARS‐CoV‐2 vaccines in recipient and/or donor before allotransplant

Abstract The impact of pre‐transplant anti‐severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccine in 20 recipients of allogeneic hematopoietic stem cell transplantation (Allo‐HSCT) and/or their donors is reported here, showing that the persistence of anti‐SARS‐CoV‐2 antibodies can be detected in almost all patients, whatever the type of vaccine used, and up to 9 months post transplant. Also, an anti‐SARS‐CoV‐2 spike glycoprotein CD3+ T‐cell response could be detected in six (35%) of 17 evaluable patients. This study provides a rationale to consider anti‐SARS‐CoV‐2 vaccination of both recipients and donors before Allo‐HSCT.


Anti-SARS-CoV-2 vaccines in recipient and/or donor before allotransplant
To the editor, Most allogeneic hematopoietic stem cell transplantation (Allo-HSCT) recipients lose their immunity to pathogens as soon as the first months after transplant, irrespective of the pre-transplant donor or recipient vaccinations. As such, almost all vaccines are not recommended both before the procedure, especially in donors where feasibility and ethical issues are also of concern and true benefit not proven. After a transplant, Allo-HSCT recipients can respond to vaccines but at a lower extent than healthy individuals, and it can take months or years before detecting adequate immune response [1].
The results of anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine are now progressively reported in Allo-HSCT.
Surprisingly, they show that these patients have the particularity to mount high humoral antibody responses (70%-80% of patients) when receiving the vaccination after transplant. Factors that have been associated with impaired response are ongoing systemic immunosuppressive treatment and severe lymphopenia, especially B lymphopenia.
Thanks to better accessibility, more and more Allo-HSCT-eligible patients, as well as their related or unrelated donors, have now been vaccinated before transplant or graft collection. If coronavirus disease 2019 (COVID-19) positive donors at the time of graft collection have been reported [9], the description and impact of such pre-transplant vaccines are not yet reported.
In this study, anti-SARS-CoV-2 antibody levels (serology 1 [S1]) and had a previously COVID-19 infection. All patients had engrafted. All (but three at S2) were under immunosuppressive drugs at S1 and S2.
Details are given in Table 1. All participants gave informed consent. The study was approved by the Ethics Review Board of Nantes University Hospital.
Remarkably, the persistence of anti-SARS-CoV-2 antibodies can be detected in 95% of patients (n = 19/20) at S1 and 89% of patients (n = 16/18) at S2, whatever the type of vaccine used, until 9 months post transplant. Only one R+/D− case showed seronegativity at S1 and S2. The median positive IgG titer for the whole group was 83.75 BAU/ml (0 → 250, the latter for four patients) at S1 and 128 BAU/ml (0 → 250, the latter for four patients) at S2. Median IgG titers at S1 and S2 differed between R+/D− (21. indicates anti-S-SAR-CoV-2 antibodies from donor and recipient origins, respectively. Also, between S1 and S2, IgG titers decreased in all patients, except in four including three who had received a boost vaccine after S1. Positivity was obtained even with no peripheral B-cells, but a median 3.9 g/L level of gammaglobulins (without supplementation) suggests the persistence of pre-transplant antibodies or germinal center B-cell responses [10].
Only one patient (with both S1 and S2 negative serology) had developed (severe) COVID-19 infection at the last follow-up (January 2022).
In contrast with current recommendations [1], this study provides a rationale to consider anti-SARS-CoV-2 vaccination of both R/D before Allo-HSCT. It remains to determine whether these antibodies and Tcell response provide sufficient protection after transplant. A threshold of an IgG titer of 250 BAU/ml has been associated with an estimate of close to 90% of mRNA-1273 efficacy in the COVE trial [11]. Based on this trial, detectable antibody responses can be classified as "weak" in the case of < 250 BAU/ml and as "good" in the case of ≥ 250 BAU/ml [12]. Here, a good titer has been detectable only in four patients after transplant, suggesting that one or more post-transplant booster shots are needed as already reported before the era of pre-transplant vaccine [13,14].