Evolution of anti-spike responses to SARS-CoV-2 vaccination within 6 months post-transplantation in patients previously vaccinated while on the transplant waiting list.

To the Editor, SARS-CoV-2 vaccination has dramatically reduced the occurrence of severe Covid-19 disease. While non immunosuppressed patients with chronic kidney disease develop a good humoral response following vaccination,1 about 35% of Kidney Transplant Recipients (KTR) remain seronegative despite three injections,2 mainly due to their immunosuppressive therapy. Thus, obtaining a strong anti-SARS-CoV-2 humoral response before transplantation has been recommended. However, there are currently no data about the development of anti-spike antibodies in patients vaccinated for whom immunosuppression has been administered. We retrospectively assessed the evolution of anti-spike IgG titers in adult KTRs previously vaccinated while on the transplant waiting list, and the safety/efficacy of mRNA boosters (Pfizer BNT162b2 or Moderna mRNA-1273) during the first 6 months post-transplant in two French university hospitals. The development of anti-spike titers was analyzed according to the occurrence and timing of Covid-19 and/or booster. The impact of boosters was considered by comparing the last serological assessment before the booster and the first serological assessment following vaccine administration, in the absence of SARS-CoV-2 infection. One-hundred and twenty-one KTRs were analyzed, and complete baseline characteristics are described in Table 1. At transplantation, 71.9% of patients had an anti-spike titer ≥250 BAU/mL (HIGH POS); 22.3% between 1 and 250 BAU/mL (LOWPOS, mean titer: 106 BAU/mL); and 5.8% were seronegative (SERONEG).In the absence of Covid-19 and/or booster, the anti-spike titer decreased by 39.6% at M1 (p < .0001), 44.1% at M3 and 63.9% at M6 post-transplantation (Figure 1A). This observation was broadly similar when immunocompromised patients before transplantation were excluded from the analysis. For HIGH POS patients, the mean anti-spike titer was 232 BAU/mL at M1, 190 BAU/mL at M3, and 160 BAU/mL at M6. For LOW POS patients, the mean anti-spike titer was 46 BAU/mL at M1, 30 BAU/mL at M3, and 7 BAU/mL at M6. Importantly, disappearance of anti-spike IgG did not occur in any of the studied patients during the first 6 months post-transplantation (Figure 1B,C). Sixty-six KTRs (54%) received a mRNA vaccine booster after transplantation, including 51 (42%) prior to 6 months, among whom 35 had a serological assessement afterward. Following vaccine boosters, 21 patients (60%) with a low humoral response (BAU < 250/mL) increased their titer, 7 (20%) did not increase their titer while the remaining patients (n = 7, 20%) had a high humoral response (≥250 BAU/mL) which persisted (Figure 1D). There was no significant appearance of rejection and/or de novo DSA (dnDSA). Non responder patients tended to have a lower lymphocyte count, higher serum creatinine and lower tacrolimus trough levels during the first months’ post-transplantation. Within our study cohort, 35 patients presented with COVID-19 during the first-year post-transplantation (19 in the first 6 months) among whom 3 (8.5%) required standard hospitalization (non ICU, no deaths). All patients who presented with Covid-19 in the absence of a post-transplant booster (n = 8) increased their anti-spike titer afterward, Figure 1E. We observed a strong decrease in anti-spike titers—as soon as the first month post-transplantation—which was deeper than the gradual decline usually observed.3 Fortunately, no patient showed a disappearance of anti-spike IgG following introduction of immunosuppressive drugs, which has been associated with a higher risk of severe Covid-19. While a humoral response persisted in all our patients, boosters are currently recommended for KTRs to maintain the highest titers, especially against the Omicron variant.5 Our study shows that humoral responses in the first 6 months’ post-transplantation remain altered, as 25% did not respond to boosters. Of note, we did not evaluate cellular immunity, nor did we perform neutralization assays which have also been demonstrated to be important during the immune response following vaccination. Despite being evaluated during the Delta pandemic, we did not observe severe Covid-19 in this vaccinated population of KTRs. In conclusion, we demonstrated that the humoral response to Covid-19 mRNA vaccines strongly decreases immediately after kidney transplantation; however, it does remain positive. Administration of vaccine boosters in the early post-transplantation period was safe and broadly efficient despite immunosuppressive therapies. All authors participated in recruitment, follow-up, and treatment of the transplanted patients. Pierre Braud performed the analysis and wrote the manuscript. Christophe Masset supervised data analysis and critically revised the manuscript. All authors participated in the follow-up of patients, data collection, reviewed the manuscript, and approved the final version. The authors declare no funding was received for this study. The authors have nothing to disclose. The data that support the findings of this study are available from the corresponding author upon reasonable request.